Europaisches Patentamt European Patent Office © Publication number: 0 537 611 A1 Office europeen des brevets EUROPEAN PATENT APPLICATION © Application number: 92117123.7 int. Ci.5; C07D 487/04, A01 N 43/90, //(C07D487/04,249:00,239:00) @ Date of filing: 07.10.92 © Priority: 08.10.91 US 772990 © Applicant: DOWELANCO 9002 Purdue Road @ Date of publication of application: Indianapolis, Indiana 46268-1 189(US) 21.04.93 Bulletin 93/16 @ Inventor: Johnson, Timothy C. © Designated Contracting States: 1047 Orange Street AT BE CH DE DK ES FR GB IT LI NL Concord, California 9451 8(US) Inventor: Nasutavicus, Wilmonte A. 1700 Reliez Valley Road Lafayette, California 94549(US) © Representative: Huber, Bernhard, Dipl.-Chem. et al Patentanwalte H. Weickmann, Dr. K. Fincke F.A. Weickmann, B. Huber Dr. H. Liska, Dr. J. Prechtel Kopernikusstrasse 9 Postfach 86 08 20 W-8000 Munchen 86 (DE) © Process for the preparation of substituted N-(aryl)-1,2,4-triazolopyrimidine-2-sulfonamides. © The preparation of N-(aryl)-1 ,2,4-triazolopyrimidine-2-sulfonamides of formula (V) by the coupling of substi- tuted 1 ,2,4-triazolopyrimidine-2-sulfonyl halides of formula (VI) with aryl amines of substantially reduced nucleophilic reactivity is facilitated by conducting the reaction in the presence of a pyridine base and a catalytic amount of dimethyl sulfoxide. CO 00 Rank Xerox (UK) Business Services (3. 10/3.5x/3.0. 1) EP 0 537 61 1 A1 EP 0 537 61 1 A1 The present invention concerns a process for the preparation of N-(aryl)-1 ,2,4-triazolopyrimidine-2- sulfonamides by the coupling of aryl amines with substituted 1 ,2,4-triazolopyrimidine-2-sulfonyl halides. More particularly, the present invention concerns the dimethyl sulfoxide catalyzed coupling of the amine and the sulfonyl halide in the presence of a pyridine base. 5 Substituted N-(aryl)-1 ,2,4-triazolo[1 ,5-a]pyrimidine-2-sulfonamides (I) 10 II n ArNHS — (/ (I) | N z 75 and substituted N-(aryl)-1 ,2,4-triazolo[1 ,5-c]pyrimidine-2-sulfonamides (II), X 20 °0 A N_ II // N \ N ArNHS — (f | . (ID 25 such as those described in U.S. Patents 4,740,233 and 5,010,195, are valuable herbicides for the selective 30 control of weeds in agronomic crops. Compounds of this family have generally been prepared by the conventional reaction between an aryl amine (III) and a substituted 1 ,2,4-triazolopyrimidine-2-sulfonyl chloride (IV) 35 ArNH 2 (III) u 40 (IV), , in the presence of a tertiary amine base (U.S. Patent 4,740,233) or an excess of the aniline (British Patent 951 ,652). This procedure is generally satisfactory for the preparation of substituted 1 ,2,4-triazolopyrimidine- 45 2-sulfonanilides when the substituted aniline employed is aniline itself or is a substituted derivative of aniline that has similar reactivity as a nucleophilic reagent. However, when the substituted aniline is of substantially reduced nucleophilic reactivity due to the presence of electron-withdrawing substituents on the ring, and especially, to the presence of such substituents in the positions ortho to the amino function, or when the aryl group is an electron-withdrawing heterocyclic group, this method is very slow and provides low yields 50 of the desired products. This reactivity problem is particularly unfortunate because the most herbicidally potent substituted 1 ,2,4-triazolopyrimidine-2-sulfonamides possess just such substituents. In order to circumvent this reactivity problem, a strong base, such as an alkali metal alkyl or an alkali metal hydride, capable of converting the poorly nucleophilic substituted aniline to its corresponding metal derivative, is employed in place of the tertiary amine base as described in U.S. Patent 4,740,233. The metal 55 derivative is preformed and then allowed to react with a substituted 1 ,2,4-triazolopyrimidine-2-sulfonyl halide. This procedure allows the compounds to be prepared, but it requires an excess of the metal derivative of the substituted aniline and is carried out below 0°C, and, therefore, is not commercially desirable. 