GB2170197A - Cyclopropane-containing amine compounds - Google Patents

Cyclopropane-containing amine compounds Download PDF

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GB2170197A
GB2170197A GB08530644A GB8530644A GB2170197A GB 2170197 A GB2170197 A GB 2170197A GB 08530644 A GB08530644 A GB 08530644A GB 8530644 A GB8530644 A GB 8530644A GB 2170197 A GB2170197 A GB 2170197A
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general formula
hydrogen
alkyl
oil
compounds
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GB8530644D0 (en
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Paul Anthony Worthington
Balasubramanyan Sugvanam
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Imperial Chemical Industries Ltd
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Imperial Chemical Industries Ltd
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Priority claimed from GB858501169A external-priority patent/GB8501169D0/en
Priority claimed from GB858512400A external-priority patent/GB8512400D0/en
Priority claimed from GB858516804A external-priority patent/GB8516804D0/en
Priority claimed from GB858520592A external-priority patent/GB8520592D0/en
Priority claimed from GB858529482A external-priority patent/GB8529482D0/en
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Priority to GB08530644A priority Critical patent/GB2170197B/en
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/02—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms containing only hydrogen and carbon atoms in addition to the ring hetero elements
    • C07D295/027—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms containing only hydrogen and carbon atoms in addition to the ring hetero elements containing only one hetero ring
    • C07D295/03—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms containing only hydrogen and carbon atoms in addition to the ring hetero elements containing only one hetero ring with the ring nitrogen atoms directly attached to acyclic carbon atoms
    • 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
    • A01N33/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic nitrogen compounds
    • A01N33/02—Amines; Quaternary ammonium compounds
    • A01N33/04—Nitrogen directly attached to aliphatic or cycloaliphatic carbon atoms
    • 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
    • A01N33/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic nitrogen compounds
    • A01N33/02—Amines; Quaternary ammonium compounds
    • A01N33/08—Amines; Quaternary ammonium compounds containing oxygen or sulfur
    • A01N33/10—Amines; Quaternary ammonium compounds containing oxygen or sulfur having at least one oxygen or sulfur atom directly attached to an aromatic ring system
    • 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
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
    • A01N43/40—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings
    • 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
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/60—1,4-Diazines; Hydrogenated 1,4-diazines
    • 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
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/84—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms six-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,4
    • 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
    • A01N55/00—Biocides, pest repellants or attractants, or plant growth regulators, containing organic compounds containing elements other than carbon, hydrogen, halogen, oxygen, nitrogen and sulfur
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
    • C07D211/10—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms
    • C07D211/14—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
    • C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D211/20—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms
    • C07D211/22—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms by oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
    • C07D295/06—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by halogen atoms or nitro radicals
    • C07D295/073—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by halogen atoms or nitro radicals with the ring nitrogen atoms and the substituents separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
    • C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
    • C07D295/096—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
    • C07F7/02—Silicon compounds
    • C07F7/08—Compounds having one or more C—Si linkages
    • C07F7/0803—Compounds with Si-C or Si-Si linkages
    • C07F7/081—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te
    • C07F7/0812—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te comprising a heterocyclic ring

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  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Pest Control & Pesticides (AREA)
  • Plant Pathology (AREA)
  • Agronomy & Crop Science (AREA)
  • Engineering & Computer Science (AREA)
  • Dentistry (AREA)
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  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Description

SPECIFICATION Tertiary amine compounds This invention relates to cyclopropane containing tertiary amines useful as fungicides, to a process for preparing them, to fungicidal compositions containing them, and to methods of using them to combat fungi, especiallyfungal infections in plants.
The invention provides compounds having the general formula (I) :
and stereoisomers thereof, wherein R, R2, R3, R4, R5 and R6 each represent a hydrogen atom, an alkyl group containing 1 to 4 carbon atoms or a halogen atom, R and R8 each represent a hydrogen atom or an alkyl group containing 1 to 4 carbon atoms or together form a ring which may contain an addition hetero atom, X and Y each represent a hydrogen or a halogen atom, or an alkyl, cycloalkyl, alkenyl, alkynyl, aryl, aralkyl, alkoxy or aryloxy group, or a
group wherein R9, R , R"can be alkyl, alkenyl, alkynyl, cycloalkyl, or aryl ; and their acid addition salts.
The compounds have fungicidal activity.
The compounds of the invention are generally obtained in the form of mixtures of geometric isomers.
However, these and other mixtures of optical isomers can be separated into individual isomers by methods in the art and such isomers constitute a part of the present invention.
When R'and R8, together with the adjacent N-atom, represent a heterocyclic ring this may be, for example, a piperidine, morpholine, thiomorpholine, pyrrolidine or piperazine ring and any of these rings may bear substituents such as one or more C 4 alkyl groups or a phenyl group, or a hydroxyalkyl group.
The alkyl and alkoxy groups, especially for X and Y, but also for R1 to R3 and R9 to R"when alkyl may be straight or branched chain groups having 1 to 6, (for X and Y) and 1 to 4, (for R'to R") carbon atoms; examples are methyl, ethyl, propyl (n-or iso-propyl) and butyl (n-, sec-, iso-, or t-butyl) and the corresponding alkoxy groups. Cycloalkyl groups for X and Y may be cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.
The hafogen atoms which R'to R6 and X and Y may represent may be fluorine, chlorine, or bromine.
The alkenyl and alkynyl groups for X and Y may contain from 2 to 6 carbon atoms and R9, R10 and R"from 2 to 4 carbon atoms.
Examples of X and Y when these are aryl, aralkyl, aryloxy or aralkoxy groups are phenyl, benzyl, phenoxy and benzyloxy. These rings may be substituted with halogen (eg. fluorine, chlorine, or bromine), Cl-6 alkyl [eg. methyl, ethyl, propy (n-or iso-propyl) and butyl (n-, sec-, iso, or t-butyl)], Ci. alkoxy (eg. methoxy, ethoxy, propoxy and butoxy) halo-Ca 6-aikoxy (eg. trifluoromethoxy), halo-Ca 6-alkyl (eg. trifluoromethyl), nitro, phenyl and phenoxy. The phenyl ring may thus be unsubstituted or substituted with ring substituents as defined above. The X and Y substituents may be at the 2-, 3-or 4-positions of the phenyl ring and the 4-position is preferred.
The acid addition salts can be salts with inorganic or organic acids eg. hydrochloric, nitric, sulphuric, acetic, 4-toluene-sulphonic or oxalic acid.
In a further aspect the invention provides compounds of general formula (I) :
and stereoisomers and acid addition salts thereof, wherein R', R2, R3, R4, R5 and R6, which may be the same or different, represent a hydrogen atom, an alkyl group containing from 1 to 4 carbon atoms, or a halogen atom; R7 and R8, which may be the same or different, represent a hydrogen atom or an alkyl group containing from 1 to 4 carbon atoms ortogether form a ring which may contain oxygen, nitrogen or sulphur as an additional heteroatom and which ring may be optionally substituted; X and Y, which may be the same or different, represent a hydrogen or a halogen atom, or an alkyl group containing from 1 to 6 carbon atoms, a cycloalkyl group containing from 3 to 6 carbon atoms, an alkenyl or alkynyl group each containing 2 to 6 carbon atoms, a phenyl group, a benzyl group, an alkoxy group containing from 1 to 6 carbon atoms, a phenoxy group, a benzyloxy group, or a
group wherein R9, R10 and R11, which may be the same or different, represent an alkyl group containing up to 4 carbon atoms, an alkenyl or alkynyl group each containing from 2 to 4 carbon atoms, a cycloalkyl group containing from 3 to 6 carbon atoms, or a phenyl group.
In a still further aspect the invention provides compounds of general formula (I) :
and stereoisomers and acid addition salts thereof wherein R1 and R2 are hydrogen, halogen or Cl. alkyl ; R3 and R4 are hydrogen; R5 and R6 are hydrogen or C1-4 alkyl ; R7 and R8 are C14 alkyl, or, together with the adjacent N-atom, represent a piperidine, morpholine, thiomorpholine or piperazine ring which may be substituted with C1 4 alkyl, phenyl or hydroxymethyl ; and X and Y are hydrogen, halogen, C1-4 alkyl, C1-4 alkoxy, phenyl, phenoxy, benzyl, benzyloxy or a
group wherein R9, R10 and R1l are Ca. 4 alkyl.
In a yet further aspect the invention provides compounds of general formula (I) :
and stereoisomers and acid addition salts thereof, wherein R1 and R2 are hydrogen, methyl or chlorine; R3 and R4 are hydrogen; R5 and R 6 are hydrogen or methyl ; R6 and R7 are piperidine, 3, 5-dimethyl piperidine, morpholine, 2,6-dimethylmorpholine, diethylamino, 4-phenyl piperidine, 3-hydroxymethyl piperidine, thiomorpholine, piperazine, or 4-phenylpiperazine ; and X and Y are substituents at the 3-or 4-positions of the phenyl ring and one of which is hydrogen or C 4 alkyl whilstthe other is hydrogen, Ca4 alkyl, Ca4 alkoxy, chlorine, bromine, phenyl, phenoxy, benzyl, benzyloxy, or Ca 4 trialkylsilyl.
The invention further provides the specific compounds set out below in Table l ; and Examples 1 to 6; and stereoisomers and acid addition saltsthereof.
The invention particularly provides the compounds having the structures below :
(Compound No.
4 of Table I) t (Compound No.
15 of Table I) (Compound No.
94 of Table I) (Compound No.
133 of Table I) Examples of the compounds of the invention are shown in Table I. These conform to formula (I). The 1H nmr chemical shifts of parts of these structures have been recorded in orderto identify the various compounds.
TABLE I
pound X Y Rl R2 R3 R R5 R6/R m. p/b. p Ccmnents 1H raw shifts NO.-N( C) (ppnfranTMS) 'R8 1 47t :-C4H9 H Ii H Li H H H--to oil cis : trans 2.3-2.6,4hum* . ai3 2 4-t-C4119 H 11 El li H 11 H H-N) oil cis : crans 1. 1-1. 3. 9Hs < 3-A. r/CH2=i : 9 (Hg) 3 4-t-C 9 H H ii fl i H H oil trans Ar/CH2 3, 6-3. 8, 41 < '.--r3 4 4-t-C4119 H H"H H H H H-N 0 oil tras Ar/CH2 3.5-3.9,2Hm+ CH3 3 5 h-t-Cq, H3 Fi H H tu H H H-N 0 oil trans Ar/CE12 3.9-4.2,211n+.
''. Cfi3 TABLE I (cont)
ZanpounLI X Y Rl R2 R3 R4 R5 R6l/R7 | m. p/b. p Convents HrmrshiEts Kb.,-N ( C) (ppntfrmTMS) R8 3 64 t-C4R) R R j 6 H H | H I c s Ar/C212 3. 4-3 6, 2Rtz 'cl3 "-Qa13 7 4-~-C4Hg El El El H H H H-N 0 oil cisAr/CH 3.8-4.1, 2thon CH3 84-t-CH9 Fl CIi3 Cti3 H H H H-0 oil trans rlr/Qi2 9 4~t-C4Hg H CH3 CE13 H H H H ~C) oil tras Ar/CH2 I-3 10 4-9 H C113 H H 11 H N trarls Ar/ai2 CH cl3 TABLE I (cont)
i udvRl ; 1 N4| N5 R6, N7 m. p/b. p Convents -Hnmr shifts No.-N ( C) (PLxn Pran ZMS) 11 4-t-C, Iig H Qi3 H H 11 11 R oil transAr/CHg 2. 0-2. 6, 4 ! W* trans Ar/CH2 H3 3. 2 4-t4fIg H CE13 H H H H H"tO oil trans Ar/CfIg 3. 6-3.8,21inF 3 trans Ar/CH2 13 4-t-C4ti9 H Fi fi I3 H H Ci3 ~ N cil trans Ar/Qi2 2.0-2.6,4han* 14 4-t-C4119 H H H H H H CH3-NJ oil cis Ar/CH2 --, CEI3 15 4-t-CH9 H If ii if H H aI lv oil trans Ar/CH2 3. 65-3.75,2bon+ ~ TABLE I (cont)
Zanpotmd X Y R1 R2 R3 R4 R5 | R6, R7 m. p/b P RnnenFs 1N rrillr shifts No.-N ( C) (ppmfrcm'ItE) R8 I 3 16'4-L-CV9 H H H 11 H H a'3 oil trans Ar/CH23.80-4.22,2Eim' '3 3 17 4-t-C4E19 H H 11 11 H El a13 Gl oil cis Ar/CEi23.62-3.71,2E0m+ a'3 3 3 18 4-t-C4H9 H if H H H H CHg-bO oil cis Ar/CH2 ~. ~c 3 19 4-t-c4H9 11 H H H H CHg H-NJ'oil transAr/CHs 20 4-t-C rH9 Ii H H H H 013 H- oil I cis Ar/Qi2 TABLE I (cont)
owipouncl x Y Rl R2 R3 R4 R5 R6 R7 m. p/b. p Comments Hnmr shifts Mo.-N ( C) (ppn'franTHS) Ru 3 21 4-t-C4Hg H H H H H Cfig FI-N-O oil trans Ar/Cfi2 r fCH3 3 22 4-t-CHg II 11 H H H C153 fi-LT oil trans Ar/CH2 CHg 3 23 4-t < 4Hg fi FI H H Fi CH3 H-N-0 oil cis Ar/CEI2 , H3 cul13 24 4-L-C4H9 H I3 H H H CHg H-iQ O oi1 cis Az'/Qi2 CH3 TABLE I (cont)
.. ouncl X Y R1 R2 R3 R4 R5 R6 R m. p/b. p Cavments 1H nmr shifts I Nb.-N ( C) (ppmfrcmTMS) . R8 25 4--CgHy H H H H H H , O oil cis: trans 2.1-2.5,4hum* Ar/CH2 2: 3 CHs 26 fi 11 H H H H H H H-N 6 oil transAr/CH 3. 8-4. 2, 2Hm "a13 -.
