AU690581B2 - Herbicidal aza bisphosphonic acid compositions - Google Patents

Description

WO 95/10188 PCITGB94/02183 HERBICIDAL AZA BISPHOSPHONIC ACID COMPOSITIONS FIELD OF THE INVENTION In one aspect, this invention relates to herbicidal aza-bisphosphonic acid compositions comprising an azabisphosphonic 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 and a suitable carrier therefor. In another aspect, this invention is directed to a method of controlling the growth of plants comprising applying to the area where control is desired an herbicidally effective amount of such an aza-bisphosphonic acid compound. In yet another aspect, this invention is directed to certain novel aza-bisphosphonic acid compounds.

BACKGROUND OF THE INVENTION 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.

wn -V;/in18 PCT/GB94/02183 -2- Accordingly, it is an object of this invention to provide effective novel herbicidal compositions and a novel method of controlling weeds, as well as certain novel herbicidal 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 preemergent 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: 0 X 0 It I II

(HO)

2 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 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.

i _M -3- Japanese Patent Publication 55-98193 discloses certain herbicidal compounds of the formula

R

I

H203P--C -PO3H 2

N

Y

wherein R is H, lower alkyl or halogen; X is -CH 2 S or 0; Y is H, lower alkyl or halogen; and alkali salts thereof.

Although certain aza-bisphosphonic acid compounds 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 discloses 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.

4e

*Q

b P~I ~s -4- SUMMARY OF THE INVENTION In one aspect, this invention is directed to a herbicidal composition comprising: A compound of the Formula 4 2 R R PO H I 132~ N-C-C- R (I) R R PO 3

H

2 wherein

R

1 is hydrogen, hydroxyt C 1

-C

4 alkoxy, halogen, C -C 4 alkyl, C -C4 haloalkyl, hydroxy-C 1 -C 4-alkyl hydroxy- -c 1

-C

4 -alkoxy or N(R 6

)(R

7 wherein R and R are each independently hydrogen or c 1

-C

3 alkyl; R 2 nd R are each independently hydrogen; hydrocarbyl; substituted hydrocarbyl; hydrocarbyloxy; substituted hydrocarbyloxy; hydrocarby1-S(O),-; or substituted hydrocarbyl-S(O)m; or R and R together form a 3-6 membered carbocyclic ring, optionally substituted with halogen, hydroxy, CI-C 6 8 9 8 alkyl, C -C 6 alkoxy, C -c 6 alkylthiu or N(R 8 (fl wherein R and R 9 are each independently hydrogen or C -C 12 alkyl; and 4p P. and R5 are each independently hydrogen; hydrocarbyl; substituted hydrocarbyl; hydrocarbyloxy; substituted hydrocarbyloxy; hydrocarbylthio; substituted hydrocarbylthio; pyridyl;, substituted pyridyl; or are of the formula

(R

11 wherein R 10 and R 1 are independently hydrogen, hydrocarbyl or substituted hydrocarbyl; or R and R. together with the nitrogen to which they 00000* are bound form an aziridine, piperazina, morpholinep thiomorpholine, thiomorpholine sulfinyl, thiomorpholine sulfonyl, hexamethyleneimine, piperidine, tetrahydropyridina pyrazole, imhidazole, pyrrole, triazole, tetrahydropyrimidiIe, dihydroimidazole, pyrroline, azetidine, perhydroindole, perhydroquinoline, perhydroisoquinoline or pyrro3idine ring, any of which may be optionally substituted with C 1 -c 12 alky3.h.lo,1ydrx -ci 0 aryl, C -Cr 0 ary3. substituted with halo or C 1

-C

6 alkyl <Zs 00 Wn <)9/1ii18 PCT/G94/02183 C7-C16 aralkyl, C 7

-C

16 aralkyl substituted with halo or C -Cg alkyl, nitro, halo-C1-C 10 -alkyl, C I-Cl alkoxy, Cl-C10 alkylthio, C 1

-C

10 alkylsulfonyl, phenoxy, phenoxy substituted with halo or C 1 -C alkyl, C 1

-C

10 alkenyl or cyano; or R and R together with the nitrogen and carbon atoms to which they are bound form an aziridine, piperazine, morpholine, thiomorpholine, tniomorpholine sulfinyl, thiomorpholine sulfonyl, hexamethyleneimine, piperidine, tetrahydropyridine, pyrazole, imidazole, pyrrole, triazole, tetrahydropyrimidine, dihydroimidazole, pyrroline, azetidine, perhydroindole, perhydroquinoline, perhydroisoquinoline or pyrrolidine ring, any of which may be optionally substituted with C -C12 alkyl, halo, C 6

-C

10 aryl, C 6

-C

10 aryl substituted with halo or

C

1

-C

6 alkyl, C 7

-C

16 aralkyl, C 7

-C

16 aralkyl substituted with halo or C 1 -Cg alkyl, nitro, halo-C 1

-C

1 0 -alkyl, C -C0 alkoxy, alkylthio, Ci-C10 alkylsulfonyl, phenoxy, phenoxy substituted with halo or C -C 6 alkyl, C1-C10 alkenyl or cyano; and m is 0, 1 or 2; and agrochemically acceptable salts thereof; and An agrochemically acceptable carrier therefor.

In another aspect, this invention is directed to a method of controlling the growth of plants comprising applying to the area where control is desired an herbicidally effective amount of a compound of Formula above.

In yet another aspect, this invention is directed to certain novel compounds having a structure within the scope of Formula above.

1

_I_

)CTIC 1194/0(121 83 rk X11911OU1U -6- DETAILEa _ESCRIPTION OF THE PREFEfRRED EMBODIMENTS The herbicidal compositions of this invention comprise a bisphosphonic acid compound of the Formula R 4 R2 PO H 3N-~3Z (I) N-C- C-R 5 1k3 1 R R PO 3H wherein

R

1 is hydrogen, hydroxy, C 1

-C

4 alkoxy, halogen, C-C 4 alyl, C 1-C haloalkyl, hydroxy-C 1 -C-alkyl, hydroxy- -C -aky, eahidroxy- -C-C 4 -alk4xy or N(R (R wherein Rl and R are each independently hydrogen or C 1

-C

3 alkyl; R 2 and 3 are each independently hydrogen; hydrocarbyl; substituted hydrocarbyl; hydrocarbyloxy; substituted hydrocarbyloxy; hydrocarbyl-S(0),m' substituted hydrocarbyl-S(O) or R2 and R3 together form a 3-6 membered carbocyclic ring, optionally substituted with halogen, hydroxy, CI-C 6 8 9 8 alkyl, C 1 7C 6 alkoxy, C 1

-C

6 alkylthio or N(Ra wherein R and R 9 are each independently hydrogen or C 1

-C

12 alkyl; and R 4 and R 5 are each independently hydrogen; hydrocarbyl; substituted hydrocarbyl; hydrocarbyloxy; substituted hydrocarbyloxy; hydrocarbylthio; substituted hydrocarbylthio; pyridyl; substituted pyridyl; or are of the formula N(R0) (R 1) wherein R 10 nd 11 are independently hydrogen, hydrocarbyl or substituted hydrocarbyl; or n4 d R 5 together with the nitrogen to which they are bound form an aziridine, piperazine, morpholine, thiomorpholine, thiomorpholine sulfinyl, thiomorpholine sulfonyl, hexamethyleneimine, pipericine, tatrahydropyridinet pyraz)ol, imidazole, pyrrole, triazole, tetrahydropyrimidine, dihydroimidazole, pyrroline, azetidine, perhydroindole, perhydro" quinoline, perhydroisoquinoline or pyrolidine ring, any of which may be optionally substituted with C 1 C1 2 alkyl, halo,

C

6 -C 1 aryl, C6-C 10 aryl zubstituted with halo or C 1 C 6 alkyl.,

C

7 -c 1 6 aralkyl, C 7 -C1 6 aralkyl substituted with halo or Cf C 6 i -7alkyl, nitro, halo-c I- CIO- akylo C 1 -Cl 0 alkoxy, CIO alkylthio, C 1 -C 1 0 alkylsulfonyl, phenoxy, phenoxy substituted with halo or C 1 -C 6 alkyl, c 1-CIO alkeny. or cyano; or R 2and R4 together with the nitrogen and carbon atoms to which they are bound form an aziridine, piperazine, morpholine, thiomorpholine, thiornorpholine sulfinyl, thiomorpholine sulfonyl, hexamethyleneimtine, piperidine, tetrahydropyridine, pyrazole, imidazole, pyrrole, triazole, tetrahydropyrimidine, dihydroimidazole, pyrroline, azetidine, perhydroindole, perhydroquinoline, perhydroisoquinoline or pyrrolidine rings any of which m~ay be optionally substituted with C I-C 1 alkyl, halo, C 6 -C 10 aryl, C 6 -C 10 aryl substituted with halo or C I-c 6 alkyl, c 7 aralkyl, C 7 -C!6 aralkcy) substituted with halo or c.-C 6 alkyl, nitro, halo-C, -C 10 -alkylt C I-C 1 alkoxy, c 1 -c 10 alkyithic, c 1 -c 10 alkylsulfonyl, phenoxy, phenoxy substituted with halo or C I-C 6 alkyl, c 1 -c 10 alkenyl or cyano; and mn is 0, 1 or 2; and agrochemically acceptable salts thereof, Preferably: RIis hydrogen, hydroxy, halogen or C CC 4 alkyl; :R 2and R 3are independently hydrogen; C 1 -C 1 a lky I C C alkeny3.; C -C 1 alkynyl; halo-C "C 1 alkyl, halo-C 2 1 alkoyl:hal-C 2 -C ~alkynvl; C 6

