NZ274000A - Use of azabisphosphonic acid derivatives as herbicides, azabisphosphonic derivatives - Google Patents

Use of azabisphosphonic acid derivatives as herbicides, azabisphosphonic derivatives

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Publication number
NZ274000A
NZ274000A NZ274000A NZ27400094A NZ274000A NZ 274000 A NZ274000 A NZ 274000A NZ 274000 A NZ274000 A NZ 274000A NZ 27400094 A NZ27400094 A NZ 27400094A NZ 274000 A NZ274000 A NZ 274000A
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New Zealand
Prior art keywords
alkyl
substituted
halo
ethyl
compound
Prior art date
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NZ274000A
Inventor
Karl Joseph Fisher
Frank Xavier Woolard
John Montgomery Gerdes
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Zeneca Ltd
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Application filed by Zeneca Ltd filed Critical Zeneca Ltd
Publication of NZ274000A publication Critical patent/NZ274000A/en

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    • 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
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
    • C07F9/40—Esters thereof
    • C07F9/4003—Esters thereof the acid moiety containing a substituent or a structure which is considered as characteristic
    • C07F9/4025—Esters of poly(thio)phosphonic acids
    • C07F9/405—Esters of poly(thio)phosphonic acids containing nitrogen substituent, e.g. N.....H or N-hydrocarbon group which can be substituted by halogen or nitro(so), N.....O, N.....S, N.....C(=X)- (X =O, S), N.....N, N...C(=X)...N (X =O, S)
    • 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
    • A01N57/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic phosphorus compounds
    • A01N57/18—Biocides, pest repellants or attractants, or plant growth regulators containing organic phosphorus compounds having phosphorus-to-carbon bonds
    • 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
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
    • C07F9/3804—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)] not used, see subgroups
    • C07F9/3839—Polyphosphonic acids
    • C07F9/3873—Polyphosphonic acids containing nitrogen substituent, e.g. N.....H or N-hydrocarbon group which can be substituted by halogen or nitro(so), N.....O, N.....S, N.....C(=X)- (X =O, S), N.....N, N...C(=X)...N (X =O, S)
    • 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
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
    • C07F9/5532—Seven-(or more) membered 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
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
    • C07F9/568—Four-membered 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
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
    • C07F9/572—Five-membered 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
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
    • C07F9/576—Six-membered rings
    • C07F9/58—Pyridine rings
    • C—CHEMISTRY; METALLURGY
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    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
    • C07F9/576—Six-membered rings
    • C07F9/59—Hydrogenated pyridine rings
    • C—CHEMISTRY; METALLURGY
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    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
    • C07F9/576—Six-membered rings
    • C07F9/60—Quinoline or hydrogenated quinoline ring systems
    • C—CHEMISTRY; METALLURGY
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    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/645—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having two nitrogen atoms as the only ring hetero atoms
    • C07F9/6503—Five-membered rings
    • C07F9/65031—Five-membered rings having the nitrogen atoms in the positions 1 and 2
    • C—CHEMISTRY; METALLURGY
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    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/645—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having two nitrogen atoms as the only ring hetero atoms
    • C07F9/6503—Five-membered rings
    • C07F9/6506—Five-membered rings having the nitrogen atoms in positions 1 and 3
    • 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
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/645—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having two nitrogen atoms as the only ring hetero atoms
    • C07F9/6509—Six-membered rings
    • C07F9/6512—Six-membered rings having the nitrogen atoms in positions 1 and 3
    • 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
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6515—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having three nitrogen atoms as the only ring hetero atoms
    • C07F9/6518—Five-membered 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
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6527—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07F9/6533—Six-membered rings

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Pest Control & Pesticides (AREA)
  • Agronomy & Crop Science (AREA)
  • Plant Pathology (AREA)
  • Engineering & Computer Science (AREA)
  • Dentistry (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Environmental Sciences (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)
  • Plural Heterocyclic Compounds (AREA)

Description

New Zealand Paient Spedficaiion for Paient Number £74000 New Zealand No. 274000 Inter national" No.
TO BE ENTERED AFTER ACCEPTANCE AND PUBLICATION Priority dates: 07.10.1993; Complete Specification Filed: 07.10.1994 Classification:^) A01N57/24,20,22; C07F9/38,553,645 Publication date: 25 March 1998 Journal No.: 1426 NEW ZEALAND PATENTS ACT 1953 COMPLETE SPECIFICATION Title of Invention: Herbicidal aza bisphosphonic acids Name, address and nationality of applicant(s) as in international application form: ZENECA LIMITED, 15 Stanhope Gate, London W1Y 6LN, United Kingdom *?4°Oo HERBICIDAL AZA BISPHOSPHONIC ACIDS FIELD OF THE INVENTION In one aspect, this invention relates to a method of controlling the growth of plants comprising applying to the area where control is desired an herbicidally effective amount of an aza-bisphosphonic acid wherein the nitrogen atom and the carbon atom to which the two phosphonic acid groups are bound are linked with a single carbon atom. In another aspect, this invention is directed to certain novel aza-bisphosphonic acid compounds and compositions containing them. -v BACKGROUND OF THE TNVFNTTON The need for effective herbicides requires no special emphasis. The control of weeds and undesirable vegetation is of great economic importance since weed competition inhibits the production of foliage, fruit or seed of agricultural crops. The presence of weeds can reduce harvesting efficiency and the quality of the harvested crop.
Weeds on noncropped areas may cause a fire hazard, undesirable drifting of sand or snow, and/or irritation to persons with allergies. Thus, suppression of undesirable weed growth is very advantageous.
Moreover, it is highly desirable to possess herbicides which exhibit desirable efficacy against plants when applied postemergently, but which further exhibit little significant activity when applied preemergently. Such herbicides will, for example, permit the control of weeds already present in a field but will not harm crops which have not yet emerged. intellectual %QP8rtv oWce o 3 Ftti W* WO 95/10188 _2_ PCT/Gpy/02183 <7.
Accordingly, it is an object of this invention to ^ ^ Q provide a novel method of controlling weeds, as well as certain novel herbi-cidal compounds. It is a further object of this invention to provide novel compositions, methods and herbicidal compounds which exhibit admirable postemergent control coupled with no significant preemtergent control.
While certain bisphosphonic and aza-bisphosphonic acid herbicidal compounds have been disclosed in the art, such herbicidal compounds do not possess a structure wherein the carbon atom to which the two phosphonic acid groups are bound is linked to the nitrogen of the amino group via a single carbon atom.
Thus, Japanese Patent Publication 54-147925 (Nissan Chemical) discloses herbicidal bisphosphonic acid compounds wherein the phosphonic acid groups are bound to a single carbon atom. Such compounds are of the Formula: 0X0 il I II (HO) 2 P C P (OH) 2 Y wherein X and Y are each hydrogen, halogen, alkyl or cycloalkyl; or salts thereof.
Herbicidal aza-bisphosphonic acid compounds wherein the carbon to which the two phosphonic acid groups are bound is directly linked to the nitrogen atom of the amino group are disclosed in U.S. Patent 4,447,256 (Suzuki et al.); British Patent 1,508,772 (Devlin); Japanese Patent Publication 54-37829 (Nissan Chemical); Japanese Patent Publication 54-144383 (Nissan Chemical); Japanese Patent Publication 55-98105 (Nissan Chemical); and in "Herbicide properties of Aminophosphonic Acid Derivatives", Dr. Y. Okamoto, 1st International Congress on Phosphorus Compounds, Rabat, October 17-21, 1977, pp. 649-652.
RECEIVED Intalloctual property Office 0 3 Ffcti tebd of New Zealand 3 Japanese Patent Publication 55-98193 disclos certain herbicidal compounds of the formula R C N Y wherein R is H, lower alkyl or halogen; X is -CH^"*/ s or 0; Y is H, lower alkyl or halogen? and alkali salts thereof. wherein the carbon to which the two phosphonic acid groups are bound is linked to a nitrogen atom via a single carbon atom have been disclosed in the art, these particular compounds are not indicated to have herbicidal activity. Thus, U.S. Patent 3,962,318 discloses compounds useful as flame retardants; German Patent DE 2754821 dirscloses compounds useful as chelators in water treatment; and U.S. Patent 5,133,972, U.S. Patent 4,990,503, European Patent Publication 96,931, European Patent Publication 96,933, European Patent Publication 186,405, European Patent Publication 274,158, European Patent Publication 522,576 and German Patent Publication DE 3,804,686 all disclose pharmaceutical uses for the specific compounds disclosed therein.
