Alkylations and acylations of .alpha.-(aryl)-4-morpholineacetonitriles (masked acyl anion equivalents) and their use in 1,4-additions

Microwave‐Assisted Synthesis of Polysubstituted 4‐Quinolones from Deprotonated α‐Aminonitriles

“…[8,9] Their alkylation with α-haloesters yields intermediates that slowly release HCN with formation of enamino esters. [10] In the case of aniline-derived aminonitriles, these compounds are susceptible to the Conrad-Limpach cyclization, which would permit the three-step synthesis of polysubstituted 2-aryl-4-quinolones from an aniline, an aromatic aldehyde, and an α-haloester (Scheme 1). The concentrations of base and aminonitrile 3 were of great importance for the suppression of the formation of byproducts.…”

Synthesis of 4‐aroyl‐5‐nitro‐1H‐imidazoles and 4‐aroyl‐5‐aminoimidazoles

“…Recrystallization from methanol with the aid of activated carbon gave 2.7 g (38%) of white crystals, mp 239-241O; 'H nmr (deuteriochloroform): & 2.50 (5,3,CH,),(m,4,aromatic). 7;H,5.5;N,20.9. Found: C,65.4;H,5.5;N,21.0.…”

“…Heterocyclic Chem., 23, 913 (1986) 4-Aroyl-5-nitro-1H-imidazoles 1 and 4-aroyl-5-amino-lHimidazoles 2 are potentially useful intermediates for the synthesis of imidazo-pyrimidines; however, routes to 4-aroyl-5-nitroimidazoles have not been reported. While there are a number of specific syntheses of 5-amino-imidazoles which contain cyano [ 1-31, alkoxycarbonyl[2,3], carboxamide [2] sulfonamide [4] and formyl[5] substituents at the 4-position, only one report [3] describes 5-amino-4benzoyl derivatives 4 (R = H, CH,) via cyclization of 3.Our interest in a-aryl-4-morpholineacetonitriles as aroyl anion equivalents [6-81 and the fact that such carbanions displace halogen from activated halobenzenes [7] (such as 4-fluoronitrobenzene) prompted us to study the reaction of 4-bromo-2-methyl-5-nitroimidazole (5) with aroyl anion equivalents. To avoid anion exchange with the NH of the imidazole 5, a blocking group on the nitrogen is required.…”

“…Our interest in a-aryl-4-morpholineacetonitriles as aroyl anion equivalents [6-81 and the fact that such carbanions displace halogen from activated halobenzenes [7] (such as 4-fluoronitrobenzene) prompted us to study the reaction of 4-bromo-2-methyl-5-nitroimidazole (5) with aroyl anion equivalents. To avoid anion exchange with the NH of the imidazole 5, a blocking group on the nitrogen is required.…”

The Chemistry of Deprotonated α-Aminonitriles

“…Aryl and hetaryl halides susceptible to nucleophilic aromatic substitution by means of an addition-elimination sequence may be subjected to nucleophilic acylations with deprotonated Strecker products. 147,148 Albright and Moran used their rugged lithiated (morpholin-4-yl)arylacetonitriles 170, which often give superior results compared to dialkylamino substituted nucleophiles, 149,150 to effect halide substitution on 1-benzyl-5-bromo-2-methyl-4-nitroimidazole. 151 The primary products were subsequently converted into the corresponding aryl ketones 172 by treatment with copper sulfate pentahydrate (Scheme 28, top).…”