Urea derivatives, alkyl acyl

Isocyanates derived from the higher aliphatic amides react more rapidly with the haloamide salts than with water and alkali, so that, when these amides are subjected to the Hofmann reaction in aqueous mediiun, only small amounts of the expected amines are formed. Although amines arise from the hydrolysis of the alkyl acyl ureas, they are largely oxidized to nitriles by the excess of hypobromite present. 

Matthews et al. described a synthetic route to hydantoins as well as thio-hydantoins on solid-supported esters in 1997 [136,137]. The hydantoin or thiohydantoin skeleton is synthesized on Wang resin by addition of an amino acid and following reductive alkylation. For the release of hydantoins, acylation with an isocyanate to urea derivatives with following base promoted cleavage takes place. For the preparation of thiohydantoins, isothiocyanates have to be reacted with the corresponding precursors these intermediates cyclize without additional treatment with bases to the corresponding thiohydantoins. 

Isocyanate, Me, 431 phenyl, 431 Isocyanates, 58 acyl isocyanates, 92 alkyl isocyanates, 92, 118 aryl versus alkyl, 118 with hydrazinothiazoles, 100, 106 with 2-imino-4-thiazolines, 125 to mesoionic compounds, 65 to thiazolyl urea, 58, 92 Isoindolenine derivative, 56 Isomerism, E-Z equilibrium, 23 Isomerization, catalyst in aji-unsaturated acids, 438... 

Solid-phase scavenger methods are employed with increasing frequency as a prehminary reaction cleanup step in combinatorial chemistry, and have recently become commercially available (Argonaut, Calbiochem-Novabiochem, Varian, Alltech). lilly researchers first reported on this approach, employing sohd supported electrophiles and nucleophiles for reaction purification in acylation and alkylation reactions. Yield and purity values reported were 90-95% and 50-99%, respectively, for a library generated by reductive amination. Parke-Davis researchers achieved the removal of known reaction product impurities by the application of custom synthesized polymer supported reagents, specifically polystyrene-divinylbenzene supported derivatives of methylisocyanate and tm(2-aminomethyl)amine for cleanup of by-products resulting from urea, thiourea,sulfonamide,amide, and pyrazole libraries. 

Alkyl-, vinyl-, and aryl-substituted acyl azides undergo thermal 1,2-carbon-to-nitrogen migration with extrusion of dinitrogen — the Curtius rearrangement — producing isocyantes. Reaction of the isocyanate products with nucleophiles, often in situ, provides carbamates, ureas, and other A-acyl derivatives. Alternatively, hydrolysis of the isocyanates leads to primary amines. 

Chemical. A large number of chitin and chitosan derivatives have been synthesized through modification of the primary (C-6) and secondary (C-3) hydroxyl groups present on each repeat imit, including amine (C-2) functionality existing on deacetylated imits (31). Reactions typical of hydroxyl and amine groups (such as acylations with acid chlorides and anhydrides) including urethane and urea formation respectively, are feasible with isocyanates. The primary amine can be quatemized by alkyl iodides or converted to an imine with a variety of aldehydes and ketones that can subsequently be reduced to an N-alkylated derivative. Chitin and chitosan are reactive with a variety of alkyl chlorides after treatment with concentrated NaOH. Important derivatives such as carboxymethylated chitin and chitosan are commonly produced in this manner with the addition of sodium chloroacetate. 

Trifluoromethylmalonic acid derivatives were used in the synthesis of 5-trifluoromethyl-substituted pyrimidines. In particular, acyl fluorides 827 were obtained by alkylation of trifluoromethyhnalonyl fluoride (826), in turn prepared from acyl fluoride 825 (Scheme 164) [509], Reaction of 827 with urea led to the formation of fluorinated barbitmates 828. 

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