摘要:

J. CHEM. SOC.PERKIN TRANS. 2 1992 FTIR Spectral Study of Hydrogen Bonding in w-Alkanedicarboxylic Acids in Dilute CCI, Solution Mamoru Takasuka," Kiyoshi Ezumi and Masumi Yamakawa Shionogi Research Laboratories, Shionogi & Co. Ltd., Fukushima- ku, Osaka 553,Japan FTIR spectra of the title compounds, HO,C(CH,),CO,H (n = 4-14) 2-12, were measured in dilute CCI, solution. For compounds 2-7, double cyclic intermolecular hydrogen bonds (11) similar to those observed for glutaric acid 1 were found between the carboxy groups, while 8-12 had cyclic intramolecular hydrogen bonds (IVb). A zigzag correlation was found between the percentage (h) of the double cyclic intermolecular hydrogen-bonded molecules and the n value. The h values of odd-membered compounds were larger than those of even-membered ones and the latter values increased with increasing n value.The h value for 7 (n = 9), which forms a 28-membered ring, was 82%. The percentages of the cyclic intramolecular hydrogen-bonded molecules showed the high value of 97% for 12 (n = 14). Conformational analyses on compounds 1-12 were carried out using the AM1 method. The hydrogen bondings observed in solution are discussed on the basis of the results. The thromboxane A, receptor antagonist S-145' and its chain- analogues [PhSO,NH(CH,),CO,H (n = 6-8, 10 and ll)] form intramolecular hydrogen bonds I involving a ring of many members which forms between the carboxy and sulphonamido groups, and there is a positive linear relationship between the percentage of the hydrogen-bonded molecules and the n However, no information is available on the intra- molecular hydrogen bonds in o-alkanedicarboxylic acids [HO,C(CH,),CO,H].It has been also reported that double cyclic intermolecular hydrogen bonds I1 involving a 16-membered ring in glutaric acid (n = 3) 1 are formed between the carboxy groups, but intramolecular hydrogen bonds are 0-H----0. I m IVa HOOC(CH,),COOH ln=3 7n=9 2n=4 8n=10 3n=5 9n=11 4n=6 10 n= 12 5n=7 11 n= 13 6n=8 12 n = 14 not. Therefore, we were interested in o-alkanedicarboxylic acids (n = 4-14) 2-12, which can form intermolecular hydrogen bonds IT and TI1 and intramolecular hydrogen bonds IVa and IVb. In order to study these hydrogen bonds, we carried out measurements of FTIR spectra on these compounds in dilute CCI, solution.The concentration dependence of the FTIR spectra of 3, 5 and 7-12 was also measured. Full optimization curve analysis was applied to all spectra because of a separation of overlapping absorption bands. The correlation between the number (n)of methylene groups and the percentage (h)of the double cyclic intermolecular hydrogen-bonded molecules of type I1 was examined for cu-alkanedicarboxylic acids. To help determine the hydrogen bond structures of 2-12, their geometries were optimized by the AM1 method.6 Experimental Compounds 2-12 were obtained from commercial sources. They were purified by recrystallization. The elemental analyses were within +0.3% of the theoretical values. FTIR spectra were recorded on a Nicolet 20SXB FTIR spectrometer at 27 "C. The solvent CCl, was dried over 4 8, molecular sieves and purified by distillation. The compounds were dissolved in CCI, at concentrations (c) below 3.1 x mol dm-3 (cell length = 5.0 cm).All operations on the solutions were performed under nitrogen in a dry box. The curve-fitting calculations for peak separation of the observed spectra were carried out using the Nicolet FOCAS program. The AM 1 calculation was carried out on a VAX 6320 computer using MOPAC (Ver. 5.0)in the SYBYL molecular modelling system. For compounds 2, 4, 6 and 8, the FTIR spectra were measured for a saturated CCI, solution because of low solubilities. Since no o-alkanedicarboxylic acid which is freely soluble in CCI, is available, the true molar absorption co- efficients for the free and dimer vC," bands of its carboxy groups were not obtained, where vCz0 indicates the C=O stretching vibration.Hence the c values for 2,4,6 and 8 were estimated by the following approximation. In CCI, solution, we had previously found the value of the integrated intensity (A/1OP8 cm2 s-' molecule-') of the free \I~=~band at 1759 cm-' and the Avalue per vca band of the dimer at 171 1 cm-' for lauric acid [CH,(CH,),oC02H] to be 133 and 170, respectively.2 If compounds 2-12, which have two carboxy groups, coexist in the free and hydrogen-bonded forms at equilibrium in CCl, solution, the total Avalues of their vCa bands are presumed to be between 266 and 340. The total Avalue of the vca bands observed for 1, 3, 5, 7 and 9-12 were in the range 292-314.30 J. CHEM. SOC. PERKIN TRANS. 