J . Chem. SOC., Faraday Trans. 1, 1982, 78, 3397-3408 Solvation and Hydrophobic Hydration of Alkyl-substituted Ureas and Amides in NN-Dimethylformamide + Water Mixtures BY AART Rouw AND Gus SOMSEN* Department of Chemistry, Free University, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands Received 31st March, 1982 Enthalpies of solution of five alkyl-substituted ureas and seven different amides have been determined at 298.15 K in mixtures of NN-dimethylformamide (DMF) and H,O. Methyl substitution of the ureas causes changes in the enthalpies of transfer from H,O to DMF which show that either side of these molecules is solvated independently. From the measurements on the amides it is concluded that methyl substitution at the N atom gives changes in the enthalpies of transfer from H,O to DMF which are different from those caused by methyl substitution at the C atom.Analysis of the data in the mixed solvent shows that introduction of more or longer alkyl groups into the molecules makes both ureas and amides considerably more hydrophobic. After accounting for the influence of the NH protons, in both ureas and amides, the enthalpic effect of hydrophobic hydration of the solutes was calculated by application of a clathrate-like hydration model. Enthalpic effect of N-substituted methyl groups in ureas and amides prove to be virtually equal. The variation in the enthalpic effects of hydrophobic hydration with the number of C atoms in the n-alkyl group is comparable to that found for alcohols and amines. This paper is part of a project in which we are investigating the solvation of hydrophobic solutes in aqueous mixed solvents.After an earlier series of reports on tetra-alkylammonium salts [for references see ref. (l)] we have recently focussed our attention on non-electrolytes. Thus far we have studied monohydric alcohols' and alkylamines, as two representative types of model compounds. In our investigations we determine the enthalpies of solution of a (hydrophobic) compound in mixtures of water and an organic solvent. Since aprotic NN- dimethylformamide (DMF) has proved to be a suitable reference solvent with regard to water and since it is completely miscible with water, we confine ourselves mainly to DMF + H,O mixtures. Due to hydrophobic hydration the enthalpy of solution of a hydrophobic solute shows a strong endothermic shift upon addition of small amounts of DMF (or other cosolvents) to water.This is caused by the collapse of the hydrophobic hydration sphere around the solute. Analysis of this effect in terms of a model description3 yields information on the hydrophobic properties of the compound. In this paper we turn our attention to two other types of organic model compounds, i.e. substituted ureas and amides. Because of their biochemical importance aqueous solutions of these compounds have been studied extensively.*-15 Among the thermo- dynamic data enthalpies of solution in water have been reported for both alkylureaslO and amides.I1-l4 Enthalpies of solution in pure non-aqueous solvents have been published for amides only.14 As far as we know enthalpies of solution of these compounds in aqueous mixtures, covering the whole composition range from pure water to pure organic solvent, have never been determined, with the exception of urea, for which such measurements were reported in an earlier study from our 1ab0ratory.l~ These data provide a useful background to this work.33973398 SOLVATION + HYDRATION OF UREAS + AMIDES In this paper we discuss the solution properties of ureas and amides substituted with alkylgroups in various ways. The comparison of the hydrophobic effects of these compounds can provide information on the properties of alkyl groups at different positions in the solute molecule. To this aim we determined calorimetrically enthalpies of solution of twelve compounds in the mixed solvent DMF+H,O over the whole composition range.We investigated the following compounds : methylurea (MU); 1,l -dimethylurea (1,l -DMU); 1,3-dimethylurea (1,3-DMU); tetramethylurea (TMU); ethylurea (EU); formamide (FA); N-methylformamide (NMF); NN-dimethyl- formamide (DMF); acetamide (AA); NN-dimethylacetamide (DMA); Nn-butyl- acetamide (NBA) and butyramide (BA). For comparison we also determined the enthalpies of solution of TMU in the non-aqueous mixtures of NN-dime t h yl formamide + N-met hy 1 formamide. EXPERIMENTAL The enthalpies of solution were measured with an LKB 8700 precision calorimetry system, equipped with a 100cm3 reaction vessel. The experimental procedure and a test of the calorimeter system have been reported before.16 Solid compounds were transferred into glass ampoules of 1 cm3, which were closed with silicone rubber stoppers and sealed with wax.Liquid solutes were transferred with a syringe into another type of 1 cm3 ampoule. These ampoules had a narrow neck which could be sealed with the aid of a microburner. NN-dimethylforrnamide (Baker, Analyzed Reagent) and N-methylformamide (Merck, zur Synthese) were purified and dried as before.' The solvent mixtures were prepared by mass. For the aqueous mixtures we used distilled deionized water. MU (EGA, Steinheim) and I ,3-DMU (Koch-Light, Purissimum) were recrystallized from absolute ethanol. 1,l -DMU (Merck, zur Synthese) was recrystallized from a mixture of ethanol and chloroform. EU (Merck, zur Synthese), AA (Baker, Analyzed Reagent) and BA (Fluka, Purum) were recrystallized from a mixture of ethanol and diethylether.These solid compounds were dried under vacuum over P,O, for at least 48 h before use. TMU (Fluka, Purum) was distilled at reduced pressure. FA (Baker, Analyzed Reagent), NMF (Merck, zur Synthese), DMA (Baker, Analyzed Reagent) and NBA (Eastman) were purified by distillation from NaOH under reduced pressure. In all cases only the middle fraction was used. DMF (Baker, Analyzed Reagent) was used as such. All these liquid solutes were dried over molecular sieve (Baker, 4A), except for FA, where we used 3A molecular sieve. The water content of these liquids, determined with a modified Karl Fisher titration," was always below 0.02 mass %. The purity of the liquids was determined by gas-liquid chromatography and found to be > 99.8 mol %.RESULTS The amount of solute used during the calorimetric experiments led to final solute concentrations between 0.005 and 0.02 mol dm-3. In this range we did not observe any concentration dependence of the enthalpies of solution, so we considered our measured enthalpy values as those at infinite dilution and hence as standard enthalpies of solution, AH?. Correction for the presence of solute vapour in incompletely filled ampoulesls proved negligible because of the low volatility of the solutes. The values of the enthalpies of solution of the urea compounds in mixtures of DMF+H,O are listed in table 1, together with the average deviations. The values represent the mean result of two to four measurements agreeing within 0.15 kJ mol-1 and they refer to 298.15 K.Corresponding results on the amides are listed in table 2. In addition table 3 gives the results for TMU in mixtures of DMF+NMF. Some of the enthalpies of solution in pure water can be compared with results from the literature. Values of 1,3-DMU and TMU have also been determined by Ahluwalia and coworkers.1° Their results differ from ours by 0.3 and 0.6 kJ mol-l, respectively.A. ROUW AND G . SOMSEN 3399 TABLE 1 .