AU645452B2 - Intermediate useful in the production of pyrimidine derivatives having herbicidal activity - Google Patents

Description

645452

AUSTRALIA

Patents Act 1990 COMPLETE SPECIFICATION STANDARD PATENT a 'a a a. a a a. *e ~0 a a *9 a a a a a a. .a a a Applicant: SUMITOMO CHEMICAL COMPANJY, LIMITED A.R.B.N. 007 509 999 Invention Title: INTERMEDIATE USEFUL IN THE PRODUCTION OF PYRIMIDINE DERIVATIVES HAVING HERBICIDAL ACTIVITY The following statement is a full description of this invention, including the best method of performing it known to us: 1A INTERMEDIATE USEFUL IN THE PRODUCTION OF PYRIMIDINE DERIVATIVES HAVING HERBICIDAL ACTIVXTY.

This application is divided from our copending application no. 76467/91 and relates to a novel compound disclosed therein as an intermediate in the production of pyrimidine derivatives having herbicidal activity.

Briefly stated, the present invention provides a compound of the formula and a method for its production, as will be described in detail below: 0 Y3

II

COA

Y 2

XH

y1 y BACKGROUND OF THE INVENTION In the abovementioned copending application 76467/91 we have described and claimed a pyrimidine derivative having the formula 25

I

Y3 z COA y2Y2 (1)

R

1 yl N N R2 wherein A is C3-C, cycloalkyl C 1

-C

6 alkyl, C 3 cycloalkyl C.-CG alkyl substituted with at least one member selected from the group consisting of C,-C alkyl, C-C, alkoxy, halo alkyl, C,-C 6 alkoxy- 2 1 carbonyl and halogen, C 3

-C

6 oxacycloalkyl, Cr-C6 oxacycloalkyl substitutea with at least one member selected f rom the group consisting Of Cr-C6 alkyl, CI-C6 alkoxy, halo C 1

-C

6 alkyl, CI-C 6 alkoxycarbonyl and halogen, C 3

-C

6 oxadycloalkyl CI-C 6 alkyl, C 3

-C

6 oxacycloalkyl C 1

-C

6 alkyl substituted with at least one member selected f rom the group consisting Of Cl-C 6 alkyl, CI-C 6 alkoxy,. halo Cl-C 6 alkyl, C 1

-C

6 alkoxycarbonyl and .halogen, C 3

-C

5 dioxacycloalkyl, C 3

-C

5 dioxacycloalkyl substituted with at least one member selected from the group consisting of Cl-C6 alkyl, Cl-C 6 alkoxy, halo Cl-C 6 alkyl, Cl-C6 alkoxycarbonyl and halogen, C 2

-C

5 dioxacycloalkyl C 1

-C

6 alkyl or C 2

-C

5 dioxacycloalkyl CI-C6 alkyl subs tituted, with at least one member selected from the group consisting of Cl-Ce alkyl, Cl-C 6 alkoxy, halo C-Cealkl, C3.C alkoxycarbonyl and halogen; each of RI and R 2 1 which may be the same or differnt, is C 1

-C

6 alkyl, C 1

-C

6 alkoxy, halo Cl-C6 alkoxy or halogen; Xis oxygen or sulfur; Z is nitrogen or Cy4; each of YI, y2 and y3, which may be the same or different, is hydrogen, halogen, Cj-Ce alkyl or C 1 -C6 alkoxy; and YZ4 is hydrogen, hydroxyl, mercapto, nitro, halogen, Cl-C6 alkyl, C 2

-C

6 alkenyl, C 2

-C

6 alkynyl, Cl-Ce alkoxy, C3-Ce alkenyloxy, Cr-C6 alkynyloxy,. halo C 1

-C

6 alkyl, halo C 2

-C

6 alkenyl, halo C 2 -C6 alkynyl, halo C 1

-C

6 I alkoxy, halo C 3

-C

6 alkenyloxy, halo C 3 -C6 alkynyloxy, Cl-C 6 alkoxy Cl-C 6 alkyl, C 3

-C

6 alkenyloxy Cl-C 6 alkyl,

C

3

-C

6 alkynyloxy CI-C 6 alkyl, cyano, formyl, carboxyl, Cl-C 6 alkoxycarbonyl, C 3

-C

6 alkenyloxycarbonyl, C 3

-C

6 alkynyloxycarba~nyl, phenyl, phenyl substituted with at least one member selected from the group consisting of

C

1

-C

6 alkyl, Cl-C 6 alkoxy, halo Cl-C 6 alkyl, Cl-C 6 alkoxycar1lonyl and halogen, phenoxy, phenoxy substituted *with at least one member selected from the group consisting of Cl-C 6 alkyl, C 1