27 4-iZ3H7 Fi fI H H ii H H vCH3 oil trans Ar/CH2 3.5-3.9,2Hn)'' 3 '3 28 4-i-C3H7 H H H H H H H CH3 oil cis 1\r/aH2 3.5-4.2,2hum+ CH3 i3 29 4-i-C3PI Fi Ii H EI H H Fi-1 O oil cis Ar/CFI2 3. 4-3.8,26m+0 ai3 TABLE I (cont)
Pound X Y R1 R2 R3 R R5 R6 R m. p/b. p Canents 1H nmr. shifts No.N\I8 ( C) (ppm fran TM R8 Cg 30 4-t < 4E19 H H li H H-N oil cis: trans C2H5 Ar/CEir2-3 31 4-t-C4Hg H Cl Cl H H H H-t oil trans Ar/C.'Iiz 2.3-2.6,4han* 'Cti3 32 4-t-C4ET9 H Cl Cl H H H H-N 0 oil trans Ar/CH2 3.6-3.8,2hum*' cl3 'C'I3 33 4-t-C4Hg H Cl Cl H H H H-N 0 oil transAr/CH 3 /fCN 34 4-t-C4Hg If ai3 H H H H H-N 0 oil transAr/CHg 3.6-3.7,2E'm+ ~ CE13 trans Ar/CH2 TABLE I (cont)
cmpound x Y Rl R2 113 R4 R5 R6 R7 m. p/b. p rentes 1H nmr shifts i No.-\ ( C) (pizn fran'RLS) 3 3 35 4-17C4H9 li CE'3 11 H ii H H-N 0 oil trans Ar/CE13 3.6-3.7,2RTn+ CR3cis Ar/CEi2 36 4-t-Cti9 H CHg H H H li H NX g0 oil trans Ar/CH3 3. 8-4. 2,2fun+ ~ ''chu trans Ar/CH2 I --, CfI3 37 4-t-C4Rg H CH3 H H li oil trans t CH3cis Ar/ 22 38 4-t-C4HgO H H H H H H H Fi- oil cis: trans 2.1-2.6,4Bu Ar/CH2 3: l r TABLE I (cont)
! I Compound X Y RI R2 R3 R4 R5 R6 R7 m. p/b. p Cannents 1Ti rcnr shifts No.-N ( C) (opnfrcmTMS) RB 13 39 4-t < 4H90 H H H H ii H Hi-N 0 oil trans Ar/ai2 4.5-4.9,2ElnF 3 3 4U 4-t-C4Hgo H H H H H 11 H-NO oil transAr/O 4. 8-5. 2,2Y, m+ i3.
.
41 4-a-13 H 3 H H H H U H Ho oil cis: trans 2.2-2.6,41tm* AR/CH2 1 : 2 3 42 4wH3 | H | H El | H | El 3.8-4.2,2Hm4' --CH3 'CH3 43 4-C ! l3 H H H H H H H-0 oil eis : trans Et~ < 0 5-4. &verbar; cis w CH3 ATt/CEI2 3 : 2 TABLE I (cont)
I anm7d X Y I Rl R2 R3 R4 R5 R6 R m. p/b. p. Cannents 1H ranr shifts No.-N C 1t frari'IrSS \rif3 reg ~ CI3 44 4-CHg H n H H H H H-N 0 oil trans 11r/CH2 3. 5-3. 9,2hum' 3 3 45 4-CHg H H H H I ! H I !-N 0 oil cisAr/CH 3.5-3. 8, 2Hm'' "cl3 46 4-Br H H H H H H H S oil cis: trans 2.1-2.6,4hum AR/CH 1 : 1 r~~CH3 47 4-Br H H H H H H H-t0 oil cis : trans 3. 8-4. 2,2Elm+ g~R33 AR/CH2 2 : 3 3 48 4-Br H H H H H H H-9 oil transAr/C ! 3. 4-3. 2fiv+ Qi3 TABLE I (cont)
pound X Y R1 R2 P3 T R6, R7 m. p/b. p Ccz ents 1H runr shifts 1 NO.-N (*C) (ppm fran Dis) Rus 'I i3 49 4-Br H H li ii H H H H 4 oil cis Ar/CH2 3.4-3.8,2hum+ CEi3 50 3-OC6H5 R El ii H H H El-NO oil cis : trans 2. 1-2.6,4Ehnk Ar/CH2 2 : 3 H3 51 3-OCgHg H H H H El H H-N 0 oil cis : trans 3.8-4.2,2Hm CH3 Ar./CH2 2 : 3 52 3-0C6EI5 H H H H H H H-N oil trans Ar/CH2 3.5-3.9,2Eh3+ a: 3 \-4 ai3 53 3-OC6H5 H H if H li H H NH oil cis Ar/CH2 3.4-3.8,2E-trn+ l CE13 TABLE I (cont)
I I l. : cmound X'Y Rl R2 R3 R4 R5 R6/R m. p/b. p Carnnents lIi rJnr shifts -N(*C) (pr-m fran rob 54 H H H H 11 H H H-N\ oil cis: trans 2.0-2.6,4Hm* Ar/CH2 1: 2 I I r'fCH3, 55 H H H H H H H H-N 0 oil trans Ar/O-I 3.5-3. S, 2Hm ! CH Ct13 1 t t 56 11 H H H H H H H-N 0 oil cis: trans 3.8-4.1, An+ CH3 Ar/Ct12 2: ; I3 57 H H H H H H H H-N 0 oil cis Ar/Ci2 3.4-3.8,2FBn+ 'CH3 ! I i CH3 58 04-tH4H9 H CEI3 CH3 H H H H oil. trans Ar/CH2 3.9-4.2,2S1l+ 'chu '0'3 TABLE I (cont)
i Cc. npound x Y R'R2 R3 R4 R5 R6 7 m. p/b. p Can-nents lli nmr shifts t ! 0.-N ( C) (ppn frcm'IMS) \S Ra 59 4--C4H9 H CHg CHg H ! I H H-NQ oil trans Ar/CH 3.6-3.8,211s+ CH3 60 3-OCH2C6H5 11 H H Fi Fl Ii Fi-I oil cis: trans 2.2-2.6,4Hm* Ar/Qi2 2: 3 r--p3 3 I 61 3-c7CEiZC6H5 H Ii Ii H Ii H H-LU oil cis : trans 3.9-4.1,2han'' 'ai3 Ar/CH2 3 : 2 ,- ? M3 62 3-OCH2C6H5 PI H H H H H H-N 0 oil trans Ar/CH2 3.6-3.7,2Ehn+ CH3 TABLE I (cont)
i npound X y R1 2 3 R4 R5 6 R7 m. pb. p Cnents 1H nnr shifts ~ l r~taI3 Ruz ! r-ais I I 63 3-OCH2C6H5 H fI H H H H | El-N 0 oil cis/GH 22mu "cl3 -\' 64 4-Cl 1 {| H H H H H ff-ND oil cis : trans 2. 0-2.6,4aD'.
Ar/T2 1 : 2 r-/ 65 4-Cl li H H H Ii ti Fi-N b I oil cis : trans 3. 8-4. 2, 2Tn+ j U 'CH3 Ar/ai2 1 : 1 a'3 66 4 I H H H H H. Ii H-N 0 oil trans Ar/CEI2 3.5-3.9,2Hm 3 -, CCH3 67 4-Cl H H 3. fi H H-N O oil. cis Ar/CZi2 3.4-3.8, ZET: i V-"ai3 TABLE I (cont)
Zonpound X Y R1 R2 tB3 R4 R5 R6/R7 m. p/b. p Cartnnents 1H rmu shifts No.'-N ( C) (ppttfromTMS) Riz I I 68 3-OC FI H H 5 H H H II H-N oil cis : trans 2.1-2.6,4Hm* Ar/C ! 3 : 7 cl3 69 3-CCH3 H II H H H H H-N 0 oil cis: trans 3.9-4. 1, 2Hm''' 3 'Ctig Ar/CH 1: 2 clip Cfi3 70 3 < CH3 H H H H H H H 0 oil trans Ar/CH2 3.6-3.8, Z2n+ CH cl 71 3-OCEI3 H H H H H H H-N 0 oil cis Ar/CH2 3. 6-3. 8, 2tim' ai3 I 72 4-X6115 H H H H H H H-N oil cis : trans 2. 1-2. 5, 4Hmk Ar/a 1 : 1 I TABLE I (cont)
und X Y Rl R2 R3 R4 R5 R6 R7 m. p/b. p Ciments 1H snnr shifts Nos( C ? (ppn fran'IMS) Ra 73 4-OCgHg H H H H H H H-N O oil cis : trans 3.9-4.1,2Hm+ ' (3i3 Ar/I2 2: 3 cri, 4-OC6H5 H H H H H H fl oil trans t1r/t3i 3.6-3.8,25*sn+ 'cl3 3 75 4-OCgHg I ! H ii 3. h Ti-LvT oil cis Ar/Qi i 3.6-3. Sr2Ekn+ 3 ai3 76 4-C6H5 li H Fi H H H H ~ oil cis: trans 2.3-2.6,4han* Ar/CH 2: 3 3 77 4-C6H5 H H H H H H H-N'Q oil cis : trans 3.9-4.1,2fun+ y Y 'CHg Ar/CHl : 2 ! TABLE I (cont)
pound X Y Rl R2 R3 R4 R5 R6/R7 | m. p/b. p CarQnents lIi nnr shifts No.-N ( C) (ppn from'IMS.) Rus 3 78 4-C6fl5 ! I H H H H H 11-N 0 oil tram Ar/CI12 3. 6-3. 8, z-fkdl* jazz ; 3 79 4-CgHg H H H H H H H-N 0 oil cisAr/Q 3.5-3.7,2jlm L al3 80 3 CH3 H li H FI H H H oil ci : trans 3. 9-3. Fi, 4i) m* Ar/CE12 1 : 2 CH3 ., CFI3 3-ai3 H H H H H H H 13 oiI > A : 3 TABLE I (cont)
i cmpound X Y R1 R2 R3 I R4 R5 I R6 R m. p/b. p G mments lH rmr shifts Nos( C) (n frar. ZMS) ( \ Ita ! ~~~ ~ ~ ~ Qi3 82 3-CH3 H H Ii cis 11 trans 3. trans Oil cis Qi3 Ar/CH2 2: 3 r 3 83 3-CH3 11 If H H H U H-N 0 oil transAr/ai 3.6-3.8,2Hm+ zain Q33 84 3-CH3 H H H H H H H-N oil cis Ar/CH2 3.4-3. S, 2Hm+ Olg 3 85 4-MI3 H H H H EX H H-N oil cis: trans 2.3-2.6,4fob* Ar/Cfi2=3 : l.
