Thiazoline synthesis

In this section, only salient features of the synthesis, physicochemical properties, and reactivity of major derivatives of 2-aminothiazole and 2-imino-4-thiazoline are summarized. Further details on each compound are found in associated references collected in Section VII. The synthetic methods reported in this section exclude heterocydization methods treated in Chapter II but given in specific references found in Section VII. 

Imino-4-thiazolines are far more basic than their isomeric 2-aminothiazoles (see Table VI-1). They react with most electrophDic centers through the exocyclic nitrogen and are easily acylated (37, 477, 706) and sulfonated (652). The reaction of 2-imino-3-methyi-4-thiazoline (378) with a-chloracetic anhydride yields 379 (Scheme 217) (707). This exclusive reactivity of the exocyclic nitrogen precludes the direct synthesis of endocyclic quaternary salts of 2-imino-4-thiazolines. although this class of compounds was prepared recently according to Scheme 218 (493). 

The synthesis of 9H-benzo[2,l-e]thiazolo-[2,3-c]-as-triazine (401) was achieved by oxydative cyclization of 2-imino-3-(o-aminophenyl)-4-phenyl-4-thiazoline (718, 719). This latter reacts also with paraformaldehyde in hot toluene yielding 3-phenyl-9H.10H-benzo[l,2-/]thiazolo-[2,3-d][l,3,5]triazepine (402) (720). This heterocyclic sytem is also formed when carboxylic acids replace paraformaldehyde (Scheme 230) (721). 

A-4-Thiazoline-2-ones and ring substituted derivatives are usually prepared by the general ring-closure methods described in Chapter II. Some special methods where the thiazole ring is already formed have been used, however. An original synthesis of 4- 2-carboxyphenyl)-A-4-thiazoline-2-one (18) starting from 2-thiocyanato-2-halophenyl-l-3-indandione (19) has been proposed (Scheme 8) (20, 21). Reaction of bicyclic quaternary salts (20) may provide 3-substituted A-4-thiazoline-2-one derivatives (21) (Scheme 9) (22). Sykes et al. (23) report the formation of A-4-thiazoline-2-ones (24) by treatment ef 2-bromo (22) or 2-dimethylaminothiazole (23) quaternary salts with base (Scheme 10). 

Although the synthesis of thiazolidine-2,4-dithione has been reported (357), no examples of a A-2-thiazoline-4-thione bearing a nonprotomeric group at C-2 are known. Some fused compounds are reported in Table 41. 

The synthesis of other A-2-thiazolin-4-ones has been reported (414. 424. 429. 436-439). However, insufficient spectroscopic data are given to show if their structures are monomeric or polymeric. 

Of all the methods described for the synthesis of thiazole compounds, the most efficient involves the condensation of equimolar parts of thiourea (103) and a-haloketones or aldehydes to yield the corresponding 2-aminothiazoles (104a) or their 2-imino-A-4-thiazoline tautomers (104b) with no by-products (Method A, Scheme 46). 

Another synthetic sequence leading to penicillin derivatives is illustrated in Scheme 61 (77MI51102). Note that the cycloaddition of azidoacetyl chloride to the thiazoline affords an azidopenam with the 6-epi configuration. Equilibration leads to a mixture of (81) and (82) in a ratio of 4 1, but repeated recycling allowed the isolation of (82) in 40% yield. A related synthesis was shown in Scheme 26. 

Hansa Yellows, 1, 334 5, 299 Hantzsch synthesis, 2, 87-88 1,4-dihydropyridine, 2, 482 thiazoles, 6, 294-299 A -thiazolines, 6, 314 Hantzsch-Widman names parent names, 1, 35 stem suffixes, 1, 12 Hantzsch-Widman system nomenclature, 1, 11-12 Hardeners in photography... 

Thiazoline, trans-2-amino-4,5-dimethyl-synthesis, 6, 310 2-Thiazoline, 2-aryl-synthesis, 6, 307, 308, 309 2-Thiazoline, 2-arylamino-tautomerism, 6, 248 2-Thiazoline, 2-dialkylamino-synthesis, 6, 308 2-liiiazoline, 5-imino-synthesis, 5, 461 2-"niiazoline, 2-mercapto-hydrolysis, 6, 272 oxidation, 6, 272 synthesis, 6, 307 2-Thiazoline, 2-methyl-aldehyde synthesis from, 1, 469 2-Thiazoline, 2-methyl-acetylation, 6, 270 acylation, 6, 270 H NMR, 6, 243... 

---