A Cu₂O/TBAB-promoted approach to synthesize heteroaromatic 2-amines via one-pot cyclization of aryl isothiocyanates with ortho-substituted amines in water

Abstract

An efficient approach to heteroaromatic 2-amine from one-pot desulfurization/dehydrogenative cyclization of aryl isothiocyanates with ortho-substituted amines in water was developed. This access tolerated a wide range of functional groups on...

A Facile Synthesis of 2-Aminobenzoxazines Based on Iodine­Catalyzed Desulfurative Cyclization

“…Benzoxazine and its derivatives are important scaffolds in biologically active molecules such as pharmaceuticals and agrochemicals (Figure 1). 1 Previous methods for the synthesis of the benzoxazines include the cyclization of thioureas mediated by 1,3-dicyclohexylcarbodiimide (DCC), 2 and starting from isothiocyanates, hypervalentiodine(III)-mediated desulfurative cyclization, 3 cyclization using 1,1′-(ethane-1,2-diyl)dipyridinium bistribromide (EDPBT) as a brominating reagent, 4 cyclodesulfurization with triphenylbismuth dichloride, 5 a Cu 2 O/TBAB-promoted approach in water, 6 and cyclization mediated by stoichiometric iodine in the presence of a base 7 (Scheme 1). However, these methods suffer from harsh reaction conditions, moderate yields, and the use of expensive and/or stoichiometric amounts of reagents.…”

Hypervalent iodine(iii) promoted tandem reaction of o-fluoroanilines with formamides to construct 2-aminobenzoxazoles

“…Then, several oxidants (PhI (OOCCF 3 ) 2 (PIFA), 1-acetoxy-1,2-benziodoxol-3-(1H)-one (IB-OAc), and TBHP) were examined, and PIDA was found to be the most effective one (Table 1, entries 3 and 8-10). Notably, when carboxylic acids, in particular acetic acid or trifluoroacetate (TFA), were added to the reaction mixture, the yields of 3a increased significantly to 71%, 86% and 78%, respectively (Table 1, entries [11][12][13]. Addition of a base such as Cs 2 CO 3 or NEt 3 (Table 1, entries 14 and 15) decreased the yield of 3a.…”

“…Then, DMF coordinated to hypervalent iodine and the trifluoroacetate group dissociated from A or B to form intermediate C. A similar process of amide coordination to hypervalent iodine has been reported in the literature. 23 Subsequently, 4-bromo-2-fluoroani-line nucleophilically attacked the coordinated formamide, and then the formamide was released to give intermediate D. Since the yields of 3a were improved after the addition of the acid (Table 1 entries [11][12][13], perhaps the acid is able to activate the carbonyl oxygen of the amide, facilitating the nucleophilic addition of the aromatic amine. Intermediate E was produced by intramolecular nucleophilic substitution.…”

“…Moreover, the direct synthesis of 2-aminobenzoxazoles utilizing N -(2-hydroxyphenyl)- N ′-arylthiourea via intramolecular desulfurization cyclization has been reported (Scheme 1c). 10 Other important routes to generate 2-aminobenzoxazoles were from 2-aminophenols with either thioisocyanates, 11 isocyanides, 12 or amines, 13 N -cyano- N -phenyl- p -toluenesulfonamide (NCTS), 14 di(imidazole-1-yl)methanimine, 15 and cyanoguanidine 16 as amine surrogates for cyclization (Scheme 1d). With regard to green and sustainable chemistry, further research into mild and metal-free methods to access diverse 2-aminobenzoxazoles from readily accessible precursors remains a great challenge.…”

Synthesis of Organosulfur and Related Heterocycles under Mechanochemical Conditions

“…The notable advantages of this method over the previously reported conventional ones are solvent-free, one-pot operation, in situ generation, and subsequent reaction of the reactive and toxic intermediate, isothiocyanate, and isolation and purification of the product through simple washing of the reaction mixture with water followed by recrystallization from EtOH/H 2 O and thus avoiding the use of huge amount of hazardous organic solvent in the workup and column chromatographic purification of products …”