Thiazole reaction with DMAD

The reaction of 2-(phenylamino)- and 2-(dimethylamino)-thiazoles (38) with DMAD produced dimethyl 6-(phenylamino)- and 6-(dimethylamino)-3,4-pyridinedicarboxyl-ates exclusively. The intermediate 2 + 2-cycloadduct (39) undergoes ring opening, 6jr-electrocyclization with the extrusion of sulfur to produce the final pyridine derivatives (40) (Scheme ll).38... 

Reaction of thiazoles with DMAD illustrates the overall reaction and the rearrangements which may be encountered. Thiazole or 2-methylthiazole (411 R=H and Me, respectively) in DMF reacted with DMAD to give an initial 1,4-dipolar species (412). Reaction with a second DMAD gave the 1 2 molar adduct, presumably (413). Ring opening to (414), followed by cyclization in the alternative mode, resulted in the formation of (415), the structure of which (R = Me) was established by X-ray analysis (78AHC(23)263) (see also Chapter 4.19). 

Addition reactions of several thiazole and benzothiazole derivatives to DMAD have been reported. Thiazole (383a), for example, gives a 1 2 adduct (384a) on treatment with DMAD, whereas in the reaction of 2-ethylthiazole (383b), a S,6-dihydrothiazolo[3,2-a]azepine (385) is... 

Benzothiazole 3-oxide reacts with some dipolarophiles yielding 2-substituted ben-zothiazoles (Scheme 53) (70CPB1176). 1,4-Cycloadditions of dipolarophiles are observed with mesoionic thiazoles. The 4- and 5-hydroxythiazolylium hydroxide inner salts (95) and (98) react with dipolarophiles, such as electron-deficient alkynes, to give cycloadducts which react further by extrusion either of sulfur (96) or of a simple molecule (97, 99 Scheme 54). An example is given for the reaction of DMAD with 4-hydroxy-2,3-diphenylthiazolylium... 

Cycloaddition reactions between thiazoles and DMAD give 1,2-adducts (76TL3463). Three isomers (414)-(416) are formed in the reaction with 5-phenylthiazole, which has been rationalized as shown. 

Dipolar cycloadditions lead to six-membered rings. Rearrangements may be encountered. Thiazole or 2-methylthiazole 132 (R = H and Me) with DMAD forms an initial 1,4-dipolar species 133. Reaction of 133 with a second molecule of DMAD gives a 1 2 adduct, presumably 134. Ring opening to 135, followed by cyclization in the alternative mode, results in 136 (Scheme 82) <1978AHC(23)263>. For the similar reactions of pyridine with DMAD and pyridazine with maleic anhydride, see Section 3.2.1.3.7. 

Photochemistry. The photochemical reaction of benzisothiazoles (46 R = H) with DMAD gives a mixture of [48 Z (30%), E (50%)] and the substituted benzothiophen (47) (Scheme 5). 5-Chlorobenzisothiazole behaves similarly. A mechanism involving initial cleavage of the thiazole ring to a diradical has... 

Only 2,3-dihydropyrrolo[2,l-(>]thiazoles have been described. Reaction of 7V-acetylthiazolidine-2-carboxylic acid (303) in the presence of acetic anhydride provides mesoionic oxazolone intermediates (304) which undergo 1,3-dipolar cycloaddition with DMAD, to give unstable intermediate (305) which rapidly eliminates carbon dioxide to give 2,3-dihydro-5-methylpyrrolo[2,l-( ]thiazole-6,7-dicarboxylate (306) (Scheme 55) <88JMC1427>. 

Dimethyl-3,5-dimethyl-l//,3//-pyrrolo[l,2-r ][l,3]thiazole-6,7-dicarboxylate 399 (R = H) was prepared from cysteine 396 using the method developed of Padwa et al. <1989JOC644>. The thiazolidine carboxylic acid 397 (R = H), obtained by reaction of the cysteine with formaldehyde, was heated in the presence of acetic anhydride and DMAD to give the sulfide 399 by dipolar cycloaddition of the acetylene to the intermediate dipole 398 (Scheme 59) <2002J(P1)1795>. 

An innovative new route to the secondary amines 198 (R2 = alkyl) has recently been described (05OL1343, 05JOC8919). This novel approach involves a multicomponent reaction of thiazole carbenes, DMAD and aryl, a,/J-unsaturated or aliphatic aldehydes. The thiazole carbenes are generated in situ by treatment of a thiazolium salt with sodium hydride (Scheme 34). The yields of 3-aminofurans 198 are moderate... 

The thiazolium-mediated three-component reaction of thiazolium salts 201, aryl aldehydes and dimethyl acetylenedicarboxylate provides a facile synthesis of 2-amino-2-arylfurans 202 <05OL1343>. The reaction pathway may involve the sequential nucleophilic addition of thiazol-2-ylidene 203 with the aldehyde and DMAD to form the spirocyclic intermediate 204 through the simultaneous formation of two C-C bonds and a C-O bond Selective ring opening of the spirocyclic intermediate 204 followed by hydrolysis leads to 3-aminofuran 202 via 205. 

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