TABLE I (cont)
anpound | R2 | R3 R4 | R5 R6/R7 p/b. p Comments 4lnmr shifts No.-\ ( C) (ppn from IMS) Ra 3 86 4 lui H H El H 11 H-N 0 oil cis: trans 3.9-4.1,2Et i73 Ar/ar2=l : 2 r-e3 87 4-CCH3 H H H H fi H H-N 0 oil transAr/CH-3. 6-3.7,2. tortu "au a ; 3 es 4-OCH3 H H H II H H H-N 0 oil cis Ar/Cl12 3.6-3.7,2E7.
--t-CH3 . eCH3 89 4ace13 11 H H Fl 1 H H 2 oil cis: trans 2.1-2.5,4Hlt+ CE3 al3/Cd3=l l cis:trans Ar/CH=l : 2 TABLE I (cont)
; ; pound X | Y Rl R2 R3 | R4 R5-R6 R7 m. p/b. p Comments 1H rmr shifts No.- ( C) (ppm from IMS) I--1 90 4-OCHg H 11 11 H H H H-N)-Ph 67-68 ci. sAr/CH 2. 1-2.6,4Hfn* I 91 -OCfI3 H Ii H 2. FI 5, H-t-r^h oil trans Ar/CH2 2.1-2.5, Hm* CH3 92 4--C H C1S3 H lI H H H H-N oil trans Ar/a ; 3 3.9-4.1,2EiDnq 'Cti3 trans Ar/Qi2 CH3 93 4-i3H7 ti CH3 H H H H H ~M0 Oil trans Ar/CE13 3.5-3.7,21in+ '-CH3 cisAr/CH I CEi3 94 4-i-C3Ci H a ; 3 H H H H H M oil trarts A^r/H3 3.5-3.8, i ~ ~ ~ ~ C7L ; 73 tr Ar/CEI2 1-I CHg trans. Ar/CH TABLE I (cont)
pound X Y Rl R2 R3 R R5 lZ6 R m. p/b. p Corcents 1H tmN shifts rlo.-\ ( C) (pxn frmn 2MS) i3 95 4-i < 3H7 H CEI3 H H H H H-NO-oil transAr/CHg 3. 5-3. 7, 2tht'' i CEi3 cis Ar./Cti2 nid 1 , 96 3-Br H H Ti H H H H NF3 oil cis: trans 2.2-2.5,4Eim* I Ar/CH=l : l CE13 97 3-Br H H H El H H H 0 oil trans Ar/CH2 3.9-4.1, 2Hm''' 'cl 3 . CH3.
98 3-Br H H H H if H Mcn3 oi ! t 3 l l TABLE I (cont)
I pund X Y Rl R2 tt3 R R5 R6 R m. p/b. p Qamvents 1H nmr shifts No. l 0 < ~ N\R8 ( C) &verbar; &verbar; (FEm irsm E) &verbar; No.-N ( C) I Ors 3 99 3-Br H H H H H I ! H-NO oil cisAr/CI 3. 6-3. 7, 2Hn 3 1 100 4--C ! g H H H H H ii-tkD-M oil transAr/CH 1. 3, 9Hs (-CHc,) 101 4-t--CATI H H H I ! H H'H-M/T) H oil transAr/CH 1. 25, 9Hs (t-c410) 102 4- (CHg) 3Si H H fi H H fi H-tQ oil trans Ar/CH2 2. 2-2.5,4Hm* i 103 4- (Qi3) 3Si H I II Ii H H H H-L oil cis Ar/CH2 2.0-2.4 4rem* TABLE I (cont)
impound X Y R*-R R R pS R R ? m. p/b. p Ccmnents Hnmr shifts No.-N ( C) (ppmfrcmTMS) R8 104 3-(CE13) 3Si El H H II H H H I-N oi1 trans r/ (i2 I 2. 2-2. 5, tEtm* 105 3- (CH3) 3Si If Ei H EE H 11--1 oil cis Ar/CH 2. 1-2. 4, 4Hm* 106 4--Clg H H H H H H H-. 9 oil transAr/CH 1. 3, 9tls (~-C4119) 107 4- LEIg H H H H H H H-Np-Ph oil eisAr/CH 1. 35, 3 ? ! s (t-C4Mg) 108 4-~-C4Hg Ir H Li 11 H H H-N N-Ph oil trans Ar/CH2 1. 3, 9Ms (t-C4FI) 109 4-t < 4Hg H CHg H FI H H CEE3t oil trans Ar/CIE3 2.1-2.6,4P=m* cisAr/CH2 I TABLE I (cont)
i pound x : 1'R 2 3 R4 5 R6 R I m. p/b. p Corrnents 1H anr shifts No.-N( C) (Pixn fr'an'IMS) rua HO 10 4"9 H CFi3 t1 H H II H ~b oil cis Ar/CH3 2. 2-2.8,411itX trar. s Ar/Q32 7. 7. 1 4-t-CIy H CIi J H H I3 H Qi3-i I oil trans Ar/CH3 2. 2-2.8, 41 ! ne transAr/CH2 2 I 112 4-~ < 3H7 H CEE3 11 H H H H Ph oil trans A~/CH3 2. 25,611, 1 cisA--/C [12 113 4-i-C3H7 H CE13 H H H H El ~2 > Ph oil trans Ar/Cìl3 2. 25, GI'. d trans Ar/CH2 (~-C3H ?) 114 4-i-C3 : i H C113 H H LI fI Ei-N-Ph oil cis Ar/CIi3 2. 25, 6rI < 1 trans Ar/CH3 (i-C3H7) v TABLE I (cont)
i Fxurid X Y Rl R2 R3 R4 R5 I R6 RT m. p/b. p Cbrtments 1H nmr shifts No. l \ i3 | (ppm fran 4S) 115 4-j-CgHy H |CT13 H H H H H-t ()-Fh oil cisAr/CHg 2.25,6Hd cis Ar/CH2 Ii-C3fil I/-.
116 4-t-c,, Hg ii CH3 H R 11 H CH3-C113 oil trans Ar/CR3 3.6-3. r), 2LLill CH3 cis Ar/CE12 CHg cis Ar/CHg cis 9-4. 1, 2r 117 4-t-C, ii9 ii C (i3 H H H H CHg-NO oil trans Ar/ai '-CHU 3 118 4-~-C4Hg H CEr3 H H H H CH3 ~ < oi. l cis Ar/CH3 3.6-3.8,2Hm+ 0trans Ar/CH TABLE I (cont)
nixouncl X Y RI R2 R3 R4 R5 R6 |/R7 | m. p/b. p Coament 1H runr shifts No.-N ( C) (pprnfrcmIUS) R ENO-\ RB 119 11 H H H CH3 0 oil trans Ar/a13 3. 9-4. 1, 2Fhii+ "CH3tr. ans Ar/Cfi2 ., s3 120 4-t-C, ti fI CfI3 Ii H H Fi CFI3-LQ Cj oil trars Ar/CH3 3.6-3.7, n+ Cd3 trans Ar/CH2 121 4-i-C3H7 H H H H 11 fi CH3 ~ Nx3 oil cis : trans Ar/CH=l : 2 ,-e, M3 122 4-i-C3H7 H H Fi H ! El CH3 NA oil cis : trans oil cis : trans 'ai3 Ar/M12=1 : 1 TABLE I (cont)
poi. tul X Y R1 R2 R3 R4 R5 R R . p/b. p Caments ZH nmr shifts / Non Rye c : FI3 123 4-j : H H H H H H 0 : 3-N 0 oil transAr/CH ! CH3 I C'd3 ! I3 124 4-l-C3E47 11 H H H H H CH3 QI3 l cis Ar/CH2 CHg /\ 125 3-t < , H H H H H H H-ND oi. 1 cis-. trans Ar/CH=l : 2 cl 3 126 3-t-C4H9 H H H H H H Nw oil cis: trans ' (N3 Ar/a ! =l : l TABLE I (cont)
compoundX Y R1 RZ R3 R'R5 R6 R m. p/b. p Cmnents 1H nmr sh ? fts tsso. l l \R8 l l (ppn fr n IMS) r. ! 6.-N ( C) (ppm frcm IMS) Rus r-- i3 I 127. 3-t-Cqjig H H H H H H li EE ~E < oil trans Ar/CEl2 1 CHg CH3 3 l 128 | 3-t-C4H9 ! H El H H Ii-O oil I cis Ar/QI2 "CH3 j i cl3 j C: I I i I 129 3-(CH3) 3Si H H H H H H El N 0 oil cis : trans 3. 9-4.1,2t. en' 'a'13 Ar/CH2=1 : 1 cl3 130 3- (ai3) 3Si 11 H 11 H H H H-N 0 oil trans Ar/CH2 3. 6-3. 8,21i-n+ 3 TABLE I (cont)
i . csnpound (X Y Rl P2 R3 R R R6 R m. p/b. p Comments -H rum-shifts No.-\ ( C) (Sn fran ZMS) ruz 3I 131 (Cl13) 3. 5-3.7,21in+ ", Qi3 I ai, 3 132 4- 4-(Cl3) 3Si H fi H H H il ; si3 \ 1r/CE12=1 : Ar/CHl : ! cl3 133 4- (CE13) 3Si H H H H U H H-NO oil transAr/CI 3. 5-3. 8, 2Hctt''' 3 X, CEI3 134 4- (a) gSi H H H H El H H-N 0 oil cis Ar/CE12 3.5-3.7, zain+ 3 Qi3 TABLE I (cont)
'ripound X Y Rt I R2 R3 R4 R5 R6 R m. p/b. p Cbnments 1H rmr. shi : ts No.-N ( C) (ppm frcm'n'E) \Ra R 135 4-n="4HO H H fi H H H H trans Ar/CH2 "'f'cHs 13S 4-nH4Hg H H H H H H H-N9 transAr/CH 3 Raz 137 4-na-ce9 11 H H H II H H NX CEl3 trans ArjCE'2 -CHg 138 4-s-C4H9 H 11 11 El fI H H b0 trans Ar/CH2 cH3 139 4-s-C4fig H Ii H H H il li-9 CH3 > A-/ CH3 TABLE I (cont)
i :cund X Y I R1 R2 R3 R RS I R6 R m. p/b. p Ccnments lIi rur shi-ts No.-H ( C) (ppnfrcmT/E) \8 R8 140 4-S-C4H9"H"H H H H"MR transAr/CH raz j3 141 4-) -CgHy H H H H n H H-) transAr/CH ruz , CF3 142 4-n-C3H7 H fi if H Ei li H vN ; CH3 trans Ar/CH2 cul13 a q; 3 143 ss-n-C31i7 H H H ii H H H CHg 144 4-i-C3H 2-CH3 H H H H H- transAr/CH TABLE I (cont)
und X Y R'R2 R3 R4 R5 R6/R7 m, p/b. p moments lli rT= shifts Nb.( C) (ppmfrcmTMS) Ruz ' 145 4-i-C3ti7 2-CfI3 FI H H H H-N trans Ar/CH2 013 a13 3 146 4-- 11 El ii H if H trans Ar/CH 3 I 147 4-(al353Si H |H H H H 11 jCHg-N trans Ar/CH 3 148 4-(Cl3) 3Si li Ei H H H H CHg-NO trans Ar/CH " (Ii3 1. .. 3 149 4- (Ci3) 3si| H li H H H H CH3-N0 trans Ar/CH2 a3 TABLE I (cont)
i I lound x Y Rl R R R5 R6 R m. p/b. p Gxenents 1Ii amr shifts I iYo. ( C) (prxn fran TVZ) Ru 155 4--CH9 H H H a Q H H-9 transAr/CtCHg) CHg cl3 156 4-t-C4Et9 H H ; H CES3 Ci3 H H-N 0 traits Ar/C (Cf ! 3) 'cul3 Cfi3 157 4-t-C4ti9 H n-II ti H H Nx 2 trans Ar/n-C4Hg C4H9,3 trans Ar/CH 3 158 4-1 ;-CH9 H n-H H H H 11 N~2\ CHg CH3 trans Ar/CHs 3 159 4--lui H n-n-H H H H-N 6 trans Ar/CH . C4Ti9l C4"91 1 Cl13 I TABLE I (cont)
jompound X Y RI R2 R3 R4 R5 | R6/R7 shifts No."N ( C) (pprnfrcmIMS) R8 \RS 160 4-j ;-CHg H n-H H H H fI trans e1r/CHZ k-C4 9--q 9 3 7 Cl 4-t-C4H HT H H H H H n--P transAr/CM 4 3 ; , CCX13 L 162 4-t-C4H9 H H H H H H n--N 0 trans Ar/CH2 C4H \NCH3 3 3 163 4-t-C4Hg H ti Fi fi H n-H C4HS--'M3 trans Ar/CH2 Ruz ; 164 4-t-C4ti9 H H Fi ti H n-Fi- trans ArCI ; 2 t CH < -\0 ~ TABLE I (cont)
une, x Y Rl R2 R3 R4 R R6 R7 m. p/b. p Coments lli m= shifts Kb.-H ( C) (ppmfrcmTMS) 8 ~... ~... ~.. i..... ~.
