214 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 214–215† Substituent Constants of the N�CH·NMe2 Group and their Application to the Prediction of the Basicity of Each Site in Bifunctional Amidines† Ewa D. Raczy�nska‡ Institute of General Chemistry, Agricultural University, 02528 Warszawa, Poland Selected s-type values of the N�CH·NMe2 group are estimated and together with literature structure–basicity relationships used to predict the so-called ‘microscopic’ basicity of each site in bifunctional compounds.Structure–reactivity relationships have always attracted the attention of chemists. In 1937 Hammett,1 looking for quantitative models of similarity, proposed eqn. (1), which describes the relationship between the equilibrium or rate constant for substituted (K or k) and unsubstituted (K0 or k0) derivatives in a reaction series, the reaction constant (r) and the substituent constant (s). log K (or k)=log K0 (or k0)+rs (1) The Hammett equation and its modifications have successfully been applied to different reactions of aromatic and aliphatic systems in solution as well as in the gaseous phase.2,3 Depending on the reaction series investigated, different types of s have been proposed,4,5 e.g.s, s0, s+ and sµ, for the description of the total substituent electronic effect, s*, sI, sF for the inductive (field) effect, sR, sR 0, sR +, sR µ for the resonance (mesomeric) effect and sa for the polarizability effect.In the case of amidines, which are interesting because of their high basicity6 and biological activity,7 many structure– basicity relations6,8–14 have been found but only a few s-type values for the amidine group have been proposed.13,15,16 The first estimates of sI and sR 0 for the N�CH·NMe2 group (Table 1) were carried out by Shorter15 on the basis of the 13C chemical shifts obtained for a series of XC6H4N�CH·NMe2 (FDMPs).17 The proposed sI and sR 0 values, when compared with the literature data for the NMe2 group (Table 1), indicate that the CH�N group decreases the effects of the NMe2 group by slightly different factors.For the inductive effect (sI) the transmission factor of the CH�N group is equal to 0.50 and for the resonance effect (sR 0) equal to 0.56. Taking the values of sI (0.03) and sR 0 (µ0.29), the parameters sm 0 and sp 0 can be calculated using the equations sm 0=sI+asR 0 and sp 0=lsI+sR 0, which separate the total electronic effect of the substituent into inductive and resonance effects.4 Values of a=0.21 and l=1.16 for water for FDMPs18 were used.The sm 0 (µ0.03) and sp 0 (µ0.255) values obtained this way are almost the same as those found from the free v(OH) bond observed for FDMP (X=4-OH and 3-OH) and phenols:16 sm 0=µ0.05�0.1 and sp 0=µ0.25�0.1 (Table 1). The s0 values for the N�CH·NMe2 group are smaller than those for the NMe2 group.4,5 This means that the N�CH·NMe2 group is less electron-donating than the NMe2 group.The same behaviour is found for the sp + (µ1.1) value estimated on the basis of the stretching vibration of the C�O group for FDMP (X=4-COMe) and acetophenones (Table 1).13 Exceptions are found for the so called ‘push–pull’ molecules19,20 in which the amidine group is directly linked with a strong electron-accepting group. IR results obtained for N�C·N�CH·NMe2 and N�C·N�C(N�CH· NMe2)2 suggest that the N�CH·NMe2 group is more electron- donating to the resonance effect than the NMe2 group.The effective polarizability (ad) calculated for the N�CH·NMe2 and NMe2 groups from the equation proposed by Gasteiger and Hutchings21 and the literature5 value for sa(NMe2) are used for estimating the sa(N�CH·NMe2). The obtained results (ad=2.89, sa=µ0.40) when compared with those for the NMe2 group (ad=3.15, sa=µ0.44) show a slightly smaller polarizability of the N�CH·NMe2 group (Table 1). For the field effect described by sF, the transmission factor (0.50) of the CH�N group obtained from comparison of sI(N�CH·NMe2) and sI(NMe2) is used.Taking the literature5 value for sF(NMe2) we obtained sF(N�CH·NMe2)=0.05 (Table 1). The sa and sF values for the (CH2)nN�CH·NMe2 group (n=2 or 3) estimated in the same way as those for the N�CH·NMe2 group, and the literature11 values for sa and sF for the (CH2)nNMe2 group are also given in Table 1. The s value obtained for the N�CH·NMe2 group (Table 1) and the literature4,5 value for s(X) can be used to predict the so-called ‘microscopic’ basicities10 corresponding †This is a Short Paper as defined in the Instructions for Authors, Section 5.0 [see J.Chem. Research (S), 1997, Issue 1]; there is therefore no corresponding material in J. Chem. Research (M). ‡Email: raczynskae@delta.sggw.waw.pl Table 1 Comparison of the s values for amidine and amine groups Group sI µsR 0 µsp 0 µsm 0 µsp + sF µsa N�CH·NMe2 0.03a 0.29a 0.255 b 0.03b 1.0b 0.05b 0.40b 0.25d 0.05d NMe2 0.06e 0.52e 0.32e 0.10e 1.7e 0.10f 0.44f (CH2)2N�CH·NMe2 (CH2)2NMe2 0.015 b 0.03g 0.52b 0.57g (CH2)3N�CH·NMe2 (CH2)3NMe2 0.005 b 0.01g 0.54b 0.59g aRef. 15. bThis work. cRef. 13. dRef. 16. eRef. 4. fRef. 5. gRef. 11. Table 2 ‘Microscopic’a and ‘macroscopic’ (measured) gas phaseb (GB) and hydrogen bondingc (log KHB) basicities for the dibasic compounds: X·N�CH·NMe2 GB X N�CH·NMe2 X Measured NMe2 (CH2)2NMe2 (CH2)3NMe2 OMe (CH2)2OMe 4-C6H4NMe2 4-C6H4OMe 4-C6H4CN 943 961 966 904 952 977 959 917 901 919 922 750 850 890 750 830 951 982 997 908 972 975 961 917.5 log KHB X N�CH·NMe2 X Measured NMe2 (CH2)2OMe CN (CH2)2CN 4-C6H4COMe 4-C6H4CN 4-C6H4NO2 2.2 2.3 s0.5 2.0 1.5 1.3 1.2 s2.0 1.2 2.1 1.1 1.7 1.2 0.6 2.43 2.75 2.10 2.15 1.84 1.49 1.28 aSee in text.bRefs. 