-ENTHALPIES OF SOLUTION OF ALKYL-SUBSTITUTED UREAS IN DMF + H20 MIXTURES AT 298.15 K MU 1,l -DMU 1,3-DMU 0.000 0.060 0.189 0.325 0.450 0.550 0.650 0.770 0.850 0.900 0.950 1 .ooo 1 1.43 f 0.04 11.13f0.02 1 1 .OO f 0.03 11.19+0.01 11.75 f 0.01 12.26 & 0.0 1 12.84f 0.01 13.07 fO.O1 12.68 f 0.03 12.24 & 0.01 11.73 f 0.01 11.19 f O .O 1 19.56 f 0.05 19.35f0.08 19.26 f 0.03 19.26 f 0.05 19.65 f 0.03 19.70&0.02 19.22 fO.01 17.76f0.01 16.09 f 0.01 14.90 f 0.03 13.47 f 0.02 12.01 fO.05 11.17 f 0.02 10.68 f0.04 10.40 f 0.05 10.30_+0.04 10.45 k0.02 10.45 & 0.0 1 10.12 f 0.01 8.58 & 0.05 6.60 & 0.03 4.91 f 0.06 3.06 f 0.07 1.05 & 0.03 x w TMU EU 0.000 0.060 0.189 0.325 0.450 0.550 0.650 0.770 0.850 0.900 0.950 1 .ooo 0.17 & 0.02 0.10 f 0.01 0.05 f 0.03 - 0.21 f 0.02 - 0.96 f 0.04 - 2.60 & 0.04 - 6.54 k 0.04 - 10.80f0.01 - 14.24 f 0.06 - 18.42&0.01 -24.53k0.01 - 13.35 f 0.03 13.19f0.01 13.16 f 0.05 13.48 f 0.04 14.20f0.01 15.06 f 0.01 15.82f0.01 15.87 & 0.01 14.91 f0.02 13.84 f 0.02 12.40 & 0.0 1 10.69 f 0.05 On the other hand the difference between our values for FA, NMF, AA and NBA and those determined by Wadso and coworkers12~13 is always smaller than 0.07 kJ mo1-l. The agreement with results for FA, NMF, DMF, AA and DMA reported by Stimson and Schrierll is also very good.In a recent study Spencer et d . 1 4 have determined enthalpies of solution of FA, NMF, DMF, AA and DMA in both water and DMF. Considering the limited precision of their results the agreement with our values is fair. No literature data are available for the enthalpies of solution of MU, 1,l -DMU, EU and BA in water and for those of the substituted ureas, BA and NBA, in DMF. DISCUSSION The results for the enthalpies of solution of the alkylureas and the amides, listed in tables 1 and 2, are visualized in fig. 1 and 2.To facilitate the comparison we have plotted the enthalpies of transfer from H20 to the DMF+H,O mixtures, AHtr3400 SOLVATION -k HYDRATION OF UREAS + AMIDES TABLE 2.-ENTHALPIES OF SOLUTION OF AMIDES IN DMF 4- H 2 0 MIXTURES AT 298.15 K x w FA NMF DMF AA 0.000 0.060 0.189 0.325 0.450 0.550 0.650 0.770 0.850 0.900 0.950 1 .ooo - 3.88 f 0.03 -3.71 f0.05 - 3.28 f 0.03 - 2.44 f 0.02 - 1.32f0.01 -0.17 f 0.02 1.05 f 0.02 2.31 fO.01 2.71 fO.01 2.76 f 0.02 2.61 f 0.05 1.97 50.01 - 0.24 f 0.0 1 - 0.22 f 0.01 - 0.07 f 0.0 1 0.21 fO.01 0.50 f 0.03 0.65f0.01 0.48f0.01 -0.52 0.01 - 2.08 f 0.05 -3.36k0.01 - 4.95 f 0.02 -7.1 1 fO.01 0.00 0.06 f 0.01 0.04 f 0.03 - -0.19f0.03 - 0.83 f 0.05 - 2.08 f 0.06 -4.89f0.01 - 7.62 f 0.04 -9.69f0.01 - 12.02 Ifr 0.01 - 15.27 f 0.01 11.56f0.01 11.51 kO.01 1 1.49 f 0.02 1 1.83 f 0.02 12.40 f 0.03 12.94f0.01 13.31 f0.02 1 3.02 f 0.04 12.25 f 0.04 1 1.49 f 0.02 10.75 f 0.04 9.73 f 0.02 DMA NBA BA 0.000 0.060 0.189 0.325 0.450 0.550 0.650 0.770 0.850 0.900 0.950 1 .ooo -0.08f0.01 - 0.34 f 0.01 - 0.66 f 0.02 - 1.05f0.01 - 1.72 f 0.03 - 2.70 f 0.02 -4.58k0.04 - 8.29 & 0.04 - 11.84_+0.02 - 14.48 f 0.03 - 17.54f0.01 - 21.46 f 0.04 3.42 f 0.01 3.35 fO.01 3.43 f 0.01 3.76 & 0.04 4.29 & 0.02 4.76 & 0.02 4.81 f0.03 3.12 f 0.01 -0.31 fO.01 -3.71 f0.03 - 8.45 f 0.01 - 14.79 f 0.03 14.31 f0.03 14.40 & 0.05 14.83 f0.02 15.64f0.01 16.82 f 0.01 17.75 f 0.03 1 8.64 f 0.05 18.56f0.01 16.84 f 0.05 14.98 fO.O1 12.33 kO.01 9.07 f 0.01 TABLE 3.-ENTHALPIES OF SOLUTION OF TETRAMETHYLUREA IN MIXTURES OF DMF + NMF AT 298.15 K X,,, AHp/kJ mol-l 0.000 - 2.43 & 0.03 0.250 - 1.39 f 0.02 0.500 -0.73 fO.01 0.750 - 0.23 f 0.02 1 .ooo 0.17 f 0.02 (H,O -+ DMF+H,O), against X,, the mole fraction of water in the mixture.Enthalpies of transfer show the same variations as enthalpies of solution, but they do not contain contributions from interactions in the pure solid or the liquid solutes. Hence they reflect directly the enthalpic differences in solvation between the different mixtures and water. For comparison we have included in fig. 1 the results for urea (U) in the earlier study of De Visser et aL.l5A. ROUW AND G . SOMSEN 340 1 s l \ . X + LL 2 t 0, E I 1 I I I 0.2 0.4 0.6 0.8 FIG. 1 .-Enthalpies of transfer from H,O to mixtures of DMF + H,O for various alkyl-substituted ureas.xw +24 - I - 0 E 2 +16 3: + LL 2 +8 t . s 0, z I I I I 0.2 0.4 0.6 0.8 FIG. 2.-Enthalpies of transfer from H,O to mixtures of DMF+H,O for various amides. *w In both figures we see that, upon introduction of either more or longer alkyl groups into the ‘parent’ compounds U and FA, the curves of AH,,(H,O+ DMF+H,O) gradually come to show the features of hydrophobic hydration which we have described in our previous work.1*2 The most striking feature is the strong endothermic shift in the enthalpy of transfer in mixtures with a small mole fraction of organic 110 FAR 783402 SOLVATION + HYDRATION OF UREAS + AMIDES TABLE 4.