J . Phys. Chem. 1994,98, 3694-3696
3694
On the Hydrogen-Bonded Status of 2-Azacyclononanone and 2-Azacyclotridecanone in the Solid State Raymond D. Skwierczynski and Samuel H. Cellman’ S. M . McElvain Laboratory of Organic Chemistry. Department of Chemistry, University of Wisconsin, 11 01 University Avenue, Madison. Wisconsin 53706 Received: November 29, 1993; In Final Form: January 26,1994”
Triggs et al. (J. Phys. Chem. 19!33,97,5535) have recently reported the results of a preresonant Raman study of 2-azacyclononanone (2) and 2-azacyclotridecanone (3) in the solid state. These workers examined a number of spectroscopic features and concluded that “all the Raman spectral indicators of hydrogen bonding are negative” for these two lactams. We have compared the published Raman data for 2 and 3 with IR data from older literature and new FT-IR data; the comparison reveals that determination of these molecules’ hydrogen-bonded state in the solid is not as straightforward as implied by Triggs et al. Previously, hydrogen bonding of amide groups has most commonly been deduced from the position of the N-H stretch band. According to the conventional interpretation, the N-H stretch band positions for 2 and 3 indicate that these molecules are hydrogen bonded in their crystalline forms. We suggest that the variations in Raman spectroscopic features reported by Triggs et al. stem from effects that are more subtle than simply the presence or absence of hydrogen bonding.
Molecules containing both hydrogen bond donor and acceptor sites usually form the maximum number of hydrogen bonds in the solid state.’ Triggs et al. have recently reported a Raman study of three lactams in the solid state, 2-azacycloheptanone (caprolactam (l)), 2-azacyclononanone (2), and 2-azacyclotridecanone (3).*These workers concluded that 1 is hydrogen
stretch and other vibrations. Bands that may be affected by hydrogen bonding include the amide I, 11, and 111.4 In their analysis of 1-3 in the solid state, Triggs et al. focused on three spectroscopic features that they have deemed to be characteristic of hydrogen bond formation in preresonant Raman spectra (266-nm excitation): (i) the position of the amide I band, (ii) the width of the amide I band, and (iii) the intensity ratio amide 1:amide 11, for cis amides, or amide I:(amide I1 amide 111)/2, for trans amides.2 This last ratio is reported to be very sensitive to hydrogen bonding and the “most compelling piece of evidence” in their study of 1-3. Since N-H stretch band data are most commonly used to detect hydrogen bonding of amide~,~*s Triggs et al. also examined this feature (position and width) in the Raman data they obtained for 1-3. On the basis of these five spectroscopic features, these workers concluded that “all the Raman spectral indicators of hydrogen bonding are negative” for 2 and 3. Triggs et al. noted that this deduction appears to contradict the available crystallographic data6 for 2 (no crystal structure for 3 has been reported). The hydrogen-bonding behavior of lactams 1-3 has also been examined by IR methods.7~8 Hallam and Jones studied a homologous lactam series, including 1-3, in the pure state and dissolved in Cc14.’ For 3 in dilute C C 4 solution, these workers reported three bands in the N-H stretch region, at 3467, 3452, and 3350 cm-1. The lowest energy band’s relative intensity grew with increasing concentration. The 3467- and 3452-cm-I bands were assigned to the N-H group in a non-hydrogen-bonded state. The lactam ring in this case is large enough that the amide group exists exclusively in the trans configuration, and the presence of two non-hydrogen-bonded bands was ascribed to the existence of two distinct conformations of the 13-memberedring. The lowest energy band (3350 cm-I) was assigned to a hydrogen-bonded N-H. Hallam and Jones were unable to dilute the sample sufficiently to eliminate this band (their lowest concentration was 2 mM). We have repeated this study with a modern FT-IR spectrometer. As shown in Figure 1, we see behavior very similar to that reported by Hallam and Jones. At 0.1 mM, there may still be a small band in the hydrogen-bonded N-H stretch region, although poor signal-to-noise and baseline distortionsarising from subtraction make it difficult to analyze this region. Hallam and Jones noted that the hydrogen-bonded N-H band for 3 moved from 3352 cm-’ in dilute C C 4 to ca. 3300 cm-l in thesolidstate. Interestingly,curve-fittinganalysisofourspectrum