9 165 4--CHg H H H H Fi n-n--P transAr/CH l C4Hg C41i CE13 3 1664-t-C : 4H ET EI H H H n-n--O tran. s IirCET2 CHgCHc"-CHg 167 4-trains H H H H H H H-NH2 trans Ar/CH2 168 4-t-C4Hg H PI H H H H H NHn-C4Hg trans Ar/CH2 CH3 169 C6Hll H H EX H H H H 0 trans Ar/CH2 yclohexyl \ CHg TABLE I (cont)
compound X Y 1 R1 R2 R3 R4 R5 R6, R7 m. p/bvP Cmnents | 1H nmr shifts No.-N ( C) ! (pZn fran LS) Rus CH 170 Celli H El H H H H H-p transAr/CH cyc].ohexy1.'' CHg I 3 171 I CIi2'fi-Cfi2-Ii Ii Ei II Ii FI H-N tran. s Ar/Cfi2 I /- 172 CEi2=Cli CE12-H j H Fi fi H H H H-0 transAr/CH . f,. 3 C (I3 I Ct13 173CM=C-C ! - H H H H H H H-N 6 transAr/CHg 2 2 'CL3 33 I 174 CH=C-CH-H H H H H H H-N 0 transAr/CH là'3 * protons in the piperidine ring &alpha; to the nitrogen atcm.
+ protons in the morpholine ring &alpha; to the oxygen atcm.
The 13C nmr chemical shifts for compounds of Formula (J) where R1-R6 equals hydrogen,
is cis 2, 6-dimethylmorpholine, and Ar/CH2 is trans are given in Table II. By Ar/CH2 is intended, with reference to formula 1, the disposition of the aryl group
at the left hand side of the cyclopropane ring in relation to the moiety
(which is-CH2-since R3 and R4 are both H) at the right hand side of the cyclopropane ring; i. e. these are trans to each other.
TABLE il
13C @m@ shifts (ppm from TMS) Compound No from table I X Y Cr C2 C3 C4 Cs C6 C7 C8 4 4-t-C4Hg H 147. 998 139. 377 125. 145 124. 927 21. 918 20. 088 14. 665 62.942 27 4-i-C3H7 H 146. 106 139.998 126.354 125.610 22.197 20. 181 14.944 63.097 39 4-t-C4HgO H 153. 187 137.446 125.956 125.933 21.979 20. 378 14.838 63.069 44 4-CH3 H 134. 943 139.625 125.548 128.990 22.290 20. 305 14.758 63.128 48 4-Br H 119. 072 141. 932 127. 405 131. 390 22. 207 20. 947 15. 240 62.940 52 3-OC6H5 H 115. 998 145. 073 120. 560 129. 553 22. 541 20. 917 15. 240 62.948 55 H H 125. 393 142.633 125.517 128. 214 22.507 20. 522 14.944 62.973 74 4-OC6Hs H 157. 657 137.742 126.927 119.133 21.979 20. 408 14.982 63.069 66 4-CI H 131. 048 141.287 128.308 128.377 22.040 20. 856 15.164 62.856 78 4-C6H5 H 140. 971 138.521 126.037 127.058 22.362 20. 760 15.185 63.065 70 3-OCH3 H 110. 814-118. 147 129. 297 22. 685 20. 628 15. 116 63.843 Compoun No from table I X Y C9 C10 C11 C12 C13 C14 C15 C16 4-t-C4H9 H 59. 221 59.532 71.345 71.345 19. 065 19.065 124.927 125. 145 27 4-i-C3H7 H 59. 346 59.625 71.593 71.593 19.220 19. 220 125. 610 126.354 39 4-t-C4H9O H 59. 441 59.707 71.599 71.577 19. 224 19.224 124.119 125. 958 44 4-CH3 H 59. 377 59.687 71.624 71.624 19.220 19. 220 128. 990 125.548 48 4-Br H 59. 456 59.692 71.668 71. 668 19.285 19. 285 131. 390 127.405 52 3-OC6H5 H 59. 396 59.638 71.630 71.599 19.232 19. 232 157. 369 116.142 55 H H 59. 315 59.594 71.500 71.500 19.158 19. 158 128. 214 125.517 74 4-OC6H5 H 59. 434 59.692 71.683 71.660 19.277 19. 277 119. 133 126.927 66 4-CI H 59. 358 59.593 71.554 71.554 19. 217 19.217 128.377 128. 308 78 4-C6H5 H 59. 438 59.705 71.608 71.608 19.236 19. 236 127. 058 126.037 70 3-OCH3 H 59. 416 59.683 71.633 71.633 19. 230 19.230 159.762 111. 536 Compounds of general formula (I) :
can be prepared by treatment of a compound of general formula (ll) :
wherein R', R2, R3, R4, R5, R6, X, and Y are as defined above and Z is a leaving group such as chlorine, bromine, mesylate or tosylate, with an amine of general formula (III) :
wherein R and R8 are as defined above, in the presence of a convenient solvent such as ethanol or tetrahydrofuran, or, preferably, in the absence of a solvent at a temperature of 20-100 C. The compounds (II) can be prepared by treating an alcohol of general formula (IV) :
wherein R', R2, R3, R4, R5, R, X, and Y are as defined above with the usual halogenating agents (eg. phosphorus trichloride, phosphorus pentachloride, or phosphorus oxychloride when Z = chlorine and phosphorus tribromide, phosphorus pentabromide, or phosphorus oxybromide when Z = bromine), or mesyl chloride in pyridine (ortriethylamine) when Z = mesylate, ortosyl chloride in pyridine (or triethylamine) when Z = tosylate.
The alcohols (IV), wherein R3 = R4 = hydrogen, can be prepared by treating an ester of general formula
wherein R', R2, R5, R6, X and Y are as defined above and R is alkyl with a reducing agent (usually lithium aluminium hydride) in a convenient solvent such as diethyl ether or tetrahydrofuran.
The alcools (IV), wherein R3 = R4 = alkyl, can be prepared by treating the above ester (V) with an excess of alkyl magnesium halide or an excess of alkyl lithium in a convenient solvent such as diethyl ether or tetrahydrofuran.
The esters (V) can be prepared by reacting the cinnamic esters of general formula (VI) :
wherein R, R5 and R5, X and Y are as defined above with a phosphorane of general formula (Vil) :
wherein R1 and R2 are defined above in a convenientsolvent such as tetrahydrofuran.
In an alternative process the esters of general formula (V) wherein R5 = hydrogen, can be prepared by adding ethyl diazoacetate to the olefin of general formu la (Vlil) :
wherein R', R2, R6, X and Y are as defined above in a convenient solvent such as chloroform or dichloromethane using an appropriate catalyst such as anhydrous copper sulphate.
The compounds of general formula (I), where R3 = R4 = hydrogen, can also be prepared by treating an amide of general formula (IX) :
wherein R', R2, R5, R6, R7, R8, X, and Y are as defined above with a reducing agent (usually lithium aluminium hydride) in a convenient solvent such as diethyl ether or tetrahydrofuran.
The amides of general formula (IX) can be prepared by reacting an acid chloride of general formula (X):
wherein R', R2, R5, R6, X, and Y are as defined above, with an amine of general formula (III) :
in a convenient solvent such as diethyl ether or tetrahydrofuran.
The acid chloride of general formula (V) can be prepared by reacting an acid of general formula (Xi) :
wherein R', R2, R5, R6, X, and Y are as defined above with the usual chlorinating agents such as thionyl chloride or oxalyl chloride in a convenient solvent such as hexane or dichloromethane.
The acid of general formula (XI) can be prepared by hydrolysing the ester (V) in the normal manner using either sodium or potassium hydroxide in methanol/water solution at room temperature.
It is normal for compounds of general formula (IV) when R'= R 2= halogen to be prepared from the substituted allyl alcohol (Xll) :
wherein R3, R4, R5, R6, X, and Y are as defined above by the addition of a dihalocarbene in a convenient solvent such as chloroform or dichloromethane.
The compounds (VI), (VIII), and (XII) can be prepared by standard methods set out in the literature.
The salts of compounds of the general formula (I) can be prepared from the latter by known methods.
The compounds, salts and metal complexes are activefungicides, particularly againstthe diseases Puccinia recondita, Puccinia striiformis and other rusts on wheat, Puccinia hordei, Puccinia striiformis and other rusts on barley, and rusts on other hosts e. g. coffee, apples, apples, vegetables and ornamental plants Erysiphe graminis (powdery mildew) on barley and wheat and other powdery mildews on various hosts such as Sphaerotheca fuliginea on cucurbits (e. g. cucumber), Podosphaera leucotricha on apples and Uncinula necator on vines Helminthosporium spp., eg. Pyrenophora teres Rhynchosporium spp. and Pseudocercosporella herpot richoides on cereals Cercospora arachidicola on peanuts and other Cercospora species on for example sugar beet, bananas and soya beans Botrytis cinerea (grey mould) on tomatoes, strawberries, vines and other hosts Venturia inaequalis (scab) on apples.
Some of the compounds have also shown a broad range of activities against fungi in vitro. They have activity against various post-harvest diseases on fruit (e. g. Penicillium digatatum and italicum on oranges and Gloeosporium musarum on bananas). Further some of the compounds are active as seed dressings against: Fusarium spp., Septoria spp., Tilletia spp. (i. e. bunt, a seed borne disease of wheat), Ustilago spp., Helminthosporium spp. and Pseudocercosporella herpotrichoides on cereals, Rhizoctonia solani on cotton and Corticium sasakii on rice.
The compounds can move acropetally in the plant tissue. Moreover, the compounds can be volatile enough to be active in the vapour phase against fungi on the plant.
They may also be useful as industrial (as opposed to agricultural) fungicides, e. g. in the prevention of fungal attack on wood, hides, leather and especially paintfilms.
The compounds may be used as such forfungicidal purposes but are more conveniently formulated into compositions for such usage. The invention thus provides a fungicidal composition comprising a compound of general formula (I) as hereinbefore defined, or a salt, metal complex, ether or ester thereof ; and, optionally, a carrier or diluent.
The invention also provides a method of combating fungi, which comprises applying to a plant, to seed of a plant, or to the locus of the plant or seed, a compound, or salt, metal complex, ether or ester thereof, as hereinbefore defined.
The compounds, salts, metal complexes, ethers and esters can be applied in a number of ways, for example they can be applied, formulated or unformulated, directly to the foliage of a plant, or they can be applied also to bushes and trees, to seeds or to other medium in which plants, bushes or trees are growing or are to be planted, or they can be sprayed on, dusted on or applied as a cream or paste formulation, or they can be applied as a vapour; or as slow release granules. Application can be to any part of the plant, bush or tree, for example to the foliage, stems, branches or roots, or to soil surrounding the roots, or to the seed before it is planted; or to the soil generally, to paddy water or to hydroponic culture systems. The invention compounds may also be injected into plants or trees and they may also be sprayed onto vegetation using electrodynamic spraying techniques.
The term"plant"as used herein includes seedlings, bushes and trees. Furthermore, the fungicidal method of the invention includes preventative, protectant, prophylactic and eradicant treatment.
The compounds are preferably used for agricultural and horticultural purposes in the form of a composition. The type of composition used in any instance will depend upon the particular purpose envisaged.
The compositions may be in the form of dusting powders or granules comprising the active ingredient and a solid diluent or carrier, for example fillers such as kaolin, bentonite, kieselguhr, dolomite, calcium carbonate, talc, powdered magnesia, Fuller's earth, gypsum, Hewitt's earth, diatomaceous earth and China clay. Such granules can be preformed granules suitable for application to the soil without further treatment.
These granules can be made either by impregnating pellets of filler with the active ingredient or by pelleting a mixture of the active ingredient and powdered filler. Compositions for dressing seed, for example, may comprise an agent (for example a mineral oil) for assisting the adhesion of the composition to the seed; alternatively the active ingredient can be formulated for seed dressing purposes using an organic solvent (for example N-methylpyrrolidone or dimethylformamide).
