Reaction with benzothiazoles

Reaction with benzothiazole. McKillop and Sayer have clarified the reaction of benzothiazole (1) with DMAD for which conflicting results had been reported. Under strictly anhydrous conditions the 1 2 adduct (2) is formed, albeit in low yield. If water is present, (3) is formed in virtually quantitative yield. The chemists suggest that an initial dipolar adduct (a) is formed, which can react with DMAD to form (2) or with water to form (b), which rearranges to (3). 

Kost et al. have studied related reactions of 2-acyl-1-phenylpyrazolidines (422) and l-phenyl-2-thiocarbamoylpyrazolidines (423). The former are converted on reaction with phosphorus oxychloride into tetrahydropyrimido[l,2-a]indoles (424) (72CHE57) and the latter into tetrahydropyrimido[2,l-f ]benzothiazoles (425) under the influence of acidic agents (80CHE169). 

Similarly, for 2-(p-substituted-anilino)benzothiazoles (180 181), the relative proportions of the isomeric A -methyl derivatives produced on reaction with methyl iodide in neutral solution has been related to... 

Methylphenyl)benzothiazole (80IC762) and 2-benzylbenzothiazole (95ICA(239)125) can be cyclopalladated. In the latter case, cylopalladation occurs upon reaction with palladium(II) acetate and gives the product 80. With lithium chloride, sodium bromide, or sodium iodide, a series of three products of substitution of the acetate group 81 (X = C1, Br, I) results. Pyridine, 2- and 3-methylpyridine, 2,6- and 3,5-dimethylpyridine cause the transformation of the chelate complexes 81 (X = C1, Br, I) and formation of the mononuclear products 82 (R = z= R" = = R = H, X = Cl, Br, I ... 

The reaction with sulfides occurs efficiently only when the resulting carbon-centered radicals are further stabilized by a a-heteroatom. Indeed, (TMSfsSiH can induce the efficient radical chain monoreduction of 1,3-dithiolane, 1,3-dithiane, 1,3-oxathiolane, 1,3-oxathiolanone, and 1,3-thiazolidine derivatives. Three examples are outlined in Reaction (12). The reaction of benzothiazole sulfenamide with (TMS)3SiH, initiated by the decomposition of AIBN at 76 °C, is an efficient chain process producing the corresponding dialkylamine quantitatively. However, the mechanism of this chain reaction is complex as it is also an example of a degenerate-branched chain process. 

Mannich and double-Mannich reaction with [l,2,4]triazolo[3,4- ]benzothiazole-3-thione 178 and />-toluidine, phenylenediamine, and benzidine, in the presence of formaldehyde, gave compounds 72-74 (unreported yields) (Scheme 3) <2002MI3, 2002MI4>. 

The reaction of dimedone with 3-alkyl-5-ercapto-1,2,4-triazoles 315 in the presence of NBS gives intermediates, which after reaction with a solution of aqueous sodium carbonate afford 2-alkyl-5a-hydroxy-6,6-dimethyl-8-oxo-5a, 6,7,8,8a-hexahydro[l,2,4]triazolo[3,2-3]benzothiazoles 49. Finally, reaction with PPA provides the dehydrated heterocyclic derivatives 316 (Scheme 30) <1999IJH127>. 

Trying to prepare precursors for the synthesis of 3-substituted [l,2,4]triazolo[5,l- ]benzothiazoles, 2-hydrazino-4-methylbenzothiazole 393 was submitted to reaction with formic acid, urea, carbon disulfide, and acetic anhydride to give compounds 230, 238, 89, and 394 (Scheme 45) <1998IJC(B)921>. 

Malononitrile and cyanoacetamide only give aminopyrans. However, in reaction with cyanoacetic ester 27b aminopyran 233 has been isolated from the mother liquor and also side product 234 from the cooled mixture. Mechanistic considerations have been proved by the isolation of a deace-tylated intermediate (95M615). Similar transformations occur in the synthesis of spiropyrans 235 from benzothiazole 236 (97G605) (Scheme 90). 

In the case of the benzothiazole system, both aldehydes and mixed ketones have been synthesized by reduction or alkylation of the appropriate carbonyl precursors. The carbonyl compounds are in turn prepared from the benzothiazole-2-anion either directly by reaction with esters or indirectly by reaction with aldehydes followed by PCC oxidation (Scheme 154) (85H2467 91BCJ3256). 

The reaction of benzothiazole (386a) with DMAD has been shown to give a mixture of products consisting of 513 (34%) and 387 (small amounts). However, Ogura and co-workers have reported that benzothiazole reacts with DMAD to give a mixture of the initial addition product 387 and an abnormal addition product 514 (Scheme 82). 

An unusual sulfur-nitrogen donor, benzothiazole-2-thiolate (58), has been reacted with Vaska s complex to produce 59 in high yield no bidentate adducts of 58 are produced even in refluxing solvent (156). Upon reaction with dioxygen, the extremely sensitive and reactive complex 60 is produced. Addition of water to 60 caused rearrangement to the carboxylate complex 61, while the addition of sulfur dioxide to 60 produces 62 (see Scheme 11). A proposed mechanism for the reaction of water with 60, based on labeling experiments, was outlined and can be found in Scheme 12. 

The synthesis of chloromethylthio heterocycles, e.g., 127 had been described by Goralski and Burk193 in the reaction of benzothiazole-2-thiones, 2-pyridinethiones, and 2-quinolinethiones with chlorobromomethane. In the case of l,3,4-thiadiazole-2,5-dithione, the reaction was made with the preformed alkali metal salt. 

Dihydro allyl adducts like (254) are obtained by reaction of thiazoles with allyltributyl tin in the presence of alkyl chloroformates acting as activators of the thiazole ring (Scheme 28) (94JOC1319). This reaction most likely takes place via the intermediate azolium salt. Under these conditions even organolithium compounds can add to thiazoles (84TL3633). Similarly, direct ethynylation of thiazole and benzothiazole can be achieved by reaction with bis(tributylstannyl)acetylene (Scheme 29) (94SL557). 

Zinc ethanoate behaves similarly to mercury(II) ethanoate on reaction with 2-(2-pyridyl)benzothiazole and gives complexes of a ring-opened ligand.928... 

The reaction of t with 1-methylimidazole is reported by Kaupp and Gunter (136) to yield the addition product 77. Unlike the reaction of It with 1-methylpyrrole, the formation of 77 does not require acid catalysis. The formation of 77 is proposed to occur via the 1,2-biradical intermediate 78, which undergoes a 1,3-hydrogen atom migration to yield 77 (eq. 27). The reaction of It with benzothiazole also yields an acyclic adduct 79 and a second adduct 80 as the major products. Both 79 and 80 are proposed to arise via a 1,4-biradical intermediate similar to 78. Irradiation of t-1 with caffeine (81) yields a [2+2] cycloadduct 82 and an acyclic adduct 83, analogous to 80, as the major products. 

Both 2-(p-tolyl)-5-phenylthiazole and 2-(p-tolyl)benzothiazole can be converted to the corresponding stilbene derivatives (see Table IX) by reaction with aromatic aldehyde anils under the influence of potassium hydroxide.11 Also, 2,5-bis(p-tolyl)thiazolo[5,4 /]thiazole (118) yields,... 

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