-C

4 aralkyl; C 1

-C

1 alkoxy, toor C 2.-C 1 2 alkylthio; .4 R. I and R are independlentl~y c 1 -c 6 alkyl; C 2-C 6 alkenyl; C C 6 alkynyl; halo-C -C 6 alkyl; halos-C C alkeny.; aio-~-c-alkyny~; pyridyl; substituted pyridyl; phenyl.; *c- 1 arly;substituted C 7

-C

14 C 7- 4aaklo sbtttdC-1 .:.aralkyl; or R4and R 5 together with the nitrogen to which they are bound torn, a tatrrzhydropyrimidinc, tatrahydropyridine, imidazole ring or a -(CHt 2 ring wherein n is 2-6, Option- SOally substituted with halogen, hydroxyt 1 -c 6 alkoxy, nitro, c -C 6 alkyll.,,-C 1 aralky. or C -CG alkylthio groups.

P('TICII'141(12 I R3 More preferably, RI is hydrogen or hydroxy; R 2 and R 3 are each independently hydrogen or ,6 alkyl; and Rand RS are each independently hydrogen, C."-C 6 alkyl, C 1

-C

6 alkenyl, benzyll benzyl substituted with 1C alkcyl or halo or R 4 and~ R 5 together with the nitrogen to which they are bound form a pyrrolidine or piperidine ring-. i which may be optionally substituted with fluor~r.. 4iK y C 1 -C 6 alkoxy or C I- C alkyl, Particularly preferred compounds for use in the harbic.' dal compositions and method of this invention inc2lude;, 2- (R-alpha-methylbenzylamino) othyl-, 1-bisphosphonic acid; 2-(2-methylpropylamino)othyl-X,i-biphopl~tonic acid; phonic acid,: 2-(l1-pyrrolidinyl) ethyl-li -bisphoophonic acid; 2-(l-piperdinyl) ethyl-I, 1-bisphosphonio acid/, 2- (propylaniino) ethyl-I, 1-biphoophonic acid; N-mthylethylamino)ethl il-biophosphonic acid,- 2- (n-butylaniino) ethyl-i, 1'-bisphiosphonic acid; 2 (2-prop any lam ino) ethyl- 1, 1 -bit;phooiphoni c acid;, phosphonic 4cid; and 2 i-dipropylazino) ethyl- I, I-oasphosphonic acid.

Tn another aspect, this invention is directed to certain classes of novel 1a bisphoophonic acid compounds.

One of ouch classes of novel aza-bisphos phonia acid compounda within the scope of this invention include those of the 5tructural Formula I fl~J/fl7 I R3 R -C -QHI (11) wherein 12and R1 are each independently hydrogen, C -6 straight chain or branched al)~yl, hy~roxy, C 2

-C

6 alkenyl, 6 1-o~ or CC ky- 1

C

6 alkyl; and agriculturally acceptable salts thernot Specifio compounds within the scope of~ this genus include: 2- (NIt-di-n-butylamino) ethyl-i, l-bisphoophonic acid, 2-(t4, N-diethylamino) ethyl-i, 1-bisphosphonic acid; 2- (NW-di-n-propylamino) ethyl-li -bisphoophonic acid; 2- (propylamino) ethyl-i 1 1-bisphoniphonic acid, 2- (isopropylamino) ethyl-I, 1-bisphosphonic acid; 2- (propylamino) ethiyl-i, 1-bisphosphonic acid, tetrabutylammionium salt; 2-(propylamin,) ethyl-i, 1-bisphosphonic acid, tributy3.azineo a3.t; 2- (t-butylamino ,rthyl-l, i-bi.-epho~e4phonic acid; 2- (n-butylamino) ethyl-i, i-bicaphoophonic acid, 2- in-hexylamino) ethyl-i, i-biophoophonic acid, tetrabutylamuionumi salt; 2-(but-3-enylanino} ethyl-i -bisphosphonic acid; 2- (n-hexyla4no) ethyl-I, l-bisphosphonic acid; 2-(n-iooutylamino) ethyl-i, I-biophosiphonic acid; 2- (n-ethylamino) ethyl-i, 1-bisphosphonic acid; 2- (prop-2--enylanino) ethyl-i, 1-biophosphonic acid,# 2-(methioxyamino) ethyl-i, l-biraphoophonic acid; 2- (Nl-?etho~y4t-rniethylamino) ethyl-ii-bi'phosphonic acid; 2- (N-hydroxy, U-i~qothylarnino) ethyl-i, l-bio-pho.&phonic acid;, and 2- (2-ethoxyethylaniao) ethyl-i, 1-biephoephonic acid.

1111A 11911 di I QU 1)(17011194/0210- Novel aza-bisphosphonic acids within the scope of this invention also include those of Formul'a III: R14 R1s8 O ,Ar N-C -CHl (III) (R )jR R POt 2 wherein q is 0-10; j is 0-31,R1 and R sare each independently hydrogen or C 1

-C

6 alkyll Ar is benzene, pyridine, pyrimidine, pyridazine, naphthalene, pyrazole, imidazole, triazole, thiazole, fi~ran, thiophene, pyrrole, oxazole or, thiadiazole; R 16 is halo, C I-C 10alkyl, aryl, svabstituted aryl, benzyl, substituted benzyl, nitro, halo-C.-C.O-alky'1, c 1 -C 10 alkoxy, C 1 -CIO alkylthio, C I-CIO alkylsulfenyl, phenoxy, substituted phenoxy, C I 'C 1 alkenyl or cyano; and

P.

17 R 18 and R9are each independently hydrogen, C 1

C)

alkyl, C 1 -C substituted alkyl, C 7 C 1 0 araikyl or C2C1 alkenyl; and agriculturally aceptable salts thereof.

When q is 2 or more, each R14 and 1ismay thamswelvea independently be hydrogen or C 1-03 alkyl, Similarly, when j is 2 or more, each R6may be the name or different.

specific compoundr, within the scope of thli s enus include: 2-(alpha-methylbenzylamino) ethyl-ll..riiposphonic acid; 2- (2-methylbenzylamino) ethyl-I., -bisphospcionic acid; a- (3-mthylbonzylamino} ethyl-.,l-bisphosphonic acid; 2 (2 -rhnylethylazino) ethyl- 1-biap1hosphonia acid; 2- t oriz"ylamnino) ethyl-I., -biopho~eiphonic acid; 2- (S-alpha-rnethylbenzylamxino) ethyl-I., -biophosphonic acid; and 2- (R-alpha-methylbrizylamino) p 1-it-bisphoophonic acid.

2- (R-alph -rnethylbonrzylarntino) ethyl-I., 1.biaphoaphonie acid, totrabutyl ammnonium salt, WO 95/10188 WO 9110I~i P&El17CO941021 8J Yet~ anotiler novel gemNu of compounds within the scope of this invention are compounds of Formula (ZV); PO H 23 wherein A is an alkylenidene radical of 3-6 carbon atoms optional.ly substituted with C 1 -C alkyl, and agriculturally acceptable salts thereof, specific compounds within the scope of this genus include: 2-(i-pyrrolidil) ethyl-i, 1-bisplhosphonic acid; 2- 5-dimethyi-i-pyrro,idinyi) ethyl-i, 1-b:isphosphonic acid; 2-(l-pyrroiildinyl) ethyl-i, l-bisph-o-sphonic acid, tetrainethylainmonium salt; 2- (1-pyrrotidinyl) ethyl-i, 1-bisphosphonic acid, tributyibmino slat, 2-()w-pyrrolidJinyl) ethiytl, 1-bisphosphonic acid, triz~ethylsulfonium salt; 2- (I-hexamethyleneiminyl} ethyl-I, i-bisphosphonic acid; 2- (4-methyi-l-piperidinyl) ethyL-l, l-bisphosphonic acid; 2- (2-methy1-l-piperidinyl) ethyl-l, l-bikphosphonic acid, and 2- (3-methylil-piperidinyi) ethyI~l 1-hisphosphonic acid.