The compositions may also be in the form of dispersible powders, granules or grains comprising a wetting agent to facilitate the dispersion in liquids of the powder or grains which may contain also fillers and suspending agents.
The aqueous dispersions or emulsions may be prepared by dissolving the active ingredient (s) in an organic solvent optionally containing wetting, dispersing or emulsifying agent (s) and then adding the mixture to water which may also contain wetting, dispersing or emulsifying agent (s). Suitable organic solvents are ethylene dichloride, isopropyl alcool, propylene glycol, diacetone alcool, toluene, kerosene, methyinaphthalene, the xylenes, trichloroethylene, furfuryl alcool, tetrahydrofurfuryl alcool, and glycol ether (eg. 2-ethoxyethanol and 2-butoxyethanol).
The compositions to be used as sprays may also be in the form of aerosols wherein the formulation is held in a container under pressure in the presence of a propellant, eg. fluorotrichloromethane or dichlorodifluoromethane.
The compounds can be mixed in the dry state with a pyrotechnic mixture to form a composition suitable for generating in enclose spaces a smoke containing the compounds.
Alternatively, the compounds may be used in a microencapsulated form. They may also be formulated in biodegradable polymeric formulations to obtain a slow, controlled release of the active substance.
By including suitable additives, for example additives for improving the distribution, adhesive power and resistance to rain on treated surfaces, the different compositions can be better adapted for various utilities.
The compounds can be used as mixtures with fertilisers (eg. nitrogen-, potassium-or phosphoruscontaining fertilisers). Compositions comprising only granules of fertiliser incorporating, for example coated with, the compound are preferred. Such granules suitably contain up to 25% by weight of the compound.
The invention therefore also provides a fertiliser composition comprising the compound of general formula (I) or a salt or metal complex thereof.
The compositions may also be in the form of liquid preparations for use as dips or sprays which are generally aqueous dispersions or emulsions containing the active ingredient in the presence of one or more surfactants eg. wetting agent (s), dispersing agent (s), emulsifying agent (s) or suspending agent (s) sor which are spray formulations of the kind suitable for use in electrodynamic spraying techniques. The foregoing agents can be cationic, anionic or non-ionic agents. Suitable cationic agents are quaternary ammonium compounds, for example cetyltrimethylammonium bromide.
Suitable anionic agents are soaps, salts of aliphatic monoesters of sulphuric acid (for example sodium lauryl sulphate), and salts of sulphonated aromatic compounds (for example sodium dodecylbenzenesulphonate, sodium, calcium or ammonium lignosulphonate, butylnaphthalene sulphonate, and a mixture of sodium diisopropyl-and triisopropyl-naphthalene sulphonates).
Suitable non-ionic agents are the condensation products of ethylene oxide with fatty alcools such as oleyl or cetyl alcohol, or with alkyl phenols such as octyl-or nonyl-phenol and octylcresol. Other non-ionic agents are the partial esters derived from long chain fatty acids and hexitol anhydrides, the condensation products of the said partial esterswith ethylene oxide, and the lecithins. Suitable suspending agents are hydrophilic colloids (for example polyvinylpyrrolidone and sodium carboxymethylcellulose), and the vegetable gums (for example gum acacia and gum tragacanth).
The compositions for use as aqueous dispersions or emulsions are generally supplied in the form of a concentrate containing a high proportion of the active ingredient (s), and the concentrate is to be diluted with water before use. These concentrates often should be able to withstand storage for prolonged periods and after such storage be capable of dilution with water in orderto form aqueous preparations which remain homogeneous for a sufficient time to enable them to be applied by conventional and electrodynamic spray equipment. The concentrates may conveniently contain up to 95%, suitably 10-85%, for example 25-60%, by weight of the active ingredient (s). These concentrates suitably contain organic acids (eg. alkaryl or aryl sulphonic acids such as xylenesulphonic acid or dodecyl benzenesulphonic acid) since the presence of such acids can increase the solubility of the active ingredient (s) in the polar solvents often used in the concentrates. The concentrates suitably contain also a high proportion of surfactants so that sufficiently stable emulsions in water can be obtained. After dilution to form aqueous preparations, such preparations may contain varying amounts of the active ingredient (s) depending upon the intended purpose, but an aqueous preparation containing 0.0005% or 0. 01% to 10% by weight of active ingredient (s) maybe used.
The compositions of this invention can comprise also other compound (s) having biological activity, eg. compounds having similar or complementary fungicidal activity or compounds having plant growth regulating, herbicidal or insecticidal activity.
The otherfungicidal compound can be, for example, one which is capable of combating ear diseases of cereals (eg. wheat) such as Septoria, Gibberella and Helminthosporium spp., seed and soil borne diseases and downy and powdery mildews on grapes and powdery mildew and scab on apple etc. These mixtures of fungicides can have a broader spectrum of activity than the compound of general formula (I) alone ; further the other fungicide can have a synergistic effect on the fungicidal activity of the compound of general formula (I). Examples of the otherfungicidal compound are carbendazim, benomyl, thiophanate-methyl, thiabendazole, fuberidazole, etridazole, dichlofluanid, cymoxanil, oxadixyl, of urace, metalaxyl, furalaxyl, benalaxyl, fosetyl aluminium, fenarimol, iprodione, procymidione, vinclozolin, penconazole, myclobutanil, R0151297, S3308, pyrazophos, ethirimol, ditalimfos, tridemorph, triforine, nuarimol, triazbutyl, guazatine, propiconazole, prochloraz, flutriafol, chlortriafol ie. the chemical 1- (1, 2,4-triazol-1-yl)-2- (2,4 dichlorophenyl) hexan-2-ol, DPX H6573 (1-((bis-4-fluorophenyl) methylsilyl) methyl)-1 H-1, 2,4-triazole, triadimefon, triadimenol, diclobutrazol, fenpropimorph, fenpropidine, triademorph, imazalil, fenfuram, carboxin, oxycarboxin, methfuroxam, dodemorph, BAS 454, blasticidin S, Kasugamycin, edifenphos, kitazin P, phthalide, probenazole, isoprothiolane, tricyclazole, pyroquilan, chlorbenzthiazone, neoasozin, polyoxin D, validamycin A, repronil, flutolanil, pencycuron, diclomezine, phenazin oxide, nickel dimethyldithiocarbamate, techlofthalam, bitertanol, bupirimate, etaconazole, streptomycin, cypofuram, biloxazol, quinomethionate, dimethirimol, fenapanil, tolclofos-methyl, pyroxyfur, polyram, maneb, mancozeb, captafol, chlorothalonil, anilazine, thiram, captan, folpet, zineb, propineb, sulphur, dinocap, binapacryi, nitrothal-isopropyl, dodine, dithianon, fentin hydroxide, fentin acetate, tecnazene, quintozene, dichloran, copper containing compounds such as copper oxychloride, copper sulphate and Bordeaux mixture, and organomercury compounds such as 1- (2-cyano-2-methoxyimino- acetyl)-3-ethyl urea.
The compounds of general formula (I) can be mixed with soil, peat or other rooting media for the protection of plants against seed-borne, soil-borne or foliar fungal diseases.
Suitable insecticides are pirimicarb, dimethoate, demeton-S-methyl, formothion, carbaryl, isoprocarb, XMC, BPMC, carbofuran, carbosulfan, diazinon, fenthion, fenitrothion, phenthoate, chlorpyrifos, isoxathion, propaphos, monocrotophas, buprofezin, ethroproxyfen and cycloprothrin.
The plant growth regulating compound can be one which controls weeds or seedhead formation, or selectively controls the growth of the less desirable plants (eg. grasses).
Examples of suitable plant growth regulating compounds, for use with the invention compounds are the gibberellins (eg. GA3, GA4, or GA7), the auxins (eg. urea, fenapanil, ofurace, propiconazole, etaconazole and fenpropemorph.
The compounds of general formula (I) can be mixed with soil, peat or other rooting media for the protection of plants against seed-borne, soil-borne or foliar fungal diseases.
Suitable insecticides are pirimicarb, dimethoate, demeton-s-methyl and formothion.
The other plant growth regulating compound can be one which controls weeds or seedhead formation, improves the level or longevity of the plant growth regulating activity of the compounds of general formula (I), selectively controls the growth of the less desirable plants (eg. grasses) or causes the compound of general formula (I) to act faster or slower as a plant growth regulating agent. Some of these other agents will be herbicides.
Examples of suitable plant growth regulating compounds, which can display synergy in admixture, or use, with the invention compounds are the gibberellins (eg. GA3, GA or GA7), the auxins (eg. indoleacetic acid, indolebutyric acid, naphthoxyacetic acid or naphthylacetic acid), the cytokinins (eg. kinetin, diphenylurea, benzimidazole, benzyladenine or benzylaminopurine), phenoxyacetic acids (eg. 2,4-D or MCPA), substituted benzoic acids (eg. triiodobenzoic acid), morphactins (eg. chlorfluorecol), maleic hydrazide, glyphosate, glyphosine, long chain fatty alcools and acids, dikegulac, paclobutrazol, flurprimidol, fluoridamid, mefluidide, substituted quaternary ammonium and phosphonium compounds (eg. chlormequat* chlor- ophonium or mepiquatchloride), ethephon, carbetamide, methyl-3, 6-dichloroanisate, daminozide*, asulam, abscisic acid, isopyrimol, 1- (4-chlorophenyl)-4, 6-dimethyl-2-oxo-1, 2-dihydropyridine-3-carboxylic acid, hyd roxybenzonitriles (eg. bromoxynil), difernzoquat, benzoylprop-ethyl 3,6-dichloropicolinic acid, and tecnazene. Synergy will be most likelyto occur with indoleacetic acid, indolebutyric acid, naphthoxyacetic acid or naphthylacetic acid), the cytokinins (eg. kinetin, diphenylurea, benzimidazole, benzyladenine or benzylaminopurine), phenoxyacetic acids (eg. 2,4-D or MCPA), substituted benzoic acids (eg. triiodobenzoic acid), morphactins (eg. chlorfluorecol), maleic hydrazide, glyphosate, glyphosine, long chain fatty alcools and acids, dikegulac, paclobutrazol, flurprimidol, fluoridamid, mefluidide, substituted quaternary ammonium and phosphonium compounds (eg. chlormequat, chlorphonium or mepiquatchloride), ethephon, carbetamide, methyl-3, 6-dichloroanisate, daminozide, asulam, abscisic acid, isopyrimol, 1- (4-chlorophenyl)- 4,6-dimethyl-2-oxo-1, 2-dihydropyridine-3-carboxylic acid, hydroxybenzonitriles (eg. bromoxynil), difenzoquat, benzoylprop-ethyl 3,6-dichloropicolinic acid, paclobutrazol, fenpentezol, inabenfide, triapenthenol and tecnazene.
The following Examples illustrate the invention; the temperatures are given in degrees Centrigrade ( C).
Example 1 This Example illustrates the preparation of 4-[2-(p-t-butylphenyl)-cyclopropylmethyl]-piperidine (Compound No 1 in Table 1). Ethyl diazoacetate (9.74g, 0.085 mol) in dichloromethane (200moi) was added dropwise to a solution of p-t-butylstyrene (13.51 g, 0.085 mol) and anhydrous copper sulphate (0.1 g) in dichloromethane (50ml) at 90 C by means of a syringe pump over a period of 4 hours. The dichloromethane was distille over during the addition. After complete addition the remaining dichloromethane was removed in vacuo and the resulting brown oil purified by column chromatography (silica eluted with petroleum ether: ethyl acetate = 4 : 1) to give ethyl-2-(p-t-butylphenyl)-cyclopropanecarboxylate (80%) as a yellow liquid.
Ethyl 2-(p-t-butylphenyl)-cyclopropanecarboxylate (10.23g, 0.042 mol) was added dropwise to a suspension of lithium aluminium hydride (1.9g, 0.05 mol) in sodium-dried diethyl ether at room temperature. After complete addition the solution was stirred for a further 2 hours at room temperature. Ethyl acetate (25ml) was carefully added dropwise, the mixture poured into water and extracted with diethyl ether (2 x 100mol).
