Benzothiazole, derivatives, preparation

The first examples were benzene disulfonimide derivatives prepared from o-benzenebis(sulfonyl chloride) or -disulfinic acid with amines or HNO2 respectively <84CHEC-I(6)914>, or benzothiazole derivatives (94) obtained from benzenesulfonamides or azides containing ortho SR or SOR groups... 

Another important way in which to achieve reaction with electrophiles is to utilize silyl derivatives (prepared in turn via metallation chemistry). Thus, for example, 2-silyl-thiazoles and -benzothiazoles react readily with esters <2001JME1286>, ketones <2005JOC8556>, and aldehydes <2001T4729>, all facilitated by fluoride from TBAF. Acid chlorides <2004JOC8903> do not require fluoride assistance. 

Benzimidazoles, (II), and benzothiazole derivatives, (III), effective as a1L-adrenoreceptor agonists were prepared by Jeon (2) and used in treating incontinence in women. 

Benzothiazole derivatives, (II), prepared by Scott (2) were useful as tyrosine inhibitor kinases and used in the treatment of hyperproliferative diseases, especially cancer. 

The Jacobson thioanilide radical cyclization has been frequently used for the synthesis of benzothiazoles as shown by the preparation of benzothiazole derivative 32 <07JMC1087>. The harsh reaction conditions (K3Fe(CN)6, NaOH, H20, EtOH, 90°C) can be overcome by using 2,6-dichloro-3,5-dicyano-l,4-benzoquinone (DDQ) (CH2CI2, 25°C) <07TL669>. This reaction probably proceeds via thiyl radical 35, which undergoes 1,5-homolytic radical... 

Benzothiazolo 3.2-a 1 quinolines C NS-C -N-Ce-Cel. The previously unknown quinolinium salt (313 X=C1 ) was prepared by photo-induced cyclisation of the corresponding benzothiazole derivative (314)326. 

Two mild and metal-ffee methods for the preparation of two types of benzothiazole derivatives (2-acylbenzothiazoles 86 and dialkyl benzothiazol-2-ylphosphonates 87) have been developed (14JOC8407). One method uses tert-butyl hydroperoxide (TBHP) which triggers a-carbon-centered phosphite radical formation, while the other involves di-tert-butyl peroxide (DTBP) which induces phosphorus-centered phosphonate radical formation. The two types of radicals lead to two different reaction pathways direct C2-acylation of benzothiazoles to give 86 and C2-phosphonation of ben-zothiazoles to afford 87. 

Bognar et al have employed this general synthesis for the preparation of monosaccharides incorporating benzothiazole. Thus, the condensation of o-aminothiophenol with acetylated aldonic acid chlorides (16) or nitriles (17) readily affords the benzothiazole derivatives (18), which may be deacetylated to the parent monosaccharides by treatment with alkali. 

Metal Complexes.—A variety of benzothiazole derivatives continue to serve as ligands in the preparation of metal complexes. ... 

The relative ease of preparation of condensed thiazole derivatives is a consequence of facile thiazole ring closure, and therefore also benzothiazole amines with an amino group on the benzene ring (except for the weakly regioselective nitration of benzothiazoles) are very easily accessible and useful substrates for the Gould-Jacobs reaction. 

Some modifications of the procedures B and C have been reported for the preparation of 5-(benzothiazol-2-yl)- or 5-acetyl derivatives 22 (88AP509) and 23 [87ZN(B)107], The use of the sulfur precursor 24 (85S432) or nonsulfur starting components 26 [87ZN(B) 107] led to biheter-ocyclic 4//-thiopyrans 25 or 27, respectively. 

Two modifications of the well-known benzothiazole preparation have been employed to prepare unusual heteropoly cycles. Konig et al.ils treated l-thiocarbamoyl-l,2,3,4-tetrahydroquinoline (236) with bromine in chloroform to give the thiazolo[3,4,5-J,i]quinoline derivative 237. In a process which requires disruption of the resonance stabilization of the pyridine ring, Harris416 reported that treatment of l-(2-pyridyl)-2-thiourcas with sulfuryl chloride or with bromine gives the hydrohalide salts of 2-imino-2//-[l,2,4]thiadiazolo[2,3-a]pyridines (238). 

Benzothiazoles have been prepared by oxidative condensation of aldehydes with resin-bound 4-mercapto-3-aminobenzoic acid derivatives (Entry 8, Table 15.18), and by dehydration of 2-mercaptoanilides (Entry 9, Table 15.18). Oxidation of 2,3-di-hydrobenzothiazoles to benzothiazoles can occur spontaneously, without the need of any additional oxidant [231]. Polystyrene-bound 4-iodobenzoate reacts with thiazole in the presence of Pd(0) to yield a 4-(4-thiazoIyl)benzoate (Entry 10, Table 15.18). If Cul is added to the reaction mixture, however, the 4-(2-thiazolyl)benzoate results [141]. 

This second mode of preparation of benzothiazoles is also well established and represents a general method for the cyclization of derivatives of arylamines. The main derivatives adapted to the formation of the thiazole ring include A-arylthioamides, arylthioureas, aryl isothiocyanates, esters of arylthiocarbamic acids and esters of aryldithiocarbamic acids. Their cyclization results from the action of an appropriate oxidizing agent. 

Azine approach. With the heteroatoms in the appropriate vicinal positions in the pyridine nucleus, cyclization with the missing one-carbon unit is by analogy to the preparation of benzothiazoles effected by using a carboxylic acid or its equivalents as for example in the preparation of (437) (77USP4038496). The use of a carbonate ester or its equivalents will yield 2-oxy, 2-amino or 2-thio substituted derivatives. 2-Amino derivatives are also available by cyclization of vicinal aminothiocyanates such as (438) (66CJC2465). 

Azine approach. Oxidative cyclization of iV-thioacetyl derivatives of anilines is a common method for the preparation of benzothiazoles. The reaction may also be applied to the azine analogues, but may proceed less readily because of the decreased nucleophilidty of the ring. In the cyclization of the pyridazine (439) the oxidizing agent is alkaline potassium ferricyanide (75JHC337). 

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