-ENTHALPIES OF TRANSFER OF SOME ALKYLUREAS AND AMIDES FROM H20 TO DMF AT 298.15 K compound AH,,(H,O -+ DMF)/kJ mol-l U MU 1,1-DMU 1,3-DMU TMU FA NMF DMF AA NMA DMA ~~ - 9.43 0.24 7.55 10.12 24.70 - 5.85 6.87 15.27 1.83 14.43a 21.38 a Calculated +731 t 9.67 /Ii1 I3 /Ii1 +9.88 \ from data in ref.(1 1) and (14). DMU \9.88, I + 34.13 FIG. 3.-Changes in the enthalpies of transfer from H,O to DMF for ureas, caused by methyl substitution. Values in parentheses were estimated. (Energies are in kJ mol-l.) solvent. This is most pronounced for TMU, the compound with the largest number of methyl groups, and for NBA, which bears the longest alkyl chain. Differences between the curves of compounds containing an equal number of methyl groups, such as MU, NMF and AA or 1,I-DMU and 1,3-DMU, show that the position of the substituents also determines the shape of these curves. From the results we have calculated enthalpies of transfer from water to pure DMF, AH,,.(H,O -+ DMF), for the parent compounds U, FA and AA and their N-methyl- substituted derivatives.The results are listed in table 4. In urea the introduction of one methyl group, to form MU, causes a shift in AH,,(H,O + DMF) of 9.67 kJ mol-l. This is distinctly higher than the effect of the introduction of a second methyl group on the same N atom, to form l,l-DMU, which amounts to 7.31 kJ mol-l. However, introduction of a second methyl group on the other N atom, to form 1,3-DMU, results in a shift (9.88 kJ mol-l) which is very close to that of the first methyl group. This is a strong indication that the NH, and NHCH, groups on either side of the molecules are solvated independently, which should imply that the enthalpy of transfer of TMU will be larger than that of U by 9.67+ 9.88 + 7.31 + 7.31 = 34.17 kJ mol-1 (see fig.3). Experimentally the difference in the enthalpies of transfer of U and TMU is found to be 34.13 kJ mol-l, in excellent agreement with the predicted value. Inspection of the data in the solvent mixtures shows that this additivity scheme also applies to aA. ROUW AND G . SOMSEN 3403 good approximation to the enthalpies of transfer from water to the mixtures. Consequently the assumption of independent solvation of both sides of the urea molecules is substantiated by the experimental results in both the pure solvents and the mixtures. Although the magnitudes of the changes depicted in fig. 3 are determined by different effects, e.g. changes in solute-solvent hydrogen bonding, we believe them to be due largely to hydrophobic hydration of the methyl groups. For the amides the enthalpies of transfer in table 4 show that in this case also the change in AH,,(H,O + DMF) caused by a first methyl group introduced into FA and AA to form NMF and NMA (12.72 and 12.60 kJ mol-l, respectively) appears to be higher than the effect of a second N-methyl substitution (8.40 and 6.95 kJ mol-l, respectively, see fig.4). Because the amides are not symmetrical, introduction of a methyl group at the other side of the molecule will give different results. Indeed the difference in AH,,(H,O -+ DMF) between AA and FA amounts to 7.68 kJ mol-l, and such a lower value is also found for the differences between NMA and NMF and between DMA and DMF (see fig.4). Hence the effect of C-methyl substitution is definitely smaller than the effect of N-methyl substitution. This is not unexpected, since on C-substitution an aprotic CH group is replaced by a CCH, group, whereas on N-methyl substitution a protic NH group is transferred into an aprotic NCH, group. + Z68 +Z56 + 6.11 In our previous study on amines2 we have shown that, besides the enthalpies of transfer, a good and even better description of the enthalpies of solution in the mixtures is