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1
2
3
bonded in the solid state, as expected, but that 2 and 3 are not hydrogen bonded in the solid state. These deductions were based primarily on interpretation of amide I, amide 11, and amide I11 band intensities, but Triggs et al. also examined N-H stretch band data and concluded that these features were consistent with their deductions. We point out here that the conclusions reached by Triggs et al. for lactams 2 and 3 actually contradict wellprecedent4 guidelines for interpretation of amide N-H stretch band positions. According to the conventional interpretation, the N-H stretch band positions reported for solid 2 and 3 by Triggs et al. imply that these lactams are hydrogen bonded in the solid state. It therefore seems likely that the spectroscopic variations detected by Triggs et al. reflect differences among hydrogen-bonding interactions rather than whether or not hydrogen bonding occurs. Vibrational spectroscopy is one of the most important methods for identifying hydrogen-bonding interactions.3 Most hydrogen bonds involve N-H or 0-H donors, and the N-H or 0-H stretch band undergoes large and characteristic changes upon hydrogen bond formation: (i) the position of the band is red-shifted, (ii) the band broadens, and (iii) the intensity of the absorption increases. Characteristicchanges may also be observed for certain types of acceptor groups, particularly carbonyls, upon hydrogen bond formation. Hydrogen bond acceptance is usually signaled by a red-shift of the C=O stretch band, although the magnitude of the shift is smaller than that observed for N-H or 0-H stretch bands. For amides, the C=O stretch band is mixed with C-N *Abstract published in Advance ACS Abstracts, March 15, 1994.
0022-3654/94/2098-3694$04.50/0
0 1994 American Chemical Society
Hydrogen Bonding in Lactams
The Journal of Physical Chemistry, Vol. 98, No. 14, 1994 3695
3 &006 2kAVENUMBER & 3 0 0
Figure 1. N-H stretch region FT-IR spectra of lactam 3 in CCl4 at various concentrations: top, 0.1 mM; middle, 1.0 mM; bottom, 10 mM. The non-hydrogen-bonded band maxima are 3467 and 3452 cm-I; the hydrogen-bonded maximum is 3353 cm-I. The data were obtained on a Nicolet 740 spectrometer at 2-cm-I resolution. Lactam 3 was purchased from Aldrich Chemical Co. and recrystallized before use. In
In
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0 1
Figure 2. Curve-fittinganalysisof the N-H stretch region IR spectrum of 10 mM 3 in CCld (see Figure 1, bottom). (a) Reconstructed spectrum superimposed on the observed spectrum. The analysis was carried out with the FOCAS software from Nicolet. (b) Four calculated bands superimposed on the observed spectrum; calculated maxima (fwhm): 3468 (11 cm-I), 3452 (14 cm-I), 3353 (52 cm-I), 3310 cm-I (50 cm-I).
for 10 mM 3 in CCl, revealed a minor band at 33 10 cm-I (Figure 2). It is not clear why there should be two hydrogen-bonded N-H stretch band positions under these conditions. The explanation cannot be related to the doubling of the non-hydrogenbonded bands of lactam 3, because N-methylacetamide also shows a doubling of the hydrogen-bonded N-H stretch bands: the maximum occurs at 3365 cm-1 in a 10 mM solution in C C 4 and a t 3310 cm-1 in a 100 mM solution (data not shown). For both 3 and N-methylacetamide, the higher energy band (3353 and 3365 cm-1, respectively) may arise from hydrogen-bonded dimers, while the lower energy band (3310 cm-I in both cases) may arise from higher aggregates. This hypothesis is consistent with the fact that both amides show only the 3310-cm-l band in the solid state. The N-H stretch data are somewhat more complex for 2 than for 3, because in solution lactam 2 exists in both the cis and trans forms. In dilute C C 4 solution, four bands were observed by Hallam and Jones between 3462 and 3397 cm-I, all assigned to non-hydrogen-bonded forms. Bands assigned to hydrogen-bonded N-H were observed at ca. 3300 and 3200 cm-I in ccl4, with the 3300-cm-1 band growing in intensity relative to the 3200 cm-I band at higher concentrations. In the solid state, the major band in the N-H region appeared at ca. 3300 cm-1. We see similar
