Isothiocyanates amidinothioureas

Di(alkyl or aryl)amino-l,2,4-thiadiazoles (90 R,R = alkyl or aryl) are similarly obtainable in 60-85% yields from the appropriate disubstituted amidinothioureas (89 R,R = alkyl or aryl).56,57 The preparation of the latter from monosubstituted guanidines (87) and isothiocyanate esters (88) might conceivably yield the isomeric ami-... 

The trisubstituted amidinothioureas (98) required as precursors of the thiadiazolines are obtained by the interaction of isothiocyanate esters and s-diarylguanidines,115 or by the action of aromatic amines on dithiazolidines (102).117 The former reaction might conceivably yield the isomeric amidinothioureas (98a) instead if so, however, oxidation and isomerization would give rise to a 2-(diphenylguanidino)benz-thiazole (100a) isomeric with, but different from, the product (100) actually obtained. The structure of this product is confirmed by synthesis from 2-aminobenzthiazole (101) and carbodiimides.115... 

Trisubstituted amidinothioureas of type 247, obtainable from formami-dinoyl isothiocyanates [R12NC(=NAr)NCS], are cyclized to 248,98,191 which are isolated advantageously as salts (hydrobromides, hydriodides) with suitable precautions, the somewhat labile bases are isolable.98... 

A general procedure for Ihe solution phase synthesis of amino-13-thiazolcs has been described. It is based on the condensation of amidines 70 or thiouronium salts 71, with isothiocyanates 72, affording amidinothioureas 73 and thiouriedothiourcas 74. Subsequent treatment with a-bromoketones 75 led to the S-alkylated intermediates 76 and 77 which yielded 13-thiazoles of types 78 and 79 via a base catalysed ring closure. This reaction sequence could conveniently be performed in one pot without isolation of the intermediates, allowing for the efficient generation of combinatorial libraries <01T153>. 

Formamidinoyl isothiocyanates (66) react additively with amines to yield amidinothioureas (67), which are cyclized by bromine to yield substituted... 

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