2 1992 Table 1 FTIR spectral data' of compounds 1-12 in CCI, solution (5 cm cell) A/ c/dm3 cm2 s-' ch/lO-S Com-Assign-mol-' Avt/ mole-N" of /~(p)~ mol cr,i pound nb SC ment vjcm-' crn-.' cm-cule-' (%) (%I (7% (%I 15 3 F 1759.5 270.1 18.4 65.8 26.9 2.0 71.1 2.8459 18.6 H 1722.8 900.0 15.1 179.5 H 1708.4 243.9 16.7 50.9 2J 4 F 1760.0 686 20.5 177 68 3 29 (0.7073) 5 H 1721.8 252 9.3 38 H 1713.7 262 18.0 65 3 5 F 1759.1 122.1 16.5 24.7 12.2 0.2 87.6 2.8969 18.9 H 1712.8 1375.1 14.2 283.0 4 6 F 1758.7 488 19.7 123 49 3 48 (1.3706) 10 H 1712.1 764 16.5 167 5 7 F 1758.7 161.9 18.1 35.7 16.1 0.6 83.3 3.0070 19.4 H 17 10.8 1315.9 14.7 268.3 6 8 F 1758.3 363 19.3 90 36 2 62 (1.7386) 13 H 171 1.2 956 15.4 200 7 9 F 1758.4 171.2 16.6 35.7 17.0 0.7 82.3 2.9221 19.0 H 1710.4 1327.2 13.7 264.2 8 10 F 1758.4 I52 19.0 35 15 0 (85) (2.3 1 15) 16 H' 1712.4 1133 16.6 265 9 11 F 1756.6 92.4 20.9 23.5 9.2 0.0 (90.8) 2.6030 17.5 H' 1711.6 1147.8 17.0 268.7 10 12 F 1759.0 38.1 18.0 8.4 3.8 0.0 (96.2) 2.6242 17.6 H' 1710.8 1337.7 15.4 289.9 11 13 F 1757.7 37.5 15.3 7.1 3.7 0.0 (96.3) 2.9884 19.3 H' 1709.4 1478.3 14.3 296.3 12 14 F 1759.0 26.8 18.0 6.0 2.7 0.0 (97.3) 2.9887 19.3 H' 1709.7 1635.6 13.1 307.I "v, c, All; and A are the band frequency, the molar absorption coefficient, the band width at half-intensity and the integrated intensity, " respectively. 'Number of methylene groups.Size of a ring formed by the double cyclic intermolecular hydrogen bonds 11, where the value in parentheses is the size of a ring formed by the cyclic intramolecular hydrogen bond IVb. F, H and H' show free vCa and intermolecular and intramolecular hydrogen-bonded vc=o bands, respectively, where vc=o is the C==Ostretching vibration. " Percentage (N) of non-hydrogen- bonded molecules, N = [~/(2x 501.9)]100, where 501.9 is the true E value of free vca band of lauric acid' and its value was doubled because compounds 1-12 have two carboxy groups. Assuming that the free molecules of 2 N% in 1-12 exist in equilibrium with dimers of the type I11 as well as in lauric acid, where the N value was doubled because compounds 1-12 have two carboxy groups, the percentage (a) of their dimers were estimated using the equation^,^.' cf = 2Nc/100, log cf = 0.245aOt -5.492 and a = a.N/lOO, where cf is the concentration of free molecules, c is the total concentration, and a. is the percentage of the dimers at cf. Because the G values estimated for all compounds are less than 3%, the existence of dimers of type 111 in 1-12 can be neglected in the curve analysis for the CCI, solutions examined. Percentage (h) of the double cyclic intermolecular hydrogen-bonded molecules, h = 100 -(N + cr), where the value in parentheses is the percentage (p) of the cyclic intramolecular hydrogen-bonded molecules, p = 100 -(N + a). Concentration, where the value in parentheses was estimated because the compound could not be completely dissolved in CCl, (see text).Percentage (a,) of dimers estimated based on the following assumptions: intermolecular I1 and intramolecular hydrogen bonds IV in 1-12 are not formed and an equilibrium in these compounds exists only between the free molecules and dimers of type 111. Regression analysis was done between the c and 0 values using the spectral parameters of lauric acid that we reported.2 The analysis gave the equation, log c = 0.2870i -5.484 (m = 7, r = 0.99), where m is the number of data points and r is the correlation coefficient. The at value of 1-12 was approximately estimated using the equation, log 2c = 0.2870,: -5.484, where the c value was doubled because these compounds have two carboxy groups.J The exact parameters were not obtained because of very