-C

6 alkoxy, halo Cj-C 6 alkyl, CI-0 6 alkoxycarbonyl and halogen, phenylthio, phenylthio substituted with at least one member selected from the group consisting Of Cl-C 6 alkyl, C 1

-C

6 alkoxy, halo Cl-C 6 alkyl, :C1-C 6 alkoxycarbonyl and halogen, benzyloxy, benzyloxy substituted with at least one member selected'from the group consisting of Cl-C 6 alkyl, C 1

-C

6 alkoxy, halo Cl-C 6 alkyl, Cl-C 6 alkoxycarbonyl and halogen, benzylthio, benzylthio substituted with at least one member selected from the group consisting of Cl-C 6 alkyl, C 1

-C

6 alkoxy, halo Cl-C 6 *555 alkyl, Cl-C 6 alkoxycarbonyl and halogen, wherein each of R 5 and R 6 which may be the same or different, is hydrogen, Cl-C 6 alkyl, C 3

-C

6 alkenyl or

C

3

-C

6 alkynyl, 4 0 II

-C-N

R6 1 wherein R5 and R 6 are as defined above, S R7 11 (0)m wherein R 7 is CI-C 6 alkyl, C 3

-C

6 alkenyl or C 3

-C

6 alkynyl and m is an integer of 0, 1 or 2,

O

"0 SX CX1 R7 wherein X1 is oxygen or sulfur, and R 7 is as defined above, or CI CF 2 S R7 )m wherein R7 and m are as defined above, and n is an integer of from 1 to 4; a method for producing the pyrimidine derivative (1) which comprises reacting a compound having the formula,

O

Y3 II Z

COA

Y2 XH (2) Y1 1 wherein A, X, Z, Y1, Y2 and Y3 are as defined above, with a compound having the formula, R1 N R (3)

N=<

\R2 wherein each of R 1 and R 2 are as defined above; W is halogen or -S R8

II

(0)e wherein R8 is Ci-C 6 alkyl, benzyl or benzyl substituted S. with at least one member selected from the group consisting of C 1

-C

6 alkyl, Ci-C 6 alkoxy, halogen or nitro; and e is an integer of 0, 1 or 2; a method for producing the pyrimidine derivative (1) which comprises the steps of reacting a carboxylic acid derivative having the formula 0 Y3 II I R1

YN

Y2 I X--l (4) R2 1 wherein X, Z, Y1, Y2, y3, R1 and R 2 are as defined above, with an acid-halogenating agent or an active esterifying agent to obtain a reaction product; and (ii) reacting the reaction product with an alcohol derivative having the formula, HO-A

O

y3

CO

.R1 R2 10 wherein A is as, Y3, and R are a defined above wi a method for produchalide having the pyrimidine derivative (ula, which. comprises reacting a carboxylic acid derivative having the formula 0 I Ri wherein X, z, yi, y2, y3, Ri and R 2 are a defined above,

W

3 -A (7) wherein A is as defined above, and W 3 is halogen; a compound having the formula, 0 y3 2COA 2 XH (2) V2 I XRI yl wherein A, X, Z, Y 2 and Y 3 are as defined above; a herbicidal composition which comprises as an active ingredient a herbicidally effective amount of the pyrimidine derivative described above, and an inert carrier or a diluent; Sa method for controlling undesirable weeds, which comprises applying the above herbicidal composition to an area where undesirable weeds grow or are likely to grow; and a use of the pyrimidine derivative as a herbicide.

In the compound of the formula the substituents R 1 and

S:R

2 which may be the same or different, are preferably C 1

C

6 alkoxy, and more preferably, both of them are methoxy.

S 25 A is preferably a C 3

-C

s dioxacycloalkyl Cl-C, alkyl group.

More preferably, A is 1,3-dioxolane-2-yl

C

1 alkyl group or 1,3-dioxan-2-yl C 1 alkyl group.

Most preferably, A is 1,3-dioxolane-2-yl ethyl group or 1,3-dioxan-2-yl ethyl group.

X is preferably oxygen.

Z is preferably nitrogen or CY 5 wherein Y 5 is hydrogen or halogen, a halo C 1

-C

6 alkyl group, a Cl-C, alkyl group, a

C

1

-C

6 alkoxy group or a substituted or unsubstituted phenyl group. More preferably, Z is nitrogen or CY 5 in which Y is hydrogen or halogen. Most preferably, Z is CY s and Y is halogen.

Y1 and Y 2 which may be the same or different, are preferably a hydrogen atom or a fluorine atom.

Y

3 is preferably hydrogen, fluorine or a C 1 alkoxy group.

