Ring Expansion to Thiazines

Ring Expansion to 1,4-Thiazines.— In recent years, Takamizawa and his co-workers have developed a general ring-expansion reaction of wide scope in the heterocyclic field. Applied to thiazolium salts, it provides a synthesis of 1,4-thiazines, an important example of which is the conversion of thiamine (100) into the thiazine (101) it is effected by the successive action of dialkyl acylphosphonates and alkali. 

Further application of this reaction to yet simpler starting materials, viz. 3,4-dimethylthiazolium bromide (110), has given entirely comparable results [(110) (111) (112 R = Me or Ph)]. The use of additional 

Takamizawa, Y. Hamashima, H. Sato, and S. Sakai, Ghent, and Pharnt. Bull. (Japan), 1969, 17, 1356. 

Organic Compounds of Sulphur, Selenium, and Tellurium PhCHaN S 

Rii Expansion to 1,4-Thiazines.— Takamizawa s ring-expansion reaction of thiazolium salts to 1,4-thiazines by the use of dialkyl acylphosphonates (see Vol. 2, p. 605 and Vol. 3, p. 577) has been extended further.  

Compound (26) is (7-methylated by diazomethane in DMF on the carbonyl oxygen atom. Compound (27 X = O) reacts similarly with the same reagent in dioxan, but, in DMF, compound (28 X = O) is formed also. Likewise, compound (28 X = NH) is formed in DMF from compound (27 X = NH).  

Compounds (28 X = O or NH) are believed to arise by sequential 0-methyl-ation and electrophilic attack by the species MczN CHOMe. 

Reactions of Thiazoles with Dimethyl Acetylenedicarhoxylate.—A re-examination of the adducts formed between thiazoles and dimethyl acetylenedicarhoxylate, using X-ray and n.m.r. techniques, has been reported. The primary adduct (29 R, R , R = H, R = COaMe) formed from thiazole apparently undergoes rearrangement, either by a [l,5]-sigmatropic shift or via the vinyl sulphide, to give compound (29 R = COaMe, R , R , R = H). The compounds 2-, 4-, and 5-mono- and 2,5-di-methyIthiazole yield similar products (29 R = COaMe, 

5-Aryl-4-hydroxy-thiazoles react with dimethyl acetylenedicarhoxylate to give ylides (30 R = H or Ph). These react further with the ester to give intermediates (31 R = H), which lose sulphur to yield a pyridone, or intermediates 

Dimerization.—The lithio-salts of thiazoles[e.g. (58)], though stable at low temperatures, rearrange and dimerize to (60) at room temperature, by way of ketenimines (59), in 90% yield. The dimers (60) are reconverted into the starting material (57) above 150 °C. The reaction is general to heteroaryl systems of type (61), and has also been performed using 2-methyl-5-phenyl-l,3,4-thiadiazole.  

Other ring-expansion reactions have already been mentioned in regard to addition reactions leading to pyrrolothiazoles (Section III. 3), which sometimes rearrange to 1,4-thiazines (333, 497). 

Another interesting case is afforded by 2-alkyl-N-phenacyl or N-acetonylthiazolium salt (239), which in basic medium gives an intramolecular cyclization product. According to Reid et al. (502), this could 

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Ring Expansion to 1,4-Thiazine. — Takamizawa s ring expansion of thiazolium salts to 1,4-thiazines by the use of dialkyl acylphosphonates (these Reports, Vol. 2, p. 605) has been extended to analogues (53)—(55) of thiamine. The synthesis of each of the model compounds was described in detail they gave, in general, the expected 1,4-thiazines (56) as the main products. For the extensive data, the original paper must be consulted. ... 

Ring Expansion to 1,4-Thiazines.—Further examples have been given of the Takamizawa ring-expansion of thiazoles (98) to 1,4-thiazines (99) (see these Reports, Vol. 2, p. 605), and its applicability to benzothiazoles has been demonstrated. Thus, the reaction of simple benzothiazolium salts (100) with diethyl acylphosphonates under the established conditions gave 1,4-benzo-thiazines of type (102), the structure of which was confirmed by an unequivocal synthesis. In contrast to the monocyclic adducts (99), the presumed intermediates (101) were not isolable. ... 

Ring Expansion to Thiazines. In continuation of their extensive work on the ring expansion of thiazoles to 1,4-thiazines (see p. 605), Takamizawa et have extended their studies to the comparable reaction of the 1,3,4-thiadiazole ring system. Thus, treatment of 4-substituted 1,3,4-thiadia-zolium iodides (173) with dialkylbenzoylphosphonates in dimethyl-formamide yields products identified by their spectral properties as 5,6-dihydro-4-substituted-5-oxo-2,6-diphenyl-477-l,3,4-thiadiazines (174). The course of this reaction is explained, in line with the one previously proposed for thiazolium salts, by the mechanism shown in Scheme 3. 

Takamizawa et al. developed a general ring-expansion reaction of heterocycles that, applied to thiazolium salts, yields 1,4-thiazines (496, 497) thiamine (220) reacts with dialkyl acylphosphonates (221) to give the tricyclic 1,4-thiazine (222) (498), which is easily hydrolyzed to dihydro-1,4-thiazinone (223) (499) (Scheme 106). In the case of thiazolium slats containing no functional groups (224), 1,4-thiazine derivatives (226) were directly obtained in fairly good yields (Scheme 107). 

Routes to dihydro-1,4-thiazines are more diverse (B-78MI22701). For example, ring expansion of the thiazolidine (273) by heating with elemental sulfur and n-butylamine affords a 3 1 mixture of the isomers (276) and (277) and it appears likely that these products are derived from their tautomers (274) and (275) respectively which are the initial reaction products (Scheme 118) (70LA(739)32). Thiazolidines also accompany dihydrothiazines as products when aldehydes or ketones are reacted with aziridines in the presence of sulfur and DMF or potassium carbonate and it seems certain that a similar mechanistic sequence is involved (79M425). 

Attempts to acylate 2-unsubstituted thiazolylium salts with dialkylacylphosphonates under basic conditions yield an intermediate (72) which rearranges with ring expansion affording a 1,4-thiazine (73 Scheme 38). Under the same reaction conditions, 2-unsubstituted benzothiazolylium salts give 1,4-benzothiazines of type (74 Scheme 39). 

When the thiazine ester (708) was treated with an isocyanate such as (709), an imidazo[5,1 -c][l,4]thiazine (710) was produced (81JAP8161384). Treatment of certain penicillin sulfoxide esters (711) with ethoxycarbonyl isocyanate results in a ring expansion of both rings to afford an imidazo[5,l-c][l,4]thiazine (712) (81JOC3026). 

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