low solubilities. Therefore, we assumed that the total A value of 2 is 280, that of 4 bonded molecules. The percentage (ol)of the dimers, which was and 6 is 290 and that of 8 is 300 because the total A value estimated based on the assumption that an equilibrium exists probably increases with increasing hvalue. The c values of these only between the free molecules and the dimers of type 111, was compounds were estimated from these A values. Although these also listed in Table 1. The FTIR spectra of 2 and 3 and the estimated c values change slightly with each FTIR spectrum results of the peak separations for their spectra are shown in Fig. measurement, the variation of the hvalues was within +2%.In 1. In general, the stronger the hydrogen bond, the greater the addition, it was assumed that the value of molar absorption lower wavenumber shift of the hydrogen-bonded vOH and coefficients and the A values of the vC," bands in 2-12 are vC," bands. equal to those of lauric acid because the pKa, and pKa, values For compounds 1-12, the intensity of the free vc,o bands of H02C(CH2),C02H are almost the same if n is greater than at ca. 1759 cm-' for the carboxy groups decreased and a new band appeared at lower wavenumbers. Correspondingly, the intensity of the free vOH band at ca. 3533 cm-' decreased and a new broad band appeared at ca. 3000 cm-'. The percentage (h Results and Discussion or p) of hydrogen-bonded molecules, 100 -(N+ o),in 1-Doubk Cyclic Intermolecular Hydrogen Bonding in 1-7 and 12 is much larger than the nt value estimated for these Cyclic Intraniolecular Hydrogen Bonding in 8-12.-The spectral compounds, and their o values are very small.These results parameters of the vcz0 bands for the carboxy groups in 1-12 suggest that compounds 2-12 form double cyclic hydrogen and their assignments are listed in Table 1, together with the bonds TI similar to those found for 1,5 indicative of a large percentages (N) of non-hydrogen-bonded molecules, (0)of association constant, or various intramolecular hydrogen dimers of type 111, (h)of double cyclic intermolecular hydrogen- bonds as shown previ~usly.~ bonded molecules and (p) of cyclic intramolecular hydrogen- The free vC4 band in 1-12 was not observed at J.CHEM. SOC. PERKIN TRANS. 2 1992 31 .0243 .206 - .0195 .165 - A .0146 A .123.123] I \ .0097 .0048 ,041 .oooo__.. .ooo 1800 1785 1770 1755 1740 1725 1710 1695 1680 1665 1790 1774 1758 1742 1726 1710 1694 1678 1662 1646 Waven umberkm-' Wavenu mbet7crn-l Fig. 1 FTIR spectra of 2 and 3 in CCl, solution and the results of peak separation of their spectra. Spectra were obtained using a 5.0 cm cell; 2 0.7073 x mol dm-3 (a) and 3 2.8969 x lo-' mol dm-3 (b). Table 2 Energy difference (Aqa between U-shaped and linear conformers and non-bonded distances (R)of U-shaped conformer for compounds 1-12 by AM1 calculation Distance b/A DistanceclA Com-AE/kcal pound mol-' 'O...O 'O...H 'O...O 'O...H 1 1.73 3.768 3.979 3.950 4.181 ( -0.76 3.166 3.229 3.561 3.868)d 2 0.83 4.249 4.458 4.602 4.821 3 2.60 2.767 2.301 2.999 2.576 4 1.47 2.826 2.20 1 2.841 2.205 5 -0.55 2.824 2.186 2.831 2.181 6 -0.33 2.866 2.134 2.846 2.137 7 -1.18 2.950 2.147 2.826 2.152 8 -1.13 3.014 2.131 2.976 2.123 9 -0.32 2.991 2.122 2.974 2.138 10 -1.53 3.023 2.101 3.062 2.127 I1 -0.21 3.035 2.102 2.93 1 2.117 12 -0.80 3.051 2.086 2.986 2.123 'Difference of the heat of formation between the conformers.Back non-bonded distance between oxygen and oxygen or hydrogen atoms (see Fig. 2). Front non-bonded distance between oxygen and oxygen or hydrogen atoms (see Fig. 2). Ref. 5; ab initio MO method at 3-21G (*) level (GAUSSIAN 86), where AE is the total energy difference.wavenumbers higher than 1760 cm-', indicative of a trans-carboxy group, in which the torsion angle H-O-C=O (z) is ca. 180".*The carboxy group, in which the zvalue had changed from 0 to 90",was found to have become extremely unstable according to the ah initio MO calculation^.^.