Hydrolysis of imidazole-2-ylidenes.

The direct reaction of an imidazole-2-ylidene in a predominantly aqueous environment [about 0.1 M solution in a H(2)O (>60%)/THF solvent system] was investigated for the first time. The reaction yielded a stable solution of the corresponding imidazolium-hydroxide of pH 13, which is in agreement with results from an ab initio molecular dynamics simulation. In contrast, hydrolysis of the carbene in a mainly aprotic environment (>80% THF) gives a hydrogen-bridged carbene-water complex which could be detected by NMR and IR spectroscopies for the first time. This complex converts slowly to two isomeric ring opened products and is at higher water concentration in dynamic equilibrium with the imidazolium hydroxide. A computational mechanistic study of the carbene hydrolysis with a gradually increasing number of water molecules revealed that the imidazolium-hydroxide structure can only be optimized with three or more water molecules as reactants, and with the increasing number of water molecules its stability is increasing with respect to the carbene-water complex. In agreement with the experimental results, these findings point out that solvent stabilization and basicity of the hydroxide ion plays a crucial role in the reaction. With increasing number of water molecules the barriers connecting the reaction intermediates are getting smaller, and the ring opened hydrolysis products can be derived from imidazolium-hydroxide type intermediates. Computational studies on the hydrolysis of a nonaromatic imidazolidine-2-ylidene analogue clearly indicated the analogous ring-opened product to be by 10-12 kcal/mol more stable than the appropriate ion pair and the carbene-water complex, in agreement with the known aromatic stabilization of imidazol-2-ylidenes. Accordingly, these molecules hydrolyze with exclusive formation of the ring-opened product.

Stepwise aromatic nucleophilic substitution in continuous flow. Synthesis of an unsymmetrically substituted 3,5-diamino-benzonitrile library.

Aromatic or heteroaromatic ring precursors with 2-3 identical functionalities are often used in sequential derivatization depending on the reactivity difference or the selective execution of the reaction such as nucleophilic aromatic substitution. Continuous flow chemistry offers an enhanced parameter space (pressure and temperature) with rapid parameter optimization that ensures selectivity in many cases. We developed a flow chemistry procedure to carry out a stepwise aromatic nucleophilic substitution of difluoro-benzenes having an activating group in meta position to the fluorines. The mono-aminated products were obtained in high yield and selectivity in an extremely short reaction time, while applying higher temperature, longer reaction zone (or time), and employing higher excess of another amine reactant, the subsequent introduction of the second amino group was also successfully achieved leading to an unsymmetrically substituted 3,5-diamino-benzonitrile library.

The effect of the primary solvate shell on the mechanism of the Stöber silica synthesis. A density functional investigation.

The target of the present computational study was the acid catalyzed bond cleavage of the Si-O and C-O bonds in siloxane, alkoxysilane and ether in aqueous media. In the present study the effect of water as a solvent has been modeled using a full primary solvate shell built up from water molecules connected via hydrogen bonds around the reacting molecules. The interaction energy between the embedding water cluster and the "solvated" molecule gives an estimate for solution effects. The cleavage of the Si-O bonds in these molecular clusters proceeds with low barriers; furthermore the reaction energies corrected with the solvent interaction energies gives a reaction thermodynamics, which is in accordance with the experimental results. Molecules with a Si-O bond form stable pentavalent silicon with the solvent water molecules if protonated, while in the case of the neutral molecules tetracoordinate silicon is obtainable. The summary of the calculated reaction paths gives a possible route of siloxane formation from methoxysilane in aqueous media. The same computational methodology predicts that the hydrolysis of dimethyl ether is hindered by a substantial barrier.