provided by the quantity 6 given by 6 = AH,,(H20 -+ DMF+H,O)-(1 -XW)AH,,(H,O -+ DMF). (1) 6 represents the deviation of the enthalpies of transfer in the mixtures from a change proportional to X,. We have shown that the values of 6 for a given solute are related to its hydrophobic properties.This relation can be described quantitatively by a model3 which involves the formation of clathrate-like cages of water molecules around each alkyl group in the water. These cages break down when cosolvent is added. According to this model 6 can be written as 6 = Hb(W) (XG-X,). (2) In this expression the two parameters Hb(W) and n represent the enthalpic effect of hydrophobic hydration of the solute in pure water and the number of hydration sites of one alkyl group, respectively. Although this model approach is a first approximation3+ l9 it has proved to be a useful means of comparing the hydrophobic properties of a wide range of solutes. However, one should realize that in this model eqn (2) assigns 6 values exclusively to the hydrophobic hydration of the alkyl groups in a solute. Any contributions from other effects are disregarded.This implies that in the absence of hydrophobic effects 6 should be zero at each mixture composition, i.e. the enthalpy of solution should change proportionally to the mole-fraction composition. Such behaviour has indeed I 10-23404 SOLVATION + HYDRATION OF UREAS + AMIDES TABLE 5.-vALUES OF 6 IN kJ m0l-l OF UREA [INTERPOLATED DATA OF REF. (1 5)] AND DIFFERENCES BETWEEN 6 VALUES OF ALKYL-SUBSTITUTED UREAS AND AMIDES AND THE RESPECTIVE PARENT COMPOUNDS x w W ) d(MU) - d(U) G(NMF) - A(FA) 0.000 0.060 0.189 0.325 0.450 0.550 0.650 0.770 0.850 0.900 0.950 1 .ooo 0.00 -0.84 - 2.20 - 3.06 - 3.33 - 3.08 -2.53 - 1.72 - 1.14 -0.77 - 0.39 0.00 0.00 0.55 1.82 2.90 3.76 4.04 4.10 3.54 2.59 1.80 0.92 0.00 0.00 0.61 1.98 3.14 3.90 4.18 4.06 3.32 2.38 1.68 0.89 0.00 x w d(1,l -DMU)-d(U) d(DMF)-&FA) d(DMA)-d(AA) 0.000 0.060 0.189 0.325 0.450 0.550 0.650 0.770 0.850 0.900 0.950 1 .ooo 0.00 1.08 3.34 5.22 6.82 7.38 7.10 5.74 4.10 2.92 1.48 0.00 0.00 1.10 3.46 5.44 6.76 7.08 7.26 5.18 3.74 2.66 1.52 0.00 0.00 0.96 3.18 5.12 6.32 6.76 6.46 5.38 4.16 3.26 1.92 0.00 been found for various non-hydrophobic solutes in DMF + H,O m i x t ~ r e s ~ 9 ~ ~ and also for hydrophobic solutes in non-aqueous mixtures such as DMF + NMF.lv2y20 This suggests that for these compounds the solvation changes gradually from one solvent to another.Fig. 1 shows that for the non-hydrophobic U in DMF+H,O the enthalpies of transfer deviate in a negative sense from linear behaviour.Values of 6(U), which were calculated by interpolation of the data in ref. (1 5), are listed in table 5. One might expect that these (negative) values for the parent compound cannot be ignored when considering the results for substituted ureas, because the latter contain similar polar groups. In this respect it is interesting to look at the behaviour of TMU. For X , < 0.5, where hydrophobic effects can be excluded, the enthalpies of transfer of TMU change linearly with X,. Consequently we think that the deviation from linear behaviour of U is mainly due to its NH protons. Support for this view is provided by our results for TMU in DMF + NMF. Inspection of table 3 shows that the enthalpies of solution of TMU in this mixture change almost linearly with composition.On the other hand the previous study of De Visser et aZ.15 has shown that the enthalpies of solution of U in DMF + NMF show negative deviations from linearity, comparable to those in DMF+H,O.A. ROUW AND G. SOMSEN 3405 Hence in order to obtain significant information from our 6 values on the hydrophobic hydration of alkyl groups in the substituted ureas we should apply a ‘correction’ which accounts for the influence of the NH protons. Because the substituted ureas contain a different number of NH protons we should apply corrections to 6 proportional to this number. For simplicity we now assume that the d(U) values are composed of four additive 6(NH) contributions : 6(NH) = 1/4 6(U) (3) and that these contributions can also be applied to the alkyl-substituted ureas.The corrected 6 values obtained in this way refer to the alkyl parts of the substituted ureas only. Regression analysis with respect to eqn (2) of a set of these values for a particular compound now yields values for the model parameter Hb(W). The results are listed in table 6. For the ureas table 6 also gives the contribution per methyl group to Hb(W). TABLE 6.