WO1997011075A1 - Triazole compounds, their production and use - Google Patents

Triazole compounds, their production and use Download PDF

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Publication number
WO1997011075A1
WO1997011075A1 PCT/JP1996/002705 JP9602705W WO9711075A1 WO 1997011075 A1 WO1997011075 A1 WO 1997011075A1 JP 9602705 W JP9602705 W JP 9602705W WO 9711075 A1 WO9711075 A1 WO 9711075A1
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group
compound
salt
substituted
formula
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PCT/JP1996/002705
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French (fr)
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Takafumi Fusaka
Osamu Ujikawa
Takeshi Kajiwara
Yasushi Tanaka
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Takeda Chemical Industries, Ltd.
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Priority to AU70013/96A priority Critical patent/AU7001396A/en
Publication of WO1997011075A1 publication Critical patent/WO1997011075A1/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N47/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid
    • A01N47/08—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having one or more single bonds to nitrogen atoms
    • A01N47/28—Ureas or thioureas containing the groups >N—CO—N< or >N—CS—N<
    • A01N47/38—Ureas or thioureas containing the groups >N—CO—N< or >N—CS—N< containing the group >N—CO—N< where at least one nitrogen atom is part of a heterocyclic ring; Thio analogues thereof
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
    • C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
    • C07D249/10—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D249/12—Oxygen or sulfur atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
    • C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
    • C07D513/04—Ortho-condensed systems

Definitions

  • the present invention relates to new triazole compounds showing an excellent selective herbicidal activity, their salts, their production, their
  • the triazole compound represented by the formula (I) of the present invention is a new compound which has a fused heterocyclic group having a nitrogen atom in the bridgehead -(CH 2 ) m -S(O) n - (wherein m is 0 or 1 and n is an integer of 0 to 2), and have an excellent herbicidal activity on a variety of paddy weeds and field weeds and show substantially no damage on culture plants such as rice, wheat, barley soybean, corn, etc., and therefore is used as an excellent selective
  • the present inventors have made investigation with a view to developing selective herbicides having excellent herbicidal activity and no damage on crops, and found that the compound of the formula:
  • Q is a fused heterocyclic group having a nitrogen atom in the bridgehead which may be
  • W is O or S
  • R 1 and R 2 each are hydrogen or a hydrocarbon group which may be substituted or R 1 and R together with the adjacent nitrogen atom may form a nitrogen-containing heterocyclic group which may be substituted
  • R 3 is hydrogen, a halogen or a
  • n is an integer of 0 to 2
  • m is 0 or 1, respectively, or a salt thereof, has a strong herbicidal activity, and shows remarkably reduced damages on the culture plants such as rice, wheat, barley, soybean and corn, and
  • Q is a fused heterocyclic group having a nitrogen atom in the bridgehead which may be
  • W is O or S
  • R 1 and R 2 each are hydrogen or a hydrocarbon group which may be substituted or R 1 and R 2 together with the adjacent nitrogen atom may form a nitrogen-containing heterocyclic group which may be substituted
  • R 3 is hydrogen, a halogen atom or a hydrocarbon group which may be substituted
  • n is an integer of 0 to 2
  • m is 0 or 1, or a salt thereof
  • rings a and b each are a 4 to 8 membered heterocyclic ring containing 1 to 4 nitrogen atoms and optionally, 1 to 3 oxygen atoms and/or 1 to 3 sulfur atoms (which may be in mono- or di-oxide form), which may be fused with a 5 or 6 membered alicyclic ring, an aromatic ring or a 5 or 6 membered heterocyclic ring, (3)
  • a fused heterocyclic group having a nitrogen atom in the bridgehead represented by Q is a group which is formed by removing one hydrogen atom bonded to a ring-constituting carbon atom at a position other than the bridgehead from imidazo[1,2-a]pyridine, imidazo[2,1-b]thiazole, imidazo[1,2-a]pyrimidine, imidazo[1,2-b]pyridazine, imidazo[1,2-a]imidazole, imidazo[2,1-b] (1,3,4)
  • substituents selected from a hydroxyl group, an amino group, a cyano group, an sulfamoyl group, a sulfamoyloxy group, a mercapto group, a nitro group, a halogen atom, an organic residue and a sulfo group,
  • Z 0 is 1) a hydrogen atom, 2) a halogen atom, 3) a C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6
  • hydrocarbon group represented by R 1 or R 2 is a C 1-19 hydrocarbon group
  • hydrocarbon group which may be substituted represented by R 1 and R 2 is 1) a C 1-6 alkyl, C 2-6 alkenyl or C 2-6 alkynyl group, each of which may be substituted with (i) 1 to 5 substituents selected from a C 1-4 alkylthio, halogen, C 1-6 alkoxy, nitro, C 1-6 alkoxy-carbonyl and mono- or di-C 1-6 alkylamino group, (ii) a C 1-3
  • hydrocarbon group represented by R 1 or R 2 is a C 1-6 alkyl group, a C 2-6 alkenyl group or a C 2-6 alkynyl group, (9)
  • R 1 or R 2 are a C 1-6 alkyl group,
  • hydrocarbon group represented by R 3 is a C 1-19
  • hydrocarbon group represented by R 3 is 1) a C 1-6 alkyl, C 2-6 alkenyl or C 2-6 alkynyl group, each of which may be substituted with (i) 1 to 5 substituents selected from a C 1-4 alkylthio, halogen, C 1-6 alkoxy, nitro, C 1-6 alkoxycarbonyl and mono- or di-C 1-6 alkylamino group, (ii) a C 1-3 alkylenedioxy or (iii) a C 2-6 alkylidenedioxy, or 2) a C 6-14 aryl or C 7-19 aralkyl group, each of which may be substituted on the aromatic ring with (i) 1 to 3 substituents selected from a C 1-6 alkyl, C 2-6 alkenyl, C 2- 6 alkynyl, C 1-6 alkoxy, acyl, acyloxy, nitro, cyano, halogen, acylamino and C 1-4 alkylthio group, (i
  • hydrocarbon group represented by R 3 is a C 1-6 alkyl group
  • Y is hydrogen atom or a group represented by the formula
  • X 2 is a leaving group and Q is as defined above, or a salt thereof with a compound of the
  • R 3 is as defined above or a salt thereof with a halogenating agent, and then reacting the resulting compound with a compound represented by the formula:
  • Q is a fused heterocyclic group having a nitrogen atom in the bridgehead which may be substituted.
  • heterocyclic group having a nitrogen atom in the bridgehead means a fused heterocyclic group in which both or either one of the bridgehead atoms, namely the atoms at the head and end of the ring junction, are nitrogen atom(s).
  • the fused heterocyclic group having a nitrogen atom in the bridgehead which may be
  • Q is, for example, the group which is formed by removing one hydrogen atom bonded to a ring-constituting carbon atom at a position other than the bridgehead from a fused heterocyclic ring represented by the formula: or
  • rings a and b are a nitrogen-containing heterocyclic ring which may be substituted.
  • fused heterocyclic groups are those of the formula: , ,
  • ring a or the ring b means a 4 to 8 (preferably 5 or 6) membered heterocyclic ring
  • bridgehead atoms including the bridgehead atoms and containing 1 to 4 nitrogen atoms and optionally, 1 to 3 oxygen atoms and/or 1 to 3 sulfur atoms (which may be in mono- or di-oxide form) which may be fused with a 5 or 6
  • cyclopentane e.g., cyclopentane
  • cyclohexane an aromatic ring (e.g., benzene or naphthalene) or a heterocyclic ring (preferably a 5 or 6 membered heterocyclic ring containing 1 to 4 hetero atoms such as nitrogen atom (which may be oxidized), oxygen atom or sulfur atom (which may be oxidized)).
  • aromatic ring e.g., benzene or naphthalene
  • heterocyclic ring preferably a 5 or 6 membered heterocyclic ring containing 1 to 4 hetero atoms such as nitrogen atom (which may be oxidized), oxygen atom or sulfur atom (which may be oxidized)
  • heterocyclic ring preferably a 5 or 6 membered heterocyclic ring containing 1 to 4 hetero atoms such as nitrogen atom (which may be oxidized), oxygen atom or sulfur atom (which may be oxidized)
  • the preferred fused heterocyclic group is a group of the formula: or
  • the ring a is preferred to be a 5 membered heterocyclic ring containing 1 to 3 nitrogen atoms and the ring b is preferred to be a 5 or 6 membered heterocyclic ring containing 1 or 2 nitrogen atoms or a 5 membered heterocyclic ring containing 1 or 2 nitrogen atoms and one sulfur atom (which may be in mono-or di-oxidized form).
  • the rings a and b may be substituted by the same or different one to three substituents of B 1 , B 2 and B 3 as defined below.
  • the group of is, for example,
  • A is a group which forms a fused ring at the [1,2jposition of the imidazole ring
  • A' is a group which forms a fused ring at the [1,5]position of the imidazole ring
  • A" is a group which forms a fused ring at the [1,5]position of the pyrazole ring
  • A"' is a group which forms a fused ring at the [1,2]position of the pyrrole ring
  • A"" is a group which forms a fused ring at the [3,4]position of the triazole ring
  • B 1 , B 2 and B 3 each are hydrogen, hydroxy, amino, cyano, sulfamoyl, sulfamoyloxy, mercapto, nitro, a halogen or an organic residue.
  • the carbon atom or nitrogen atom constituting a ring atom in the group A, A', A", A"' or A”" may be substituted by the same or different 1 to 3 suitable substituents such as hydroxy, amino, cyano, sulfamoyl, sulfamoyloxy, mercapto, nitro, a halogen, an organic residue or sulfo.
  • the carbon atom and nitrogen atom, or the carbon atom and carbon atom which are adjacent to each other, and which constitute a ring atom in the group A, A', A", A"', or A”” may form another fused ring (5 or 6 membered fused ring).
  • the ring-constituting sulfur atom may be in mono or dioxide form.
  • the organic residue of B 1 , B 2 or B 3 has the same meaning as that of the substituent on the fused heterocyclic ring which is defined below.
  • the group A, A', A", A"' or A"" contains 1 to 4, preferably 2 to 4 of carbon atoms as the ring-constituting atom and may further contain 1 to 3 of nitrogen atom, oxygen atom and/or sulfur atoms (which may be in mono- or di-oxide form).
  • heterocyclic rings are The preferred heterocyclic rings are imidazo[1,2-a]pyridine, imidazo[2,1-b]thiazole, imidazo[1,2-a]pyrimidine, imidazo[1,2-b]pyridazine, imidazo[1,2-a]imidazole, imidazo[2,1-b](1,3,4)thiadiazole,
  • imidazo[1,2-a]pyridine imidazo[2,1-b]thiazole, imidazo[1,2-b]pyridazine, pyrazolo[1,5-a]pyrimidine, and pyrazolo[5,1-b]thiazole.
  • the fused heterocyclic group having a nitrogen atom in the bridgehead represented by Q is the group which is formed by removing one hydrogen atom bonded to a ring-constituting carbon atom at other position than the bridgehead from the fused
  • heterocyclic ring For example, the fused heterocyclic group corresponding to imidazo[1,2-a]pyridine as a fused heterocycle are:
  • the ring-constituting atoms comprise preferably four carbon atoms; two or three carbon atoms and one nitrogen atom; two carbon atoms and one sulfur atom (which may be in mono- or di-oxide form); each one of carbon atom, sulfur atom and
  • nitrogen atom or one carbon atom and two nitrogen atoms.
  • the ring-constituting atoms comprise preferably four carbon atoms .
  • the ring-constituting atoms comprise preferably four carbon atoms; three carbon atoms and one nitrogen atom; and two carbon atoms and one sulfur atom.
  • the ring-constituting atoms comprise preferably two carbon atoms and one sulfur atom.
  • the fused heterocyclic group having a nitrogen atom in the bridgehead, represented by Q may be
  • substituents such as hydroxy, amino, cyano, sulfamoyl, sulfamoyloxy, mercapto, nitro, a halogen, an organic residue or sulfo, as mentioned above.
  • the preferred substituents are cyano, sulfamoyl, sulfamoyloxy, nitro, a halogen or an organic residue and th ore preferred ones are a halogen or an organic residu
  • halogen atom used here is, for example, fluorine, chlorine, bromine or iodine.
  • the organic residue is, for example, a hydrocarbon group, a heterocyclic group, an acyl group, a group of the formula -T-Q 0 (Q 0 is a hydrocarbon group, a
  • Q 1 is hydrogen, a hydrocarbon group or an acyl group and Q 2 is a hydrocarbon group or an acyl group or both Q 1 and Q 2 are combined with the adjacent nitrogen atom to form a ring), a group of the formula
  • heterocyclic group and acyl group as the example of the organic residue; the hydrocarbon group, heterocyclic group and acyl group for Q 0 ; and the hydrocarbon group and acyl group for Q 1 or Q 2 are explained in detail below.
  • carbamoyl group carbamoyloxy group, ureido group and thiocarbamoyl group may be substituted with the same or different 1 or 2
  • heterocyclic group as the example of the organic residue and in Q 0 may be substituted with one to three of such below-mentioned hydrocarbon group, acyl group and halogen atom.
  • hydrocarbon groups examples include a straight chain, branched chain or cyclic aliphatic group which may have one or more double or triple bonds, or an aryl or aralkyl group, more
  • an alkyl, alkenyl, alkynyl, aryl or aralkyl group concretely, an alkyl, alkenyl, alkynyl, aryl or aralkyl group .
  • the alkyl group is preferably a straight chain, branched chain or cyclic alkyl group containing 1 to 6 carbon atoms, such as methyl, ethyl, n-propyl,
  • the alkenyl group is preferably a straight chain, branched chain or cyclic alkenyl group containing 2 to
  • the alkynyl group is preferably an alkynyl group containing 2 to 6 carbon atoms, such as propargyl, 2-butynyl, 3-butynyl, 3-pentynyl or 3-hexynyl.
  • the aryl group is preferably an aryl group
  • containing 6 to 14 carbon atoms such as phenyl, naphthyl, biphenylyl or anthryl.
  • the aralkyl group is preferably an aralkyl group containing 7 to 19 carbon atoms, such as benzyl, phenethyl, phenylpropyl, biphenylylmethyl, benzhydryl or trityl.
  • heterocyclic group is, for example, a 3 to 8 membered heterocyclic group
  • heterocyclic group examples include 1- or 2-aziridinyl, 1- or 2-azirinyl, 2- or 3-azetyl, 1-, 2- or 3-azetidinyl, 1-, 2-, 3- or 4-perhydroazepinyl, 1-, 2-, 3-, 4- or 5-perhydroazocinyl, 2- or 3-pyrrolyl, 3-, 4- or 5-pyrazolyl, 2-, 4- or 5-imidazolyl, 1,2,3-triazol-4-yl, 1,2,4-triazol-3-yl, 1H- or 2H- tetrazol-5-yl, 2- or 3-furyl, 2- or 3-thienyl, 2- or 3-thienyl-1,1-dioxide, 2-, 4- or 5-oxazolyl, 3- ,4- or 5-isoxazolyl, 1,2,3-oxadiazol-4 or 5-yl, 1,2,4-oxadiazol-3 or 5-yl, 1,2,5-oxadiazol-3 or 4-yl, 1,3,
  • pyrido[2,3-d]pyrimidin-2-yl 1,5-, 1,6-, 1,7-, 1,8-, 2,6- or 2,7-naphthyridinyl (e.g., 1,5-naphthyridin-2 or 3-yl), thieno[2,3-d]pyridyl (e.g., thieno[2,3-d]pyridin-3-yl), pyrazinoquinolyl (e.g., pyrazinof 2,3-d]quinolin-2-yl) and chromenyl (e.g., 2H-chromen-2 or 3-yl).
  • thieno[2,3-d]pyridyl e.g., thieno[2,3-d]pyridin-3-yl
  • pyrazinoquinolyl e.g., pyrazinof 2,3-d]quinolin-2-yl
  • chromenyl e.g., 2H-chro
  • acyl group is an acyl group derived from an organic carboxylic acid, such as an alkanoyl group preferably containing 1 to 7 carbon atoms (for example, formyl, acetyl, propionyl, butyryl, isobutyryl, pentanoyl, hexanoyl or heptanoyl), an arylcarbonyl group preferably containing 6 to 14 carbon atoms (for example, benzoyl or naphthalenecarbonyl), an alkoxycarbonyl group preferably containing 1 to 6 carbon atoms (for example, methoxycarbonyl,
  • ethoxycarbonyl propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, sec-butoxycarbonyl or tert-butoxycarbonyl), an aryloxy carbonyl group preferably containing 6 to 14 carbon atoms (for
  • phenoxycarbonyl an aralkylcarbonyl group preferably containing 7 to 19 carbon atoms (for
  • a 5 or 6 membered heterocyclecarbonyl group preferably containing 1 to 4 hetero atoms such as nitrogen atom (which may be oxidized), oxygen atom or sulfur atom (which may be mono- or di-oxidized) in the heterocycle, such as, 2-, 3- or 4-pyrrolylcarbonyl, 3-, 4- or 5-pyrazolylcarbonyl, 2 - , 4- or 5-imidazolylcarbonyl, 1,2,3-triazol-4-ylcarbonyl, 1,2,4-triazol-3-yl-carbonyl, 1H- or 2H-tetrazol-5-ylcarbonyl, 2- or 3-furylcarbonyl, 2- or 3-thienylcarbonyl, 2-,4- or 5-oxazolylcarbonyl, 3-, 4- or 5-isoxazolylcarbonyl, 1,2,3-oxadiazol-4 or 5-ylcarbonyl, 1,2,4-oxadiazol-3 or 5-ylcarbonyl,
  • thieno[2,3-d]pyridylcarbonyl e.g., thieno[2,3-d]pyridin-3-yl-carbonyl
  • pyrazinoquinolylcarbonyl e.g., 1,5-naphthyridin-2 or 3-ylcarbonyl
  • chromenylcarbonyl e.g., 2H-chromen-2 or 3-ylcarbonyl
  • chromenylcarbonyl e.g., 2H-chromen-2 or 3-ylcarbonyl
  • heterocycle-acetyl group
  • heterocycle preferably containing 1 to 4 hetero atoms such as nitrogen atom (which may be oxidized), oxygen atom or sulfur atom (which may be mono- or di-oxidized) in the heterocycle, such as 2-pyrrolylacetyl, 3-imidazolylacetyl or 5-isoxazolylacetyl.
  • heterocycle such as 2-pyrrolylacetyl, 3-imidazolylacetyl or 5-isoxazolylacetyl.
  • the group of the formula -T-Q 0 includes an
  • alkyloxy alkenyloxy, aryloxy, aralkyloxy
  • heterocyclyloxy acyloxy, alkylthio, alkenylthio, arylthio, aralkylthio, heterocyclylthio, acylthio, alkyldithio, aryldithio, aralkyldithio, alkylsulfinyl, alkenylsulfinyl, arylsulfinyl, aralkylsulfinyl,
  • heterocyclylsulfinyl alkylsulfonyl, alkenylsulfonyl, arylsulfonyl, aralkylsulfonyl and heterocyclylsulfonyl groups.
  • the alkyloxy group means a straight chain, branched chain or cyclic alkyloxy group preferably containing 1 to 6 carbon atoms, such as methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, n-pentyloxy, sec-pentyloxy, isopentyloxy, neopentyloxy, cyclopentyloxy, n-hexyloxy, isohexyloxy or cyclohexyloxy.
  • the alkenyloxy group means a straight chain, branched chain or cyclic alkenyloxy group preferably containing 2 to 6 carbon atoms, such as allyloxy, isopropenyloxy, 1-butenyloxy, 2-pentenyloxy or 2-hexenyloxy.
  • the aryloxy group menas an aryloxy group preferably containing 6 to 14 carbon atoms, such as phenoxy, naphthyloxy or biphenylyloxy.
  • the aralkyloxy group means an aralkyloxy group
  • preferably containing 7 to 19 carbon atoms such as benzyloxy, phenethyloxy or phenylpropyloxy.
  • the heterocyclyloxy group means a group of the formula T'-O- (T' is the heterocyclic group as
  • the acyloxy group means a group of the formula T"-O- (T" is the acyl group as mentioned above), such as acetoxy, propionyloxy, butyryloxy, pentanoyloxy, hexanoyloxy, benzylcarbonyloxy,
  • alkylthio group means a straight chain, branched chain or cyclic alkylthio group preferably containing 1 to 6 carbon atoms, such as methylthio, ethylthio, n- propylthio, isopropylthio, n-butylthio, isobutylthio, sec-butylthio, tert-butylthio, n-pentylthio, sec-pentylthio, isopentylthio, neopentylthio,
  • alkenylthio group means a straight chain, branched chain or cyclic alkenylthio group preferably containing 2 to 6 carbon atoms, such as allylthio, isopropenylthio, 1-butenylthio, 2-pentenylthio or 2-hexenylthio.
  • the arylthio group means an arylthio group preferably containing 6 to 14 carbon atoms, such as phenylthio, naphthylthio or biphenylylthio.
  • the aralkylthio group means an aralkylthio group preferably containing 7 to 19 carbon atoms, such as benzylthio, phenethylthio or phenylpropylthio.
  • the heterocyclethio group means a group of the formula T'-S- (T' denotes a heterocyclic group as mentioned above), such as 2- or 3-pyrrolylthio, 3-, 4- or 5-pyrazolylthio, 2-,4- or 5-imidazolylthio, 1,2,3-triazol-4-ylthio, 1,2,4-triazol5-ylthio 1H- or 2H-tetrazol-5-ylthio, 2- or 3-furylthio, 2- or 3-thienylthio, 2- or 3-thienylthio ⁇
  • acylthio group means a group of the formula T"-S- (T" is an acyl group as mentioned above), such as
  • alkyldithio group means a straight chain, branched chain or cyclic alkyldithio group preferably containing 1 to 6 carbon atoms, such as methyldithio, ethyldithio, n-propyldithio or cyclopentyldithio.
  • the aryldithio group means an aryldithio group preferably containing 6 to 14 carbon atoms, such as phenyldithio, naphthyldithio or biphenylyldithio.
  • the aralkyldithio group means an aralkyldithio group preferably containing 7 to 19 carbon atoms, such as benzyldithio or phenethyldithio.
  • the alkylsulfinyl group means a straight chain, branched chain or cyclic alkylsulfinyl group preferably containing 1 to 6 carbon atoms, such as methylsulfinyl, ethylsulfinyl, n-propylsulfinyl, isopropylsulfinyl, n-hexylsulfinyl or cyclohexylsulfinyl.
  • the alkenylsulfinyl group means a straight chain, branched chain or cyclic
  • alkenylsulfinyl group preferably containing 2 to 6 carbon atoms such as alkylsulfinyl .
  • the arylsulfinyl group means an arylsulfinyl group preferably containing 6 to 14 carbon atoms such as phenylsulfinyl .
  • the aralkylsulfinyl group means an aralkylsulfinyl group preferably containing 7 to 19 carbon atoms, such as benzylsulfinyl; the heterocyclylsulfinyl group means a group of the formula T'-SO- (T' denotes the
  • heterocyclic group as mentioned above), such as 2- or 3-pyrrolylsulfinyl or 3-, 4- or 5-pyrazolylsulfinyl.
  • the alkylsulfonyl group means a straight chain
  • alkylsulfonyl group preferably containing 1 to 6 carbon atoms, such as methylsulfonyl, ethylsulfonyl, n-propylsulfonyl, isopropylsulfonyl or cyclohexylsulfonyl.
  • alkenylsulfonyl group means a straight chain, branched chain or cyclic
  • alkenylsulfonyl group preferably containing 2 to 6 carbon atoms, such as allylsulfonyl.
  • the arylsulfonyl group means an arylsulfonyl group preferably containing 6 to 14 carbon atoms, such as phenylsulfonyl,
  • aralkylsulfonyl group means an aralkylsulfonyl group preferably containing 7 to 19 carbon atoms, such as benzylsulfonyl, phenethylsulfonyl or
  • the heterocyclylsulfonyl group means a group of the formula T'-SO 2 - (T' is the
  • heterocyclic group such as 2- or 3-pyrrolylsulfonyl or 3-, 4- or 5-pyrazolylsulfonyl.
  • an alkylamino group preferably, a mono- or di-alkylamino group containing 1 to 6 carbon atoms in each alkyl, such as methylamino, ethylamino, n- propylamino, n-butylamino, tert-butylamino, n- pentylamino, n-hexylamino, dimethylamino, diethylamino, methylethylamino, di-(n-propyl)amino or di-(n-butyl)- amino; (2) a cycloalkylamino group, preferably, a mono- or di-cycloalkylamino group containing 3 to 6 carbon atoms in each cycloalkyl, such as cyclopropylamino, cyclopentylamino, cyclohexylamino or dicyclohexylamino; (3) an arylamino group preferably containing 6 to
  • both Q 1 and Q 2 may be combined with the adjacent nitrogen atom to form a ring, preferably 3 to 7 membered ring such as
  • each alkyl preferably containing 1 to 6 carbon atoms in each alkyl, such as methylsulfamoyl, ethylsulfamoyl, n-propylsulfamoyl, n-hexylsulfamoyl, dimethylsulfamoyl, diethylsulfamoyl, methylethylsulfamoyl or di-(n-butyl)sulfamoyl; (2) a cycloalkylsulfamoyl group preferably containing 3 to 6 carbon atoms, such as cyclopropylsulfamoyl or cyclohexylsulfamoyl; (3) an arylsulfamoyl group preferably containing 6 to 14 carbon atoms, such as phenylsulfamoyl; (4) an
  • aralkylsulfamoyl preferably containing 7 to 19 carbon atoms, such as benzylsulfamoyl, 1-phenylethylsulfamoyl, 2-phenylethylsulfamoyl, benzhydrylsulfamoyl or
  • both Q 1 and Q 2 may be combined with the adjacent nitrogen atom to form a ring such as pyrrolidino or piperidino.
  • the group of the formula Q 2 -SO 2 -O- includes (1) an alkylsulfonyloxy group preferably containing 1 to 6 carbon atoms, such as methanesulfonyloxy or
  • aralkylsulfonyloxy group preferably containing 7 to 19 carbon atoms, such as benzylsulfonyloxy or
  • phenethylsulfonyloxy phenethylsulfonyloxy
  • an acylsulfonyloxy group such as acetylsulfonyloxy or butyrylsulfonyloxy.
  • alkyl alkyloxy (or alkoxy), alkylthio, alkyldithio, alkylsulfinyl, alkylsulfonyl, alkylamino, cycloalkylamino, alkenyl, alkenyloxy, alkenylthio, alkenyldithio, alkenylsulfinyl,
  • alkenylsulfonyl, alkynyl, alkoxycarbonyl, alkanoyl and alkylsulfonyloxy groups may be further substituted by one to five of alkylthio group (for example, a straight chain or branched chain alkylthio group containing 1 to 4 carbon atoms, such as methylthio, ethylthio, n-propylthio or isobutylthio), a halogen atom (for exaaple, fluorine, chlorine, bromine or iodine), an alkoxy group (for example, a straight chain or branched chain alkoxy group containing 1 to 6 carbon atoms, such as methoxy, ethoxy, n-propoxy, tert-butoxy or n-hexyloxy), nitro, an alkoxycarbonyl group (for example, an alkoxycarbonyl group containing 1 to 6 carbon atoms in the alkoxy moiety, such as
  • alkoxy groups may be combined to form alkylenedioxy group containing 1 to 3 carbon atoms, such as methylenedioxy,
  • aryloxycarbonyl arylcarbonyl, arylthio, aryldithio, arylsulfinyl, arylsulfonyl, arylamino, aralkyl,
  • aralkyldithio, aralkylsulfinyl, aralkylsulfonyl, aralkylamino, aralkylcarbonyl, arylsulfonyloxy, and aralkylsulfonyloxy groups may be further substituted on their aromatic ring by one to three of alkyl, alkenyl, alkynyl, alkoxy, acyl, acyloxy, nitro, cyano, halogen, acylamino or alkylthio.
  • alkyl, alkenyl, alkynyl, alkoxy, acyl, acyloxy, acylamino or alkylthio group or halogen atom as mentioned above are used.
  • these groups may be combined to form a bivalent group such as trimethylene or
  • telomeres in case of being substituted by two alkenyl groups adjacent to each other, they may be combined to form a bivalent group such as propenylene, 1-butenylene, 2-butenylene or butadienylene, in which case the resulting bivalent group makes an additional 5 or 6 membered alicyclic ring (e.g. cyclopentane, cyclohexane, cyclohexadiene), aromatic ring (e.g.
  • heterocyclylthio heterocyclylsulfinyl
  • heterocyclecarbonyl and heterocyclylsulfonyl groups may be substituted on their heterocyclic group by one to three of the above mentioned alkyl, alkenyl, alkynyl, aryl, aralkyl, alkanoyl, arylcarbonyl, alkoxycarbonyl, aryloxycarbonyl, aralkylcarbonyl, nitro, amino,
  • hydroxyl, cyano, sulfamoyl or mercapto group or a halogen atom for example, fluorine, chlorine, bromine, iodine.
  • Preferred examples of the substituent in the fused heterocyclic group having a nitrogen atom in the bridgehead represented by Q include, among others, (1) an alkyl (preferably, a C 1-6 alkyl group), alkoxy
  • halogen atoms e.g. fluorine, chlorine, bromine, etc.
