2- 3- benzothiazole

Benzothiazole (pK, = 1.2) is a weaker base than thiazole (pKg = 2.52). Protonation occurs at the N-atom alkyl halides give N-alkylbenzothiazolium salts. 

Electrophilic substitution occurs only in the benzo part of benzothiazole nitration, for instance, with HNO3/H2SO4 at room temperature affords a mixture of aU possible (4, 5, 6, 7) monosubstitution products. 

The SNAr-reaction 1 2 proceeds about 400 times faster than the corresponding substitution with methoxide at 2-chlorothiazole. 

N-Alkylbenzothiazolium ions are readily ring-opened by hydroxide ion [340]  

The resulting thiophenols 3 have been utilized for the synthesis of benzo-N,S-heterocycles (in analogy to thiazolium ions, cf. p. 202). 

The most important derivative of benzothiazole, commercially, is 2-mercaptoben-zothiazole, which is obtained in 95% yield by the reaction of aniline with CS2 and sulfur (see Chapter 5.5.3.2). 

This is an example of nucleophilic catalysis. The aduct from the ylide and pyruvic acid eliminates carbon dioxide to give an enamine which accepts a proton on its exocyclic C-atom. Upon removal of a proton, this intermediate product decomposes to the nucleophilic catalyst and acetaldehyde [99]. 

Compounds structurally similar to thiamine, e.g. 5-(2-hydroxyethyl)-3,4-dimethylthiazolium iodide 13, in the presence of triethylamine, catalyse the condensation of aldehydes to acyloins [100]. By analogy to a cyanide ion, the ylide acts as a nucleophilic catalyst. 

Thiazoles occur in nature as substances with an aromatic odour, for instance 4-methyl-5-vinylthiazole in the aroma of cocoa beans and passion fruit, 2-isobutylthiazole in tomatoes and 2-acetylthiazole in the aroma of roasted meat. 

Many thiazole derivatives are biologically active compounds. For instance, 2-(4-chlorophenyl)-thiazole-4-acetic acid 14 is a pharmaceutical used as an anti-inflammatory agent and niridazol 15 is applied in the treatment of bilharzia (schistosomiasis). 

By analogy to the synthesis of benzoxazoles, benzothiazoles Eire obtained by cyclocondensation of o-aminothiophenols or their salts with carboxylic acids, their derivatives or with aldehydes [101]  

Annweiler E, W Michaelis, RU Meckenstock (2001) Anaerobic cometabolic conversion of benzothiophene by a sulfate-reducing enrichment culture and in a tar-oil-contaminated aquifer. Appl Environ Microbiol 67 5077-5083. 

Besse P, B Combourieu, G Boyse, M Sancelme, H de Wever, A-M Delort (2001) Long-range H- N heteronuclear shift correlation at natural abundance a tool to study benzothiazole biodegradation by two Rhodococcus strains. Appl Environ Microbiol 67 1412-1417. 

Bressler DC, PM Fedorak (2001a) Purification, stability, and mineralization of 3-hydroxy-2-formylbenzothio-phene, a metabolite of dibenzothiophene. Appl Environ Microbiol 67 821-826. 

Gilbert SC, 1 Morton, S Buchanan, C Oldfield, A McRoberts (1998) Isolation of a unique benzothiophene-desulphurizing bacterium, Gordona sp. strain 213E (NCIMB 40816), and characterization of the desulphurization pathway. Microbiology (UK) 144 2545-2553. 

Five hundred grams (4.14 moles) of dimethyl aniline and 800 g. (25.0 gram atoms) of sulfur are heated to reflux for 18 hours and 

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Studies on benzothiazoles indicate that sulfenamide formation probably occurs via the mechanism given for the formation of 132 (Scheme 67)... 

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 first empirical and qualitative approach to the electronic structure of thiazole appeared in 1931 in a paper entitled Aspects of the chemistry of the thiazole group (115). In this historical review. Hunter showed the technical importance of the group, especially of the benzothiazole derivatives, and correlated the observed reactivity with the mobility of the electronic system. In 1943, Jensen et al. (116) explained the low value observed for the dipole moment of thiazole (1.64D in benzene) by the small contribution of the polar-limiting structures and thus by an essentially dienic character of the v system of thiazole. The first theoretical calculation of the electronic structure of thiazole. benzothiazole, and their methyl derivatives was performed by Pullman and Metzger using the Huckel method (5, 6, 8). 

The first mass spectrometric investigation of the thiazole ring was done by Clarke et al. (271). Shortly after, Cooks et al., in a study devoted to bicydic aromatic systems, demonstrated the influence of the benzo ring in benzothiazole (272). Since this time, many studies have been devoted to the influence of various types of substitution upon fragmentation schemes and rearrangements, in the case of alkylthiazoles by Buttery (273) arylthiazoles by Aune et al. (276), Rix et al. (277), Khnulnitskii et al. (278) functional derivatives by Salmona el al. (279) and Entenmann (280) and thiazoles isotopically labeled with deuterium and C by Bojesen et al. (113). More recently, Witzhum et al. have detected the presence of simple derivatives of thiazole in food aromas by mass spectrometry (281). 

The same isomerization also occurs with diarylthiazoles, but when two adjacent phenyl groups are present, even in the final product, a photochemical cyclization gives rise to a polycyclic benzothiazole (Scheme 3) (213,218,219). 

The piC values of polymethine dyes depend on terminal group basicity (64) thus the protonation abHity diminishes if the basic properties of the residues decrease, passing from benzimidazole, quinoline, benzothiazole, to indolenine. On the other hand, the piC of higher homologues increases with chain lengthening. The rate constant of protonation is sensitive to other features, for example, substituents and rings in the chain and steric hindrance for short-chain dyes. 

MET, mercaptobenzothiazole TMTM, tetramethylthiuram mono sulfide TMTD, tetramethylthiuram disulfide and CBTS, Al-cyclohexyl-2-benzothiazole... 

Oxidation of the hydrazone of 2-hydrazinopyrazole (226) with Pb(OAc)4 in CH2CI2 is a two-step reaction. The azine (227) was formed as an intermediate and this underwent ring closure to the 3H-pyrazolo[5,l-c][l,2,4]triazole (228) (79TL1567). A similar reaction applied to the benzal derivative of 2-hydrazinobenzothiazole (229) gave 3-phenyl-[l,2,4]triazolo[3,4-6]benzothiazole (230) together with a by-product (231) (72JCS(P1)1519). 

Ethyl propiolate reacted with (416) in boiling benzene giving ethyl l-oxo-2-phenyl-liT-pyrido[2,l-6]benzothiazole-4-carboxylate in 83% yield, and no trace of the other possible isomer was found. 

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). 

Benzothiazole, 3-methyl-N-ethyl-N-(3-cyanoethyl)aniline-4,2 -azo-6 -nitro-visible, 1, 343 <67MI11201)... 

H,12H-Dibenz[67]azocin-6-one, 5-benzoyl-AG7AG+, 7, 705 <73JCS(P1)205) Dibenzo[e,g]benzothiazol-l-ium, l-ethyl-2-[A -(1 -ethyl-2 -dibenzo[e,g]benzothiazolylidene)-3-y lidene-1 -propen]-1 -yl-visible, I, 345 B-76MI11201)... 

H NMR, 3, 893 (73X2009) 6H-Pyrano[2,3-e]ben20thiazole-8-carboxylic acid, 2-methyl-6-oxo-MS, 3, 615 (70JCS(C)1553) 8ff-Pyrano[3,2-/]benzothiazole 6-carboxylic acid, 2-methyl-8-oxo-MS, 3, 615 <70JCS(C)1553)... 

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