Experimental and Computational Determination of the Effect of the Cyano Group on Carbon Acidity in Water

Abstract

Rate constants k DO (M-1 s-1) for the deprotonation of cyanoalkanes by deuterioxide ion in D2O at 25 °C were determined by following the appearance of the deuterium-labeled cyanoalkanes by 1H NMR. These data were evaluated to give the following pK a's in water: CH3CN, 28.9; CH3CH2CN, 30.9; NCCH2CH2CN, 26.6. High level ab initio calculations on cyanoalkanes and α-cyano carbanions and combined QM/Monte Carlo calculations of their free energies of solvation were carried out. The interaction between a carbanionic center and an α-cyano substituent is concluded to be largely polar. The 5.1-fold difference in α-cyano and β-cyano substituent effects on carbon acidity in water which, nominally, is consistent with significant resonance stabilization of α-cyano carbanions is attributed to the differential solvation of cyanoalkanes and cyanocarbanions. The free energy change for the highly unfavorable tautomerization of acetonitrile to ketenimine in water was computed as ΔG T = 30.7 kcal/mol. We propose that the large instability of the ketenimine cumulative double bond favors the valence bond resonance form of the α-cyanocarbanion in which there is a formal carbon−nitrogen triple bond and the negative charge is localized at the α-carbon.

The kinetics and mechanisms of organic reactions in liquid ammonia

“…However, the exact pK a of these carbon acids in liquid ammonia are 148 unknown (Table 3.7 and Figure 3.9). The positive deviation of malonodinitrile anion from the correlation line is observed in other systems, 262 and reason for this is probably due to the negative charge mainly resting on the central carbon as charge delocalisation is accompanied by an unfavourable structure, 194,196 thus makes malonodinitrile a better nucleophile compared with strongly delocalised carbanions. Interestingly, the aqueous pK a of some common used carbon acids, except for nitroalkanes, correlate well with their corresponding pK a in DMSO, and has a slope of 1.05 (Figure 3.10, for details, see: Appendix A: Table A31).…”

“…The rates of reactions which involve different types of carbanions as nucleophiles are often found to be poorly correlated with the corresponding pK a of their conjugate acids in various solvents. 196,257 Some specific factors for a certian types of carbanion, such as solvent reorganisation and rehybridisation of nitroalkanes carbanions, 258 cyano carbon acids, 194,259 must be considered in order to rationalise the abnormal reactivities of these carbanions in nucleophilic substitution reactions. a 0.5M malonitrile and 0.01M benzyl chloride.…”

C-Metalated Nitriles: Electrophile-Dependent Alkylations and Acylations

“…19,31 Prior coordination between the electrophile and the magnesium atom of 11 does not appear to control the stereoselectivity 32 since alkylation with Me 2 SO 4 , an electrophile capable of metal-directed alkylation, 33 affords exactly the same axially methylated nitrile 9b as that obtained by alkyating with MeI (Table 1, entries 1-2). Intercepting 11 with the more sterically demanding propyl iodide maintains the preference for axial alkylation despite the increased steric compression relative to alkylation with MeI (Table 1, entry 3).…”

Base-Catalyzed Dehydration of 3-Substituted Benzene cis-1,2-Dihydrodiols: Stabilization of a Cyclohexadienide Anion Intermediate by Negative Aromatic Hyperconjugation

“…A difference between Richard and Williams's study 21 and our own is that they use hydrogen isotope exchange of nitriles to measure their rates of ionisation to form anions. Where reprotonation of the anion is sufficiently exothermic, the isotope exchange ceases to be catalyzed by buffer base, and Richard supposes that the rate-determining step for the exchange is rearrangement of a HDO solvent molecule, with a rate constant k reorg .…”