Another~ novel genus of compounds within the scope of thin invention are those of Formula N1 PO4Lit PO PU 2

MV

wherein R 0in hydrogen or hydroxyl;- and a is a 2'.4 alkylidene linkinq groupt optional.ly substituted with Cl~ alkyl;f rm~ B~PI11(~ 71-~1 NVO 9110108 I'MIG 11/02 I H3 and agriculturally acceptable salts thereof.

Specific compounds within the stope of this genus include: 1-(2-piperidinyl) -l-hydroxymethane-,l-bisphosphonic acid; 1-(2-pyrrolidinyl)-l-hydroxymethane-, 1-bisphosphonic ac±d- and 1-(2-pyrrolidinyl)-1-hydroxymethane-,1-bisphosphonic acid, tributylamine salt.

Another class of compounds within the scope of this invention are those of Formula VI: R21 POH C-N C OH (VT) 22 1O 3

H

wherein R21 and R22 are each independently c1-C 6 alkyl or together constitute a C 3

-C

5 alkylidene group optionally substituted with C 1 alkyl; and agrochemically acceptable salts thereof.

Illuotrative compounds within the scope of this invention include: 2-amino-1-hydroxy-2-methylpropyl-4, -bisphosphonic acid, hydrochloride salt;, an( 1-(1-aminocyclopentyl) -1-hydroxymethyl-l,1-bisphosphonic acid, vet another novel genus of compounds Within the scope of this invention are compounds of Formula (VII):

R

2 5 PO H 2 X= c-C N -CH -C C (VIX) (CR RIII4 t v lllll~ 6 14 AllI WO 95/10 (II IPC1(T/; 94(/0218, wherein t is 2, 3 or 4; R 23 and R 24 are each independently hydrogen, C 1

-C

10 alkyl, halo, nitro, Cl-C 9 alkoxy, C 1

-C

10 aralkyl, cyano, trifluoromethyl or represent a unit of unsaturation; and R 25 is hydrogen, c 1 -c 6 alkyl, C7-C0 aralkyl, 23 24 halo, nitro, trifluoromethyl or cyano. Each R and R 24 may themselves be different members of the group listed above.

Illustrative compounds within the scope of this invention include: methyl 1,4,5,6 tetrahydro 1,3 pyrimidinyl)]ethyl-1,1bisphosphonic acid; and 2-l-(4-methyl-l,3-imidazolyl)]ethyl-l,l-bisphosphonic acid.

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 latticer 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 otherwise.

The compounds of such formulae can exist in enantiomeric forms. The invention includes both individual enantiomers and mixtures of the two in all proportions.

As is employed herein, the term "hydrocarbyl", whether representing a substituent on its own or whether it is part of the definition of a larger group as in hydrocarbyloxy, hydyocarbyl-S(O) etc.) is intended to include hydrocarbyl groups having from 3 to 16 carbon atoms. The term hydrocarbyl therefore includes, for example, C I to c16 alkyl including both straight and branched chain isomers methyl, ethyl, propyl, isopropyl, sec-hexyl and hexyl); cycloalkyl of 3 to 16 carbon atoms cyclopropyl, cyclobutyl and cyclohexyl); C 2 to C16 alkenyl including for example allyl

I

I_ WO( 95/1O88 1OCT/G 119410ll~2103 -14and crotyl; C 2 to C 16 alkynyl propynyl); phenyl; phenylalkyl; alkylphenyl, alkenylphenyl, alkynylphenyl, alkylbenzyl, alkenylbenzyl, alkynyl benzyl, naphthyl and the like.

The term "substituted" when applied to the term "hydrocarbyl" (or to a similar term unless specifically defined otherwise) is intended to include hydrocarbyl groups, as defined above, having one or more substituents selected from the group consisting of halogen fluorine, chlorine, bromine, and iodine); C1- 10 alkoxy; Ci-0 alkyl-S(0)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- 10 alkyl, C- 10 alkoxy, C 1 10 alkyl-s(0) nitro, fluorine, chlorine, bromine, cyano, or

CF

3 groups. In the above definitions, m is 0, 1 or 2.

Further, when the hydrocarbyl radical is a substituted aryl radical 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 tb same or different.

The compounds of the present invention have been found to be active herbicides, possessing utility as postemergence herbicides and useful against a wide range of plant species including broadleaf and grassy species.

This invention therefore also relates to a method for controlling undesirable vegetation comprising applying to a locus where control of such vegetation is desired subsequent I I L- SWO 95/10188 1107("1194/0218.) 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 which these plants are growing.

The term "plants" is iin ended 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 R 1 is hydrogen may generally be prepared by reacting tetraethyl vinylidene 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, preparation from the corresponding bromides by a Gabriel Synthesis (see Vogel, "A Textbook of Practical Organic Chemistry", 3d Ed., pp 569).

.I WO 95/I01i' POCTICI1g,4/02183 For the production of compounds wherein the amine contains sensitive groups, the ester groups may first be transesterified by the use of a compound such as bromotrimethylsilane. Such groups can be subsequently unblocked by hydrolysis with water.

Alternatively, for producing compounds wherein RI is other than H, the appropriate carboxylic acid, amide or nitrile can be converted employing PCI 3 and phosphorous acid or P 2 03 utilizing means Well known to those of skill in the art.

The compositions of this invention comprise a compound of Formula 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 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 pounds per acre, preferably from about 0.02 to about 4 pounds per acre( Itfilk 010 1 It au IP(C/GI1g,1I01 83 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 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 954 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 material3, styrene-butadiene copolymers, polyacrylonitriles, polyacrylates, polyesters, polyamides, polyureas, polyurethanes and starch xanthates.

wno/ Iii n K"(7 (694102(10l 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. Those 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. Benzo-2,t1,3-thiadiazin-4-one-2,2-dioxides such as bantazone; I- M WO 911111I08 VT(I9IZ JOCTICA194/02103 B. hormone herbicides, particularly the phenoxy alkanoic acids such as MCPAI MCPA-thioethyl, dichiorprop, 214,5-T, MCPB, 2,4-Do 2,4-DB, inecoprop, trichlopyr, fluroxypyr, clopyralid, and their derivatives salts, esters and amicdes); C. 1,3-dimethylpyrazole der~ivatives3 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, ethalf3,uralin, pendimethaltn; and oryzalin; F. arylurea herbicides such as diuron, flumeturon, metoxuron, neburan, isoproturon, chlorotol.uront chioroxuron, ]inuron, mc'nolinuron, chiorobroinuroni daimruron, and mnethabenzthiazuron; G. phenylcarbamoyloxyphenylcarbaznates such as phenmediphamn and desmedipham; H. 2-phenylpyridazin-3-ones such as chloridazone and norflurazon; 1. uracil herbicides such as )lenacil, bromacil and terbaci.; J. triazine herbicides such as atrazine, sixnazine, aziprotryne, cyanazine, prometryn, dimethametryn, simetryno# and terbutryn, 1K. phosphorothioate herbicides such as piperophoz, bensulide, and butarnifoz, thiolcarbamate herbicides such as cycloate, vernolato, molinate, thiobencarb, butylata*, EPTC*, triajllate, diallate, ethyl esprocarb, tiocarbaz2., pyridate, and dimepiperate; M4. I,2,4-triazin-5-one herbicideo such as metamitron and metribuzinf* benzoic, acid herbicides such as 2,3,6-TflA, dicamba and chloramben; 0. anilido herbicidea 5uch aa pretilachior, butachior, the corresponding alachlort the corresponding compound propachlo.- propanil, nitazachloro metolachior, acetochlor, and dimaethachlort, I W091/10too P( 114),1102 1 H.) P, dihalobatzonitrile herbiidik 1 such as clichlobonil, broxuoxynil and ioxynil; q. haloalkanoic herbioideo ouch ag- 4mdaponj TCA and salts thereof; R. diPhenYlether herbicides such as lactof en, fluroglycofen or salts or esters thereof, nitrofen, bifenox, acifJuorfen and salts and esters thereof, oxyfluorfen and fomesafen; chl'. .nitrofen and chlonethoxyf en; S, phenoxyphenoxypropionate herbicides such as diclof op and esters thereof such as the mnethyl. ester, fluazitop and esters therece, haloxyfop and esters thereof, quizalof op and esters thpereof and fenioxaprop and esters thereof such as the ethyl ester; T. cyclohexanediona herbicides such as alloxyim and salts thereof, sethoxydim, oycloxydim, sulcotrione, tralkoxydin, and clethodiu; U. sulfonyl urea herbicides such as chlo.-osailfuron, sulfometuron, rMetsu3.furon and esters thereof; bengsulfuron and esters thereof such as the ester thereof mnethyl, DPX-'M6313, chiorimuron and esters such as the ethyl ester thereof, piriinisulfuron and esters such as the mnethyl. aster thereof, DPX-LS300 and pyrazosulfuron; V. imidazolidinone herbicides such as imazaquin, imazamothabenz, imazapyr and isopropylaminonium salts thereof, imazethapyr; arylanilide herbicides such as flaimprop and esters thereof, benzoylprop-athy3,, diflufenican; X. amino acid herbicides such as glyphosate and gluyfosinate and their saltz and esters, suJlphosate, and bilanafos,# Y# organoarsenical herbicides ouch as MSMA; Z. herbicidal amide derivati, ,o such as napropamide, propyzamido, carbetarnide, tebutam, broinobutidet iso~aben, naproanilicle, di,,henamido and naptalamp; AA. misce llaneous herbicides including ethofumes ate, cinimethylin, dIten""oquat and zalts therof such as the mathyl sulfate salt, clomazone, oxcadiazon, bromofenoxim, barban, tridiphane, (in the ratio flurachloridona, quinchlorac and mefanacett; a I r n~~l WQ 1~,41181RH 11('176119,110WO WO 0I14W 020lf. examples of useful contact herbicides include bipyridylium herbicides ouch as thoce in which the active entity is paraquat and those in which the active entity in diquat, Those compounds are preferably employed in combination with a Oafenor such as 2,2-dichloro-N,-ci'-2-propenylacetamide (dichlormid).

