The Alcoholysis Reaction of Isocyanates Giving Urethanes:  Evidence for a Multimolecular Mechanism

Abstract

A kinetic and mechanistic investigation of the catalyzed alcoholysis of isocyanates was undertaken. Both experimental and theoretical results showed that the alcoholysis should be understood by a multimolecular intervention of the alcohols. The alcoholysis of isocyanate was examined experimentally for 2-propanol and cyclohexanol in low and high concentrations. It is suggested that either two or three molecules of the alcohol are implicated from the kinetic study, while the reaction with trimers becomes dominant at high alcohol concentrations. In accordance with these results, theoretical study suggests an active participation of at least three alcohol molecules in a reacting supersystem, giving rise to a genuine effect. The detailed reaction mechanism for the alcoholysis reaction by methanol and methanol clusters (HN=C=O + n(CH(3)OH), n = 1-3) was modeled by ab initio methods, both in the gas phase and in solution. The nucleophilic addition occurs in a concerted way across the N=C bond of the isocyanate rather than across the C=O, similar to the isocyanate hydrolysis. The bulk solvent effect, which is treated by a polarizable continuum model (PCM), does not affect the preference of the alcohol to attack across the N=C bond as pointed out by the gas-phase values.

Total Synthesis of the Antimitotic Marine Macrolide (−)‐Leiodermatolide

“…Initially, we explored the introduction of the carbamate functionality on triol 24 itself by treatment with Cl 3 CCONCO (CH 2 Cl 2 , −78 °C),[28] but this reaction only afforded a disappointing 4:1 mixture of the C7 and C9 carbamates,[23], [29] a result anticipated from earlier studies with a truncated macrolide core. [5] To solve this problem, an effective sequence of hydroxy-group differentiation was sought to overturn the intrinsic substrate selectivity.…”

Photochemical Ring-Opening Reaction in 2(1H)-Pyrimidinones: A Matrix Isolation Study

“…The carbon atom in the -NdCdO moiety is electrophilic and susceptible to the attack of nuceophilic SCHEME 1: UV-Induced Ring-Opening Reaction in 1-Methyl-2(1H)-pyrimidinone reagents. The classic schemes of the reactions of isocyanates with alcohols or amines [38][39][40] are shown in Scheme 2. Direct application of these patterns to the reaction of the postulated open-chain isocyanate transient leads to final products presented in Schemes 3 and 4.…”

Use of Local Softness for the Interpretation of Reaction Mechanisms

“…The most interesting result for this type of addition is perhaps the finding that the most kinetically favored channel does not always lead to the most thermodynamically stable adduct. Formation of novel reaction intermediates, namely the less stable enols, was frequently predicted, and this theoretical prediction was finally verified by experimental evidence [20,21,24,25].…”

“…We have considered the mechanism of hydration [19][20][21][22][23] and similar alcololysis [24] and amination [25] reactions in several typical cumulenes such as isocyanates (R-C=N=O), ketenes (RRC=C=O), ketenimines (RRC=C=NR), carbodiimides (RN=C=NR), carbon dioxide (O=C=O) and carbon suboxide (O=C=C=C=O). The most interesting result for this type of addition is perhaps the finding that the most kinetically favored channel does not always lead to the most thermodynamically stable adduct.…”