^ If compounds 2-12 do not form the double cyclic intermolecular I1 and cyclic intramolecu-lar hydrogen bonds TVa or IVb, the 100 -(N + a) values are less than 50%. However, these values of all compounds were estimated to be more than 60%, when the values of 2,4 and 6 at 3 x mol dm-3 were estimated as mentioned below. These results suggest that if these compounds form hydrogen bonds, they should form bonds of type TI, IVa or IVb.For compounds S12, one sharp hydrogen-bonded vC4 band was observed in the narrow range of 1713-1 709 cm-'. These values are similar to the 1711 cm-' band of the lauric acid dimer.2 Furthermore, the hydrogen bonding interaction ability of n-electrons on the C=O bond as in IVa is much weaker than that of n-electrons as in 1Vb.l These results suggest that compounds 31 2 do not form hydrogen bonds of type IVa, but those of type IVb or 11. For compounds 1-12, a linear conformer and several U-shaped conformers were energetically optimized by the AM 1 method. The energy differences (AE)between the U-shaped and the linear conformers are listed in Table 2 together with the non-bonded distances (Ro...o and Ro...H) of the U-shaped Conformer.Stereoviews of the U-shaped conformer optimized for 1-12 are shown in Fig. 2. The U-shaped conformers of 5-12 are more stable than the linear one, but unstable in 14.However, the latter compounds have U-shaped conformations with local minimum energy. The U-shaped conformer of 1 with the h value of 71% has been found to be more stable than the linear one by ab initio calculation^.^ As shown in Fig. 2, all of the carboxy groups exist in planar conformation (z cu. 0') as predicted by the ab initio calculations5,9and the larger the n value, the flatter the two carboxy groups are in relation to each other. For compound 2, the Ro. .. values optimized by the AM1 calculation are much larger than the sum (2.6 A) of the van der Waals radii of these atoms.This suggests that compound 2 does not form cyclic intramolecular hydrogen bonds IVb, but does form double cyclic intermolecular hydrogen bonds I1 similar to those observed for l.5 In addition, compound 2 gave two intermolecular hydrogen-bonded v,-.~ bands as shown in Fig. 1, suggesting that an equilibrium exists between two conformers of the 18-membered ring. Although the R,. .. values of 3-12 are smaller than 2.6 A, it is presumed that in compounds with a small n value, cyclic intramolecular hydrogen bonds IVb cannot form because their two carboxy groups do not lie in the same plane due to the conformational restriction, but the double cyclic intermolecular hydrogen bonds I1 can form. On the other hand, it is also presumed that in compounds with a large n value, the cyclic intramolecular hydrogen bonds IVb can form because the two carboxy groups nearly lie in the same plane.When the n value is more than nine, these groups nearly lie on the same plane, as shown in Fig. 2. To examine these assumptions, the concentration dependence of the FTIR spectra of $5 and 7-12 was measured. A significant decrease in the 100 -(N + a) value was observed for 3, 5 and 7 at concentrations below 3 x mol dm-3, when compared with the result for that at 3 x mol dmP3,but not for %12. These results indicate that compounds 3,5 and 7 form a very large ring due to double cyclic intermolecular hydrogen bonds I1 similar to those found for 1 and 2, while compounds 8-12 form cyclic intramolecular hydrogen bonds IVb.From these findings, it is deduced that the hydrogen bonds in 4 and 6 are of the same type as those of the former compounds. Thus, the hydrogen-bonded structures of 2-12 in dilute CCI, solution were revealed, and the result was found to be consistent with those from the AM 1 calculations. These phenomena markedly differ from those observed for PhS0,NH(CH2),C02H.4 CorreZations between h and n Values.-Fig. 3 shows plots of the N, 0, h and p values against the n and S values, where S is the size of the ring formed by the double cyclic intermolecular or cyclic intramolecular hydrogen bonds. The h values of 2, 4 32 J. CHEM. SOC. PERKIN TRANS. 