-ENTHALPIC EFFECTS OF HYDROPHOBIC HYDRATION OF N-METHYL-SUBSTITUTED UREAS - Hb(W)/kJ mol-l solute ‘correction’ total per methyl group ~ MU - id( U) 7.1 7.1 1 , l - D M U -$6(U) 1 3 . 0 6.5 1 , 3 - D M U -@(U) 1 3 . 2 6.6 TMU - 24.6 6.2 We note that they are very similar, which indicates that to a good approximation the hydrophobic hydration of the methyl groups is independent of the solvation of the neighbouring group in the solute molecule.A similar independence has been found for other types of ~ 0 1 u t e s . ~ ~ ~ ~ Table 6 also shows a small trend in the Hb(W) values per methyl group (from MU to TMU). In our view this trend bears limited significance, because of the approximations made in the correction procedure. Some of the amides contain NH protons comparable to those in the ureas, so we can expect that in the analysis of the results for these compounds corrections will again be necessary. However, the situation is more complicated here, because amides other than FA contain alkyl groups substituted in different ways, i.e. at the C atom and/or at the N atom. These may contribute to 6 differently. Consequently the data cannot be treated in the same manner as for the ureas.For both ureas and amides, however, the effects of N-methyl substitution alone can be estimated by elimination of the contribution to 6 of the CH or C-substituted alkyl groups. This is done by comparing the differences 6(MU) - 6(U) and G(NMF) -&FA) and the differences 6( 1 , 1 -DMU) - 6(U), G(DMF) - 6(FA) and S(DMA) - 6(AA). The first are due to one methyl group and one NH group, the second to two methyl groups and one NH, group. The results given in table 5 show a close agreement between these differences. This strongly suggests that ureas, formamides and acetamides possess equal contributions of the methyl and NH groups to 6. This implies that the 6(NH) values of the ureas [eqn (3)] can also be used as a correction for the amides.Corrected 6 values obtained in this way were subjected to a curve-fitting program with respect to eqn (2). The resulting values for H6(W) are listed in table 7. It appears that in FA the hydrophobic effect of the CH group is equal to - 3.7 kJ mo1-l. Hb(W) of the CH3406 SOLVATION + HYDRATION OF UREAS + AMIDES group in the formamides can also be obtained from the difference between $Hb(W) for TMU and Hb(W) for DMF (see table 6). The result, -3.8 kJ mol-', is in remarkable agreement with the value from table 7. Since no corrections have been applied to the experimental results for TMU and DMF, this close agreement corroborates the reliability of our correction procedure for the amides. These considerations show that FA is slightly hydrophobic.Indeed the curve for FA in fig. 2 shows a slight maximum at high X , and is distinctly different from the curve for (non-hydophobic) U in fig. 1. The Hb(W) values in table 7 for AA and BA refer to a methyl and an n-propyl group, respectively, as C-substituents. For NMF and NBA the Hb(W) values are the sum of contributions of two different groups. In TABLE 7.