The pyrimidine derivative can also be produced by reacting a compound represented by the formula 0 Y3 Z COH y2 (4) N yN N R 2 wherein R 1

R

2 X, y 1 y Y 3 and Z are as defined above, represented by the formula SO-A 1 wherein A is as defined above (hereinafter reaction (ii).

In the above reaction specific examples of the acid-halogenating agent are thionyl chloride, thionyl broi.de, phosphorus trichioride, phosphorus tribroiuide, phosphorus pentachioride, phosphorus oxychioride, phosgene, oxalic acid dichloride, etc.

Specific examples of the active esterifying agent are N,N'-disubstituted carbodiimides such as N,Nldicyclohexylcarbodiimide, N,N' -ciisopropylcarbodiimide, l-ethyl-3- (3-d imethylaminopropyl) carbodiimide hydrochloride, etc.; arylsulfonyl chlorides such as 214 ,6-trimethylbenzenesulfonyl chloride, 2,4,6triLisopropylbenzenesulfonyl chloride, etc.; N,N' carbonyldiimidazole; diphenyiphosphorylazide; N- :::.ethoxycarbonyl-2-ethoxy-l, 2-dihydroguinoline; N-ethyl- 2' -hydroxybenzisoxazolium trifluoroborate; phenylisoxazolium-3 '-sulfonate; etc.

By this reaction, a compound represented by the formula Y3 z C-W2 Y2 1 (6) R1 Y1

N

N R2 1 wherein R1, R2, X, Y1, Y2, y3 and Z are as defined above, is produced in the reaction system.

In the above formula a substituent W2 represents a halogen atom when the acid-halogenating agent was used; W2 represents an N,N'-disubstituted-2isoureido group when N,N'-disubstituted carbodiimide was used as the active esterifying agent; W2 represents an arylsulfonyloxy group when arylsulfonyl chloride was used as said agent,; W2 represents an imidazolyl group when N,N'-carbonyldiimidazole was used as said agent; W2 represents an aside group when diphenylphosphorylazide was used as said agent; W2 represents an ethoxycarbonyloxy group when N-ethoxycarbonyl-2-ethoxy-1,2dihydroquinoline Was used as said agent; W2 represents a 3-(N-cthylaminocarbonyl)-2-hydroxyphenoxy group when Nethyl-2'-hydroxybenzisoxazolium trifluoroborate was used as said agent; and W2 represents a group

SO

3 e O- when H CONHC 2

H

3'-sulfonate was used as said agent.

S 20 In the reaction system, W2 can also take a form of acid anhydride containing the moiety represented by the formula, 11

O

y3 Z CO- Y2

R

1 N :R2 1 wherein Ri, R2, X, y1, y2, y3 and Z are as defined above.

The amount of the foregoing acid-halogenating agent or active esterifying agent used is usually 1 to equivalents based on 1 equivalent of the compound represented by the formula The amount of the alcohol derivative of the formula used is usually 1 to 5 equivalents based on 1 equivalent of. the compound represented by the formula The reactions and (ii) can also be carried out, if necessary, in the presence of a base. Such a base includes organic bases 1-methylimidazole, 3nitro-lH-1,2,4-triazole, 1H-tetrazole, 1H-1,2,4- 0 *"triazole, imidazole, pyridine, triethylamine) and 15 inorganic bases potassium carbonate). The amount of the base used is usually 1 to 20 equivalents based on 1 equivalent of the compound represented by the formula The reactions and (ii) are usually carried out in the presence of an inert solvent. Such a solvent includes aliphatic hydrocarbons hexane, heptane, 1 ligroin, petroleum ether), aromatic hydrocarbons (e.g.

benzene, toluene, xylene), halogenated hydrocarbons chloroform, carbon tetrachloride, dichloroethane, chlorobenzene, dichlorobenzene), ethers diethyl ether, diisopropyl ether, dioxane, tetrahydrofuran, diethylene glycol dimethyl ether), ketones (e.g.

.acetone, methyl ethyl ketone, methyl isobutyl ketone, isophorone, cyclohexanone), esters ethyl formate, ethyl acetate, butyl acetate), nitro compounds (e.g.

nitroethane, nitrobenzene), nitriles acetonitrile, isobutyronitrile), tertiary amines pyridine, triethylamine, N,N-diethylaniline, tributylamine, N- S methylmorpholine), acid amides N,N-dimethylformamide), sulfur compounds dimethyl sulfoxide, 15 sulfolane) and the mixtures thereof.

e Generally, the reaction temperature usually ranges from 0 C to the boiling point of the solvent in any of the reactions and The reaction time usually ranges from 1 to 24 hours for each reaction, and from about 1 to about 48 hours through the reactions (i) and (ii).