  • a halogen atom e.g. fluorine, chlorine, bromine, etc.
  • a dialkylamino group preferably, a di-C 1-6 alkylamino
  • an alkyl preferably, a C 1-6 alkyl
  • alkoxy preferably, a C 1-6 alkoxy group
  • alkylthio group preferably, a C 1-6 alkylthio group
  • each of which may be substituted with 1 to 3, the same or different alkoxy groups (preferably a C 1-6 alkoxy group) and/or alkylthio groups (preferably, a C 1-6 alkylthio group)
  • pyrrolidino piperidino, morphorino, piperazino, aziridino, azetidino, pyrazolyl, imidazolyl, furyl, pyrrolyl, pyridyl, pyrazinyl, etc.) and so on.
  • the particularly preferred examples include (1) a C 1-6 alkyl, C 1-6 alkoxy or C 1-6 alkylthio group, which may be substituted with 1 to 5, the same or different, halogen (especially, fluorine, etc.) (2) chlorine, (3) a di C 1-3 alkylamino group, (4) a C 1-6 alkyl, C 1-6 alkoxy or C 1-6 alkylthio group, which may be substituted with 1 to 3, the same or different, C 1-6 alkoxy groups and/or C 1-6 alkylthio groups, (5) a 5 to 6 membered nitrogencontaining heterocyclic group which may be substituted with a C 1-6 alkyl group, (especially, pyrroridino, pyrazolyl, etc.).
  • Q is, preferably, a group represented by the formula:
  • Z 0 is 1) a hydrogen atom, 2) a halogen atom, 3) a lower alkyl, lower alkoxy, lower alkylthio, lower alkylsulfinyl, lower alkylsulfonyl or mono- or di-lower alkylamino group, each of which may be substituted with 1 to 5 halogen atoms, 4) a lower alkoxy-alkyl, lower alkoxy-lower alkoxy or lower alkoxy-lower alkylthio group, each of which may be substituted with 1 to 5 halogen atoms; Z 1 and Z 2 each are 1) a hydrogen atom, 2) a halogen atom or 3) a lower alkyl group which may be substituted with 1 to 5 halogen atoms; Z 3 and Z 4 each are 1) hydrogen atom, 2) a halogen atom, 3) a lower alkyl, lower alkoxy, lower alkylthio or mono- or di-lower alkylamino
  • lower alkyl in a lower alkyl group, a lower alkylthio group, a lower alkylsulfonyl group, a lower alkylsulfonyl group and a mono- or di-lower alkylamino group are used an alkyl group having 1 to 6 carbon atoms (e.g. methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, etc.).
  • lower alkoxy in a lower alkoxy group, a lower alkoxy-lower alkyl group, a lower alkoxy-lower alkoxy group and a lower alkoxy-lower alkylthio group are used an alkoxy group having 1 to 6 carbon atoms (e.g. methoxy, ethoxy, propoxy, isopropoxy, butoxy, etc.).
  • halogen atom used here is for example, fluorine, chlorine, bromine, etc.
  • W is O or S and preferably, O.
  • R 1 and R 2 each are hydrogen atom or a hydrocarbon group which may be substituted.
  • hydrocarbon group and its substituent there may be used the same alkyl, alkenyl, alkynyl, aryl and aralkyl group and those substituents as mentioned above.
  • the preferred examples of the hydrocarbon group include an alkyl group, an alkenyl group or an alkynyl group.
  • an alkyl group an alkenyl group or an alkynyl group, which may be substituted with 1 to 5 halogen atoms is particularly preferable.
  • the alkyl group include, preferably, a straight chain, branched chain or cyclic alkyl group containing 1 to 6 carbon atoms such as methyl, ethyl, n-propyl,
  • alkynyl group includes preferably, a straight chain or branched chain alkenyl group having 2 to 4 carbon atoms such as allyl, 1-propenyl, 2-propenyl, 2-methylallyl, etc.
  • alkynyl group include preferably an alkynyl group containing 2 to 4 carbon atoms such as propargil, 1-propynyl, 2-butynyl, etc.
  • the substituents halogen atoms include, for example, fluorine, chlorine,
  • R 1 and R 2 each are a lower alkyl group (for example, an alkyl group having 1 to 4 carbon atoms such as methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, etc.) or allyl group, etc.
  • the most preferable one is ethyl.
  • nitrogen atom may form a nitrogen containing
  • the nitrogen containing heterocyclic group there may be used a 4 to 8 membered, preferably 5 to 7 membered nitrogen containing heterocyclic group which may be constituted with 1 to 3 hetero atoms selected from a group consisting of nitrogen, oxygen and sulfur atoms other than at least one nitrogen atom and carbon atom, specifically, pyrrolidino, piperidino,
  • pyrrolyl 1-pyrazolyl, 1-imidazolyl, 1H-1, 2, 3-triazol-1-yl, 1H-1, 2, 4-triazol-1-yl, 1H-tetrazol-1-yl, 1H-indol-1-yl, etc.
  • pyrrolidino, piperidino, hexamethylenimino, morpholino, 4-methylpiperazino, etc. are preferable.
  • a lower alkyl e.g. a C 1-6 alkyl such as methyl, ethyl, etc.
  • a halogen atom e.g. fluorine, chlorine, bromine, etc.
  • R 1 and R 2 together with the adjacent nitrogen atom form a nitrogen containing heterocyclic group, R 1 and R 2 may preferably be
  • alkylene chain examples include an alkylene chain having 3 to 7 carbon atoms, specifically, for example, propane-1, 3-diyl, butane-1, 4-diyl, pentane-1, 5-diyl, hexane-1, 6-diyl, heptane-1, 7-diyl, etc.
  • substituent on the alkylene chain include a lower alkyl group (e.g. a C 1-6 alkyl group such as methyl, ethyl, etc.), a halogen atom (e.g. fluorine, chlorine, bromine, etc.).
  • R 3 is hydrogen atom, a halogen atom or a
  • hydrocarbon group which may be substituted examples include fluorine, chlorine, bromine, etc.
  • hydrocarbon group which may be substituted and its substituent there may be used the same alkyl, alkenyl, alkynyl, aryl and aralkyl group and those substituents as mentioned above.
  • hydrocarbon group examples include a substituted or unsubstituted alkyl (a C 1-6 alkyl group such as methyl, ethyl, etc.).
  • a halogen atom e * g * fluorine, chlorine, bromine, etc.
  • the like is particularly preferable.
  • R 3 is hydrogen, a halogen atom (e.g. fluorine, chlorine, bromine, etc.), a C 1-6 alkyl (e.g. methyl, ethyl, etc.) and the like.
  • a halogen atom e.g. fluorine, chlorine, bromine, etc.
  • a C 1-6 alkyl e.g. methyl, ethyl, etc.
  • R 3 is hydrogen.
  • n is an integer of 0 to 2, preferably 1 or 2 and more
  • m is 0 or 1 and preferably 0.
  • W is O or S
  • R 1 and R each are hydrogen atom or an alkyl group
  • an alkenyl group (preferably a C 2-6 alkenyl group) which may be
  • an alkynyl group (preferably, a C 2-6 alkynyl group) which may be
  • R 1 and R 2 combined together, form an alkylene group which may be substituted
  • R 3 is hydrogen, a halogen atom or an alkyl group (preferably, a C 1-6 alkyl group)
  • n is an integer of 0 to 2 and m is 0 or 1.
  • R 1 and R 2 each are an alkyl group (preferably a C 1-6 alkyl group)
  • R 3 is hydrogen atom
  • n is an integer of 0 to 2 and m is 0 or 1.
  • fused heterocyclic group having a nitrogen atom in the bridgehead which may be substituted which is represented by Q in the compounds for (1) and (2) mentioned above
  • the compound (I) of the present invention can form an inorganic or organic base salt at an acidic group in the substituent such as sulfo or carboxyl in the molecule, or an inorganic or organic acid addition salt at a basic nitrogen atom in the molecule and a basic group in the substituent such as amino.
  • Examples of the inorganic base salts of the compounds (I) include the salt with a conventional base such as alkali metal such as sodium or potassium, an alkaline earth metal such as calcium, or ammonia.
  • a conventional base such as alkali metal such as sodium or potassium, an alkaline earth metal such as calcium, or ammonia.
  • organic base salts of the compounds (I) include a conventional salt such as a salt with
  • Examples of the inorganic acid addition salts of the compounds (I) include a salt with a conventional acid such as the salt with hydrochloric acid,
  • hydrobromic acid sulfuric acid, nitric acid or
  • organic acid addition salts of the compounds (I) include a conventional salt with p-toluenesulfonic acid, methanesulfonic acid, formic acid or trifluoroacetic acid.
  • the compounds (I) or their salts of this invention can be used as agricultural chemicals such as
  • the compounds (I) or their salts exhibit in an extremely low application amount an excellent herbicidal effect against a broad range of weeds, for example, paddy weeds such as Echinochloa oryzicola, Cyperus difformis, Scirpus iuncoides, Monochoria vaginalis, Sagittaria pygmaea, Eleocharis acicularis, Cyperus serotinus.
  • paddy weeds such as Echinochloa oryzicola, Cyperus difformis, Scirpus iuncoides, Monochoria vaginalis, Sagittaria pygmaea, Eleocharis acicularis, Cyperus serotinus.
  • Eleocharis kuroguwai Alisma canaliculatum. Sagittaria trifolia. Scirpus wallichii, Lindernia procumbens,
  • dichotaomiflorum Sorghum halepense, Cyperus rotundus.
  • Avena fatua Alopecurus myosuroides, Bromus tectorum, Stellaria media, Brassica Sp., Cassia obtusifolia, Matricaria chamomilla or Commelina communis.
  • the compounds (I) or their salts exhibit an excellent herbicidal effect selectively on various weeds only, and not on culture crops, and are only slightly toxic to mammals, fishes and shellfishes.
  • the compounds (I) or their salts are useful as a herbicide for paddy fields.
  • the compounds (I) or their salts of this invention also exhibit an excellent fungicidal effect and are useful as fungicidal agents against late blight of tomato, potato, etc., downy mildew of cucumber, grape, etc.
  • the compounds (I) or their salts of this invention can be used as an agricultural chemical, particularly, herbicide in any application form suited for general agricultural chemicals. That is, one, or more than two kinds of the compounds (I) or their salts are used in the form of preparation such as emulsifiable
  • emulsifying agent suspending agent, spreading agent, penetrating agent, wetting agent, thickening agent, stabilizer, etc., and can be prepared by any
  • liquid carriers Suitable examples of the liquid carriers
  • solvents include solvents such as water, alcohols (for example, methanol, ethanol, 1-propanol, 2-propanol or ethylene gylcol), ketones (for example, acetone or methyl ethyl ketone), ethers (for example, dioxane, tetrahydrofuran, ethylene glycol mono-methyl ether, diethylene glycol monomethyl ether or propylene glycol monomethyl ether), aliphatic hydrocarbons (for example, kerosene, kerosene oil, fuel oil or machine oil), aromatic hydrocarbons (for example, benzene, toluene, xylene, solvent naphtha or methylnaphthalene),
  • solvents such as water, alcohols (for example, methanol, ethanol, 1-propanol, 2-propanol or ethylene gylcol), ketones (for example, acetone or methyl ethyl ketone), ethers (for example, diox
  • halogenated hydrocarbons for example, dichloromethane, chloroform or carbon tetrachloride
  • acid amides for example, dimethylformamide or dimethylacetamide
  • esters for example, ethyl acetate, butyl acetate or fatty acid glycerol ester
  • nitriles for example, acetonitrile or propionitrile
  • Suitable examples of the solid carriers include vegetable powder (for example, soy-bean meal, tobacco meal, wheat flour or wood flour), mineral powders (for example, clays such as kaolin, bentonite, or acid clay, talcs such as talc powder or pyrophyllite powder), silicas (for example, diatomaceous earth or mica powder), aluminas, sulfur powder or active carbon. They are used individually or as a suitable mixture of two, more of them.
  • liquid carriers or solid carriers as mentioned above may be used in rate of about 1 to 99 wt%, preferably about 1 to 80 wt% of the whole preparation usually.
  • nonionic or anionic surface active agents such as soaps; polyoxyethylene alkylaryl ethers (e.g. Noigen EA 142 ® from Dai-ichi Kogyo Seiyaku K.K., Japan);
  • polyoxyethylene aryl esters e.g. Nornal ® from Toho Chemical K.K., Japan
  • alkyl-sulfates e.g. Emal 10 ® from Kao Soap K.K., Japan
  • sulfonates e.g. Neogen ® and Neogen T ® from Dai-ichi Kogyo Seiyaku Co. and Neopelex ® from Kao Soap K.K.
  • polyethylene glycol ethers e.g. Nonipol 85 ® , Nonipol 100 ® , Nonipol 160 ® from Sanyo Kasei K.K., Japan
  • polyhydric alcohol esters e.g. Tween 20 ® and Tween 80 ® from Kao Soap K.K.
  • the surface active agent as mentioned above may be used in rate of about 0.1 to 50 wt%, preferably, about 0.1 to 25 wt% of the whole preparaiton, usually.
  • the concentration of the compound (I) or a salt thereof contained in an herbicidal preparation is about 1 to 90% by weight in the case of emulsifiable
  • concentration may vary, depending on the purpose of use.
  • emulsifiable concentrates, wettable powders or the like can be suitably diluted or extended (for example, to 100 to 100000 times) with water or the like, on the occasion of use, and then applied.
  • an active ingredient (the compound (I) or its salt thereof) is used in general, in an amount of about 0.05 to 50 g, preferably about 0.1 to 10 g, per are of paddy field and in an amount of about 0.05 to 50 g, preferably about 0.1 to 10 g, per are of field.
  • the herbicidal preparation of this invention can safely be used just after the rice-planting or even 2 to 3 weeks after the planting without revealing any injury on the rice-plant, and its effect continues for a long period of time.
  • the agricultural chemicals (particularly,
  • herbicidal preparation containing the compound (I) or a salt thereof of this invention can be used, as occasion demands, in combination with or as an
  • herbicidal agents for example, organochlorine series fungicide, organosulfur series fungicide or azole series fungicide, antibiotics
  • insecticidal agent for example, pyrethroid series insecticide, organophosphorus series insecticide or carbamate series insecticide
  • miticide for example, nematocide, synergist, attractant, repellent, dyestuff, fertilizer and the like.
  • herbicidal agents include (1) sulfonylurea herbicides [e.g. bensulfuron-methyl, pyrazosulfuron-ethyl, imazosulfuron, sulfosulfuron, cinosulfuron,
  • pyrazole herbicides e.g. pyrazolate, pyrazoxyfen, benzofenap, etc.
  • carbamate herbicides e.g. benthiocarb, molinate, esprocarb, pyributicarb, dimepiperate, swep, etc.
  • chloroacetanilide herbicides e.g.
  • phenoxycarboxylate herbicides e.g. 2,4-PA, MCP, MCPB, phenothiol, etc.
  • invention is a new compound and can be prepared by known methods (for example, the process described in Japanese Unexamined Patent Publication No. 2149/1972) or by similar methods thereto.
  • the compound (I) or a salt thereof can be prepared according to the following reaction schemata 1 to 3.
  • the same as that of the compound (I) mentioned above is used.
  • a leaving group represented by X there may be used, for example, a halogen atom (e.g. fluorine, chlorine, bromine, etc.) or a group represented by the formula:
  • Q 0 and k are as defined above, (for example, methylsulfonyloxy, trifluoromethylsulfonyloxy, p-toluenesulfonyloxy, benzenesulfonyloxy, etc.) and so on. Above all, a halogen atom is preferable and chlorine is particularly suitable.
  • the reaction is performed in a solvent which does not hamper the reaction.
  • suitable solvents include an aromatic hydrocarbon such as benzene, toluene, etc., a halogenated hydrocarbon such as dichloromethane, chloroform, carbon tetrachloride, etc., an ether such as ethyl ether, isopropyl ether, dioxane, tetrahydrofuran (hereafter, abbreviated as THF), etc., a nitrile such as acetonitrile, etc., a ketone such as acetone, methyl ethyl ketone, etc., an ester such as ethyl acetate, butyl acetate, etc., or dimethylformamide (hereafter, abbreviated as DMF) or dimethylacetamide, or dimethylsulfoxide (hereafter, abbreviated as DMSO), etc., or a mixture thereof.
  • DMF dimethylformamide
  • Suitable bases include an organic base such as triethylamine, tri-n-propylamine, pyridine, 1, 8-diazabicyclo[5.4.0]undec-7-ene
  • DBU 1,4- diazabicyclo[2.2.2]octane, 1,5-diazabicyclo[4.3.0]non-5-ene, etc.
  • an inorganic base such as sodium h ride, p assium hydroxide, potassium carbonate, s ium carbonate, sodium hydroxide, etc.
  • the base may be usually used in an amount of about 0.01 to 3 moles per 1 mole of the compound (II).
  • reaction temperature is usually about -10 to 150°C, preferably about 10 - 100°C.
  • the reaction is completed within about 30 minutes to 20 hours, and its completion can be confirmed by means of thin-layer chromatography or high performance liquid chromatography, etc.
  • a halogen atom e.g. fluorine, chlorine, bromine, etc. is particularly preferred.
  • the compound (II) or a salt thereof is reacted with more than 1 equimolar amount of the compounds (VIII) and (X) in turn in the two steps.
  • the reaction is performed in a solvent which does not hamper the reaction.
  • the solvent the same solvents as used for the reaction of Reaction schema 1 may be used. Preferred examples of the solvents are
  • the reaction is advantageously conducted in the presence of a base.
  • a base one as used in the reaction of Reaction schema 1 may be used. Preferred examples of the bases are
  • This reaction is performed in two steps. After isolation of the compound (IX) or a salt thereof from the reaction mixture obtained by the reaction of the compound (II) or a salt thereof with the compound
  • the compound (VIII) is used in an amount of about 1 to 10 moles, preferably 1 to 3 moles per the compound (II) or a salt thereof.
  • the reaction temperature is usually -10 to 150°C, preferably 20 to 120°C.
  • the reaction is
  • the compound (X) is used in an amount of about 1 to 10 moles, preferably 1 to 3 moles per the compound (II) or a salt thereof.
  • the reaction temperature is usually -10 to 150°C, preferably 20 to 120°C.
  • the reaction is completed within about 30 minutes to 20 hours. The completion of the reaction can be confirmed by thin- layer chromatography or high performance liquid
  • the compound (I-b), namely the compound (I) in which n is 1 or 2, or a salt thereof is prepared by oxidizing the compound (I-a), namely the compound (IV) in which Y is the group represented by the formula:
  • the compound is identical with the compound (I) in which n is O.) or a salt thereof with an oxidizing agent and the like.
  • the oxidizing agent include hydrogen peroxide, potassium permanganate, peracetic acid, metachloroperbenzoic acid, sodium percarbonate, etc.
  • the oxidizing agent may be used suitably in an amount necessary for completing the reaction. It is, for production of the compound (I-b) in which p is 1, theoretically the amount generating an equivalent of active oxygen per 1 mole of the compound (I-a) or its salt used as the starting material and, for production of the compound (I-b) wherein p is 2, the amount generating 2 equivalents of active oxygen per 1 mole of the compound (I-a) or its salt used as the starting material.
  • the reaction is generally conducted in a solvent which does not hamper the reaction. Suitable examples of the solvent include an inert solvent such as water, an alcohol, e.g.
  • methanol e.g. benzene, toluene, xylene, nitrobenzene, chlorobenzene, etc., a halogenated hydrocarbon, e.g. dichloromethane, 1, 2-dichloroethane, chloroform, carbon tetrachloride, etc., a ketone, e.g. acetone, etc., a nitrile e.g.
  • acetonitrile, etc. a carboxylic acid, e.g. acetic acid, trifluoroacetic acid, etc., DMF, etc. or a mixture thereof.
  • the reaction temperature is usually -60 to 100°C, preferably -20 to 60°C
  • the reaction time is 5 minutes to about 50 hours. The completion of the reaction can be confirmed by thin-layer chromatography or high performance liquid chromatography and the like.
  • the compound (I) obtained by the above mentioned reaction has an acidic group such as sulfo or carboxyl in the molecule, it may be obtained as its salt with a base employed. In such case, it can be converted, if necessary, to the free form by addition of, for example, an inorganic acid such as hydrochloric acid, sulfuric acid, phosphoric acid, nitric acid and an organic acid such as formic acid, acetic acid, trifluoroacetic acid, p-toluenesulfonic acid.
  • an inorganic acid such as hydrochloric acid, sulfuric acid, phosphoric acid, nitric acid
  • an organic acid such as formic acid, acetic acid, trifluoroacetic acid, p-toluenesulfonic acid.
  • the compound (I) since the compound (I) has a basic nitrogen atom, it may form its acid addition salt with an inorganic or organic acid mentioned above. In addition, when the compound (I) has a substituent which is a basic group such as amino, it may form its acid addition salt.
  • the compound (I) when obtained in the free form may be converted into its acid addition salt by addition of an inorganic or organic acid mentioned above according to conventional methods, and when obtained in the form of the acid addition salt, may be converted into its free form by addition of a base mentioned above.
  • the compound (I) or its salt thus obtained can be isolated and purified by a known procedure per se such as concentration, concentration under reduced pressure, extraction, phase transfer, crystallization,
  • the compound (III) or its salt, and the compounds (VIII) and (X), which are used as the starting material of the processes of this invention, are known or can be easily prepared from known compounds.
  • the compound (III) or its salt can be prepared, for example, by the processes described in Yakugaku- Zasshi, 76, 968-970 (1956) (Chemical Abstracts 51, 2771 g), Rumanian Patent No. 62087 (1977) (Chemical
  • the compound (VIII) is, for example, phosgen or thiophosgen and they are known compounds.
  • the compound (X) is a usual secondary amine, etc. and known or prepared easily from known compounds.
  • the compound (I-a) is the same compound as the compound (I) in which n is O, and can be prepared from the compound (II) in which n is O (compound II-a) according to the reaction schemata 1 and 2 shown in the process for production of the compound (I) mentioned above.
  • the compound (II) or its salt is new and can be prepared by a method known per se (for example, methods described in Japanese Unexamined Patent Publication Nos. 2149/1972 and 58675/1982) or by similar process thereto.
  • the compound (III) or its salt can be prepared according to the following reaction
  • the compound (Il-b), namely the compound (II) in which n is 1 or 2, or a salt thereof is prepared by oxidizing the compound (Il-a), namely the compound (IV) in which Y is hydrogen atom (also identical with the compound (II) in which n is O) or a salt thereof with an oxidizing agent and the like.
  • oxidizing agent examples include hydrogen peroxide, potassium permanganate, peracetic acid, metachloroperbenzoic acid, sodium percarbonate, etc. Above all, sodium percarbonate is particularly
  • the oxidizing agent may be used suitably in an amount necessary for completing the reaction. It is, for production of the compound (II-b) in which p is 1, theoretically the amount generating an equivalent of active oxygen per 1 mole of the compound (Il-a) or its salt used as the starting material and, for production of the compound (Il-b) in which p is 2, theoretically the amount generating 2 equivalents of active oxygen per 1 mole of the compound (II-a) or its salt used as the starting material.
  • the reaction is performed in a solvent which does not hamper the reaction. Examples of the suitable solvents are an inert solvent such as water, an alcohol, e.g.
  • methanol e.g. benzene, toluene, xylene, nitrobenzene, chlorobenzene, etc., a halogenated hydrocarbon, e.g. dichloromethane, 1, 2-dichloroethane, chloroform, carbon tetrachloride, etc., a ketone, e.g. acetone, etc., a nitrile, e.g.
  • acetonitrile etc., a carboxylic acid, e.g. acetic acid, trifluoro acetic acid, etc., DMF, etc., or a mixture thereof.
  • the reaction temperature is usually -60 to 100°C, preferably -20 to 60°C.
  • the reaction time is 5 minutes to about 50 hours. The completion of the reaction can be confirmed by means of thin-layer chromatography or high performance liquid
  • halogen atom e.g. fluorine, chlorine, bromine, iodine, etc.
  • Q 0 and k are as defined above, (e.g.
  • methylsulfonyloxy trifluoromethylsulfonyloxy, p-toluenesulfonyloxy, benzenesulfonyloxy, etc.). Above all, an halogen atom is preferable and chlorine is particularly preferable.
  • the reaction can be performed in a solvent which does not hamper the reaction.
  • the solvents are applicable the same ones as used for the reaction of Reaction schema 1 as well as an alcohol such as methanol, ethanol, 1-propanol, ete., water or a mixture thereof.
  • preferred solvents are acetonitrile, acetone, methanol, DMF, etc., or a mixture thereof.
  • This reaction is usually accelerated by addition of a base.
  • a base not only the same as those in the reaction of Reaction schema 1 but also an alkoxide such as sodium methoxide, sodium ethoxide, potassium tertbutoxide, etc. can be used. Above all preferred bases are sodium hydride, potassium carbonate, sodium
  • the compound (II") namely the compound (II) in which n and m each are O, or a salt thereof can be prepared according to the process in the following
  • the compound (VII) or a salt thereof and more than 1 mole equivalent of the compound (VI) or a salt thereof are usually reacted in the presence of a base and a halogenating agent.
  • the reaction can be performed in a solvent which does not hamper the reaction.
  • the solvents are used the same as those mentioned for the reaction of Reaction schema 1 and an alcohol such as methanol, ethanol, 1-propanol, etc. or a mixture thereof. Above all, preferred solvents are methanol, ethanol, DMF, etc. and a mixture thereof.
  • X 3 is a halogen atom or a group represented by the formula:
  • the compound (VII) or a salt thereof can be added to the reaction mixture to react with the compound (XI).
  • halogen atom represented by X 3 there may be used, for example, chlorine, bromine, iodine, etc.
  • Examples of the base used in this reaction include the some ones as those used in the reaction of Reaction schema 1 and an alkoxide such as sodium methoxide, sodium ethoxide, potassium tert-butoxide, etc. Among them, sodium methoxide, sodium ethoxide, sodium
  • the base may usually be used in an amount of 0.01 mole to 3 moles per 1 mole of the compound (VI).
  • halogenating agent used in this reaction examples include an element of halogen, e.g. chlorine, bromine, iodine, etc., an N-haloimide, e.g. N- chlorosuccinimide, N-bromosuccinimide, N-iodosuccinimide, etc. or sulfuryl chloride, etc.
  • the halogenating agent may be usually used in an amount of 1 mole to 3 moles per 1 mole of the compound (VI).
  • the reaction temperature is usually about -80 to 160°C, preferably about -70 to 120°C.
  • the reaction is usually about -80 to 160°C, preferably about -70 to 120°C.
  • the compound (II) or a salt thereof obtained by the reaction mentioned above can be isolated and purified by a known procedure per se such as
  • compound (II) is known or can be prepared easily from known compounds by the processes described in, for example, Organic Syntheses Collective Volume (John Wiley and Sons, Inc., New York) Vol. 5, 1070 - 1074 (1973) or the process corresponding thereto.
  • the compound (Il-a) is the same as the compound (II') or (II") which is identical with the compound (II) in which n is 0, and can be prepared according to the process for production of the compound (II) mentioned above, which is shown in Reaction schemata 5 and 6.
  • the compounds (V), (VII) and a salt thereof are known as mentioned below or can be prepared easily from the known compounds.
  • the compounds (I), (II) and their salt of the present invention can be prepared by the processes shown in Reaction schemata 1 to 6 mentioned above and the substituent on the substituent Q in the compounds (I), (II) or their salt can be easily converted to another one as is shown in the following Reaction schemata 7 to 9.
  • L and L each are a halogen atom or methylsulfonyl group
  • q is an integer of 0 or 1 and other symbols are as defined above.
  • r is an integer of 1 or 2, other symbols are as defined above.
  • X 4 is a halogen atom and other symbols are as defined above.
  • halogen atom defined as L 0 , L 1 and X 4 include fluorine, chlorine, bromine, etc.
  • Hal is a halogen atom
  • R 4 is hydrogen, a lower alkyl group which may be substituted with a halogen atom
  • R 5 is a lower alkyl group which may be
  • R 6 is hydrogen, or a lower alkyl or lower alkylthio group which may be substituted with a halogen atom
  • R 7 , R 8 , R 9 , R 10 is hydrogen, a lower alkyl group which may be substituted with a halogen atom and other symbols are as defined above.
  • the halogen atom used here includes, for example, fluorine, chlorine, bromine, etc.
  • the "lower alkyl group" in the lower alkyl group or lower alkylthio group there may be used an alkyl group having 1 to 4 carbon atoms (e.g. methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, etc.)
  • the reaction shown for the compound having an imidazo[1,2-a]pyridine ring is similarly applicable to other fused imidazoles such as imidazo[1,2-a]pyrimidine, imidazo[1,2-a]pyrazine, imidazo[1,2-b]pyridazine, imidazo[1,2-b](1,2,4)triazine, imidazo[1,2-a]imidazole,
  • room temperature means any temperature within the range of 10 to 30°C.
  • 1 H-NMR means the proton nuclear magnetic resonance spectra and measured on BRUKER AC-200P type spectrometer (200MHz) using tetramethyl silane as the internal standard and being indicated in chemical sift ( ⁇ ) value in ppm.