9'nese 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 powerdusters, boom and hand sprayers and spray dustes, The formu-' lations can also be applied from airplanes a. a dust or a spray or ty rope wick applications.

The following are examples of typical formulations, dust: 5 parts active compound parts talc 2. dust: 2 parts active compound I part highly disperred silicic acid 97 parts talc These dusts are formed by mixing the components then grinding the mixtura to the desired particle size.

Wettable powders: 7Q: O70 parts active compound a parto oadium dbuylnaphthyloulfonato 3 partn naphthaloneoulfonic acid/phenoloulfonie acid/ formaldehyde condensate (3:2:1) parts kaolin 12 parts champagne ch,,ilk I -mrpr*- 40 paro activo compound s partc ocxium liqrin sul.fon.t I part 5ocium dibuty1naphthalano ur ufonic acid 64 parto silioic acid 25 parto active compaund parts calcium lignin sulfata 1.9 parts Champagne chalk/hydroxycthyl qellulooe (1:1) parts sodium dibuty1naphthalene suifonate 19.S silicio acid~ 19.S parts Champagne chalk 28.1 parts kaalin, 25 parto active conpound parts ipoo~typhnxy-ppolyethylene-I Othanol 1.7 parts Champagnow ohalk/hydroxyethyl celltilooe (14-1) 3.3 parts sodium auminum silicate 16.S partst kieoelgqklr 46 parts %aoin 10,0: 10 parts activ.q compound Z parts of (A tixture of sodium salts of sturatedl tattty aleohol sulfates parts naphthalonesulfnic acid/ formaldehyde coadenaate 82 pautt kalain These wettaiblo powders arce propared by intinatoyy mixing tho activ compoundo with tho alditive in suitable mixora and grinding th#h resulting n.ixturO in mi.ills or roloer.

II BU~e~Y~ nlJ to 11 X010911/112 1 Wt) 51 IUIUHl Emulsifiable concentrate: 25 parts active substanee parts opoxidized vegetabae oil partsJ of an alkylarylalfonata/fatty alcohol po-Iyglycol other mixture parts dimethylformamide j'7.f; parts xyloe The amount of the present compositions which constitute a harbicidally effective amount depends upon the nature of tho seodas or plantsp to be controlled, The rate of applioalion of active ingredients varies from aboUt 0.01 to about 2S pounds per acre, preferably about 0.10 to about 10 pounds per apre with the actual. amount depending on the overall costs and the desired result., It will be readily apparznt to one skilled in the art that oompo.itions exhibiting lower herbicid1 activity will require a higher dopage than more active compounds for the oame degree of control.

The fo1lowingj exampes are intended to further illustrate tha present invention and are not intended to limit the scope ot this invention in any manrpr whatsoever.

biph:~JvErF~,ni z. rui d ~Wcmp~nind Ah One gram of 1,24-triaozolo was dissolvedi in 40 z1 of, TVW and cooled to -4a 3C in a nitrogon atmosphere. n-Butyllithiiu (974 mgq wac thon addad dropwice ane the resultant white ouunpoenion astirred at -U78W for five minutoc. After warrninq to room tctnperatura, the ruxture waa atirrod for minutc3 and then e olod aain to PEtraethYl Vinyl- I lr. IOCI(YII94/02 I Wn OKI 1111 "R idihebiphosphonate (178 gin) was then added dropwise over a minute per'iod, When the addition was complete, the mixture was stirred for 15 minutes at -780C, then warmed to 0 0 C 6-.d stirring continued for one hour. The reaction was quenched with 10 ml of water anO the THiF removed undez raduced pressure to give the crude product which was then comnbined with 35 ml of aqueous X 2 CO 3 solution. The resulting mixture was extracted with 3 X 100 ml] portions of dichloroinethane, The extracts were combined, dried (MqSO 4 )1 and the solvent removed under reduced pressure to afford a mobile oil. column chromatography on silica gal with 10s methanol/dichloromothane provided 1.3 gmn of tetraethyl 2-(l-(1,2,4-triazole)ethyl-1,lbiophosphonate. Hydrolysis of this material t6. form C,pound 3 was achieved by heati+ng a di~hloroietne solution of the tetraethyl. ester and 500 mo).60 of broiotrimethylailane at 45 0

C

for four hours and then removing the volatiles azn vacuc.

ZRefluxinq the residuai. oil with water for 30 minutes followed by cooling to room temperature and removal of the water under high vacuum resulted in the isolation of 3 in quantitative yield.

PrP.aration of 1-h.

To a throo-nCOked 250 ml round-bottomed 41ask oquipped with a condenser, mechanical atirrer, oil bath and thermomer were added 5m. of 2-aminoizsobutyrio acid, 8S ml of chlorobenzeno and 3.2 gm of pho'~phorno acid. Th mixture wan heated at ref lux for one hour and then cooled to SV~C. thosphorua triohlorida (9.62 gmn) wan then added and the mixture again heatod to reluxing with stirring tor five hourn. At, the ond of this time, the mixture was allowed to cool to room tonperature and the chlorobenzene carefully deca,.ted. Fre~h chlorobenziena (8Su ml) and 80) ml of 6N IIC waretn added and the ixture hetated to ref luxing with cotirring. Afto six hourn,, the yellowi~h sunpennion was cooled to Ill~ CCIII~ rr~-crr~ -r WO 91018 0 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 AE as a white solid after isolation by vacuum filtration.

EXMP2 43 Prenaration of -hvdroxv-i-(2-rv rolidi)r1-ibisphosphonic cid (Compound 2o. 9) To a 20o ml three-neckeJ flask equipped with a mechanical stirrer and reflux condenser carrying a nitrogen bubbler were added 4 gm of proline; 5.7 q of phosphorous acid and 25 mi of dioxane. Phosphorus trichloride (9.6 gm) was then added dropwise at So0C and the mixture stirred at 80 0

C

for two hours. After cooling the reaction mixture to room temprature, 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 (600C) 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 600C afforded 5.9 qm of Compound Q.

APtLr 4 Prearation of 2 but-3-enviamino ethy1-1,1-bigrhoShSniC qid ra ound No.9 291 A solution of 1.08 gm of I-aminobut-3-ene in five ml of methanol was added to 3.8 gzi of tetraethyl vinylidinebisphosphonate at room temperature. After the resulting nixture had amirred overnight, an additional 0.12 gm of I-aminobut-3ene was added and the stirring continued for an additional four hours. The reaction nixture was then concectrated under 1 1.311 i: I 1- I~ BI~IRIIIWIIIBILIII~ BlsllLII~II- JOCT6I1941/02183 Wo (J'II/01H8 4 -26reduced pressure to yield 4.56 gm of tetraethyl 2-(but-3-enylamino)ethyl-l,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 gn of Compound 2_10 as a stiff, colorless, hygroscopic foam.

EXAMPLE Preparation of 2-(3-methl-i-pineridiy let _l.1'1 bisphosphonic acid o ampound No. 37) A solution of one ml of 3-mnethylpiperidine 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- I-piperidinyl)oethyl-,l-bisphosphonate. A portion of this material (3.37 gm) was dissolved in five mi of acetonitrile followed by the addition of five mi 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 n as a stiff, hygroscopic, colorless foam.

I I~ W11 014/1 (11 AN POX"DIM/02 1 HJ wfl ~I~fhffl PC/G114102I H EX&MPLE 6 PrepiiratioI3 of 2-4MthVI aDZvlaino) ethyj-i, 1bisiphosphonic ncid (compound Yo.-671 To a 100 ml boiling flask were added 3.5 gm of tetraethyl vinylidine-ll-bisphosphonate, 20 ml of acetonitrule, and 1.5 gmn of 4-nethylbenzylamine. 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-methylben :ylainQn)etbyl-l,1-bisphiosphonate. A portion of this material (3.87 gmn) was placed in a 100 ml boiling flask equipped with a magnetic stirrer and ref luxed for four hours with 25 ml of concentrated HCi. Removal of the volatile materials under high vacuum afforded 3.21 gmn of k7 as a colorless, hygroscopic glass.