Although certain aza-bisphosphonic acid compounds 0 3 FEB 1998 of Haw Zealand wo 95/10188 PCT/GB94/02183 STTMMRRY OF THE INVENTION ?7t000 In one aspect, this invention is directed to a method of controlling the growth of plants conpri sing applying to the locus of such plants an herbicidally effective amount of a compound of the Formula (I): * R4 C C R"1" (I) r5/ R2 i *°3H2 C C R 1 3 R io3H2 wherein R1 is hydrogen, hydroxy, C. -C. alkoxy, halogen, '1 4 C^-C^ alkyl, C1~C4 haloalkyl, hydroxy-C^-C^-alkyl, hydroxy--C1-C4-alkoxy; 2 3 R and R are each independently hydrogen; hydro- carbyl; substituted hydrocarbyl; hydrocarbyloxy; substituted hydrocarbyloxy; hydrocarbyl-S(0)^-; or substituted hydrocar- byl-S(O) -; or ' m _ _ 2 3 R and R together form a 3-6 membered carbocyclic ring, optionally substituted with halogen, hydroxy, alkyl, alkoxy, alkylthio or N(R8)(R9) wherein R8 and R9 are each independently hydrogen or C.-C_0 alkyl; and 4 5' R and R are each independently hydrogen,' hydrocarbyl; substituted hydrocarbyl; hydrocarbyloxy; substituted hydrocarbyloxy; hydrocarbylthio; substituted hydrocarbylthio; pyridyl; s'<ibstituted pyridyl; or are of the formula N(R10)(R11) wherein R10 and R11 are independently hydrogen, hydrocarbyl or substituted hydrocarbyl; or 4 5 R and R together with the nitrogen to which they are bound form an aziridine, piperazine, morpholine, thiomorpholine, thiomorpholine sulf.inyl, thiomorpholine sulfor.yl, hexamethyleneimine, piperidine, tetrahydropyridine, pyrazole, imidazole, pyrrole, triazole, tetrahydropyrimidine, dihydro-imidazole, pyrroline, azetidine, perhydroindole, perhydro-quinoline, perhydroisoquinoline or pyrrolidine ring, any of which may be optionally substituted with C]_""C12 alkyl, ^a^°' hydroxy, C6~c10 arY1' cs~C10 arY^* substituted with halo or alkyl, RBCEI VBB- Intallaotuil Preptrty Offloe o 3 m m WO 95/10188 e PCT/GB94/02183 |7"*c16 aralkyl, C?-C16 aralkyl substituted with halo or C^Cg alkyl, nitro, halo-c^-c^-alkyl, C1-C1Q alkoxy, al3cY1_ thio, C^-c alkylsulfonyl, phenoxy, phenoxy substituted with halo or C^-Cg alkyl, ci~cio or cyano; or R2, and R4 together with the nitrogen and carbon atoms to which they are bound form an aziridine, piperazine, morpholine, thiomorpholine, thiomorpholine sulfinyl, thiomorpholine sulfonyl, hexamethyleneimine, piperidine, tetrahydro-pyridine, pyrazole, imidazole, pyrrole, triazole, tetrahydro-pyrimidine, dihydroimidazole, pyrroline, azetidine, perhydro-indole, perhydroquinoline, perhydroisoquinoline or pyrrolidine ring, any of which may be optionally substituted with c1~c12 alkyl, halo, Cg-C10 aryl, Cg-^g substituted with halo or C1-Cg alkyl, C?-C16 aralkyl, Caralkyl substituted with halo or alkyl, nitro, halo-c^-c^-alkyl, C1-C1Q alkoxy, C1-C1Q alkylthio, C1-C1Q alkylsulfonyl, phenoxy, phenoxy substituted with halo or C1-Cg alkyl, C1-C1Q alkenyl or cyano; and id is 0, 1 or 2; and agrochemically^-acceptable salts thereof.
In another aspect, this invention is directed to certain novel compounds having a structure within the scope of Formula (I) above.
In-yet another aspect, this'invention is directed to compositions containing cfertain novel compounds having a structure within the scope of Formula (I) above together with acceptable carriers.
R B 0 B I V 8 InnfcSLl W""8* 0 3 FEB 1998 of New Zealand ft DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS D "y The method of this invention comprises applying to the locus of plants a herbicidally effective amount of a bisphosphonic acid compound of the Formula (I) : R4 R2 PO.H- \ I ' 3 Zi , N C C R-1- (I) S 13 ■ R R P03H2 wherein R1 is hydrogen, hydroxy, C1~c4 alkoxy, halogen, C1~C4 alkyl, C^-C4 haloalkyl, hydroxy-c^-c^-alkyl, hydroxy--C1"C4-alkoxy; 2 3 R and R are each independently hydrogen; hydrocarbyl; substituted hydrocarbyl; hydrocarbyloxy; substituted hydrocarbyloxy; hydrocarbyl-S(O) -; substituted hydrocar-byl-S(0)n; or R and R together form a 3-6 membered carbocyclic ring, optionally substituted'with halogen, hydroxy, C1-Cg alkyl, C_-C- alkoxy, C,-c. alkylthio or N(R8)(R9) wherein R8 Q and R" are each independently hydrogen or C..-C., alkyl; and 4 5 11A R and R are each independently hydrogen; hydrocarbyl; substituted hydrocarbyl; hydrocarbyloxy; substituted hydrocarbyloxy; hydrocarbylthio; substituted hydrocarbylthio; pyridyl; substituted pyridyl; or are of the formula N(R10)(R11) wherein R10 and R11 are independently hydrogen, hydrocarbyl or substituted hydrocarbyl; or 4 5 R and R together with the nitrogen to which they are bound form an aziridine, piperazine, morpholine, thiomorpholine, thiomorpholine sulfinyl, thiomorpholine sulfonyl, hexamethyleneimine, piperidine, tetrahydropyridine, pyrazole, imidazole, pyrrole, triazole, tetrahydropyrimidine, dihydro-imidazole, pyrroline, azetidine, perhydroindole, perhydro-quinoline, perhydroisoquinoline or pyrrolidine ring, any of which may be optionally substituted with c1~c12 al^ylf halo, hydroxy, C5~C10 aryl, c6~c10 arYl substituted with halo or C1-Cg alkyl, .C7~C16 aralkyl, C_-Clg aralkyl substituted with halo or Fi fc a i iw * fLrB intellaotual Propar'.y Office 0 3 FEB 1998 of New Zealand WO 95/10188 _7_ PCT/GB^021?3 4 n /) lkyl, nitro, halo-c^c^-alkyl, C1-C1Q alkoxy, al*Yl~ ^ IS thio, ci~cio alkylsulfonyl, phenoxy, phenoxy substituted with halo or c1~cg alkyl, C1~C^0 alkenyl or cyano; or R^ and R4 together with the nitrogen and carbon atoms to which they are bound form an aziridine, piperazine, morpholine, thiomorpholine, thiomorpholine sulfinyl, thiomorpholine sulfonyl, jhexamethyleneimine, piperidine, tetrahydro-pyridine, pyrazole, imidazole, pyrrole, triazole, tetrahydro-pyrimidine, dihydroimidazole, pyrroline, azetidine, perhydro-indole, perhydroquinoline, perhydroisoquinoline or pyrrolidine ring, any of which may be optionally substituted with c1~c12 alkyl, halo, Cg-C10 aryl, c6~c10 arY1 substituted with halo or C^-Cg alkyl, Cy-C^g aralkyl, C7~Clg aralkyl substituted with halo or alkyl, nitro, halo-c^-c^-alkyl, C1-C1Q alkoxy, c1-c10 alkylthio, C1-C1Q alkylsulfonyl, phenoxy, phenoxy substituted with halo or ^-Cg alkyl, C1~C1Q alkenyl or cyano; and m is 0, 1 or 2; and agrochemically acceptable salts thereof. -*r Preferably: R1 is hydrogen, hydroxy, halogen or C -C. alkyl; 2 3 14 R and R are independently hydrogen; C^-C.^ alkyl; C2-C12 alkenyl; c2~ci2 alkynyl; halo-c^-c^ alkyl, halo-C2'-C12 alkenyl; halo-c2-c12-alkynyl; c6"c14 aralkyl; Cj-C^ alkoxy; or C1~C12 alkylthio; R4 and RS are independently a-UcY1' C2~C6 alkenyl; C2~Calkynyl; halo-C^-Cg alkyl; halo-C2-Cg alkenyl; halo-C1-Cg-alkynyl; pyridyl; substituted pyrddyl; phenyl; substituted phenyl; C?-c14 aralkyl; or substituted C?-C14 aralkyl; or 4 5 .
R and R together with the nitrogen to which they are bound form a tetrahydropyrimidine, tetrahydropyridine, imidazole ring or a -(CH2)n~N- ring wherein n is 2-6, optionally substituted with halogen, hydroxy, C.-c. alkoxy, nitro, L 6 C^-Cg alkyl, C7~Clg aralkyl or C1-Cg alkylthio groups.
H 5 6 E I V E B intellastual fnfitrtv 0mce 0 3 FEB 1998 of New Zealand WO 95/10188 PCT/GB94/02183 #«.2?<00 alkyl; and R is hydrogen or hydroxy; 2 3 R and R are each independently hydrogen or C^-Cg 4 ' 5 R and R are each independently hydrogen, C -C.
X o alkyl, C.-C,. alkenyl, benzyl, benzyl substituted with C,-C..
X o ' 16 alkyl or halo or , 4 5 R and R together with the nitrogen to which they are bound form a pyrrolidine or piperidine ring, either of which may be optionally substituted with fluorine, hydroxy, C^-Cg alkoxy or ^"Cg alkyl.
Particularly preferred compounds for use in the method of this invention include: 2-(R-alpha-merhylbenzylamino)ethyl-1,1-bisphosphonic acid; 2-(2-methylpropylamino)ethyl-1,1-bisphosphonic acid; 2-[l-(4-methy1-1,3-imidazoly1)]ethyl-l,1-bisphos-phonic acid; 2-(l-pyrrolidinyl)*ethyl-l, 1-bisphosphonic acid; 2-(1-piperdinyl)ethyl-l,l-bisphosphonic acid; 2-(propylamine)ethyl-l,1-bisphosphonic acid; 2-(N,N-methylethylamino)ethyl-1,1-bisphosphonic acid ; 2-(n-butylamino)ethyl-l,l-bisphosphonic acid; 2-(2-propenylamino)ethyl-1,1-bisphosphonic acid; 2-[1-(1,2,3,6-tetrahydropyridiny1)]ethyl-1,1-bis-phosphonic acid; and 2-(N,N-dipropylamino)ethyl-1,1-bisphosphonic acid.
In another aspect, this invention is directed to certain classes of novel aza-bisphosphonic acid compounds.