behavior on a modern FT-IR instrument (not shown). The ca. 3300-cm-l band may be assigned to hydrogen-bonded N-H of 2 containing the trans configuration about the amide C-N bond, and the ca. 3200-cm-I band may be assigned to the hydrogenbonded N-H of 2 containing the cis configuration about the amide C-N bond. These assignments are supported by structural correlations. Lactam 2 is exclusively trans in the solid state, where only theca. 3300-cm-1 band is observed. Further, lactam 1, which must always exist in the cis form (because of the small ring size) shows hydrogen-bonded N-H stretch bands at ca. 3200 cm-1 in solution and the solid state. We may summarize the detailed analysis in the three preceding paragraphs in a simple way: the conventional interpretation of the N-H stretch IR data for 2 and 3 is that intermolecular hydrogen bonding does not occur in very dilute CC14 (all N-H stretch bands 1 3397 cm-1); in more concentrated C C 4solution and in the solid state, the presence of bands I3353 cm-I indicates the occurrence of intermolecular hydrogen bonding. This interpretation is in line with many other IR-based studies of hydrogen bonding in amides.395J In their preresonant Raman analysis of solid 2 and 3, Triggs et al. observed N-H stretch bands at 3314 and 3309 cm-1, respectively, consistent with the IR data.2 These authors concluded that these band positions constituted “strong substantiating evidence” for their hypothesis that lactams 2 and 3 are not hydrogen bonded in the solid state. This conclusion is clearly at odds with the standard interpretation of N-H stretch band positions in IR spectra. (Curiously, Triggs et al. noted that N-methylacetamide in the solid state, which they acknowledged to be fully hydrogen bonded, shows an N-H stretch band a t 33 10 cm-I.) Since the N-H stretch band positions for solid 2 and 3, as monitored either by preresonant Raman or IR, are completely consistent with the conventional expectation that these molecules are hydrogen bonded in the solid state, it is not correct to assert that “all the Raman spectral indicators of hydrogen bonding are negative” for 2 and 3.9 Triggs et al. also concluded that preresonant Raman N-H stretch bands widths for solid 2 and 3 indicated that these materials were not hydrogen bondeda2 For the N-H stretch bands of 2 and 3, they observed fwhm values of 15 and 32 cm-I, respectively, while the corresponding values for 1 and N-methylacetamide were 42 and 60 cm-l, respectively, in the solid state. For 3 in C C 4solution (Figure 2), the 3353-cm-1 hydrogen-bonded N-H stretch band shows a fwhm of 52 cm-I, and the 3310-cm-I hydrogen-bonded band shows a fwhm of 50cm-1. (FT-IR analysis of a solid sample of 3 (KBr pellet; not shown) indicated an N-H band fwhm of ca. 75 cm-I.) The non-hydrogen-bonded N-H stretch bands in Figure 2, at 3468 and 3452 cm-I, show fwhm values of 11and 14 cm-1, respectively. Thus, the band broadening typically associated with hydrogen bond formation is observed for N-H stretch bands I3353 cm-1 in the IR spectra. It is not clear to us why such broadening is not observed in the preresonant Raman spectra, but the difference between the Raman and IR bandwidths suggests that one should be cautious in attributing the narrowness of the former to a lack of hydrogen bonding. In addition to problems associated with the interpretation of N-H stretch band data, there appears to be an inconsistency in the interpretation of amide 1-111 band intensity ratio data by Triggs et ale2 These workers state that changes in the ratios amide 1:amide I1 (for cis amides) and amide I:(amide I1 + amide III)/2 (for trans amides) are “the quantitatively most pronounced effect of hydrogen bonding” among the Raman data. For 266nm excitation, according to these authors, this ratio is ca. 2.6 for non-hydrogen-bonded states (gas phase or dilute solutions in aprotic solvents); however, “in protic solvents or neat liquid solutions of secondary amides, where hydrogen bonding will be appreciable”, ratios in the range 0.2-0.5 are expected. These interpretational guidelines are based in part on an earlier study
Skwierczynski and Gellman
