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IR Spectroscopic study of intermolecular interactions in molecular crystals of amino acid conjugates
Advances in Molecular Relaxation and Interaction Processes, 11 (1977) 221-232 0 Elsevier Scientific Publishing Company, Amsterdam - F’rinted in The Netherlands
IR
SPECTROSCOPIC
IN
~~IOLECULAR CRYSTALS
ALFRED
STUDY
OF
INTERMOLECULAR
OF AMINO
ACID
221
INTERACTIONS
COPJJUGRTES
KOLBE
Sektion Chemie aer Martin-Luther-UniversitBt 402 Halle, DDR ana ADELJ~EID KOLBE Institut fiirBioohemie der Pflanzen, 402 IIalle, Forschungszentrum fiirXlolekularbiologieuna Medizin, AdW der DDR (Received
15 December
1976)
ABSTRACT
The IR spectra of some crystalline amino acid conjugates of diphenylacetic acid and of p-chlorophenoxyisobutyric acid are investigated, paying special attention to those features of the spectra, which allow one to draw conclusions about the intermolecular interactions in the crystals. In most cases it is clearly to be recognized whether dimerization by associative linking of the carboxyl groups takes place or not and, more specifically, the amount of associated carboxylic groups can be estimated. The NH groups as well as the CO amide groups of the derivates of the diphenylacetic acid usually take part in the association, but in the other class they generally do not. In one case the existence of polymorphism has been discussed in terms of IR spectroscopic, X-ray, and calorimetric results. Special differences in the interaction behaviour are obtained, if one considers the spectra of some optically active substances and compares them with their racemic analogous. INTRODUCTION
Extensive IR investigations have been performed on molecular arrangement and intermolecular interactions in the crystalline states of some conjugates of diphenylacetic acid (DPAA) and
222
or p-chlorophenoxyisobutyricacid (Ci'RA).The molten substances and the substances dissolved in dioxan give almost identical.spectra in the accessible spectral rnC;ions,but very sfmilar compounds, which differ only insignificantly in their chemical formulae by variation of the amino acid component, show substantial dif:ferencesin the spectra of the crystalline state. This phenomenon is to be discussed in terms of intermol.ecul.ar interactions. It is our intention, using the spectra and Some results of other methods ‘-, to characterize the dominant intermolecular actions for as many cases as possibl.e. RESlJJdSAL1 DISCUSSTOIJ Y/ehave paid special.attention to two regions of the IR spectra. The first one is that of the NH str. vibration (3000 3500 cm-') ,andthe second one is the region extending from 1500 to 1800 cm-'. There the amide b,a_nd II appears, which was proved without doubt by deuteration as due to the NE bending vibration. Further the amide band I (CO str. vibration of the amide group) and the str. vibration of the carbonyl group of the dfmer as well.as of the free carboxylic group absorb in this range. The IR spectra of the molten substances snd those of the dissolved ones behave in the interesting regions to a high degree similarly to each other. In both cases the re1ativel.y high frequencies of the carbonyl absorptions (1745
-1 the neighbourhood of 3500 cm . But because the behaviour of the HH and OR groups of molecules dissolved in dioxan is essentially determined by the interaction with the basic centers of the solvent molecules, which are acting as acceptors, a comparison of the spectra of the solution and the molt is not reasonable in this region. There risquite another finding, when we look at the spectra of the crystalline substances, recorded as K!!+discs, For the purpose of discussion, we have listed the substances, the positions of their bands and their assignments in table 1. The Hom,annumerals given in the table 1 ctreused as abbreviations for the names of the substances throughout the paper. In the high wave number region the spectra of the conjugates of I>PAAshow only EJIJ bands between 3260 and 3310 cm-1 - three exceptional cases are discussed below. The half width of these bands are about twice those of the corresponding bands i.nthe spectra of the derivates of CPBA, which absorb about IO0 cm-' higher. (Also here one exceptional finding is to be mentioned below.) In the CUBA case the NIIgroups may be considered as free ones. This assertion is based on the positions of the free and associated NH bands of CPBA isopropylamLae in CC14 solution, namely 3426 cm-1 and 334% cm-? , respectively. The associated band belongs to the intermolecular association NH-OC. 'Thisassignment has been confirmed by the NJ&?result, for the IJHproton of the substance just mentioned i.spart of the spin-spin coupling system, because its signal appears as a doublet, thus exclu'dinga NH-B association. Xvidcntly there is no association, too, between the NH group and the carboxylic group of the acid because in this case a shift of the NH str. frequency of about 250 - 300 cm-' would be expected. This can be checked by adding a small quantity of acetic acid to the solution of CPBA isopropylamide in CC14. Transfering these results to those of the DPM conjugates, we believe position and half width of their NH bands is due to NH-OC interaction. The slightly lower frequency of the
224 TABLE
1
List of investigated compounds The assignments and the positions (cm-I) of the bands, which are important for the discussion are given in the rows 3 - 6. The signs > ,>) , CM , < , and << refer to the relative intensities of the particular bands. br. means broad. 1510 . Conjugates of
"r&~i~e
C!;OAmi-
C=O dim. mon.
HII
I
CPBA DI,-Asparticacid 1536M 525 I ST,-Phenylalanine 1533 II III !j-Alanine 1540>1532 DL-d-Alanine IV 1544 DL-Serine V 1545 DkProllne VI Glycine stable VII 1555 below 560 C Glycine stable 1548 above 56O C VIII Glycyl-L-leucine 1535
IX X XI XII XIII XIV xv
DPAA DL-c+Alanine Glycine Glycyl-L-leucine DL-Nethionine DELeucine L-Leucine DZ-Serine
1547
1647
1735
1652 1634 1647 1652 159691635 1662
br. 3427)3361 1731 3373 1727 3427 1713>1736 3361 1705<<17443388 1738 1713 3300 br.
