Thieno thiazoles

The fused hetero rings of aromatic or pseudoaromatic character on the 4,5 bond as, for example, benzothiazole, naphthothiazole, thieno[2,3ci]-thiazole, benzthieno[2,3d]thiazole, and so forth (Scheme 8), do not appear in the tables. 

The 2-thienylthiourea (245) on oxidation with bromine in acetic acid gave the thieno[3,2-djthiazole (247). It has been suggested that the intermediate electrophilic sulfenyl bromide adds to the 2,3-bond of the thiophene ring to form (246) when then loses HBr to give (247) (71AJC1229, 78JHC81). Pyrazolo(3,4- /]thiazoles are formed in a similar fashion (76GEP2429195). 

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-... 

Thiazolo] 2,3fl) indole, in synthesis of chain-bridged thiazolocyanines, 58 Thiazolosemicyanines, tables of, 119 Thiazolostyryl dyes, tables of, 107 Thieno [ 2,3d ] thiazole. 30 2-[2-Thienyl) selenazole, formylation in 5-position, 239... 

Relatively few examples of metallation of the subject heterocycles have been reported. Metallation of thieno[2,3 i/ thiazole 9 with Bu"Li occurred at the 2-position of the thiazole ring the lithium salt could be reacted with electrophiles, for example, trimethylsilyl chloride to give 10, in good yield (Equation 4) <1998J(P1)685>. 

These methods are limited in scope. Direct thiation has been reported for the transformation of vicinal diketones to [3,4]-annelated thiophenes <1996CHEC-II(7)49>. Thionations and selenations of vicinal halomethyl ketones with thioacetamide or iV,iV-diethylselenopropionamide as sulfur and selenium donors, respectively, have also been reported <1996CHEC-II(7)49>. In a recent example, thieno[3,4-f]pyrazoles 160 were readily prepared from aryl 5-bromomethyl-l//-l-phenylpyrazole-4-yl ketones 159 by reaction with thioacetamide (Equation 35) <1998JHC71>. Additionally, an example of an amination cyclization by reaction of 161 with benzylamine to afford pyrrolo[3,4-i/ thiazole 162 has been described (Equation 36) <1998JHC71>. 

The 2-thienylthiourea (287) with bromine in acetic acid gives the thieno[3,2-d]thiazole (288) (71AJC1229,78JHC81). Pyrazolo[3,4-t/Jthiazoles are formed similarly (76GEP2429195). 

More recently, this approach was used in the synthesis of 3-(thiazol-2-yl)thieno [3,2-Z>]pyridines 137 from the corresponding ethylenedithiolates 138 (2003MI2). 

The synthesis of some new substituted thieno[2,3-Z>]thiophenes (369)-(372) has been achieved <93BCJ201l> in a one-pot reaction employing solid-liquid phase transfer catalysis (PTC) conditions (K2C03, benzene, tetrabutylammonium bromide catalyst) and starting from acetylacetone, CS2, and a-chloro compounds in 1 1 2 molar ratio. The reaction of acetylacetone and CS2 with ethyl chloroacetate, chloroacetonitrile, 2-(chloroacetylamino)thiazole, or chloroacetanilide was carried out under PTC conditions by stirring the reactants reaction times and temperatures were optimized. The corresponding thieno[2,3-6]thiophenes (369)-(372) were obtained in excellent yields (51-93%). 

The isomeric thieno[3,4-J]thiazoles (45), selenolo[3,4-d]thiazoles (46), and furo[3,4-d]isoxazoles... 

Table 1 Thieno[2,3- thiazoles (X = S), furo[2,3- thiazoles (X = O), selenolo[2,3- thiazoles (X = Se).

Thiation is used predominantly for the synthesis of annelated thiazoles (e.g., (109)—(111)) from heterocyclic acylamides bearing either adjacent phenol or halogen substituents (Equations (33)— (35)) (70KGS1624, 77KGS1495, 87KGS410). The thieno[3,2-c]isothiazolium perchlorate (113) was obtained from the 2-benzoyl-3-(phenylamino)thiophene (112) by sequential reaction with phosphorus pentasulfide and perchloric acid (Equation (36)) <77CJC1123>. 

Other one-carbon closures include the synthesis of the thieno[2,3-d]thiazoles (125) from the thiolamine (124) and orthoesters (Equation (40)) <88JPR866> and the thermal cyclization of the isothiocyanate (126) to the 2-acylthieno[2,3- /]thiazoles (127) (Equation (41)) <74KGS1204>. 

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