AU617756B2 - Cyano-dienes, halopyridines, intermediates and a process for their preparation - Google Patents

Description

I^

OPI DATE 01/08/89 APPLN. ID 29468 89 PCT AOJP DATE 31/08/89" PCT NUMBER PCT/US89/00001 INTERNATIONAL APPLICATION PUBLISHED UNDER TIftA" NT C BOP19ATK TOPT Y (PCT) (51) lrpernational Patent Classification 4 (11) Internal~lal Plblication Number: WO 89/ 06230 C07C 147/02, 121/417 Al C07D 213/82, 213/71 (43) International Publicatien Date: 13 July 1989 (13.07.89) (21) International Application Number: PCT/US89/00001 (72) Inventors; and Inventors/Applicants (for US only) CHIANG, George, (22) International Filing Date: 3 January 1989 (03.01.89) Chih-Shu [US/US]; 107 Banbury Drive, Wilmington, DE 19803 GRANCHELLI, Felix, Edward [US/ (31) Priority Application Numbers: 140,673 US]; 120 Spring Street, Arlington, MA 02173 (US).

232,535 WRIGHT, Christopher [GB/US]; 98 Jacques Street, Somerville, MA 02145 (US).

(32) Priority Dates: 4 January 1988 (04.01.88) 16 August 1988 (16.08.88) (74) Agent: GREGORY, Theodore, 1007 Market Steet, E.1. du Pont de emours and Company, Wilmington, (33) Priority Country: US DE 19898 (US).

Parent Applications or Grants (81) Dsignated States: AT (European patent), AU, BE (Eu- (63) Related by Continuation rcpean patent), CH (European patent), DE (Euro- US 140,673 (CIP) pean patent), FR (European patent), GB (European Filed on 4 January 1988 (04.01.88) patent), IT (European patent), JP, LU (European pa- US 232,535 (CIP) tent), NL (European patent), SE (European patent), Filed on 16 August 1988 (16.08.88) SU, US.

(71) Applicant (for all designated States except US): E.I. DU Published PONT DE NEMOURS AND COMPANY [US/US]; With international search report.

1007 Market Street, Wilmington, DE 19898 Before the expiration of the time limit for amending the claims and to be republished in the event of the receipt of amendments.

(54)Title: CYANO-DIENES, HALOPYRIDINES, INTERMEDIATES AND A PROCESS FOR THEIR PREPARA-

TION

(57) Abstract This invention relates to certain cyano-dienes and halopyridines and the processes for their preparation from a protected 1,3-dialdehyde and a cyano-diene.

WO 89/06230 PCT/US89/00001 1 CYANO-DIENES, HALOPYRIDINES, INTERMEDIATES AND A PROCESS FOR THEIR PREPARATION Related Application This application is a continuation-in-part of copending application U.S. Serial No. 232,535 filed August 16, 1988 which is a continuation of application U.S. Serial No. 140,673 filed January 4, 1988.

Background of the Invention This invention relates to certain cyano-dienes and halopyridines and the processes for their preparation from a protected 1,3-dialdehyde and a cyano-diene.

The "sulfonylurea" herbicides are an extremely potent class of herbicides discovered within the last few years which generally consist of a sulfonylurea bridge, -SO 2 NHCONH-, linking two aromatic or heteroaromatic rings. Research directed to methods for preparing sulfonylurea herbicides is continually producing new processes. The search for improved methods for more effectively preparing such compounds and intermediates required for preparing such compounds continues.

South African Patent Application 870,436 filed January 21, 1987 discloses the use of compounds of Formula I in the preparation of pyridine sulfonylureas.

EP-A-237,292 published September 16, 1987 discloses the use of compounds of the above Formula I in the preparation of pyridine sulfonylureas.

WO 89/06230 WO 8906230PCT/US89/00001 J. Org. Chem. 41, 2066 (1:976) discloses the preparation of 2-bromonicotinic esters acco,,ding to the following piocedure.

GOGH

23 CHO CN CO R 3 RRNH -N GN 2R

HBR

HOAC

Q O 2R aQBr J. Org. Chem. 3.9, 3436 (1974) discloses the preparation of nicotinamide from the 2-bromonicotinic esters according to the following procedure.

HC (OCH 3 2

CH

2 HC(OCH 3 2 0 2 CH3

CH

2

CN

a CO2 3H 2 Q Br Steps 0

CNH

L~i 2

N

Japanese Patent 80-76,863, priority date December 6, 1978, discloses the preparation of 2-chloro- nicotinic acids according to the following procedure.