The ethereal extracts were washed with water, dried over anhydrous sodium sulphate, and the solvent evaporated to give 2-(p-t-butylphenyl)-cyclopropylmethanol (90%) as a colourless liquid. Methanesulphonyl chloride (5.92g, 0.052 mol) was added dropwise to a solution 2-(p-t-butylphenyl)-cyclopropylmethanol (4.79g, 0.023 mol) in pyridine (50mi) and stirred at room temperature for 10 hours. The mixture was poured into water, extracted with diethyl ether (2 x 50ml) ; the ethereal extracts were washed with water (4 x 75ml) and dried over anhydrous sodium sulphate. Removal of the solvent gave 2- (p-t-butylphenyl)- cyclopropylmethylchloride as a brown liquid which was used without purification in the final stage.
A solution of 2-(p-t-butylphenyl)-cyclopropylmethylchloride (0.53g, 0.0024 mol) and piperidine (1 mi, 0.01 mol) in pyridine (1 Oml) was heated to 80 C for 10 hours. After cooling to room temperature the mixture was poured into water and extracted with diethyl ether. The ethereal extracts were washed with water, dried over anhydrous sodium sulphate, and the solvent removed to give an orange oil. Purification of this oil using column chromatography (silica gel eluted with petroleum ether: ethyl acetate = 1 : 1) gave the title compound as a pale yellow oil (0.3g, cis: trans CH2/Ar = 1 : 9).
Example 2 This Example illustrates the preparation of 4-[2-(p-t-butylphenyl)-3, 3-dimethylcyclopropylmethyl]- morpholine (Compound No 8 in Table 1). n-butyl lithium (30ml, 0.048 mol) was added dropwise to a suspension of isopropyltriphenylphosphonium idodide (20.4g, 0.047 mol) in drytetrahydrofuran (50ml) at -5 C. After complete addition, the solution was stirred for 40 minutes at-5 C and p-t-butyl-ethylcinnamate (1 Og, 0.043 mol) in dry tetrahydrofuran (1 Oml) added dropwise at-5 C. The solution was allowed to warm upto room temperature, stirred at room temperature for 5 hours, poured into water and extracted with diethyl ether. The ethereal extracts were washed with water, dried over anhydrous sodium sulphate, and evaporated to give an orange oil. This oil was dissolved in chloroform (50moi), stirred with cuprous chloride (5g), and the chloroform evaporated. The residue was dissolved in ether (50moi), filtered, and the ether removed to give ethyl 2- (p-t-butylphenyl)-3, 3-dimethylcyclopropanecarboxylate (12. 2g) as a brown oil, used in the next stage without further purification. Ethyl-2 (P-t-butylphenyl)-3, 3-dimethylcyclopropanecarboxylate (8.7g, 0.032 mol) was added dropwise to a stirred suspension of lithium aluminium hydride (1. 2g, 0. 032 mol) in diethyl ether (30ml) at room temperature. After stirring at room temperature for 4 hours, ethyl acetate (15ml) was added, the mixture poured into water (50mi) and extracted with diethyl ether (2 x 50ml). The ethereal extracts were washed with water (4 x 50mi), dried over anhydrous sodium sulphate, and the solvent removed to give 2-(p-t-butylphenyl)-3, 3-dimethylcyclopropanemethanol (7.5g) as a yellow oil.
Methanesulphonyl chloride (3.5mut) was added dropwise to a stirred solution of 2- (p-t-butylphenyl)-3, 3dimethylcyclopropanemethanol (2.2g, 0.04 mol) in pyridine (35mi) at 10 C. The mixture was stirred at room temperature after the addition for 10 hours, poured into 10N HCI (50mi), and extracted with diethyl ether (2 x 75mi). The combined ethereal extracts were washed with water (4 x 75ml), dried anhydrous sodium sulphate, and the solvent removed to give a colourless oil. Purified by hplc (silica eluted with hexane) to give 2- (p-t-butyl phenyl)-3, 3-dimethylcyclopropanemethyl chloride (3.5g).
A mixture of 2-(p-t-butylphenyl)-3, 3-dimethylcyclopropanemethyl chloride (0.8g, 0.003 mol), morpholine (0.52g, 0.006 mol), and triethylamine (0.6g, 0.006 mol) were stirred at 80 C for 10 hours. The solution was cooled to room temperature, poured into water (20ml). The ethereal extracts were washed with water, and the solvent removed to give the title compound (0.91 g) as a colourless oil.
Example 3 This Example illustrates the preparation of4- [2- (p-t-butylphenyl)-trans-cyclopropylmethyl]-2, 6-cis- diemethylmorpholine (Compound No 4 in Table I). Ethyl 2-(p-t-butylphenyl)-cyclopropanecarboxylate (8.0g, 0.0325 mol) was dissolved in methanol (80ml) and a solution of potassium hydroxide (3.65g, 0.065 mol) in water (80mi) added dropwise at room temperature. The solution was refluxed for 3 hours, cooled to room temperature and carefully neutralized with 2M HCI. Saturated sodium chloride was added; the aqueous solution extracted with ethyl acetate (4 x 100mol) and dried over anhydrous sodium sulphate. Removal of the solvent gave 2- (p-t-butylphenyl)-cyclopropanecarboxylic acid (7.8g) as a white crystalline solid m. p. 55-60 C.
A mixture of 2-(p-t-butylphenyl)-cyclopropanecarboxylic acid (7.8g, 0.036 mol) and oxalyl chloride (5.5g, 0.043 mol) in hexane (80mi) was stirred at room temperature for 3 hours and then warmed at 60 C for 2 hours. The hexane and excess oxalyl chloride were removed in vacuo to give 2- (p-t-butylphenyl)-cyclo- propanecarbonyl chloride as a pale yellow liquid which was used in the next stage without further purification.
2,6-Dimethylmorpholine (9.2g, 0.008 mol) was added dropwise to a solution of 2- (p-t-butylphenyl)- cyclopropanecarbonyl chloride (4.96g, 0.02 mol) in sodium dried ether (40ml) at 10 C and after complete addition the solution was stirred at 20 C for 3 hours. The reaction was poured into water and extracted with diethyl ether (2 x 100ml). The ethereal extracts were washed with water, dried over anhydrous sodium sulphate, and the solventto removed to give [2- (p-t-butylphenyl)-cyclopropane] carbonyl 2,6dimethylmorpholine (5.6g) as an orange oil.
A solution of [2-(p-t-butylphenyl)-cyclopropane] carbonyl 2,6-dimethylmorpholine (1.35g, 0.0043 mol) in sodium-dried diethyl ether (10mi) was added dropwise to a suspension of lithium aluminium hydride (0.2g, 0.0053 mol) in sodium-dried diethyl ether (20mi) and the mixture stirred at 20 C for 3 hours. The reaction mixture was poured into water and extracted with diethyl ether. The ethereal extracts were washed with water, dried over anhydrous sodium sulphate, and the solvent removed to give a colourless oil. This oil was purified by column chromatography (silica gel eluted with ethyl acetate/petroleum ether 1: 1) to give the title compound (0.48g) as a colourless oil.
13C nmr (Shifts in ppm from TMS) C-1 147.998 C-8 59.221 C-2 139.377 C-9 34.075 C-3 125.145 C-10 31.222 C-4 124.927 C-11 21.918 C-5 71.345 C-12 20.088 C-6 62.942 C-13 19.065 C-7 59.532 C-14 14.665 Example 4 This Example illustrates the preparation of 4- [2- (p-trimethylsilyl phenyl)-trans-cyclopropyl methyl]-2, 6-cis- dimethylmorpholine (Compound No. 133 in Table I). n-Butyl lithium (0.12 mol, 73.6 mol of 1.6M solution) was added dropwise at-60 --70 C to a solution of p-bromostyrene (21.6g, 0.12 mol) in drytetrahydrofuran (160 ml) under nitrogen. After complete addition the reaction mixture was stirred at-60 C for 11/2 hours, and trimethylsilyl chloride (12.8g, 0.12 mol) added dropwise at-50 C and stirred for a further 1/2 hour at-50 C after the addition. The mixture was stirred at room temperature for 1 hour, poured carefully into water, and extracted with diethyl ether. The ethereal extracts were washed with water (x3), dried over anhydrous sodium sulphate, and the solvent removed to give an orange oil. Purification by column chromatography [silica gel eluted with petroleum ether (bp. 40-60 C)] gave p-trimethylsilylstyrene (18.90g, 91.2%) as a colourless liquid.
Ethyl diazoacetate (17.6g, 0.15 mol) in dry dichloromethane (250 ml) was added dropwise to a solution of p-trimethylsilylstyrene (18.13g, 0. 103 mol) and anhydrous copper sulphate (0.4g) in dry dichloromethane (50 ml) at 90 C by means of a syringe pump over a period of 51/2 hours. The dichloromethane was distille over during the addition. After complete addition the remaining dichloromethane was removed in vacuo and the resulting brown oil purified by column chromatography (silica gel eluted with petroleum ether: ethyl acetate = 9 : 1) to give ethyl-2- (p-trimethylsilyl phenyl)-cyclopropanecarboxylate (13. 8g, 51%).
Ethyl-2- (p-trimethylsilylphenyl)-cyclopropanecarboxylate (13. 7g, 0.052 mol) was dissolved in methanol (125 mi) and a solution of potassium hydroxide (5.86g, 0.105 mol) in water (125 ml) added dropwise at room temperature. The solution was refluxed for 5 hours, cooled to room temperature and carefully neutralised with 2M HCI. Saturated sodium chloride was added; the aqueous solution extracted with ethyl acetate (4 x 150 ml, and dried over anhydrous sodium sulphate. Removal of the solvent gave 2 (p-trimethylsilyl- phenyl)-cyclopropanecarboxylic acid (11. 6g, 95%) as a white crystalline solid.
A mixture of 2-(p-trimethylsilylphenyl)-cyclopropanecarboxylic acid (11. 6g, 0.05 mol) and oxalyl chloride (18. 9g, 0.15 mol) in hexane (90 ml) was stirred at room temperature for 1 hour and then warmed at 60 C for 5 hours. The hexane and excess oxalyl chloride were removed in vacuo to give 2- (p-trimethylsilylphenyl)- cyclopropanecarbonyl chloride (12. 2g, 97.5%) as a pale yellow liquid which was used in the next stage without further purification.
2,6-Dimethylmorpholine (22.2g, 0.19 mol) was added dropwise to a solution of 2- (p-trimethylsilylphenyl)- cyclopropanecarbonyl chloride (12. 2g, 0.048 mol) in sodium dried ether (100 ml) at 10 C and after complete addition the solution was stirred at 20 C for 3 hours. The reaction mixture was poured into water and extracted with diethyl ether (2 x 150 ml). The ethereal extracts were washed with water, dried over anhydrous sodium sulphate, and the solvent removed to give 2- (p-trimethylsilylphenyl)- cyclopropanecarbonyl-2, 6-dimethylmorpholine (16.1g).
A solution of 2-(p-trimethylsilyiphenyl)-cyclopropanecarbonyl-2, 6-dimethylmorpholine (3.94g, 0.012 mol) in dry sodium-dried diethyl ether (25 ml) was added dropwise to a suspension of lithium aluminium hydride (0.68g, 0.18 mol) in sodium-dried diethyl ether (15 ml) and the mixture stirred at 20 C for 3 hours. The reaction mixture was poured into water and extracted with diethyl ether. The ethereal extracts were washed with water, dried and anhydrous sodium sulphate, and the solvent removed to give a colourfess oil. This oil was purified by column chromatography (silica gel eluted with ethyl acetate/petroleum ether 1: 1) to give the title compound (2.0g). Two further isomers (compound Nos. 132 and 134 in Table I) were also isolated.
Example 5 This Example illustrates the preparation of4- [2- (p-t-butylphenyl)-2-methyl-trans-cyclopropylmethyl]-2, 6- cis-dimethylmorpholine (Compound No. 15 in Table I). Sodium hydride (5.45g-50% suspension in oil, 0.11 mol) was washed with petroleum ether, suspended in dry DMSO (90 ml) and heated with stirring at 60 -70 C for 21/2 hours. The reaction mixture was then cooled to 15 C and methyl triphenylphosphonium bromide (40.1 g, 0.11 mol) was added portionwise with rapid stirring over a 1/2 hour period. The reaction mixture was stirred at room temperature for a further 1 hour afterthe addition and 4-t-butylacetophenone (20.0g, 0.11 mol) was added dropwise over a period of 1 hour. The resultant reaction mixture was stirred at room temperature for 12 hours, poured into water (250 mi) and extracted with ether (4 x 150 ml). The ethereal extracts were washed with water (4 x 100 ml) and dried over anhydrous sodium sulphate. Removal of the solvent gave an orange oil which was purified by column chromatography (silica gel eluted with petroleum ether) to give a-methyl-4-t-butylstyrene (17.83g, 90%) as a colourless liquid.
