2-Benzothiazoles

Nalepa and E. Bulka, Acta Univ. Palacki Olomuc., Fac. Return Nat., 1978, 57,191 (Chem, Abstr, 1980, 92,215 326). 

A new route to 2-chloro-phenothiazines that contain C atoms has been described in which 2-amino-4-chlorobenzenethiol is condensed with [2- C]cyclohexanone to give the spiro-2,3-dihydrobenzothiazole (91) acylation of (91) followed by treatment with sulphuryl chloride gives a mixture of (92) and (93).  

Lebedenko, Deposited Document, 1978, VINITI 1805-78 (Chem. Ahstr., 1980,92,94 288). N. Yu. Deeva, Sint. Issled. Biol. Soedin., Tezisy Dokl. Konf. Molodykh Uch.,6th, 1978. 30 (Chem. Abstr., 1980,92. 215 323). 

An interesting formation of partially hydrogenated benzothiazoles involves the reaction between 1-trimethylsilylcyclohexene (and its 4-t-butyl derivative) and iodine/lithium thiocyanate. The reaction occurs in a highly regio- and stereoselective manner to give the adducts (100 R = H or CMca), which subsequently react with KOH in MeOH to give (101).  

Type D Syntheses (5—A—C). A novel ring-contraction of benzo-1,2,4-thiadiazines (102), which extends the scope of a similar benzoxazine reaction, takes place either thermally, in the presence of tervalent phosphorus compounds, or photochemically (but in lower yields) to give the benzothiazoles (103).  

Synthesis. - From oviho-Aminobenzenethiols (Type A S-C 4 N + C). The cyclization between RNC and 0-NH2C6H4SH gives a 2-substituted benzothiazole.  

Type B Syntheses of Benzothiazoles (CfJBs-N-C-S). Following a known method, arylthioureas were oxidized to give substituted 2-aminobenzo-thiazoles and 2-[(2-thioxoimidazolidin)-3-yl] benzothiazole by bromine, and substituted 2-aminobenzothiazoles by SOCl2 or Br2 (CI2) and 

Type E Syntheses (C Hs-N + C-S). Treatment of substituted anilines with NH4SCN gives substituted 2-aminothiazoles and there are also references concerning the synthesis of benzothiazoles. 

FIVE-MEMBERED HETEROCYCLES FUSED TO A BENZENE RING 

Replacement of the urethane carbonyl function by an aromatic ring leads to a benzo-thiazole that is described as an immune function modulator. In an analogous approach to that used above, anilinothiol (63-1) is condensed with the thiocarbamoyl chloride (63-2) again in the presence of a base. This leads directly to frentizole (63-3) [66]. 

Dopamine and dopamine-like compound have been found to alleviate Parkinson s disease symptoms. One of the main problems in this treatment devolves about the difficulty of delivering compounds to the brain. A benzimidazole with a reduced 

Haiogen, CN, COjEt, etc R = phenyi, substituted phenyi, NHBn Pd = PdCij, PdCijCcod), PdBtj 

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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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