2 2 3 HCI CH 3 0 r TN CN0 HOAC N Cl 1) NAOH a O 2H N Cl

I

WO 89/06230 PCT/US89/00001 3 Summary of the Invention A process for making intermediates useful for the preparation of herbicidally active sulfonylureas has been discovered as well as novel intermediate compounds. In accordance with the invention, the process for preparing a compound of formula I and its corresponding salts,

I

1

I

wherein

R

1 is COR 2 or SO2CH2CH3;

R

2 is C1-C 3 alkyl or C1-C 2 dialkylamino; and X is F, Cl or Br;

V

p ii

H

1*1

V

comprises reacting a compound of the a compound of Formula III Formula II with

CH(OR)

2

CH

2 CH(OR) 2 1

CH

C 2

CN

III

wherein R is -CH 3 or -CH2CH 3 and R 1 is defined above; in the presence of acetic anhydride, catalyst where X is as defined above acetic acid at a temperature of 1100 a compound of the formula as a ZnX 2 and optionally to 150 0 C to form -4-

CN

RO

IV

indcuding all geometric isomers thereof, wherein

R

1 and R are as defined above; and reacting in the presence of acetic acid at a temperature of 0" to 60'C the compound of Formula IV with HX where X is as defined above.

The compounds of Formula IV

CN

RO

including all geometric isomers thereof, wherein "R and R 1 are as defined; prepared by the process of the invention are novel and useful for preparing intermediates for the preparation of sulfonylurea herbicides.

wherein

R

1 and X are defined as above; provided that when R 2 is C 1

-C

2 dialkylamino; then X is F or Br, and their corresponding salts prepared by the process of the invention are novel and useful compounds for the preparation of sulfonylurea herbicides.

i

L

WO 89/06230 PcT/us89/0000 1 Preferred for reasons of ease of synthesis and efficiency are: 1. The process of the invention wherein R 1 is C(O)R 2 2. The process of Preferred 1 wherein R 2 is

C

1

-C

2 dialkylamino.

3. The process of the invention wherein R is SO2CH 2

CH

3 4. The process of the invention wherein X is Br.

The process of the invention wherein the corresponding salt of Formula I is the HBr salt.

The compounds of the invention preterred for their efficiency and ease of synthesis are: 6. The compounds of Formula IV wherein R is C(O)R 2 7. The compounds of Preferred 6 wherein R is Ci-C 2 dialkylamino.

8. The compounds of Formula TV wherein R is SO 2

CH

2 CH3' 9. The compounds of Formula I wherein R is CON(CH3) 2 and X is F or Br.

The compounds of Formula I wherein R is SO2CH 2

CH

3 11. The corresponding HBr salt of compounds of Preferred 9.

12. The corresponding HBr salt of compounds of Preferred The process of the invention can generally be carried out by reacting 1.0 to 3 moles of Compound II, preferably 1.2 to moles, per mole of Compound III in the presence of with 1-5 moles of acetic ahhydride, preferably 1.5-2.5 moles. Acetic acid can be advantageously used but is not requi-ed. Lower WO 89/06230 PCT/US89/00001 6 temperatures can be used with acetic acid. ZnX 2 the catalyst, can be used in amounts of 0.5-2% by weight based on Compound II. The temperature for the reaction may be generally 110 0 -150 0 C, preferably 120 0 -130 0 C: the yield of Compound II will vary depending on the condition but yields of 85-90% are achievable.

The second step for the process involving the reaction of Compound IV with HX can generally be carried out with 0.5-8 moles of HX, preferably 2-4 moles of HX. The amount of acetic acid required is generally from 0.2 to 1 liter per mole of reactant, preferably 0.4 to 0.6 liter. The temperature may range from 0°-600C, preferably 10 0 -30 0

C.

By C 1

-C

2 dialkylamino is meant dimethylamino and diethylamino.

Detailed Description of the Invention More specifically, the process of this invention may be carried out by reacting 1.2 to 1.5 moles of a malonodialdehyde bis(acetal) with one mole of a substituted acetonitrile and 1-5 moles of acetic anhydride in acetic acid containing 0.5-2% of a catalytic amount of zinc chloride or zinc bromide.

Alternatively, the reaction can be carried out in the absence of acetic acid. The reaction mixture is heated to 110 0 -150 0 C and then distilled overhead until analysis of the pot contents shows a disappearance of starting materials and the formation of Compound IV, which is a mixture of geometric isomers.