  • IR means the infrared absorption spectra and measured on Infrared Spectrophotometer produced by Shimadzu
  • 6-methylsulfonylimidazo[2,1-b]thiazole-5-carboxylate was added to the suspension and the resulting mixture was stirred for 2 hours at room temperature.
  • the reaction mixture was poured into 100 ml of ice water and the resulting mixture was extracted with chloroform (25 ml each, 4 times). The extracts were combined, washed with an aqueous saturated sodium chloride solution, dried over magnesium sulfate and
  • the product was dissolved in 15 ml of ethylene glycol. To the solution were added 0.6 g (15.0 mmol) of sodium hydroxide and 5 ml of water and the resulting mixture was stirred under heating for 1.5 hours at 80°C. To the reaction mixture was added 1.2 ml (14.4 mmol) of hydrochloric acid, then the mixture was stirred for another 10 minutes at the same temperature. The reaction mixture was poured into 50 ml of ice water and the resulting mixture was extracted with chloroform (20 ml each, 3 times). The extracts were combined, washed with an aqueous saturated sodium chloride solution, dried over magnesium sulfate and concentrated.
  • This compound was prepared in a similar manner to that in (1) and obtained as yellowish oil.
  • IR(neat) 1550, 1463, 1352, 1312, 1252, 1063, 1035, 977, 855
  • This compound was prepared in a similar manner to that in (1) and obtained as yellowish oil.
  • This compound was prepared in a similar manner to that in (1) and obtained as colorless crystals, m.p. 72-73°C
  • This compound was prepared in a similar manner to that in (1) and obtained as yellowish oil.
  • IR(neat) 1530, 1490, 1365, 1340, 1215, 750
  • This compound was prepared in a similar manner to that in (1) and obtained as pale yellowish brown crystal.
  • IR(nujol) 3150, 3080, 1615, 1525, 1500, 1480, 1430, 1415, 1335, 1295, 1245, 1225, 1130, 1030, 945, 785, 765, 705, 645
  • This compound was prepared in a similar manner to that in (1) and obtained as pale yellowish oil.
  • This compound was prepared in a similar manner to that in (1) and obtained as yellowish oil.
  • This compound was prepared in a similar manner to that in (1) and obtained as yellowish oil.
  • This compound was prepared in a similar manner to that in (1) and obtained as pale yellowish oil.
  • IR(nujol) 1550, 1390, 1290, 1100, 1040, 720
  • This compound was prepared in a similar manner to that in (1) and obtained as greenish crystals,
  • IR(nujol) 1530, 1500, 1340, 1280, 1125, 1090, 1060, 1020, 930, 790, 750
  • This compound was prepared in a similar manner to that in (1) and obtained as greenish crystals.
  • IR(nujol) 1530, 1510, 1270, 1170, 1090, 1030, 930,
  • IR(nujol) 3120, 1630, 1540, 1295, 1205, 1040, 800, 720
  • IR(nujol) 3110, 3040, 1615, 1550, 1485, 1470, 1410, 1375, 1350, 1320, 1295, 1195, 1115, 1030, 905, 835, 750
  • This compound was prepared in a similar manner to that in (1) and obtained as pale greenish crystal.
  • reaction mixture was concentrated and to the residue was added water and 20% sodium hydroxide aqueous solution.
  • the resulting mixture (pH 8) was extracted with ethyl acetate. The extract was dried and
  • This compound was prepared in a similar manner to that in (1) and obtained as pale brownish crystal, m.p. 134°C
  • This compound was prepared in a similar manner to that in (1) and obtained as pale yellowish crystals. m.p. 71-72°C
  • This compound was prepared in a similar manner to that in (1) and obtained as pale yellowish crystals. m.p. 67-69°C
  • IR(neat) 1530, 1290, 1220, 1185, 1140, 1100, 1040, 980, 940, 745
  • This compound was prepared in a similar manner to that in (1) and obtained as pale yellowish oil.
  • IR(neat) 2900, 1460, 1290, 1220, 1040
  • IR(neat) 1500, 1340, 1090, 750
  • This compound was prepared in a similar manner to that in (1) and obtained as colorless crystals,
  • IR(nujol) 3100, 3050, 1635, 1550, 1530, 1410, 1330, 1310, 1235, 1105, 1025, 1000, 970, 810, 800, 790, 595
  • This compound was prepared in a similar manner to that in (1) and obtained as colorless crystals.
  • dichloromethane 350 ml was added a solution of dicyclohexylcarbodiimide (DCC) (116.3 g, 0.564 mol) in dichloromethane (100 ml) dropwise over 1 hour (2 - 10°C). The resulting mixture was stirred under cooling in an ice-water bath for 30 minutes and then at room temperature one night. To the reaction mixture was added an additional portion of a solution of DCC (20.0 g, 0.097 mol) in dichloromethane (50 ml) dropwise over 15 minutes and the resulting mixture was stirred for 3 hours. The insoluble solid was filtered with suction and washed with dichloromethane. The filtrate was concentrated and to the residue was added acetone (400 ml). The insoluble solid was filtered with suction and the filtrate was concentrated. The residue was
  • Oil-containing 60% sodium hydride (0.97 g, 24.3 mmol) was washed with n-hexane and suspended in DMF (70 ml) under a dried nitrogen stream. To the suspension was added 7-ethoxycarbonyl-6-hydroxy-3-methylpyrazolo[5,1-b]thiazole (5.0 g, 22.1 mmol) gradually. The resulting mixture was stirred at 40°C for 10 minutes and to the mixture was added iodoethane (2.7 ml, 33.8 mmol) and then an additional portion of DMF (10 ml). The reaction mixture was stirred at 55°C for 1 hour and then at room temperature one night. The reaction mixture was poured into ice-water (200 ml).
  • This compound was prepared in a similar manner to that in (1) and obtained as colorless oil.
  • This compound was prepared in a similar manner to that in (1) and obtained as colorless oil.
  • IR(neat) 1500, 1460, 1320, 1110, 920
  • This compound was prepared in a similar manner to that in (1) and obtained as yellowish oil.
  • IR(neat) 1510, 1460, 1375, 1320, 1115, 1020, 695
  • This compound was prepared in a similar manner to that in (1) and obtained as colorless crystal.
  • IR(nujol) 3150-2500, 1495, 1460, 1360, 1348, 1253, 1160 , 762 , 678
  • IR(nujol) 3150-2400, 1492, 1450, 1330, 1250, 1160, 1142, 1125, 760, 740
  • IR(nujol) 3250, 1520, 1490, 1405, 1350, 1330, 1173, 1150, 1100
  • IR(nujol) 3100, 1540, 1520, 1450, 1400, 1360, 1280, 1240, 1165, 1130, 1020, 950, 830, 820, 740, 720, 620, 605
  • IR(nujol) 3400, 2780, 1620, 1525, 1490, 1390, 1360, 1340, 1290, 1260, 1220, 1155, 1120, 1005, 960, 890, 820, 725, 715, 650, 620
  • IR(nujol) 1710, 1435, 1358, 1340, 1160, 1150, 760,
  • the reaction mixture was added with 40 ml of water and then with potassium carbonate to adjust to pH 10, and extracted with chloroform (20 ml each, twice). The extracts were combined, washed with an aqueous saturated sodium hydrogen carbonate solution, dried over magnesium sulfate and concentrated. The obtained residue was purified by silica gel column chromatography (eluent: ethyl acetate). The solid obtained was washed with ethyl ether, collected by filtration and dried to give 0.26 g of the title compound as colorless crystals, m.p. 125-126°C
  • IR(nujol) 1720, 1460, 1440, 1360, 1342, 1270, 1210,
  • N-diethylcarbamoyl chloride was further added and the resulting mixture was stirred at the same temperature for 1 hour.
  • the reaction mixture was added with 30 ml of ice water and extracted with chloroform (20 ml each, 2 times). The extracts were combined, washed with water, dried over magnesium sulfate and concentrated.
  • the obtained residue was purified by silica gel column chromatography (eluent : n-hexane-ethyl acetate, 1 : 2, v/v). The obtained solid was washed with n-hexane, collected by filtration and dried to give 1.85 g of the title compound as colorless crystals. m.p. 113-114°C
  • IR(nujol) 1712, 1420, 1350, 1340, 1260, 1160, 1150,
  • the reaction mixture was added with 60 ml of ice-water and extracted with ethyl acetate (20 ml each, 2 times). The extracts were combined, washed with an aqueous saturated sodium hydrogencarbonate solution, dried over magnesium sulfate and concentrated. The obtained residue was purified by silica gel column
  • IR ( nujol ) 1720 , 1460 , 1440 , 1343 , 1295 , 1265 , 12 10 ,
  • IR(nujol) 1712, 1460, 1435, 1365, 1320, 1158, 1145, 1133
  • IR(nujol) 1715, 1460, 1440, 1343, 1270, 1255, 1210, 1150, 750
  • IR(nujol) 1720, 1340, 1280, 1260, 1200, 1150, 1020
  • Emulsifiable concentrates containing:
  • Wettable powders as prepared by blending and grinding the following components:
  • Granules as prepared by adding water to the mixture containing the following components, blending and granulating:
  • Granules as prepared by adding water to the mixture containing the following components, blending and granulating:
  • Granules as prepared by adding water to the mixture containing the following components, blending and granulating:
  • Granules as prepared by adding water to the mixture containing the following components, blending and granulating:
  • Paddy soil was put in a square-shaped plastic pot having a surface area of 150 cm . After introducing water and pudding the soil, seeds of Echinochloa oryzicola, Cyperus difformis, Scirpus juncoides and Rotala indica were sowed. The plants were grown for a prescribed term, while keeping flooding water constant in 2 cm depth. When monocotyledon weeds grew up to 1 leaf stage and Rotala indica grew up to 2 leaf stage, the flooding water depth was maintained at 3 cm and a diluted herbicidal solution containing a compound (I) was applied on the water surface to give prescribed dosage (g/a) finally.
  • the diluted herbicidal solution was prepared by dissolving 3.0 mg of the compound (I) in 1 ml of acetone containing 2% of Tween 20 and diluting with pure water up to 10 ml in total and further diluting with pure water up to a prescribed concentration of the compound (I). After application of the diluted herbicidal solution, the plants were grown in a green house, and three weeks after the application, herbicidal effect against various weeds was evaluated according to the standards shown in
  • Paddy soil was put in a square-shaped plastic pot having a surface area of 150 cm . After introducing water and puddling the soil, seeds of Echinochloa oryzicola and Scirpus juncoides were sowed and further a rice-plant seedling was transplanted to the soil. The flooding water depth was maintained at 3 cm and a diluted herbicidal solution containing a compound (I) was applied on the water surface to give prescribed dosage (g/a) finally.
  • the dilute solution was prepared in a similar way to Test Example 1. After application of the dilute solution, the plants were grown in a green house. Three weeks after the application, herbicidal effect against various weeds and injury on the transplanted rice-plant were evaluated according to the standards shown in [Table 34]. The test results were shown in [Table 39] to [Table 42].
  • ECHOR Echinochloa oryzicola
  • the compounds (I) or their salts in accordance with the present invention have an excellent herbicidal activity on a variety of weeds such as paddy weeds and field weeds in a very low application level, and show less damage on culture plants such as rice, wheat, barley, soybean or corn, and therefore exhibit an excellent selective herbicidal effect which is

Abstract

A compound of formula (I), wherein Q is a fused heterocyclic group having an N atom in the bridgehead, W is O or S, R?1 and R2¿ each are hydrogen or a hydrocarbon group or R?1 and R2¿ together with the adjacent N atom may form an N-containing heterocyclic group, R3 is H, a halogen or a hydrocarbon group, n is an integer of 0 to 2, m is 0 or 1, and a salt thereof, a method of production thereof, an intermediate and agricultural chemicals containing the above compound (I). The compounds (I) of this invention have an excellent herbicidal activity on a variety of weeds in a very low application level and show low damage on culture plants and exhibit an excellent selective herbicidal effect which is long-lasting. They also can be very safely used as herbicides for paddy fields, fields, orchards or non-farmed land, showing substantially no toxicity on mammals or fishes and shell fish without causing substantially any environmental pollution.

Description

DESCRIPTION
TRIAZOLE COMPOUNDS, THEIR PRODUCTION AND USE
Technical Field
The present invention relates to new triazole compounds showing an excellent selective herbicidal activity, their salts, their production, their
intermediates and agricultural chemicals containing the said triazole compounds.
The triazole compound represented by the formula (I) of the present invention is a new compound which has a fused heterocyclic group having a nitrogen atom in the bridgehead -(CH2)m-S(O)n- (wherein m is 0 or 1 and n is an integer of 0 to 2), and have an excellent herbicidal activity on a variety of paddy weeds and field weeds and show substantially no damage on culture plants such as rice, wheat, barley soybean, corn, etc., and therefore is used as an excellent selective
herbicide in paddy, field and so on.
Background Art
Hitherto, various carbamoyltriazole derivatives having herbicidal activity have been reported. For example, Japanese Unexamined Patent Publication Nos. 178980/1986, 106883/1989, 1481/1990, 17472/1993,
194494/1993 255314/1993, 345779/1993, 116263/1994, 157515/1994 describe carbamoyltriazole derivatives. However, in these publications a fused heterocyclic group having a nitrogen atom of the bridgehead
through -(CH2)n-S(O)n-, is not described as a
substituent at the 3-position of the 1,2,4-triazole ring.
These prior art compounds are not satisfactory with respect to herbicidal effect on weeds, damage on culture plants, toxicity to mammals, fishes and shellfish and environmental pollution, and therefore, the development for a selective herbicide improved on those aspects has been keenly desired.
Disclosure of Invention
The present inventors have made investigation with a view to developing selective herbicides having excellent herbicidal activity and no damage on crops, and found that the compound of the formula:
Figure imgf000004_0001
wherein Q is a fused heterocyclic group having a nitrogen atom in the bridgehead which may be
substituted, W is O or S, R1 and R2 each are hydrogen or a hydrocarbon group which may be substituted or R1 and R together with the adjacent nitrogen atom may form a nitrogen-containing heterocyclic group which may be substituted, R3 is hydrogen, a halogen or a
hydrocarbon group which may be substituted, n is an integer of 0 to 2, m is 0 or 1, respectively, or a salt thereof, has a strong herbicidal activity, and shows remarkably reduced damages on the culture plants such as rice, wheat, barley, soybean and corn, and
accordingly exhibits a high selectivity in herbicidal activity. On the basis of such finding, the inventors have made various further investigations and completed the present invention.
(1) A compound represented by the formula:
Figure imgf000005_0001
wherein Q is a fused heterocyclic group having a nitrogen atom in the bridgehead which may be
substituted, W is O or S, R1 and R2 each are hydrogen or a hydrocarbon group which may be substituted or R1 and R2 together with the adjacent nitrogen atom may form a nitrogen-containing heterocyclic group which may be substituted, R3 is hydrogen, a halogen atom or a hydrocarbon group which may be substituted, n is an integer of 0 to 2, m is 0 or 1, or a salt thereof, (2) The compound according to (1), in which a fused heterocyclic group having a nitrogen atom in the bridgehead represented by Q is a group represented by the formula:
Figure imgf000005_0002
Figure imgf000005_0003
,
Figure imgf000005_0004
, or
Figure imgf000005_0005
wherein the rings a and b each are a 4 to 8 membered heterocyclic ring containing 1 to 4 nitrogen atoms and optionally, 1 to 3 oxygen atoms and/or 1 to 3 sulfur atoms (which may be in mono- or di-oxide form), which may be fused with a 5 or 6 membered alicyclic ring, an aromatic ring or a 5 or 6 membered heterocyclic ring, (3) The compound according to (1), in which a fused heterocyclic group having a nitrogen atom in the bridgehead represented by Q is a group which is formed by removing one hydrogen atom bonded to a ring-constituting carbon atom at a position other than the bridgehead from imidazo[1,2-a]pyridine, imidazo[2,1-b]thiazole, imidazo[1,2-a]pyrimidine, imidazo[1,2-b]pyridazine, imidazo[1,2-a]imidazole, imidazo[2,1-b] (1,3,4)thiadiazole, pyrazolo[1,5-a]pyrimidine,
pyrazolo[5,1-b]thiazole or pyrazolo[1,5-aJpyridine,
(4) The compound according to (1), in which Q is a fused heterocyclic group having a nitrogen atom in the bridgehead which may be substituted with 1 to 3
substituents selected from a hydroxyl group, an amino group, a cyano group, an sulfamoyl group, a sulfamoyloxy group, a mercapto group, a nitro group, a halogen atom, an organic residue and a sulfo group,
(5) The compound according to (1), in which Q is a group represented by the formula:
Figure imgf000006_0003
Figure imgf000006_0002
or
Figure imgf000006_0005
Figure imgf000006_0001
wherein Z0 is 1) a hydrogen atom, 2) a halogen atom, 3) a C1-6 alkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6
alkylsulfinyl, C1-6 alkylsulfonyl or mono- or di-C1-6 alkylamino group, each of which may be substituted with 1 to 5 halogen atoms, or 4 ) a C1-6 alkoxy-C1-6 alkyl, C1-6 alkoxy-C1-6 alkoxy or C1-6 alkoxy-C1-6 alkylthio group, each of which may be substituted with 1 to 5 halogen atoms; Z1 and Z2 each are 1) a hydrogen atom, 2) a halogen atom or 3) a C1-6 alkyl group which may be substituted with 1 to 5 halogen atoms; Z3 and Z4 each are 1) a hydrogen atom, 2) a halogen atom, 3) a C1-6 alkyl, C1-6 alkoxy, C1-6 alkylthio or mono- or di-C1-6 alkylamino group, each of which may be substituted with 1 to 5 halogen atoms,
(6) The compound according to (1), in which a
hydrocarbon group represented by R1 or R2 is a C1-19 hydrocarbon group,
(7) The compound according to (1), in which a
hydrocarbon group which may be substituted represented by R1 and R2 is 1) a C1-6 alkyl, C2-6 alkenyl or C2-6 alkynyl group, each of which may be substituted with (i) 1 to 5 substituents selected from a C1-4 alkylthio, halogen, C1-6 alkoxy, nitro, C1-6 alkoxy-carbonyl and mono- or di-C1-6 alkylamino group, (ii) a C1-3
alkylenedioxy group or (iii) a C2-6 alkylidendioxy group, or 2) a C6-14 aryl or C7-19 aralkyl group, each of which may be substituted on the aromatic ring with (i) 1 to 3 substituents selected from a C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, acyl, acyloxy, nitro, cyano, halogen, acylamino and C1-4 alkylthio group, (ii) a C3-4 alkylene group or (iii) a C3-4 alkenylene group, (8) The compound according to (1), in which a
hydrocarbon group represented by R1 or R2 is a C1-6 alkyl group, a C2-6 alkenyl group or a C2-6 alkynyl group, (9) The compound according to (1), in which R1 or R2 are a C1-6 alkyl group,
(10) The compound according to (1), in which a
hydrocarbon group represented by R3 is a C1-19
hydrocarbon group,
(11) The compound according to (1), in which a
hydrocarbon group represented by R3 is 1) a C1-6 alkyl, C2-6 alkenyl or C2-6 alkynyl group, each of which may be substituted with (i) 1 to 5 substituents selected from a C1-4 alkylthio, halogen, C1-6 alkoxy, nitro, C1-6 alkoxycarbonyl and mono- or di-C1-6 alkylamino group, (ii) a C1-3 alkylenedioxy or (iii) a C2-6 alkylidenedioxy, or 2) a C6-14 aryl or C7-19 aralkyl group, each of which may be substituted on the aromatic ring with (i) 1 to 3 substituents selected from a C1-6 alkyl, C2-6 alkenyl, C2- 6 alkynyl, C1-6 alkoxy, acyl, acyloxy, nitro, cyano, halogen, acylamino and C1-4 alkylthio group, (ii) a C3.4 alkylene group or (iii) a C3-4 alkenylene group,
(12) The compound according to (1), in which a
hydrocarbon group represented by R3 is a C1-6 alkyl group,
(13) The compound according to (1), in which R3 is hydrogen atom,
(14) The compound according to (1), in which m is 0 and n is 2,
(15) The compound according to Claim 1, which is N,N-diethyl-3-(2-chloro-6-ethoxyimidazo[1,2-b]pyridazin-3-ylsulfonyl)-1H-1,2,4-triazole-1-carboxamide, N,N-diethyl-3-(2-methyl-6-ethoxyimidazo[1,2-b]pyridazin-3-ylsulfonyl)-1H-1,2,4-triazole-1-carboxamide, or N,N-diethyl-3-(6-propoxy-3-methylpyrazolo[5,1-b]thiazol-7-ylsulfonyl)-1H-1,2,4-triazole-1-carboxamide or a salt thereof,
(16) A process for producing the compound according to (1) or a salt thereof which comprises reacting a compound of the formula:
Figure imgf000008_0001
wherein Q, R3, m and n are as defined above, or a salt thereof with a compound of the formula
Figure imgf000008_0002
wherein X1 is a leaving group and other symbols are as defined above, or a salt thereof,
(17) The process for producing a compound of the formula:
Figure imgf000009_0003
wherein p is 1 or 2, Y is as defined above and other symbols are as defined above, or a salt thereof, which comprises oxidizing a compound of the formula:
Figure imgf000009_0002
wherein Y is hydrogen atom or a group represented by the formula
Figure imgf000009_0001
(wherein the symbols are as defined above) and the other symbols are as defined above, or a salt thereof,
(18) An agricultural chemical composition which
comprises an effective amount of the compound according to (1) or a salt thereof,
(19) The agricultural chemical composition according to (18), which is a herbicidal composition,
(20) The agricultural chemical composition according to (18), which is a herbicidal composition effective against paddy weeds,
(21) A compound represented by the formula:
Figure imgf000010_0001
wherein Q, R3, m and n are as defined above, or a salt thereof,
(22) A process for producing a compound of the formula:
Figure imgf000010_0002
wherein Q and R3 are as defined above, or a salt thereof which comprises reacting a compound of the formula:
Q-CH2-X2 (V)
wherein X2 is a leaving group and Q is as defined above, or a salt thereof with a compound of the
formula:
Figure imgf000010_0003
wherein R3 is as defined above, or a salt thereof, (23) A process for producing a compound represented by the formula:
Figure imgf000010_0004
wherein Q and R3 are as defined above, or a salt thereof, which comprises reacting a compound
represented by the formula:
Figure imgf000011_0001
wherein R3 is as defined above or a salt thereof with a halogenating agent, and then reacting the resulting compound with a compound represented by the formula:
Q-H (VII)
wherein Q is as defined above, or a salt thereof.
(24) Use of the compound according to (1) or a salt thereof in the preparation of a herbicidal composition.
In the above mentioned formulae, Q is a fused heterocyclic group having a nitrogen atom in the bridgehead which may be substituted. The fused
heterocyclic group having a nitrogen atom in the bridgehead means a fused heterocyclic group in which both or either one of the bridgehead atoms, namely the atoms at the head and end of the ring junction, are nitrogen atom(s). The fused heterocyclic group having a nitrogen atom in the bridgehead which may be
substituted and which is represented by the symbol Q is, for example, the group which is formed by removing one hydrogen atom bonded to a ring-constituting carbon atom at a position other than the bridgehead from a fused heterocyclic ring represented by the formula: or
Figure imgf000011_0002
Figure imgf000011_0003
(wherein the rings a and b are a nitrogen-containing heterocyclic ring which may be substituted). Examples of such fused heterocyclic groups are those of the formula:
Figure imgf000012_0001
,
Figure imgf000012_0002
,
Figure imgf000012_0003
, or
Figure imgf000012_0004
, wherein
Figure imgf000012_0007
is a bonding arm, and the other symbols are as defined above.
The nitrogen-containing heterocyclic ring
represented by the ring a or the ring b means a 4 to 8 (preferably 5 or 6) membered heterocyclic ring
including the bridgehead atoms and containing 1 to 4 nitrogen atoms and optionally, 1 to 3 oxygen atoms and/or 1 to 3 sulfur atoms (which may be in mono- or di-oxide form) which may be fused with a 5 or 6
membered alicyclic ring (e.g., cyclopentane or
cyclohexane), an aromatic ring (e.g., benzene or naphthalene) or a heterocyclic ring (preferably a 5 or 6 membered heterocyclic ring containing 1 to 4 hetero atoms such as nitrogen atom (which may be oxidized), oxygen atom or sulfur atom (which may be oxidized)). The preferred fused heterocyclic group is a group of the formula: or
Figure imgf000012_0005
Figure imgf000012_0006
In the above formula, the ring a is preferred to be a 5 membered heterocyclic ring containing 1 to 3 nitrogen atoms and the ring b is preferred to be a 5 or 6 membered heterocyclic ring containing 1 or 2 nitrogen atoms or a 5 membered heterocyclic ring containing 1 or 2 nitrogen atoms and one sulfur atom (which may be in mono-or di-oxidized form). The rings a and b may be substituted by the same or different one to three substituents of B1, B2 and B3 as defined below.
Specifically, the group of is, for example,
Figure imgf000013_0001
,
Figure imgf000013_0002
and the group of is, for example,
Figure imgf000013_0003
,
Figure imgf000013_0004
, wherein A is a group which forms a fused ring at the [1,2jposition of the imidazole ring, A' is a group which forms a fused ring at the [1,5]position of the imidazole ring, A" is a group which forms a fused ring at the [1,5]position of the pyrazole ring, A"' is a group which forms a fused ring at the [1,2]position of the pyrrole ring, A"" is a group which forms a fused ring at the [3,4]position of the triazole ring, and B1, B2 and B3 each are hydrogen, hydroxy, amino, cyano, sulfamoyl, sulfamoyloxy, mercapto, nitro, a halogen or an organic residue. The carbon atom or nitrogen atom constituting a ring atom in the group A, A', A", A"' or A"" may be substituted by the same or different 1 to 3 suitable substituents such as hydroxy, amino, cyano, sulfamoyl, sulfamoyloxy, mercapto, nitro, a halogen, an organic residue or sulfo. The carbon atom and nitrogen atom, or the carbon atom and carbon atom which are adjacent to each other, and which constitute a ring atom in the group A, A', A", A"', or A"" may form another fused ring (5 or 6 membered fused ring). The ring-constituting sulfur atom may be in mono or dioxide form.
The organic residue of B1, B2 or B3 has the same meaning as that of the substituent on the fused heterocyclic ring which is defined below.
The group A, A', A", A"' or A"" contains 1 to 4, preferably 2 to 4 of carbon atoms as the ring-constituting atom and may further contain 1 to 3 of nitrogen atom, oxygen atom and/or sulfur atoms (which may be in mono- or di-oxide form).
Examples of the fused rings represented by as the skelton of the group of the
Figure imgf000014_0001
formula: or
Figure imgf000014_0002
Figure imgf000014_0003
include:
Figure imgf000015_0001
Examples of the fused rings represented by the formula: as the skelton of the group of the
Figure imgf000016_0001
formula: or
Figure imgf000016_0002
Figure imgf000016_0003
are:
Figure imgf000016_0004
Examples of the fused rings represented by the formula: as the skelton of the group of the
Figure imgf000016_0005
formula:
or
Figure imgf000016_0006
Figure imgf000016_0007
are:
Figure imgf000016_0008
Examples of the fused rings represented by the formula: as the skelton of the group of the
Figure imgf000017_0005
formula: or
Figure imgf000017_0006
Figure imgf000017_0007
are:
Figure imgf000017_0008
Examples of the fused rings represented by the formula: as the skelton of the group of the
Figure imgf000017_0001
formula: or
Figure imgf000017_0002
Figure imgf000017_0003
are:
Figure imgf000017_0004
Preferred examples of these heterocyclic rings are
Figure imgf000018_0001
The preferred heterocyclic rings are imidazo[1,2-a]pyridine, imidazo[2,1-b]thiazole, imidazo[1,2-a]pyrimidine, imidazo[1,2-b]pyridazine, imidazo[1,2-a]imidazole, imidazo[2,1-b](1,3,4)thiadiazole,
pyrazolo[1,5-a]pyrimidine, pyrazolo[5,1-b]thiazole, and pyrazolo[1,5-a]pyridine.
The more preferred heterocyclic rings are
imidazo[1,2-a]pyridine, imidazo[2,1-b]thiazole, imidazo[1,2-b]pyridazine, pyrazolo[1,5-a]pyrimidine, and pyrazolo[5,1-b]thiazole.
As stated above, the fused heterocyclic group having a nitrogen atom in the bridgehead represented by Q is the group which is formed by removing one hydrogen atom bonded to a ring-constituting carbon atom at other position than the bridgehead from the fused
heterocyclic ring. For example, the fused heterocyclic group corresponding to imidazo[1,2-a]pyridine as a fused heterocycle are:
or
Figure imgf000019_0001
Suitable above mentioned groups are of the
formula:
Figure imgf000020_0001
In the group A, the ring-constituting atoms comprise preferably four carbon atoms; two or three carbon atoms and one nitrogen atom; two carbon atoms and one sulfur atom (which may be in mono- or di-oxide form); each one of carbon atom, sulfur atom and
nitrogen atom; or one carbon atom and two nitrogen atoms.
In the groups A' and A"', the ring-constituting atoms comprise preferably four carbon atoms .
In the group A", the ring-constituting atoms comprise preferably four carbon atoms; three carbon atoms and one nitrogen atom; and two carbon atoms and one sulfur atom.
