The study of the thermodynamic properties and cooperativity involved in three centered hydrogen (THB) bond formation using aromatic ortho-A substituted amides, oxalamates and bisoxalamides (A = H, OMe, F, CH 2 OH, NO 2 , COCH 3 ) as model molecules is reported. ∆H° and ∆S° associated with disruption of intramolecular hydrogen bonding by solvent were estimated using temperature dependence data of the N-H chemical shift. The results suggest that the influence of the A group is more important when

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... electron-withdrawing, increasing both the enthalpy and entropy with an important contribution from conformational changes. The data allowed the estimation of the Ph=NH + rotational barrier of 14.0 kJ mol -1 in the amide and 16.7-18.0 kJ mol -1 in oxalyl moiety. Correlations between ∆H° and ∆S° with NH temperature gradients predicted an enthalpy change of 18.7(1.0) and 24.4(1.7) kJ mol -1 for the energy required to break a full THB bond (A⋅⋅⋅H⋅⋅⋅O=C) and entropy differences between the non hydrogen bonded and hydrogen bonded state of 42.0(4.7) and 61.9(11) J mol -1 K -1 in oxalamate and bis-oxalamide series, respectively, in agreement with the participation of cooperative effects. ARKAT USA, Inc. bonded rings can be evaluated. It should be mentioned that derivatives from o-hydroxyaniline were not included to avoid the interference of exchange phenomena between N-H and O-H hydrogen atoms in solution. Reliability of experimental data The graphs of temperature vs N-H chemical shifts for a-c series are shown in Figures 1a-c. In every case the NH chemical shifts decrease as the temperature increases. The method adjusts the data to a sigmoidal curve by Non Linear Fitting Procedures (NLFP) (Figure 1d ), from which δ HB and δ SB values are predicted. The results of the non-linear fitting procedure are listed in Table 1 and van't Hoff results are in Table 2 . The method estimates δ HB values with the lowest error whereas K R is estimated with the highest error. ∆H° and δ SB values are moderately well estimated but the van't Hoff estimations for ∆H° are more accurate, thus these last values, are used for discussion purposes. ARKAT USA, Inc. 18.7(1.0) -1.4(0.2) |∆δΝΗ/∆T|, R = 0.9511; ∆H°c = 24.4(1.7) -2.6(0.4) |∆δΝΗ/∆T|, R =0.9585, estimated error in brackets], whereas no correlation was found for amides ( Figure 2a) . These results are in agreement with low energy requirements for hydrogen bonding disruption at high ∆δΝΗ/∆T values. In oxalamate and oxalamide series, ∆H° values register a decrease of 1.4(0.2) and 2.6(0.4) kJ mol -1 , respectively, for each unit of |∆δNH/∆T| change in ppb K -1 . The larger value for the slope in bis-oxalamide c series than in oxalamate b series is in agreement with the participation of cooperative effects on THB formation in the former. The linear equations predict an enthalpy change of 18.7(1.0) and 24.4(1.7) kJ mol -1 for the energy required to break a full THB (|∆δΝΗ/∆T| = 0) in oxalamate and bis-oxalamide series, respectively. Correlations between entropy and ∆δNH/∆T values were done after the exclusion of data points for compounds 4a, 2b and 2c. The entropy difference between non-bonded and hydrogen ARKAT USA, Inc. results obtained herein point to the energetic superiority of THB disruption than for regular HB, and the participation of cooperative effects in the former. General Procedures. Acetanilide 1a, aniline, 2-methoxybenzylamine, 2-fluoroaniline, (2aminophenyl)methanol, 1-(2-aminophenyl)ethanone, 2-methoxymethylaniline, acetyl chloride, ethyl chlorooxoacetate and oxalyl chloride were purchased from Aldrich and used as received. Elemental analyses were performed in a Perkin-Elmer 2400 elemental analyzer. Melting points were measured on an Electrothermal IA 9100 apparatus and were uncorrected. IR spectra were recorded in KBr disks using a Perkin-Elmer 16F PC IR spectrophotometer. 1 H and 13 C NMR spectra were recorded on a Varian Mercury 300 (300.8 MHz) equipment in [ 2 H 6 ]DMSO or CDCl 3 solutions. Chemical shifts are reported in ppm and coupling constants in Hz. COSY, APT and HETCOR experiments were performed to unequivocally assign 1 H and 13 C NMR signals, and NOE experiments on amide NH to assign H6 signal, using standard techniques. Variable temperature experiments were performed with a temperature controller to keep temperature constant within 0.2 °C. A microprogram was used to change temperature automatically in 10 °C increments with a delay of 5 min for the temperature stabilization. Each spectrum was obtained with 32 scans. Samples concentration was maintained at 5 mg/0.4 mL or less in [ 2 H 6 ]DMSO solutions. Temperature controller was calibrated using standard techniques given by the purchaser. General preparative procedures Compounds 1a-c, 2a-c, 3a-c, 4a-c, 5a-c, 6a-c and 7a-c were prepared according to previously reported procedures starting from the corresponding amine and acetyl chloride, ethyl chlorooxoacetate or oxalyl chloride. Characterization of compounds 1b and 1c, 29 2a and 2c, 1 2b and 4c, 18 3a, 30 3b, 31 5b 19 and 6a 32 by 1 H and 13 C NMR, IR and melting points were in agreement with reported data. 1 H and 13 C NMR in [ 2 H 6 ]DMSO solutions (only 6c in CDCl 3 ), IR and melting points of compounds 3c, 4a, 4b, 5c, 6b-c, 7a-c are herein reported. N,N'-bis[(2-Fluoro)phenyl]oxalamide (3c). Obtained from 2-fluoroaniline and ethyl oxalyl chloride as a white crystalline solid in 30% yield, m.p. = 208 °C, 1 H NMR (δ): 10.68 (s, 1H, NH), 7.79 (m, 1H, H6), 7.44 (m, 3H, H3-5). 13 C NMR (δ): 159.0 (s, C=O), 155.9 (d, J C-F =