From 2-aminothiazole

Halothiazoles are usually obtained from 2-aminothiazoles through the Sandmeyer reaction. Nevertheless, ammonolysis has sometimes proved useful for the preparation of 2-aminothiazole derivatives. Detweiler et al. (18) obtained 2-(u-pyridinylamino)thiazole (1) from 2-bromothiazole (Scheme 1). The reaction is easier if a nitro group occupies the 5-position of the thiazole ring (19-21). Ethylene diamine derivatives undergo this reaction with 2-haiothiazoles (22-24). 

Decomposition of diazonium salts obtained from 2-aminothiazole (4) (29, 34. 35) could be an interesting reaction to introduce O in A-4-thiazoline-2-one. Acidic hydrolvsis of ethers (36. 37). oxidative hydrolysis... 

The replacement of 2-amino group by a hydrogen can be achieved by diazotization, followed by reduction with hypophosphorous acid (1-8, 13). Another method starting from 2-aminothiazole is to prepare the 2-halo-thiazole by the Sandmeyer reaction (prepared also from the 2-hydroxy-thiazole), which is then dehalogenated chemically or catalytically (1, 9, 10). 

All four 2-halogenothiazoles are known. 2-Chloro (l- ll). 2 bromo (1, 2. 5, 8-10, 12-24), and 2-iodothiazole (8, 10, 25, 26) can be prepared from 2-aminothiazole by Sandmeyer reactions, with yields between 30... 

The only case of this type reported in the literature concerns the preparation of the substituted hydroxy-thiazolo [3,2 -a -benzimidazole 408 from 2-aminothiazole 407 and 1,4-benzoquinone in glacial acetic acid (Equation 185)... 

A benzotriazole-assisted synthesis of ethyl 5-aminoimidazo[2,l-h]thia-zole-6-carboxylate 65 has been developed (96TL1787). Traces of compound 63 were isolated from 2-aminothiazole 23 using benzotriazole and freshly distilled ethyl glyoxylate in benzene, whereas by application of a-benzotria-zolyl-a-morpholino acetate with methyl iodide in THF, 63 was isolated in 40% yield. Subsequent treatment of 63 with potassium cyanide in ethanol at rt involves substitution of the benzotriazole moiety. Intramolecular cycli-zation of 64 yields 65, albeit in 10% yield. a-Ketoester 66 is also obtained (Scheme 3). 

Hydroxythiazolo[3,2-fi][l,2,4]triazoles (176, R = OH) are also available by this route. Treating 167 with methyl chloroformate (sodium hydroxide) and subsequently with sodium methoxide yields 176 (R = OH) (71GEP1942015 72GEP2032173, 72USP3682943). Thiazolo[3,2-fi][l,2,4] triazoles are also available from 2-aminothiazoles via amidines 178. Lead tetra-acetate dehydrogenation of 178 leads to 179 (94MI1). 

Aminothiazole is easily diazotized in a concentrated solution of nitric and phosphoric acid. A large-scale procedure for the diazotization of 2-aminothiazole and its conversion to 2-bromothiazole has been reported . The synthesis of 2-halothiazoles can be easily achieved from 2-aminothiazole by (i) diazotization and (ii) treatment with CuCl, CuBr, or Nal <85JHC1621>. When the diazonium salt derived from 2-aminothiazole is treated with sodium azide the 2-azido derivative in equilibrium with its tetrazole cyclization product are obtained <92BMC1603>. 

In addition to cyclization of 2-mercaptoadenines with dibromoethane to a mixture of [2,3-Z>] and [3,2-a] isomers (86, 85) shown in Scheme 23, the method starting from 2-aminothiazole also produced this heterocycle. This compound—a cyclic isothiourea—was condensed with ethyl nitrosocyanoacetate to 5-amino-6-nitroso-thia/o 1 o[3,2-nitroso group with sodium dithionite to 6-amino derivative 91 followed by acylation with acyl chloride yielded 5-amino-6-acylaminothiazolo[3,2-u]pyrimidin-7-one (92). Heating 92 with polypho-sphoric acid produced 2-aryl- or 2-heteroaryl-thiazolo[2,3-/)]purin-4(3//)-ones 93. 

Thiazolo- and benzothiazolopyrimidines are generally prepared by thermal cyclization of the enaminones prepared from 2-aminothiazoles and 2-aminobenzothiazoles with diethyl ethoxymethylenemalonate (Table IX). Two methods have been employed. Method A is a one-pot reaction of aminothiazoles with malonate in refluxing 1,2,4-trichlorobenzene without isolation of the enaminone intermediates. In method B. isolation of the enaminone intermediates prior to cyclization in trichlorobenzene usually provides purer products (72JMC1203). 

Thiazolo[3,2-a][l,3,5]triazines [C3NS-C3N3].—A further report of the synthesis of compound (73) from 2-aminothiazole (see Vol. 3, p. 645) has appeared, whilst the structure of the major product from the reaction of 2-amino-A -thiazoline with ethoxycarbonyl isothiocyanate has been confirmed as being 2,3,6,7-tetra-... 

Imidaz6[2,l-b]thiazoles (132) are further obtainable in good yield from 2-aminothiazoles (131) by the action of phenylacyl bromide, " or from 2-imino-3-(2-propynyl)-A -thiazolines (133) by alkahne cyclization. Thiocyanation of (132) and (134) yields the corresponding 5-thiocyanato-derivatives. The synthesis by established routes of further examples of this ring-system has been recorded. ... 

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