One class-of compounds within the scope of this invention are compounds of Formula (VII): ?25 P03H2 N C N CH. CH (VII) P°3H2 REGBlVEP„ (CR** R ) t intallwtual Property Office 0 3 m 1998 of Now Zealand <00 0 R I e E | V E E) lntell»etuel Property Office 0 3 FEB 1U9E of New Zealand o 0 3 FEB 1998 0f Now Zealand <?> 400 InteUaotiSl Property Office 0 3 FEB 1998 of New Zealand 40(J o HE6E1VE D intellectual Property Office 0 3 FtB 1SK8 of New Zealand PCT/GB94/021» . *'400 ^Jwherein t is 2, 3 or 4; R23 and R24 are each independently hydrogen, c1~c10 halo< nitro, C1-Cg alkoxy, crcio aralkyl, cyano, trifluoromethyl or represent a unit of unsat- uration; and R25 is hydrogen, C. -C. alkyl, C_-C1f1 aralkyl, 23 24 halo, nitro, trifluoromethyl or cyano. Each R and R may themselves be different members of the group listed above.
Illustrative compounds within the scope of this invention include: 2-[1-(2 methyl 1,4,5,6 tetrahydro 1,3 pyrimidinyl)]■ ethyl-l,1,bisphosphonic acid? and 2-[1-(4-methyl-1,3-imidazolyl)]ethyl-1,1-bisphos-phonic acid.
Another class of compounds within the scope of this invention are compounds of the Formula (VIII): H P03H2 -H H PO3H2 wherein R26-R33 are each independently H or C1-C5 alkyl.
The formulae given above are intended to include , •tautomeric forms of the structures drawn therein, as well as physically distinguishable modifications of the compounds which may arise, for example, from different ways in which the molecules are arranged in a crystal lattice, or from the inability of parts of the molecule to rotate freely in relation to other parts, or from geometrical isomerism, or from intra-molecular or inter-molecular hydrogen bonding, or v g B vise. Intellaotuel Property Office (followed bQ $a§£B3$98 of New Zealand -13a- 27''00 The compounds of such formulae can exist in enantiomeric forms. The invention includes both individual enan-tiomers and mixtures of the two in all proportions.
As is employed herein, the term "hydrocarbyl", whether representing a subsrituent on its own or whether it is part of the definition of a larger group (e.g., as in hydrocarbyloxy, hydrocarbyl-S(0) -, etc.) is intended to include in hydrocarbyl groups having from 1 to 16 carbon atoms. The term hydrocarbyl therefore includes, for example, to Clg alkyl including both straight and branched chain isomers (e.g., methyl, ethyl, propyl, isoprapyl, sec-hexyl and hexyl); cyclo-alkyl of 3 to 16 carbon atoms (e.g., cyclopropyl, cyclobutyl and cyclohexyl); C2 to c alkenyl including for example allyl (followed by page 14) B Q Q g | V g © Intellootuil Property Office 0 3 FtB 1H98 of New Zealand WO 95/10188 PCT/GB94/02183 OttOOn 4^nd crotyl; C2 to clg alkynyl (e.g., propynyl); phenyl; phenylalkyl; alkylphenyl, alkenylphenyl, alkynylphenyl, alkyl- " benzyl, alkenylbenzyl, alkynyl benzyl, naphthyl and the like.
The term "substituted" when applied to the term "hydrocarbyl" (or to a similar term unless specifically defined otherwise1) is intended to include hydrocarbyl groups, as defined above, having one or more substituents selected from the group consisting of halogen (i.e., fluorine, chlorine, bromine, and iodine); alkoxy; C1-10 alkyl-S(Q)m-; cyano; nitro; carboxy, and salts, amides and esters thereof; alkanoyl of 2 to 10 carbon atoms; and phenyl optionally substituted by one or more C1-1Q alkyl, alkoxy, alkyl-S(0)m-, nitro, fluorine, chlorine, bromine, cyano, or CF3 groups. In the above definitions, m is 0. 1 or 2.
Further, when the hydrocarbyl radical is a substituted aryl radical (e.g., phenyl, benzyl or naphthyl), the substituents may include one or more of the substituents listed in the last foregoing*paragraph, and may also include nitro. The term "substituted pyridyl" is intended to include those substituents detailed above for substituted aryl radicals.
In addition, unless specified otherwise, the term "alkyl" is intended to include straight chain, branched and cycloalkyl compounds. The above definitions the term "halogen" includes fluoro, chloro, bromo and iodo groups. In polyhalogenated groups the halogens may be the same or different.
The compounds of the present invention have been found to be active herbicides, possessing utility as post-emergence herbicides and useful against a wide range of plant species including broadleaf and grassy species.
This invention therefore relates to a method for controlling undesirable vegetation comprising applying to a locus where control of such vegetation is desired subsequent RECEIVED Intellectual Property Office 0 3 FEB 1998 of Now Zealand to the emergence of such vegetation a herbicidally effective amount of a compound as described herein, together with an inert diluent or carrier suitable for use with herbicides.
The terms "herbicide" and "herbicidal" are used herein to denote the inhibitive control or modification of undesired plant growth. Inhibitive control and modification include all deviations from natural development such as, for example, total killing, growth retardation, defoliation, desiccation, regulation, stunting, tillering, stimulation, leaf burn and dwarfing. The term "herbicidally effective amount" is used to denote any amount which achieves such control or modification when applied to the undesired plants themselves or to the area in vhich these plants are growing. The term "plants" is intended to include germinated seeds, emerging seedlings and established vegetation, including both roots and above-ground portions.
The term "agriculturally acceptable salt" is easily determined by one of ordinary skill in the art and includes alkali metal, ammonium, phosphonium, sulfonium salts, organic derivatives thereof, and the like.
The compounds of this invention wherein R1 is hydrogen may generally be prepared by reacting tetraethyl vinyl-idene bis(phosphonate) with an appropriate amine. Such reaction is typically carried out at between about 0° and about 100°C in the presence of a suitable nonreactive solvent, such as acetonitrile, diethyl ether, tolene, tetrahydrofuran, and the like. The ester groups may then be removed using bromotrimethylsilane or aqueous hydrochloric acid.
Tetraethyl vinylidene bis(phosphonate) may be prepared in accordance with the method disclosed by C. Degenhardt et al., J. Org. Chem., Vol 51, pp 3488-3490 (1986). The amines employed are either commercially available or may be prepared by means well known to one of skill in the art, e.g., preparation from the corresponding bromides by a Gabriel Synthesis (sea Vogel, "A Textbook of Practical Organic Chemistry", 3d Ed., pp 569).
WO 95/10188 PCT/GB94/02183 ^4 oo For the production of compounds wherein the amine 1/ \J contains sensitive groups, the ester groups may first be transesterified by the use of a compound such as bromotri-methylsilane. Such groups can be subsequently unblocked by hydrolysis with water.
/ Alternatively, for producing compounds wherein R1 is other than H, the appropriate carboxylic acid, amide or nitrile can be converted employing PCl^ and phosphorous acid or P2°3 utilizing means well known to those of skill in the art.
The compositions of this invention comprise a compound of Formula (VII) or Formula (VIII) above and a suitable carrier, which carriers are well known to one of ordinary skill in the art.
The compounds of the present invention are useful as herbicides and can be applied in a variety of ways known to those skilled in the art, at various concentrations. The compounds are useful in controlling the growth of undesirable vegetation by post-emergent application to the locus where control is desired. In practice, the compounds are applied as formulations containing the various adjuvants and carriers known to or used in the industry for facilitating dispersion. The choice of formulation and mode of application for any given compound may affect its activity, and selection will be made accordingly. The compounds of the invention may thus be formulated as wettable powders, as emulsifiable concentrates, as powders or dusts, as flowables, as solutions, suspensions or emulsions, or in controlled-release forms such as microcapsules. These formulations may contain as little as about 0-5% to as much as amount 95% or more by weight of active ingredient. The optimum amount for any given compound will depend upon the nature of plants to be controlled. The rate of application will generally vary from about 0.01 to about 10 pounds par acre, preferably from about 0.02 to about 4 pounds per acre.
JLMWWk- 0 3 FEB, 1998 of New Zealand Wettable powders are in the form of finely divided particles which disperse readily in water or other liquid carriers. The particles contain the active ingredient retained in a solid matrix. Typical solid matrices include fuller's earth, kaolin clays, silicas and other readily wet organic or inorganic solids. Wettable powders normally contain about 5% to about 95% of the active ingredient plus a small amount of wetting, dispersing, or emulsifying agent.
Emulsifiable concentrates are homogeneous liquid compositions dispersible in water or other liquid, and may consist entirely of the active compound with a liquid or solid emulsifying agent, or may also contain a liquid carrier, such as xylene, heavy aromatic naphthas, isophorone and other nonvolatile organic solvents. In use, these concentrates are dispersed in water or other liquid and normally applied as a spray to the area to be treated. The amount of active ingredient may range from about 0.5% to about 95% of the concentrate.
Dusts are free-flowing admixtures of the active ingredient with finely divided solids such as talc, clays, flours and other organic and inorganic solids which act as dispersants and carriers.
Microcapsules are typically droplets or solutions of the active material enclosed in an inert porous shell which allows escape of the enclosed material to the surroundings at controlled rates. Encapsulated droplet are typically about 1 to 50 microns in diameter. The enclosed material typically constitutes about 50 to 95% of the weight of the capsule, and may include solvent in addition to the active compound. Shell or membrane materials include natural and synthetic rubbers, cellulosic materials, styrene-butadiene copolymers, poly-acrylonitriles, polyacrylates, polyesters, polyamides, poly-ureas, polyurethanes and starch xanthates.
WO 95/10188 PCT/GB94/02183 ™ 18 — Other useful formulations for herbicidal applications include simple solutions of the active ingredient in a solvent in which it is completely soluble at the desired concentration, such as water acetone, alkylated naphthalenes, xylene and other organic solvents. Pressurized sprayers, wherein the active ingredient is dispersed in finely-divided form as a result of vaporization of a low boiling dispersant solvent carrier, such as the Freons, may also be used.