In the group A"", the ring-constituting atoms comprise preferably two carbon atoms and one sulfur atom.
The fused heterocyclic group having a nitrogen atom in the bridgehead, represented by Q may be
substituted by one to three the same or different substituents, such as hydroxy, amino, cyano, sulfamoyl, sulfamoyloxy, mercapto, nitro, a halogen, an organic residue or sulfo, as mentioned above. The preferred substituents are cyano, sulfamoyl, sulfamoyloxy, nitro, a halogen or an organic residue and th ore preferred ones are a halogen or an organic residu
The halogen atom used here is, for example, fluorine, chlorine, bromine or iodine.
The organic residue is, for example, a hydrocarbon group, a heterocyclic group, an acyl group, a group of the formula -T-Q0 (Q0 is a hydrocarbon group, a
heterocyclic group or an acyl group and T is O,
Figure imgf000021_0001
or S-S, k being 0, 1 or 2), a group of the formula
Figure imgf000021_0002
(Q1 is hydrogen, a hydrocarbon group or an acyl group and Q2 is a hydrocarbon group or an acyl group or both Q1 and Q2 are combined with the adjacent nitrogen atom to form a ring), a group of the formula
Figure imgf000021_0003
(Q1 and Q2 are as defined above), carbamoyl,
carbamoyloxy, ureido, thiocarbamoyl, carboxyl, a group of the formula -O-SO2-Q2 (Q2 is as defined above), or the like.
The above-mentioned hydrocarbon group,
heterocyclic group and acyl group as the example of the organic residue; the hydrocarbon group, heterocyclic group and acyl group for Q0; and the hydrocarbon group and acyl group for Q1 or Q2 are explained in detail below.
The above-mentioned carbamoyl group, carbamoyloxy group, ureido group and thiocarbamoyl group may be substituted with the same or different 1 or 2
substituents of the below-mentioned hydrocarbon group, heterocyclic group and acyl group.
The heterocyclic group as the example of the organic residue and in Q0 may be substituted with one to three of such below-mentioned hydrocarbon group, acyl group and halogen atom.
Examples of the above-mentioned hydrocarbon groups include a straight chain, branched chain or cyclic aliphatic group which may have one or more double or triple bonds, or an aryl or aralkyl group, more
concretely, an alkyl, alkenyl, alkynyl, aryl or aralkyl group .
The alkyl group is preferably a straight chain, branched chain or cyclic alkyl group containing 1 to 6 carbon atoms, such as methyl, ethyl, n-propyl,
isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, sec-pentyl, isopentyl, neopentyl, cyclopentyl, n-hexyl, isohexyl or cyclohexyl.
The alkenyl group is preferably a straight chain, branched chain or cyclic alkenyl group containing 2 to
6 carbon atoms, such as allyl, isopropenyl, isobutenyl,
2-pentenyl or 2-hexenyl.
The alkynyl group is preferably an alkynyl group containing 2 to 6 carbon atoms, such as propargyl, 2-butynyl, 3-butynyl, 3-pentynyl or 3-hexynyl.
The aryl group is preferably an aryl group
containing 6 to 14 carbon atoms, such as phenyl, naphthyl, biphenylyl or anthryl.
The aralkyl group is preferably an aralkyl group containing 7 to 19 carbon atoms, such as benzyl, phenethyl, phenylpropyl, biphenylylmethyl, benzhydryl or trityl.
The above-mentioned heterocyclic group is, for example, a 3 to 8 membered heterocyclic group,
preferably a 5 or 6 membered heterocyclic group containing 1 to 4 hetero atoms such as nitrogen atom (which may be in an oxide form), oxygen atom or sulfur atom (which may be in a mono- or di-oxide form), or a fused ring group thereof, preferably a fused ring group of said 5 or 6 membered heterocyclic group with 5 or 6 membered ring which may contain 1 to 4 hetero atoms of nitrogen atom (which may be in an oxide form), oxygen atom or sulfur atom (which may be in a mono- or di=oxide form).
The examples of the heterocyclic group include 1- or 2-aziridinyl, 1- or 2-azirinyl, 2- or 3-azetyl, 1-, 2- or 3-azetidinyl, 1-, 2-, 3- or 4-perhydroazepinyl, 1-, 2-, 3-, 4- or 5-perhydroazocinyl, 2- or 3-pyrrolyl, 3-, 4- or 5-pyrazolyl, 2-, 4- or 5-imidazolyl, 1,2,3-triazol-4-yl, 1,2,4-triazol-3-yl, 1H- or 2H- tetrazol-5-yl, 2- or 3-furyl, 2- or 3-thienyl, 2- or 3-thienyl-1,1-dioxide, 2-, 4- or 5-oxazolyl, 3- ,4- or 5-isoxazolyl, 1,2,3-oxadiazol-4 or 5-yl, 1,2,4-oxadiazol-3 or 5-yl, 1,2,5-oxadiazol-3 or 4-yl, 1,3,4-oxadiazol-2 or 5-yl 2-, 4- or 5-thiazolyl, 3-, 4- or 5-isothiazolyl, 1,2,3-thiadiazol-4 or 5-yl, 1,2,4-thiadiazol-3 or 5-yl, 1,2,5-thiadiazol-3 or 4-yl, 1,3,4-thiadiazol-2 or 5-yl, 2- or 3-pyrrolidinyl, 2-, 3- or 4-pyridyl, 2-, 3- or 4-pyridyl-N-oxide, 3- or 4-pyridazinyl, 3- or 4-pyridazinyl-N-oxide, 2-, 4- or 5-pyrimidinyl, 2-, 4- or 5-pyrimidinyl-N-oxide, pyrazinyl, 2-, 3- or 4-piperidinyl, piperazinyl, 3H-indol-2 or 3-yl, 2-, 3- or 4-pyranyl, 2-, 3- or 4-thiopyranyl, 2-, 3- or 4-thiopyranyl-1,1-dioxide, benzopyranyl, 3-, 4-, 5-, 6-, 1 - or 8-quinolyl, pyrido[2,3-d]pyrimidinyl (e.g.,
pyrido[2,3-d]pyrimidin-2-yl), 1,5-, 1,6-, 1,7-, 1,8-, 2,6- or 2,7-naphthyridinyl (e.g., 1,5-naphthyridin-2 or 3-yl), thieno[2,3-d]pyridyl (e.g., thieno[2,3-d]pyridin-3-yl), pyrazinoquinolyl (e.g., pyrazinof 2,3-d]quinolin-2-yl) and chromenyl (e.g., 2H-chromen-2 or 3-yl). The above-mentioned acyl group is an acyl group derived from an organic carboxylic acid, such as an alkanoyl group preferably containing 1 to 7 carbon atoms (for example, formyl, acetyl, propionyl, butyryl, isobutyryl, pentanoyl, hexanoyl or heptanoyl), an arylcarbonyl group preferably containing 6 to 14 carbon atoms (for example, benzoyl or naphthalenecarbonyl), an alkoxycarbonyl group preferably containing 1 to 6 carbon atoms (for example, methoxycarbonyl,
ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, sec-butoxycarbonyl or tert-butoxycarbonyl), an aryloxy carbonyl group preferably containing 6 to 14 carbon atoms (for
example, phenoxycarbonyl), an aralkylcarbonyl group preferably containing 7 to 19 carbon atoms (for
example, benzylcarbonyl, phenethylcarbonyl,
phenylpropylcarbonyl, benzhydrylcarbonyl or
naphthylethylcarbonyl), a 5 or 6 membered heterocyclecarbonyl group preferably containing 1 to 4 hetero atoms such as nitrogen atom (which may be oxidized), oxygen atom or sulfur atom (which may be mono- or di-oxidized) in the heterocycle, such as, 2-, 3- or 4-pyrrolylcarbonyl, 3-, 4- or 5-pyrazolylcarbonyl, 2 - , 4- or 5-imidazolylcarbonyl, 1,2,3-triazol-4-ylcarbonyl, 1,2,4-triazol-3-yl-carbonyl, 1H- or 2H-tetrazol-5-ylcarbonyl, 2- or 3-furylcarbonyl, 2- or 3-thienylcarbonyl, 2-,4- or 5-oxazolylcarbonyl, 3-, 4- or 5-isoxazolylcarbonyl, 1,2,3-oxadiazol-4 or 5-ylcarbonyl, 1,2,4-oxadiazol-3 or 5-ylcarbonyl, 1,2,5-oxadiazol-3 or 4-ylcarbonyl, 1,3,4-oxadiazol-2- or 5-ylcarbonyl, 2-, 4- or 5-thiazolylcarbonyl, 3-, 4- or 5- isothiazolylcarbonyl, 1,2,3-thiadiazol-4 or 5-ylcarbonyl, 1,2,4-thiadiazol-3 or 5-ylcarbonyl, 1,2,5- thiadiazol-3 or 4-ylcarbonyl, 1,3,4-thiadiazol-2 or 5- ylcarbonyl, 2- or 3-pyrrolidinylcarbonyl, 2-, 3- or 4- pyridylcarbonyl, 2-, 3- or 4-pyridyl-N-oxide-carbonyl, 3- or 4-pyridazinylcarbonyl, 3- or 4-pyridazinyl-N-oxide-carbonyl, 2-, 4- or 5-pyrimidinylcarbonyl, 2-,4- or 5-pyrimidinyl-N-oxide-carbonyl, pyrazinylcarbonyl, 2-, 3- or 4-piperidinylcarbonyl, piperazinylcarbonyl, 3H-indol-2 or 3-ylcarbonyl, 2-, 3- or 4-pyranylcarbonyl, 2- ,3- or 4-thiopyranylcarbonyl, 3-,4-,5-, 6-, 7- or 8-quinolylcarbonyl, pyrido[2,3-d]pyrimidinylcarbonyl (e.g., pyrido[2,3-d]pyrimidin-2-ylcarbonyl), 1,5-, 1,6-, 1,7-, 1,8-, 2,6- or 2,7- naphthyridinylcarbonyl
(e.g., 1,5-naphthyridin-2 or 3-ylcarbonyl), thieno[2,3-d]pyridylcarbonyl (e.g., thieno[2,3-d]pyridin-3-yl-carbonyl), pyrazinoquinolylcarbonyl (e.g.,
pyrazino[2,3-b]quinolin-2-ylcarbonyl), or
chromenylcarbonyl (e.g., 2H-chromen-2 or 3-ylcarbonyl); or a 5 or 6 membered heterocycle-acetyl group,
preferably containing 1 to 4 hetero atoms such as nitrogen atom (which may be oxidized), oxygen atom or sulfur atom (which may be mono- or di-oxidized) in the heterocycle, such as 2-pyrrolylacetyl, 3-imidazolylacetyl or 5-isoxazolylacetyl.
The group of the formula -T-Q0 includes an
alkyloxy, alkenyloxy, aryloxy, aralkyloxy,
heterocyclyloxy, acyloxy, alkylthio, alkenylthio, arylthio, aralkylthio, heterocyclylthio, acylthio, alkyldithio, aryldithio, aralkyldithio, alkylsulfinyl, alkenylsulfinyl, arylsulfinyl, aralkylsulfinyl,
heterocyclylsulfinyl, alkylsulfonyl, alkenylsulfonyl, arylsulfonyl, aralkylsulfonyl and heterocyclylsulfonyl groups.
Here, the alkyloxy group means a straight chain, branched chain or cyclic alkyloxy group preferably containing 1 to 6 carbon atoms, such as methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, n-pentyloxy, sec-pentyloxy, isopentyloxy, neopentyloxy, cyclopentyloxy, n-hexyloxy, isohexyloxy or cyclohexyloxy. The alkenyloxy group means a straight chain, branched chain or cyclic alkenyloxy group preferably containing 2 to 6 carbon atoms, such as allyloxy, isopropenyloxy, 1-butenyloxy, 2-pentenyloxy or 2-hexenyloxy. The aryloxy group menas an aryloxy group preferably containing 6 to 14 carbon atoms, such as phenoxy, naphthyloxy or biphenylyloxy. The aralkyloxy group means an aralkyloxy group
preferably containing 7 to 19 carbon atoms, such as benzyloxy, phenethyloxy or phenylpropyloxy.
The heterocyclyloxy group means a group of the formula T'-O- (T' is the heterocyclic group as
mentioned above), such as 2- or 3-pyrrolyloxy, 3- ,4- or 5-pyrazolyloxy, 2-,4- or 5-imidazolyloxy, 1,2,3-triazol-4-yloxy, 1,2,4-triazol-3-yloxy, 1H- or 2H-tetrazol-5-yloxy, 2- or 3-furyloxy, 2- or 3-thienyloxy, 2- or 3-thienyloxy-1,1-dioxide or 2-, 4- or 5-oxazolyloxy. The acyloxy group means a group of the formula T"-O- (T" is the acyl group as mentioned above), such as acetoxy, propionyloxy, butyryloxy, pentanoyloxy, hexanoyloxy, benzylcarbonyloxy,
phenethylcarbonyloxy, benzoyloxy, naphthoyloxy, thienylcarbonyloxy or benzothienylcarbonyloxy. The alkylthio group means a straight chain, branched chain or cyclic alkylthio group preferably containing 1 to 6 carbon atoms, such as methylthio, ethylthio, n- propylthio, isopropylthio, n-butylthio, isobutylthio, sec-butylthio, tert-butylthio, n-pentylthio, sec-pentylthio, isopentylthio, neopentylthio,
cyclopentylthio, n-hexylthio, isohexylthio or
cyclohexylthio. The alkenylthio group means a straight chain, branched chain or cyclic alkenylthio group preferably containing 2 to 6 carbon atoms, such as allylthio, isopropenylthio, 1-butenylthio, 2-pentenylthio or 2-hexenylthio.
The arylthio group means an arylthio group preferably containing 6 to 14 carbon atoms, such as phenylthio, naphthylthio or biphenylylthio. The aralkylthio group means an aralkylthio group preferably containing 7 to 19 carbon atoms, such as benzylthio, phenethylthio or phenylpropylthio. The heterocyclethio group means a group of the formula T'-S- (T' denotes a heterocyclic group as mentioned above), such as 2- or 3-pyrrolylthio, 3-, 4- or 5-pyrazolylthio, 2-,4- or 5-imidazolylthio, 1,2,3-triazol-4-ylthio, 1,2,4-triazol5-ylthio 1H- or 2H-tetrazol-5-ylthio, 2- or 3-furylthio, 2- or 3-thienylthio, 2- or 3-thienylthio¬
1,1-dioxide, 2-,4- or 5-oxazolylthio or the like. The acylthio group means a group of the formula T"-S- (T" is an acyl group as mentioned above), such as
acetylthio, propionylthio, butyrylthio, pentanoylthio, hexanolylthio, benzylcarbonylthio,
phenethylcarbonylthio, benzoylthio, naphthoylthio, thienylcarbonylthio or benzothienylcarbonylthio. The alkyldithio group means a straight chain, branched chain or cyclic alkyldithio group preferably containing 1 to 6 carbon atoms, such as methyldithio, ethyldithio, n-propyldithio or cyclopentyldithio.
The aryldithio group means an aryldithio group preferably containing 6 to 14 carbon atoms, such as phenyldithio, naphthyldithio or biphenylyldithio. The aralkyldithio group means an aralkyldithio group preferably containing 7 to 19 carbon atoms, such as benzyldithio or phenethyldithio. The alkylsulfinyl group means a straight chain, branched chain or cyclic alkylsulfinyl group preferably containing 1 to 6 carbon atoms, such as methylsulfinyl, ethylsulfinyl, n-propylsulfinyl, isopropylsulfinyl, n-hexylsulfinyl or cyclohexylsulfinyl. The alkenylsulfinyl group means a straight chain, branched chain or cyclic
alkenylsulfinyl group preferably containing 2 to 6 carbon atoms such as alkylsulfinyl . The arylsulfinyl group means an arylsulfinyl group preferably containing 6 to 14 carbon atoms such as phenylsulfinyl . The aralkylsulfinyl group means an aralkylsulfinyl group preferably containing 7 to 19 carbon atoms, such as benzylsulfinyl; the heterocyclylsulfinyl group means a group of the formula T'-SO- (T' denotes the
heterocyclic group as mentioned above), such as 2- or 3-pyrrolylsulfinyl or 3-, 4- or 5-pyrazolylsulfinyl. The alkylsulfonyl group means a straight chain,
branched chain or cyclic alkylsulfonyl group preferably containing 1 to 6 carbon atoms, such as methylsulfonyl, ethylsulfonyl, n-propylsulfonyl, isopropylsulfonyl or cyclohexylsulfonyl. The alkenylsulfonyl group means a straight chain, branched chain or cyclic
alkenylsulfonyl group preferably containing 2 to 6 carbon atoms, such as allylsulfonyl. The arylsulfonyl group means an arylsulfonyl group preferably containing 6 to 14 carbon atoms, such as phenylsulfonyl,
naphthylsulfonyl or biphenylylsulfonyl. The
aralkylsulfonyl group means an aralkylsulfonyl group preferably containing 7 to 19 carbon atoms, such as benzylsulfonyl, phenethylsulfonyl or
phenylpropylsulfonyl. The heterocyclylsulfonyl group means a group of the formula T'-SO2- (T' is the
heterocyclic group as mentioned above), such as 2- or 3-pyrrolylsulfonyl or 3-, 4- or 5-pyrazolylsulfonyl.
The group of the formula
Figure imgf000028_0001
includes (1) an alkylamino group, preferably, a mono- or di-alkylamino group containing 1 to 6 carbon atoms in each alkyl, such as methylamino, ethylamino, n- propylamino, n-butylamino, tert-butylamino, n- pentylamino, n-hexylamino, dimethylamino, diethylamino, methylethylamino, di-(n-propyl)amino or di-(n-butyl)- amino; (2) a cycloalkylamino group, preferably, a mono- or di-cycloalkylamino group containing 3 to 6 carbon atoms in each cycloalkyl, such as cyclopropylamino, cyclopentylamino, cyclohexylamino or dicyclohexylamino; (3) an arylamino group preferably containing 6 to 14 carbon atoms, such as anilino or N-methylanilino; (4) an aralkylamino group preferably containing 7 to 19 carbon atoms, such as benzylamino, 1-phenylethylamino, 2-phenylethylamino, benzhydrylamino or tritylamino; (5) an acylamino group of the formula T"-NH- or (T")2N- (T" is the acyl group as mentioned above, and the two T" groups may form a ring together with the nitrogen atom), for example, an alkylcarbonylamino group, an arylcarbonylamino group or a heterocyclylcarbonylamino group (here, the alkyl, aryl and heterocyclic groups are preferably the same as those mentioned above), such as acetamido, propionamido, butyrylamino,
pentanoylamino, hexanoylamino, succinimido,
benzylcarbonylamino (benzylcarboxamido),
phenethylcarbonylamino (phenethylcarboxamido),
benzoylamino (benzamido), naphthoylamino, phthalimido, thienylcarbonylamino (thienylcarboxamido) or
benzothienylcarbonylamino (benzothienylcarboxamido) and (6) a cyclic imido group. Here, both Q1 and Q2 may be combined with the adjacent nitrogen atom to form a ring, preferably 3 to 7 membered ring such as
pyrrolidino, piperidino, morpholino, piperazino, aziridino or azetidino.
The group of the formula
Figure imgf000029_0001
includes (1) a mono- or di-alkylsulfamoyl group
preferably containing 1 to 6 carbon atoms in each alkyl, such as methylsulfamoyl, ethylsulfamoyl, n-propylsulfamoyl, n-hexylsulfamoyl, dimethylsulfamoyl, diethylsulfamoyl, methylethylsulfamoyl or di-(n-butyl)sulfamoyl; (2) a cycloalkylsulfamoyl group preferably containing 3 to 6 carbon atoms, such as cyclopropylsulfamoyl or cyclohexylsulfamoyl; (3) an arylsulfamoyl group preferably containing 6 to 14 carbon atoms, such as phenylsulfamoyl; (4) an
aralkylsulfamoyl preferably containing 7 to 19 carbon atoms, such as benzylsulfamoyl, 1-phenylethylsulfamoyl, 2-phenylethylsulfamoyl, benzhydrylsulfamoyl or
tritylsulfamoyl; and (5) an acylsulfamoyl group of the formula T"-NHSO2- or (T")2N-SO2- (T" is the acyl group as mentioned above), such as acetylsulfamoyl,
benzylcarbonylsulfamoyl or thienylcarbonylsufamoyl.
Here, both Q1 and Q2 may be combined with the adjacent nitrogen atom to form a ring such as pyrrolidino or piperidino.
The group of the formula Q2-SO2-O- includes (1) an alkylsulfonyloxy group preferably containing 1 to 6 carbon atoms, such as methanesulfonyloxy or
ethanesulfonyloxy; (2) an arylsulfonyloxy group
preferably containing 6 to 14 carbon atoms such as benzenesulfonyloxy or p-toluenesulfonyloxy; (3) an aralkylsulfonyloxy group preferably containing 7 to 19 carbon atoms, such as benzylsulfonyloxy or
phenethylsulfonyloxy; and (4) an acylsulfonyloxy group such as acetylsulfonyloxy or butyrylsulfonyloxy.
The above mentioned alkyl, alkyloxy (or alkoxy), alkylthio, alkyldithio, alkylsulfinyl, alkylsulfonyl, alkylamino, cycloalkylamino, alkenyl, alkenyloxy, alkenylthio, alkenyldithio, alkenylsulfinyl,
alkenylsulfonyl, alkynyl, alkoxycarbonyl, alkanoyl and alkylsulfonyloxy groups may be further substituted by one to five of alkylthio group (for example, a straight chain or branched chain alkylthio group containing 1 to 4 carbon atoms, such as methylthio, ethylthio, n-propylthio or isobutylthio), a halogen atom (for exaaple, fluorine, chlorine, bromine or iodine), an alkoxy group (for example, a straight chain or branched chain alkoxy group containing 1 to 6 carbon atoms, such as methoxy, ethoxy, n-propoxy, tert-butoxy or n-hexyloxy), nitro, an alkoxycarbonyl group (for example, an alkoxycarbonyl group containing 1 to 6 carbon atoms in the alkoxy moiety, such as methoxycarbonyl,
ethoxycarbonyl, n-propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, sec-butoxycarbonyl or tert-butoxycarbonyl), or an alkylamino group (for example, mono- or di-(C1-6 alkyl) amino group, such as methylamino, ethylamino, n-propylamino, n-butylamino, tert-butylamino, n-pentylamino, n-hexylamino,
dimethylamino, diethylamino, methylethylamino, di-(n-propyl) amino or di-(n-butyl)amino).
In case where any of the above mentioned groups is substituted by two alkoxy groups, these alkoxy groups may be combined to form alkylenedioxy group containing 1 to 3 carbon atoms, such as methylenedioxy,
ethylenedioxy or propylenedioxy, or alkylidenedioxy containing 2 to 6 carbon atoms, such as
ethylidenedioxy, propylidenedioxy or
isopropylidenedioxy.
The above-mentioned aryl, aryloxy,
aryloxycarbonyl, arylcarbonyl, arylthio, aryldithio, arylsulfinyl, arylsulfonyl, arylamino, aralkyl,
aralkyloxy, aralkyloxycarbonyl, aralkylthio,
aralkyldithio, aralkylsulfinyl, aralkylsulfonyl, aralkylamino, aralkylcarbonyl, arylsulfonyloxy, and aralkylsulfonyloxy groups may be further substituted on their aromatic ring by one to three of alkyl, alkenyl, alkynyl, alkoxy, acyl, acyloxy, nitro, cyano, halogen, acylamino or alkylthio. Here, the same alkyl, alkenyl, alkynyl, alkoxy, acyl, acyloxy, acylamino or alkylthio group or halogen atom as mentioned above are used.
In case of being substituted by two alkyl groups adjacent to each other, these groups may be combined to form a bivalent group such as trimethylene or
teteramethylene and in case of being substituted by two alkenyl groups adjacent to each other, they may be combined to form a bivalent group such as propenylene, 1-butenylene, 2-butenylene or butadienylene, in which case the resulting bivalent group makes an additional 5 or 6 membered alicyclic ring (e.g. cyclopentane, cyclohexane, cyclohexadiene), aromatic ring (e.g.
benzene), or 5 or 6 membered heterocyclic ring on the fused hetrocyclic group.
The above mentioned heterocyclyloxy,
heterocyclylthio, heterocyclylsulfinyl,
heterocyclecarbonyl and heterocyclylsulfonyl groups may be substituted on their heterocyclic group by one to three of the above mentioned alkyl, alkenyl, alkynyl, aryl, aralkyl, alkanoyl, arylcarbonyl, alkoxycarbonyl, aryloxycarbonyl, aralkylcarbonyl, nitro, amino,
hydroxyl, cyano, sulfamoyl or mercapto group or a halogen atom (for example, fluorine, chlorine, bromine, iodine).
Preferred examples of the substituent in the fused heterocyclic group having a nitrogen atom in the bridgehead represented by Q include, among others, (1) an alkyl (preferably, a C1-6 alkyl group), alkoxy
(preferably, a C1-6 alkoxy group) or alkylthio group (preferably, a C1-6 alkylthio group), each of which may be substituted with 1 to 5, the same or different, halogen atoms (e.g. fluorine, chlorine, bromine, etc.), (2) a halogen atom (e.g. fluorine, chlorine, bromine, etc.), (3) a dialkylamino group (preferably, a di-C1-6 alkylamino), (4) an alkyl (preferably, a C1-6 alkyl), alkoxy (preferably, a C1-6 alkoxy group) or alkylthio group (preferably, a C1-6 alkylthio group), each of which may be substituted with 1 to 3, the same or different alkoxy groups (preferably a C1-6 alkoxy group) and/or alkylthio groups (preferably, a C1-6 alkylthio group), (5) a 3 to 6 membered heterocyclic group containing 1 to 4 hetero atoms selected from the group consisting of nitrogen atom, oxygen atom and sulfur atom, which may be substituted with 1 to 3, the same or different alkyl groups (preferably, C1-6 alkyl group), (e.g. pyrrolidino, piperidino, morphorino, piperazino, aziridino, azetidino, pyrazolyl, imidazolyl, furyl, pyrrolyl, pyridyl, pyrazinyl, etc.) and so on.
The particularly preferred examples include (1) a C1-6 alkyl, C1-6 alkoxy or C1-6 alkylthio group, which may be substituted with 1 to 5, the same or different, halogen (especially, fluorine, etc.) (2) chlorine, (3) a di C1-3 alkylamino group, (4) a C1-6 alkyl, C1-6 alkoxy or C1-6 alkylthio group, which may be substituted with 1 to 3, the same or different, C1-6 alkoxy groups and/or C1-6 alkylthio groups, (5) a 5 to 6 membered nitrogencontaining heterocyclic group which may be substituted with a C1-6 alkyl group, (especially, pyrroridino, pyrazolyl, etc.).
Q is, preferably, a group represented by the formula:
Figure imgf000033_0001
wherein Z0 is 1) a hydrogen atom, 2) a halogen atom, 3) a lower alkyl, lower alkoxy, lower alkylthio, lower alkylsulfinyl, lower alkylsulfonyl or mono- or di-lower alkylamino group, each of which may be substituted with 1 to 5 halogen atoms, 4) a lower alkoxy-alkyl, lower alkoxy-lower alkoxy or lower alkoxy-lower alkylthio group, each of which may be substituted with 1 to 5 halogen atoms; Z1 and Z2 each are 1) a hydrogen atom, 2) a halogen atom or 3) a lower alkyl group which may be substituted with 1 to 5 halogen atoms; Z3 and Z4 each are 1) hydrogen atom, 2) a halogen atom, 3) a lower alkyl, lower alkoxy, lower alkylthio or mono- or di-lower alkylamino group, each of which may be substituted with 1 to 5 halogen atoms .
As the "lower alkyl" in a lower alkyl group, a lower alkylthio group, a lower alkylsulfonyl group, a lower alkylsulfonyl group and a mono- or di-lower alkylamino group are used an alkyl group having 1 to 6 carbon atoms (e.g. methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, etc.).
As the "lower alkoxy" in a lower alkoxy group, a lower alkoxy-lower alkyl group, a lower alkoxy-lower alkoxy group and a lower alkoxy-lower alkylthio group are used an alkoxy group having 1 to 6 carbon atoms (e.g. methoxy, ethoxy, propoxy, isopropoxy, butoxy, etc.).
The halogen atom used here is for example, fluorine, chlorine, bromine, etc.
W is O or S and preferably, O.
R1 and R2 each are hydrogen atom or a hydrocarbon group which may be substituted.
As the hydrocarbon group and its substituent, there may be used the same alkyl, alkenyl, alkynyl, aryl and aralkyl group and those substituents as mentioned above. The preferred examples of the hydrocarbon group include an alkyl group, an alkenyl group or an alkynyl group.
