Benzothiazoles cyclization

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). 

Intramolecular cyclization of benzothiazole derivative 698 by a Claisen self-condensation afforded 699 (81JHC1273) (Scheme 120). 

Manganese(III)-promoted radical cyclization of arylthioformanilides and a-benzoylthio-formanilides is a recently described microwave-assisted example for the synthesis of 2-arylbenzothiazoles and 2-benzoylbenzothiazoles. In this study, manganese triacetate is introduced as a new reagent to replace potassium ferricyanide or bromide. The 2-substituted benzothiazoles are generated in 6 min at 110°C imder microwave irradiation (300 W) in a domestic oven with no real control of the temperature (reflux of acetic acid) (Scheme 15). Conventional heating (oil bath) of the reaction at 110 °C for 6 h gave similar yields [16]. 

Thiazolonaphthyridinium salts 331 can be produced either by bromination of the 2-alkenylpyridine precursor, or by thermal cyclization of the 2-(bromoacetyl)pyridine (Scheme 81) <1997CL1203>, and reaction of the pyrano-pyrimidine 332 with o-aminothiophenol gives the benzothiazole-fused pyridopyrimidinedione 333 (Equation 118) <2003JCCS887>. 

The Jacobson thioanilide radical cyclization chemistry has been extensively used for the synthesis of benzothiazoles as shown by the preparation of 4-fluoro-2-(3,4-dimethoxy-phenyl)benzothiazole 47 <06JMC179>. The harsh reaction conditions (K3Fe(CN)6, NaOH,... 

The Liebeskind group cross-coupled 4-chloro-2-cyclobutenone 69 with 2-tribuylstannyl-benzothiazole to synthesize a-pyridone-based azaheteroaromatics [48], The adduct 70 underwent a thermal rearrangement to afford a transient vinylketene 71, which then intramolecularly cyclized onto the C—N double bond of benzothiazole, giving rise to thiazolo[3,2-a]pyridin-5-one 72. In another case, 2-acetyl-4-trimethylstannylthizaole (73) was coupled with an acid chloride 74 to form the desired ketone 75 [49]. 

The reaction of compound 98 with Michael acceptors such as acrylonitrile in the presence of pyridine gives a product which reveals to be the /3-(3-hydroazino-l,2,4-triazolo[3,4-A]benzothiazole)propanenitrile 203, which on reflux with hydrochloric acid underwent hydrolysis, followed by simultaneous cyclization, forming 3-(pyrazol-5-one-l-yl)-[l,2,4]triazolo[3,4-A]benzothiazole 204 (Scheme 10) <2004IJH241>. 

Similarly, benzothiazol-2-ylcarbonylhydroximoyl chloride 255 reacts with 2-methylthiobenzimidazole in refluxing ethanol to give an intermediate that cyclizes to 3-(benzothiazol-2-yl)carbonylbenzimidazo[l,2-rf][l,2,4]oxadiazole 256 (Equation 33) <1997T17461>. 

Oxidative cyclization, promoted by manganese dioxide or phenyliodo(m) diacetate (PIDA), amidinobenzothiazoles 303 afford [l,2,4]triazolo[3,2- ]benzothiazoles 304 (Equation 48) (Table 52) <2001IJH315, 19960PP362>. 

Intermediate quinones 307 spontaneously cyclize in refluxing ethanol to give the corresponding [ 1,2,4]triazolo[3,2-4 -benzothiazoles 308 (Equation 51) <1997IJH255>. 

Because of its importance in biological areas, special efforts have been made with the synthesis of the thiazolo[2,3-t]-[l,2,4]thiadiazole derivative 308 <2001BML1805>. The pathway started from the benzothiazole derivative 305 which was treated with chlorosulfonylacetyl chloride to form an intermediate 306, which underwent cyclization to a second intermediate 307 with hydrogen chloride elimination. The last step is the attack of the first intermediate 306 at the thiadiazine carbon atom to form the final product 308. 

When position 4 of the 5-benzothiazole moiety (e.g., 962) was substituted, thermal cyclization in refluxing Dowtherm A for 10-15 min led to the linear thiazolo[5,4-g]quinolinecarboxylate (963) in 81% yield [77JAP(K)125196 79CPB1],... 

At this point, an unsuccessful attempt deserves to be mentioned. Creating a nonacidic procedure of benzothiazole syntheses. Bowman et al. (1982) tried to perform intramolecular cyclization according to reaction a, as depicted in Scheme 7.38. 