Many of these formulations include wetting, dispersing or emulsifying agents. Examples are alkyl and alkylaryl sulfonates and sulfates and their salts; polyhydric alcohols; polyethoxylated alcohols; esters and fatty amines. These agents when used normally comprise from 0.1% to 15% by weight of the formulation.
Each of the above formulations can be prepared as a package containing the herbicide together with other ingredients of the formulation (diluents, emulsifiers, surfactants etc.). The formulations can also be prepared by a tank mix method, in which the ingredients are obtained separately and combined at the grower site.
The compounds of the present invention are also useful when combined with other herbicides and/or defoliants, desiccants, growth inhibitors, and the like. These other materials can comprise from about 5% to about 95% of the active ingredients in the formulations. These combinations frequently provide a higher level of effectiveness in controlling weeds and often provide results unattainable with separate formulations of the individual herbicides.
Examples of other herbicides, defoliants, desiccants and plant growth inhibitors with which the compounds of this invention can be combined are: A. Renzo-2,1,3-thiadiazi.n-4-one-2, 2-dioxides such as bentazone; -19 — B. hormone herbicides, particularly the phenoxy alkanoic acids such as MCPA, MCPA-thioethyl, dichlorprop, 2,4,5-T, MCPB, 2,4-D, 2,4-DB, mecoprop, trichlopyr, fluroxy-pyr, clopyralid, and their derivatives (e.g. salts, esters and amides); C. 1,3-dimethylpyrazole derivatives such as pyrazoxyfen, pyrazolate and benzofenap; D. Dinitrophenols and their derivatives (e.g. acetates such as DNOC, dinoterb, dinoseb and its ester, dinoseb acetate; E. dinitroaniline herbicides such as dinitramine, trifluralin, ethalfluralin, peni'imethalin; and oryzalin; F. arylurea herbicides such as diuron, flumeturon, metoxuron, neburon, isoproturon, chlorotoluron, chloroxuron, linuron, monolinuron, chlorobromuron, daimuron, and meth-abenzthiazuron; G. phenylcarbamoyloxyphenylcarbamates such as phen-medipham and desmedipham; H. 2-phenylpyrida2in-3-ones such as chloridazon, and norflurazon; I. uracil herbicides such as lenacil, bromacil and terbacil; J. triazine herbicides such as atrazine, simazine, aziprotryne, cyanazine, prometryn, dimethainetryn, simetryne, and terbutryn; K. phosphorothioate herbicides such as piperophos, bensulide, and butatnifos; L. thiolcarbamate herbicides such as cycloate, vernolate, molinate, thiobencarb, butylate*, EPTC*, triallate, diallate, ethyl esprocarb, tiocarbazil, pyridate, and dimepi-perate; M. 1,2,4-triazin-5-one herbicides such as metamitron and metribuzin; N. benzoic acid herbicides such as 2,3,6-TBA, dicamba and chloramben; 0. anilide herbicides such as pretilachlor, butachlor, the corresponding alachlor, the corresponding compound propachlor, propanil, metazachlor, metolachlor, aceto-chlor, and dimethachlor; P. dihalobenzonitrile herbicides such as dichlo-benil, bromoxynil and ioxynil; Q. haloalkanoic herbicides such as dalapon, TC*. and salts thereof; R. diphenylether herbicides such as lactofen, fluroglycofen or salts or esters thereof, nitrofen, bifenox, acifluorfen and salts and esters thereof, oxyfluorfen and fomesafen; chlornitrofen and chlomethoxyfen; S. phenoxyphenoxypropionate herbicides such as diclofop and esters thereof such as the methyl ester, fluazi-fop and esters thereof, haloxyfop and esters thereof, quizalofop and esters thereof and fenoxaprop and esters thereof such as the ethyl ester; T. cyclohexanedione herbicides such as alloxydim and salts thereof, sethoxydim, cycloxydim, sulcotrione, tralkoxydim, and clethodim; U. sulfonyl urea herbicides such as chlorosulfuron, ^ulfometuron, metsulfuron and esters thereof; benzsulfuron and esters thereof such as the ester thereof methyl, DPX-M6313, chlorimuron and esters such as the ethyl ester thereof, pirimisulfuron and esters such as the methyl ester thereof, DPX-LS3 00 and pyrazosulfuron; V. imidazolidinone herbicides such as imazaquin, imazamethabenz, imazapyr and isopropylammonium salts thereof, imazethapyr; W. r^rylanilide herbicides such as flamprop and esters thereof, benzoylprop-ethyl, diflufenican; X. amino acid herbicides such as glyphosate and gluyfosinate and their salts and esters, sulphosate, and bilanafos; Y. organoarsenical herbicides such as MSMA; Z. herbicidal amide derivative such as napropamide, propyzamide, carbetamide, tebutam, bromobutide, isoxaben, naproanilide, diphenamid, and naptalam; AA. miscellaneous herbicides including ethofumesate, cinmethylin, difenzoquat and salts thereof such as the methyl sulfate salt, clomazone, oxadiazon, bromofenoxim, barban, tridiphane, (in the ratio 3:i) flurochloridone, quinchlorac and mefanacet; WO 95/10188 PCT/GB94/02183 BB. examples of useful contact herbicides include bipyridylium herbicides such as those in which the active entity is paraquat and those in which the active entity is diquat.
* These compounds are preferably employed in combination with a safener such as 2,2-dichloro-N,N-di-2-propenylacetamide (dichlormid).
These formulations can be applied to the areas where control is desired by conventional methods. Dust and liquid compositions, for example, can be applied by the use of power-dusters, boom and hand sprayers and spray dusters. The formulations can also be applied from airplanes as a dust or a spray or by rope wick applications.
The following are examples of typical formulations. % dust: 5 parts active compound 95 parts talc 2% dust: 2 parts active compound 1 part highly dispersed silicic acid 97 parts talc These dusts are formed by mixing the components then grinding the mixture to the desired particle size.
Wettable powders: 70%: 70 partis active compound parts sodium dibutylnaphthylsulfonate 3 parts naphthalenesulfonic acid/phenolsulfonic acid/formaldehyde condensate (3:2:1) 10 parts kaolin 12 parts Champagne chalk 4 0%: 4 0 parts active compound parts sodium lignin sulfonate 1 part sodium dibutylnaphthalene sulfonic acid 54 parts silicic acid %: 25 parts active compound 4.5 parts calcium lignin sulfate 1.9 parts Champagne chalk/hydroxyethyl cellulose (1:1) 1.5 parts sodium dibutylnaphthalene sulfonate 19.5 silicic acid 19.5 parts Champagne chalk 28.1 parts kaolin %: 25 parts active compound 2.5 parts isooctylphenoxy-polyethylene-ethanol 1.7 parts Champagne chalk/hydroxyethyl cellulose (1:1) 8.3 parts sodium aluminum silicate 16.5 parts kieselguhr 4 6 parts kaolin %: 10 parts active compound 3 parts of a mixture of sodium salts of saturated fatty alcohol sulfates 5 parts naphthalenesulfonic acid/ formaldehyde condensate 82 parts kaolin These wettable powders are prepared by intimately mixing the active compounds with the additives in suitable mixers, end grinding the resulting mixture in mills or rollers.
Emulsifiable concentrate: %: 25 parts active substance 2.5 parts epoxidized vegetable oil 10 parts of an alkylarylsulfonate/fatty alcohol polyglycol ether mixture 5 parts dimethylformamide 57.5 parts xylene The amount of the present compositions which constitute a herbicidally effective amount depends upon the nature of the seeds or plants to be controlled. The rate of application of active ingredients varies from about 0.01 to about 25 pounds per acre, preferably about 0.10 to about 10 pounds per acre with the actual amount depending on the overall costs and the desired results. It will be readily apparent to one skilled in the art that compositions exhibiting lower herbicidal activity will require a higher dosage than more active compounds for the same degree of control.
EXAMPLES The following examples are intended to further illustrate the present invention and are not intended to limit the scope of this invention in any manner whatsoever.
EXAMPLE 1 Preparation of 2-f1-(1.2.4-triazole')1ethvl-1.1-bisphosphonic acid (Compound No. 3^ One gram of 1,2,4-triazole was dissolved in 40 ml of THF and cooled to -78°C in a nitrogen atmosphere. n-Butyl-lithium (974 mg) was then added dropwise and the resultant white suspension stirred at -78°C for five minutes. After ■warming to room temperature, the mixture was stirred for 45 minutes and then cooled again to -78°C. Tetraethyl vinyl- WO 95/10188 PCT/GB94/02183 idinebiphosphonate (4.78 gm) was then added dropwise over a 20 minute period. When the addition was complete, the mixture was stirred for 15 minutes at -78°C, then warmed to 0°C and stirring continued for one hour. The reaction was quenched with 10 ml of water and the THF removed under reduced pressure to give the crude product which was then combined with 35 ml of aqueous K2C03 solution. The resulting mixture was extracted with 3 X 100 ml portions of dichloromethane. The extracts were combined, dried (MgS04), and the solvent removed under reduced pressure to afford a mobile oil. Column chromatography on silica gel with 10% methanol/dichloromethane provided 1.3 gm of tetraethyl 2-[1-(1,2,4-triazole)ethyl-1,1-bisphosphonate. Hydrolysis of this material to form Compound 3 was achieved by heating a dichloromethane solution of the tetraethyl ester and "500 mol% of bromotrimethylsilane at 45°C for four hours and then removing the volatiles in vacuo. Refluxing the residual oil with water for 30 minutes followed by cooling to room temperature and removal of the water under high vacuu™ resulted in the isolation of 3 in quantitative yield.
