2.5- Disubstituted imidazo thiazoles

Disubstituted imidazo[2,l-ft]thiazoles 41 have been prepared (55JCS1695 57JCS566) by eyelization of 1,5-disubstituted 2-mereaptoim-idazoles 40 in eonc. hydroehloric aeid. The latter eompounds were synthesized via eyelization of the thiourea derivatives 39. No aldehyde (42) was isolated from the reaetion obviously the thiourea eyelized more readily by reaetion with the aldehyde than with the keto group. 

Veerabhadraiah et al. (89SUL167) treated 4,5-disubstituted 2-mercapto-imidazoles with 3-(a>-bromoacetyl)coumarins and obtained ketones that on subsequent cyclization with PPA furnished 2,5,6-trisubstituted imidazo[2,l-h]thiazoles 38. 

Scheme 61, yielded thiazole 200 as the major product, along with minor amounts of carbinol 201 [152]. On the other hand, treatment of the imine formed from 199 and p-methoxyphenylamine with catalytic tetrabutylammonium cyanide, produced suc-cinimide derivative 202. In both cases, the process is initiated by nucleophilic attack to the carbaldehyde C=0 (or azomethine s C=N) group, which is followed up by an anionic rearrangement. A variation of the above process using as catalysts /V-heterocyclic carbenes (NHC) derived from base treatment of azolium, imidazo-lium, or triazolium salts, has also been developed to access gem-disubstituted succinimides [153, 154]. Unfortunately, an attempt of kinetic resolution of racemic 4-formyl (3-lactams by using chiral NHC resulted in moderate selectivities only [154]. 

Of the reported routes to imidazo[l,5-c]thiazoles, the (4 + 1) type BC and (3 + 2) type BD routes are more generally applicable and involve milder reaction conditions. Imidazo[l,2-Z>]pyrazoles can be obtained by both (5 + 0) syntheses (types B and C) and (3 + 2) syntheses (type BD). The (3 + 2) synthesis allows access to a range of 2,3-disubstituted heterocycles whereas the (5 + 0) type B route allows simple analogues to be synthesized from already functionalized aminopyrazoles. The (5 + 0) type C synthesis is limited in scope due to the multistep route to the required precursors. 

---