3 EP 0 537 61 1 A1 Alternatively, the nucleophilicity of the aniline can be increased by converting it into the corresponding N-trialkylsilylaniline. U.S. Patent 5,003,096 describes the enhanced reactivity of N-trialkylsilylanilines in their coupling with substituted 1 ,2,4-triazolo[1 ,5-a]pyrimidine-2-sulfonyl halides; U.S. Patent 5,010,195 describes the similar enhanced reactivity in the case of the corresponding 1 ,2,4-triazolo[1 ,5-c]pyrimidines. Although 5 this procedure allows a wider range of products containing electron-withdrawing groups to be prepared, it requires additional steps to synthesize the N-trialkylsilylanilines and to recover and recycle the valuable silicon-containing reagent. In view of the valuable herbicidal properties of the sulfonamides (I) and (II), it is highly desirable to have a direct process which can be used to prepare a wide variety of materials in which the aryl groups contain io electron-withdrawing substituents. Ideally, this process should avoid exceedingly long reaction times and the need of a strong base. Additionally, this process should avoid superfluous reaction steps and the recovery and recycle of expensive reagents. The present invention concerns a process for the preparation of N-(aryl)-1 ,2,4-triazolopyrimidine-2- sulfonamides of the formula (V): 15 X 20 25 wherein one of A or B is N and the other is C-Z, X represents H, R, OR, SR or CF3, Y represents H, R, OR, F, CI, Br or CF3, Z represents H, R, OR, F, CI, Br, CF3 or phenyl, 30 R represents a lower alkyl group optionally substituted with one or more halogen or with a lower alkoxy group, and Ar is a substituted phenyl group of the formula: in which 45 R1 represents H, F, CI, Br, R, OR, SR or C02R, R2 represents H, R or OR, R3 represents H, F, CI, Br, CF3, C02R or N02, and R is as previously defined, or Ar is a substituted pyrazole group (PRZ) of the formula: 50 55 4 EP 0 537 61 1 A1 r6 Y-7 N N or R7 i K i 10 5-pyrazolyl 4-pyrazolyl 3-pyrazolyl in which R+ represents R, phenyl or pyridinyl, is R5 represents H, NO2 or CF3, RG represents H, F, CI, Br, I or C02R, R7 represents H or R, and R is as previously defined, which is characterized by contacting a substituted 1 ,2,4-triazolopyrimidine-2-sulfonyl halide of the formula 20 (VI): X wherein A, B, X, Y, Z and R are as previously defined, with an aryl amine of the formula ArNH2 35 wherein Ar is as previously defined, in an inert aprotic organic solvent in the presence of a pyridine base and of a catalytic amount of dimethyl sulfoxide (DMSO). 40 By conducting the reaction in the presence of a pyridine base and a catalytic amount of DMSO, it is possible to directly prepare a wide variety of N-(aryl)-1 ,2,4-triazolopyrimidine-2-sulfonamides containing electron-withdrawing substituents in the N-(aryl) group. As used herein, the terms "lower alkyl" and "lower alkoxy" are meant to designate straight or branched, saturated alkyl or alkoxy groups of from 1 to 4 carbon atoms. 45 Where individual members of the halogen family are not specifically listed, the general terms "halogen", "halide", "halo" and "hal", as used herein, are meant to be construed as being limited to chloro and bromo. By pyridine base is meant pyridine or a methylpyridine such as the picolines or the lutidines. Pyridine itself is generally preferred. The substituted 1 ,2,4-triazolopyrimidine-2-sulfonyl halides (VI) 55 5 EP 0 537 61 1 A1 X 5 VI w wherein one of A or B is N and the other is C-Z, X represents H, R, OR, SR or CF3, Y represents H, R, OR, F, CI, Br or CF3, is Z represents H, R, OR, F, CI, Br, CF3 or phenyl, and R represents a lower alkyl group optionally substituted with one or more halogen or with a lower alkoxy group, utilized in the process of this invention are known compounds and can be prepared as described in U.S. Patent Nos. 4,886,883, 4,954,163 or 5,010,195 or by other conventional methods. Examples of suitable 20 reactants include the following: 8-chloro-7-methoxy-5-methyl-1 ,2,4-triazolo[1 ,5-c]pyrimidine-2-sulfonyl chlo- ride; 8-chloro-5-methoxy-1 ,2,4-triazolo-[1 ,5-c]pyrimidine-2-sulfonyl chloride; 7-fluoro-5-methoxy-1 ,2,4- triazolo[1 ,5-c]pyrimidine-2-sulfonyl chloride; 7-chloro-5,8-dimethoxy-1 ,2,4-triazolo[1 ,5-c]pyrimidine-2-sulfonyl chloride; 5-methoxy-1 ,2,4-triazolo[1 ,5-c]pyrimidine-2-sulfonyl chloride; 7-chloro-5-methoxy-1 ,2,4-triazolo[1 ,5- c]pyrimidine-2-sulfonyl chloride; 7-chloro-5-ethoxy-1 ,2,4-triazolo[1 ,5-c]pyrimidine-2-sulfonyl chloride; 5- 25 methoxy-7-methyl-1 ,2,4-triazolo[1 ,5-c]pyrimidine-2-sulfonyl chloride; 5-ethoxy-7-methyl-1 ,2,4-triazolo[1 ,5-c]- pyrimidine-2-sulfonyl chloride; 5-chloro-7-methoxy-1 ,2,4-triazolo[1 ,5-c]pyrimidine-2-sulfonyl chloride; 8- bromo-5-chloro-7-methoxy-1 ,2,4-triazolo[1 ,5-c]pyrimidine-2-sulfonyl chloride; 5,7-dimethyl-1 ,2,4-triazolo[1 ,5- a]pyrimidine-2-sulfonyl chloride; 5-methyl-1 ,2,4-triazolo[1 ,5-a]pyrimidine-2-sulfonyl chloride; 5-methyl-7- trifluoromethyl-1 ,2,4-triazolo[1 ,5-a]pyridimine-2-sulfonyl bromide; 1 ,2,4-triazolo[1 ,5-a]pyrimidine-2-sulfonyl 30 chloride; 5-methoxy-7-butyl-1 ,2,4-triazolo[1 ,5-a]pyrimidine-2-sulfonyl bromide; 6-chloro-1 ,2,4-triazolo[1 ,5-a]- pyrimidine-2-sulfonyl chloride; 5-methylethyl-7-methylthio-1 ,2,4-triazolo[1 ,5-a]pyrimidine-2-sulfonyl chloride; 5,7-dimethyl-6-fluoro-1 ,2,4-triazolo[1 ,5-a]pyrimidine-2-sulfonyl chloride; and 5,7-dimethoxy-1 ,2,4-triazolo[1 ,5- a]pyrimidine-2-sulfonyl chloride.