EXAMPLE 2 Preparation of l-hvdroxv-(2-amino-2-methyl)propvl-l.1-bisphosphonic acid (Compound No. 8^ To a three-necked 250 ml round-bottomed flask equipped with a condenser, mechanical stirrer, oil bath and thermometer were added 2.37 gm of 2-aminoisobutyric acid, 85 ml of chlorobenzene and 3.2 gm of phosphorous acid. The mixture was heated at reflux for one hour and then cooled to 50°C. Phosphorus trichloride (9.62 gm) was then added and the mixture again heated to refluxing with stirring for five hours. At the end of this time, the mixture was allowed to cool to room temperature and the chlorobenzene carefully decanted. Fresh chlorobenzene (85 ml) and 80 ml of 6N HC1 •were then added and the mixture heated to refluxing with stirring. After six hours, the yellowish suspension was cooled to room temperature, vacuum filtered through dicalite, and the volatiles removed under high vacuum to afford a colorless syrup. Trituration with ethanol under steam heating provided 3.09 gm of product 8 bs a white solid after isolation by vacuum filtration.
* EXAMPLE 3 Preparation of l-hvdroxv-i-(2-pvrrolidino)-1.1-bisphosphonic acid /Compound No. 9) To a 200 ml three-necked flask equipped with a mechanical stirrer and reflux condenser carrying a nitrogen bubbler were added 4 gm of proline; 5.7 gm of phosphorous acid and 25 ml of dioxane. Phosphorus trichloride (9.6 gm) was then added dropwise at 80°c and the mixture stirred at 80°C for two hours. After cooling the reaction mixture to room temperature, water (150 ml) was added to the resulting mixture was filtered through activated carbon. The filtrate was evaporated under reduced pressure and the residual clear oil placed in a vacuum oven (60°C) overnight. At the end of this time- the residue was triturated with EtOH and the resulting white solid isolated by vacuum filtration. Drying the solid in a vacuum oven at 60°C afforded 5.9 gm of Compound 9.
EXAMPLE 4 Preparation of 2-fbut-3-envlamino^ethvl-l.1-bisphosphonic acid (Compound No. 29^ A solution of 1.08 gm of l-aminobut-3-ene in five ml of methanol was added to 3.8 gm of tetraethyl vinylidinebis-phosphonate at room temperature. After the resulting mixture had stirred overnight, an additional 0.12 gm of l-aminobut-3-ene was added and the stirring continued for an additional four hours. The reaction mixture was then concentrated under reduced pressure to yield 4.56 gm of tetraethyl 2-(but-3-enyl-amino)ethyl-1,1-bisphosphonate. A 4.4 gm sample of this material was combined with five ml of acetonitrile and 7.2 ml of bromotrimethylsilane. After stirring at room temperature for 48 hours, the solution was heated to refluxing for four hours and then concentrated under reduced pressure. The resulting tetra(trimethylsilyl) ester was hydrolyzed by refluxing with 25 ml of water for 30 minutes. Removal of the volatile materials by lyophylization afforded 3.2 gm of Compound 20 as a stiff, colorless, hygroscopic foam.
EXAMPLE 5 Preparation of 2-(3-methvl-l-pjperidinvHethvl-1.1-bisphosphonic acid (Compound No. 37) A solution of one ml of 3-methylpiperidine in five ml of methanol was added dropwise to 2.43 gm of tetraethyl vinylidinebisphosphonate at room temperature. The reaction was stirred overnight and the mixture then concentrated under reduced pressure to yield 3.4 grams of tetraethyl 2-(3-methyl-1-piperidinyl)ethyl-1,1-bisphosphonate. A portion of this material (3.37 gm) was dissolved in five ml of acetonitrile followed by the addition of five ml of bromotrimethylsilane. The resulting mixture was refluxed overnight, then allowed to cool to room temperature, and then concentrated under reduced pressure. Water (25 ml) was added to the residual oil and the mixture stirred for three hours. Removal of the water and other volatile components under high vacuum afforded 2.84 gm of 37. as a stiff, hygroscopic, colorless foam.
WO 95/10188 PCT/GB94/02183 EXAMPLE 6 Preparation of 2-C4 methvlbenzvlamino)ethvl-1.1-bisphosphonic acid (Compound No. 67) To a 100 ml boiling flask were added 3.5 gm of tetraethyl vinylidine-l,1-bisphosphonate, 20 ml of acetonitrile, and 1.5 gm of 4-methylbenzylamine. The resulting mixture was magnetically stirred overnight at room temperature. At the end of this time, the solvent was removed under reduced pressure to give 4.66 gm of tetraethyl 2-(4-methyl-benzylamino)ethyl-1,1-bisphosphonate. A portion of this material (3.87 gm) was placed in a 100 ml' boiling flask equipped with a magnetic stirrer and refluxed for four hours with 25 ml of concentrated HC1. Removal of the volatile materials under high vacuum afforded 3.21 gm of 67. as a color less, hygroscopic glass.
EXAMPLE 7 Employing a process similar to those described above, the following compounds, listed in Table I, were prepared: • H W 03 s h CI OS N S3 I w n e> 2 1 O -U -0, r>j n in os «l as i S3 CJ 1 Si I S3 O £ i i fN S3 U I fN CM I M S3 U I *4 / ^ in « n a S3 N K\ S3 S3 rl Kl S3 S3 . S3 . K 6 § 8 85 cm r> RECEIVED Intellectual Property Office 0 3 FtB 'isbti of New Zealand comp. no. r3 R r" R r~ C/l oo 00 . h h h -ch2ch2-ch2-ch2- tetramethylammonium salt 6. ii h h -CH2-CH2-CH2-CH2-CH2- 7. -oh ii h —ch=n-ch=ch— M ID I 8. -oh -ch3 -ch3 h h hydrochloride salt 9.
P°3H2 -n oh p03h2 n H § £ © s» 00 COMP. NO. R1 4 5 R . ?°3H2 CH -OH P°3H2 tributylamine salt 11. H H H -CH2-CH2-CH2-CH2- tributylamine salt 12. H H H H -nc3H? uj 0 1 13. H H H -CH2~CH2'CH2'CH2 trixnethylsulfonium salt 14. H ° S am 15. H z So ® ~n -lJ < m -oin N 5 — 2. _ • ^ §. ic Jin J -,ri CO O" H H H H H -O 3 n <?? a\ in Kl u 4J I m 6 *<d pi n S3 0 1 w «l W w M K • 04 • o o S5 u *0 H H eo H in..il.M Www Ml" 0 3 FEB W98 of New Zealand cm ir> Oil u I ci cm n U i u—o ■ 1 cm ►T* cm 0 1 U i 1 cm vm i cm o •J"1 i. n u a—o U—U in cm u i in cm u i as n U C I n U C I cn n S 0 1 u c I ft al (M Oil DSl cm K Z I a, s o o o z o cm CN cm cm n cm cn in cm vo <n r* cm in «l n S3 u 0 1 CM . 8 W CJ CM 03 CJ CM n H e CJ c I <M 03 CJ I CM as o ii £S CJ N g K «n CJ G I n as o § i « 53 W n a C i n n ? n «l 33 S3 ■ ■ W CM S3 S3 « "U X ta § d 8 * 00 CM a\ CM o n H C) CM <n cn ■*r in <*> n r e e g I v g p intollootuftl Property Office 0 3 FEB 1**8 of New Zealand o COMP. NO.
R R~ R R~ VO Ui 36. H H H H -C2H5 37. H H H CH.