3696 The Journal of Physical Chemistry, Vol. 98, No. 14, 1994 by Triggs and Valentini,lo but careful reading of that earlier study provides contradictions to these simple rules of thumb. Figure 10 of the earlier paperlo shows preresonant Raman data for N-methylacetamide under various conditions, including the neat liquid, where the molecule “is most certainly hydrogen bonded”, according to the authors. In discussing thesedata, Triggs and Valentini note that the amide I:(amide I1 + amide III)/2 ratio for neat liquid N-methylacetamide is 1.6.l This value clearly falls between the two diagnostic ranges discussed by Triggs et al. for determining whether or not hydrogen bonding occurs. Given the apparent ambiguity of the N-methylacetamide data, it is not clear that variations in the preresonant Raman amide I:(amide I1 +amide III)/2 (or amide 1:amide 11) ratios will provide reliable indications of the presence or absence of hydrogen bonding. We suggest that one should not try to define interpretational rules regarding preresonant Raman amide I:(amide I1 amide III)/2 ratios until a larger number of amides have been characterized by Raman spectroscopy under conditions in which independent information on the hydrogen-bonded state is available. In summary, we have shown that the most conventional interpretation of the total body of preresonant Raman and IR data for lactams 2 and 3 is that these molecules are hydrogen bonded in the solid state. We suggest that the variations in spectroscopic signature detected among 1-3 by Triggs et a1.2 may stem from effects that are more subtle than simply the presence or absence of hydrogen bonding. If this hypothesis is borne out, then preresonant Raman data like those reported by Triggset al.2mayultimately provideinformation on subtle aspects of hydrogen-bonding interactions (e.g., aqueous solvation) that are not available from other spectroscopic methods. Verification of this promising possibility, however, must await systematic studies of larger numbers of examples.
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Acknowledgment. We thank Professor James J. Valentini for helpful discussions. This work was supported by the National Science Foundation (Grant CHE-9224561). R.D.S. is a Fellow of the Pharmaceutical Manufacturers’ Association Foundation. S.H.G. is a Fellow of the Alfred P. Sloan Foundation. References and Notes (1) Etter, M. C. Acc. Chem. Res. 1990,23,120 and references therein. (2) Triggs, N. E.;Bonn, R. T.;Valentini, J. J. J . Phys. Chem. 1993,97, 5535. (3) Pimentel, G.C.; McClellan, A. L. The Hydrogen Bond; Freeman: San Francisco, 1960. Hamilton, W. C.; Ibers, J. A. Hydrogen Bonding in Solids; W . A. Benjamin: Reading, MA, 1968. (4) Krimm, S.; Bandekar, J. Adu. Protein Chem. 1986, 38, 181. (5) Aaron, H. S. Top. Stereochem. 1980, 2 2 , 1. (6) Winkler, F. K.;Dunitz, J. D. Acta Crysrallogr. 1975, B32, 268. (7) Hallam, H. E.;Jones, C. M . J . Mol. Srruc?. 1967,2 , 413,425. (8) Lord. R. C.: Porro. T. J. Z . Elektrochem. 1960.672. Chen. C. Y. S.; Swenson, C. A. J: Phys.’Chem. 1969,73,1363. Krikorian, S . E.J Phys. Chem. 1982,86,1875. (9) Triggs et aL2rationalizedtheir useof N-H stretch positions to support the conclusion that 2 and 3 are not hydrogen bonded in the solid state by noting that lactam 1,which they believe to be hydrogen bonded in the solid state, shows an N-H stretch band at 3190 cm-I, >lo0 cm-1 lower than the solid-state N-H stretch bands for 2 and3. Such a comparison is not legitimate, however, because 2 and 3 adopt trans configurations about the amide C-N bond in the solid state, while 1 adopts a cis configuration. Triggs et al. acknowledged possible complicationsfrom this structural difference, but they dismissed these complicationsby noting that the differences in non-hydrogenbonded N-H stretch band positions are typically 550 cm-I for cis and trans secondary amides. There is g o d precedent in the IR literature, however, for larger N-H stretch band differences between cis and tram secondary amides in the hydrogen-bonded than in the non-hydrogen-bonded state. (10) Triggs, N. E.; Valentini, J. J. J . Phys. Chem. 1992, 96,6922. (11) From the text of ref 2,it was not clear to us whether the reported value of 1.6for N-methylacetamide referred to the amide I:(amide I1 + amide III)/2 ratio or the amide 1:amide I1 ratio. Professor Valentini has informed us that the former ratio was used to calculate the reported value.