-E)X&MPLE 7 Employing a process similar to those described above, the following compounds, listed in Table 1, were prepared: R4 TABLE I R 2 po H 13 1 R PO 3 1

COMP.

1. it 2. It 3. H

H

HN

-N=CH-N=CH-

4. H H -H-l-I C -H2-C 2- 2-C 2km.

COMP.-

110.

-CH CU 2-CU -CH 2tetrainethylammonium salt -011

-CIU

3

H

H

-H2-C 2-0 2 C2-I 2 -CUi=I-CH=CII- -011 PO112 Z O PO 3H hydrochloride salt C' Z

COME'.

tributylamile salt

-OH

P0 H2 -CH 2-c 2-i -C 2 tributylamifle salt 13- 14.

-nC 3 1 -H2 CH 2 -CH 2 CH2 trimethylsulfofliuf salt -iC 3Hn It

H

H H z HE Od

HO--

zH cod N c£HO- 181 H O z E 0

H

ILI

H l- 4dHOZ)

COMP.

110.

21.

22.

23.

24.

26.

cif 1 3 CI-H2-C 2 C'2- 2- CHI CHI -CU1-Cl 2-CU 2-CIIif -iC 4H9 -C211 -C 2H

H

H

H

-nC 3H7 -nC 3H7 tributylamine salt tetrabutylammonium salt -NH 2 -CH 3 27. 11 H H H-C H -nC4H9 COJ4p.

110.

28- 29- 31- Z2.

3:3.

34.

H

H

_n 3 H1 Hel -OCHl 3 -CII 2Cel CH=CH2 -nC It 1 -CHl CH=CH2 -nC 3H7 -QCH 3 H HH H -Cll 3

-H

-OH

COUP.

110.

36.

37.

381.

39.

41.

42.

IL-C 2if

CHI

-CHI -CII-CH 2-CII 2-CI 2- 21 2 H 2- -i 2 cf2 if -CH 3 -nC 4H 9 -nCRH -011

II

H

-nC 6 1 3 tetrabutyanronium salt -H3

COMP.

110- 44-

CH

r', II H 11 12 CH 3 46.

47.

It II CH 3 -CH Ilii 2

L

HZ)-:;-C-HZ-ZRD-

H cZt- H3-H H3- zH3-ZHZ-ZH-Za 4 6t, -CNf lo(' 11(iII9,1102 Wt WO 91411t1 ilI 1- 4

II

I

CI

(4

(I

r~~I ~j

(I

L~ (\4

U

fn

(VII

U I

C

(~J

U

U I

II

U

0

U

COMP.

61.

62.

64.

-C2" -nC 3I -H2 3 -CII-CFiC -CII -CLL.-ClI=CH2

H-<

-CII -CII2- -CII-CII-CII 66. it II if

CH

To II 1L ii 0L 169 it I L -oil COMp.

NO 72.

73.

74- 76.

-CU -CH=CH-Cll 2-CT 2- (31

CHI

21 23 -Cl2 Cu 3 i2 -c i2 l2

CII

-C-CU CH3 23 ~HJ- 25" z~ 3 £fl3 H 6L

C'

I

~IID

z IIzD- 18L

ZHD

H 'LL 1011 'dWOZ COlp.

110.

CH 3

H

81..

82.

83, 84.

-CHi -CH=CHI-CHI -C l l 2 -CH 2-CH 2CIf Cl Cl' 1 3 -C=N-CH 2-CI 2-CH 2-

CH

-nC3 H 7 -CII 2-CHn-CH 86. H 8 HH H

COMP.

234 No. R R R 3 R R 87. if If 11 -nC 3 H 7 -nC 4Hf

CIH

1 2 as. it If H -CU-CI 2-CI 2-CI 2-CH 2- 0 11 89. ItU -nC3 H 7 -CUi CiI Coll H- If H H -CHC HC H 91. It H H H C1wiH CU1 CH 92. H l~H H -CU.-CU-CH 2-CU -CH 2-

COMP.

No0.

CHI3 -CH=NQ=CH- 93- 94.

97'.

0 -Cni 2 61o -nC 3H7 2-C -l 2- i 2- -nC 3 1 -nC 6H 1

CH

1 3

-IN=CH-C=CR-

-C=N-CH=CUl- 98. 11 98.. II I If

COMP.

NO 99.

100.

101.

102.

103.

104.

CH 2

CH

j13 -CUl-CU 2-CU CH-CH 2- -Cl 2-CU 2-CH 2- -nC 3H 7 -nC5H 1

COMP-

No1 2 RR4 R 105. H H H -CH! FO-~

F

106. it H H H -CH 2

F

107. It H Ht H -Cif 2 Cl 108. If it H H -CH 2 Gf

F

COMP.

NO.

109.

-CH!

cl 112.

CH! CII

-C=N-C=CH-

-CH=N-CH=CH-

-nC 3H -C10 H21 -C 22C 2 113. H H H-l Ci-l Comp.

110- R 2R 3 R_ R 114. 1 if It -CH NCIll 2 22

CHL

13 7 118. it If -CH-CH 2 -CH 2 -C-1 2 -CH 2

CORP.

1119.

120- 121.

122.

CH

f 3 IIl-l 2 c 2 i 3 C H 12 -C=11-CI;=CH H -CH 2 123.

Z, 13, 11 itI 1 7 it HOD1-11-10 1 I1 129.

45 R R CIH2

-CU

2 -C11 2 -CU-C'12-C'12- -C=11-CI -Cx, 1-CI 111: Qll bis NH! y salt 132, 32.-C-H 2 -CI(01)1)

C

3 -C11 2 -CH!(OH)

-CU

3 hydrochloride salt trinethylsulfaniui salt 133.

134. it H! If C1-H(U)-u erbtyanoims If (0111 -C"3 tetrabutylanmonium salt

CII

-3 _C11 135.

136.

137., hydrochloride Falt CH 3 vci

KU)

Of 3 -CHi CH 3

-CHI

CH3

-CII

hydrochloride salt 1 3S.

I 39.

tetrabutylammoniuta salt trimethylsulfonium salt WO 91/10100 0(i76fl94/021 J t I analgloadgagggla The compoundo 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, Result obtained in herbicidal screening are affected by a number of factors including: the amount of ounlight, 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 scrooeening process to remain coniateant and reliable.

PRE-MMEMBRENJM ERB=cDAL _CREENI G On the day preceding treatment, oeeds of several different weed spe4eas were planted in sandy loam soil contaning only trace organic matter. Propaguies were aown in individual rows using one species per row across the width of an aluminum flat (19. x 9.5 x 6 cm), The grass wooda planted were green foxtail (otaria vidis) ("sETVX"), wild oat (Avna iatua) ("AVEFA"I), barnyardgrae (Y6chinohaloa cruagallI) ("ECcG"II). Broadleaf weoeds utilized were wild mustard (Drassica kaber) also known as (Sinapi arvonals) ("SINAR"), velvetleaf (Abutilon thoophrasti) ("ABUTH"I) and morningglory (Xpomoa a app.) ("1TPOSS"I. Additionally, yellow nutsedge (Cypoeus ea ulontua) ('CYPESIW), nutlets were oown. Sooding depths ranged from 1.0 to 1.5 eom and plant densities ranged from 3 to 25 plants per row depending ot individual plant species.

Solutions of the toot compounds were prepared by weighing out 10.8 and 74.7 mg for 1 and 4 kg/ha applications respectively, of the test compound into a 60 ml wide-mouth bottle, then disabsolving the compound in 14.0 ml of deionized water containing 0 vS v/v Tweon o2" (polyoxyethylone zorbitan monolaurate emulaitirl as a surfactant. Additional solvents, 1 WO 91/108t0 1107IG0f94t/02 103 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 kg/ha or 1.0 kg/ha (as indicated in Table XZ 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 290 and 21 0 C respectively.

The degree of weed control was evaluated and recorded 17-21 days 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 1004 represents complete kill, A dash indicates that no test was performed at that level of application, ROST_-VEMR(ENCD EHVALOATION The soil was prepared and seeded with the same species and methodology described for the pro-emergence test.

Post-emergence flats were placed in the greenhouse under the same environmental conditions as described for the proemergence flats and watered overhead by sprinkling. Plant.

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 I to 2 leaf stage.

Yellow nutsedge was S to 7 cm tall at application.

W091/01011 P('T/I6 IO UI/011 Plants were sprayed 30.5 cm (12 inches) above the toliage with the same spray solution as prepared for the pre-emergenme tent. The application rate was 4.0 kg/ha or 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 as 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.