I ^ -CI12 -CH-CH2 -CII2 -CH2 - 39. -OH H H H -CH, 40. H H H -nC4"9 -nC4H9 00 oo 38. H H 11 H C2H5-°-CH2CH2- I UJ I 41. H 42. H H H H H II H "nC6H13 S«3 tetrabutylammonium salt o w SO £ © k-» 00 w ^4Q0q r> © tg in | M m / tn „ / u t=K % \ 1 Xr, JN K g ° 1 L tc CJ 1 TT 1 (4 » w w K K nd S3 a K E V s E 55 S3 H 1 «l « SB SB « .6 ro M 8 i « cu • S S 8 55 n ■*r in <d" vo ■<* «r RECEIVED Intellootual Property Office 0 3 FtB 1998 of New Zealand < in m «l CM X u I CM x cj I CM x U I CM X u I CM X cj I CM x cj CM x 0 1 CM x u n | x x CJ—u I m U c I n cj •H CM x U I CM x u n X u I m x cj I I x n CJ x i CJ—CJ I 0 en | x x CJ—o 1 CM x CJ I (*> Oil CM «l QSl x & s o O 2 O CO a\ ■*7 O in in cm in ro in n in «l (M x n O x ii u—u I <N a a i i CM x u m i x x u—o I CM x u tn I x x o— u I (M x u II x u I CM x 0 1 (N CM x u I x u II x u I CM x a i X 0 n l X X u-u 1 CM x u I oa x a i CM x u I CM x a i 0 1 CM x 0 1 CM x 0 1 m m CM al m cu s o o z u in in in vo in t-» in CO in (Ti in 9 oj oj i X SB oj U O X '.o II II U fr. X S I I- O U O r 7 OJ I x i i i \ / as cj n oj cj oj \ / U X u a x s Y i u c o u cj oj i in i i i i i is oj p5i uk I U oj i as oj u x in in i u 33 s3 m oj n i oj oj re as x x -a- I O U O U U—O «l i a i i a i m K\ a cm «l o< s o O 2 U o vo rH vo oj vo n vo v vo in vo vo vo 9 n in PS as o "vJ OJ U l CM K U I Oil m Kl a: (N Kl «l 04 s o O 2 u vo CO vo CTi vo O I Hd *>400 m in «l P3 D I b & i <N a 0 1 V M in in K ta X U M (M CNJ 0 U W \ / y \ V / f eg ac SC u u cc fM 8 I B I OJ X 0 n 5s 8-A 1 en n | as as u—u I <N X tt n 0 e 1 o M B S3 CN csl X X w & O 8 * 00 tN CO o CO CO in oo vo «D RECEIVED Intellootual Property Office 0 3 FEB tebti of New Zealand in «l CT> 0 c 1 (N X u I (N a i o o=u oj u oj OJ u I u I oj oi oj L> oj X a oj x u I X u I oj X u I oj _ in n — X X — oj U—r— U T X u r> l X X u—u «I X X a—a x r> m 0 c 1 in a X I oj X u—o i u c n «l OJ CC\ (XI a, 2 O O 2 U r-co co co G\ co o cn o\ oj Oi CM If) I n CJ U Kl I 2 II X a i o 0=0 CJ I CM CM a i u m I U-CJ fM n U c I u n I MM MM U-O I cn VO U C I r> 0 C 1 I X ■ r> U X II CJ—u I X u II z I X o II X 0 1 n Z X II u-u I n «l CJ osl (XI cu s o O 2 U cn a\ •<r cn IT) a\ vo r-cn CO o\ ci in I 051 cj c*i l a; x u—o i oj CN O u c I I CN x u H I x x u-u I CN u I CN G n l U-U I I CN X 0 1 CN X u 1 CN X 0 1 H in O c I m cj C I A 04 \V n K\ CN QSl Kl 0« z o O 2 U CT\ cn o o o rH CM O cn o o WO 95/10188 PCT/GB«M/02183 -Alio fXl cc •a CM I s n u X II u—a n z a: ii o—o I s 0 1 2 U I u c I r> 0 c 1 CN X CJ I fM X u I CN K u I m Kl CN (X (X! S X a, s o O 2 u cn o CM n COMP. 12 3 NO. KZ e_ £_ 4 114. H H H 115. H H H 116. H H H i c=> 5=3* 117. H H H w s™ -n SO m 3— m < tc 3B* 00 ^ 118. h h h -CH=N—C=CH- -CH2-CH2 •£l CH_ C H I 3 | 2 5 -ch-ch2ch2-ch-ch2 ■ n-ch=ch- c_h7 J 3 7 ch-ch2-ch2 ch2.ch2 • - • comp. no. si el e 1 R2 R3 r! R? I 122. H H 123. H 00 00 CH3 119. 11 H H H -CH-CH2CH2CH3 C2H5 120. H H H -C=N-CH=CH- I U3 121. II H H " "CH2""4_V H H ~CH H H H -CH2—\J} n H § I) N S si 00 w o •-r in csi u./ o n u I «l in X CN u I n U I CN U I OJ u I CN U I OJ X u I CM X o CN CN CN I x a a: x o-u —o—u / I / OJ X u I CN X u OJ X u I 01 X 0 1 CN CJ I OJ X osl c, s o O 2 U OJ in OJ <o CN r-CN CO OJ 9 129. h h h -ch2-ch2-ch-ch2-ch2- 131. h II h -c=n-ch2-ch2-ch2- bis NH y salt 132. H h h h -ch2-ch(oh)-ch3 hydrochloride salt comp. 1 2 3 4 5 no. r r r r r O v© VI td\ ch, oc 00 130. h h h | 2 5 -ch., -ch2 -ch-ch2 -cii2 - l Ln H I 133. h h h h -ch2-ch(oh)-ch3 trimethylsulfonium salt Q <n w vo ■u 134. h h h h -ch2-ch(oh)-ch3 tetrabutylammonium salt 00 U> COMP.
WO.
R 135.
H H H H 136.
H H H H 137.
H H H H 9. z N <D 2. 3° 3 a.
CO -r-rr cc t1 u oc K S co u m 3 — -D ^ O <■ 3 m nO 138, H H H /I* / H 139.
H H H H e£ ?3 -CH \w > hydrochloride salt CH3 f -CH CH„ CH, •I-© CH 17 -CH oi KJ I ^ _/n\ -CH \0/ hydrochloride salt tetrabutylammonium salt C/rs' £ \ZL/ trimethylsulfonium saj^^ HERBICIDAL SCREENING TESTS The compounds listed in the foregoing table were tested for herbicidal activity by various methods and at various rates of application. The results of some of these tests are given below. Results obtained in herbicidal screening are affected by a number of factors including: the amount of sunlight, soil type, soil pH, temperature, humidity, depth of planting, plant growth stage, application rate as well as many other factors. All testing procedures are administered with the least amount of variability possible. State of the art equipment and techniques are employed to enable the screening process to remain consistent and reliable.
PRE-EMERGENCE HERBICIDAL SCREENING TEST On the day preceding treatment, seeds of several different weed species were planted in sandy loam soil containing only trace organic matter. Propagules were sown in individual rows using one species per row across the width of an aluminum flat (19.5 x 9.5 x 6 cm). The grass weeds planted were.green foxtail (Setaria viridis) ("SETVI"), wild oat (Avena fatua) ("AVEFA"), barnyardgrass (Echinochloa crus-galli) ("ECHCG"). Broadleaf weeds utilized were wild mustard (Brassica kaber) also known as (Sinapis arvensis) ("SINAR"), velvetleaf (Abutilon theophrasti) ("ABUTH") and morningglory (Ipomoea spp.) ("IPOSS")-. Additionally, yellow nutsedge (Cyperus esculentus) ("CYPES"), nutlets were sown. Seeding depths ranged from 1.0 to 1.5 cm and plant densities ranged from 3 to 25 plants per row depending on individual plant species.
Solutions of the test compounds were prepared by weighing out 18.8 and 74.7 mg for 1 and 4 kg/ha applications respectively, of the test compound into a 60 ml wide-mouth bottle, then dissolving the compound in 14.0 ml of deionized water containing 0.5% v/v Tween 20® (polyoxyethylene sorbitan monolaurate emulsifier) as a surfactant. Additional solvents, WO 95/10188 PCT/GB94/02183 not exceeding 2 ml (15% of spray volume), were used if needed to dissolve the compound.
The soil surface was sprayed inside an enclosed linear spray table with the nozzle set at 30.5 cm (12 inches) above the soil line. The spray table was calibrated to deliver 748 L/ha (80 gal/A) with the application rate being 4.0 <kg/ha or 1.0 kg/h?. (as indicated in Table II below).
After treatment the flats were placed into a greenhouse and watered overhead by sprinkling. The greenhouse environmental systems provided the plants with natural and artificial (via metal halide lamps) lighting to attain 14 hours of light per day. Day and night temperatures were maintained at 29° and 21°C respectively.
The degree of weed control was evaluated and recorded 17-21 d=»ys after treatment as a percentage of weed control as compared to the growth of the same species of the same age in an untreated control flat. Percent control is the total injury to the plants due to all factors including: inhibited emergence, stunting, malformation, chlorosis and other types of plant injury. The control ratings range from 0 to 100 percent, where 0% represents no effect with growth equal to the untreated control and where 100% represents complete kill. A dash indicates that no test was performed at that level of application.
POST-EMERGENCE HERBICIDAL EVALUATION The soil was prepared and seeded with the same species and methodology described for the pre-emergence test. Post-emergence flats were placed in the greenhouse under the same environmental conditions as described for the pre-emergence flats and watered overhead by sprinkling. Plants were grown for 10 to 12 days (or to the appropriate growth stage) prior to compound application. Grasses were sprayed at a 3 to 4 leaf stage and broadleaves at a 1 to 2 leaf stage. Yellow nutsedge was 5 to 7 cm tall at application.
