K. Morris, Charles S. Johnson
Apr 1, 1992
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Journal of the American Chemical Society
Abstract
diamide’s behavior on the basis of spectroscopic data should be more straightforward than for 1. Previously reported variabletemperature IH NMR measurements (AG(NH)/A.T) indicated that the intramolecularly hydrogen-bonded and non-hydrogenbonded6 states of 2 are of very similar enthalpy in CD2C12.2a In contrast, when an attempt was made to account for solvation by including three CH2C12 molecules in a “supermolecule” calculation, AM1 predicted the minimum energy intramolecularly hydrogen-bonded conformation of 2 to be 1.9 kcal/mol more enthalpically favorable than the minimum energy non-hydrogen-bonded c~nformat ion .~ In order to provide a more quantitative comparison with the calculations, we have now carried out an IR-based van’t Hoff analysis of the intramolecular hydrogen bonding equilibrium occurring in a 1 mM CH2C12 solution of 2 over the temperature range -69 to 23 OC. Figure 1 shows the N-H stretch region of the IR spectra obtained at high and low temperatures. Both hydrogen-bonded (3340-50 cm-l) and non hydrogen-bonded6 (3443-8 cm-I) bands are observed at each temperature. No hydrogen-bonded N-H stretch band can be detected at any temperature for a 1 mM sample of N-methylcyclohexylactamide (3) in CH,Cl,; therefore, we used this compound to estimate the extinction coefficient of the non-hydrogen-bonded N-H stretch band of 2 as a function of temperature. van’t Hoff analysis (intramolecularly hydrogen-bonded vs non-hydrogen-bonded states; each “state” comprises a set of conformations) indicated that the internally hydrogen-bonded state of 2 is 0.25 f 0.06 kcal/mol less enthalpically favorable and 0.67 f 0.48 eu more entropically favorable than the non-hydrogen-bonded state.’ Since CH2C12 is relatively nonpolar, it is interesting that the internally hydrogen-bonded and non-hydrogen-bonded states of 2 have very similar enthalpies, with the state containing the N-H-O=C interaction slightly less enthalpically favorable. An ideal amide-amide hydrogen bond should be enthalpically superior to any interaction between the amide group and the solvent. The enthalpic similarity of the internally hydrogen-bonded and non-hydrogen-bonded states of 2 may result from at least two factors: (1) the geometry of the seven-membered-ring hydrogen bond is not optimal for the amide-amide interaction (e.g., a nonlinear N-H-0 angle is unavoidable); (2) closure of the hydrogen-bonded ring may involve the development of torsional strain and/or other enthalpically unfavorable interactions. The entropic similarity between the internally hydrogen-bonded and non-hydrogen-bonded states may arise from the fact that these two states enjoy similar degrees of conformational mobility2c and/or from desolvation associated with intramolecular hydrogen bond formation.* (The breadth and asymmetry of the hydrogen-bonded N-H stretch band in Figure 1 is consistent with the existence of multiple hydrogen-bonded ring conformations.) Why does AM1 overestimate the enthalpic favorability of the intramolecularly hydrogen-bonded state of 2? One potential source of error is indicated by the comparison between ab initio and AM1 results for the hydrogen-bonded formamide dimer reported by Novoa and Whangboe3 When interaction energy was examined as a function of the N-H--0 angle, the ab initio calculations predicted that the hydrogen bond energy becomes increasingly unfavorable as the angle decreases below 150°.9 For an N-H-0 angle of 120’ (the smallest angle examined), the ab initio interaction energy was 1.5 kcal/mol less favorable than in the