Compound IV can be isolated by distillation or crystallization. In the next step, it is treated with to 8 equivalents of HF, HC1 or HBr in acetic acid (200-1000ml/mole) at 0°-60°C to undergo the cyclization reaction to yield Compound I. Alternatively, Compound IV can be directly cyclized to Compound I without isolation. To help facilitate the isolation WO 89/06230 PCT/US89/00001 7 of Compound I, excess acid such as HBr may be added to the reaction mixture. The resulting crystalline salt of Compound I can then be separated from the reaction mixture by such means as filtration. The salt of Compound I can be used directly in the preparation of sulfonylurea herbicides. The salt of Compound I can also be neutralized with base to liberate Compound I.

The following Examples further illustrate the invention: Example 1 Preparation of 2-cyano-5-methoxy-N, N-dimethyl-2,4pentadienamide To a 250 ml 3-necked R.B. flask was charged g malonodialdehyde bis(dimethylacetal), 22.5 g i N,N-dimethyl-2-cyanoacetamide, 60 g acetic anhydride, g zinc chloride and 100 ml acetic acid. It was heated to reflux to distill off low boilers until the pot temperature reached 125 0 C and head reached 110 0

C

and a total of 60 ml distillate was collected. GC analysis of the pot content showed disappearance of N,N-dimethyl-2-cyanoacetamide. The reaction mixture was filtered to remove zinc catalyst and then rotovapped. The pot residue was crystallized from a methanol in dry ice-acetone bath to afford 16 g of the title compound.

NMR(DMSO-d6): 2.95 3.80 6.85 (1H, 7.65 (lH, dd), m/e=180 (theoretical 180) Example 2 Preparation of 2-chloro-N,N-dimethyl-3-pyridinecarboxamide To a 250 ml 3-necked R.B. flask was charged 16 g of Compound IV from Example 1 and 150 ml acetic acid. At ambient temperature, 15 g gaseous HC1 was fed into the mixture over 20 minutes. The resulting

I

I i: li WO 89/06230 PCrL/tS89/0000I 8 solution was allowed to stand overnight and was then rotovapped. The residue was diluted with 500 ml water and extracted 3 times with 500 ml chloroform.

The combined chloroform was dried with anhydrous MgSO 4 filtered, rotovapped and then distilled to produce 5.5 g of the title compound which was identical to an authentic sample by GC, NMR and MS.

Example 3 Preparation of 2-chloro-N,N-dimethyl-3-pyridinecarboxamide (without isolating the intermediate) To a 250 ml 3-necked flask was charged 40 g malonodialdehyde bis(dimethylacetal), 22.5 g N,Ndimethyl-2-cyanoacetamide, 60 g acetic anhydride, g zinc chloride and 100 ml acetic acid. The mixture was heated to reflux to distill off 60 ml of byproducts and then cooled to ambient temperature.

The mixture was diluted with 100 ml acetic acid, charged with 60 g gaseous HC1 and was allowed to stand overnight. It was rotovapped to remove all solvents and then diluted with water and extracted 3 times with 500 ml chloroform. After drying the chloroform solution with anhydrous MgSO 4 and filtering, the filtrate was rotovapped to afford 14.5 g of the title compound which was identical to an authentic sample by GC, NMR and MS.

Example 4 Preparation of 2-Bromo-3-(ethylsulfonyl)pyridine A mixture of 12.3 g (.075 mole) malonodialdehyde bis(dimethylacetal), 25 ml (.25 mole) acetic .08 g zinc chloride was treated at anhydride, and .08 g zinc chloride was treated at WO 89/06230 PCT/US89/00001 9 91 0 C for 25 minutes. Cyanomethyl ethylsulfone (6.7 g, .050 mole) was added and the mixture was heated at reflux (95 0 -109 0 C) for 16 hours.

The reaction mixture was cooled to 16 0 C, and ml of 30% hydrobromic acid in acetic acid was added.

An additional 6.5 g of hydrogen bromide gas was added at 15 0 -20 0 C. After one hour, the reaction was quenched with 100 ml of ice water. After neutralizing with sodium hydroxide, the mass was extracted twice with methy.ene chloride, washed with water, dried with magnesium sulfate, filtered, and the solvent evaporated to leave 7.2 g of an oil.

H-NMR (CDC13): 6 8.58 1H); 8.45 1H); 7.53 1H); 3.55 1H); 1.30 2H, J=.04).

A sample prepared similarly and recrystallized from ethyl acetate melted at 78°-79 0

C.

Elemental analysis calc. for C7H8BrNO2S.

Calculated: C, 33.61; H, 3.22; Br, 31.95; N, 5.60; S, 12.82.

Found: C, 33.87; H, 3.27; Br, 32.60; N, 5.64; S, 12.83.