In some cases, ring opening of oxazolones and subsequent cyclization of the intermediate leads to new heterocyclic systems. For example, reaction of saturated 5(47/)-oxazolones with hydrazonoyl halides under phase-transfer conditions yields the 5-pyrazolones 249. Ring opening of 248 with 2-aminothiophenol generates benzothiazoles 250 (Scheme 7.80). ... 

Monosubstituted amino groups (e.g. anilino) in amidinothioureas can participate in this cyclization, as shown by the ready oxidation of l-(2V,jV -diphenylamidino)-3-phenylthiourea (98 R = H, Ar = Ph) (and its analogs) to 5-anilino-2-phenyl-3-phenylimino-AM,2,4-thia-diazoline (99 R = H, Ar = Ph).116 This reaction, in which the alternative cyclization to benzothiazoles might be expected to predominate,68... 

Singh and Lai [73IJC959 76IJC(B)685] prepared 8,9,10,11-tetrahydro-benzothiazolo[3,2-c]quinazolin-7-ium perchlorate (287) by dehydrative cyclization of 4-[(2-oxocyclohexyl)thio]quinazoline (286) with sulfuric acid and then perchloric acid. 2-(2-Azidophenyl)benzothiazole (288) reacted with triphenylphosphine to give the iminophosphorane, which cyclized to 289 on treatment with ethoxycarbonyl isocyanate (89T4263). 

Wikel and Paget153 showed that a benzyne intermediate was not participating in the cyclization of 154a to the fused benzothiazole 155 with sodium hydride since the isomeric chloro compound 154b did not give 155 either under the same conditions or on treatment with potassium amide in liquid ammonia. 

The first published example of the anodic cyclization with carbon-sulfur bond formation was the oxidation of thiobenzanilide to 2-phenyl-l,3-benzothiazole.120 The oxidation of the thioacetanilides (106) and /V-(3-coumaryl)thioacetamide (108) at a platinum electrode in CH3CN-Et4NC104 gave the expected 1,3-thiazole derivatives 107 and 109 in 60-75% yield169 [Eqs. (81) and (82)]. 

This method has found particular application in the synthesis of spiro-annelated chromenes, which are of interest because of their photochromic behaviour. The alkene is commonly a 2-methylenedihydroindole, which leads to spiro 2//-l-benzopyranoindolines, or the corresponding benzothiazole (67BSF2824). Provided a base is present to liberate the free heterocyclic base, indolinium or thiazolinium salts may be used in the synthesis. Enamine attack at the carbonyl group is followed by dehydration and cyclization (Scheme 9). 

Keywords 2-aminothiophenol, cinnamic acid, phenylpropynoic acid, condensation, cyclization, benzothiazepinone, benzothiazole... 

At this point, one unsuccessful attempt deserves to be mentioned. Creating a nonacidic procedure for benzothiazole syntheses, Bowman and co-authors (1982) tried to perform intramolecular cyclization according to the top line of Scheme 6-33. However, the cyclization did not take place, irrespective of solvent polarity or the strength of the base. UV irradiation did not help either. Nevertheless, the cyclization appears to be successful in the presence of acetone see the bottom reaction in Scheme 6-33 (Bowman et al. 1982). As usual, inhibitors stop this anion radical reaction 3-iodothiobenzanilide does not experience the cyclization. 

The synthesis of thieno[3,4-6][ 1,5]benzothiazepin-10(9/7)-ones (60) was carried out by cyclizing mercaptans 59 in the presence of polyphosphoric acid the reaction afforded compounds 60 and benzothiazoles 61 in approximately equal amounts. Lactams 60 were transformed into 10-piperazinyl derivatives 63 directly on treatment in refluxing toluene with piperazines or through the formation of iminochloride intermediates 62, which then reacted with an excess of piperazines under the same experimental... 

Reaction of recently synthesized 1 -al kvnyl />-( trifluoromethyl )phenyl]( tetrafluoro-borato)-X3-bromanes with 2-mercapto- benzimidazole or benzothiazole in dichloro-methane at 0°C under argon resulted in a domino Michael addition-carbene rearrangement-cyclization reaction to produce directly tricyclic heterocycles in high yields (Scheme 67).103... 

A convenient synthesis of l//-indolyl-2-benzothiazoles in moderate yield by the direct conversion of indole-2- and 5-carboxylates with in situ generated trimethylaluminum-2-aminothiophenol was described. [95H1045] 2-Substituted 1,3-benzothiazoles having a variety of substituents can be prepared from 2-methylthio-N-triphenylphosphoranylideneaniline and acid chlorides by iminophosphorane-mediated cyclization. [95H455]... 

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