Benzothiazole radical substitution

The reaction of nucleophilic radicals, under acidic conditions, with heterocycies containing an imine unit is by far the most important and synthetically useful radical substitution of heterocyclic compounds. Pyri-dines, quinolines, diazines, imidazoles, benzothiazoles and purines are amongst the systems that have been shown to react with a wide range of nucleophilic radicals, selectively at positions a and y to the nitrogen, with replacement of hydrogen. Acidic conditions are essential because A-protonation of the heterocycle... 

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]. 

Thiadiazolines and thiadiazolium salts can undergo a thermally promoted rearrangement to yield 2-guanidinoben-zothiazoles. Thus the thiadiazoline 42 when heated in ethanol at reflux affords the benzothiazole 43 (Equation 11). There is evidence to suggest that this could be an electrophilic aromatic substitution reaction but a free radical mechanism was also proposed <2003SC2053>. 

Heating thiazole with phenylazotriphenylmethane at 75 °C for 24 hours affords 2-phenyl-5-triphenylmethyl thiazole (75 Scheme 43). The 1-adamantyl radical and other nucleophilic alkyl and acyl radicals react with 2-substituted benzothiazoles in a homolytic ipso substitution yielding the corresponding 2-alkyl or 2-acylbenzothiazole (Scheme 44) (77CC316). 

Recently, the synthesis of 2-substituted benzothiazoles has been reported via an intramolecular cyclization of arylthioamides 237 by using hypervalent iodine reagents (typically Dess-Martin periodinane, DMP) in CH2GI2 at ambient temperature. The reaction proceeds via a thiyl radical 238 in high yields (85-95%) to give benzothiazoles 239 and is also amenable to solid-phase synthesis (Scheme 95) <2006JOC8261>. 

There is an early report that thiophene reacts at the 3-position in phenylation with benzenediazonium chloride and aluminum trichloride,8 but in the Gomberg reaction thiophene has been found to substitute mainly at the 2-position both with p-tolyl and with p-chloro-phenyl radicals.04 Benzothiazole is phenylated at the 2-position in low yield by dibenzoyl peroxide a small quantity of the 4-isomer is also obtained.24... 

A copper-catalyzed redox condensation reaction between benzothia-zoles 101 and aldehydes (RCHO) or benzylic alcohols (RCH2OH) provides 2-aryl- and 2-alkyl-substituted benzothiazoles 102 (14TL1806).The reactions are carried out under mild conditions using environmentally benign TBHP as the oxidant. The proposed mechanism involves the ring opening of benzothiazoles initiated by the attack of an acyl radical on the thiazole ring followed by intramolecular condensation. This mechanism is based on the isolation of an anilide disulfide intermediate. 

In 2012, Li and coworkers [33] reported an aerobic visible-light-mediated protocol for the construction of 2-substituted benzothiazoles (Scheme 13.16). The authors found that the reaction mixture turned green early in the reaction, as is often considered an indication of the presence of Ru(bpy). As a result, a pathway involving oxidative quenching by molecular oxygen was proposed. Single-electron transfer between the deprotonated thioamide and the Ru(lll) species produces the radical 109, which facilitates radical cyclization followed by an aromatization cascade to yield the final products. 

Details of the reaction of 1-adamantyl and other radicals with 2-acyl-benzo-thiazoles, effecting displacement of the acyl group, have appeared. The reaction is facilitated by electron-withdrawing groups in the 5- and 6-positions of the benzothiazole nucleus. A related homolytic aromatic ip50-substitution occurs in the reactions of nitrobenzenes bearing electron-withdrawing para-substituents... 

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