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United States Patent (19) 11 3,905,991 Schlatter Et Al

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United States Patent (19) 11 3,905,991 Schlatter Et Al United States Patent (19) 11 3,905,991 Schlatter et al. (45) Sept. 16, 1975 54) 2-BENZMDAZOLECARBAMIC ACID 247,453 4/1912 Germany......................... 260/482 C ESTERS BY THE CYANAMIDE PROCESS OTHER PUBLICATIONS 75) Inventors: Rudolph Schlatter, Chadds Ford, Derwent Pharmaceutical Documentation Specification Pa.; Charles De Witt Adams, Book No. 463, Feb. 4, 1966, 19,779-19,841, pp. Wilmington, Del. 239-243. 73 Assignee: E. I. Du Pont de Nemours and Hofmann Imidazole and Its Derivatives Part I, pp. Company, Wilmington, Del. 260-267, N.Y., Interscience, 1953 QD401.H6. Kaiser et al., Jour. Org. Chem. Vol. 17, pp. 185-192, 22 Filed: June 25, 1969 (1952), OD241.J6. (21) Appl. No.: 836,580 Pierron Comptes Rendus Vol. 151, pp. 1364-1366, Related U.S. Application Data (1910), O46. A 14. 63 Continuation-in-part of Ser. No. 745,403, July 17, 1968, abandoned, which is a continuation-in-part of Primary Examiner-Natalie Trousoe Ser. No. 674,739, Oct. 12, 1967, abandoned, which is a continuation-in-part of Ser. No. 594,384, Nov. 15, 57 ABSTRACT 1966, abandoned. A process for making 2-benzimidazolecarbamic acid, alkyl esters by reacting cyanamide or a cyanamide salt 52 U.S. Cl....... 260/309.2: 260/471 C; 260/482 C; with an alkyl chloroformate in a weakly acidic to basic 260/999; 424/300 medium at a temperature between 0 and 105°C. to (51 Int. Cl.’........................................ C07D 235/32 form an alkyl cyanocarbamate salt; then reacting the 58 Field of Search.................................. 260/309.2 alkyl cyanocarbamate salt with al On phenylenediamine in an acidic medium at a tempera 56 References Cited ture between 40 and 130°C. to form the desired prod UNITED STATES PATENTS uct and recovering it from the reaction mixture. 3,147,274 9/1964 Moyle et al...................... 260/309.2 The 2-benzimidazolecarbamic acid, alkyl esters are 3,255,202 6/1966 Johnson........................... 260/309.2 useful as fungicides and also useful as intermediates in the preparation of dialkyl esters of FOREIGN PATENTS OR APPLICATIONS 2-carboxyaminobenzimidazole-l-carboxylic acids. 61, 189 9/1913 Austria............................ 260/482 C 666,795 l/1966 Belgium........................... 260/309.2 13 Claims, No Drawings 3,905,991 2 2-BENZMDAZOLECARBAMIC ACD ESTERS BY These compounds are disclosed in U.S. Pat. No. THE CYANAMIDE PROCESS 2,933,504 and are very useful as fungicides. CROSS-REFERENCE TO RELATED U.S. Pat. No. 3,010,968 describes a process for mak ing the 2-benzimidazolecarbamic acid esters of formula APPLICATIONS 5 (I) by reacting thiourea with dimethyl sulfate to pro This application is a continuation-in-part of our co duce 2-methylthiopseudourea sulfate. This reaction pending application Ser. No. 745,403, filed July 17, product is then reacted with an alkyl chloroformate 1968, now abandoned, which application is a continua and a base to produce an acylated 2 tion-in-part of our copending application Ser. No. methylthiopseudourea, which is then reacted further 674,739, filed Oct. 12, 1967, now abandoned, which O with an o-phenylenediamine in the presence of a pro application is a continuation-in-part of our then co tonic acid to produce the desired product. pending application Ser. No. 594,384, filed Nov. 15, The process of this invention has several advantages 1966, now abandoned. over the process set forth in the above patent. One par BRIEF SUMMARY OF THE INVENTION ticular advantage is that commercially available, inex 15 pensive, technical-grade cyanamide salts or cyanamide This invention relates to novel processes for the man solutions can be used instead of the relatively more ex ufacture of alkyl esters of certain benzimidazolecar pensive thiourea materials. Further, the process of this bamic acids. More particularly, this invention relates to invention does not require the handling or disposal of processes for the manufacture of such esters from cy obnoxious methyl mercaptan materials which are by anamide or cyanamide Salts. products of the art process. Additionally, the process of Alkyl esters of 2-benzimidazolecarbamic acids repre this invention can be conducted in a batch or continu sented by the formula: ous manner with normal reaction vessels. The process of this invention can be summarized by the following equations when a cyanamide salt and 25 water as a solvent are employed: () X 30 (Step ) N N -N-COOR pH 4 - 13. m MNCN) + m (ClCOR) --> MCI -- MIN(CN)COR) N / H HO 35 H cyanamide alkyl alkyl salt chloro cyanocarbamate for mate salt where R is alkyl of