Example Preparation of 2-(ethylsulfonyl)-5-methoxy-2,4pentadienenitrile A mixture of 57 g (.342 mole) malonodialdehyde bis(dimethylacetal), 95 ml (1.0 mole) acetic anhydride, and 0.5 g of zinc chloride was heated to L. 1 WO 89/06230 PCT/US89/00001 0 C. After heating at 90 0 -95 0 C, while allowing the methylacetate to distill off for 20 minutes, 33.2 g (0.25 mole) of cyanomethyl ethylsulfone was added.

The reaction mass was heated to 120 0 C while distilling off further amounts of methylacetate. The reaction was held at 120 0 C for 4 hours and then cooled to 0 C. Water, 200 ml, was added, then the mass was extracted twice with 200 ml each of methylene chloride. The combined methylene chloride extracts were washed with 10% sodium carbonate and then with water. After drying with anhydrous magnesium sulfate I and filtering, the filtrate was evaporated to yield 63.6 g of the desired product. The crude product was recrystallized from chlorobutane to yield yellow crystals, m.p. 72 0 -74oC.

Elemental analysis calc. for C8H 1 1

NOS.

I Calculated: C, 47.74; H, 5.51; N, 6.91; S, 15.94.

Found: C, 47.83; H, 5.39; N, 7.18; S, 16.14.

H-NMR (CDC13): 6 7.70 1H); 7.38 1H); 6.04-5.98 (dd, 1H); 3.91 3H); 3.21 2H); 1.38 S(t, 3H).

The following entries in Tables I and II may be prepared using the methods taught in the above examples.

WO 89/06230 WO 8906230PCT/US89/0000 I 11 TABLE I RO- I CN1

R

CH 3 CH 3 CH 3 CH 2CH3 23- R 1 CON (CH 3 )2 CON(C 2 CH 3 2 so2 CH 2CH CON(CH 3 )~2 Physical Data NMR 2.95 s) m.p. 72-74*C f6 i i kl i i -1-1 1-11 I ~2 3 CH 2

CM

C 2 C H 3 CON(CH 2 CH 3 )2 so2 CHM CH 3

I

ii ~A4V~ y;' mb -I AN WO0 89/06230 PCT/US89/0000 I TABLE II N x so2CH 2CH3 CON

CK

3 2 CON(CH 2 CH 3 2 'eCM (CII 2 Clii 3 z CON(CH 2 CH3) 2 SO 2 CH 2

CHM

3 CON(CH 8) 2 Physical Data M. P. 78-79 0

C

(HBr salt) (HCl salt) (HBr siKlt) (HBr salt) m.p. 196-198 0

C

t

Claims (12)

1. A process for preparing a compound of the formula Ri N X I wherein R is C(O)R 2 or SO 2 CH 2 CHy R2 is C 1 -C 2 dialkylamino; and X is F, Cl or Br; said process comprising reacting a compound of the Formula II with a compound of Formula ITl CI R CI-(OR) 2 R S' CH 2 CH 2 S: CH(OR) 2 CN U m where R is -CH 3 or -CH 2 CH 3 and R 1 is as defined above i the presence of acetic anhydride, a ZnX 2 catalyst where X is as defined above at a temperature of 110'-150"C to form a compound of the formula NN. R 1 *CN RO IV including all geometric isomers thereof, wherein R, and R are as defined above and reacting the compound of Formula IV with HX where X is as defined above in the presence of acetic acid at a temperature of 0' -60" C.

2. The process of Claim 1, wherein R 1 is C(O)R 2 and R 2 is C 1 dialkylamino.

3. The process of Claim 1, wherein R 1 is S0 2 CH2CH 3 ~J U i -14 S. S S S**

4. The process of any one of claims 1 to 3, wherein X is Br. The process of any one of claims 1 to 4, wherein an excess HX is used in order to form crystalline salt of Compound I in the reaction mixture and separating the salt from the mixture.

6. A process for preparing a compound of the formula I as defined in claim 1 which process is substantially as herein described with reference to any one of the Examples.

7. A compound of Formula I as defined in claim 1 whenever prepared by the process of any one of claims 1 to 6.

8. A compound of Formula IV CN RO IV including all geometric isomers thereof, wherein R is CH 3 or C 2 Hy and Ri is C(O)R 2 or SO 2 CH 2 CH and R is C 1 -C 2 dialkylamino.

