The free energy profile of the piperidine catalyzed Knoevenagel condensation reaction of acetylacetone with benzaldehyde has been obtained by theoretical calculations. The carbinolamine formation step involves catalysis by methanol solvent, and its decomposition takes place via hydroxide ion elimination without a classical transition state, leading to the iminium ion. Hydroxide ion deprotonates the acetylacetone, forming an enolate that attacks the iminium ion and leads to an addition intermediate. The final step involves elimination of piperidine catalyst. Our analysis suggests the iminium ion formation has the highest barrier and the catalytic effect of piperidine is facilitating the elimination step rather than activation of the benzaldehyde electrophile. Experimental measures of the kinetics lead to an observed free energy barrier of 20.0 kcal mol, in good agreement with the theoretical value of 21.8 kcal mol based on the free energy profile.

A reliable theoretical calculation of the free energy profile of a base-catalyzed Knoevenagel reaction shows that hydroxide ion elimination step is rate determining.

Anion-molecule reactions have a substantial solvent effect, which decreases with the solvent polarity. However, less solvation leads to the formation of ion pairs and higher aggregates that are usually less reactive. Consequently, theoretical determination of the best solvent for the reaction needs to consider all the species in equilibrium. In this report, we have investigated the wide range of solvent polarity in the S N Ar reaction of the tetramethylammonium fluoride (TMAF) with 2-bromobenzonitrile, as well as the formation of ion pairs, dimers and tetramers using molecular dynamics and density functional calculations with continuum solvation. Five solvents were considered: methanol, dimethylformamide, pyridine, tetrahydrofuran and benzene. The TMAF exists predominantly as free ions in methanol, as ion pairs in dimethylformamide and pyridine, and as tetramers in tetrahydrofuran and benzene. The reaction takes place through free ions in methanol, ion pairs in dimethylformamide, pyridine and tetrahydrofuran, and via dimer in benzene. The calculations suggest that dimethylformamide and pyridine are the best solvents for this reaction.

New macrocycles derived from dibenzo-18-crown-6 and molecules derived from pentaethylene glycol were designed and investigated as catalysts for nucleophilic fluorination of alkyl mesylates with potassium fluoride by reliable computational methods....

Acid catalyzed decomposition of C 5 and C 6 sugars has been considered an important source of biomass derived chemicals. An essential step in this process is the extraction of furfural, hydroxymethylfurfural and levulinic acid from aqueous phase. In this work, a computational screening of 178 organic solvents for simultaneous extraction of these chemicals from aqueous phase has been done with the continuum SMD (solvation model based on density) model. Our analysis has taken in account the partition coefficient, water miscibility, boiling point and toxicity of the organic solvents. The present theoretical results indicate that C 6 and C 7 ketones are the most adequate solvents, and 4-heptanone is predicted to be particularly useful. Keywords: partition coefficient, green chemistry, MIBK, 4-heptanone, tributyl phosphate IntroductionPetroleum remains as the main source of feedstock for manufacture of fuels and chemicals. Nevertheless, the increased concern on environmental problems related to carbon dioxide emissions and the petroleum dependence have encouraged the development of biomass based fuels and chemicals. [1][2][3][4][5] Among the different processes for biomass transformation, acid catalyzed hydrolysis of xylan and glycan components of wood to form C 5 and C 6 sugars have received attention. 6 In the catalytic process, xylose and glucose (or fructose) are transformed to furfural, 5-hydroxymethylfurfural (HMF) and levulinic acid via acid-catalyzed dehydration (Scheme 1).In the acid medium used for generation of the products, more degradation can take place, leading to formic acid. Scheme 1. Formation of furfural, HMF and levulinic acid from acid catalyzed dehydration of C 5 and C 6 sugars. Dalessandro and Pliego Jr. 431 Vol. 29, No. 2, 2018 Current processes for recovering of furfural makes use of steam. However, the yield is limited and recently the use of solvent extraction has been advocated as more effective process. 6,7 In the same way, extraction of HMF during the reaction is desirable because it avoids degradation of this compound. 5 An efficient extraction requires an adequate solvent, which should have low miscibility with water and lead to a high partition coefficient for each compound. Recent experimental studies have investigated different solvents for extraction [7][8][9][10] and some authors have suggested that 2-butanol and 2-butanone are effective for HMF, while methyl isobutyl ketone (MIBK) is effective for both HMF and furfural compounds. 5,6,9 Other possibility for identifying efficient solvents for extraction is via computational methods. Thus, Sandler and co-workers 11 have used the COSMO-SAC method to investigate the ability of several linear and branched alcohols to extract HMF from aqueous solution and have found that the method produces reasonable partition coefficients. Following this work, Blumenthal et al. 12 have reported a very extensive screening of solvents for extraction of HMF using the COSMO-RS method and they have suggested 110 potential solvents superior to that i...

Finding the most efficient solvent for a chemical reaction can demand costly experimental procedure and the screening is usually limited to few solvents. The use of theoretical methods could accelerate the search for the best solvent, able to promote most effective kinetics and thermodynamics of a reaction. In this work, it was proposed an automated procedure that calculates the solvent effect for a chemical reaction using all the 179 solvents available in SMD (solvation model density). The reaction of 2-bromoacetophenone with pyridine was used as a test. The SMD model correctly predicts the reactivity trends for five solvents, which experimental data are available. We have found that sulfolane, a less usual solvent, is the best one for this reaction. The present study points out that computational screening of large set of solvents using the SMD model is a viable approach and could be useful for chemical reactions optimization.

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