2 1992 8 w 9 10 11 12 Fig. 2 Stereoviews of the conformations for 1-12 optimized by AM 1 calculations.These may not be the most stable U-shaped conformers because a complete systematic search was not carried out over all the conformational space. Numbers indicate compounds. and 6 are estimated to be small due to low solubilities. Assuming that the relationships between the c and h values in these compounds are similar to those between the c and h values in glutaric acids,5 the h values of 2,4 and 6 at 3 x lop5mol dmp3 were estimated from these relationships to be 61% for 2,65% for 4 and 72% for 6. These values are plotted against the n and S values in Fig. 3. In even-membered compounds, the h values increased with increasing n or S value. The p values also increased with increasing n or S value.The correlation between the h and n values was found to be a zigzag line, and the h values of the odd- membered compounds were larger than those of the even-membered ones.* This indicates that the formation of 16, 20-, 24- and 28-membered rings due to the double cyclic inter- molecular hydrogen bonds IT in the odd-membered compounds occurs more easily than that of 18-, 22-and 26-membered rings in the even-membered ones. It has been reported that in dimeric cyclophanes (n = 4-9), the calculated strain energies, which are mainly attributed to the methylene chains, of the odd- membered compounds are smaller than those of the even-membered ones. This suggests that the h values in w-alkane- dicarboxylic acids are primarily governed by these strain energies.In conclusion, we have found that compounds 2-7 form double cyclic intermolecular hydrogen- bonded dimers involving 18- to 28-membered rings, respectively, while compounds 8-12 form the cyclic intramolecular hydrogen-bonded monomer * The zigzag correlation between the melting point (m.p.) and the n value in o-alkanedicarboxylic acids is well known. Thus the correlation between the h and m.p. values was examined. In spite of the fact that these values widely differ in their physical properties, two correlations were found between these values: the h value of the odd-membered compounds roughly increases with an increasing m.p. value while, in the case of the even-membered compounds, the h value decreases. S 16 18 20 22 24 26 28 15 16 17,A-A-x 18 19 I 90 L J"' 80 h 70 $ v P 60 Uc a 50 .sr 6' 40 z-30 20 10 t \ 0 3 4 5 6 7 8 9 1011 121314 n CJ h (0)and p (x) with chain Fig.3 Variations of N (A), (O),length for HO,C(CH,),CO,H in CCl, solution at concentrations below 3.1 x mol dm-3. * Estimated h value at 3 x mol dm-3 (see text). involving 15-to 19-membered rings, respectively. This inform- ation should be very important for understanding the hydrogen bonding of dicarboxylic acids, and studying their molecular interactions. References 1 M. Narisada, M. Ohtani, F. Watanabe, K. Uchida, H. Arita, M. Doteuchi, K. Hanasaki, H. Kakushi, K. Otani and S. Hara, J. Med. Chem., 1988,31,1847. J.CHEM. SOC. PERKIN TRANS. 2 1992 2 M. Takasuka, M. Yamakawa and F. Watanabe, J. Chem. SOC., Perkin Trans. 2, 1989, 1173. 3 M. Takasuka, M. Yamakawa and M. Ohtani, J. Chem. Soc., Perkin Truns. 2, 1990, 1467. 4 M. Takasuka, M. Yamakawa and M. Ohtani, J. Med. Chem., 1991, 34, 1885. 5 M. Takasuka, T. Saito and M. Yamakawa, J. Chem. Soc., Perkin Trans. 2, 1991, 1513. 6 M. J. Dewar, E. G. Zoebisch, E. F. Healy and J. J. P. Stewart, J. Am. Chem. Soc., 1985, 107, 3902. 7 (LI) L. S. Darken, J. Am. Chem. Soc., 1941,63, 1007; (h)W. J. Hamer, J. 0.Burton and S. F. Acree, J. Research Natl. Bur. Standards, 1940, 24, 269; (c.) G. D. Pinching and R. G. Bates, J. Research Natf. Bur. Stuntlurcls, 1950,45,322,444;(d)R. Gane and C. K. Ingold, J. Chem. Soc., 1928, 1594; (P) M. L. Dondon, J. Chim. Phys. Phys.-Chim. Biol., 1957,54, 290. 8 M. 6ki and M. Hirota, Bull. Chem. Soc. Jpn., 1961,34, 374. 9 K. B. Wiberg and K. E. Laidig, J. Am. Chem. SOC.,1987, 109, 5935. 10 (a)L, Joris and P. R. Schleyer,J. Am. Chem. SOC.,1968,90,4599; (b) M. Oki, H. Iwamura, J. Aihara and H. Iida, Bull. Chem. Soc. Jpn., 1968,41, 176; (c)P. M. Rust and J. P. Glusker, J. Am. Chem. Soc., 1984,106,1018; (d) A. C. Legon, Chem. SOC.Rev., 1990,19, 197. 11 R. B. Bates, S. Gangwar, V. V. Kane, K. Suvannachut and S. R. Taylor, J. Org. Chem., 1991,56, 1696. Paper 1104219J Received 13th August 1991 Accepted 25th September 1991

ISSN:1472-779X    

DOI:10.1039/P29920000029

出版商:RSC    

年代:1992

数据来源: RSC