477-Pyrrolo thiazoles

Pyrrolo[2,l-A]thiazoles [CgNS-CiN].—An A -ray crystallographic study has been made of 3,6-dimethyl-5-thioformylpyrrolo[2,l-A]thiazoIe (see Vol. 3, p. 643). 

Thieno[2,3- /]tliiazoles [C3NS-C4S].—The thieno[2,3-d]thiazoles [72 R = R = Me R R = (CHa)4] may be prepared by heating 2-acylamino-3-thiocyanato-thiophens in ethyl benzoate.  

7 Structures Comprising One Five-membered and One Six-membered Ring (5,6) 

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- 

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Fluorophenyl)indol-l-ylzinc chloride 3-(Pyridin-3-yl)-l /7,3-f -pyrrolo[l, 2-c]thiazole-7-carbonyl chloride >45 [8]... 

In aprotic conditions acetic anhydride sodium acetate induces formation of a fused ring through an intra molecular condensation. It results in a pyrrolo[2,l-fc]thiazole (39), which constitutes an interesting intermediate for the synthesis of dyes (Scheme 18) (40). 

H,5H-Pyrrolo[l,2-c]thiazole-6,7,8,9-tetracarboxylic acid, 3,5-etheno-5-methyl-, tetramethyl ester H NMR, 6, 977 (80JOC5396)... 

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... 

A type Ilbc approach to pyrroles was employed in the synthesis of pyrrolo[2,l-fc]thiazoles <06S1433>. The key step involved a formylation with the Vilsmeier-Haack reagent followed by a cyclocondensation of the putative iminium intermediate. 

The synthesis of pyrazolo[4,3-rf]-l,2,3-triazine starting from a pyrazolo-3-carbaldehyde derivative has been reported <00JIC168>. Azolo-l,2,4-triazine derivatives have been prepared via the reaction of functionalized thiazole derivatives with several heterocyclic diazonium salts <00JCR(S)206>. The reaction of 1,2,4-triazolium salt 67 with alkene 68 gives the pyrrolo[2,l-/][l,2,4]triazine 69 <00H(53)213>. 

Pyrrolo[l,2-A]thiazoles are aromatic compounds but only one fully conjugated derivative has been described. A few dihydro and tetrahydro derivatives have been prepared, mainly in connection with search for biologically active drugs. Saturated compounds are also known. 

Only 2,3-dihydropyrrolo[2,l-3]thiazoles have been described. When refluxing in POCl3, compounds 378 were found to give pyrrolo[2,l-b]thiazole derivatives 379 in good yields. Formally, this reaction is like a Chichibabin pyrrolothi-azole synthesis however, in contrast with the basic conditions used in the typical procedure, acidic conditions were employed in the present case (Equation 66) <2004S2317>. 

When dimethyl-2,2-dioxo-5-methyl-177,377-pyrrolo[l,2-r-][l,3]thiazole-6,7-dicarboxylate was heated under flash vacuum pyrolysis at 700°C/10 3mmHg, sulfur dioxide was eliminated and the vinylpyrrole 391 was obtained, which can be explained by allowed suprafacial [1,8]H shifts in the 871 1,7-dipolar system 390. Concerted sigmatropic shifts can only occur when the methyl groups adopt an inward (Z)-conformation (Scheme 57) <2002J(P1)1795, 2004TL3889, 2005JOC6629>. 

Reaction of the thia-amino acid 392 with trifluoroacetic anhydride gave the 2,2,2-trifluoro-l-[7-(trifluoromethyl)-l//-pyrrolo[l,2-c]-[l,3]thiazol-6-yl] ethanone pyrrole 395. The formation of the pyrrole can be rationalized by a sequence involving trifluoroacetylation of the enamine 392 affording dione 393 followed by loss of water and carbon dioxide to give the aromatic product 395. These decarboxylations afford fluorinated derivatives of heterocyclic skeletons known to exhibit interesting biological activity (Scheme 58) <2000T7267>. 

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>. 

The sulphur TT-electron analogue of indolizine, pyrrolo [2,1-6 ]-thiazole [ 178], and some methyl substituted derivatives protonate in... 

Anderson et al. (67,68) used the mtinchnone generation-DMAD trapping protocol to synthesize various pyrrolizines as potential antileukemic agents, such as 111 and the pyrrolo[l,2-c]thiazoles 112. 

Gyorgydeak et al. (69) converted a series of 2-substituted 3-acyl-l,3-thiazoli-dine-4-carboxylic acids (113) into the corresponding pyrrolo[l,2-c]thiazoles (115)... 

Pinho e Melo et al. (89) employed an intramolecular miinchnone cycloaddition to constmct several l/7-pyrrolo[l,2-c]thiazole derivatives from N-acylthiazolidines and acetic anhydride. Martinelli and co-workers (90,91) employed an intramolecular miinchnone cycloaddition to craft a series of 4-keto, 5,6,7-tetrahydroindoles (168-171) in two steps. The requisite acetylenic precursors were prepared from glutaric anhydride (or 3-methylglutaric anhydride). The overall sequence is illustrated for the synthesis of 168. An electrophilic acetylenic unit appears to be necessary for successful intramolecular 1,3-dipolar cycloaddition. 

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