9. The compounds of Claim 8, wherein R 1 is C(O)R 2 The compounds of Claim 8, wherein R 1 is SO 2 CH 2 CH 3

11. The compounds of the Formula I aR (or0 N X I and their corresponding salts, wherein R, is C(O)R 2 or SO 2 CH 2 CH3 R 2 is C 1 -C 2 dialkylamino; and X is F, Cl or Br; provided that when R 1 is C(O)R 2 then X is F or Br.

12. The compounds of Claim 11, wherein Ris C(O)R 2 R 2 is C, dialkylaniino and X is F or Br.

13. The compound of Claim 11, wherein Ris SO CH C-H 3 DATED this 12th day of September 1991. E.I. DUi PONT DE NEMOURS AND COMPANY By their Patent Attorneys: CALLINAN LAWRIE so:J*J V~ o 1 o 0 0 o 0 o *o 0. Vso: INTERNATIONAL SEARCH REPORT International Application No pCr/TTq q 0 I. CLASSIFICATION OF SUBJECT MATTER (it several classification symools apply, indicate all i According to International Patent Classification (IPC) or to both National Classification and IPC IPC4: C 07 C 147/02; C 07 C 121/417; C 07 D 213/82; C 07 D 213/71 II, FIELDS SEARCHED Minimum Documentation Searched 7 Clasification System Classification Symbols 4 IPC C 07 D 213/00; C 07 C 121/00; C 07 C 147/00 Documentation Searched other than Minimum Documentation to the Extent that auch Documents are Included In the Flelds Searched Ill. DOCUMENTS CONSIDERED TO BE RELEVANT' Category Citation of Document, with Indication, whire appropriate, of the relevant passages 12 Relevant to Claim No. l A Journal of Organic Chemistry, volume 39, 1 no. 23, 1974, (Columbus, Ohio, US), T.A. Bryson et al.: "Biological probes! II. Ring labeled nicotinamide", pages 3436-3438 see page 3437, scheme I cited in the application A Journal of Organic Chemistry, volume 41, 1 no. 11, 1976, (Columbus, Ohio, US), T.A. Bryson et al.: "Biological probes. 3. Methods for carbon-4 and labeling in nicotinamide", pages

2066-2067 see page 2066 cited in the application A Chemical Abstracts, volume 94, 1981, 1 (Columbus, Ohio, US), see page 680, abstract 121332j, JP, A, 8076863 (YOSHITOMI PHARMACEUTICAL INDUSTRIES, LTD) June 1980 cited in the application Special categories of cited documents: io later document published after the International filing date document defnng the gneral itte of the art which I not or priority dat and not In conf'ct with the aoolicaton but clited to understand the prlncipie or theory Unoerlyng the Considered to be of particular relevance Invention earlier document but published on or after the international document of particular relevance: the claimed invention filing date cannot be considered novel or cannot be considered to document which may throw doubts on priority claim(s) or Involve an inventive step which is cited to establish the publication date of another document of particular relevance; the claimed invention citation of other special reason (as soecified) cannot De considered to Involve an inventive stiD when the document referring to an oral disclosure, use, exhibition or document is combined with one or more other such docu. other means ments, such combination being obvious to a person skilled document published prior to the international filing date but In the art. Iater than the priority date claimed document member of the same patent family IV, CERTIFICATION Date of the Actual Completion of the International Search Date of Malling of this International Search Report April 1989 0 3, 9 International Searching Authority Signature of Authoruz Officer EUROPEAN PATENT OFFICE .OSS Form PCTIISA/210 (second sheet) (January 1985) -2- Imtormstlonal Applicgflon No. PCT/US 89/00001 111, DOCUMENTS CONSIDERED TO 01 RELEVANT (CONTINUED FROM THE SECOND SHEET) category' Citation of Document. wan~ indicatsoni. whwer appro~ite. of Me rotevant passages iRelevant to Claim No A DE, A, 1595900 (LABORATORIES 9 26 February 1970 see examples 7,10 Form PCT ISA 2t0 (extra shoeot) (January 1985) 1 t i I ANNEX TO THE INTERNATIONAL SEARCH REPORT ON INTERNATIONAL PATENT APPLICATION NO. US 8900001 SA 26395 This annex lists the patent family members relating to the patent documents cited in the above-mentioned international search report. The members are as contained in the European Patent Office EDP file on 26/04/89 The European Patent Office is in no way liable for these particulars which are merely given for the purpose of information. Patent document Publication Patent family Publication cited in search report date member(s) date DE-A- 1595900 26-02-70 FR-A- 1604911 15-05-71 SFor more details about this annex see Official Journal of the European Patent OfficeNo. 12/8 f For more details about this annex :see Official Journal of the European Patent Office, No. 12/82