Imidic acids from 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]. 

Piroxicam Piroxicam, 1,1 -dioxid-4-hydroxy-2-methyl-iV-2-pyradyl-2//-1,2-benzothiazine-3-carboxamide (3.2.78), is synthesized from saccharin (3.2.70). Two methods for saccharin synthesis are described. It usually comes from toluene, which is sulfonated by chlorosulfonic acid, forming isomeric 4- and 2-toluenesulfonyl chlorides. The isomeric products are separated by freezing (chilling). The liquid part, 2-toluenesulfonyl chloride (3.2.68) is separated from the crystallized 4-toluenesulfochloride and reacted with ammonia, giving 2-toluenesul-fonylamide (3.2.69). Oxidation of the product with sodium permanganate or chromium (VI) oxide in sulfuric acid gives saccharin—o-sulfobenzoic acid imide (3.2.70) [123-126]. 

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