Thiazole synthesis

Thiazolium salts can be obtained successfully by a modification of the Hantzsch s thiazole synthesis. This method is particularly valuable for those thiazolium compounds in which the substituent on the ring nitrogen cannot be introduced by direct alkylation, for example, aryl or heteroaryl thiazolium salts (Scheme 42). 

Imidazo[ 1,2-e]thiazoles biological activity, 6, 1024 reactions, 6, 1041 synthesis, 6, 1048 Imidazo[2, l-6]thiazoles electrophilic substitution, 6, 979 synthesis, 6, 992, 993, 1010, 1018 Imidazo[3,l-6]thiazoles synthesis, 6, 986 Imidazo[5,l-6]thi azoles biological activity, 6, 1024 synthesis, 6, 1017 Imidazo[2,l-6]thiazolium chloride synthesis, 6, 1013... 

Pyrrolo[3,4-d]thiazole-4,6-dione, 5-ethyl-2-phenylazo-synthesis, 6, 1005 Pyrrolof 1,2-c]thiazoles reactions, 6, 1040 synthesis, 6, 988, 1047 Pyrrolo[2,1 - ijthiazoles synthesis, 6, 293, 992 1 /7,3/7-pyrrolo[l,2-c]thiazoles synthesis, 6, 1006 Pyrrolo[3,2-d]thiazoles synthesis, 6, 1009... 

Thieno[2,3 -h]selenophenes lithiation, 4, 950 Thienospirans synthesis, 4, 760 Thieno[3,4-c][l,2,5]thiadiazoles cycloaddition reactions, 6, 534 reactions, 6, 1036 synthesis, 6, 1042, 1044 Thieno[2,3-d]thiazole, 2-acylamino-synthesis, 6, 1010 Thieno[2,3-d]thiazoles synthesis, 5, 116 6, 988, 994 Thieno[3,2-d]thiazoles synthesis, 5, 135 6, 1015 Thieno[3,4-d]thiazolidine-2-thione, perhydro-... 

Further investigation on this type of thiazole synthesis in subsequent years led to the preparation of 5-aminothiazoles in which the 2-position was varied through reaction of the aminonitrile with salts and esters of dithioacids, carbon disulfide, carbon oxysulfide, and isothiocyanates. 

Phenyliodonium ylids of cyclic dicarbonyl compounds (46) react with thiourea to form the thiouronium ylid (47) which on heating is converted into the fused thiazole (48), this method is applicable to subtituted thioureas provided they have at least one free amino group. This reaction can be considered to be a modification of the Hantzsch thiazole synthesis <96JHC575>. 

Another modification of the Hantzsch thiazole synthesis afforded C-4 thiazolylmethyl phosphonium salts (49). These ylids could then undergo Wittig condensations to furnish a wide variety of 2,4-disubstituted thiazoles <96TL983>. 

Aguilar, E., and Meyers, A. I. (1994). Reinvestigation of a modified Hantzsch thiazole synthesis. Tetrahedron Lett. 35, 2473-2476. 

The reaction of difunctional nucleophiles with alkyl isocyanides has been described in an earlier section on imidazoles an example of the use of this simple approach in thiazole synthesis is illustrated in Scheme 114.169... 

A general scheme, which constructs the thiazolo variety of various bridgehead heterocycles, is basically an extension of HTIB-mediated modification of Hantzsch thiazole synthesis (Scheme 51). Thus, synthesis of 3-substituted-5,6-dihydro-4//-imidazo[2,l-b]thiazoles 202 has been achieved by the treatment of a-tosyloxyacetophenones (generated by the oxidation of 51 with HTIB) with ethylenethiourea [92JCS(P1)707], The method is successfully extended to synthesize 4,5,6,7-tetrahydrothiazolo[3,2-a]pyrimidines 203... 

Thiazoles, synthesis of, 6, 8 Thiele-Winter acetoxylation of quinones, 19, 3... 

Reacting this with thiourea in the classic scheme of thiazole synthesis by reacting of a-halogencarbonyl compounds with thioamides forms the ethyl ester of (Z)-2-(2-aminoth-iazole-4-yl)-2-hydroxyminoacetic acid (32.1.2.74). The amino group in this molecule is protected by a reaction with triphenylchloromethane in dimethylformamide in the presence of triethylamine, which gives the ethyl ester of (Z)-2-(2-tritylaminothiazole-4-yl)-... 

Van Leusen and Wildeman101 have realized a 1,3-thiazole synthesis, using the reagent TosMIC (tosylmethyl isocyanate) (56)102 and CS2. 

Qualitatively the novelty of reactions is difficult to assess. One can for example compare a novel reaction with different similar reactions known from literature in terms of mechanism, educts and products and scope and limitation. Scheme 3.4 compares three reactions Schollkopf s thiazole synthesis, the thiazole 4-CR described by us in 1999 and the classical U-4CR. The shaded areas show the common educts and products of these reactions. Obviously reaction 2 has common educts and products with reactions 1 and 3. Each reaction also has at least two unique components. The products of all the reactions are not identical. Thus reactions 1... 

Several variants of this useful and novel MCR thiazole synthesis have since been reported, including complexity-oriented syntheses of thiazolo-/> -lactams [18], in which two ring systems and five heavy atom bonds are newly formed (2 C-N, 2 C-S, 1 C-C), solid phase synthesis [19], and a Passerini variant of this reaction leading to 2-hydroxymethyl thiazoles [20], Scheme 3.13 illustrates some of the possibilities [21]. 

The mechanism of this oxazole formation is identical to that of the Hantzch thiazole synthesis. However, because of the reduced nucleophilicity of a carbonyl group as compared to a thiocarbonyl (due to the higher electronegativity of oxygen), this synthesis only proceeds under vigorous conditions (high temperatures, amide component as solvent, etc). 

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