After completion of the reaction, the reaction solution may be after-treated as usual. That is, water is added to the solution which is then extracted with an organic solvent and concentrated, and if necessary, the product obtained is subjected to the chromatography, distillation, recrystallization, etc. Thus, the desired compound can be obtained.

13 THE PRESENT INVENTION The present invention provides a compound having the formula, y3 0 z

COA

Y2 XH Y1 wherein A, X, Z, Y 1

Y

2 and Y 3 are as defined above.

The compound of the present invention represented by the formula can be produced by reacting an aromatic 15 carboxylic acid derivative represented by the formula

O

SY3 coH y2 XH (9; Y1 wherein X, yl, Y 2

Y

3 and Z are as defined above, with an acid-halogenating agent or an active esterifying agent (hereinafter reaction (iii), and reacting the resulting 25 reaction product with the alcohol derivative represented by the formula (hereinafter reaction The above reactions (iii) and (iv) can be carried out according to the foregoing reactions and (ii), respectively.

The aromatic carboxylic acid derivative can be produced according to J. Org. Chem., 27, 3551 (1962), Chem. Pharm.

Bull., 31, 407 (1983), Yakugaku Zasshi, 99, 657 (1979), Chem. Pharm. Bull., 27, 1468 (1979), J. Med. Chem., 21, 1093 (1978), Yakugaku Zasshi, 92, 1386 (1972), Eur. J. Med.

Chem-Chim. Ther., 21, 379 (1986), J. Chem. Soc., Perkin Trans. 1, 2069 (1979), JT. Chem. Soc., Perkin Trans. 1, 2079 (1979), J. Chem. Soc., Chem. Commun., 1127 (1968), J. Med.

Chem., 31, 1039 (1988), Indian J. Chem., 25B, 796 (1986), J. Am. Chem. Soc.k, 107, 4593 (1985), J. Org. Chem., 50, 718 (1985), J. Agric. Food Chem., 32, 747 (1984), J. Pharm.

Pharmacol., 35, 718 (1983), J. Org. Chem., 48, 1935 (1983), J. Chem. Soc., Chem. Commun., 1974 362, etc.

Compound includes its stereo isomers.

Production Examples for the compound are shown below.

*e Production Exaimples 9.00 Grams of acetylasalycilic acid and 9.95 g of 2-(2bromoethyl)-1,3-dioxane were dissolved in 100 ml of N,Ndimethylformaide was mixed with 7.60 g of anhydrous potassium carbonate. The resulting solution was stirred at 120°C to 130°C for 3 hours. The reaction solution was 0* 25 poured into diluted hydrochloric acid, and extracted with ethyl acetate. The organic layer separated from the aqueous layer was washed with saturated sodium chloride eo solution and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure, and the residue obtained was distilled under reduced pressure to obtain 10.5 g of 2-(l,3-dioxan-2-yl)ethyl salycilate in yield of 83%.

12OOC-122OC/O.O7 mmHg no 1.5246 Table 2 illustrates specific examples of the compound which can be produced by using the corresponding starting materials.

*So So. feet too.S Table- 2 0 11

.Y

3 A

Y

1

I

CH

2 A< H. H CH2H

H

CH2H H IH H C I-*CI*

I-

Cont'd 17 Table 2 (cont'd) A y'1 y 2

CH

2 0H 2 H H

CH

2

CH

2

CH

2 -4 H H CH2H

H

cl clH

H

CH

2

CH

2

CH

2

CH

2 H H H H ~I Cl1 2

CH

2

CH

2 H H *to *I

CC

H

2H 2 H H 60060 r w I H H Cont'd Table 2 (cont'd) t o C ont'd -fable 2 (cont'd) 0 ~0* A Y IY 2 Y 3 X Z CoH H H 0001I H H H 0 CH H H H S CC! H H H 0 CBr H H H S CBr H H H 0 COCH 3 H H H 0001I 0H H H 0001I -KD, 'H H H 0 CF -KIo H H H 0 N H H H 0 CGF 3 Cont'd Table 2 (cont'd) Cont'd 121 Table 2 (cont'd) A y i y 2

CH

2 Q H H CH2H H CH2H H

CH

2

CHCH

2 H H

CH

2

CH

2 H H H H

(CH

2 5 .f

CH

2

CH

2 74<I> H H 011

HH

Cont t d Table 2 (cont'd) H CI 1 0H

H

4o> H H O\ HA H 0 H H cI Cont'd 23 Table 2 (cont'd) t A y y 2 y 3 x z 0C H H H S CBr _C CHH H H 0 COQH, 0{JOX25n 0H 2 CA< H H H 0 OHI

CH

2

CH

2 H H H 0 OH 0 0 CHC2-<H H H 0 CHI 0

OH

2 H H H 0 OHI

CH

2 -1 IIo 3 CH OCH3 H H H S OCH 0 0 CH1 H H H 0 COCH 0 0 H_ H_ H_ 0 CO Oont'd 24 Table 2 (co nt'd)

S.