As R1 and R2, an alkyl group, an alkenyl group or an alkynyl group, which may be substituted with 1 to 5 halogen atoms is particularly preferable. Examples of the alkyl group include, preferably, a straight chain, branched chain or cyclic alkyl group containing 1 to 6 carbon atoms such as methyl, ethyl, n-propyl,
isopropyl, cyclopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, cyclobutyl, n-pentyl, sec-pentyl,
isopentyl, neopentyl, cyclpentyl, n-hexyl, isohexyl, cyclohexyl, etc. Examples of the alkenyl group
includes preferably, a straight chain or branched chain alkenyl group having 2 to 4 carbon atoms such as allyl, 1-propenyl, 2-propenyl, 2-methylallyl, etc. Examples of the alkynyl group include preferably an alkynyl group containing 2 to 4 carbon atoms such as propargil, 1-propynyl, 2-butynyl, etc. The substituents halogen atoms include, for example, fluorine, chlorine,
bromine, etc.
More preferred R1 and R2 each are a lower alkyl group (for example, an alkyl group having 1 to 4 carbon atoms such as methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, etc.) or allyl group, etc. The most preferable one is ethyl.
Also R1 and R2, together with the adjacent
nitrogen atom, may form a nitrogen containing
heterocyclic group which may be substituted.
As the nitrogen containing heterocyclic group, there may be used a 4 to 8 membered, preferably 5 to 7 membered nitrogen containing heterocyclic group which may be constituted with 1 to 3 hetero atoms selected from a group consisting of nitrogen, oxygen and sulfur atoms other than at least one nitrogen atom and carbon atom, specifically, pyrrolidino, piperidino,
hexamethylenimino, morpholino, 4-methylpiperazino, 1-pyrrolyl, 1-pyrazolyl, 1-imidazolyl, 1H-1, 2, 3-triazol-1-yl, 1H-1, 2, 4-triazol-1-yl, 1H-tetrazol-1-yl, 1H-indol-1-yl, etc. Above all, pyrrolidino, piperidino, hexamethylenimino, morpholino, 4-methylpiperazino, etc. are preferable.
Examples of the substituent on the nitrogen containing heterocyclic group include those described for the substituents on the above-mentioned
heterocyclic group. Specifically, a lower alkyl (e.g. a C1-6 alkyl such as methyl, ethyl, etc.), a halogen atom (e.g. fluorine, chlorine, bromine, etc.) and the like are preferable.
In the case that R1 and R2 together with the adjacent nitrogen atom form a nitrogen containing heterocyclic group, R1 and R2 may preferably be
combined to form an alkylene chain. Examples of the alkylene chain include an alkylene chain having 3 to 7 carbon atoms, specifically, for example, propane-1, 3-diyl, butane-1, 4-diyl, pentane-1, 5-diyl, hexane-1, 6-diyl, heptane-1, 7-diyl, etc. Preferred examples of the substituent on the alkylene chain include a lower alkyl group (e.g. a C1-6 alkyl group such as methyl, ethyl, etc.), a halogen atom (e.g. fluorine, chlorine, bromine, etc.).
R3 is hydrogen atom, a halogen atom or a
hydrocarbon group which may be substituted. Examples of the halogen atom include fluorine, chlorine, bromine, etc. As the hydrocarbon group which may be substituted and its substituent, there may be used the same alkyl, alkenyl, alkynyl, aryl and aralkyl group and those substituents as mentioned above.
Particularly preferred examples of the hydrocarbon group include a substituted or unsubstituted alkyl (a C1-6 alkyl group such as methyl, ethyl, etc.). As the substituent of the hydrocarbon group, a halogen atom (e*g* fluorine, chlorine, bromine, etc.) and the like is particularly preferable.
More preferable R3 is hydrogen, a halogen atom (e.g. fluorine, chlorine, bromine, etc.), a C1-6 alkyl (e.g. methyl, ethyl, etc.) and the like.
The most preferred R3 is hydrogen. "n" is an integer of 0 to 2, preferably 1 or 2 and more
preferably 2.
"m" is 0 or 1 and preferably 0.
All the compounds obtained from the combination of the respective groups optionally selected from the symbols mentioned above are preferable and the
following compounds are particularly preferable.
(1) The compound (I) in which Q is a fused
heterocyclic group having a nitrogen atom in the bridgehead which may be substituted, W is O or S, R1 and R each are hydrogen atom or an alkyl group
(preferably, a C1-6 alkyl group) which may be
substituted with a halogen atom, etc., an alkenyl group (preferably a C2-6 alkenyl group) which may be
substituted with a halogen atom, etc., an alkynyl group (preferably, a C2-6 alkynyl group) which may be
substituted with a halogen atom, etc., R 1 and R2, combined together, form an alkylene group which may be substituted, R3 is hydrogen, a halogen atom or an alkyl group (preferably, a C1-6 alkyl group), n is an integer of 0 to 2 and m is 0 or 1.
(2) The compound (I) in which Q is a fused
heterocyclic group having a nitrogen atom in the bridgehead which may be substituted, W is O or S, R1 and R2 each are an alkyl group (preferably a C1-6 alkyl group), R3 is hydrogen atom, n is an integer of 0 to 2 and m is 0 or 1.
As the fused heterocyclic group having a nitrogen atom in the bridgehead which may be substituted which is represented by Q in the compounds for (1) and (2) mentioned above, there may be used a preferable fused heterocyclic group mentioned above, and the preferred substituents on the groups represented by the
respective symbols in the compounds for (1) and (2) may be selected from the substituents mentioned above. The compound (I) of the present invention can form an inorganic or organic base salt at an acidic group in the substituent such as sulfo or carboxyl in the molecule, or an inorganic or organic acid addition salt at a basic nitrogen atom in the molecule and a basic group in the substituent such as amino.
Examples of the inorganic base salts of the compounds (I) include the salt with a conventional base such as alkali metal such as sodium or potassium, an alkaline earth metal such as calcium, or ammonia.
Examples of the organic base salts of the compounds (I) include a conventional salt such as a salt with
dimethylamine, triethylamine, piperazine, pyrrolidine, piperidine, 2-phenylethylamine, benzylamine,
ethanolamine or diethanolamine.
Examples of the inorganic acid addition salts of the compounds (I) include a salt with a conventional acid such as the salt with hydrochloric acid,
hydrobromic acid, sulfuric acid, nitric acid or
phosphoric acid. Examples of the organic acid addition salts of the compounds (I) include a conventional salt with p-toluenesulfonic acid, methanesulfonic acid, formic acid or trifluoroacetic acid.
The compounds (I) or their salts of this invention can be used as agricultural chemicals such as
herbicidal agents, insecticidal agents and fungicidal agents in extremely high safety. Particularly, the compounds (I) or their salts exhibit in an extremely low application amount an excellent herbicidal effect against a broad range of weeds, for example, paddy weeds such as Echinochloa oryzicola, Cyperus difformis, Scirpus iuncoides, Monochoria vaginalis, Sagittaria pygmaea, Eleocharis acicularis, Cyperus serotinus.
Eleocharis kuroguwai, Alisma canaliculatum. Sagittaria trifolia. Scirpus wallichii, Lindernia procumbens,
Rotala indica, Potamogeton distinctus, Ludwiga prostrata or Flatine triandra, and field weeds, such as Digitaria adscendens, Setaria viridis, Amaranthus viridis, Abutilon theophrasti. Chenopodium album.
Polygonum longisetum, Portulaca oleracea, Sida spinosa, Datura stramonium, Ipomoea purpurea, Xanthium
strumarium, Echinochloa crus-galli, Panicum
dichotaomiflorum, Sorghum halepense, Cyperus rotundus. Avena fatua. Alopecurus myosuroides, Bromus tectorum, Stellaria media, Brassica Sp., Cassia obtusifolia, Matricaria chamomilla or Commelina communis. Moreover, they exhibit substantially no culture damage on crops such as rice, wheat, barley, corn, soybean, etc. and show a high grade of safety.
The compounds (I) or their salts exhibit an excellent herbicidal effect selectively on various weeds only, and not on culture crops, and are only slightly toxic to mammals, fishes and shellfishes.
Therefore, they can be used as herbicides for paddy fields, fields (farm field), orchards or non-farming land, in extremely high safety, without polluting the environment. Particularly, the compounds (I) or their salts are useful as a herbicide for paddy fields.
The compounds (I) or their salts of this invention also exhibit an excellent fungicidal effect and are useful as fungicidal agents against late blight of tomato, potato, etc., downy mildew of cucumber, grape, etc.
The compounds (I) or their salts of this invention can be used as an agricultural chemical, particularly, herbicide in any application form suited for general agricultural chemicals. That is, one, or more than two kinds of the compounds (I) or their salts are used in the form of preparation such as emulsifiable
concentrates, oil solution, sprays, wettable powders, dusts, DL(Driftless)-type dusts, granules, fine
granules, fine granules F, tablets or the like, according to the purpose of use, by dissolving or dispersing them in suitable liquid carriers or mixing them with or adsorbing them on suitable solid carriers. These preparations may contain, if necessary,
emulsifying agent, suspending agent, spreading agent, penetrating agent, wetting agent, thickening agent, stabilizer, etc., and can be prepared by any
conventional method known per se., e.g. mixing each ingredient.
Suitable examples of the liquid carriers
(solvents), include solvents such as water, alcohols (for example, methanol, ethanol, 1-propanol, 2-propanol or ethylene gylcol), ketones (for example, acetone or methyl ethyl ketone), ethers (for example, dioxane, tetrahydrofuran, ethylene glycol mono-methyl ether, diethylene glycol monomethyl ether or propylene glycol monomethyl ether), aliphatic hydrocarbons (for example, kerosene, kerosene oil, fuel oil or machine oil), aromatic hydrocarbons (for example, benzene, toluene, xylene, solvent naphtha or methylnaphthalene),
halogenated hydrocarbons (for example, dichloromethane, chloroform or carbon tetrachloride), acid amides (for example, dimethylformamide or dimethylacetamide), esters (for example, ethyl acetate, butyl acetate or fatty acid glycerol ester) or nitriles (for example, acetonitrile or propionitrile). These solvents are used individually or as a suitable mixture of two, or more, of them.
Suitable examples of the solid carriers (diluents or dust carrier) include vegetable powder (for example, soy-bean meal, tobacco meal, wheat flour or wood flour), mineral powders (for example, clays such as kaolin, bentonite, or acid clay, talcs such as talc powder or pyrophyllite powder), silicas (for example, diatomaceous earth or mica powder), aluminas, sulfur powder or active carbon. They are used individually or as a suitable mixture of two, more of them.
The liquid carriers or solid carriers as mentioned above may be used in rate of about 1 to 99 wt%, preferably about 1 to 80 wt% of the whole preparation usually.
As surface active agents used as the emulsifying agent, spreading agent, penetrating agent or dispersing agent, nonionic or anionic surface active agents such as soaps; polyoxyethylene alkylaryl ethers (e.g. Noigen EA 142® from Dai-ichi Kogyo Seiyaku K.K., Japan);
polyoxyethylene aryl esters (e.g. Nornal® from Toho Chemical K.K., Japan); alkyl-sulfates (e.g. Emal 10® from Kao Soap K.K., Japan); alkyl and Emal 40®
sulfonates (e.g. Neogen® and Neogen T® from Dai-ichi Kogyo Seiyaku Co. and Neopelex® from Kao Soap K.K.); polyethylene glycol ethers (e.g. Nonipol 85®, Nonipol 100®, Nonipol 160® from Sanyo Kasei K.K., Japan); or polyhydric alcohol esters (e.g. Tween 20® and Tween 80® from Kao Soap K.K.) are used, if necessary.
The surface active agent as mentioned above may be used in rate of about 0.1 to 50 wt%, preferably, about 0.1 to 25 wt% of the whole preparaiton, usually.
The concentration of the compound (I) or a salt thereof contained in an herbicidal preparation is about 1 to 90% by weight in the case of emulsifiable
concentrates or wettable powders, about 0.01 to 10% by weight in the case of oil solution, dusts or DL-type dusts and about 0.05 to 10% by weight in the case of fine granules F or granules. However, such
concentration may vary, depending on the purpose of use. For example, emulsifiable concentrates, wettable powders or the like can be suitably diluted or extended (for example, to 100 to 100000 times) with water or the like, on the occasion of use, and then applied.
When the compound (I) or a salt thereof is used as herbicide, its amount may also vary depending on the place, the season and the method of application, the kinds of target weeds, the kinds of culture crops, and so on. However, an active ingredient (the compound (I) or its salt thereof) is used in general, in an amount of about 0.05 to 50 g, preferably about 0.1 to 10 g, per are of paddy field and in an amount of about 0.05 to 50 g, preferably about 0.1 to 10 g, per are of field.
For paddy field weeds, it is suitable to use the compound (I) or a salt thereof in the soil treatment before emergence or in the foliar and soil treatment.
For example, the herbicidal preparation of this invention can safely be used just after the rice-planting or even 2 to 3 weeks after the planting without revealing any injury on the rice-plant, and its effect continues for a long period of time.
The agricultural chemicals (particularly,
herbicidal preparation) containing the compound (I) or a salt thereof of this invention can be used, as occasion demands, in combination with or as an
admixture with other herbicidal agents, plant-growth regulating agents, fungicidal agents (for example, organochlorine series fungicide, organosulfur series fungicide or azole series fungicide, antibiotics), insecticidal agent (for example, pyrethroid series insecticide, organophosphorus series insecticide or carbamate series insecticide), and also with miticide, nematocide, synergist, attractant, repellent, dyestuff, fertilizer and the like. Examples of suitable
herbicidal agents include (1) sulfonylurea herbicides [e.g. bensulfuron-methyl, pyrazosulfuron-ethyl, imazosulfuron, sulfosulfuron, cinosulfuron,
azimsulfuron, halosulfuron, ethoxysulfuron, 1-(2- (cyclopropylcarbonyl)phenylsulfamoyl)-3-(4,6- dimethoxypyrimidin-2-yl)urea, etc.], (2) pyrazole herbicides [e.g. pyrazolate, pyrazoxyfen, benzofenap, etc.], (3) carbamate herbicides [e.g. benthiocarb, molinate, esprocarb, pyributicarb, dimepiperate, swep, etc.], (4) chloroacetanilide herbicides [e.g.
butachlor, pretilachlor, thenylchlor, etc.], (5) diphenylether herbicides [e,g. chlomethoxynil, bifenox, etc.], (6) triazine herbicides [e.g. simetryn,
dimethametryn, etc.], (7) phenoxycarboxylate herbicides [e.g. 2,4-PA, MCP, MCPB, phenothiol, etc.], (8)
carboxamide or urea herbicides [e.g. mefenacet,
clomeprop, naproanilide, bromobutide, daimuron, cumyluron, etobenzanid, 3-(1-(3,5-dichlorophenyl)-1-methylethyl)-2,3-dihydro-6-methyl-5-phenyl-4H-1,3-oxazin-4-one, etc.], (9) organic phosphate herbicides [e.g. piperophos, butamifos, anilofos, etc.], (10) other herbicides [bentazon, benfuresate, oxadiazon, oxadiargyl, pentoxazone, cyhalofop-butyl, cafenstrole, pyriminobac-methyl, bispyribac-sodium, 1-(2-chlorophenyl)-4-(N-cyclohexyl-N-ethylcarbamoyl)-5(4H)-tetrazolinone, 2-(2-(3-chlorophenyl)-2,3-epoxypropyl)-2-ethylindane-1,3-dione, ACN, etc.], etc.
The compound (I) or a salt thereof of this
invention can be used in a manner similar to that described above even when used as an insecticide or a fungicide.
The compound (I) or a salt thereof of this
invention is a new compound and can be prepared by known methods (for example, the process described in Japanese Unexamined Patent Publication No. 2149/1972) or by similar methods thereto.
More specifically, the compound (I) or a salt thereof can be prepared according to the following reaction schemata 1 to 3. Incidentally, as a salt of the compounds (II), (III), (IX), (I-a) and (I-b), the same as that of the compound (I) mentioned above is used.
Reaction schema 1
Figure imgf000044_0001
wherein the symbols are as defined above.
As a leaving group represented by X , there may be used, for example, a halogen atom (e.g. fluorine, chlorine, bromine, etc.) or a group represented by the formula:
-O-Q0, -S(O)k-Q0 or -O-SO2-Q0
wherein Q0 and k are as defined above, (for example, methylsulfonyloxy, trifluoromethylsulfonyloxy, p-toluenesulfonyloxy, benzenesulfonyloxy, etc.) and so on. Above all, a halogen atom is preferable and chlorine is particularly suitable.
In this reaction are usually used almost equimolar amount of the compounds (II) and (III) or salts
thereof . The reaction is performed in a solvent which does not hamper the reaction. Examples of suitable solvents, include an aromatic hydrocarbon such as benzene, toluene, etc., a halogenated hydrocarbon such as dichloromethane, chloroform, carbon tetrachloride, etc., an ether such as ethyl ether, isopropyl ether, dioxane, tetrahydrofuran (hereafter, abbreviated as THF), etc., a nitrile such as acetonitrile, etc., a ketone such as acetone, methyl ethyl ketone, etc., an ester such as ethyl acetate, butyl acetate, etc., or dimethylformamide (hereafter, abbreviated as DMF) or dimethylacetamide, or dimethylsulfoxide (hereafter, abbreviated as DMSO), etc., or a mixture thereof.
The reaction is generally accelerated by addition of a base. Examples of suitable bases include an organic base such as triethylamine, tri-n-propylamine, pyridine, 1, 8-diazabicyclo[5.4.0]undec-7-ene
(hereafter, abbreviated as DBU), 1,4- diazabicyclo[2.2.2]octane, 1,5-diazabicyclo[4.3.0]non-5-ene, etc., or an inorganic base such as sodium h ride, p assium hydroxide, potassium carbonate, s ium carbonate, sodium hydroxide, etc. The base may be usually used in an amount of about 0.01 to 3 moles per 1 mole of the compound (II). The reaction
temperature is usually about -10 to 150°C, preferably about 10 - 100°C. The reaction is completed within about 30 minutes to 20 hours, and its completion can be confirmed by means of thin-layer chromatography or high performance liquid chromatography, etc.
Reaction schema 2
Figure imgf000045_0001
wherein the symbols are as defined above.
As a leaving group represented by X1, a halogen atom (e.g. fluorine, chlorine, bromine, etc.) is particularly preferred.
In this reaction, the compound (II) or a salt thereof is reacted with more than 1 equimolar amount of the compounds (VIII) and (X) in turn in the two steps. The reaction is performed in a solvent which does not hamper the reaction. As the solvent, the same solvents as used for the reaction of Reaction schema 1 may be used. Preferred examples of the solvents are
chloroform, toluene, acetonitrile, THF, dioxane, etc., or the mixture thereof. The reaction is advantageously conducted in the presence of a base. As the base, one as used in the reaction of Reaction schema 1 may be used. Preferred examples of the bases are
triethylamine, pyridine, DBU, etc.
This reaction is performed in two steps. After isolation of the compound (IX) or a salt thereof from the reaction mixture obtained by the reaction of the compound (II) or a salt thereof with the compound
(VIII) in the first step, it can be reacted with the compound (X). Alternatively, without isolation of the compound (IX) and a salt thereof from the reaction mixture, the subsequent reaction in the second step can be effected by adding the compound (X) into the
reaction mixture.
In the reaction of the first step, the compound (VIII) is used in an amount of about 1 to 10 moles, preferably 1 to 3 moles per the compound (II) or a salt thereof. The reaction temperature is usually -10 to 150°C, preferably 20 to 120°C. The reaction is
completed within about 30 minutes to several days and its completion can be confirmed by thin-layer
chromatography or high performance liquid
chromatography and the like.
In the reaction of the second step, the compound (X) is used in an amount of about 1 to 10 moles, preferably 1 to 3 moles per the compound (II) or a salt thereof. The reaction temperature is usually -10 to 150°C, preferably 20 to 120°C. The reaction is completed within about 30 minutes to 20 hours. The completion of the reaction can be confirmed by thin- layer chromatography or high performance liquid
chromatography, etc.
Reaction schema 3
Figure imgf000047_0001
wherein p is 1 or 2, other symbols are as defined above.
In this reaction, the compound (I-b), namely the compound (I) in which n is 1 or 2, or a salt thereof is prepared by oxidizing the compound (I-a), namely the compound (IV) in which Y is the group represented by the formula:
Figure imgf000047_0002
wherein the symbols are as defined above (the compound is identical with the compound (I) in which n is O.) or a salt thereof with an oxidizing agent and the like. Examples of the oxidizing agent include hydrogen peroxide, potassium permanganate, peracetic acid, metachloroperbenzoic acid, sodium percarbonate, etc.
In this reaction, the oxidizing agent may be used suitably in an amount necessary for completing the reaction. It is, for production of the compound (I-b) in which p is 1, theoretically the amount generating an equivalent of active oxygen per 1 mole of the compound (I-a) or its salt used as the starting material and, for production of the compound (I-b) wherein p is 2, the amount generating 2 equivalents of active oxygen per 1 mole of the compound (I-a) or its salt used as the starting material. The reaction is generally conducted in a solvent which does not hamper the reaction. Suitable examples of the solvent include an inert solvent such as water, an alcohol, e.g. methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, tert-butyl alcohol, etc., an aromatic hydrocarbon, e.g. benzene, toluene, xylene, nitrobenzene, chlorobenzene, etc., a halogenated hydrocarbon, e.g. dichloromethane, 1, 2-dichloroethane, chloroform, carbon tetrachloride, etc., a ketone, e.g. acetone, etc., a nitrile e.g.
acetonitrile, etc., a carboxylic acid, e.g. acetic acid, trifluoroacetic acid, etc., DMF, etc. or a mixture thereof. The reaction temperature is usually -60 to 100°C, preferably -20 to 60°C The reaction time is 5 minutes to about 50 hours. The completion of the reaction can be confirmed by thin-layer chromatography or high performance liquid chromatography and the like.
When the compound (I) obtained by the above mentioned reaction has an acidic group such as sulfo or carboxyl in the molecule, it may be obtained as its salt with a base employed. In such case, it can be converted, if necessary, to the free form by addition of, for example, an inorganic acid such as hydrochloric acid, sulfuric acid, phosphoric acid, nitric acid and an organic acid such as formic acid, acetic acid, trifluoroacetic acid, p-toluenesulfonic acid. When the compound (I) is obtained in the free form, it can be converted to its base salt by addition of base
mentioned above. Also, since the compound (I) has a basic nitrogen atom, it may form its acid addition salt with an inorganic or organic acid mentioned above. In addition, when the compound (I) has a substituent which is a basic group such as amino, it may form its acid addition salt.
The compound (I) when obtained in the free form may be converted into its acid addition salt by addition of an inorganic or organic acid mentioned above according to conventional methods, and when obtained in the form of the acid addition salt, may be converted into its free form by addition of a base mentioned above.
The compound (I) or its salt thus obtained can be isolated and purified by a known procedure per se such as concentration, concentration under reduced pressure, extraction, phase transfer, crystallization,
recrystallization or chromatography and the like.
The compound (III) or its salt, and the compounds (VIII) and (X), which are used as the starting material of the processes of this invention, are known or can be easily prepared from known compounds.
The compound (III) or its salt can be prepared, for example, by the processes described in Yakugaku- Zasshi, 76, 968-970 (1956) (Chemical Abstracts 51, 2771 g), Rumanian Patent No. 62087 (1977) (Chemical
Abstracts 89, 42491d), Organic Syntheses Collective Volume (John Wiley and Sons, Inc., New York), 4, 307-310 (1963) or process corresponding thereto. The compound (VIII) is, for example, phosgen or thiophosgen and they are known compounds. The compound (X) is a usual secondary amine, etc. and known or prepared easily from known compounds.
The compound (I-a) is the same compound as the compound (I) in which n is O, and can be prepared from the compound (II) in which n is O (compound II-a) according to the reaction schemata 1 and 2 shown in the process for production of the compound (I) mentioned above.
The compound (II) or its salt is new and can be prepared by a method known per se (for example, methods described in Japanese Unexamined Patent Publication Nos. 2149/1972 and 58675/1982) or by similar process thereto.
Specifically, the compound (III) or its salt can be prepared according to the following reaction
schemata 4 to 5. Incidentally, as a salt of compounds (Il-a), (II-b), (II'), (V) and (VI), there may be used the same as those described above for the salt of the compound (I).
Reaction schema 4
Figure imgf000050_0001
wherein the symbols are as defined above.
In this reaction, the compound (Il-b), namely the compound (II) in which n is 1 or 2, or a salt thereof is prepared by oxidizing the compound (Il-a), namely the compound (IV) in which Y is hydrogen atom (also identical with the compound (II) in which n is O) or a salt thereof with an oxidizing agent and the like.
Examples of the oxidizing agent include hydrogen peroxide, potassium permanganate, peracetic acid, metachloroperbenzoic acid, sodium percarbonate, etc. Above all, sodium percarbonate is particularly
suitable.
In this reaction, the oxidizing agent may be used suitably in an amount necessary for completing the reaction. It is, for production of the compound (II-b) in which p is 1, theoretically the amount generating an equivalent of active oxygen per 1 mole of the compound (Il-a) or its salt used as the starting material and, for production of the compound (Il-b) in which p is 2, theoretically the amount generating 2 equivalents of active oxygen per 1 mole of the compound (II-a) or its salt used as the starting material. The reaction is performed in a solvent which does not hamper the reaction. Examples of the suitable solvents are an inert solvent such as water, an alcohol, e.g. methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, tert-butyl alcohol, etc., an aromatic hydrocarbon, e.g. benzene, toluene, xylene, nitrobenzene, chlorobenzene, etc., a halogenated hydrocarbon, e.g. dichloromethane, 1, 2-dichloroethane, chloroform, carbon tetrachloride, etc., a ketone, e.g. acetone, etc., a nitrile, e.g.
acetonitrile, etc., a carboxylic acid, e.g. acetic acid, trifluoro acetic acid, etc., DMF, etc., or a mixture thereof. The reaction temperature is usually -60 to 100°C, preferably -20 to 60°C. The reaction time is 5 minutes to about 50 hours. The completion of the reaction can be confirmed by means of thin-layer chromatography or high performance liquid
chromatography and the like.
Reaction schema 5
Figure imgf000051_0001
wherein the symbols are as defined above.
As the leaving group represented by X are used, for example, an halogen atom (e.g. fluorine, chlorine, bromine, iodine, etc.) or a group represented by the formula:
-O-Q0, -S (O)k-Q0 or -O-SO2-Q0
wherein Q0 and k are as defined above, (e.g.
methylsulfonyloxy, trifluoromethylsulfonyloxy, p-toluenesulfonyloxy, benzenesulfonyloxy, etc.). Above all, an halogen atom is preferable and chlorine is particularly preferable.
In this reaction, almost equimolar amount of the compounds (V) and (VI) or their salts are used. The reaction can be performed in a solvent which does not hamper the reaction. As the solvents are applicable the same ones as used for the reaction of Reaction schema 1 as well as an alcohol such as methanol, ethanol, 1-propanol, ete., water or a mixture thereof. Among them, preferred solvents are acetonitrile, acetone, methanol, DMF, etc., or a mixture thereof.
This reaction is usually accelerated by addition of a base. As the base, not only the same as those in the reaction of Reaction schema 1 but also an alkoxide such as sodium methoxide, sodium ethoxide, potassium tertbutoxide, etc. can be used. Above all preferred bases are sodium hydride, potassium carbonate, sodium
carbonate, sodium methaxide, potassium tert-butoxide, etc. The amount of the base used, the reaction
temperature, the time required for completion of the reaction, confirmation method for completion of the reaction and so on are the same as those for the reactions of Reaction schema 1.
The compound (II"), namely the compound (II) in which n and m each are O, or a salt thereof can be prepared according to the process in the following
Reaction schema 6. As the salt of the compounds (II") and (VII) can be used the same as those described above for the compound (I).
Reaction schema 6
Figure imgf000052_0001
wherein the symbols are as defined above.
In this reaction, the compound (VII) or a salt thereof and more than 1 mole equivalent of the compound (VI) or a salt thereof are usually reacted in the presence of a base and a halogenating agent. The reaction can be performed in a solvent which does not hamper the reaction. As the solvents are used the same as those mentioned for the reaction of Reaction schema 1 and an alcohol such as methanol, ethanol, 1-propanol, etc. or a mixture thereof. Above all, preferred solvents are methanol, ethanol, DMF, etc. and a mixture thereof.
In this reaction, first, the compound (VI) or its salt is reacted with a halogenating agent in the presence of a base to give a reactive intermediate of the formula:
Figure imgf000053_0001
wherein X3 is a halogen atom or a group represented by the formula:
Figure imgf000053_0002
and then without isolating the intermediate, the compound (VII) or a salt thereof can be added to the reaction mixture to react with the compound (XI).
As the halogen atom represented by X3, there may be used, for example, chlorine, bromine, iodine, etc.
Examples of the base used in this reaction include the some ones as those used in the reaction of Reaction schema 1 and an alkoxide such as sodium methoxide, sodium ethoxide, potassium tert-butoxide, etc. Among them, sodium methoxide, sodium ethoxide, sodium
hydride, etc. are preferable. The base may usually be used in an amount of 0.01 mole to 3 moles per 1 mole of the compound (VI).
Examples of the halogenating agent used in this reaction include an element of halogen, e.g. chlorine, bromine, iodine, etc., an N-haloimide, e.g. N- chlorosuccinimide, N-bromosuccinimide, N-iodosuccinimide, etc. or sulfuryl chloride, etc. The halogenating agent may be usually used in an amount of 1 mole to 3 moles per 1 mole of the compound (VI). The reaction temperature is usually about -80 to 160°C, preferably about -70 to 120°C. The reaction is
completed within about 30 minutes to 60 hours and its completion can be confirmed by means of thin-layer chromatography or high performance liquid
chromatography, etc. The compound (XI) produced by this reaction is new and a present reaction for
producing the compound (II) or a salt thereof is new as well.
