Conformational preferences for some 2-substituted N-methoxy-N-methyl- acetamides through spectroscopic and theoretical studies Paulo R. Olivato a, * , Roberto da Silva Gomes a , Alessandro Rodrigues a , Adriana K.C.A. Reis b , Nelson L.C. Domingues c , Roberto Rittner d , Maurizio Dal Colle e a Conformational Analysis and Electronic Interactions Laboratory, Institute of Chemistry, University of Sao Paulo, CP 26077, 05513-970 Sao Paulo, SP, Brazil b Universidade Federal de São Paulo, UNIFESP, Diadema, SP, Brazil c Faculdade de Ciências Exatas e Tecnologia, Universidade Federal da Grande Dourados, CP 533, 79.804-970 Dourados, MS, Brazil d Physical Organic Chemistry Laboratory, Chemistry Institute, State University of Campinas, CP 6154, 13083-970 Campinas, SP, Brazil e Dipartimento di Chimica, Università di Ferrara, Ferrara, Italy article info Article history: Received 19 April 2010 Received in revised form 12 May 2010 Accepted 13 May 2010 Available online 21 May 2010 Dedicated to Prof. Giuseppe Distefano for his outstanding contribution in Theoretical Physical Organic Chemistry Keywords: Conformational analysis Infrared spectroscopy Theoretical calculations 2-Substituted N-methoxy-N-methyl acetamides abstract The analysis of the IR carbonyl band of the 2-substituted N-methoxy-N-methylacetamides Y–CH 2 C(O)- N(OMe)Me (Y = F 1, OMe 2, OPh 3, Cl 4), supported by B3LYP/6-311++G(3df, 3pd) calculations along with the NBO analysis for 1–4, indicated the existence of cis–gauche conformers i.e. (c) and (g) for 1 and 3,(c 1 , c 2 ) and (g 1 ,g 2 ) for 2, and (c) and (g 1 ,g 2 ) for 4. In the gas phase, the g conformer population prevails over the c one, for 1 and 3, the (c 1 + c 2 ) population prevails over the (g 1 + g 2 ) one for 2, and the (g 1 + g 2 ) con- former population is more abundant than (c) one for 4. In n-hexane solution, the cis conformer is more abundant for 1–3. The occurrence of Fermi resonance in the m CO region, in n-hexane, precludes the esti- mative of relative populations of the (c, g 1 , g 2 ) conformers for 4. The SCI-PCM calculations agree with the solvent effect on the m CO band component relative intensities for 1–3. NBO analysis showed that the n N ? p  co orbital interaction is the main factor which stabilizes the gauche (g, g 1 , g 2 ) conformers for 1–4 into a larger extent relative to the cis (c, c 1 , c 2 ) ones. The n Y ? p  co , r CAY ? p  co , p co ? r  CAY and p  co ? r  CAY orbital interactions still contribute, but into a minor extent for the stabilization of the gauche conformers relative to the cis ones. The existence of some pyramidalization at the nitrogen atom of the Weinreb amides 1–4 is responsible for the occurrence of Y d (4)O d (9) and Y d (4)N d (7) short contacts in the gauche (g, g 1 , g 2 ) conformers, which originates strong repulsive Coulombic interactions, acting in opposition to the large orbital stabilization of the gauche conformer with respect to the cis one. Therefore, a delicate balance of the Coulombic and orbital interactions seems to be responsible for the observed sta- bilization of the gauche (g, g 1 , g 2 ) and cis (c, c 1 , c 2 ) conformers, both in the gas phase and in the solution for 1–4. However, the cis conformer predominance, in non polar solvents, for the 2-substituted N-methoxy- N-methyl acetamides 1–3, bearing in a first raw (fluorine and oxygen) atoms, is in the opposite direction to the gauche conformer preference for the corresponding 2-substituted N,N-dialkyl-acetamides. Ó 2010 Elsevier B.V. All rights reserved. 1. Introduction Previous infrared and theoretical studies of some 2-heterosub- stituted N,N-dialkylacetamides [1–3] Y–CH 2 C(O)NR 2 (R = Et, Me; Y = F, OMe, NR 2 , Cl, Br, SEt and I) have shown that in the gas phase and in solvent of low relative permittivity (CCl 4 ) they prefer the gauche conformation. However, going from fluorine to iodine sub- stituent, the cis/gauche population ratio decreases progressively in this direction, being the gauche conformer practically the only one present for the iodine and bromine derivatives. The increasing sta- bilization of gauche conformer of the 2-heterosubstituted N,N-dial- kylacetamides compounds has been ascribed to the increasing contribution of the n X /p  co , r CAX /p  co and p  co /r  CAX orbital interactions. A comparison between the energies of some relevant orbitals (computed at HF/6-31G(d,p) level) of N,N-diethylacetamide (a) with those of the N-methoxy-N-methylacetamide (b) was per- formed in our previous paper [4]. In the amide (b), containing the electron attracting methoxy group bonded to the nitrogen atom, the ionization energy of the nitrogen lone pair n N is in- creased by 0.64 eV with respect to amide (a) and, simultaneously the electron affinity of the p  co orbital increases in the same direc- tion by 0.45 eV. The increased ionization energy of the n N lone pair of (b) in relation to (a) is responsible for both the smaller n N /p  co 0022-2860/$ - see front matter Ó 2010 Elsevier B.V. All rights reserved. doi:10.1016/j.molstruc.2010.05.021 * Corresponding author. Address: Instituto de Química, Universidade de São Paulo-USP, Av. Prof. Lineu Prestes, 748, Caixa Postal 26077, 05513-970 São Paulo, SP, Brazil. Tel.: +55 11 3091 2167; fax: +55 11 3815 5579. E-mail address: prolivat@iq.usp.br (P.R. Olivato). Journal of Molecular Structure 977 (2010) 106–116 Contents lists available at ScienceDirect Journal of Molecular Structure journal homepage: www.elsevier.com/locate/molstruc