through 4 carbon atoms, and 40 (Step 2 - condensed equation form) X is hydrogen, halogen, nitro or alkyl of 1 through 4 carbon atoms; are useful as fungicides. The compounds when X is hydrogen and R is alkyl of I to 4 carbon atoms are particularly useful. The above compounds are also useful as intermediates in the prep 45 X aration of dialkyl esters of 1-carboxy-2- -NH pH 1 - 6 MIN(CN)COR) + m 2m H' --> benzimidazolecarbamic acids represented by the for -NH. A mula: HO alkyl o-phenylene cyano diamine carbamate salt 55 N C-N-COOR + mNH + M" H N H 60 alkyl ester of 2-benzimidazolecarbamic acid where X is as defined in formula (I) above and 65 R and R are the same or different and are alkyl of Step 2 above can be represented in more detail by the 1 through 4 carbon atoms. following equations: 3,905,991 4. (a) HO pH. Step 1 in this embodiment is illustrated by the fol M(N(CN)COR) + mH - m HN(CN)COR + Mnt lowing equation when water is employed as solvent: pH 1 - 6 alkyl cyanocar- alkyl cyanocarbamate bamate salt (Step i) O | HO (b) X mHNCN + mc-C-OR + 2M(OH) --> -NH HO pH 4 - 13 -- mHN(CN)COR -- mH* --> cyana- alkyl base -NH, pH 1 - 6 mide chloro formate 15 MIN(CN)COR + MC + 2mHO alkyl cyanocarbamate salt in this reaction the base used is not critical. All that is necessary is that it be able to take up the HCL gener X ated and thereby maintain the reaction mass weakly acidic to basic. Thus, for example, any basic alkali C-NHCOR -- mNH metal or alkaline earth metal compound can be used as N / the base. Alkali metal and alkaline earth metal hydrox H ides are preferred, although oxides and carbonates can alkyl ester of be used. 2-benzimidazolecarbamic acid 25 Ouaternary ammonium hydroxides can be used as base when cyanamide is employed. Step 1 in this em bodiment is illustrated by the following equation when where water is employed as solvent. R is alkyl of 1 through 4 carbon atoms; and X is hydrogen, halogen, nitro or alkyl of 1 through 4 30 carbon atoms; M is an alkali metal or an alkaline earth metal; and (Step 1) m is the valence of M, and O H* may be derived from any acid. | HO The second step which results in producing the 2 35 HNCN + CICOR - 2 NRRRR.OH --> benzimidazolecarbamic acid ester can be summarized pH 4 - 13 as comprising reacting an alkyl cyanocarbamate of the cyana- alkyl base formula: mide chloro formate 40 (NRRRR). N(CN)0OR) + NRRRRC) -- 2HO alkyl cyanocarbamate salt where where R is alkyl of 1 through 4 carbon atoms; with an R, R2, and Ra are alkyl of 1 through 4 carbon atoms; o-phenylenediamine of the formula: 45 and R is either alkyl of 1 through 4 carbon atoms or aral kyl of 7 through 12 carbon atoms. The cheaper and more readily available quaternary ammonium hydroxides, such as tetramethylammonium 50 hydroxide or benzyltrimethylammonium hydroxide, are preferred. Tertiary amine can also be used as bases when cyana -NH mide is employed. Step 1 in this embodiment is illus trated by the following equation when water is em 55 ployed as solvent: where X is hydrogen, halogen, nitro or alkyl of 1 (Step 1) O through 4 carbon atoms; in the presence of sufficient 60 acid to neutralize the NH3 formed, until the precipita HO tion of the 2-benzimidazolecarbamic acid ester is com HNCN + CICOR + 2NRRR --> plete. The 2-benzimidazolecarbamic acid ester can pH 4 - 13 then be recovered from the reaction mixture. cyana- alkyl amine In Step 1 above, when a cyanamide salt is employed, mide chloro- base the cyanamide is present in the solution in anion form. 65 formate However, cyanamide can also be used in Step 1 if a HNRRR). N(CN)0OR) -- (HNRRR, ).Cl base is added to the solution to maintain the desired alkyl cyanocarbomate salt 3,905,991 5 6 where substituted o-phenylenediamines to give 2 R5 and Rs are alkyl of 1 through 4 carbon atoms; and benzimidazolecarbamic acid, alkyl esters. These reac R7 is alkyl of 1 through 4 carbon atoms, or aralkyl of tions are illustrated by the following equation when 7 through 12 carbon atoms. - , water is used as solvent: Tertiary amines such as trimethylamine and triethyl 5 amine are preferred. Certain other substituted tertiary amines, such as tri ethanolamine and triethylenediamine, can be used as bases when cyanamide is employed. Step 1 in this em X bodiment is illustrated by the following equation when 10 -NH. HO water is employed as solvent: + HN(CN)COR - Ht -mb -NH pH 1 - 6 o-phenylenediamine alkyl cyano carbamate (Step 1) O 15 | HO HNCN + CICOR + 2N(R) -mb pH 4 - 13 X cyana- alkyl amine NN mide chloro- base Sc-NHCOR + NH" formate N1 H HN(R)). (N(CN)0OR) -- HN(R)). Cl alkyl ester of alkyl cyanocarbamate salt 2-benzimidazolecarbamic acid where N(Rs) is triethanolamine or triethylenediamine.
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