TABLE II Pre-Emergent Testing (4.0 kqlha)- COMP. 11O. AVEFA ECHCG SETVI ABUTH IPOSS SIHAR CYPES 1. 0 0 0 0 0 0 0 0 0 0 0 0 0 3. 0 0 0 0 0 0 0 4. 0 0 25 0 0 0 0 0 0 0 0 0 0 0 6. 0 0 0 0 0 0 0 7. 0 0 0 cl 0 0 0 0 0 0 0 00 91 0 00 0 0 0 0 0 IQ 0 30 0 0 0k 0 10 0 30 0 11.* 0 0 0 0 0 0 12.* 0 0 0 0 0 0 0 14.* 0 0 0 0 0 0 0 14. 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1.000 0 0 0 0 17, 0 0 0 0 0 0 0 18. 0 0 0 0 0 0 0 0 0 0 0 000 COMP. 11. AVEFA ECHCG SETVI ABUTH IPOSS SINAR CYPES 21. 0 00 0 0 0 0 22. 0 0 0 0 0 00 23.* 0 0 0 0 0 00 24.* 0 0 0 0 0 00 25*0 0 0 0 0 0 0 26. 0 0 0 0 0 00 27.* 0 0 0 0 0 0 0 0 0 0 0 0 0 29*0 0 0 0 0 0 0 30.-1 0 0 0 0 0 0 0 0 0 0 0 0 0 32.* 0 0 0 0 0 0 0 33.* 0 0 0 0 0 0 0 34.* 0 0 0 0 0 0 0 0 0 0 0 0 00 36*0 0 0 0 0 00 37.* 0 0 0 0 0 0 0 38.* 0 0 0 0 0 0 0 39- 0 0 0 0 0 0 0 0 0 0 0 0 0 0 41.* 0 0 0 0 0 0 0 42*0 0 0 0 0 0 0 43.* 0 0 0 0 0 0 0 COMP. UO. AVEFA ECHCG SETVI ABUTH IPOSS SINAR CYPES 44-* a 0 0 0 0 0 0 0 0 0 0 0 0 0 46.* 0 0 0 3 0 0 0 47.* 0 0 0 0 0 0 0 48*0 0 0 0 0 0 0 49.* 0 0 0 0 0 0 0 0 0 0 0 0o 0 0 51.* 0 0 0 0 0 0 0 52-* 0 0 0 0 0 0 6 53.* 0 0 0 0 0 0 0 0 0 1525 5 0 0 0 0 00 0 0 56.* 0 0 0 00 0 0 57.* 0 0 0 0 0 0 0 58. 0 0 0 0 0 0 0 59.* 0 0 0 0 0 0 0 60*0 0 0 0 0 0 0 61.* 0 0 0 0 0 0 0 62.* 0 0 0 0 0 0 0 63.* 0 0 0 0 0 0 0 64.* 0 0 0 0 0 0 0 Comp.. NO. AVEFA ECHCG SETV ABUM! IPOSS SINAR CYPES 0 0 0 1 0 0 0 0 00 1 67*0 0 0 0 0 0 1 68*0 0 0 a 0 0 1 69-* 0 0 03 00 0.*0 0 0 0 0 0 03 71*0 13 0 0 0 0 0 020 0 0 0 0 0 73.* 0 0 0 0 0 1 0 0 001 0 1 0 0 31 013C 76*0 0 0 130 0 1 77-* 0 0 03131 0 03 08 a 0 0 13 0 79.* 0 0 0 0 0 Q 0 0 0 0 0 0 0 al.* 0 0 0 13 0 0 03 82.3 0 0 0 0 0 13 0 0 0 0 0 0 a 13 0 0 03 0 13 85.*1 0 0 0 0 0 13 86.* 0 0 0 0 0 0 a 87. 0 0 a 0 0 0 13 88.* 0 0 0 0 0 0 0 COMP. NO. AVEFA ECHCG SETVI AELUT1I IPQSS SINAR eYPES 89.* 0 0 0 0 0 03 90*0 0 0 0 0 0 *3 91.* 0 0 0 0 0 0* 92-* 0 0 0 80 0* 93*0 0 0 *30 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 *300 97-* 0 0 0 *30 0 08* 0 0 03 0 0 *3 99.* 0 0 0 *3 0 0 100.1* 0 0 0 G3 0 0* 101.* 0 0 0 80 0* 102.* 0 0 0 .0 0 Q3 10,0 0 0 *30 00 104.* 0 0 0 *30 0 105. 0 0 0 *30 0 106. 0 0 0 *30 0 17*0 0 0 *30 0 1081.* 0 0 0 Of 0 0 109.* 0 03 0 *3 0 00 0 0 0 0 0 03 11*0 0 0 *3 0 00 0 0 *3 0 0

I

comp.. 110..

113.* 114- 115..* 116-.* 131,* AVEFA ECHCG SETVI ABUTH IPOSS SINAR 0

CYPES

0 Tested at 1-0 Ikgfha

I

TABLE III pnst-Ereraent Testirt= i!4.0 kc/h COMP. tiJ.z AVEFA ECIIOG F SINAR CYPES 1 a 0 00,- j 2- 5 95 9 5 25 60 s0 a. 105 Z0 5 60 0 100I 1C 0 100 2 10 10 0 0~0 100 G2s C7,11 70 100 0 00 C, 00 9.00 0 0 905 101o. SO 11*1095 95 80 31 100 12, ~1010 0 70 95 100 13.* 6D 90 3C 100 1.98 98 98 f2 60 100 so 6060 is 70 100 16. 85 50 6060 100 1 17. 0 0 1000 10 G 18. 5 5 E3 19. 60 30 Ico 30 30 .100 is Q.1085 85 50 39g 100 I WO 95/101011 N# 1/6119'4U011II0 p1 (4 m to p Ps (V CO in) 0) I) a) C) 0 to Q) C) C) C) 0) a) C) a) Q) Q co C) a) at )(1C 0)sI m riG)C) It) rs ol M r m m fn M H 01 vi ro'4viP o Mn to 0- 0 0 0 c -I rl n) 4 1 a C) 0) 0)CO ON P i (A ri (4 (f*1 1(1 Ps C) (O0 C C) to C) l C) C) co M C) C) 0 C) 0 fa t tA C)C tI 1 C C (P1 (P1 qj (o (11 tyi li to [it ti (4 w 0 1) (0 C) c co 'n C) C t t o C ul 0 CO to C) C III Ol f) mS Of f1) OA M I I I I I P 1 f 9 N fq m M) m~ mi C" 41 '14 I I I I C ~4N~ I~ 14.

WO 91/101011 P( 1/61194/02110 In inIOM0 010 n0 0n0 0 0 00 0 000 0 0 r1 4 r- vi $I l #1 W~ N C4 0 Q t0 0 10 0 0 0 In n to 0 co 0 o a0 0 If) C) 7 Q W ro-l to (0 c Q JU: (I4H clO J rH rH r4 sl H- H H i el i) 1n0 Q: 0 0Q 0 41 In to 0 0 to 44 10 0 Q 0 to Q 4) to, to 0 to 0 In 0 C in to 0 0 0 to 0 m~ ti 1 1*H l C-1 ri, (1 IIr U w 0 t O0 to C) tn 0 (n 0 41 t 0 0 0 In 0 tO 0 Q n in to cjy jti uw0 *i 0 (1fl 0 in 10 0 0 n 0 in i 0 1 0 1 0 C0 0 4 inC 4t OH 0 OO(0 (n U M *l0Innk:0 t* 0100M0 S I I I Il L In S 1 4a to to 0 to k to to W09910100 IT-1/G119,110218) In 0 0 (4)0 0 0 0 0 0 10 to to 10 0 C- a to In (1 rl ri I 41 r4p4 i C0 C- 0 rn r) 0- to In l0 0in 1 in Inn in n 0 0 t 4 r-4l U) r U Q) si 4 wi Cd Q~ Mi r i ci~~r ri') i t-4i i~1 i)0 0 C 0 0) l C) n C) In in Cl M ~C )C in C) in 0 0lC (i i) I i (I (ji q) t i lt it t I 1'i ti) i ci li I II (P 1 r il VA V CO 10 0 l0, n )ClC C) l C) 0 4 Cl 0 n (I C) in 0~ 0 04 I W 1 la fl tit UJ i~t v II I 1 4 t1 4 (T 4 f MI C)U 11 (Yi 1-i ri t C) tit i f 14 tit t ol 1 (14 1 1n It Ii i tO (ti 11 t C C CO CO C UC) (D (f CO to COMP.. 110- 91.* 92.* 93.* 94. 96.* 97.