The compound (II) or a salt thereof obtained by the reaction mentioned above can be isolated and purified by a known procedure per se such as
concentration, concentration under reduced pressure, extraction, phase transfer, crystallization,
recrystallization or chromatography in the same as those in case of the compound (I).
The compound (VI) or its salt, which is used as the starting material for the production of the
compound (II) is known or can be prepared easily from known compounds by the processes described in, for example, Organic Syntheses Collective Volume (John Wiley and Sons, Inc., New York) Vol. 5, 1070 - 1074 (1973) or the process corresponding thereto.
The compound (Il-a) is the same as the compound (II') or (II") which is identical with the compound (II) in which n is 0, and can be prepared according to the process for production of the compound (II) mentioned above, which is shown in Reaction schemata 5 and 6.
The compounds (V), (VII) and a salt thereof are known as mentioned below or can be prepared easily from the known compounds. The compounds (I), (II) and their salt of the present invention can be prepared by the processes shown in Reaction schemata 1 to 6 mentioned above and the substituent on the substituent Q in the compounds (I), (II) or their salt can be easily converted to another one as is shown in the following Reaction schemata 7 to 9.
All the reactions shown in Reaction schemata 7 to 9 are per se known, and can be carried out according to the method described in, for example, Japanese
Unexamined Patent Publication No. 38091/1989 or the similar methods thereof.
Reaction schema 7
Figure imgf000055_0001
wherein L and L each are a halogen atom or methylsulfonyl group, q is an integer of 0 or 1 and other symbols are as defined above.
Figure imgf000056_0001
wherein r is an integer of 1 or 2, other symbols are as defined above.
As the oxidizing agent are used the same ones as mentioned in the reactions of Reaction schemata 3 and 4.
Figure imgf000057_0001
wherein X4 is a halogen atom and other symbols are as defined above.
As the halogenating agent are used the same ones as mentioned in the reaction of Reaction schema 6.
Examples of the halogen atom defined as L0, L1 and X4 include fluorine, chlorine, bromine, etc. The compounds described in Reaction schemes 7 to 9
mentioned above may be employed in a form of a salt with a base or acid addition salt thereof.
The compounds (V), (VII) and their salts are known or can be easily prepared from the known compounds.
These compounds can be prepared by methods described in the Chemistry of Heterocyclic Compounds (Interscience Publishers) Vol. 15, Parts 1 and 2; ibid Vol. 30;
Comprehensive Heterocyclic Chemistry (Pergamon Press)
Vols. 4 and 5; Liebigs Annalen der Chemie Vol. 663, 113 to 117 (1963), ibid Vol. 647, 138 (1961); Journal of Organic Chemistry Vol. 49, 3534 (1984); ibid Vol. 38, 1995 (1973); ibid Vol. 36, 11 (1971); ibid Vol. 30, 4081 (1965); ibid Vol. 30, 2403 (1965), Journal of
Heterocyclic Chemistry Vol. 2, 53 (1965); ibid Vol. 5, 695 (1968); Journal of Medicinal Chemistry Vol. 12, 1031 (1969); ibid Vol. 15, 415 and 982 (1972); ibid Vol. 20, 387 (1977); ibid Vol. 21, 235 (1978); Journal of the Chemical Society, 1075 (1946); 2834 (1955); 3277 (1963); Chemical and Pharmaceutical Bulletin Vol. 11, 1564 (1963); Chemical and Pharmaceutical Bulletin Vol. 11, 1564 (1963); ibid Vol. 12, 813 (1964); ibid Vol. 22, 482 (1974); Yakugakuzasshi Vol. 91, 1154 (1971); ibid Vol. 94, 839 (1974); ibid Vol. 98, 631 (1978);
Gazzetta Chmica Italiana Vol. 105, 777 (1975); Chemical Abstracts Vol. 50, 313 (1956); ibid Vol. 73, 87855m and 120548p (1970); ibid Vol. 88, 22752r (1978); US Patent No. 3901903; Japanese Examined Patent Publication No. 32793/1969; Farmaco Edizione Scientifica Vol. 36, 994 (1981); Japanese Unexamined Patent Publication No. 38091/1989; Japanese Unexamined Patent Publication No. 247969/1994; or methods corresponding to them.
The methods for the preparation of representative compounds among these starting compounds are given in the following Reaction schemata 10 to 13.
Figure imgf000060_0001
Figure imgf000061_0001
Figure imgf000062_0001
Figure imgf000063_0001
wherein Hal is a halogen atom, R4 is hydrogen, a lower alkyl group which may be substituted with a halogen atom, R5 is a lower alkyl group which may be
substituted with a halogen atom, R6 is hydrogen, or a lower alkyl or lower alkylthio group which may be substituted with a halogen atom, R7, R8, R9, R10 is hydrogen, a lower alkyl group which may be substituted with a halogen atom and other symbols are as defined above.
The halogen atom used here includes, for example, fluorine, chlorine, bromine, etc. As the "lower alkyl group" in the lower alkyl group or lower alkylthio group, there may be used an alkyl group having 1 to 4 carbon atoms (e.g. methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, etc.)
In the Reaction schema 10, the reaction shown for the compound having an imidazo[1,2-a]pyridine ring is similarly applicable to other fused imidazoles such as imidazo[1,2-a]pyrimidine, imidazo[1,2-a]pyrazine, imidazo[1,2-b]pyridazine, imidazo[1,2-b](1,2,4)triazine, imidazo[1,2-a]imidazole,
imidazo[1,2-b]pyrazole, imidazo[2,1-b]thiazole, imidazo[2,1-b](1,3,4)thiadiazole and the like. Best Mode for Carrying Out of the Invention
The present invention is illustrated in further detail in the following reference examples, examples, formulation examples and test examples but those are not to be construed to limit the invention.
In the following Reference Examples and Examples, the term "room temperature" means any temperature within the range of 10 to 30°C. "1H-NMR" means the proton nuclear magnetic resonance spectra and measured on BRUKER AC-200P type spectrometer (200MHz) using tetramethyl silane as the internal standard and being indicated in chemical sift (δ) value in ppm. "IR" means the infrared absorption spectra and measured on Infrared Spectrophotometer produced by Shimadzu
Seisakusho IR420 or IR435, and the positions of absorption bands are indicated as the wavenumber (cm-1). The other symbols in Reference Examples and
Examples have the following meanings. DMSO-d6:
dimethyl sulfoxide-d6; S: singlet; d: doublet; t:
triplet; q: quartet; dd: doublet doublet; ddd: doublet doublet doublet; dt: doublet triplet; td: triplet doublet; qd: quartet doublet; m: multiplet; br.:
Broad; J: coupling constant; % : weight percent; v/v: volume per volume ratio; Me: methyl; Et: ethyl; n-Pr: normal propyl; i-Pr: isopropyl; n-Bu: normal butyl; i-Bu: isobutyl; s-Bu: secondary butyl; Ph: phenyl;
Figure imgf000065_0001
dec.: decomposition
In the following Reference Examples, among the starting compounds (V), (VII) or a salt thereof, processes for producing new compounds which have not been yet disclosed in any prior art will be illustrated in detail. [Reference Example 1]
(1) 6-Ethoxyimidazo[2,1-b]thiazole
0.87 g (21.8 mmol) of 60% sodium hydride was washed with n-hexane and suspended in 20 ml of DMF under a dry nitrogen gas stream, followed by adding 1.0 g (21.7 mmol) of ethanol under ice-cooling. After the generation of bubbles ceased, 5.0 g (18.2 mmol) of ethyl
6-methylsulfonylimidazo[2,1-b]thiazole-5-carboxylate was added to the suspension and the resulting mixture was stirred for 2 hours at room temperature. The reaction mixture was poured into 100 ml of ice water and the resulting mixture was extracted with chloroform (25 ml each, 4 times). The extracts were combined, washed with an aqueous saturated sodium chloride solution, dried over magnesium sulfate and
concentrated. The obtained residue was purified by silica gel column chromatography (eluent:
chloroform-ethyl acetate, 7 : 1, v/v) to give 2.5 g of ethyl 6-ethoxyimidazo[2,1-b]thiazole-5-carboxylate .
The product was dissolved in 15 ml of ethylene glycol. To the solution were added 0.6 g (15.0 mmol) of sodium hydroxide and 5 ml of water and the resulting mixture was stirred under heating for 1.5 hours at 80°C. To the reaction mixture was added 1.2 ml (14.4 mmol) of hydrochloric acid, then the mixture was stirred for another 10 minutes at the same temperature. The reaction mixture was poured into 50 ml of ice water and the resulting mixture was extracted with chloroform (20 ml each, 3 times). The extracts were combined, washed with an aqueous saturated sodium chloride solution, dried over magnesium sulfate and concentrated. The obtained residue was purified by silica gel column chromatography (eluent: chloroform-ethyl acetate, 7 : 1, v/v) to give 1.23 g of the title compound as a yellowish oil. 1H-NMR(CDCl3) δ: 1.41(3H,t,J=7.0Hz),
4.16(2H,q,J=7.0Hz), 6.74(1H,d,J=4.4Hz), 6.86(1H,s), 7.34(1H,d,J=4.4Hz)
IR(neat) : 1545, 1460, 1345, 1303, 1252, 1045, 850 (2) 6-Methoxyimidazo[2,1-b]thiazole
This compound was prepared in a similar manner to that in (1) and obtained as yellowish oil.
1H-NMR(CDCl3) δ: 3.88(3H,s), 6.73(1H,1,J=4.4Hz),
6.86(1H,s), 7.33(1H,d,J=4.4Hz)
IR(neat) : 1550, 1463, 1352, 1312, 1252, 1063, 1035, 977, 855
( 3) 6-Propoxyimidazo[2,1-b]thiazole
This compound was prepared in a similar manner to that in (1) and obtained as yellowish oil.
1H-NMR(CDCl3) δ: 1.03(3H,t,J=7.4Hz), 1.81(2H,m),
4.05(2H,t,J=6.6Hz), 6.73(1H,d,J=4.4Hz), 6.85(1H,s), 7.33(1H,d,J=4.4Hz)
(4) 6-(2,2,3,3,3-Pentafluoropropoxy)imidazo[2,1-b]thiazole
This compound was prepared in a similar manner to that in (1) and obtained as colorless crystals, m.p. 72-73°C
1H-NMR(CDCl3) δ: 4.73(2H,tq,J=13.0&1.1Hz),
6.80(1H,d,J=4.5Hz), 7.00(1H,s), 7.36(1H,d,J=4.5Hz) IR(nujol) : 1560, 1355, 1200, 1155, 1030, 980
(5) 2-Phenoxyimidazo[1,2-a]pyridine
This compound was prepared in a similar manner to that in (1) and obtained as yellowish oil.
1H-NMR(CDCl3) δ: 6.79(1H,td,J=6.8&1.2Hz), 7.06(1H,s), 7.08-7.24(4H,m), 7.30-7.54 (3H,m),
8.01(1H,dt,J=6.7&1.2Hz)
IR(neat) : 1530, 1490, 1365, 1340, 1215, 750
[Reference Example 2]
(1) 2-Chloro-7-methylimidazo[1,2-a]pyridine
A mixture of 9.55 g (0.10 mol) of chloroacetic acid, 10.1 g (0.10 mol) of triethylamine and 20 ml of water was stirred at room temperature, to which 10.8 g (0.10 mol) of 2-amino-4-methyl pyridine was added and the resulting mixture was stirred for 3 hours at 85 -90°C. After cooling, the reaction mixture was
ice-cooled and the precipitated solid was collected by filtration, washed with acetone and dried. The
obtained solid (6.9 g) was suspended in 50 ml of toluene and 13.0 g(0.083 mol) of phosphorus oxychloride was added to the suspension and the resulting mixture was stirred for 3 hours at 80 to 90°C. After cooling, toluene was removed from the reaction mixture by decantation and water was added to the remaining. The resulting mixture was neutralized with aqueous ammonia and extracted with dichloromethane. The extract was dried and concentrated. The obtained residue was purified by silica gel column chromatography (eluent: chloroform-ethyl acetate, 5 : 1, v/v) to give 0.67 g of the title compound as pale green crystals,
m.p. 101-102°C
1H-NMR(CDCl3) δ: 2.38(3H,s), 6.66(1H,dd,J=6.9&1.6Hz), 7.28(1H,s), 7.40(1H,s), 7.91(1H,dd,J=7.0&0.5Hz)
IR(nujol) : 1640, 1480, 1360, 1350, 1300, 1240, 780 (2) 2-Chloroimidazo[1,2-a]pyrimidine
This compound was prepared in a similar manner to that in (1) and obtained as pale yellowish brown crystal.
m.p. 156-157°C
1H-NMR(CDCl3) δ: 6.95(1H,dd,J=6.8&4.2Hz), 7.50(1H,s), 8.40(1H,dd,J=6.8&2.0Hz), 8.57(1H,dd,J=4.2&2.0Hz)
IR(nujol) : 3150, 3080, 1615, 1525, 1500, 1480, 1430, 1415, 1335, 1295, 1245, 1225, 1130, 1030, 945, 785, 765, 705, 645
[Reference Example 3]
2-Difluoromethoxyimidazo[1,2-a]pyridine
A mixture of 10.0 g (0.106 mol) of chloroacetic acid, 14.8 ml (0.106 mol) of triethylamine and 30 ml of water was stirred under ice-cooling, to which 10.0 g (0.106 mol) of 2-aminopyridine was added and the resulting mixture was stirred at 85°C for 3 hours.
After cooling, the reaction mixture was ice-cooled. The precipitated solid was collected by filtration, washed with cold water and dried. The solid (7.61 g) was suspended in 20 ml of water. To the suspension was added 6.0 g (0.15 mol) of sodium hydroxide and the resulting mixture was stirred for 30 minutes at 80°C. To the reaction mixture was added 25 ml of dioxane, followed by introduction of chlorodifluoromethane with stirring at 55°C over 3 hours. The reaction mixture was further stirred at room temperature overnight, to which 35 ml of water was added. The resulting mixture was extracted with chloroform (30 ml each, 3 times). The extracts were combined, washed with water, dried over magnesium sulfate and concentrated. The obtained residue was purified by silica gel column
chromatography (eluent: n-hexane-ethyl acetate, 1 : 1, v/v) to give 0.48 g of the title compound as a
yellowish oil.
1H-NMR(CDCl3) δ: 6.85(1H,td,J=6.8&1,2Hz),
7.11(1H,t,J=73.7Hz), 7.15-7.27(2H,m),
7.50(1H,dd,J=9.7&0.6Hz), 8.06(1H,dt,J=6.7&1.2Hz)
IR(neat) : 1640, 1550, 1510, 1350, 1160, 980, 750, 737 [Reference Example 4]
(1) 2,3,6-Trimethylpyrazolo[5,1-b]thiazole
To 384 g (5.06 mol) of a solution of ammonia in methanol (22.4 %), 82 ml (1.69 mol) of hydrazine hydrate was added, to which 107 ml (1.77 mol) of carbon disulfide was added dropwise at 5 - 15°C over 1 hour. The reaction mixture was stirred for 1 hour at 5°C and cooled to -20°C. The precipitated solid was collected by filtration, washed with cold methanol to give 224.8 g of ammonium dithiocarbazate as pale yellowish
crystals. In 500 ml of ice water, 168.8 g (1.35 mol) of the obtained compound was suspended, to which 138 ml (1.37 mol) of 3-chloro-2-butanone was added dropwise below 5°C over 1 hour. The reaction mixture was stirred under ice-cooling for 30 minutes and at room
temperature for 1 hour. The organic layer was
separated out and the aqueous layer was extracted with chloroform (100 ml each, 2 times). The organic layer and the extracts were combined, washed with an aqueous saturated sodium chloride solution and concentrated. The obtained residue was dissolved in 500 ml of
methanol, to which 50 ml of hydrochloric acid was added under ice-cooling over 10 minutes. The resulting mixture was stirred at room temperature overnight. The reaction mixture was concentrated and the obtained solid was washed with water, collected by filtration and dried to give 129.3 g of 3-amino-4,
5-dimethylthiazole-2(3H)-thione as orange crystals, m.p. 76-79°C
In 100 ml of ethyl acetate, 10.0 g (62.4 mmol) of the obtained compound was dissolved, to which 9.1 ml (65.2 mmol) of ethyl 2-chloroacetoacetate was added, and the reaction mixture was heated with stirring under reflux for 4 hours. After cooling, the reaction mixture was concentrated. To the residue, acetone was added and insolubles were filtered off. The filtrate was concentrated and the obtained residue was purified by silica gel column chromatography (eluent:
chloroform-n-hexane, 3 : 2, v/v, then chloroform-ethyl acetate, 7 : 1, v/v). The obtained solid was washed with cold n-hexane to give 11.3 g of ethyl
2,3,6-trimethylpyrazolo[5,1-b]thiazole-7-carboxylate as pale yellowish crystals, m.p. 86-87°C.
In 20 ml of ethylene glycol, 5.00 g (21.0 mmol) of the obtained compound was suspended. To the
suspension, 1.26 g (31.5 mmol) of sodium hydroxide and 10 ml of water were added and the resulting mixture was stirred under heating at 100°C for 30 minutes. To the reaction mixture, 3.0 ml (36.0 mmol) of hydrochloric acid and 4 ml of acetic acid were added and the
resulting mixture was stirred under heating at 110°C for another 3 hours. After cooling, 30 ml of water was added to the reaction mixture and the resulting mixture was extracted with chloroform (30 ml each, 3 times). The extracts were combined, washed with an aqueous sodium hydrogen carbonate solution, dried over
magnesium sulfate and concentrated. The obtained solid was washed with cold n-hexane to give 2.97 g of the title compound as colorless crystals,
m.p. 110-111°C
1H-NMR(CDCl3) δ: 2.32(3H,q,J=0.9Hz),
2.40(3H,q,J=0.9Hz), 2.41(3H,s), 6.09(1H,s)
IR(nujol) : 1493, 1360, 1320, 800
(2) 3-Ethyl-6-methylpyrazolo[5,1-b]thiazole
This compound was prepared in a similar manner to that in (1) and obtained as pale yellowish oil.
1H-NMR(CDCl3) δ: 1.39(3H,t,J=7.5Hz), 2.43(3H,s),
2.90(2H,qd,J=7.5&1.3Hz), 6.16(1H,s), 6.32(1H,t,J=1.3Hz) IR(neat) : 1495, 1352, 810
(3) 6-Methyl-3-phenylpyrazolo[5,1-b]thiazole
This compound was prepared in a similar manner to that in (1) and obtained as yellowish oil.
1H-NMR(CDCl3) δ: 2.46(3H,s), 6.24(1H,s), 6.82(1H,s),
7.36-7.56(3H,m), 8.03-8.13(2H,m)
IR(neat) : 1500, 1482, 1355, 1300, 710
(4) 6-Ethyl-3-methylpyrazolo[5,1-b]thiazole
This compound was prepared in a similar manner to that in (1) and obtained as yellowish oil.
1H-NMR(CDCl3) δ: 1.32(CH,t,J=7.6Hz),
2.50(3H,d,J=1.3Hz), 2.81(2H,q,J=7.6Hz), 6.21(1H,s), 6.35(1H,q,J=1.3Hz)
IR(neat) : 1500, 1385, 1370 (5) 3-Methyl-6-propylpyrazolo[5,1-b]thiazole
This compound was prepared in a similar manner to that in (1) and obtained as pale yellowish oil.
1H-NMR(CDCl3) δ: 1.00(3H,t,J=7.3Hz), 1.64-1.83(2H,m), 2.50(3H,d,J=1.2Hz), 2.74(2H,t,J=7.7Hz), 6.19(1H,s), 6.35(1H,q,J=1.2Hz)
IR(neat) : 1495, 1390
[Reference Example 5]
(1) 6-Chloro-2-methoxyimidazo[1,2-b]pyridazine
A mixture of 7.8 g (60 mmol) of 3-amino-6-chloropyridazine, 10 g (60 mmol) of ethyl bromoacetate and 70 ml of acetonitrile was heated under reflux with stirring for 5 hours. After cooling, precipitated solid was collected by filtration and washed with acetonitrile. To the solid which 70 ml of 30% aqueous sodium hydroxide was added and the resulting mixture was heated under reflux with stirring for 3 hours.
After cooling, precipitated solid was collected by filtration and washed with acetone. In 10 ml of DMF, 1.91 g among the obtained solid (6.0 g) was dissolved, to which 1.33 g (10 mmol) of dimethylsulfate was added. The resulting mixture was stirred at room temperature for 3 hours. The reaction mixture was poured into water and the resulting mixture was extracted with ethyl acetate. The extract was dried and concentrated. The obtained residue was purified by silica gel column chromatography (eluent : chloroform-ethyl acetate, 5 : 1, v/v) to give 0.6 g of the title compound as pale yellowish crystals.
1H-NMR(DMSO-d6) 6: 3.92(3H,s), 7.27(1H,d,J=9.4Hz), 7.90(1H,s), 8.02(1H,dd,J=9.4&0.6Hz)
IR(nujol) : 1550, 1390, 1290, 1100, 1040, 720
(2) 6-Chloro-2-propoxyimidazo[1,2-b]pyridazine
This compound was prepared in a similar manner to that in (1) and obtained as greenish crystals,
m.p. 68-69°C 1H-NMR(CDCl3) δ: 1.06(3H,t,J=7.4Hz), 1.8(2H,m),
4.23(2H,t,J=6.6Hz), 7.00(1H,d,J=9.3Hz), 7.39(1H,s),
7.69(1H,d,J=9.3Hz)
IR(nujol) : 1530, 1500, 1340, 1280, 1125, 1090, 1060, 1020, 930, 790, 750
(3) 2-Butoxy-6-chloroimidazo[1,2-b]pyridazine
This compound was prepared in a similar manner to that in (1) and obtained as greenish crystals.
m.p. 56-57°C
1H-NMRfCDClj) δ: 0.98(3H,t,J=7.3Hz), 1.4-1.6(2H,m),
1.7-1.9(2H,m), 4.27(2H,t,J=6.5Hz), 6.99(1H,d,J=9.4Hz),
7.39(1H,s), 7.68(1H,d,J=9.3Hz)
IR(nujol) : 1530, 1510, 1270, 1170, 1090, 1030, 930,
790, 700
[Reference Example 6]
(1) 6-Ethoxy-2-methoxyimidazo[1,2-b]pyridazine
To a mixture of 1.2 g (6.54 mmol) of 6-chloro-2-methoxyimidazo[1,2-b]pyridazine and 12 ml of ethanol, 0.49 g (7.20 mmol) of sodium ethoxide was added and the resulting mixture was heated under reflux with stirring for 2 hours. After cooling, the reaction mixture was poured into water and the resulting mixture was
extracted with ethyl acetate. The extract was dried and concentrated. The obtained solid after addition of a small amount of diisopropyl ether was collected by filtration and washed with n-hexane to give 0.79 g of the titled compound as pale reddish crystals .
m.p. 83-87°C
1H-NMR(CDCl3) δ: 1.42(3H,t,J=7.1Hz), 3.97(3H,s),
4.33(2H,q,J=7.1Hz), 6.58(1H,d,J=9.5Hz), 7.18(1H,s), 7.60(1H,d, J=9.5Hz)
IR(nujol) : 3120, 1630, 1540, 1295, 1205, 1040, 800, 720
(2) 2,6-Diethoxyimidazo[1,2-bJpyridazine
This compound was prepared in a similar manner to that in (1) and obtained as pale reddish crystal. m . p . 74-75 °C
1H-NMRfCDCl3) δ: 1.3-1.5(6H,m), 4.2-4.4(4H,m),
6.58(1H,d,J=9.5Hz), 7.17(1H,s), 7.59(1H,d,J=9.5Hz) IR(nujol) : 3120, 1620, 1535, 1380, 1290, 1190, 1110, 1040, 1030, 790, 710
(3) 2-Ethoxy-6-(2,2,2-trifluoroethoxy)imidazo[1,2-b]¬pyridazine
This compound was prepared in a similar manner to that in (1) and obtained as pale yellowish crystal. m.p. 93-94°C
1H-NMRfCDCl3) δ: 1.45(3H,t,J=7.1Hz),
4.31(2H,q,J=7.1Hz), 4.70(2H,q,J=8.3Hz),
6.70(1H,d,J=9.5Hz), 7.21(1H,s), 7.68(1H,d,J=9.5Hz) IR(nujol) : 3100, 1625, 1540, 1460, 1420, 1380, 1370, 1300, 1260, 1200, 1170, 1150, 1105, 1065, 1045, 960, 890, 800, 750, 710, 685
[Reference Example 7]
(1) 2-Chloro-6-ethoxyimidazo[1,2-b]pyridazine
In 20 ml of ethanol, 0.25 g (0.011 mol) of metallic sodium was dissolved, to which 2.0 g (0.011 mol) of 2,6-dichloroimidazo[1,2-b]pyridazine was portion-wise added at room temperature. The reaction mixture was stirred at room temperature for 17 hours, and then under reflux for 5.5 hours. After cooling, the reaction mixture was concentrated and to the residue was added 30 ml of water and 1 ml of IN hydrochloric acid to adjust to pH 1. The mixture was neutralized with sodium hydrogen carbonate and the precipitated solid was collected by filtration, washed with water, then with n-hexane and dried to give 1.9 g of the title compound as yellowish powder,
m.p. 101-102°C
1H-NMR(CDCl3) δ: 1.44(3H,t,J=7.1Hz),
4.35(2H,q,J=7.1Hz), 6.69(1H,d,J=9.7Hz),
7.62(1H,d,J=0.5Hz), 7.67(1H,dd,J=9.6&0.6Hz)
IR(nujol) : 3110, 3040, 1615, 1550, 1485, 1470, 1410, 1375, 1350, 1320, 1295, 1195, 1115, 1030, 905, 835, 750
(2) 2-Chloro-6-methoxyimidazo[1,2-b]pyridazine
This compound was prepared in a similar manner to that in (1) and obtained as pale yellowish crystal. 1H-NMR(CDCl3) δ: 3.97(3H,s), 6.72(1H,d,J=9.6Hz), 7.6-7.7(2H,m)
(3) 2-Chloro-6-propoxyimidazo[1,2-b]pyridazine
This compound was prepared in a similar manner to that in (1) and obtained as pale greenish crystal.
m.p. 55-56°C
1H-NMR(CDCl3) δ: 1.05(3H,t,J=7.4Hz), 1.7-1.8(2H,m),
4.24(2H,t,J=6.6Hz), 6.70(1H,d,J=9.6Hz), 7.62(1H,s),
7.67(1H,d,J=9.6Hz)
IR(nujol) : 1320, 1280, 1190
[Reference Example 8]
(1) 6-Chloro-2-methylimidazo[2,1-b](1,3,4)thiaziazole A mixture of 11.9 g (0.10 mol) of 2-amino-5-methyl-1,3,4-thiadiazole, 9.55 g (0.10 mol) of
chloroacetic acid, 50 ml of 1,2-dimethoxyethane and 25 ml of ethanol was heated under reflux with stirring for 16 hours. After cooling, the precipitated solid was collected by filtration, washed with acetonitrile and dried. The solid (8.8 g) was added with 50 ml of phosphorus oxychloride and heated under reflux with stirring for 6 hours. After cooling, the reaction mixture was concentrated. The obtained residue was added with water, neutralized with aqueous ammonia and then extracted with ethyl acetate. The extract was dried and concentrated. The obtained residue was purified by silica gel column chromatography (eluent : chloroform-ethyl acetate, 3 : 1, v/v) to give 0.52 g of the title compound as pale yellowish crystals,
m.p. 80-85°C
1H-NMR(CDCl3) δ: 2.71(3H,s), 7.62(1H,s)
IR(nujol) : 1330, 1290, 1200, 1140, 1020
(2 ) 6-Chloroimidazo[2,1-b](1,3,4)thiadiazole This compound was prepared in a similar manner to that in (1) and obtained as colorless crystal,
m.p. 110-111°C
1H-NMR(CDCl3) δ: 7.78(1H,s), 8.59(1H,s)
IR(nujol) : 1320, 1240, 1220, 950, 860, 820, 720, 700 [Reference Example 9]
(1) 2-Methyl-6-trifluoromethylimidazo[1,2-a]pyridine
A mixture of 2-amino-5-trifluoromethylpyridine( 6.0 g, 37.0 mmol), bromoacetone (6.2 g, 40.7 mmol) and ethanol (10 ml) was stirred and heated under reflux for 8 hours. After cooling to room temperature the
reaction mixture was concentrated and to the residue was added water and 20% sodium hydroxide aqueous solution. The resulting mixture (pH 8) was extracted with ethyl acetate. The extract was dried and
concentrated. The residue was subjected to column chromatography (silica gel, chloroform-ethyl acetate, 2 : 1, v/v) to give 1.1 g of the title compound as pale reddish crystals.
m.p. 102-103°C
1H-NMR(CDCl3) δ: 2.49(3H,s), 7.27(1H,dd,J=9.4&1.8Hz), 7.44(1H,br.s), 7.61(1H,dd,J=9.4&0.7Hz), 8.4(1H,m) IR(nujol) : 1360, 1330, 1120, 1050
(2) 8-Chloro-2-methyl-6-trifluoromethylimidazo[1,2- a]pyridine
This compound was prepared in a similar manner to that in (1) and obtained as pale brownish crystal, m.p. 134°C
1H-NMR(CDCl3) δ: 2.53(3H,s), 7.38(1H,d,J=1.4Hz),
7.51(1H,br.s), 8.37(1H,t,J=1.3Hz)
IR(nujol) : 1210, 1160, 1120
(3) 6-Chloro-2-trifluoromethylimidazo[1,2-a]pyridine This compound was prepared in a similar manner to that in (1) and obtained as colorless crystal.
m.p. 113-114°C
1H-NMR(CDCl3) δ: 7.2-7.3(1H,m), 7.63(1H,d,J=9.7Hz), 7 . 87 ( 1H, s ) , 8 . 2 ( 1H,m)
(4) 6-Chloro-2-ethylimidazo[1,2-b]pyridazine
This compound was prepared in a similar manner to that in (1) and obtained as pale yellowish crystals. m.p. 71-72°C
1H-NMRfCDCl3) δ: 1.36(3H,t,J=7.6Hz),
2.86(2H,q,J=7.5Hz), 7.01(1H,d,J=9.4Hz), 7.72(1H,s),
7.82(1H,dd,J=9.4&0.6Hz)
IR(nujol) : 1510, 1280, 1090, 800
(5) 6-Chloro-2-ethylimidazo[1,2-a]pyridine
This compound was prepared in a similar manner to that in (1) and obtained as pale yellowish crystals. m.p. 67-69°C
1H-NMR(CDCl3) δ: 1.34(3H,t,J=7.5Hz),
2.82(2H,q,J=7.7Hz), 7.09(1H,dd,J=9.5&2.0Hz),
7.32(1H,s), 7.48(1H,dd,J=9.5&0.7Hz),
8.09(1H,dd,J=1.9&0.9Hz)
IR(nujol) : 1070, 790
(6) 6-Ethyl-2-methylimidazo[2,1-b](1,3,4)thiadiazole This compound was prepared in a similar manner to that in (1) and obtained as pale yellowish oil.
