Computational studies benzaldehyde

A DFT study found a corresponding TS to be the lowest energy.167 This study also points to the importance of the solvent, DMSO, in stabilizing the charge buildup that occurs. A further computational study analyzed the stereoselectivity of the proline-catalyzed aldol addition reactions of cyclohexanone with acetaldehyde, isobu-tyraldehyde, and benzaldehyde on the basis of a similar TS.168 Another study, which explored the role of proline in intramolecular aldol reactions, is discussed in the next section.169... 

In the computational study a possibility of simultaneous binding of both reagents with hydrogen bonds with both N-H protons in different thiourea units was investigated. It was foxmd, however, that the most stable complex of this kind is significantly (by 6 kcal/mol) less stable than a complex of nitronate anion with the catalyst and free benzaldehyde, whereas the binding of free benzaldehyde is very weak. It was concluded therefore that the complex in which both reagents are boxmd to tire catalyst is not an important intermediate due to its low concentration and aldehyde 26 preferentially remains unboimd before the formation of the transition state. ... 

The migration of the phenyl group or the proton was computed to occur in a concerted but asynchronous process. The concreteness of this step implies serious limitations on the relative orientation of the two reactants leaving in each case only two stereochemical possibilities for the formation of the C-C bond between coordinated benzaldehyde and diazoester 2 (Figure 3.14). Hence, totally four reaction pathways were considered in the computational study. 

Hydroboration of carbonyl compounds by pinacolborane is chemoselectively catalysed by titanocene bis(catecholborane) (A). Aryl aldehydes and ketones produce alkoxypinacolboronate esters (B) in moderate to high yields. The facile hydrolysis of B over silica affords alcohols in good yields. The catalytic hydroboration of electron-poor acetophenones is faster than that for electron-rich acetophenones. Computational studies with benzophenone and benzaldehyde indicated that hydroboration is spontaneous and probably proceeds via Ti metallacycle intermediates whose structures... 

Cp2Zr(Me)Cl, respectively. Their NMR spectra clearly reveal that the O-bond character of the enolate, indicated by the carbon-carbon double bond, is maintained in solution (Scheme 3.8) [53]. Crystal structures were also obtained for O-bound zirconium acetophenone enolate 21 [55], titanium ketone enolate 22, derived from/) r -methylacetophenone, and amide enolate 23 [56]. Whereas the latter readily added to benzaldehyde, the ketone enolate 22 (X = Ph) failed to undergo an aldol addition. This difference in reactivity was explained - based on a computational study - by a higher electron density at the methylene carbon atom in the amide compared to the ketone enolate [56]. 

The effect of the electronic properties of the substituted benzaldehydes (la-c) on the allylation reaction is another interesting issue. While most catalysts shown in Figures 15.1 and 15.2 generally exhibit a rather minor variation in ee (typically with less than 20% difference between the electron-rich and electron-poor aldehydes), METHOX (22) appears to be a particularly tolerant catalyst, exhibiting practically the same enantioselectivity (93-96% ee Table 15.2, entries 1-3) and reaction rate across a range of substrates [28f, 28g]. In contrast, QUINOX (23) stands at the opposite side of the spectrum, showing the most dramatic differences between the electron-rich and electron-poor substrate aldehyde (16-96% ee entries 4-6) [30]. Kinetic and computational studies shed some light on the latter behavior it seems that METHOX prefers an ionic transition state with a pentacoordinate silicon (Scheme 15.4), whereas QUINOX favors the neutral, hexacoordinate species. This hypothesis is, inter alia, supported by the choice of solvents, namely. 

A computational study of the Baeyer-Villiger oxidation of benzaldehyde and acetaldehyde has been reported. Computational studies with peroxyacetic acid suggest that the first step is rate limiting and the addition of the peroxyacetic acid oxidation catalyst to the ketone carbonyl to produce the Criegee or tetrahedral intermediate (Scheme 163) "... 

Use of medium-scale heat flow calorimeter for separate measurement of reaction heat removed via reaction vessel walls and via reflux condenser system, under fully realistic processing conditions, with data processing of the results is reported [2], More details are given elsewhere [3], A new computer controlled reaction calorimeter is described which has been developed for the laboratory study of all process aspects on 0.5-2 1 scale. It provides precise data on reaction kinetics, thermochemistry, and heat transfer. Its features are exemplified by a study of the (exothermic) nitration of benzaldehyde [4], A more recent review of reaction safety calorimetry gives some comment on possibly deceptive results. [5],... 

Several studies have tackled the structure of the diketopiperazine 1 in the solid state by spectroscopic and computational methods [38, 41, 42]. De Vries et al. studied the conformation of the diketopiperazine 1 by NMR in a mixture of benzene and mandelonitrile, thus mimicking reaction conditions [43]. North et al. observed that the diketopiperazine 1 catalyzes the air oxidation of benzaldehyde to benzoic acid in the presence of light [44]. In the latter study oxidation catalysis was interpreted to arise via a His-aldehyde aminol intermediate, common to both hydrocyanation and oxidation catalysis. It seems that the preferred conformation of 1 in the solid state resembles that of 1 in homogeneous solution, i.e. the phenyl substituent of Phe is folded over the diketopiperazine ring (H, Scheme 6.4). Several transition state models have been proposed. To date, it seems that the proposal by Hua et al. [45], modified by North [2a] (J, Scheme 6.4) best combines all the experimentally determined features. In this model, catalysis is effected by a diketopiperazine dimer and depends on the proton-relay properties of histidine (imidazole). R -OH represents the alcohol functionality of either a product cyanohydrin molecule or other hydroxylic components/additives. The close proximity of both R1-OH and the substrate aldehyde R2-CHO accounts for the stereochemical induction exerted by RfOH, and thus effects the asymmetric autocatalysis mentioned earlier. 

Fuchs et al. have reported that their study on the ozonolytic reactivity of transposed cyclic vinyl phosphonates attempted to probe the anticancer SAR (structure-activity relationship) of a series of computer-designed (-i-)-discodermolide analogs [85] (Scheme 41). Ozonolytic cleavage of 200 and 201 in the presence of O3 followed by quenching with Me2S provided 202 and 203 along with the desired lactones 204 and 205 as minor products in a 6 1 ratio. Addition of catalytic DBU to 203 could drive lactonization to completion giving lactone 205 in excellent yield. As aldehyde 202 was less tolerant to DBU, it required a dropwise addition of NaHMDS in the presence of p-nitro-benzaldehyde to trap the expelled diethyl phosphate. 

A detailed computational investigation of the enantioselective addition of n-BuLi to benzaldehyde in the presence of a chiral lithium A,P-amide has been presented. Five different chiral ligands originally synthesized from amino acids were studied using dispersion-corrected DFT, and the resulting enantioselectivity has been compared with experimentally available enantiomeric ratios. 

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