9S.* 1Q2.* 103..* 104.* 105..* 106.* 107. 109.* 112.* 113.*

AVEFA

75 100 100 100 0 85 10

IGO

100 100 100 100 0 75 5,0 50 100 10 0

ECHCG

s0 100 100 98 10 40 90 30 98 98 100 60 90 85, 5 70 60, 50 30 90 98 15 5

SETVI

100 100 100 100 l0 80 95 30 95 95 g0 70 70 95 10 60 15 50 30 20 98 100 10 10

ABUTH

95 80 98 10 10 30 10 50 70 70 40 10 15 20 10 5 0l 5 5 30 75 5 0

IPOSS

98 90 90 is 20 5 50 100 30 20 25 30 5 5 5 5 10 5 15 100 10 5

SIIAR

100 100 98 100 100 100 100

CYPES

COMP- 110. AVEFA 115. 116.* 0 100 100

ECIICG

10 q8 70 100 S ETV I 5 98 40 zo0

ABUTH

0 70 5 100 IPOS S 5 20 10 100

SINAR

5 98 20 100O

CYPES

0 0 Tes:ted at 1.0 kg/ha Tho abovo date indicatos the offloacy of tho prosont claimed compounds whon ctpphod post~omorOontly, coupiod with thoir safoty to piont~ whon applied pr&ornorgontiy.

Throughout the description and claims of the spe~Aication the word "comprise" and variations of the word, such as "comprising" and "comprises" is not intended to exclude other additives, components, integers or steps.

0 0004 0 0400 0000 *0 0 @0 00

I,

9.

.9.

9.

900 a 90 @0 0 9, 0 0@ *900 *0 0* *9 000000 0 *0 @4 *4e 0 S. 4 4@ 4@ 9 ?W1 04 1XIC

Claims (2)