-ENTHALPIC EFFECTS OF HYDROPHOBIC HYDRATION OF AMIDES ACCOUNTING FOR NH CONTRIBUTIONS solute ' corrections ' - Hb(W)/kJ mol-l FA - is( U) NMF - @(U) AA - id( U) NBA - as( U) BA - $3(U) DMF - DMA - 3.7 10.9 16.1 8.0 19.3 22.6 14.9 NMF the effect is due to a CH and a methyl group. Adoption of a contribution from CH as -3.7 kJ mol-l leaves a value of -7.2 kJ mol-1 for the methyl group, which compares very well with the Hb(W) value for the methyl group in AA.In the same way the contribution of the n-butyl group in NBA can be estimated at - 14.6 kJ mol-l. The procedures applied above give us the opportunity to calculate Hb(W) and n values for the separate alkyl groups of all compounds used in this study. For example, subtracting the 6 values of DMF from the contributions of the CH group [equal to 6(F)-@(U)], gives the sum of the contribution of two methyl groups. The resulting 6 values can be analysed by means of eqn (2). For the substituted acetamides DMA and NBA we have eliminated the contribution of the C-substituted methyl group by substraction of the values of 6(AA). In this way we obtained values for Hb(W) and n of methyl groups in various compounds and of ethyl, n-propyl and n-butyl groups in one solute.They are given in table 8, together with A, the mean deviation of the fit to eqn (2). Table 8 also indicates the different subtraction procedures used. From table 8 it is clear that Hb(W) values of methyl groups in ureas and amides are comparable. In our view any differences are mainly caused by deficiencies in the calculation procedures. Table 8 also shows that the values of n increase with the size of the alkyl group. The same trend has been observed with other compounds.' We have shown earlier3 that absolute values of n do not bear any physical significance and that only trends are important. The change in Hb(W) with the number of C atoms in the alkyl groups is shown in fig. 5, in which we used an average value for the methyl groups.Fig. 5 includes earlier results for alcohols' and amines.2 Although the amount of data from ureas and amides is limited, a distinct parallelism between the three classes of compounds can be observed. The value of Hb(W) for an n-propyl group in the curve for the amides seems to deviate. It originates from BA. This is not surprising since BA has a backbone of four carbon atoms. A similar high value of Hb(W) can be observed for AA.A. ROUW AND G . SOMSEN 3407 TABLE 8.-ENTHALPIC EFFECTS OF HYDROPHOBIC HYDRATION AND THE NUMBER OF HYDRATION SITES PER ALKYL GROUP FOR ALKYL GROUPS IN VARIOUS COMPOUNDS alkyl group subtraction procedure -Hb(W)/kJ mol-' n A/kJ mol-I Me Me Me Me Me Me Me Me Et n-Pr n-Bu d(MU) -;d(U) t[d( 1 1 -DMU) - @(U)] &[d( 173-DMU) -+d(U)] G(NMF) - [d(F) - td(U)] +(d(DMF)-[d(F)-&d(U)]) 6(AA) - @(U) d(EU) -id(U) d(BA) - &S(U) G(NBA) - [d(AA) -$d(U)] $d(TMU) t@(DMA) - [ W A ) - mJ>l> 7.1 6.5 6.6 6.2 8.1 7.0 5.6 8.0 10.7 14.9 15.1 4.0 0.07 3.5 0.08 4.3 0.08 5.1 0.02 3.4 0.06 3.0 0.08 4.0 0.03 4.4 0.09 5.5 0.09 6.6 0.14 8.7 0.16 I I I I I I I 1 2 3 4 5 6 number of carbonatoms FIG.5.-Variation of Hb(W) with the number of C atoms in alcohols (x), amines (0) and ureas + amides (0). Recently Spencer et aZ.14 discussed the enthalpic effects caused by the transfer of amides from non-aqueous solvents to water. From an analysis of the transfer process they calculated the difference in the enthalpic effect caused by the structuring of the water molecules around DMF and DMA, and found a value of 6.8 kJ mol-l.From our results we calculate a difference of only 3.2 kJ mol-l. In our view this discrepancy may be caused by the fact that the value of Spencer et al. was obtained as a remainder, after calculation of several other contributions to the transfer enthalpies. This remainder is exclusively assigned to the water-structuring effect, without accounting for differences between the transfer enthalpies of the CON groups in DMF and DMA. We are grateful to Dr M. Booij for helpful discussions.3408 SOLVATION + HYDRATION OF UREAS + AMIDES A. C. Rouw and G. Somsen, J. Chem. Thermodyn., 1981, 13, 67. A. C. Rouw and G. Somsen, J. Solution Chem., 1981, 10, 533. W. J. M. Heuvelsland, M. Bloemendal, C. de Visser and G. Somsen, J. Phys. Chem., 1980,84,2391. I. M. Klotz and J. S. Franzen, J. Am. Chem. 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