WO 95/10188 PCT/GB94/02183 Plants were sprayed 30.5 cm (12 inches) above the foliage with the same spray solution as prepared for the pre-emergence test. The application rate was 4.0 kg/ha or 1.0 kg/ha (as indicated in Table III below). Treated plants were then returned to a greenhouse and watered daily without wetting the foliage. The degree of weed control was evaluated 17-21 days after application and recorded as percentage of control zs compared to the growth of the same species in an untreated control flat of the same age. The percent control scale (0-100%) used to evaluate the pre-emergence treatment was also applied to the post-emergence treatment. 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 • • TABLE II Pre-Emergent - Testing M.O kg/ha) AVE FA ECHCG SETVI ABUTH IPOSS SINAR 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 25 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 10 0 20 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 COMP. NO. AVEFA ECHCG SETVI 21. 0 0 0 22. 0 0 0 23.* 0 0 0 24.* 0 0 0 .* 0 0 0 26. 0 0 0 27.* 0 0 0 28.* 0 0 0 29.* 0 0 0 .* 0 0 31.* 0 0 0 32.* 0 0 0 33.* 0 0 0 34.* 0 0 0 .* 0 0 0 36.* 0 0 0 37.* 0 0 0 38.* 0 0 0 39. 0 0 0 40.* 0 0 0 41.* 0 0 0 42.* 0 0 0 43.* 0 0 0 * O ABUTH IPOSS SINAR CYPES « © 00 0 0 0 0 00 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 o I 0 0 0 0 iJJ 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 o oo o q 0 0 0 0 g 0 0 0 o I 0 0 0 os w 0 0 0 0 0 0 0 0 COMP. NO. AVEFA ECHCG 44.* 0 0 45.* 0 0 46.* 0 0 47.* 0 0 48. * 0 0 49.* 0 0 50.* 0 0 51.* 0 0 52. * 0 0 53.* 0 0 54 .* 0 0 55.* 0 0 56. * 0 0 57.* 0 0 58.* 0 0 59.* 0 0 60. * 0 0 61.* 0 0 62.* 0 0 63.* 0 0 64.* 0 0 SETVI 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 * ABUTH IPOSS SINAR CYPES ® ^ >»* o 0 0 0 0 « 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 ( cn 0 0 0 0 CD 25 5 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 o 0 0 0 0 0 0 0 0 * 3 0 0 0 0 0 a 0 0 0 0 I © 0 0 0 o Ej 00 COMP. NO. AVEFA ECHCG SETVI 65.* 0 0 0 66.* 0 0 0 67.* 0 0 0 68.* 0 0 0 69.* 0 0 0 70. * 0 0 0 71.* 0 0 0 72 . * 0 0 0 73 . * 0 0 0 74 . * 0 0 0 75.* 0 0 0 76. * 0 0 0 77.* 0 0 0 78.* 0 0 0 79.* 0 0 0 * • o CO 0 0 0 81. * 0 0 0 82. * 0 0 0 83 . * 0 0 0 03 * 0 0 0 85. * 0 0 0 86.* 0 0 0 87.* 0 0 0 * • CO CO 0 0 0 ABUTH IPOSS SINAR CYPES J! O VO Ul 0 0 0 0 o 0 0 0 0 00 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 $ 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 * 9 0 0 0 op 00 0 0 0 o 1 o 0 0 0 0 £ u 0 0 0 o 0.0 0 0 COMP. NO. AVEFA ECHCG SETVI * • o CO 0 0 0 90. * 0 0 0 91.* 0 0 0 92.* 0 0 0 93 . * 0 0 0 94.* 0 0 0 95.* 0 0 0 96.* 0 0 0 97. * 0 0 0 98.* 0 0 0 99.* 0 0 0 100. * 0 0 0 101.* 0 0 0 102.* 0 0 0 103.* 0 0 0 104 .* 0 0 0 105.* 0 0 0 106. * 0 0 0 107.* 0 0 0 108. * 0 0 0 109. * 0 0 0 110. * 0 0 0 111.* 0 0 0 112. * 0 0 0 ABUTH 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 IPOSS 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 SINAR 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 CYPES 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 3 © VO L/l 06 00 CTi 0 1 3 <n w u © SI ta* 00 c*> COMP. NO. AVEFA ECHCG SETVI 113.* 0 0 0 114.* 0 0 0 115.* 0 0 0 116.* 0 0 0 131.* 0 0 0 * Tested at 1.0 kg/ha * ABUTH IPOSS SINAR CYPES ~ 0 0 0 0 oo 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 i CTl vo 4k N> 00 Iji 0 0 50 00 0 0 0 Post- TABLE III Emeraent - Testina M.O ka/ha) AVEFA ECHCG SETVI ABUTH IPOSS SINAR 0 0 0 0 — 0 95 95 60 90 0 60 100 100 100 100 100 100 100 100 100 100 100 100 200 100 100 70 100 100 60 100 300 75 70 100 0 0 0 0 0 0 0 0 60 0 0 90 70 80 100 95 95 80 70 100 100 100 100 70 95 100 60 90 100 100 98 98 98 60 60 100 50 60 60 70 100 85 50 60 60 100 0 0 0 0 50 0 85 60 100 100 100 85 85 50 90 100 COMP. NO. AVEFA ECHCG SETVI 21. 30 50 50 22. 100 98 98 23.* 40 40 80 24.* 100 100 100 .* 100 100 100 26. 5 0 5 27.* 70 90 95 28.* 0 0 0 29.* 80 100 90 .* 75 50 60 31.* 90 70 80 32.* 100 98 98 33.* 100 100 98 34.* 5 10 40 .* 5 0 60 36.* 40 60 50 37.* 50 30 50 3 8.* 0 15 20 39. 0 0 0 40.* 98 98 85 41.* 95 60 95 42.* 100 100 100 43.* 80 80 60 g ABUTH IPOSS SINAR CYPES vo O 0 30 95 0 » 98 90 100 70 10 95 5 70 100 100 25 60 100 100 20 0 10 10 0 10 85 15 0 0 0 0 10 100 20 ( 0 10 50 0 2) 10 10 30 70 100 50 100 60 100 10 0 0 50 0 0 10 0 0 0 10 1r 0 10 30 5 5 40 0 q 0 0 0 0 <5 w 0 5 30 10 | o 0 0 98 25 £ 00 98 90 100 85 10 40 5 COMP. NO. AVEFA ECHCG SETVI 44.* 80 90 90 45.* 30 85 50 46.* 80 50 40 47.* 60 5 30 48.* 60 60 60 49.* 90 90 95 50. 0 0 0 51.* 100 95 100 52.* 100 100 95 53.* 5 0 5 54.* 95 95 95 55.* 98 15 50 56. 0 0 0 57.* 95 95 100 58.* 40 70 90 59.* 95 25 40 60.* 100 100 100 61.* 20 0 5 62.* 85 90 80 63.* 100 95 95 64.* 100 95 95 65.* 100 100 100 vo Ih OB 00 ABUTH IPOSS SINAR CYPES ^ O n 75 5 100 7f< 5 60 5 10 15 15 5 50 10 0 15 85 0 30 100 5 0 0 0 0 75 85 100 25 50 65 100 10 0 5 25 O oO 60 100 15 0 30 25 0 0 0 0 0 15 98 10 5 20 5 95 15 0 70 90 100 10 0 0 0 0 10 95 10 rj 85 85 100 60 0 CO 90 100 20 I © 70 100 100 20 J* w cn i COMP. NO. AVEFA ECHCG SETVI 66.* 100 98 98 67.* 95 60 75 68.* 95 70 30 69.* 30 20 30 70.* 10 30 20 71.* 90 100 100 72.* 100 100 100 73.* 50 15 20 74.* 0 0 10 75.* 100 98 95 76.* 60 50 15 77.* 50 15 10 78.* 60 10 5 79.* 75 30 15 80.* 90 70 25 81.* 50 60 85 82.* 98 100 98 83.* 100 100 98 84.* 100 98 98 85.* 15 40 20 86.* 100 98 98 87.* 100 100 100 88.* 98 100 98 89.* 0 0 10 ABUTH IPOSS SINAR CYPES £ O 60 100 5 10 20 20 10 10 10 0 5 20 15 0 10 10 10 60 10 90 60 90 ' 100 100 50 0 5 10 0 0 5 0 60 95 100 50 70 30 90 5 0 5 10 0 VO (A 00 00 I cn 10 10 10 ui 5 15 5 0 5 5 5 10 5 5 15 25 10 5 85 5 15 100 30 50 35 100 30 25 100 50 * 9 0 10 90 0 2 CD 70 15 100 5 75 20 100 20 00 W COMP. NO. AVEFA ECHCG SETVI 90.* 75 80 100 91.* 100 100 100 92.* 100 100 100 93.* 100 98 100 94.* 0 10 10 95.* 40 40 80 96.* 85 90 95 97.* 10 30 30 98.* 100 98 95 99.* 100 93 95 100.* 100 100 90 101.* 100 60 70 102.* 50 90 70 103.* 100 85 95 104.* 0 5 10 105.* 75 70 60 106.* 50 60 15 107.* 50 50 50 108.* 60 30 30 109.* 30 50 20 110.* 85 90 98 111.* 100 98 100 112.* 10 15 10 113.* 0 5 10 ABUTH IPOSS SINAR CYPES ^ O VO c* 60 10 100 30 S 95 98 100 60 " 80 90 100 15 *8 90 100 10 5 10 0 15 15 10 20 90 5 5 20 0 50 50 98 5 70 100 100 15 i 70 30 90 10 S 40 20 30 0 25 100 5 30 85 10 5 10 0 5 20 5 5 15 10 0 5 15 10 10 30 10 * 3 5 15 OP 09 15 100 5 i o 75 100 100 30 - 10 20 0 0 5 10 0 • • COMP. NO. AVEFA ECHCG SETVI 114.* 0 10 5 115.* 100 98 98 116.* 100 70 40 131.* 95 100 100 * Tested at 1.0 kg/ha • - • 0 5 5 0 ABUTH IPOSS SINAR CYPES 3 O NO in 70 20 98 5 « 10 20 0 100 100 100 5 l cr> -j I 9 § VO o 00

Claims (18)

WO 95/10188 PCT/GB94/02183 -68- Th e above date indicates the efficacy of the present claimed compounds when applied post-emergently, coupled with their safety to plants when applied pre-emergently. WO 95/10188 PCT/GB94/02183 -69-.
1. A method of controlling the growth of plants comprising applying to the locus of such plants a herbicidally effective amount of a compound df the Formula (I): N— R I C PO.H, 1 21 C R y k2 i (i) °3H2 wherein R1 is hydrogen, hydroxy, C1-C4 alkoxy, halogen, c1-c4 alkyl, c1~c4 haloalkyl, hydroxy-C1-C4-alkyl, hydroxy--c1~c4-alkoxy; 2 3 R and R are each independently hydrogen; hydrocarbyl; substituted hydrocarbyl; hydrocarbyloxy; substituted hydrocarbyloxy; hydrocarbyi^S(0)m-; or substituted hydrocar-byl-S(O) 2 3 R and R together form a 3-6 membered carbocyclic ring, optionally substituted with halogen, hydroxy, C1-Cg alkyl, alkoxy, C^-Cg alkylthio or N(RS) (R9) wherein R8 and R9 are each independently hydrogen or C.-C., alkyl; and 4 5 R and R are each independently hydrogen; hydrocarbyl; substituted hydrocarbyl; hydrocarbyloxy; substituted hydrocarbyloxy; hydrocarbylthio; substituted hydrocarbylthio; pyridyl; or are of the formula N(R10)(R11) ^wherein R10 and R11 are independently hydrogen, hydrocarbyl or substituted hydrocarbyl; or 4 5 R and R together with the nitrogen to which they are bound form an aziridine, piperazine, morpholine, thiomorpholine, thiomorpholine sulfinyl, thiomorpholine sulfonyl, hexamethyleneimine, piperidine, tetrahydropyridine, pyrazole, imidazole, pyrrole, triazole, tetrahydropyrimidine, dihydro-imidazole, pyrroline, azetidine, perhydroindole, perhydro-quinoline, perhydroisoquinoline or pyrrolidine ring, any of which may be optionally substituted with C1"C12 alkyl, ha^o^ IntalleetiH Praparty Office 0 7 FFR 1098 of New Zealand WO 95/10188 PCT/GB94/02183 -70- Cg-C10 aryl, Cg-C1Q aryl substituted with halo or C^-Cg a-j C^-C^g aralkyl, C7-Clg aralkyl substituted with halo or C1-Cg alkyl, nitro, halo-C^-C^g-alkyl, alkoxy, allcY'1~ thio, C1~C10 alkylsulfonyl, phenoxy, phenoxy substituted with halo or C.-C- alkyl, C,-Cin alkenyl or cyano; or X - O a X XU * R and^ R together with the nitrogen and carbon atoms to which they are bound form an aziridine, piperazine, <r morpholine, thiomorpholine, thiomorpholine sulfinyl, thiomorpholine sulfonyl, hexamethyleneimine, piperidine, tetrahydro-pyridine, pyrazole, imidazole, pyrrole, triazole, tetrahydro-pyrimidine, dihydroimidazole, pyrroline, azetidine, perhydro-indole, perhydroquinoline, perhydroisoquinoline or pyrrolidine ring, any of which may be optionally substituted with c1~c12 alkyl, halo, Cg-C1Q aryl, Cg-C1Q aryl substituted with halo or C^—cg alkyl, c7~clg aralkyl, C7-Clg aralkyl substituted with halo or C1-Cg alkyl, nitro, halo-c^-c^g-alkyl, al^oxY/ alkylthio, alkylsulf°nylf phenoxy, phenoxy substituted with halo or C1~Cg alkyl, alkenyl or cyano; or m is 0, 1 or 2; or an agrochemically acceptable salt thereof.