Ethyl diazoacetate (13.9g, 0.12 mol) in dry dichloromethane (200 ml) was added dropwise to a solution of a-methyl-4-t-butylstyrene (17.65g, 0.10 mol) and anhydrous copper sulphate (0.3g) in dry dichloromethane (50 ml) at 90 C by means of a syringe pump over a period of 51/2 hours. The dichloromethane was distille over during the addition. After complete addition the remaining dichloromethane was removed in vacuo and the resulting brown oil purified by column chromatography (silica gel eluted with petroleum ether: ethyl acetate = 9.1) to give ethyl-2- (p-t-butylphenyl)-2-methylcyclopropanecarboxylate (19.3g, 73.6%) as a colourless oil.
Ethyl-2- (p-t-butylphenyl)-2-methylcyclopropanecarboxylate (18.9g, 0.073 mol) was dissolved in methanol (165 ml) and a solution of potassium hydroxide (8.13g, 0.145 mol) in water (165 ml) added dropwise at room temperature. The solution was refluxed for 4 hours, cooled to room temperature and carefully neutralised with 2 M HCI. Saturated sodium chloride was added; the aqueous solution extracted with ethyl acetate (4 x 150 ml) and dried over anhydrous sodium sulphate. Removal of the solvent gave 2- (p-t-butylphenyl)-2- methylcyclopropanecarboxylic acid (16. 9g, 100%) as an off-white solid.
A mixture of 2-(p-t-butylphenyl)-2-methylcyclopropanecarboxylic acid (16. 2g, 0.07 mol) and oxalyl chloride (12. 3g, 0.1 mol) in hexane (130 ml) was stirred at room temperature for 1 hour and then warmed at 60 C for 5 hours. The hexane and excess oxalyl chloride were removed in vacuo to give 2- (p-t-butylphenyl)-2- methylcyclopropanecarboxylic chloride (17.3g, 100%) as a pale yellow liquid which was used in the next stage without further purification.
2,6-Dimethylmorpholine (15. 6g, 0.14 mol) was added dropwise to a solution of 2- (p-t-butylphenyl)-2- methylcyclopropane carbonyl chloride (8.6g, 0.035 mol) in sodium dried ether (65 ml) at 10 C and after complete addition the solution was stirred at 20 C for 31/2 hours. The reaction mixture was poured into water and extracted with diethyl ether (2 x 150 ml). The ethereal extracts were washed with water, dried over anhydrous sodium sulphate, and the solvent removed to give 2- (p-t-butylphenyl)-2- methylcyclopropanecarbonyl-2, 6-dimethylmorpholine (12. 4g, 100%).
A solution of 2-(p-t-butylphenyl)-2-methylcyclopropanecarbonyl-2, 6-dimethylmorpholine (11. 89, 0.036 mol) in sodium dried ether (60 ml) was added dropwise to a suspension of lithium aluminium hydride (1.6g, 0.042 mol) in sodium-dried ether (40 ml) and the mixture stirred at room temperature for 3 hours. The reaction mixture was poured carefully into water and extracted with diethyl ether. The ethereal extracts were washed with water, dried over anhydrous sodium sulphate, and the solvent removed to give a colourless oil.
This oil was purified by column chromatography (silica gel eluted with ethyl acetate/petroleum ether 1: 1) to give the title compound (1.5g). Two further isomers (compound Nos. 16 and 17 in Table I) were also isolated.
Example 6 This Example illustrates the preparation of 4-[2-(p-t-propylphenyl)-3-methyl-trans-cyclopropylmethyl]-2, 6 cis-dimethylmorpholine (Compound No. 94 in Table I). Sodium hydride (7.2g-50% suspension in oil, 0.15 mol) was washed with petroleum ether, suspended in dry DMSO (120 ml) and heated with stirring at 60 -70 for 2 hours. The reaction mixture was then cooled to 15 C and ethyl triphenylphosphonium bromide (57.4g, 0.15 mol) was added portionwise with rapid stirring over a 1/2 hour period. The reaction mixture was stirred at room temperature for a further 1 hour afterthe addition and 4-i-propylbenzaldehyde (20g, 0.13 mol) was added dropwise over a period of 1 hour. The resultant reaction mixture was stirred at room temperature for 12 hours, poured intowater (300ml) andextractedwith ether (4 x 150 ml). Theethereal extractswere washed with water (4 x 100 ml) and dried over anhydrous sodium sulphate. Removal of the solvent gave a yellow oil which was purified by column chromatography (silica gel eluted with petroleum ether: ethyl acetate-9: 1) togive -methyl-i-propylstyrene (19.0g, 90%).
Ethyl diazoacetate (13.0g, 0.11 mol) in dry dichloromethane (150 ml) was added dropwise to a solution of (3-methyl-i-propylstyrene (18.0g, 0.11 mol) and anhydrous copper sulphate (0.3g) in dry dichloromethane (50 mi) at 90 C by means of a syringe pump over a period of 5 hours. The dichloromethane was distille over during the addition. After complete addition the remaining dichloromethane was removed in vacuo and the resulting brown oil purified by column chromatography (silica gel eluted with petroleum ether: ethyl acetate 1: 1) to give ethyl-2- (p-i-propylphenyl)-3-methylcyclopropanecarboxylate (26.0g, 96%).
Ethyl-2- (p-i-propylphenyl)-3-methylcyclopropanecarboxylate (24.8g, 0.1 mol) was dissolved in methanol (130 mi) and a solution of potassium hydroxide (13. g, 0.23 mol) in water (130 ml) added dropwise at room temperature. The solution was refluxed for 3 hours, cooled to room temperature and carefully neutralised with 2 M HCI. Saturated sodium chloride was added, the aqueous solution extracted with ethyl acetate (4 x 150 ml) and dried over anhydrous sodium sulphate. Removal of the solvent gave 2- (p-i-propylphenyl)-3- methylcyclopropanecarboxylic acid (17. 0g, 78%).
A mixture of 2- (p-i-propylphenyl)-3-methylcyclopropanecarboxylic acid (15. 7g, 0.07 mol) and oxalyl chloride (10g, 0.08 mol) in hexane (120 ml) wasstirred atroomtemperaturefor2 hoursandthenwarmed at 60 C for 3 hours. The hexane and excess oxalyl chloride were removed in vacuo to give 2- (p-i-propylphenyl)- 3-methyl-cyclopropanecarbonyl chloride (17. 0g, 100%) as a pale yellow liquid which was used in the next stage without further purification.
2,6-Dimethylmorpholine (5.0 g, 0.043 mol) was added dropwise to a solution of 2- (p-i-propylphenyl)-3- methylcyclopropanecarbonyl chloride (5.0g, 0.021 mol) in sodium dried ether (40 ml) at 10 C and after complete addition the solution was stirred at 20 C for 3 hours. The reaction mixture was poured'into water and extracted with diethyl ether (2 x 100 ml). The ethereal extracts were washed with water, dried over anhydrous sodium sulphate, and the solvent removed to give 2- (p-i-propylphenyl)-3- methylcyclopropanecarbonyl-2, 6-dimethylmorpholine (6.3g, 95%) as a yellow oil.
A solution of 2-(p-t-propylphenyl-3-methylcyclopropanecarbonyl-2, 6-dimethylmorpholine (5.8g, 0.018 mol) in sodium dried ether (30 ml) was added dropwise to a suspension of lithium aluminium hydride (0.8g, 0.02 mol in sodium dried ether (20 ml) and the mixture stirred at room temperature for 3 hours. The reaction mixture was poured carefully into water and extracted with diethyl ether. The ethereal extracts were washed with water, dried over anhydrous sodium sulphate, and the solvent removed to give a colourless oil. This oil was purified by column chromatography (silica gel eluted with ethyl acetate/petroleum ether 2: 3) to give the title compound (1.1 g). Three further isomers (Compound Nos. 92,93 and 95 in Table I) were also isolated.
Example 7 An emulsifiable concentrate was made up by mixing the ingredients, and stirring the mixture until all the constituents were dissolved.
Compound of Example 1 10% Ethylene dichloride 40% Calcium dodecylbenzenesulphate 5% "Lubrol"L 10% "Aromasol"H 35% Example 8 A composition in the form of grains readily dispersible in a liquid, e. g. water, was prepared by grinding together the first three ingredients in the presence of added water and then mixing in the sodium acetate.
The resultant mixture was dried and passed through a British Standard mesh sieve, size 44-100, to obtain the desired size of grains.
Compound of Example 2 50% "Dispersol"T 25% "Lubrol"APN5 1.5% Sodium acetate 23.5% Example 9 The ingredientswere all groundtogetherto producea powderformulation readily dispersible in liquids.
Compound of Example 1 45% "Dispersol"T 5% "Lissapol"NX 0. 5% "Cellofas"B600 2% Sodium acetate 47.5% Example 10 The active ingredient was dissolved in a solvent and the resultant liquid was sprayed onto the granules of China clay. The solvent was then allowed to evaporate to produce a granular composition.
Compound of Example 2 5% China clay granules 95% Example 11 A composition suitable for use as a seed dressing was prepared by mixing the three ingredients.
Compound of Example 1 50% Mineral oil 2% China clay 48% Example 12 A dusting powder was prepared by mixing the active ingredientwith talc.
Compound of Example 2 5% Talc 95% Example 73 A Col formulation was prepared by ball-milling the constituents set out below and then forming an aqueous suspension of the ground mixture with water.
Compound of Example 1 40% "Dispersol"T 10% "Lubroltt APN5 1% Water Example 14 A dispersible powder formulation was made by mixing together the ingredients set out below and then grinding the mixture until all were thoroughly mixed.
Compound of Example 2 25% "Aerosol"OT/B 2% "Dispersol"A. C. 5% China clay 28% Silica 40% Example 15 This Example illustrates the preparation of a dispersible powder formulation. The ingredients were mixed and the mixture then ground in a comminution mill.
Compound of Example 1 25% "Perminal"BX 1% "Dispersol"T 5% Polyvinylpyrrolidone 10% Silica 25% China clay 34% Example 16 The ingredients set out below were formulated into a dispersible powder by mixing then grinding the ingredients.
Compound of Example 2 25% "Aerosol"OT/B 2% "Dispersol"A 5% China clay 68% In Examples 4 to 13 the proportions of the ingredients given are by weight.
The compounds set out in Table 1 and numbered 3 to 33 can be similarly formulated as specifically described in Examples 4 to 13.
There now follows an explanation of the compositions or substances represented by the various Trade Marks mentioned above.
LUBROL L : a condensate of nonyl phenol 1 mole) with ethylene oxide (13 moles) AROMASOL H : a solvent mixture of alkylbenzenes DISPERSOL T & AC: a mixture of sodium sulphate and a condensate of formaldehyde with sodium naphthalene sul phonate LUBROL APN5 : a condensate of nonyl phenol (1 mole) with naphthalene oxide (5.5 moles) CELLOFAS B600: a sodium carboxymethyl celluose thickener LISSAPOL NX: a condensate of nonyl phenol (1 mole) with ethylene oxide (8 moles) AEROSOL OT/B: dioctyl sodium sulphosuccinate PERMINAL BX: a sodium alkyl naphthalene sulphonate Example 17 The compounds were tested against a variety of foliar fungal diseases of plants. The technique employed was as follows.
The plants were grown in John Innes Potting Compost (No 1 or 2) in 4 cm diameter minipots. The test compounds were formulated either by bead milling with aqueous Dispersol T or as a solution in acetone or acetone/ethanol which was diluted to the required concentration immediately before use. For the foliage diseases, the formulations (100 ppm active ingredient) were sprayed on to the foliage and applied to the roots of the plants in the soil. The sprays were applied to maximum retention and the root drenches to a final concentration equivalent to approximately 40 ppm a. i./dry soil. Tween 20, to give a final concentration of 0.05%, was added when the sprays were applied to cereals.
For most of the tests the compound was applied to the soil (roots) and to the foliage (by spraying) one or two days before the plant was inoculated with the disease. An exception was the test on Erysiphe graminis in which the plants were inoculated 24 hours before treatment. Foliar pathogens were applied by spray as spore suspensions onto the leaves of test plants. After inoculation, the plants were put into an appropriate environment to allow infection to proceed and then incubated until the disease was ready for assessment.