1H-NMR(CDCl3) δ: 1.29(3H,t,J=7.5Hz), 2.67(3H,s),
2.70(2H,qd,J=7.6&0.9Hz), 7.42(1H,t,J=0.9Hz)
IR(neat) : 1530, 1290, 1220, 1185, 1140, 1100, 1040, 980, 940, 745
(7) 2,6-Diethylimidazo[2,1-b](1,3,4)thiadiazole
This compound was prepared in a similar manner to that in (1) and obtained as pale yellowish oil.
1H-NMR(CDCl3) δ: 1.29(3H,t,J=7.5Hz),
1.40(3H,t,J=7.6Hz), 2.71(2H,qd,J=7.6&0.9Hz),
2.99(2H,q,J=7.6Hz), 7.42(1H,t,J=0.9Hz)
IR(neat) : 2900, 1460, 1290, 1220, 1040
[Reference Example 10]
2-Ethoxymethylimidazo[1,2-a]pyridine
To a suspension of sodium ethoxide (3.1 g, 45.6 mmol) in ethanol (30 ml) was added 2- chloromethylimidazofl, 2-a]pyridine (5.0 g, 30.0 mmol). The resulting mixture was stirred and heated under reflux for 1 hour. After cooling to room temperature the reaction mixture was concentrated. To the residue was added ice-water (100 ml) and the resulting mixture was extracted with chloroform (20 ml x 3). The
extracts were combined, dried over magnesium sulfate and evaporated. The residue was subjected to column chromatography (silica gel, chloroform-acetone, 3 : 1, v/v) to give 5.2 g of the title compound as yellowish oil.
1H-NMR(CDCl3) 6: 1.28(3H,t,J=7.0Hz),
3.67(2H,q,J=7.0Hz), 4.70(2H,d,J=0.7Hz),
6.76(1H,td,J=6.8&1.2Hz), 7.15(1H,ddd,J=9.2&6.7&1.3Hz), 7.53-7.60(2H,m), 8.08(1H,dt,J=6.8&1.2Hz)
IR(neat) : 1500, 1340, 1090, 750
[Reference Example 11]
(1) 5-Ethoxy-2-methylpyrazolo[1,5-a]pyrimidine
A solution of 3-amino-5-methylpyrazole (24.9 g, 0.26 mol) and ethyl propiolate (27.6 g, 0.28 mol) in dioxane (130 ml) was stirred and heated under reflux for 4 hours. After cooling to room temperature the precipitated solid was filtered with suction, washed with toluene (x2) and air-dried to give 22.3 g of white solid. The filtrate was concentrated and the residue was washed with toluene. The precipitated solid was filtered with suction, washed with toluene (x2) and air-dried to give 5.4 g of another portion of the same product (white solid). The two portions of the product was combined and suspended in ethanol (320 ml). The mixture was stirred under cooling in an ice-water bath and to this was added a 28% solution of sodium
methoxide in methanol (30.9 g, 0.16 mol) gradually. The reaction mixture was stirred at room temperature for 80 minutes and then under reflux for 1.5 hours.
After cooling to room temperature the reaction mixture was concentrated and to the residue was added ice-water (150 ml) and then hydrochloric acid (12 ml) (pH 3-4). The precipitated solid was filtered with suction, washed with water (x2) and air-dried to give 19.0 g of 5-hydroxy-2-methylpyrazolo[1,5-a]pyrimidine as
colorless crystals. m.p. 233-234°C
To this compound (14.0 g, 0.094 mol) was added phosphorus oxychloride (75 ml, 0.80 mol) gradually under cooling in an ice-water bath. The reaction mixture was stirred and heated under reflux for 4 hours. After cooling to room temperature the reaction mixture was concentrated and to the residue was added ice-water (80 ml). The resulting mixture was extracted with chloroform (50 ml × 3). The extracts were
combined, washed with brine (30 ml × 2), dried over magnesium sulfate and evaporated to give reddish brown solid (11.7 g). The solid was subjected to column chromatography (silica gel, chloroform) to give 5.3 g of 5-chloro-2-methylpyrazolo[1,5-a]pyrimidine as colorless crystals, m.p. 123-124°C.
Sodium (0.23 g, 0.010 mol) was dissolved in ethanol (40 ml) to prepare a solution of sodium
ethoxide. To the solution was added 5-chloro-2-methylpyrazolo[1,5-a]pyrimidine (1.51 g, 9.0 mmol) gradually. The reaction mixture was stirred at room temperature for 9 hours and concentrated. To the residue was added water (30 ml) and then IN
hydrochloric acid (0.5 ml ) (pH 6). The precipitated solid was filtered with suction, washed with water (x2) and then n-hexane (xl) and dried by removing moisture as an azeotropic mixture with toluene (x3) to give 1.38 g of the title compound as colorless crystals, m.p.
79°C.
1H-NMR(CDCl3) δ: 1.41(3H,t,J=7.1Hz), 2.43(3H,s),
4.41(2H,q,J=7.1Hz), 6.10(1H,S), 6.20(1H,d,J=7.4Hz), 8.29(1H,dd,J=0.75&7.4Hz) IR(nujol) : 3070, 3040, 1640, 1590, 1555, 1540, 1530, 1450, 1395, 1380, 1335, 1310, 1235, 1105, 1035, 1010, 905, 785, 760, 730
(2) 5-Methoxy-2-methylpyrazolo[1,5-a]pyrimidine
This compound was prepared in a similar manner to that in (1) and obtained as colorless crystals,
m.p. 85-86°C
1H-NMR(CDCl3) δ: 2.44(3H,s), 3.98(3H,s), 6.13(1H,s), 6.23(1H,d,J=7.4Hz), 8.31(1H,dd,J=0.79&7.4Hz)
IR(nujol) : 3100, 3050, 1635, 1550, 1530, 1410, 1330, 1310, 1235, 1105, 1025, 1000, 970, 810, 800, 790, 595
(3) 2-Methyl-5-propoxypyrazolo[1,5-a]pyrimidine
This compound was prepared in a similar manner to that in (1) and obtained as colorless crystals.
m.p. 86-87°C
1H-NMR(CDCl3) δ: 1.03(3H,t,J=7.4Hz),
1.81 (2H, sextet, J=7.1Hz), 2.43(3H,s),
4.31(2H,t,J=6.7Hz), 6.10(1H,s), 6.21(1H,d,J=7.4Hz), 8.29(1H,dd,J=0.79&7.4Hz)
IR(nujol) : 3090, 3050, 1640, 1560, 1530, 1450, 1380, 1330, 1315, 1295, 1230, 1040, 1020, 995, 975, 795, 780 [Reference Example 12]
(1) 6-Ethoxy-3-methylpyrazolo[5,1-b]thiazole
To a stirred and ice-cooled solution of 3-amino-4-methylthiazole-2(3H)-thione (75.0 g, 0.513 mol) and ethyl hydrogen malonate (74.5 g, 0.564 mol) in
dichloromethane (350 ml) was added a solution of dicyclohexylcarbodiimide (DCC) (116.3 g, 0.564 mol) in dichloromethane (100 ml) dropwise over 1 hour (2 - 10°C). The resulting mixture was stirred under cooling in an ice-water bath for 30 minutes and then at room temperature one night. To the reaction mixture was added an additional portion of a solution of DCC (20.0 g, 0.097 mol) in dichloromethane (50 ml) dropwise over 15 minutes and the resulting mixture was stirred for 3 hours. The insoluble solid was filtered with suction and washed with dichloromethane. The filtrate was concentrated and to the residue was added acetone (400 ml). The insoluble solid was filtered with suction and the filtrate was concentrated. The residue was
subjected to column chromatography (silica gel, chloroform-acetone, 20:1 and then 7:1, v/v) to give solid product, which was washed with n-hexane, filtered with suction and air-dried to give 148.9 g of 3-(ethoxycarbonylacetylamino)-4-methylthiazole-2(3H)-thione as pale yellowish crystals, m.p. 90-95°C.
This compound (148.9 g) was dissolved in acetone (700 ml) and to this solution was added iodomethane (64 ml, 1.03 mol). The reaction mixture was stirred at room temperature for 3 days. The precipitated solid was filtered with suction, washed with acetone and dried to give 161.8 g of 3-(ethoxycarbonylacetylamino)-4-methyl-2-methylthiothiazolium iodide as colorless crystals. m.p. 127-129°C.
To a solution of potassium tert-butoxide (94.0 g, 0.754 mol) in tert-butyl alcohol (1500 ml) was added 3-(ethoxycarbonylacetylamino)-4-methyl-2-methylthiothiazolium iodide (151.8 g, 0.377 mol) in some portions over 20 minutes. The reaction mixture was stirred at room temperature for 3 hours . The reaction mixture was poured into ice-water (3000 ml) and to the resulting mixture was added hydrochloric acid (pH 4). The precipitated solid was filtered with suction, washed with water and dried to give 55.2 g of 7-ethoxycarbonyl-6-hydroxy-3-methylpyrazolo[5, 1-b]thiazole as colorless powder, m.p. 209-210°C.
Oil-containing 60% sodium hydride (0.97 g, 24.3 mmol) was washed with n-hexane and suspended in DMF (70 ml) under a dried nitrogen stream. To the suspension was added 7-ethoxycarbonyl-6-hydroxy-3-methylpyrazolo[5,1-b]thiazole (5.0 g, 22.1 mmol) gradually. The resulting mixture was stirred at 40°C for 10 minutes and to the mixture was added iodoethane (2.7 ml, 33.8 mmol) and then an additional portion of DMF (10 ml). The reaction mixture was stirred at 55°C for 1 hour and then at room temperature one night. The reaction mixture was poured into ice-water (200 ml). The precipitated solid was filtered with suction, washed with water and dried to give 4.62 g of 6-ethoxy-7-ethoxycarbonyl-3-methylpyrazolo[5,1-b]thiazole as pale yellowish crystals, m.p. 110-111°C.
To a suspension of this compound (4.62 g, 18.2 mmol) in ethylene glycol (25 ml) was added sodium hydroxide (1.45 g, 36.3 mmol) and water (10 ml). The resulting mixture was stirred and heated at 90°C for 2 hours. After cooling to room temperature to the reaction mixture was added hydrochloric acid (3.0 ml, 36.0 mmol) and then acetic acid (4 ml) and the
resulting mixture was stirred and heated under reflux for 1.5 hours. After cooling to room temperature to the reaction mixture was added ice-water (100 ml) and the resulting mixture was extracted with chloroform (20 ml x 3). The extracts were combined, washed with saturated sodium bicarbonate aqueous solution, dried over magnesium sulfate and evaporated. The residue was subjected to column chromatography (silica gel, chloroform-ethyl acetate, 30:1, v/v) to give 3.16 g of the title compound as colorless crystals,
m.p. 58-60°C
1H-NMR(CDCl3) δ: 1.42(3H,t,J=7.0Hz),
2.44(3H,d,J=1.2Hz), 4.25(2H,q,J=7.0Hz), 5.82(1H,s), 6.22(1H,q,J=1.2Hz)
IR(nujol) : 1510, 1450, 1350, 1315, 1120, 1100, 1050 (2) 3-Methyl-6-propoxypyrazolo[5,1-b]thiazole
This compound was prepared in a similar manner to that in (1) and obtained as colorless oil.
1H-NMR(CDCl3) δ: 1.04(3H,t,J=7.4Hz), 1.73-1.92(2H,m), 2.44(3H,d,J=1.3Hz), 4.14(2H,t,J=6.6Hz), 5.82(1H,s), 6 . 22 ( 1H, q, J=1 . 3Hz )
IR(neat) : 1510, 1455, 1370, 1320, 1110
(3) 3-Methyl-6-(2-propoxy)pyrazolo[5,1-b]thiazole
This compound was prepared in a similar manner to that in (1) and obtained as colorless oil.
1H-NMR(CDCl3) δ: 1.39(6H,d,J=6.1Hz),
2.44(3H,d,J=1.3Hz), 4.78(1H,septet,J=6.1Hz),
5.80(1H,br.s), 6.23(1H,q,J=1.3Hz)
IR(neat) : 1500, 1460, 1320, 1110, 920
(4) 6-Butoxy-3-methylpyrazolo[5, l-b]thiazole
This compound was prepared in a similar manner to that in (1) and obtained as yellowish oil.
1H-NMR(CDCl3) δ: 0.97(3H,t,J=7.3Hz), 1.40-1.60(2H,m),
1.71-1.88(2H,m), 2.45(3H,d,J=1.3Hz),
4.19(2H,t,J=6.5Hz), 5.82(1H,br.s), 6.23(1H,q,J=1.3Hz)
IR(neat) : 1510, 1460, 1375, 1320, 1115, 1020, 695
(5) 6-Chloro-3-methylpyrazolo[5,1-b]thiazole
This compound was prepared in a similar manner to that in (1) and obtained as colorless crystal.
m.p. 77-78°C
1H-NMR(CDCl3) δ: 2.50(3H,d,J=1.2Hz), 6.34(1H,s),
6.47(1H,q,J=1.2Hz)
[Example 1]
3-(2-Chloroimidazo[1,2-a]pyridin-3-ylthio)-1H-1,2,4-triazole (Compound No. II-1-3)
Figure imgf000083_0001
With 20 ml of methanol was diluted 3.03 g (15.7 mmol) of a methanolic sodium methoxide solution (28%). To the solution was portion-wise added 1.59 g (15.7 mmol) of 3-mercapto-1H-1, 2, 4-triazole. The resulting solution was cooled at -60°C and added with 0.74 ml (14.4 mmol) of bromine at the same temperature and stirred for 10 minutes. After addition of 2.0 g (13.1 mmol) of 2-chloroimidazo[1,2-a]pyridine at the same temperature, the reaction mixture was stirred at room temperature overnight and then poured into 100 ml of ice water. The precipitated solid was collected by filtration, washed with water and dried to give 2.94 g of the title compound as light gray crystals .
m.p. 198-202°C
1H-NMR(DMSO-d6) δ: 7.17(1H,td,J=6.8&1.1Hz),
7.53(1H,ddd,J=9.0&6.8&1.2Hz), 7.69(1H,d,J=9.0Hz),
8.46(1H,d,J=6.8Hz), 8.55(1H,br.s), 14.16(1H,br.s)
IR(nujol) : 3100-2400, 1460, 1290, 1265, 1247, 765
[Example 2]
3- ( 2-Chloroimidazo[1,2-a]pyridin-3-ylsulfonyl)-1H-1,2,4-triazole (Compound No. II-1-4)
Figure imgf000084_0001
In a mixture of 20 ml of acetonitrile and 20 ml of water was suspended 1.0 g (3.97 mmol) of
3-(2-chloroimidazo[1,2-a]pyridin-3-ylthio)-1H-1,2,4-triazole. The suspension was added with 2.08 g (15.9 mmol) of sodium percarbonate (effective oxygen content: 12.2%) at room temperature. The reaction mixture was stirred for 3 hours while keeping an internal
temperature below 30°C. The reaction mixture was added with 30 ml of water and then with hydrochloric acid under ice-cooling to make the mixture acidic. The precipitated solid was collected by filtration, washed with water and dried to give 0.77 g of the title compound as colorless crystals,
m.p. 238-240°C (dec.)
1H-NMR(DMSO-d6) δ: 7.41(1H,td,J=6.8&1.6Hz), 7.70- 7.87(2H,m), 8.84(1H,s), 8.95(1H,dt,J=6.9&1.1Hz),
15.11(1H,br.s)
IR(nujol) : 3150-2500, 1495, 1460, 1360, 1348, 1253, 1160 , 762 , 678
[ Example 3 ]
3- ( 2-Methylimidazo [ 1 , 2-a ]pyridin-3-ylthio ) - 1H-1 ,2 , 4-triazole (Compound No . II-1-5 )
Figure imgf000085_0001
After washing with n-hexane, 0.45 g (11.3 mmol) of 60% sodium hydride was suspended in 15 ml of DMF under a dry nitrogen gas stream, followed by addition of 1.15 g (11.4 mmol) of 3-mercapto-1H-1, 2, 4-triazole under ice-cooling. After the generation of bubbles ceased, the reaction mixture was cooled to 0 - 10°C, to which 1.46 g (10.9 mmol) of N-chlorosuccinimide was added gradually. The resulting mixture was stirred for 15 minutes at 0°C. To the mixture, 1.00 g (7.57 mmol) of 2-methylimidazo[1,2-a]pyridine was added and the reaction mixture was stirred at room temperature for 1.5 hours, and then at 70°C for 3 hours. The reaction mixture was concentrated and the residue was washed with ethyl ether twice. (The washings were removed by decantation.) The insoluble solid after addition of methanol was filtered off. The filtrate was
concentrated and the residue was added with water. The precipitated solid was collected by filtration, washed with water, then with ethyl ether and dried to give 0.80 g of the title compound as pale yellowish
crystals.
m.p. 224-226°C (dec.)
1H-NMR(DMSO-d6) δ: 2.44(3H,s), 7.02(1H,td,J=6.8&1.2Hz), 7.38(1H,ddd,J=7.9&6.8&1.3Hz), 7.58(1H,dt,J=9.0&1.1Hz), 8.38(1H,dt,J=6.7&1.2Hz), 8.40(1H,br.s), 14.08(1H,br.s) IR(nujol) : 3050-2300, 1495, 1350, 1260, 1240, 950, 763 [Example 4]
3-(2-Methylimidazo[1,2-a]pyridin-3-ylsulfonyl)- 1H-1,2,4-triazole (Compound No. II-1-6)
Figure imgf000086_0001
In a similar way to Example 2, 0.29 g of the title compound was obtained from 0.38 g (1.64 mmol) of 3-(2-methylimidazo[1,2-a]pyridin-3-ylthio)-1H-1,2,4-triazole as colorless crystals.
m.p. 260-262°C (dec.)
1H-NMR(DMSO-d6) δ: 2.63(3H,s), 7.26(1H,td,J=6.9&1.4Hz), 7.61(1H,ddd,J=7.9&6.8&1.3Hz), 7.73(1H,dt,J=8.9&1.2Hz), 8.87(1H,dt,J=6.9&1.1Hz), 8.80(1H,s), 15.00(1H,s)
IR(nujol) : 3150-2400, 1492, 1450, 1330, 1250, 1160, 1142, 1125, 760, 740
[Example 5]
3-(2-Ethoxyimidazo[1,2-a]pyridin-3-ylsulfonyl)-1H-1,2,4-triazole (Compound No. II-1-12)
Figure imgf000086_0002
After washing with n-hexane, 0.64 g (16.0 mmol) of 60% sodium hydride was suspended in 10 ml of DMF under a dry nitrogen gas stream. To the suspension, 1.50 g (5.29 mmol) of 3-(2-chloroimidazo[1,2-a]pyridin-3-ylsulfonyl)-1H-1,2,4-triazole was portion-wise added under ice-cooling. After the generation of bubbles ceased, 0.49 g (10.6 mmol) of ethanol was added to the mixture and the resulting mixture was stirred at room temperature until the generation of bubbles ceased. The reaction mixture was further stirred for 2 hours at 50°C, poured into 100 ml of ice water and adjusted to pH 4 by addition of hydrochloric acid. The
precipitated solid was collected by filtration, washed with water and dried to give 1.40 g of the title compound as yellowish crystals.
m.p. 244-246°C (dec.)
1H-NMRfDMSO-dg) δ: 1.34(3H,t,J=7.0Hz),
4.48(2H,q,J=7.0Hz), 7.25(1H,td,J=6.8&2.4Hz), 7.57-7.71(2H,m), 8.76(1H,s), 8.83(1H,dt,J=6.8&1.1Hz),
14.89(1H,br.s)
IR(nujol) : 3250, 1520, 1490, 1405, 1350, 1330, 1173, 1150, 1100
[Example 6]
3-(6-Chloro-2-methoxyimidazo[1,2-b]pyridazin-3-ylthio)-1H-1,2,4-triazole (Compound No. II-3-1)
Figure imgf000087_0001
With 50 ml of methanol was diluted 5.70 g (35.3 mmol) of a methanolic sodium methoxide solution (28%). To the solution was added 3.57 g (35.3 mmol) of
3-mercapto-1H-1,2,4-triazole. The resulting solution was cooled to -60°C, to which 5.20 g (32.4 mmol) of bromine was added at the same temperature . The resulting mixture was stirred for 15 minutes. After addition of 5.40 g (29.4 mmol) of
6-chloro-2-methoxyimidazo[1,2-b]pyridazine at the same temperature, the reaction mixture was stirred at room temperature for 2 days and poured into water. The precipitated solid was collected by filtration, washed with water and dried to give 8.5 g of the title compound as pale yellowish crystals.
m.p. 186-187°C
1H-NMR(DMSO-d6) δ: 4.04(3H,s), 7.47 1H,d,J=9.3Hz), 8.16(1H,d,J=9.3Hz), 8.44(1H,br.s), 14.02(1H,br.s) IR(nujol) : 3300-2700, 1540, 1520, 1380, 1290, 1280, 1150, 966, 820
[Example 7]
3-(6-Chloro-2-methoxyimidazo[1,2-b]pyridazin-3- ylsulfonyl)-1H-1,2,4-triazole (Compound No. II-3-2)
Figure imgf000088_0001
In a mixture of 40 ml of acetonitrile and 40 ml of water was suspended 8.50 g (29.4 mmol) of 3-(6-chloro-2-methoxyimidazo[1,2-b]pyridin-3-ylthio)-1H-1,2,4-triazole, followed by addition of 15.4 g (117 mmol) of sodium percarbonate (effective oxygen content : 12.2%) at room temperature. The reaction mixture was further stirred for 3 hours while keeping an internal
temperature below 30°C. In the course of process, 7.70 g (58.7 mmol) of sodium percarbonate was further added. The reaction mixture was poured into water and adjusted to pH 2 by addition of hydrochloric acid. The
precipitated solid was collected by filtration, washed with water and dried to give 4.7 g of the title
compound as colorless crystals.
m.p. 234°C (dec.)
1H-NMR(DMSO-d6) δ: 4.10(3H,s), 7.69(1H,d,J=9.5Hz), 8.29(1H,d,J=9.5Hz), 8.78(1H,s), 14.92(1H,br.s)
IR(nujol) : 3100, 1540, 1520, 1450, 1400, 1360, 1280, 1240, 1165, 1130, 1020, 950, 830, 820, 740, 720, 620, 605
[Example 8]
3-(2,6-Dimethoxyimidazo[1,2-b]pyridazin-3-ylsulfonyl)-1H-1,2,4-triazole (Compound No. II-3-3)
Figure imgf000088_0002
To the stirred solution of 0.62 g (1.97 mmol) of 3-(6-chloro-2-methoxyimidazo[1,2-b]pyridazin-3- ylsulfonyl)-1H-1,2,4-triazole in 10 ml of DMF was added 0.43 g (7.88 mmol) of sodium methoxide at room temperature. The reaction mixture was stirred for 30 minutes at 50°C, poured into 50 ml of water and adjusted to pH 2 with hydrochloric acid. The
precipitated solid was collected by filtration, washed with water and dried to give 0.45 g of the title compound as colorless crystals,
m.p. 231-234°C (dec.)
1H-NMR(DMSO-d6) δ: 3.74(3H,s), 4.06(3H,s),
7.14(1H,d,J=9.6Hz), 8.07(1H,d,J=9.7Hz), 8.75(1H,s), 14.87(1H,br.s)
IR(nujol) : 3400, 2780, 1620, 1525, 1490, 1390, 1360, 1340, 1290, 1260, 1220, 1155, 1120, 1005, 960, 890, 820, 725, 715, 650, 620
The compounds (II) of the present invention which may be produced in a similar method to Examples 1 - 8 will be shown in [Table 1] to [Table 15] described below together with the compounds produced in Examples 1 - 8.
Figure imgf000090_0001
Figure imgf000091_0001
Figure imgf000092_0001
Figure imgf000093_0001
Figure imgf000094_0001
Figure imgf000095_0001
Figure imgf000096_0001
Figure imgf000097_0001
Figure imgf000098_0001
Figure imgf000099_0001
Figure imgf000100_0001
Figure imgf000101_0001
Figure imgf000102_0001
Figure imgf000103_0001
Figure imgf000104_0001
[Example 9]
3-(Imidazo[1,2-a]pyridin-2-ylmethylsulfonyl)-1H-1,2,4-triazole (compound No. II-8-1)
Figure imgf000105_0001
A mixture of 1.0 g (6.00 mmol) of
2-chloromethylimidazo[1,2-a]pyridine, 0.61 g (6.03 mmol) of 3-mercapto-1H-1,2,4-triazole, 0.83 g (6.01 mmol) of potassium carbonate and 10 ml of acetonitrile was stirred and heated at 70°C for 3 hours. After cooling, to the reaction mixture were added 10 ml of water and then 3.15 g (24.02 mmol) of sodium
percarbonate (effective oxygen content : 12.2%). The reaction mixture was stirred for 3 hours while keeping an internal temperature below 30°C. The reaction mixture was added with 30 ml of water and then adjusted to pH 7 with hydrochloric acid under ice-cooling. The precipitated solid was collected by filtration, washed with water and dried to give 1.24 g of the title compound as pale yellowish crystals,
m.p. 230°C (dec.)
1H-NMR(DMSO-d6) δ: 4.90(2H,s), 6.88 (1H, td, J=6.8&1.2Hz), 7.22(1H,ddd,J=9.1&6.7&1.3Hz), 7.47 (1H,dd, J=9.1&0.7Hz), 7.87(1H,s), 8.53(1H,dt,J=6.8&1.2Hz), 8.88(1H,s),
14.85(1H,br.s)
IR(nujol) : 3150-2200, 1323, 1252, 1145, 1130, 958
The compounds (II) of the present invention which may be produced in a similar manner to Example 9 will be shown in the following [Table 16] together with the compound produced in Example 9.
[Table 16]
Figure imgf000106_0002
In the above Tables 1 - 16, the compound (II) marked with * in the column of m.p. was subjected to the subsequent reaction without isolation and its structure was confirmed as the compound (I), and the compound (II) marked with ** in the column of m.p. was subjected to the subsequent reaction without isolation and its structure was confirmed as the corresponding sulfone compound.