Cont'd Table 2 (co nt'd)

A

CH

2

CH

2 H H o

CH

2

CH

2 H H f H H

CCH

2 H H 0- CHC2H* H**H CHH H H

CH

2

CH

2 H H

CH

2

CH

2 H H 0:.

Cont'd 26 Table 2 (co nt'd) A y'1 y 2

CH

2

CH

2 H H

CH

2

CH

2 H H 0

*CH

2

GH

2 H H 0

*CH

2

CH

2 H H :0

CH

2

C

2 H H 0 0H 2 0H 2 H H

D

*0 Cont'd 27 Table 2 (pont'd) A y y 2 y o

CH

2

CH

2 H H H o

CHCH

2 H H H o 0H-20H-2-<J H H H o

CH

2

CH

2 H H H 0 0*0

::CH

2

CH

2 -D H H H 0H 2 0H 2

H

0H I o0- Cont'd Table 2 (cont'd) A y y2 Y 0HC 2 H H

H

CH

2

CH

2 OOH H H

CH

2

CH

2 H H of 3 H H

H

*.CH

2

CH

2 0 C3 CH.C9 OH 3 H H H CH2OH2-( CH3, H H H 0H 0(

H

3 H H

H

0 3 This application is divided from application 76467/91 and the entire disclosure in the specification of the said application 76467/91 is by this cross-reference incorporated into the present specification.

It will be clearly understood that the invention in its general aspects is not limited to the specific details referred to hereinabove.

S.

Claims (9)

1. A compound having the formula, 0 Y2-1 XE (2) wherein A is C 3 -C 6 oxacycloalkyl, C 3 oxacycloalkyl substituted with at least one member selected from the group consisting of C 1 C 6 alkyl and halogren, C 3 -C 6 oxacycloalkyl C,-C 6 alkyl, C 3 06 oxacycloalkyl Cl-C. alkyl substituted with at least one member selected from the group consisting of alkyl and halogen, C 3 -C 5 dioxacycloalkyl, C 3 dioxacyc,.loalk,-l substituted with at least one member selected from the group consisting. of C.,-C6 alkyl and halogen, C 3 -C, dioxacycloalkyl C,-C 6 alkyl or C 3 C. dioxacycloalkyl C,.-C 6 alkyl substituted with at least one member selected from the group consisting of C 1 C. alkyl and halogen; X isoxygen or sulfur; Z is nitrogen; and each of y 2 and y 3 which may be the same or different, is hydrogen, halogen, C, 1 -C 6 alkyl or alkoxy.

2. A compound according to Claim 1, wherein A is C3- dioxyacycloalkyl Ci-C 6 alkyl.

3. A compound according to Claim 2, wherein A is (1,3-dioxolane-2-yl) C 1 alkyl or (1,3-dioxan-2-yl) C 1 -C 6 alkyl.

4. A compound according to Claim 3, wherein A is (1,3-dioxolane-2-yl)ethyl or (1,3-dioxan-2-yl)ethyl.

A compound according to Claim 1, wherein X is oxygen.

6. A compound according to Claim 1, wherein both Y 1 and Y 2 are hydrogen or fluorine, and Y 3 is hydrogen, fluorine or C 1 -C 6 alkoxy.

7. A method for producing a compound of formula (2) as defined in claim 1, which comprises reacting an aromatic carboxylic acid derivative represented by the formula (9) as hereinbefore defined with an acid-halogenating agent or an active esterifying agent, and reacting the resulting reaction product with an alcohol derivative represented by the formula as hereinbefore defined.

DATED THIS 4TH DAY OF NOVEMBER 1993 SUMITOMO CHEMICAL COMPANY, LIMITED By its Patent Attorneys: GRIFFITH HACK CO Fellows Institute of Patent Attorneys of Australia. 0 *se ABSTRACT An intermediate of formula useful in t~.e preparation of pyrimidine derivatives having herbicidal activity the subject of applicant's earlier aliplication 76467191, is disclosed and claimed, in which the substituents A, X, Y1, 2 3 Y ,Y and Z are as defined in the specification. 0 y3 11 z C0O\ y2 XB(2) y1 9999 too* 0 00.0

9.boo