Benzothiazole 2-amino-, cyclization

Monosubstituted amino groups (e.g. anilino) in amidinothioureas can participate in this cyclization, as shown by the ready oxidation of l-(2V,jV -diphenylamidino)-3-phenylthiourea (98 R = H, Ar = Ph) (and its analogs) to 5-anilino-2-phenyl-3-phenylimino-AM,2,4-thia-diazoline (99 R = H, Ar = Ph).116 This reaction, in which the alternative cyclization to benzothiazoles might be expected to predominate,68... 

Azine approach. With the heteroatoms in the appropriate vicinal positions in the pyridine nucleus, cyclization with the missing one-carbon unit is by analogy to the preparation of benzothiazoles effected by using a carboxylic acid or its equivalents as for example in the preparation of (437) (77USP4038496). The use of a carbonate ester or its equivalents will yield 2-oxy, 2-amino or 2-thio substituted derivatives. 2-Amino derivatives are also available by cyclization of vicinal aminothiocyanates such as (438) (66CJC2465). 

On the other hand, oxidation of secondary 1,1-enediamines 176 with bromine results in the formation of isothioazole derivatives 179. The yields of the oxidation-cyclization reaction depend strongly on the substituent R2 (equation 71)21,143. It is noteworthy that oxidation of 177 under the same conditions does not furnish isothioazoles but, instead, benzothiazoles 180 are formed (equation 72)21. A similar product, 180, has been obtained in the case of the nitro-substituted enediamines of pyrrolidine143. The different outcomes of these reactions reveal that the reactivity of the secondary amino group of 1,1-... 

Difluorobenzonitrile and methylthioglycolate cyclize to give 4-fluorobenzo[fe]thiophene [91JFC(54)104]. The reaction of trifluoromethyl-substituted 2,4-dinitrochloro- and 2,6-dinitrochlorobenzene with alkyl thi-oglycolates and amino acid esters at room temperature in the presence of triethylamine follows the same mechanistic concept to yield trifluoromethyl-substituted benzothiazole and benzimidazole derivatives [88JFC(38)327] (Scheme 25). 

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