Thiazolo thiadiazole

Thiazolo]2,3-hj f 1,3,4 thiadiazoles [C2N2S-C Sj. 2-Amino-5-allylthiothia-diazole is acylated with RCOCl to give amides, which undergo cyclization with NaOH to yield 5-methyl-[l,3] thiazolo[2,3-Z ] [1,3,4] thiadiazol-4-ylium-2-amidates (220). ° These amidates are alkylated, giving thiazolothiazolium salts. 

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Equimolar amounts of aromatic aldehydes, thioglycolic acid and thionohydrazides in sulphuric acid at room temperature afforded 2-methylthio-5-aryl-5ff-thiazolo[4,3-h]-l,3,4-thiadiazoles in a one pot procedure <96HC243>. 

Thiazolidinones 290 give substituted thiazolo[4,3-A [l,3,4]thiadiazoles 112, 113, and 291 after intramolecular cyclization mediated by concentrated sulfuric acid (Equation 39) (Table 51) <2001IJC(B)440, 2004IJC(B)901, 1996JCR(S)388>. 

The reaction of 3-methyl-6-(4-chlorophenyl)[l,2,4]triazolo[3,4-7]-l,3,4-thiadiazole 319 with thioglycolic acid gives thiazolo[2,3-3]-.r-triazolo[3,4-7][l,2,3]thiadiazol-6(7//)-one 320 (Equation 56) <2002IJH167>. 

Because of its importance in biological areas, special efforts have been made with the synthesis of the thiazolo[2,3-t]-[l,2,4]thiadiazole derivative 308 <2001BML1805>. The pathway started from the benzothiazole derivative 305 which was treated with chlorosulfonylacetyl chloride to form an intermediate 306, which underwent cyclization to a second intermediate 307 with hydrogen chloride elimination. The last step is the attack of the first intermediate 306 at the thiadiazine carbon atom to form the final product 308. 

In the case of thiazoline-2(3//)-thiones, the mesoionic thiazolo[2,3-h][l,3,4]thiadiazoles are obtained by two different routes (Scheme 65). On the one hand, thione 166 reacts with isothiocyanate via intermediate 167 and with a second equivalent isothiocyanate to afford the mesoionic 168 on the other hand, in the presence of isocyanate, the thione preferentially dimerizes 167 with the open-chain carbodiimide 169 to give the mesoionic 170. Addition of acid with removal of an amine group converts 170 into the symmetric heteroaromatic amine (171) (88CB1495 92T1285). The related transformation of an imidazoline into 1,3,4-thiadiazoles has also been described (90T4353). 

Molina et al. were able to prepare the mesoionic thiadiazole (292) from iminophosphorane 297 and carbon disulfide. As Scheme 106 shows, 298 reacts with a,w-dihalo compounds to form dimer 299 [91JCS(P1)1159]. The synthesis of the mesoionic thiazolo[2,3-6][l,3,4]thiadizole is described in (92T1285). 

Compound 185 can also be obtained by direct bromination of the corresponding thiazolo[3,2-ft][l,2,4]triazole (Bt2, acetie acid) (91AP49). Bromination at C-5 can also be affected by bromine/NBS in chloroform (72YZ935). Thiocyanation, which was possible in the imidazo[2,l-b]thia-zole and -[l,3,4]thiadiazole series (see Sections VI,B,l,a and VII,B,l) failed (72YZ935). 

The condensation reaction of cyclic amidines with trichloromethylsulfenyl chloride yields sul-fenamides, which afford 5-arylimino-l,2,4-thiadiazolines on treatment with aromatic amines <84CHEC-I(6)463>. An example of this type of reaction starting from 2-amino-4-arylthiazoles (271) affords 3/f-thiazolo[2,3-c]-l,2,4-thiadiazoles (272), via the sulfenamide (270) (Scheme 60) <88IJC(B)501>. 

The last step in a stereospecific total synthesis of ( )-biotin consists of the facile reaction of the precursor diamine with phosgene (equation 5) (77JA6754). The reaction of a cyclic amidrazone precursor with phosgeniminium chloride gives thiazolo[3,2-6]-s-triazoles (equation 6) (73AG(E)405). Treatment of 4,5-diaminopyrazoles with thionyl chloride forms pyrazolo[3,4-c][l,2,5]thiadiazoles (equation 7) (68JMC1164). 

The effects of solvent (polarity), temperature, and substituents (the Hammet cr constants) have been studied in the azide-tetrazole equilibrium for thiazolo [2,3 -e]tetrazoles (75BSB1189 77CJC1728, 77JHC1299) oxazolo[2,3-e]- and isoxazolo[2,3-d]-tetrazoles (77CJC1728) and tetra-zolo[4,5- >]-1, 3,4-thiadiazoles (81CHE721). A rough parallelism has been proposed between the azido-tetrazole isomerism and prototropic tau-tomerism (75BSB1189). 

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