Thieno isothiazoles

Thieno[2,3-c]isothiazoles. - The reaction of (78) with Na in liquid NH3 and then H2O gives 5-methoxythieno[2,3-c] isothiazole (79).  

Isothiazolo[3,4-6]pyridines - Diazotization of 3-amino-5-cyanoisothiazolo-[3,4-Z)]pyridines (80) and coupling with m-diethylaminoacetanilide gives the corresponding azo-compounds (81). Other similar compounds are also described.  

Isothiazolo[5,4-d]pyrimidines. - 5-Formyl-6-mercaptouracil, when treated with NH2OH, gives isothiazolo[5,4- i] pyrimidine (82). This compound is also prepared by heating the oxime (83) with NaSH. 

Hirota, T. Asao, T. Fujioka, and S. Senda, Nippon Kagaku KaisM, 1981, 721 (Chem. Abstr., 1981, 95, ISO 597). 

Naphtho[2,l-t/]isothiazole. - The compound (85) is prepared by the reaction of 1-halo-2-(dihalomethyl)naphthalene or l-halo-2-formylnaphthalene with S and NH3, at elevated temperature and pressure, in the presence of an alcohol.  

---

Thieno[2,3-6]indoles synthesis, 4, 1074 Thieno[2,3-d]isothiazole, amino-synthesis, 6, 1016... 

Thieno[3,4-d]isothiazole, 2,3-dihydro-3-oxo-1,1-dioxide, 6, 989 biological activity, 6, 1024 Thieno[2,3-c]isothiazole-3-carboxylic acid synthesis, 6, 1023... 

Thieno[3,4-d ]isothiazole-4-carboxylic acid synthesis, 6, 1023 Thienoisothiazoles benzisothiazoles from, 6, 172 Thieno[3,4-c]isothiazoles reactions, 6, 1034 synthesis, 6, 1043... 

Double cyclizations can occur one interesting example is the formation of the thieno[2,3-c]isothiazole (97) from the cyano-substituted ketoester... 

Benzo[e]thieno[3,2- 7]thiepin-10(5fJ)-one 388 under Schmidt conditions undergoes a ring contraction into 2-benzylthieno[3,2-d]isothiazol-3(2fJ)-one 390 through initial intermediate 389 by nitrogen loss and intramolecular nucleophilic... 

In other investigations by the authors (2,3), poly(thieno[3,4-d]isothiazole), (II), and 2-pentafluorosulfanyl-thieno[3,4-b]thiophene, (III), respectively, were prepared. Poly(thieno[3,4-d]isothiazole) was prepared using (NH SaOg... 

The electron-withdrawing effect of the isothiazole unit is evident in the proton chemical shifts of H-3 and H-4 in 5-phenylfuro[3,2-d]isothiazole (15), V-methyl-5-phenylpyrrolo[3,2-parent monocyclic heterocycles <80BSB773,85KGS223). As expected, changing the orientation of the isothiazole subunit (i.e., thieno[2,3-c]isothiazole (17)) vis-a-vis the thiophene subunit has little effect on the chemical shift of H-4 (see structures (14a) and (17)) <82AJC385>. 

Direct alkylation has been reported for thieno[3,2-c]isoxazole (4) and 5-phenylfuro(pyrrolo or thieno)[3,2-rf]isothiazoles (14)-(16) to afford the hydrolytically sensitive jV-methylisothiazolium salts (31) (Equation (6)) <85KGS223> and N-alkylisoxazolium salt (32) (Equation (7)) <76CS165>. In contrast, thieno[2,3-c]isothiazole (17) is a weak base and does not react with alkyl halides <82AJC385>. 

Few examples of photochemical transformations of the 10n heterocycles in this series have been reported. Notable is the conversion of thieno[2,3-c]isothiazoles (33) to thiophenes (37) by homolytic cleavage of the nitrogen-sulfur bond (Scheme 4). The enedithione (34) which arises from the initial diradical may undergo (a) cyclization via the bicyclic thiirane (35) or (b) electrocyclization to the 1,2-dithiine (36) <88H(27)2539>. Since similar rearrangements do not occur with isothiazoles, benzoisothiazoles, or the isomeric thieno[3,2-d]isothiazoles, this unique transformation is a direct consequence of the thieno[2,3-c]annelation. However, substituent effects on the efficiency of the transformation have not been explored. 

Few examples of substitution reactions on intact heterocycles have been reported. Notable is the synthesis of 3-aminothieno[3,4-d]isothiazole 1,1-dioxides (51) by the fusion of thieno[3,4-d]iso-... 

This approach is used exclusively for the synthesis of the isomeric annelated isothiazoles and isoselenazoles. The first reported example was the phosphorus pentasulfide-mediated cyclization of a-ketoester (61) to the thieno[2,3-c]isothiazole (17) (Scheme 13) <82AJC385). A wide variety of oxidative cyclization conditions, some including an amination step, have been employed for the... 

---