1. 4. substituted with halogen, hydroxy, 0 1 -CG alkyl. 01-Co alkoxy, Cl-Co aikyithlo or seeN(R 8 wherein R8 and R 9 are Independently hydrogen or CI-0 12 alkyl; and V4
2. 44. Fl4 and R6 are each independently hydrogen; hydrocarbyl; substituted hydrocarbyl, hydrocarbyloxy,- substituted hydrocarbyloxy; hydrocarbyl-S (0)m; substituted hydrocarbyl-S(0)m-; pyridyl; substitu.ted pyridyl; or are of the formula N(R1 0 j(R 1 wherein Rio and Rtj are Independently hydrogen, hydrocarbyi or substituted hydrocarbyl; or R 4 and R 5 together with the nitrogen to which they are bound form an aziridinie, piporazine, morpholine, thiomorpholine, thiomnorpholine suifinyl, thlomorphoine sulfonyl hexamethyleneimine, piperidine, tetrahydropyridine, pyrazole, imidazole, pyrroie, triazole,, tetrahydropyrimidine, dihydrolmidazoie, pyrroline, azetidine, perhydroindole, perhydroquinoline, perhydrolsoqulnoline or CkW.MrO~t4YjNjLVWTK 14 MOQ pyrrolidino ring, any of which may be optionally 8ubstitutod with' 01-012 allyl halo, hydroxy, 0001( aryl, CO-C0o aryl oubotitutod with halo or 01-Co alkyl, 0 7- 0 10 aralkyl, 07-010 aralkyl substitutod with halo or 0 rj-a alkyl, nitro, holo-01- 01-alKyl, 01-010 alkoxy, 0jCO~ alkylthie, Cj'Qj() alkylsulfonyl, phenoxy, phenoxy substituted with halo or 01-Ca alkyl, 01-010 alkenyl or cyano; or and R 4 together with the nitrogen and carbon atoms to which they are bound form an aziridine, piperazino, morpholine, thiomorpholine, thiomorpholine suifinyl, thiomorpholine sulfonyl, hexamethylenuilmine, piperidine, tetrahydropyridine, pyrazole, imIdazole, pyrrole, triazole, tetrahydropyrimldine, dihydroimidazole, pyrroline, azetidine, perhydroindole, perhydroquinoline, perhydrolsoqulnoline or pyrrolidine ring, any of which may be optionally substituted with 01-012 alkyl, halo, CO-Cl, aryl, 06-010 aryl substituted with halo or CI-CO alkyl, 07-Cio aralkyl, OCi aralkyl substituted with halo or 01-06 alkyl, nitro, halo-0 1 -C 10 -alkyl, 0j-0jo alkoxy, 01-Cj0 alkylthio, Cj-Cj alkyisulfonyl, phenoxy, phenoxy substituted with halo or Cj-CQ alkyl, C1- CI alkenyl or cyano; and m Is 0, 1 or 2; or an agrochemIcally acceptable salt thereof. A method in accordance with claim I wherein R' Is hydrogen or hydroxy, 20 3. A method In accordance with claim 1 or claim 2. wherein RA 2 and R 3 are too each Independently hydrogen or Cj-CO alkyl, 0O4 4. A method In accordance with any one of claims I to 3 wherein R 4 and R6 are each Independently hydrogen, 0j-06 alkyl, C,-C6 alkenyl, benzyl or benzyl with 01-06 alkyl or halo. A method in accordance with any one of claims 1 to 3 wherein R 4 and R6 together with the nitrogen to which they are bound form a pyrrolidine or too piperidine ring. 00*.6. A method in accordance with claim 1 wherein Fl' Is hydrogen, hydroxy, halogen or 01-04 alkyl; $1 z C WWW4UrJ*4WthOO6LtV1W~flht OAW0 112 and~ A' are Indopendently hydrogon I Cj-Cj Alkyl; Cg"Ci alkanyll C2 C~ 12Alkynyl;- hao-CIC~ 12dakyl, halo-c 2 -C 1 alkenyl; halo-.C 'C-aynl CC aralkyl; c loy R 4 and R 5 are independently hydrogen; c I-c alYyl;, c2-c. alkenyl; C? .aikynyl; hdoC-.alkyl; halo-c 2 _C 6 alkenyl; halo-C 1 A. 6 alkynyi; pyridyl; substituted pyridyl; phenyl; or substituted phenyl; c 7 -c 4 aralkyl; c 7 -C 4 substi- tuted aralkyl; or R 4and R5 together with the nitrogen to which they are bound form a tetrahydropyrimidine, tetrahydropyridine or imidazole ring or a -(cH 2 ring wherein n is 3-6, option- ally substituted with halogen, hydroxyj C 1 -C 6 alkoxy, nitro, C 1 alkyl, C 7 -c 1 araikyl or c C. alkylthio groups. 7. A method in accordance with claim 6 wherein RIis hydrogen or hydroxy; R 2and R 3are each independently hydrogen or 1C alkyl; and R4 and R 5are each independently hydrogen, C 1 -C 6 alkyl, C.-C 6 alkenyl, benzyl, benzy. substituted with ,C P ~alkyl. or halo or Rand R 5 together with the nitrogen to which they are bound form a pyrrolidine or a piperidine ring optionally substituted with fluorine, hydroxy, C-C 6 alkoxy or C 1-6 alkyl. 8. A method .In accordance with claim 1 wherein said compound is 2-(i-pyrroiidinyl) ethyl-1, 1-bisphosphonic acid; 2-(i-piperdinyl) ethyl-i, 1-bisphosphonic acid; 2-(propylamino) ethyl-l, -bisphosphoiic acid; 2- (N,N-methylethylamino) ethyl- 1, 1-bisphosphonic acid; 2-(n-butylamino) ethyl-Ii -bisphos- V. a phonic acid; 2-(2-propenyiamino)ethyl-10i-bisphosphonic acid; 2-(R-alpha-m11thylbenzylamino) ethyl-li -bisphosphonic acid; 2- (2-methylpropylamino) ethyl-li-bisphosphonic acid; (4-methyPli, 3-imidazolyl) Jethyl-i, 1-biaphosphonic acidk* or 2-C 3,6-tatrahydropyridinyl) 3ethyl-Ii -bisphosphonic 1'~ 72 9. A compound of tho Formulta (VII) 1 1 2 N~=C N -0H 2 -CH (OR 23 R1 24 t P1 R 2 (VII) wherein t Is 2, 3 or 4; R 23 and RH 24 are each independently hydrogen, CjCj alkyl, halo, nitro, Cl-Co alkoxy, 01-010 aralkyl, cyano, trifluorornethyl or represent a unit of unsaturation; and R 25 Is hydrogen, Cl-Co alkyl, C7-Clo aralkyl, halo nitro, trifluoromethyl or cyano. A compound of the Formula (VilI) F ,7 R 2'H POjH 2 N -C-c;-H 29 31 R 0 29 31-H PqH-2 R (Vill) 16 wherein R 2 6-113 3 are each independently H or 01-C6 alkyl. 11, A method according to claim 1 substatially as horeinbefore described with reference to any of the examples. 4.4 20 DATED: 22 January 1998 ZENECA LIMITED RA~. By their Patent Attorneys SPHILLIPS ORMONDE FITZPATRICK IN'FPIAA IONA1, N3PARVI 1(114111010 liffy ioil Apjio#ARiii Nii .Aeconhlng to InterntionAl IlAtenm (IlafcatillffiII) or to hothn iionAl dlaiificniooo ond IC Minimum docurocniAiion icarchod(tlieun yinllwdbylailuosiiil) XPC 6 AOXN C07F Documcntation searchcd other than minimum documentation to Ohe Wxent thal, such dwlomnii Arc includcd in the icidi searched Ellectronic dlat base consulted during the internalional search (name of data bA,14 and, whcre practical, scrch terms mcd) C. 00CUIJIINTS CONSIDIW TOI 'I0 13 REIVANT Category' Niation of document, with indication, where appropriate, of the relevant pamililcl Itelevant to claim No. x JOURNAL OF ENVIRO1'MENTAL SCIENCE AND 1,9 HEALFH, PART B, I vol .B18, no.4&5, 1983 pages 485 496 E. BAKUNIA( ET AL, 'Further studies on biological activity of aminophosphonates structurally related to n-(Phosphonomethyl)glycine, I see page 495; table x EP,AoO 274 158 (NORWICH EATON 1391 PHARMACEUTICALS) 13 July 1988 see claim 1 see page 9, line LM 7urther documents art listd tn the ton'jlnuaion of boX C. j]I, ily mcmblert are listed iii Annex# special categiories or ted docments IT' later document publihed after thc inatonal fling dAte opnnydate and not in tontlict with the applicatiort hut document defining the general state of the art which is not t e d the pninciple: of theory Underlying tht considered to tle of particular relevance Iin VI carlier document btlt published on or atker the international *X1 douml or pairtieuat relevance; the claimed Invention Ring date cannot be considered, novel or caNt be Ct1onsdrd to *W document which may throw doubts on p crity claim(s) or involve an invenive step When the document ii taken aRMe which ii cited to estblihl the publication datte or Another IY diocument of paruculat relevance; the Claimed invention citation, -other special reason (it specified) cannot be considered to involve An Inventive step wh thell 1' documet. refering to aro oral diedosure, use, c~iuitiofl or document is combined With one or more other such docu. other means menu~l such Comibination being obvious to a peirson skile document Published p"l to the international filicg date bu in the ar. later thn the pnorsty date claimed 'A document member of the same patent family Date of the actual completion of the internlational searth, Date of toalling of tile intemAti0n0 search, repor 16 January 1995 05, 04.95 Name and mailing address of the, ISA Atuthoized o~filcet t1tziWOPea PAtt1fflee1, 5511Paniar2 Nt. *2250 1i I Ktwilk TOl.(+317) 3402WT4Y l3t 651 tpon DEORE d4 lPax 3 1.70) 340.30161 OR SUN PNtn PCV/ISA2i0 ieceod silat) (July~ 10121 page I of 2 2 ICA[)t 94/02183 V,(CoIIIIBUAwol) DUCAIMI WK5 4 ON41ISt'I) 10 111 101 RANNU 'Atogfry' (Ilallon of ilcumn.~ Mill 11)i11000, where hpprpln~w. W ilia foIovMol Im gQ I(oivMn 11 1.41 CIM l N X01) KOAM9 24496 (PROCTER GAMBLE -36 PHARMACEUTICALS) 9 Decemiber 1993 9'li see Claimi 6 see page 36, line 18 -line x SOVIET INVENTIONS ILLUSTRATED 17 Week 8106, Dorwent Publications Ltd., London, GOl; AN 81-093080/06 SUA,739 076 (AS SIDE CHEM KINETI) 6 June 1980 see abstract xCHEMICAL ABSTRACTS, vol. 100, no, 15, 17 1984, Colum~bus, Ohio, US; abstract no, 121244z, I. S. ALFEREV El AL. 'Reaction of vinylidenediphosphp-ic acid with nucleophiles., see abstract IZV. AKAD. NAUK SSSR, SER. KHIMI, no.12, 1983 pages 2802 2806 x CHEMICAL ABSTRACTS, vol. 101, no. 19, 17 1984, Columbus, Ohio, US; abstract no, 171346, 1. S. ALFEREV ET AL 'Addition of nucleophilic agents to vinylidenediphosphonic acid.' see abstract IZV. AKAD. NAUK SSSR, SERW. KHIM., 1984 pages 1122 1126 X EPsAt0 252 604 (BOEHRINGER MANNHEIM) 13 17 January 1988 see claim 1 2 wt IA10(OMsiho wi o)(l 11 page 2 of 2 VNrITAlNAr11ONAIL SEARACII REOR PCT/)~J OfMill 9pIM412181 Jiox I 0IbservalionA whe~re ceottln drinhs wof~r~~ fun tittrd h 0 aminit~ti or lItont I or Not olicet) cr1113 intoron~l oich ~3U report him flot b10 ost011111 Inl 1,1o of carti'n U014 ufldlr Ai1do O 2R) for 11to iLWillij remoli Wicaugf they i Ilate to liubj12ct mg'veq not roqutral to boi togochad by tu1 Aulbi~oity, nbon12ly because they reIM'o. t14 PA, A, of (ho imnntrl 4mpauan WiM do viot cotipy wit lv prcbod cquirernant to xumh oni extent that no ri rnngut int~rnooolnl AqW6o can 04 cArr;i ows 3rQcihIy; 3. ClaimsR No$.: bw~Ausc they are dependient ;Iaoms and are not draftcd In Atgovdan" W4i the scoot and NOr~ srentencete of Rulo 6.4(a). Bt~x 11 Observations Where Unity or invention Is Ie.cking (confirnua3ion 0 Ier 2 of~ir't sheet) This International Searching Authority fourkd Mntipyc 1AY010otis in thl$ Intitmatfoal pplhcAudn, Agflo 2.Claim 18 3.Clairn 19 See for further info~rmation~ PCT/ISA/906( extra ghoot) sent to you At: 09-02-19S. I. As all requited addtiontl #t~j~ch fees Yetc rocW paio by (he apphtant. this intttnat~onat seach- report covets all searchable cIims. 2. As all searchable doirns could be searches without cffort u tying sz idditionaI fc, thil Amthof 1Y did not vnvitt psymeni of mny additbonli fee. 3. I As only some of the tequitz4 aditionall oearch fees Wert, umely paid by the applitmit, this imeteaons.1 iogroh, ttptrt cover$ only those claims for Whi'i4 (gas weft, p&Ad sp nifially claims No. 4,.9 o, required additional search fees were tigTely pai b~y tho ippiman Copgqtmently" this Isuerta~in~t starch tt"crt 4 restirictod to the invention (Ip t nsuntd in the ainis; It IA eovertd, by c ain Nog. 1-17 Remurk si Protest 1l Tht WditiortA seatch fe4s weric sc."mpisd by the jLaWfroet LJNo protest Olatw ~a e n KAYM o tiNOnAl sr ifet. Form PCVI~ISA#j2IO (0itin"UtOf e 1113L Sheet (MuY 19R21 ~;-U~-,~?~unnmn~lRim*~n~il~n'Rn*nl~~ni~ IN 9 1IPiNAIUNAI t I'Ali1Ii U 1 1101111 I'M~iiL i~otut11~1L f'uri~kfrtiw1 I'MliL fitilill PIII(U f Lslted In looth ropott dolo lllBII 7 t= j'l lluJ Ii RrjC I I pOFI I~u o IflCorflIYTrI(l) j __ICI II 13-011100 AU11- 16391 31-1091 AU-A- 0269407 93-06-86 CA~An t3~[1968 10B)tPR3 DU0 3709436 20-04-94 iThdT 3709436 2B-00-94 JPA- 63239291 05-10-00 US-A- 5071840 10-12-91 JS-A- 5334586 02-08-94 ZA-A- 8709454 10-06-88 WO-A-9324496 09-12-93 AU-f- 4391693 30-12-93 AU-0l 4391793 30-12-93 JU-0l- 4523193 30-12-93 CA-A- 2136818 09-12-93 CA-A- 2136823 09-12-93 CA-A" 2136824 09-12-93 EP-, 0642518 15-03-95 EP-A- 0642519 15-03-95 Fi-A- 945592 28-11-94 Fl-A- 945593 28-11-94 FI-A- 945599 25-01-95 NO-A- 944498 26-01-95 NO-A- 944499 30-01-95 NO-A- 944515 30-01-95 WO-A- 9324495 09-12-93 WO-A- 9324131 09-12-93 EP-A-A';'G04 la-01-88 OE-A- 3623397 14-01-88 AU-B- 598279 21-06-90 AU-A- 7529187 14-01-88 AU-B- 598569 28-06-90 AU-A- 7648787 10-02-88 CA-A- 1296739 03-03-92 CA-A- 1305166 14-07-92 DE-A- 3781730 22-10-92 GK-8- 168629 09-05-94 WO-A- 8800590 28"01-88 EP-AB 0252505 13-01-88 ES-T- 2043622 01-01-94 IE-- 60345 29-06-94 page 1 ot 2 I I la fil 14 011 AIIIIr yi 111or 0 111611 jJ l 9 4 O (PAt o o i O It It' FildoI9ol ,1I1-A, 61OUP31lfl) U 1O Pp IOO'66 02 0139111 o1048/1 13-01-00 Poi KPCmi tot(stsm~y AAti 041'd Iotli pag 2 of 2