11, 12 and 23. cRefs. 13, 14 and 19.Me2N N (CH2) n H X¢ + Me2N N (CH2) n H X¢ OR J. CHEM. RESEARCH (S), 1997 215 to the basicity of the individual functional groups in the bifunctional XN�CH·NMe2 with basic sites in the amidine and X groups (Table 2). For the gas-phase basicity (GB) prediction of the amidine group in XN�CH·NMe2, linear structure–basicity relationships found previously for the monofunctional RN�CH·NMe2 (FDMs) [eqns.(5) and (8b) for alkyl and aryl FDMs from refs. 11 and 12, respectively] and the corresponding s(X) values are applied. The relationships obtained for the series of RNMe2 [eqn. (8f ) from ref. 11] and the s(N�CH·NMe2) values used to estimate the GB(X) in Me2N(CH2)nN�CH·NMe2.For MeO(CH2)2N�CH· NMe2, no equation is used and the estimation of the GB(X) is made on the basic of the literature data for ethers24 containing a similar number of carbon atoms as the bifunctional amidine. For other derivatives the GB(X) values calculated previously by an AM1 method12,22 are given in Table 2. For the estimation of the log KHB(N�CH·NMe2) in XN�CH·NMe2 in CCl4 equations log KHB=2.70µ4.58sF and log KHB=1.95µ0.90s0 found for the alkyl and aryl FDMs on the basis of literature data,13,14 together with the sF(X) and s0(X) values,4,5 were applied.An exception is N�C–N�CH·NMe2 for which the log KHB vs. Dv(OH) relationship and the value of Dv(OH) for the N�CH·NMe2 group, equal to that for the CN group,19 are used. The log KHB vs. Dv(OH) relationships obtained for the series of amines, ethers, nitriles and ketones25,26 and the Dv(OH) values for the NMe2, OMe, CN and COMe groups found for bifunctional amidines13,14 are used in estimating log KHB(X).For the NO2 group log KHB is estimated according to eqn. (7) from ref. 27. The ‘microscopic’ and measured basicities are given in Table 2. The results obtained confirm that in the gas phase (as in solution) the amidine group is more basic (by 40–200 kJ molµ1) than the basic group in X (Table 2) and is protonatecules.22. The hydrogen bond in the non-polar solvent CCl4 is preferentially formed with an electron-accepting group only for so called ‘push–pull’ molecules (e.g.for X=CN).19,20 When both groups are separated by the phenyl ring their hydrogen bonding basicities are of the same order of magnitude (e.g. for X=4-C6H4COMe and 4-C6H4CN).13 An exception is the nitro group for which a very weak hydrogen-bond basicity is observed. Separation by the (CH2)n group eliminates the ‘push–pull’ effect and a hydrogen bond is preferentially formed with the amidine group [e.g.for X=(CH2)2OMe and (CH2)2CN].14 Compounds with flexible conformation are interesting cases: Xp(CH2)nN�CH·NMe2 containing the OMe or NMe2 group, with n=0, 2 or 3, for which the measured basicities in the gas phase (GB) as well as in non-polar solvents (log KHB) are higher than these predicted for the amidine group (Table 2). In the gas phase this may result from proton ‘internal solvation’ by two basic groups, the amidine and Xp groups.23 In a non-polar solvent the formation of a three-centred complex is possible.In such a complex a hydrogen bond may be formed between ROH and two basic sites, the amidine group and the Xp substituent. Proton chelation by two basic groups increases the gasphase basicity of bidentate ligands by 8, 22 and 31 kJ molµ1 for derivatives with Xp=NMe2 and n=0, 2, 3, and by 4 and 20 kJ molµ1 for Xp=OMe and n=0, 2, respectively. The formation of a three-centred complex increases the hydrogen bonding basicity by ca. 0.4 log KHB units for derivatives with X=OMe and n=2. In conclusion the application of s together with the structure –basicity relationships in the prediction of ‘microscopic’ basicities for individual sites in bifunctional (or generally polyfunctional) compounds enables the explanation and estimation of additional effects, e.g. ‘internal’ solvation or the formation of a three-centred complex. I thank the Polish State Committee for Scientific Research for financial support.Received, 12th November 1996; Accepted, 12th March 1997 Paper E/6/07685H References 1 L. P. Hammett, J. Am. Chem. Soc., 1937, 59, 96. 2 J. Shorter, in Similarity Models in Organic Chemistry, Biochemistry and Related Fields, ed. R. I. Zalewski, T. M. Krygowski and J. Shorter, Elsevier, Amsterdam, 1991, ch. 2. 3 R. W. Taft and R. W. Topsom, Prog. Phys. Org. Chem., 1983, 14, 247. 4 O. Exner, in Correlation Analysis in Chemistry: Recent Advances, ed.N. B. Chapman and J. Shorter, Plenum Press, London, 1978, ch. 10. 5 C. Hansch, A. Leo and R. W. Taft, Chem. 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