The period between inoculation and assessment varied from fourto fourteen days according to the disease and environment.
The disease control was recorded by the following grading: 4 = no disease 3 = trace-5% of disease on untreated plants 2 = 6-25% of disease on untreated plants 1 = 26-59% of disease on untreated plants 0 = 60-100% of disease on untreated plants The results are shown in Table Ill.
TABLEIII Compound Puccinia Erysiphe Venturia Cercospora Number Recondita Graminis Inaequalis Arachidicola (Wheat) fBarley) (Apple) (P#anut) 1 4 4 0 1 2 4 4 0 0 3 2 4 0 0 4 3 4 3 0 5 3 4 0 0 6 0 4 4 4 7 3 4 0 0 8 0 4 3 3 9 0 4 0 1 10 0 4 4 4 11 4 4 0 4 12 4 4 4 4 13 3 4 2 15 3 4 3 16 3 4- 17 0 4- 25 0 3 0 0 26 2 2 0 0 27 3 4 4 4 28 0 4 0 0 29 0 4 3 0 30 3 4 0 0 31 0 4 4 0 32 0 4 4 3 34 4 4 3 35 1 4 36 0 4 3 38 0 3 0 0 39 3 4-- 40 3 4- 42 2 0-- 43 0 3- 44 0 4- 45 3 4 0 0 47 0 2 0 0 48 3 4 0 0 49 0 4 2 0 50 0 2 0 0 51 0 3 4 2 52 2 4 4 4 53 2 4 3 4 54 1 0 0 0 55 1 4 0 0 56 1 3 0 0 57 2 4 0 0 58 2 4- 59 2 4- 60 0 1 0 62 0 3 0 0 TABLE III CONT/D Compound Puccinia Erysiphe Venturia Cercospora Number Recondita Graminis Inaequalis Arachidicola (Wheat) (Barley) bApple) (Peanut) 63 0 4 0 0 65 0 2 0 0 66 3 4 0 2 67 0 4 0 1 69 0 3 0 0 703400 71 0 4 0 0 72 0 1 0 0 74 0 3 0 1 75 0 4 0 1 76 0 1 0 1 77 0 4 0 0 78 3 3 0 0 79 3 4 0 3 80 0 3 0 0 81 0 3 0 1 82 0 4 0 0 83 0 4 0 0 84 0 4 0 0 85 0 0 0 2 86 0 3 0 1 87 0 4 0 3 88 0 4 0 1 89 0 2 0 4 90 0 3 0 0 91 0 4 4 0 92 1 4 3 3 93 3 4 3 3 94 4 4 4 4 95 2 4 3 1 97 3 2 0 2 98 3 4 0 3 99 1 4 0 1 100 3 4 0 2 101 4 4 0 3 102 4 4 0 3 103 3 4 0 0 104 3 4 4 2 105* 0 0 0 1 109 0 0 1 0 110 4 4 3 3 111 2 4 - 1 113 0 3 4 3 114 0 3 3 1 116 4 4 4 4 117 0 4 3 2 118 4 4 4 4 119 3 4 4 4 120 0 4 0 0 *25 ppm foliar spray

Claims (14)

  1. TABLE III CONT/D Compound Puccinia Erysiphe Venturia Cercospora Number Recondita Graminis Inaequalis Arachidicola (Wheat) (Barley) (Apple) (Peanut)
    129 2 4 4 3
    130 2 4 1 4
    131 1 4 4 4
    132 3 4 4 0
    133 4 4 4 3
    134 1 4 4 4 CLAIMS 1. Compounds having the general formula (I)
    and stereoisomers and acid addition salts thereof, wherein R', R2, R3, R4, R5 and R5 each represent a hydrogen atom, an alkyl group containing 1 to 4 carbon atoms or a halogen atom, R7 and R8 each represent a hydrogen atom or an alkyl group containing 1 to 4 carbon atoms or together form a ring which may contain an addition hetero atom; and X and Y each represent a hydrogen or a halogen atom, or an alkyl, cycloalkyl, alkenyl, alkynyl, aryl, aralkyl, alkoxy or aryloxy group, or a
    group wherein R9, R10, R11 are alkyl, alkenyl, alkynyl, cycloalkyl, or aryl.
  2. 2. Compounds as claimed in claim 1 and of general formula (I) :
    and stereoisomers and acid addition salts thereof, wherein R', R2, R3, R4, R5 and R6, which may be the same or different, represent a hydrogen atom, an alkyl group containing from 1 to 4 carbon atoms, or a halogen atom; R and R8, which may be the same or different, represent a hydrogen atom or an alkyl group containing from 1 to 4 carbon atoms or together form a ring which may contain oxygen, nitrogen or sulphur as an additional heteroatom, and which ring may be optionally substituted; X and Y, which may bethe same or different, represent a hydrogen or a halogen atom, or an alkyl group containing from 1 to 6 carbon atoms, a cycloalkyl group containing from 3 to 6 carbon atoms, an alkenyl or alkynyl group each containing 2 to 6 carbon atoms, a phenyl group, a benzyl group, an alkoxy group containing from 1 to 6 carbon atoms, a phenoxy group, a benzyloxy group, or a
    group wherein R9, R10 and R11, which may be the same or different, represent an alkyl group containing up to 4 carbon atoms, an alkenyl or alkynyl group each containing from 2 to 4 carbon atoms, a cycloalkyl group containing from 3 to 6 carbon atoms, or a phenyl group.
  3. 3. Compounds as claimed in claim 1 or claim 2 and of general formula (I) :
    and stereoisomers and acid addition salts thereof, wherein R1 and R2 are hydrogen, halogen or Caikyi ; R3 and R4 are hydrogen ; R5 and R6 are hydrogen or C, 4 al kyl ; R7 and R3 are C1 4 alkyl, or, together with the adjacent N-atom, represent a piperidine, morpholine, thiomorpholine or piperazine ring which may be substituted with Cl-4 alkyl, phenyl, or hydroxymethyl ; and X and Y are hydrogen, halogen, Ci. alkyl, C1-4 alkoxy, phenyl, phenoxy, benzyl, benzyloxy or a
    group wherein R9, R10, and R11 are c1-4 alkyl.
  4. 4. Compounds as claimed in any of the preceding claims and of general formula (1) :
    and stereoisomers and acid addition salts thereof, wherein R'and R2 are hydrogen, methyl, or chlorine; R3 and R4 are hydrogen; R'and R'are hydrogen or methyl ; R and R are piperidine, 3,5-dimethyl piperidine, morpholine, 2,6-dimethylmorpholine, diethylamino, 4-phenyl piperidine, 3-hydroxymethyl piperidine, thiomorpholine, piperazine, or 4-phenylpiperazine ; and X and Y are substituents at the 3-or 4-positions of the phenyl ring and one of which is hydrogen or Cn 4 alkyl whilst the other is hydrogen C1-4 alkyl, C1-4 alkoxy, chlorine, bromine, phenyl, phenoxy, benzyl, benzyloxy, or C1-4 trialkylsily.
  5. 5. The specific compounds set out in Table l ; and stereoisomers and acid addition salts thereof.
  6. 6. The compounds described in Examples 1 to 6 inclusive; and stereoisomers and acid addition salts thereof.
  7. 7. The compounds
    (Compound No.
    4 of Table I) (Compound No.
    15 of Table I)
    (Compound No. < 94 of Table I) (Compound No.
    133 of Table I)
  8. 8. A process for preparing the compounds defined in c)aims1 to 7 which comprises the treatment of a compound of general formula (11) :
    wherein R', R2, R3, R4, R5, R6, X and Y are as defined and Z is a leaving group such as chlorine, bromine, mesylate or tosylate, with an amide of general formula (111) :
    wherein R'and R8 are as defined above, in the presence of a convenient solvent such as ethanol or tetrahydrofuran, or, preferably, in the absence of a solvent at a temperature of 20 to 100 C.
  9. 9. A process as claimed in claim 8 wherein the compounds (II) are prepared by treating an alcohol of general formula (IV) :
    wherein R', R2, R3, R4, R5, R6, X and Y are as defined with the usual haiogenating agents (eg. phosphorus trichloride, phosphorus pentachloride, or phosphorus oxychloride when Z = chlorine and phosphorus tribromide, phosphorus pentabromide, or phosphorus oxybromide when Z = bromine), or mesyl chloride in pyridine (or triethylamine) when Z = mesylate, or tosyl chloride in pyridine (or triethylamine) when Z = tosylate and wherein, if desired, either (a) the alcohols (IV) wherein R3 and R4 are both hydrogen are prepared by treating an ester of general formula (V)
    wherein R', R2, R5, R6, X, and Y are as defined above and R is alkyl with a reducing agent (usually lithium aluminium hydride) in a convenient solvent such as diethyl ether or tetrahydrofuran or (b) the alcohols (IV), wherein R3 and R4 are both alkyl, are prepared by treating the above ester (V) with an excess of alkyl magnesium halide or an excess of alkyl lithium in a convenient solvent such as diethyl ether or tetrahydrofuran, the esters (V) being prepared either by reacting the cinnamic esters of general formula (Vl) :
    wherein R, R5 and R6, X and Y are as defined above with a phosphorane of general formula (Vil) :
    wherein R1 and R2 are defined above in a convenient solvent such as tetrahydrofuran or, in an alternative process the esters of general formula (V) wherein R5 is hydrogen are prepared by adding ethyl diazoacetate to the olefin of general formula (VIII) :
    wherein R', R2, R6, X and Y are as defined above, in a convenient solvent such as chloroform or dichloromethane using a suitable catalyst such as anhydrous copper sulphate.
  10. 10. A process for preparing the compounds of general formula (I) as claimed in claims 1 to 7 and where R3 and R4 are both hydrogen, which comprises treating an amide of general formula (IX) :
    wherein R', R2, R5, R6, R7, R8, X and Y are as defined with a reducing agent (usually lithium aluminium hydride) in a convenient solvent such as diethyl ether or tetrahydrofuran.
  11. 11. A process as claimed in claim 10 which comprises preparing amides of general formula (IX) by reacting an acid chloride of general formula (X):
    wherein R', R2, R5, R6, X and Y are as defined with an amide of general formula (III) :
    in a convenient solvent such as diethyl ether or tetrahydrofuran, the acid chloride of general formula (X) being prepared by reacting an acid of general formula (Xl) :
    wherein R', R2, R5, R6, X and Y are as defined above with the usual chlorinating agents such as thionyl chloride or oxalyl chloride in a convenient solvent such as hexane or dichloromethane, the acid of general formula XI being itself prepared by hydrolysing the ester (V) in the normal manner using either sodium or potassium hydroxide in methanol/water solution at room temperature.
  12. 12. A fungicidal composition comprising a compound of general formula 11) as claimed in any of claims 1 to 7 or acid addition salt or stereoisomer thereof ; and, optionally, a carrier or diluent.
  13. 13. A method of combating fungi, which comprises applying to a plant, to seed of a plant, or to the locus of a plant or seed, a compound, or an acid addition salt or stereoisomer thereof as claimed in any of claims 1 to 7 or a composition as claimed in claim 12.
  14. 14. As novel compounds, the intermediates of formulae 11, IV, V, IX, X and Xi.
GB08530644A 1985-01-17 1985-12-12 Tertiary amine compounds Expired GB2170197B (en)

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GB858516804A GB8516804D0 (en) 1985-07-03 1985-07-03 Tertiary amine compounds
GB858520592A GB8520592D0 (en) 1985-08-16 1985-08-16 Tertiary amine compounds
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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1086191A (en) * 1963-11-05 1967-10-04 Whitefin Holding Sa Phenylcyclopropane derivatives
GB1268243A (en) * 1968-03-11 1972-03-22 Wallace & Tiernan Inc 0,2,4,5,-tetrahydro-3h,3-benzazepines

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1086191A (en) * 1963-11-05 1967-10-04 Whitefin Holding Sa Phenylcyclopropane derivatives
GB1268243A (en) * 1968-03-11 1972-03-22 Wallace & Tiernan Inc 0,2,4,5,-tetrahydro-3h,3-benzazepines

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
CHEMICAL ABSTRACTS VOL 59 NO. 3824L *
CHEMICAL ABSTRACTS, VOL 90 (9) NO. 71791C CHEMICAL ABSTRACTS, VOL 82 (11) NO. 72551W *

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