Substituent Effect on the Reaction Mechanism of Proton Transfer in Formamide Heidar Raissi* and Mehdi Yoosefian* MP2 and B3LYP methods at 6-311þþG** basis set have been used to explore proton transfer in keto-enol forms of formamide and to investigate the effect of substituent, i.e., H, F, Cl, OH, SH, and NH 2 on their transition states. Additionally, the vibrational frequencies of aforementioned compounds are calculated at the same levels of theory. It is proposed that the barrier heights values in kJ/mol for F, Cl, OH, and SH substituents are significantly greater than that of the bare tautomerization reaction, implying the importance of the substituents effect on the intramolecular proton transfer. V C 2011 Wiley Periodicals, Inc. DOI: 10.1002/qua.23235 Introduction Proton transfer (PT) reactions via intermolecular hydrogen bonding (HB) have been analyzed in detail. [1,2] The double PT for the centrosymmetric dimer of formic acid has also been examined both theoretically and experimentally, [3] and that carboxylic acids possessing two equivalent hydrogen bonds were also probed. [4] An asymmetrical double potential well exists, when the product of the PT becomes identical and geo- metrically the same as reactants. [5] Grabowski et al. [6] studied centrosymmetric dimers of formamide (FO) and related species in which two equivalents NAHO HB occur, proving the exis- tence of a nonsymmetric potential energy well. Here, the products of the double PT process which are the tautomeric forms of the reactants contain OAHN HB. Nonetheless, there is a particular type of PT in which a sub- stituent group can manipulate the reaction by steric or electron effects. On this basis, we have examined the effect of substitu- ents on formamide (FO) ! formamidic (FOA) conversion. We believe that the NH 2 CHO (FO) ! HN¼¼CHOH (FOA) tautomeriza- tion could be used as a model to mimic PT in nucleic acids bases of guanine and uracil. Recently, the barrier energy value for the bare FO ! FOA isomerization in the gas phase was derived by Wang et al. [7] as 204.6 kJ/mol. On the other hand, Bell et al. [8] performed the ab initio dynamics calculations based on a canonical variational transition state theory at 6-31g (d,p) basis set level using different density functional theory (DFT) methods. They tested the accuracy of different DFT methods, found the rate constant for the forward and the reverse reac- tion. They also evaluated the effects of different substituents on FO regarding the geometrical parameters, the activation energy reduction, and the reaction paths for FO ! FOA isomerization. There have been numerous investigations on different kinds of PT reactions. [5] To the best of our knowledge, there are a few studies on the effects of substituents on the PT reactions. Computational Methods DFT methods are known to give reliable geometric and thermo- dynamic properties for hydrogen bonded clusters. [9,10] However, the superiority of DFT methods has been doubted by several recent studies. [10–12] Some commonly used gradient-corrected functionals give barriers too low values compared with post-HF and experimental methods. [10–12] The geometries of the reac- tants, transition states and products for the tautomerization are optimized using the B3LYP/6-311þþG** level of theory. [13] For comparison, the MP2 calculations [14] are performed at chosen ba- sis set. The vibrational frequencies were obtained at the same lev- els for characterization of stationary points and zero point energy (ZPE) corrections. Intrinsic reactions coordinate (IRC) paths calcu- lations, [15,16] which connect pairs of tautomers with the corre- sponding transition state, were carried out. All calculations are conducted using the GAUSSIAN 03 program package. [17] Results and Discussion Geometries Figure 1 compares the geometries of the reactants, transition states and products involved in the Cl, F, OH, SH, and NH 2 assisted PT reactions alongside geometries of the unsubsti- tuted reaction. The calculated geometric parameters indicate that the MP2 and B3LYP methods at 6-311þþG** basis set lev- els are in good agreement with each other. For example, in FO molecule, CAN, C¼¼O bond lengths and NCO bond angle are 1.364, 1.217 A ˚ and 124.8 at MP2 level, respectively, which are in good consensus with B3LYP results (see Fig. 1). For simplic- ity, we have only listed the geometric parameters at B3LYP/ 6-311þþG** level. The tautomerization causes significant change in bond length, in the range of about 0.09 to 0.14 A ˚ , except for CH and NH which is about 0.01 A ˚ . For the normal mechanism of FO ! TS ! FOA, the transition state (TS) assumes a coplanar four-membered ring. Our findings suggest that first NCO bond angle undergoes a compression, and then H. Raissi, M. Yoosefian Chemistry Department, Birjand University, Birjand, Iran E-mail: hraissy@yahoo.com or myoosefian@yahoo.com V C 2011 Wiley Periodicals, Inc. FULL PAPER WWW.Q-CHEM.ORG 2378 International Journal of Quantum Chemistry 2012, 112, 2378–2381 WWW.CHEMISTRYVIEWS.ORG