[Example 10]
3-(2-Chloroimidazo[1,2-a]pyridin-3-ylsulfonyl)-N,N-diethyl-1H-1,2,4-triazole-1-carboxamide (Compound No 1-1-4)
Figure imgf000106_0001
In 6 ml of DMSO were suspended 0.77 g (2.71 mmol) of 3-(2-chloroimidazo[1,2-a]pyridin-3-ylsulfonyl)-1H-1,2,4-triazole and 0.45 g (3.26 mmol) of potassium carbonate. To the suspension, 0.44 g (3.25 mmol) of N,N-diethylcarbamoyl chloride was added and the resulting mixture was stirred at room temperature overnight. The reaction mixture was added with 30 ml of water and extracted with chloroform (20 ml each, 2 times). The extracts were combined, dried over magnesium sulfate and concentrated. The obtained residue was purified by silica gel column chromatography (eluent :
chloroform-ethyl acetate, 2 : 1, v/v) to give 0.91 g of the title compound as colorless crystals,
m.p. 138-139°C
1H-NMR(CDCl3) δ: 1.26 (6H,t,J=7.1Hz), 3.55 (4H,br.s),
7.17(1H,td,J=6.9&1.5Hz), 7.53-7.72 (2H,m), 8.83(1H,s),
9.11(1H,dt,J=7.0&1.2Hz)
IR(nujol) : 1710, 1435, 1358, 1340, 1160, 1150, 760,
740
Elemental analysis (C14H15N6O3SCl ) :
Calcd. (%): C 43.92; H 3.95; N 21.95
Found (%): C 43.66; H 3.87; N 21.85
[Example 11]
N,N-Diethyl-3-(2-methylpyrazolo[1,5-a]pyrimidin-3-ylthio)-1H-1,2,4-triazole-1-carboxamide (Compound No. 1-6-3)
Figure imgf000107_0001
In 10 ml of DMSO were suspended 1.0 g (4.31 mmol) of 3-(2-methylpyrazolo[1,5-a]pyrimidin-3-ylthio)-1H-1,2,4-triazole and 0.65 g (4.70 mmol) of potassium carbonate. To the suspension, 0.64 g (4.72 mmol) of N,N-diethylcarbamoyl chloride was added and the resulting mixture was stirred at 40°C overnight. The reaction mixture was added with 50 ml of ice-water. The
precipitated solid was collected by filtration, washed with water and dried to give 1.00 g of the title compound as pale yellowish crystals,
m.p. 160-162°C
1H-NMR(CDCl3) δ: 1.05(6H,br.s), 2.57(3H,s),
3.42(4H,q,J=7.0Hz), 6.88 (1H,dd,J=6.9&4.1Hz),
8.57(1H,dd,J=4.1&1.7Hz), 8.65 (1H,dd,J=7.0&1.8Hz), 8.67(1H,s)
IR(nujol) : 1685
[Example 12]
N,N-Diethyl-3-(2-methylpyrazolo[1,5-a] pyrimidin-3-ylsulfonyl)-1H-1,2,4-triazole-1-carboxamide (Compound No. 1-6-4)
Figure imgf000108_0001
In 10 ml of chloroform, 0.50 g (1.51 mmol) of N,N-diethyl-3-(2-methylpyrazolo[1,5-a]pyrimidin-3-ylthio)-1H-1,2,4-triazole-1-carboxamide was dissolved, to which 0.74 g (3.00 mmol) of metachloroperbenzoic acid (70%) was added in small portions under ice-cooling. The reaction mixture was stirred under ice-cooling for 30 minutes, then at room temperature for 5 hours. After another addition of 0.10 g (0.41 mmol) of metachloroperbenzoic acid (70%), the reaction mixture was stirred at room temperature overnight. The reaction mixture was added with 40 ml of water and then with potassium carbonate to adjust to pH 10, and extracted with chloroform (20 ml each, twice). The extracts were combined, washed with an aqueous saturated sodium hydrogen carbonate solution, dried over magnesium sulfate and concentrated. The obtained residue was purified by silica gel column chromatography (eluent: ethyl acetate). The solid obtained was washed with ethyl ether, collected by filtration and dried to give 0.26 g of the title compound as colorless crystals, m.p. 125-126°C
1H-NMR(CDCl3) δ: 1.25 (6H,t,J=7.0Hz), 2.80(3H,s),
3.57(4H,br.s), 7.09 (1H,dd,J=6.9&4.2Hz),
8.70(1H,dd,J=6.9&1.8Hz), 8.76-8.80(2H,m)
IR(nujol) : 1720, 1460, 1440, 1360, 1342, 1270, 1210,
1155
Elemental analysis (C14H17N7O3S) :
Calcd. (%): C 46.27; H 4.72; N 26.98
Found (%): C 46.21; H 4.61; N 27.03
[Example 13]
N,N-Diethyl-3-(2-ethylthioimidazo[1,2-a] pyridin-3-ylsulfonyl)-1H-1,2,4-triazole-1-carboxamide (Compound No. 1-1-25)
Figure imgf000109_0001
In 10 ml of DMSO were suspended 1.50 g (4.85 mmol) of 3-(2-ethylthioimidazo[1,2-a]pyridin-3-ylsulfonyl)-1H-1,2,4-triazole and 0.74 g (5.35 mmol) of potassium carbonate. To the suspension, 0.73 g (5.38 mmol) of N,N-diethylcarbamoyl chloride was added and the
resulting mixture was stirred at 50°C for 1 hour. To the reaction mixture, 0.33 g (2.43 mmol) of N,
N-diethylcarbamoyl chloride was further added and the resulting mixture was stirred at the same temperature for 1 hour. The reaction mixture was added with 30 ml of ice water and extracted with chloroform (20 ml each, 2 times). The extracts were combined, washed with water, dried over magnesium sulfate and concentrated. The obtained residue was purified by silica gel column chromatography (eluent : n-hexane-ethyl acetate, 1 : 2, v/v). The obtained solid was washed with n-hexane, collected by filtration and dried to give 1.85 g of the title compound as colorless crystals. m.p. 113-114°C
1H-NMR(CDCl3) δ: 1.26(6H,t,J=7.1Hz),
1.42(3H,t,J=7.4Hz), 3.29 (2H,q,J=7.4Hz), 3.55(4H,br.s),
7.01(1H,td,J=6.9&1.4Hz), 7.46 (1H,ddd,J=9.0&6.9&1.3Hz), 7.60(1H,dt,J=9.0&1.2Hz), 8.80(1H,s),
8.98(1H,dt,J=6.9&1.1Hz)
IR(nujol) : 1712, 1420, 1350, 1340, 1260, 1160, 1150,
1130, 755
Elemental analysis (C16H20N6O3S2) :
Calcd. (%): C 47.04; H 4.94; N 20.57
Found (%): C 46.80; H 4.93; N 20.68
[Example 14]
N,N-Diethyl-3-(2-ethylsulfinylimidazo[1,2-a]pyridin-3-ylsulfonyl)-1H-1,2,4-triazole-1-carboxamide (Compound No. 1-1-26)
Figure imgf000110_0001
To a solution of 0.60 g (1.47 mmol) of N,N-diethyl-3-(2-ethylthioimidazo[1,2-a]pyridin-3-ylsulfonyl)-1H-1,2,4-triazole-1-carboxamide in 10 ml of acetic acid was added 0.17 g (1.50 mmol) of 30% aqueous hydrogen peroxide solution and the resulting mixture was stirred at room temperature overnight. To the reaction mixture was added 0.07 g (0.62 mmol) of 30% aqueous hydrogen peroxide solution and the resulting mixture was stirred for 5 hours at room temperature. The reaction mixture was added with 60 ml of ice-water and extracted with ethyl acetate (20 ml each, 2 times). The extracts were combined, washed with an aqueous saturated sodium hydrogencarbonate solution, dried over magnesium sulfate and concentrated. The obtained residue was purified by silica gel column
chromatography (eluent : chloroform-acetone, 2 : 1, v/v). The obtained solid was washed with ethyl ether. collected by filtration and dried to give 0.56 g of the title compound as colorless crystals.
m.p. 130-131°C
1H-NMR(CDCl3) δ: 1.24 (6H,t,J=7.1Hz),
1.41(3H,t,J=7.4Hz), 3.34 (2H,qd,J=7.5&2.3Hz),
3.55(4H,br.s), 7.22 (1H,td,J=7.0&1.0Hz),
7.62(1H,ddd,J=9.1&6.9&1.0Hz), 7.91 (1H,dt,J=9.1&1.0Hz),
8.83(1H,s), 9.06(1H,dt,J=7.0&1.0Hz)
IR ( nujol ) : 1720 , 1460 , 1440 , 1343 , 1295 , 1265 , 12 10 ,
1160 , 1145 , 1132 , 1062 , 1048 , 765
Elemental analys is ( C16H20N6O4S2 ) :
Calcd . ( % ) : C 45 . 27 ; H 4 . 75 ; N 19 . 80
Found (%): C 45.04; H 4.70; N 19.92
[Example 15]
N,N-Diethyl-3-(2-ethylsulfonylimidazo[1,2-a]pyridin-3-ylsulfonyl)-1H-1,2,4-triazole-1-carboxamide (Compound No. 1-1-27)
Figure imgf000111_0001
In 5 ml of DMF was dissolved 0.50 g (1.22 mmol) of N,N-diethyl-3-(2-ethylthioimidazo[1,2-a]pyridin-3-ylsulfonyl)-1H-1,2,4-triazole-1-carboxamide. To the solution, 0.60 g (2.43 mmol) of metachloroperbenzoic acid (70%) was portion-wise added under ice-cooling. The reaction mixture was stirred under ice-cooling for 30 minutes and then at room temperature for 4 hours. The reaction mixture was poured into 50 ml of ice-water and the resulting mixture was adjusted to pH 10 with potassium carbonate. The precipitate solid was
collected by filtration, washed with water, dried and purified by silica gel column chromatography (eluent : chloroform-ethyl acetate, 1 : 1, v/v). The obtained solid was washed with n-hexane, collected by filtration and dried to give 0.47 g of the title compound as colorless crystals,
m.p. 161-162°C
1H-NMR(CDCl3) δ: 1.21 (6H,br.s), 1.42 (3H,t,J=7.5Hz), 3.53(4H,br.s), 3.67 (2H,q, J=7.5Hz),
7.31(1H,td,J=7.0&1.3Hz), 7.67 (1H,ddd,J=9.0&6.9&1.2Hz), 7.94(1H,dt,J=9.0&1.2Hz), 8.78(1H,s),
9.35(1H,dt,J=7.1&1.1Hz)
IR(nujol) : 1712, 1460, 1435, 1365, 1320, 1158, 1145, 1133
[Example 16]
N,N-Diethyl-3-(imidazo[1,2-a]pyridin-2-ylmethylsulfonyl)-1H-1,2,4-triazole-1-carboxamide (Compound No. 1-8-3)
Figure imgf000112_0001
In 10 ml of DMSO were suspended 1.24 g (4.71 mmol) of 3-(imidazo[1,2-a]pyridin-2-ylmethylsulfonyl)-1H-1,2,4-triazole and 0.78 g (5.64 mmol) of potassium carbonate. To the suspension, 0.70 g (5.16 mmol) of N,N-diethylcarbamoyl chloride was added and the resulting mixture was stirred at room temperature for 1 hour and then at 50°C for 2 hours. The reaction mixture was added with 30 ml of water and extracted with chloroform (20 ml each, 3 times). The extracts were combined, dried over magnesium sulfate and concentrated. The obtained residue was purified by silica gel column chromatography (eluent : chloroform-acetone, 1 : 1, v/v) to give 1.07 g of the title compound as colorless crystals.
m.p. 187-189°C
1H-NMR(CDCl3) δ: 1.20 (6H,br.s), 3.49 (4H,q,J=7.1Hz), 4.89(2H,s), 6.80(1H,td,J=6.8,1.2Hz),
7.17(1H,ddd,J=9.1&6.7&1.3Hz), 7.47 (1H,dd,J=9.1&0.8Hz), 7.78(1H,d,J=0.5Hz), 8.09 (1H,dt,J=6.8&1.2Hz), 8.86(1H,s) IR(nujol) : 1700, 1450, 1385, 1338, 1275, 1205, 1145,
860
[Example 17]
N,N-Diethyl-3-(3-chloroimidazo[1,2-a]pyridin-2-ylmethylsulfonyl)-1H-1,2,4-triazole-1-carboxamide
(Compound No. 1-8-5)
Figure imgf000113_0001
In 6 ml of DMF was suspended 0.50 g (1.38 mmol) of N,N-diethyl-3-(imidazo[1,2-a]pyridin-2-ylmethylsulfonyl)-1H-1,2,4-triazole-1-carboxamide. To the suspension, 0.20 g (1.50 mmol) of N-chlorosuccinimide was added under ice-cooling, and the resulting mixture was stirred under ice-cooling for 1 hour and then at 50°C overnight. The reaction mixture was added with 30 ml of water and extracted with chloroform (15 ml each, 2 times). The extracts were combined, washed with water, dried over magnesium sulfate and concentrated. The obtained residue was purified by silica gel column chromatography (eluent : n-hexane-acetone, 1 : 1, v/v) to give 0.28 g of the title compound as colorless crystals.
m.p. 129-131°C
1H-NMR(CDCl3) δ: 1.21(6H,br.s), 3.53 (4H,q,J=7.0Hz), 4.89(2H,s), 6.96(1H,td,J=6.8&1.1Hz),
7.24(1H,ddd,J=9.2&6.7&1.3Hz), 7.49(1H,dt,J=9.2&1.1Hz), 8.04(1H,dt,J=6.9&1.1Hz), 8.89(1H,s)
IR(nujol) : 1715, 1460, 1440, 1343, 1270, 1255, 1210, 1150, 750
Elemental analysis (C15H17N6O3SCl ) :
Calcd. (%): C 45.40; H 4.32; N 21.18
Found (%): C 45.55; H 4.30; N 21.42
[Example 18]
3-(6-Ethoxy-2-methylimidazo[1,2-b]pyridazin-3- ylsulfonyl)-N,N-diethyl-1H-1,2,4-triazole-1-carboxamide (Compound No. 1-3-24)
Figure imgf000114_0001
0.24 g (6.0 mmol) of 60% sodium hydride was washed with n-hexane and suspended in 10 ml of DMF under a dry nitrogen gas stream. The suspension was stirred under ice-cooling and added with 0.18 g (3.9 mmol) of
ethanol. The reaction mixture was stirred at room temperature for 1 hour, then at 50°C for 0.5 hour. To the reaction mixture, 0.6 g (2.0 mmol) of 3-(6-chloro-2-methylimidazo[1,2-b]pyridazin-3-ylsulfonyl)-1H-1,2,4-triazole was added and the resulting mixture was stirred at 50 - 60°C for 1 hour. To the reaction mixture 0.84 g (6.2 mmol) of N,N-diethylcarbamoyl chloride was added and the resulting mixture was stirred at the same temperature for 1 hour. After cooling, the reaction mixture was poured into 100 ml of water and the resulting mixture was extracted with ethyl acetate. The extract was dried and concentrated, and the residue was purified by silica gel column chromatography (eluent: chloroform-ethyl acetate, 2 : 1, v/v) to give 0.4 g of the title compound as
colorless crystals,
m.p. 123-124°C
1H-NMR(CDCl3) δ: 1.24(6H,m), 1.36 (3H,t,J=7.0Hz),
2.82(3H,s), 3.50(4H,m), 4.28 (2H,q,J=7.0Hz),
6.87(1H,d,J=9.7Hz), 7.79 (1H,d,J=9.6Hz), 8.81(1H,s)
IR(nujol) : 1720, 1340, 1280, 1260, 1200, 1150, 1020
The compounds (I) of the present invention which may be produced in a similar method to Examples 10 - 18 will be shown in the following [Table 17] to [Table 33] together with the compounds produced in Examples 10 to 18.
Figure imgf000115_0001
Figure imgf000116_0001
Figure imgf000117_0001
Figure imgf000118_0001
Figure imgf000119_0001
Figure imgf000120_0001
Figure imgf000121_0001
Figure imgf000122_0001
Figure imgf000123_0001
Figure imgf000124_0001
Figure imgf000125_0001
Figure imgf000125_0002
Figure imgf000126_0001
Figure imgf000127_0001
Figure imgf000128_0001
Figure imgf000129_0001
Figure imgf000130_0001
[Formulation Example 1]
Emulsifiable concentrates, containing:
Figure imgf000131_0001
[Formulation Example 2]
Wettable powders, as prepared by blending and grinding the following components:
Figure imgf000131_0002
[Formulation Example 3]
Granules, as prepared by adding water to the mixture containing the following components, blending and granulating:
Figure imgf000131_0003
[Formulation Example 4]
Granules, as prepared by adding water to the mixture containing the following components, blending and granulating:
Figure imgf000132_0001
[Formulation Example 5]
Granules, as prepared by adding water to the mixture containing the following components, blending and granulating:
Figure imgf000132_0002
[Formulation Examples 6]
Granules, as prepared by adding water to the mixture containing the following components, blending and granulating:
Figure imgf000132_0003
[Test Example 1]
Test for post emergence application against paddy field weeds.
Paddy soil was put in a square-shaped plastic pot having a surface area of 150 cm . After introducing water and pudding the soil, seeds of Echinochloa oryzicola, Cyperus difformis, Scirpus juncoides and Rotala indica were sowed. The plants were grown for a prescribed term, while keeping flooding water constant in 2 cm depth. When monocotyledon weeds grew up to 1 leaf stage and Rotala indica grew up to 2 leaf stage, the flooding water depth was maintained at 3 cm and a diluted herbicidal solution containing a compound (I) was applied on the water surface to give prescribed dosage (g/a) finally. The diluted herbicidal solution was prepared by dissolving 3.0 mg of the compound (I) in 1 ml of acetone containing 2% of Tween 20 and diluting with pure water up to 10 ml in total and further diluting with pure water up to a prescribed concentration of the compound (I). After application of the diluted herbicidal solution, the plants were grown in a green house, and three weeks after the application, herbicidal effect against various weeds was evaluated according to the standards shown in
[Table 34]. The test results were shown in [Table 35] to [Table 38].
[Test Example 2]
Test for pre emergence application against paddy field weeds.
Paddy soil was put in a square-shaped plastic pot having a surface area of 150 cm . After introducing water and puddling the soil, seeds of Echinochloa oryzicola and Scirpus juncoides were sowed and further a rice-plant seedling was transplanted to the soil. The flooding water depth was maintained at 3 cm and a diluted herbicidal solution containing a compound (I) was applied on the water surface to give prescribed dosage (g/a) finally. The dilute solution was prepared in a similar way to Test Example 1. After application of the dilute solution, the plants were grown in a green house. Three weeks after the application, herbicidal effect against various weeds and injury on the transplanted rice-plant were evaluated according to the standards shown in [Table 34]. The test results were shown in [Table 39] to [Table 42].
Figure imgf000134_0001
Figure imgf000134_0002
In [Table 35] to [Table 42], each plant used in the test will be expressed in the abbreviated name:
ECHOR: Echinochloa oryzicola
CYPDI : Cyperus difforms
SCPJO: Scirpus juncoides
ROTIN: Rotala indica
ORYSA: rice-plant
Figure imgf000135_0001
Figure imgf000136_0001
Figure imgf000137_0001
Figure imgf000138_0001
Figure imgf000139_0001
Figure imgf000140_0001
Figure imgf000141_0001
Figure imgf000142_0001
Industrial Applicability
The compounds (I) or their salts in accordance with the present invention have an excellent herbicidal activity on a variety of weeds such as paddy weeds and field weeds in a very low application level, and show less damage on culture plants such as rice, wheat, barley, soybean or corn, and therefore exhibit an excellent selective herbicidal effect which is
long-lasting. They also can be very safely used as a herbicide for paddy fields, fields, orchards or non-farming land, showing substantially no toxicity on mammals or fishes and shell fish without causing any environmental pollution.

Claims

1. A compound represented by the formula:
Figure imgf000144_0002
wherein Q is a fused heterocyclic group having a nitrogen atom in the bridgehead which may be
substituted, W is O or S, R1 and R2 each are hydrogen or a hydrocarbon group which may be substituted or R1 and R2 together with the adjacent nitrogen atom may form a nitrogen-containing heterocyclic group which may be substituted, R3 is hydrogen, a halogen atom or a hydrocarbon group which may be substituted, n is an integer of 0 to 2, m is 0 or 1, or a salt thereof.
2. The compound according to Claim 1, in which a fused heterocyclic group having a nitrogen atom in the bridgehead represented by Q is a group represented by the formula:
Figure imgf000144_0001
wherein the rings a and b each are a 4 to 8 membered heterocyclic ring containing 1 to 4 nitrogen atoms and optionally, 1 to 3 oxygen atoms and/or 1 to 3 sulfur atoms which may be in mono- or di-oxide form, which may be fused with a 5 or 6 membered alicyclic ring, an aromatic ring or a 5 or 6 membered heterocyclic ring. 3. The compound according to Claim 1, in which a fused heterocyclic group having a nitrogen atom in the bridgehead represented by Q is a group which is formed by removing one hydrogen atom bonded to a ring-constituting carbon atom at a position other than the bridgehead from imidazo[1,2-a]pyridine, imidazo[2,1-b]thiazole, imidazo[1,2-a]pyrimidine, imidazo[1,2-b]pyridazine, imidazo[1,2-a]imidazole, imidazo[2,1-b] (1,
3,4)thiadiazole, pyrazolo[1,5-a]pyrimidine,
pyrazolo[5,1-b]thiazole or pyrazolo[1,5-a]pyridine.
4. The compound according to Claim 1, in which Q is a fused heterocyclic group having a nitrogen atom in the bridgehead which may be substituted with 1 to 3
substituents selected from a hydroxyl group, an amino group, a cyano group, an sulfamoyl group, a sulfamoyloxy group, a mercapto group, a nitro group, a halogen atom, anorganic residue and a sulfo group.
5. The compound according to Claim 1, in which Q is a group represented by the formula:
Figure imgf000145_0001
wherein Z0 is 1) a hydrogen atom, 2) a halogen atom, 3) a C1-6 alkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6
alkylsulfinyl, C1-6 alkylsulfonyl or mono- or di-C1-6 alkylamino group, each of which may be substituted with 1 to 5 halogen atoms, or 4 ) a C1-6 alkoxy-C1-6 alkyl, C1-6 alkoxy-C1-6 alkoxy or C1-6 alkoxy-C1-6 alkylthio group, each of which may be substituted with 1 to 5 halogen atoms; Z and Z each are 1) a hydrogen atom, 2) a halogen atom or 3) a C1-6 alkyl group which may be substituted with 1 to 5 halogen atoms; Z3 and Z4 each are 1) a hydrogen atom, 2) a halogen atom, 3) a C1-6 alkyl, C1-6 alkoxy, C1-6 alkylthio or mono- or di-C1-6 alkylamino group, each of which may be substituted with 1 to 5 halogen atoms .
6. The compound according to Claim 1, in which a hydrocarbon group represented by R1 or R2 is a C1-19 hydrocarbon group.
7. The compound according to Claim 1, in which a hydrocarbon group which may be substituted represented by R1 and R2 is 1) a C1-6 alkyl, C2-6 alkenyl or C2-6 alkynyl group, which may be substituted with (i) 1 to 5 substituents selected from a C1-4 alkylthio, halogen, C1- 6 alkoxy, nitro, C1-6 alkoxy-carbonyl and mono- or di-C1- 6 alkylamino group, (ii) a C1-3 alkylenedioxy group or (iii) a C2-6 alkylidendioxy group, or 2) a C6-14 aryl or C7-19 aralkyl group, each of which may be substituted on the aromatic ring with (i) 1 to 3 substituents selected from a C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, acyl, acyloxy, nitro, cyano, halogen, acylamino and C1-4 alkylthio group, (ii) a C3-4 alkylene group or (iii) a C3-4 alkenylene group.
8. The compound according to Claim 1, in which a hydrocarbon group represented by R1 or R2 is a C1-6 alkyl group, a C2-6 alkenyl group or a C2-6 alkynyl group.
9. The compound according to Claim 1, in which R1 or R2 are a C1-6 alkyl group.
10. The compound according to Claim 1, in which a hydrocarbon group represented by R3 is a C1-19
hydrocarbon group.
11. The compound according to Claim 1, in which a hydrocarbon group represented by R3 is 1) a C1-6 alkyl, C2-6 alkenyl or C2-6 alkynyl group, each of which may be substituted with (i) 1 to 5 substituents selected from a C1-4 alkylthio, halogen, C1-6 alkoxy, nitro, C1-6 alkoxycarbonyl and mono- or di-C1-6 alkylamino group, (ii) a C1-3 alkylenedioxy group or (iii) a C2-6 alkylidenedioxy group, or 2) a C6-14 aryl or C7-19 aralkyl group, each of which may be substituted on the aromatic ring with (i) 1 to 3 substituents selected from a C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, acyl, acyloxy, nitro, cyano, halogen, acylamino and C1-4 alkylthio group, (ii) a C3-4 alkylene group or (iii) a C3-4 alkenylene group.
12. The compound according to Claim 1, in which a hydrocarbon group represented by R3 is a C1-6 alkyl group.
13. The compound according to Claim 1, in which R3 is hydrogen atom.
14. The compound according to Claim 1, in which m is 0 and n is 2.
15. The compound according to Claim 1, which is N,N-diethyl-3-(2-chloro-6-ethoxyimidazo[1,2-b]pyridazin-3-ylsulfonyl)-1H-1,2,4-triazole-1-carboxamide, N,N-diethyl-3-(2-methyl-6-ethoxyimidazo[1,2-b]pyridazin-3-ylsulfonyl)-1H-1,2,4-triazole-1-carboxamide, or N,N-diethyl-3-(6-propoxy-3-methylpyrazolo[5,1-b]thiazol-7-ylsulfonyl)-1H-1,2,4-triazole-1-carboxamide or a salt thereof.
16. A process for producing the compound according to Claim 1 or a salt thereof which comprises reacting a compound of the formula:
Figure imgf000147_0001
wherein Q, R3, m andd nn are as defined in Claim 1, or a salt thereof with a compound of the formula
Figure imgf000148_0004
wherein X is a leaving group and other symbols are as defined in Claim 1, or a salt thereof.
17. The process for producing a compound of the formula:
Figure imgf000148_0003
wherein p is 1 or 2 , Y is as defined above and other symbols are as defined in Claim 1, or a salt thereof, which comprises oxidizing a compound of the formula:
Figure imgf000148_0002
wherein Y is hydrogen atom or a group represented by the general formula
Figure imgf000148_0001
(wherein the symbols are as defined in Claim 1) and the other symbols are as defined above, or a salt thereof.
18. An agricultural chemical composition which
comprises an effective amount of the compound according to Claim 1 or a salt thereof.
19. The agricultural chemical composition according to Claim 18, which is a herbicidal composition.
20. The agricultural chemical composition according to Claim 18, which is a herbicidal composition effective against paddy weeds.
21. A compound represented by the formula:
Figure imgf000149_0001
wherein Q, R3, m and n are as defined in Claim 1, or a salt thereof.
22. A process for producing a compound of the formula:
Figure imgf000149_0002
wherein Q and R3 are as defined in Claim 1, or a salt thereof which comprises reacting a compound of the formula:
Q-CH2-X2 (V)
wherein X2 is a leaving group and Q is as defined in Claim 1, or a salt thereof with a compound of the formula:
Figure imgf000149_0003
wherein R3 is as defined in Claim 1, or a salt thereof.
23. A process for producing a compound represented by the formula:
Figure imgf000149_0004
wherein Q and R3 are as defined in Claim 1, or a salt thereof, which comprises reacting a compound
represented by the formula:
Figure imgf000150_0001
wherein R3 is as defined in Claim 1 or a salt thereof with a halogenating agent, and then reacting the resulting compound with a compound represented by the formula:
Q-H (VII)
wherein Q is as defined in Claim 1, or a salt thereof 24. Use of the compound of Claim 1 or a salt thereof in the preparation of a herbicidal composition.
PCT/JP1996/002705 1995-09-22 1996-09-19 Triazole compounds, their production and use WO1997011075A1 (en)

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Cited By (14)

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US7820821B2 (en) 2006-02-10 2010-10-26 Transtech Pharma, Inc. Benzazole derivatives, compositions, and methods of use as aurora kinase inhibitors
US8563550B2 (en) 2007-09-27 2013-10-22 Centro Nacional De Investigaciones Oncologicas (Cnio) Imidazolothiadiazoles for use as protein kinase inhibitors
EA017817B1 (en) * 2008-01-24 2013-03-29 Общество С Ограниченной Ответственностью "Инновационная Фармацевтика" 3-ARYLSULFONYLPYRAZOLO[1,5-a]PYRIMIDINES - ANTAGONISTS OF SEROTONIN 5-HTRECEPTORS, METHODS FOR THE PRODUCTION AND THE USE THEREOF
US8552005B2 (en) 2008-01-24 2013-10-08 Avincuro Pharmaceuticals, Inc. (EN) 3-sulfonyl-pyrazolo[1,5-a] pyrimidines / antagonists of serotonin 5-HT6 receptors, methods for the production and the use thereof
WO2009093206A3 (en) * 2008-01-24 2009-10-29 Алла Хем, Ллс 3-sulfonyl-pyrazolo[1,5-a] pyrimidines / antagonists of serotonin 5-ht6 receptors, methods for the production and the use thereof
US8829009B2 (en) 2008-01-24 2014-09-09 Alexander Vasillevich Ivashtchenko Substituted 2-amino-3-(sulfonyl)pyrazolo[1,5-a]pyrimidines - serotonin 5-HT6 receptor antagonists, method for use thereof
US8815918B2 (en) 2009-04-02 2014-08-26 Centro Nacional De Investigaciones Oncologicas (Cnio) Imidazo [2, 1-B] [1, 3, 4] thiadiazole derivatives
WO2016162318A1 (en) * 2015-04-08 2016-10-13 Bayer Cropscience Aktiengesellschaft Condensed bicyclic heterocycle derivatives as pest control agents and intermediate product
US10188108B2 (en) 2015-04-08 2019-01-29 Bayer Cropscience Aktiengesellschaft Fused bicyclic heterocycle derivatives as pesticides

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