The textile and dyeing industry have shown dramatic growth alongside synthetic chemistry in the last century. With operations and economic importance, challenges also increase, including environmental pollution, work safety, and...

This work demonstrates that the copper acetate promoted N-arylation of imides with boronic acids can be employed as a major method for the synthesis of N 3 -aryl hydantoins. Palladium-catalysed cross-coupling of organoboranes with organic halides or their equivalents is known as the Suzuki reaction 1 and provides one of the most general methods for the synthesis of stereodefined biaryls, alkadienes and trienes. The commercial availability of many boronic acids has further expanded organoboron chemistry. For instance, the copper(II) acetate mediated crosscoupling of aryl boronic acids with heteroatom nucleophiles reported by Chan, 2 Evans 3 and Lam 4 leading to the formation of O-and N-arylation products has modified and improved the Ullman and Goldberg reactions. 5 Other modifications have included the utility of potassium aryltrifluoroborates 6 (Batey), aryl iodonium salts 7 (Beringer-Kang), aryl lead compounds 8 (Barton), aryl bismuth compounds 9 (Barton), aryl stannanes 10 and aryl silanes 11 (Lam), as aryl-transfer reagents in cupric acetate promoted heteroatom-aryl bond constructions.During the last two decades, aryl hydantoins have found uses in many therapeutic applications. Mephenytoin 12 has anti-convulsant action while phenytoin 12 displays anti-arrhythmic, anti-convulsant and anti-neuralgic behaviour. Fosphenytoin 13 is a sodium channel antagonist effective for combating epilepsy, and nilutamide 14 is a non-steroidal orally-active anti-androgen used for the treatment of metastatic prostate cancer. BIRT-377 is a lymphocyte function antigen-1 antagonist, 15 RU 56279 the precursor of RU 58841 is a topically-active non-steroidal antiandrogen 16 with therapeutic applications in the treatment of skin disorders such as acute acne, androgenetic alopecia (male-pattern baldness) and hirsutism (female excess hair). These, and other N 3 -arylated hydantoin compounds, 17 are generally prepared by base-mediated cyclisation reactions of amino esters with isocyanates or phosgene to construct the substituted hydantoin. We report here the first direct approach to the synthesis of N 3 -aryl hydantoin derivatives using copper(II) acetate promoted cross-coupling of triaryl bismuthanes with aryl boronic acids.Our initial approach involved the N-arylation of the sodium hydride generated 5,5-dimethyl hydantoin N 3 anion reacting with fluoro or chloro aryl halides (Scheme 1), but on a 10-g scale the product yields were disappointing and did not exceed 30%.Inspired by the achievements of the research groups of Buchwald 18 and Hartwig, 19 who developed the popular Narylation of amides, carbamates and hydrazides using palladium-mediated protocols, our efforts to transfer this methodology to imide N-arylation was fruitless. We then revisited the well-defined arylation of heteroatoms using aryl bismuthanes first reported by Barton 9 and Chan. 20 Scheme 1 Nucleophilic aromatic substitutionThe results of the N-arylation of succinimide, phthalimide and 5,5-dimethylhydantoin (Scheme 2) are provided in Table 1. The slow imide N-arylatio...

Acids. -The N-arylation of nitrogen heterocycles including the chemoselective N3-monoarylation of 5,5-dimethyl hydantoin is easily achieved with boronic acid or triarylstibines in the presence of Cu(II) acetate. -(HUEGEL*, H. M.; RIX, C.

No abstract