3698
J. Phys. Chem. A 2010, 114, 3698–3702
Boryl Substitution of Acetaldehyde Makes It an Enol: Inconsistency between Gn/CBS and Ab Initio/DFT Data Roman M. Balabin* Department of Chemistry and Applied Biosciences, ETH Zurich, 8093 Zurich, Switzerland ReceiVed: December 14, 2009; ReVised Manuscript ReceiVed: January 21, 2010
Tautomerism, a particular case of isomerism, plays an important role in modern organic chemistry, biochemistry, medicinal chemistry, pharmocology, and molecular biology. Inconsistency between results of complex energy computation methods Gn/CBS (G2, G3, CBS-4M, and CBS-QB3) and high-level ab initio/DFT ones (CCSD(T)/ CBS, MP2/CBS, and B3LYP/aug-cc-pVTZ) is found. Gn/CBS methods provide a qualitatively different description of tautomeric (keto-enol) equilibrium in 2-substituted acetaldehydes. According to valence focal point analysis (FPA) based on CCSD(T)/aug-cc-pVTZ, MP3/aug-cc-pVQZ, and MP2/aug-cc-pV5Z energies, boryl substitution of acetaldehyde makes it an enol. In other words, enol was found to be the global minimum on the potential energy surface (PES) of C2H5BO. Gn/CBS methods predict the keto form to be the minimum. The relative energy of alkenol, CH(BH2)dCH(OH), is calculated to be -1.67 ( 0.82 kcal mol-1 at CCSD(T)/ CBS level of theory. Hydrogen shift effects are also calculated in two other 2-substituted acetaldehydes, namely, 3-oxopropanenitrile (C3H3NO) and ethanal (C2H4O), with a general formula of XH2C-CHO (X ) BH2, CN, and H). Electron density (charge) transfer between the CdC double bond and the free p orbital of the boron atom (B) in a boryl group (BH2) greatly stabilizes enol with respect to ketone, CH2(BH2)-CHO. The first known stabilization of enol in an acetaldehyde derivative, without an intramolecular hydrogen bond (H-bond), questions the accuracy of complex energy computation methods for boron-containing molecules. The possible reasons and consequences of this finding are discussed. 1. Introduction Tautomerism (Gr.: tauto, same; meros, part), a particular case of isomerism, plays an important role in modern organic chemistry, biochemistry, medicinal chemistry, pharmacology, and molecular biology.1-3 Understanding the mechanisms of the many (bio)organic reactions, including those involving specific interactions with proteins, enzymes, and receptors, in which a reagent, a product, or an active intermediate tautomerizes, requires knowledge of the tautomerization phenomenon.4-6 Processes involving proton transfer (shift) between interconversion tautomers include the keto-enol,7,8 imine-enamine,9 oxime-nitroso,10 hydrazo-azo,11 and phenol-keto12 isomerizations. Among these processes, the most common studied form of tautomerism is that between a keto (carbonyl) and an enol (alkenol).7 Enols have been found to be reactive intermediates in numerous reactions, electrophilic substitution in carbonyl compounds, oxy-Cope, Conia, and Carroll rearrangements, retroDiels-Alder reactions, and so forth.13-15 In many cases, the enolization of the carbonyl compound determines the reaction rate.7 In most cases, keto forms are thermodynamically more stable than their enol counterparts by ∼10 kcal mol-1.16 However, there are known stable enols, for example, acetylacetone and malonaldehyde, in which the hydrogen bonding (Hbond)17 enhances enol stabilities.7 Acetaldehyde and its derivatives represent one of the simplest but important examples of molecular systems with keto-enol equilibrium. The interest in their chemistry has a long history.1,7,16,18-31 Unfortunately, most theoretical estimations of H-shift32,33 in such systems were limited to rather mediumaccuracy ab initio/DFT methods or parametrized complex energy * To whom correspondence should be addressed. Tel.: +41-44-632-4783. E-mail:
[email protected].
computations methods (mostly from Gn and CBS families).1,7,16 Recent advances in hardware possibilities can greatly increase the accuracy of these theoretical data. Focal point analysis (FPA)34-37 is one of the most effective methods of modern high-accuracy ab initio theory. Its use in a wide range of molecular systems (from diatomic molecules to normal pentane) has yielded excellent results.34-39 The theoretical analysis of conformational equilibria in normal alkanes (nbutane and n-pentane) is one of the best examples of the use of FPA (see refs 38 and 39 and the references therein). Recently, Kasalova´ et al.40 used this FPA scheme to estimate the barrier to planarity of the cis-cis-cis (ccc) conformation of glycine with a (5 cm-1 accuracy. Balabin41 has used the same approach to estimate relative energies of glycine conformers with an error of just 17-70 cm-1. Valence FPA of tetrazole and triazole tautomers (and transition states) was able to reach an accuracy of 0.10-0.25 kcal mol-1 (35-87 cm-1) for relative energy differences.42 FPA has already been applied to the acetaldehyde molecule with great success; a benchmark-quality potential of acetaldehyde, obtained by FPA, has enabled calculation of torsional transition frequencies within 2 cm-1 of available experimental values.43 Although the computational resources required to implement the FPA method are considerable, its application to the tautomeric equilibrium in substituted acetaldehydes is merited. Data obtained from such calculations could be useful in understanding the sophisticated potential energy surfaces (PES) of these molecules and particularly in understanding the factors leading to stabilization of their enol tautomer. These results may also be useful as benchmark data for evaluation of other (simpler) quantum chemical models (e.g., widely used G2/G3 methods).44-48
10.1021/jp911802v 2010 American Chemical Society Published on Web 02/15/2010
Boryl Substitution of Acetaldehyde Making It an Enol
J. Phys. Chem. A, Vol. 114, No. 10, 2010 3699 MF2 EXMF2 ) ECBS + aX-3
(2)
where X ) (Q, 5) for aug-cc-pVQZ and aug-cc-pV5Z, respectively. CCSD(T)/CBS values were obtained using the addition scheme of Csa´sza´r et al.34,35 Core correlation shifts (