2. A method in accordance with claim 1 wherein R^" is hydrogen or hydroxy. 2
3. A method m- accordance with claim 2 wherein R 3 and R are each independently hydrogen or C,-Cc alkyl. X O
4. A method in accordance with claim 3 wherein R4 5 and R are each independently hydrogen, C^-Cg alkyl, C^-Cg alkenyl, benzyl or benzyl substituted with C.-C. alkyl or X o halo.
5. A method in accordance with claim 3 wherein R4 and R5 together with the nitrogen to which they are bound form a pyrrolidine or piperidine ring.
6. A method in accordance with claim 1 wherein R1 is hydrogen, hydroxy, halogen or C -c. alkvla 6 \ V E D 1 4 lntellootu.1 0™ Q 9 PCR 10Q8 of Now Zealand WO 95/10188 -71- i 2 3. R and R are independently hydrogen; C1-C12 alkyl; C2-C12- alkenyl; C2"C12 al3cyny1' halo~ci",ci2 alIcy1' halo""(-2,"C12 alkenyl; halo-c2-c12-alkynyl; cg-c14 aralkyl; alkoxy; or C1~C12 alkylthio; R4 and R5 are independently hydrogen; C.-c, alkyl; C2-C6 alkenyl; C2~C6 alkynyl; halo-^-Cg alkyl; halo-Cj-Cg alkenyl; halo-C^Cg-alkynyl; pyridyl; substituted pyridyl; phenyl; or substituted phenyl; C7~C14 aralkyl; C7~C14 substituted aralkyl; or 4 5 R and R together with the nitrogen to which they are bound form a tetrahydropyrimidine, tetrahydropyridine or imidazole ring or a -(CH,) -N- ring wherein n is 3-6, option-ally substituted with halogen, hydroxy, C1"C6 alkoxy, nitro, C^-Cg alkyl, C7-Clg aralkyl or C^-Cg alkylthio groups.
7. A method in accordance with claim 6 wherein R1 is hydrogen or hydroxy; R alkyl; and 2 „3 and R are each independently hydrogen or C1-C{. 4 5 R and R are each independently hydrogen, C1-Cg alkyl, C^-Cg alkenyl, benzyl, benzyl substituted with alkyl or halo or 4 5 R and R together with the nitrogen to which they are bound form a pyrrolidine or a piperidine ring optionally substituted with fluorine, hydroxy, C1-Cg alkoxy or C^-Cg alkyl.
8. A method in accordance with claim 1 wherein said compound is 2-(1-pyrrolidinyl)ethyl-1,1-bisphosphonic acid; 2-(i-piperidinyl ) ethyl-1,1-bisphosphonic acid; 2-(propylamine)-ethyl-1,l-bisphosphonic acid; 2-(N,N-methylethylamino)ethyl-1,1-bisphosphonic acid; 2-(n~butylamino)ethyl-1,l-bisphosphonic acid; 2-(2-prope:iylamino) ethyl-1,1-bisphosphonic acid; 2-(R-alpha-methylbenzylamino)ethyl-1,1-bisphosphonic acid; 2-(2-methylpropylamina)ethyl-l,1-bisphosphonic acid; 2-[l-(4-methyl-lf3-imidazolyl)]ethyl-1,1-bisphosphonic acid; or 2-[1-(1,2,3,6-tetrahydropyridinyl)]ethyl-1,l-bisphosphonic aCid* « 1 ° * 1 V 1 5m, IntttllOQtunl ProptrtY Office 0 31-fc.b of Nqw Zofltend -72- & 4 000
A compound of the Formula (VII) N: 25 ■ N CH, (CR23R24K' PO.H. I 3 2 ■CH i°3H2 (VII) wherein t is 2, 3 or 4; R23 and R24 are each independently hydrogen, C1~C1(J alkyl, halo, nitro, Cj-Cg alkoxy, ^-c^ aralkyl, cyano, trifluoromethyl or represent a unit of 25 unsaturation; and R is hydrogen, C,-C- alkyl, C_-C,„ 1 o / 10 aralkyl, halo, nitro, trifluoromethyl or cyano.
10. A compound of the Formula (VIII) H P03H2 ■H H PO3H2 wherein r26_r33 are independently H or C-j-Cs alkyl.
11. A composition containing a compound of the Formula (VII) as defined in claim 9 together with an acceptable carrier.
12. A composition containing a compound of the Formula (Vl!l) as defined in claim 10 together with an acceptable carrier.
13. A composition as claimed in claim 11 or claim 12 which is a herbicidal composition.
14. A compound as claimed in claim 9 as specifically set forth herein. jmswlw"- D 3 PF.B 1MB ef New Zealand -73- & 4 0,
15. A compound as claimed in claim 10 as specifically set forth herein.
16. A composition containing a compound of claim 9 or claim 10 substantially as herein described with reference to any one of the formulation examples.
17. A process for the preparation of a compound of claim 9 or claim 10 substantially as herein described with reference to the Examples.
18. A method as claimed in claim 1 substantially as herein described. . -"'"vis; RECEIVED ltrt4ll«oW«! Property Office 0 J FEB 1998 of Now Zealand
NZ274000A 1993-10-07 1994-10-07 Use of azabisphosphonic acid derivatives as herbicides, azabisphosphonic derivatives NZ274000A (en)

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PCT/GB1994/002183 WO1995010188A2 (en) 1993-10-07 1994-10-07 Herbicidal aza bisphosphonic acid compositions

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US5728650A (en) * 1993-10-07 1998-03-17 Zeneca Limited Herbicidal aza bisphosphonic acids and compositions containing the same
WO1995034207A1 (en) * 1994-06-13 1995-12-21 Zeneca Limited Method of controlling plants by inhibition of farnesyl pyrophosphate synthase
IL115041A0 (en) * 1995-08-23 1995-12-08 Yissum Res Dev Co Novel bisphosphonates process for their preparation and pharmaceutical compositions containing them
WO2007039635A2 (en) * 2005-10-06 2007-04-12 Innate Pharma Phosphoantigen salts of organic bases and methods for their crystallization
EP2001486A4 (en) * 2006-03-17 2010-12-29 Univ Illinois Bisphosphonate compounds and methods
PT103600B (en) * 2006-11-06 2009-01-30 Hovione Farmaciencia Sa PROCESS FOR THE PREPARATION OF BIOSPHONIC ACIDS AND THEIR PHARMACEUTICALLY ACCEPTABLE SALTS

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SU739076A1 (en) * 1976-05-19 1980-06-05 Институт Химической Кинетики И Горения Со Ан Ссср Method of preparing beta-aminoethylidenediphosphonic acids
DE3623397A1 (en) * 1986-07-11 1988-01-14 Boehringer Mannheim Gmbh NEW DIPHOSPHONIC ACID DERIVATIVES, METHOD FOR THE PRODUCTION THEREOF AND MEDICINAL PRODUCTS CONTAINING THESE COMPOUNDS
IL84731A0 (en) * 1986-12-19 1988-05-31 Norwich Eaton Pharma Heterocycle-substituted diphosphonic acids and salts and esters and pharmaceutical compositions containing them
NZ253524A (en) * 1992-05-29 1997-01-29 Procter & Gamble Pharma Sulphur-containing phosphonate derivatives and medicaments (for treating abnormal calcium and phosphate metabolism)

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NO961389D0 (en) 1996-04-03
IL111180A0 (en) 1994-12-29
IL114381A0 (en) 1995-10-31
HU9600839D0 (en) 1996-05-28
TW401276B (en) 2000-08-11
CZ101596A3 (en) 1996-07-17
AU7790194A (en) 1995-05-04
SK45296A3 (en) 1996-09-04
EP0722268A1 (en) 1996-07-24
PL313820A1 (en) 1996-07-22
ZA947814B (en) 1995-08-14
HUT74893A (en) 1997-02-28
AU690581B2 (en) 1998-04-30
CA2173607A1 (en) 1995-04-20
JPH09506075A (en) 1997-06-17
FI961520A0 (en) 1996-04-04
FI961520A (en) 1996-05-27
CN1134657A (en) 1996-10-30
WO1995010188A2 (en) 1995-04-20
BR9407762A (en) 1997-03-04
NO961389L (en) 1996-06-03
WO1995010188A3 (en) 1995-05-04
IL111180A (en) 1999-09-22

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