Amidines from carboxamides

From Isatoic Anhydrides and Guanidine, Amidines, or Carboxamides... 

The first step in the ring closure of carboxamide 107 (R=NH2) with imidates is the formation of an amidine intermediate, with subsequent nucleophilic attack of the imino group of the amidine on the carbonyl group this takes places with loss of the carboxamide iV-substituent [117]. This observation formed the basis of a simple synthesis of CHINOIN 143 enantiomers. From carboxamides 39 and 40 with ethyl m-chlorobenzimidate, 109 and 110 were obtained in high enantiomeric purity. The absolute configurations were determined by hydrolysis of 109 and 110 to the corresponding amino acid, which was identified by HPLC [79]. 

Nitriles, which are important intermediates in the manufacture of a wide variety of organic compounds such as amines, aldehydes, amidines, and heterocycles, are manufactured either from alkali cyanides or from carboxamides. The cyanides route is obviously highly toxic, whereas the carboxamide consumes the reagent in stoichiometric quantities. Solid superacids offer a clear alternative to the traditional catalysts. Thus the use of sulfated zirconia enables the dehydration to be accomplished under much milder conditions in the liquid state (Joshi and Rajadhyaksha, 1986 Rajadhyaksha and Joshi, 1991). 

From A(-substituted carboxamides, the 3-unsubstituted derivatives were formed, with loss of the corresponding amine. This reaction is to be expected from the mechanism of the ring closure amidine formation and subsequent nucleophilic attack of the amidine nitrogen on the carbonyl group. 

N1 -Carboxamide-N-Guanyi Triazene [Triazendi-carbon saureamid-amidin (Ger)] H2N.CO.N N.NH.C( NH).NH2+H2 Of C2H8N602 mw 132.16 N 63.60% OB to C02 +24.21% yel ndles (from hot w) mp, decomps explosively at 95°, puffs off at 139° on rapid heating. V sol in alkalies si sol in w. Prepn is by gently warming N-aminoim inome thy 1- N-carb onic acid ethyl ester-triazene with ammonia. The compd forms expl salts such as the Hydrochloride, C2H6N60+HC1 mw 167.09 N 50.31% ... 

Applications in organic synthesis of the iminoacylation reaction of oximes have recently been found at kinetically labile Zn11- or Con-oxime systems. The former catalyzes the hydrolysis of nitriles to carboxamides (23)37 and the Co11 system catalyzes the conversion of nitriles into amidines (24) (also involving C N bond formation upon reaction with ammonia, formed from competitive hydrolysis of the nitrile).110... 

Methods derived from this fundamental process involve the condensation of one-, two- and three-carbon units such as amidines, amino-nitriles and carboxamides, which represent intermediate stages of the ammonia/hydrogen cyanide reaction. Pyrimidines or imidazoles are usually intermediates. ... 

Reactions of Cyano- and Carboxy-thiophens.—-Amidines and imino-ethers as well as triazoles and tetrazines have been prepared from cyano-thiophens. The modified Lossen rearrangement of sodium JVA -dihydroxythiophen-2,3-di-carboxamide with benzenesulphonyl chloride furnished a mixture of (176) and (177) in 54% yield in a 1 3 ratio. Azo dyes have been prepared by diazotiza-tion of A -(4 -aminophenyl)thiophen-2-carboxamides. 2-Thienylthiocarbonyl... 

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