1662
l713B1748
3370
1730
3425
1712<1740
3288
1640
1561
1626
1550>1560
1635
1670
1763>1702
3293
1717
3274
1519
lG65
1723
3344
1539
1657
1722M728
3312
3339
1511
1662
1695C1737
3314
1548<1552
1647wI652
1708>1717
3268>3358
>I725
XVI XVII xv111 XIX xx XXI XXII XXIII
L-Serine D-Phenylalanine DLPhenylalanine L-Phenylalanine DL-Aspartic acid L-Aspartic acid D-Alanine DL-Proline
1520 1548>1530 1539 1548 1544 "1535 1546
1645
1705>1737
3412
1655
1720
3290
3470
1660
1710
327733310
1653
1721
3257
1628>1650
1705
3290
1635<1652
1706<1725
3299<3349
164091668
1701
332OW3280
1622
1702
225
free NH band in the crystal compared with that of the dissolved substance arises from the change of state. The results given here are modified slightly in the following cases. The optically active compounds XIV and XVI show no interaotion between NH and OC, but their NH groups are free. The second exception, the substnnce XII, bearing a long chain, absorbs at about 3360 cm-1 , thus presenting a free NH band, in accordance with the extremely low NH bending -1 vibration at 1515 cm . The conjugates with combined amino acids (VIII and XI) show either broad unresolved NFIstr. bands, or possess clearly-divided two NH bands (XI). Another irregularity, now concerning the class of CI'BAconjugates, is the substance I, which shows a clearly free NH str. band at 3427 cm-' , besides an additional one at 3361 cm-', which is of low intensity. 17econclude from the intensities of both bands, that about IO - 15 ?Iof the molecules, with their NH bonds, either take part in an association or, less probable, exist in another conformation. In addition to the interaction between NH and CO amide there is the tendency of the carboxylic groups to form dimers. Information concerning this particular association we take -1 from the 1500 to 1800 cm region. In contrast to the rather uniform behaviour of the NH bands discussed above, the positions snd intensities of the bands in this range vary in part considerably. Therefore we believe it more reasonable to discuss the spectra one by one. Clearly in the CPBA conjugates the dimerieation of the carboxylic groups is the dominant effect. In the spectra of II end of III only associated oarboxylic groups can be seen, but in IV a part (> 50 5) of the carboxylic groups is free. In V the main quantity of carboxylic groups evidently does not dimerize. Probably this is caused by the involvement of the alcoholic OH group in the association. As can be demonstrated by Courtauld atomic models, this result can be understood only if the OH group of the alcohol and that one of the osrboxylio group are arranged side by side. In accordance to the
226
spectrum, in this case the ac:i.dfc CO groups arc free and the intermolecular interactions take place between the 011groups. Thus the associated mol.ecules‘arelinked always by two hydrogen bonds, but, under these ci.xcumst,ances, we believe the fosmation of dimers as a consequence of this interaction to be impr0babI.e;on the contrary,doubl.ebonded chains will exist. The compound VI also behaves somewhat irregularly. Since these molecules do not possess a NH bond, a NH bending vibration is absent also. The CC pert of the carboxylic group evidently acts only in very few oases as an acceptor, but a strong intramol.ecul,ar hydrogen bond can be recognized, formed between the amide carbonyl.group and the OH part of the carboxyl_j.c group. This effect i.saccompanied by a decrease of the amide band I -1 wave number by about 50 cm-' to a value I.owerthan 1600 cm , The sterl.cfavouring of such an internal.H bond is also demonstrated by atomic models. Probably the dimerization by assooiatj.onof the carboxylic groups in thj.scase is sterically hindered by the bulkiness of its neighbouring groups, which does not al.Lowthe carboxylic group to move out of the influence of the amide carbonyl group. This interpretation is supported by the spectrum of the molten substance. Just above the melting temperature, the band of the intramolecular H bonded CO amide group remaining at the original position given above can be seen, as well as a new band ne
227
which are obtained by crystallization from the solution, are completely associated. The association between the carboxyllc groups in this case is nn unusually strong one, if a broad -1 band (+,2 SY 300 cm-') of medium intensity near 2500 cm is correctly assipged as the carb0xy:Lj.c ~JHband. From atomic models we see, that the NH groups interact intramolecularly with the ri-electrons of the phenyl ring of CPBA. This Interpretation is also i.naccordance with slight variations of several vibration frequencies of the aromatic ring nenr 1000 cm-1 , when the spectra of different modificatLons are compared. The intramolecular IIbond between a NH grou? and 'li-electrons enforces a.relatively spherical ,arrangementof the molecule and its associate, too. Thus the low melting (or transformation) point of this modification may be understood vie I1 .
The molecules stretch themselves considerably, when this l.nternalIIbond is broken at 56', and the melting properties of the crys,talsformed now are also changed. Spectroscopically we find here free NH b,ands,besides a aonsiderable amount of free carboxylic CO bands. Ve cannot crystallize again the substance once molten. Analogously the substance that has been heated higher than 56' cannot be retransformed to the stable low temperature modification. This result is in accordance with the calorimetric ffndlng. In spi_teof a decreasing intermolecular interaction the melting point of the modification last mentioned is remarkably higher. This fact is t,akenas nn expression, that the molecules in this actual conformation are especially approIQ_ate for a special arrangement in the crystal. The extraordinarily unequal arr,angementsof the molecules in the dkfferent modifications are also to be recognized in the IR spectra (Fig. 1). Also Debye diagrams of both modifications differ strongly from each other. Xthout special discussion, the modification stable below 56' may be characterized as more highly ordered. Probably one lattj.ceconstant.remains unaltered in both modifications. In accordance with the results given here, an adiabatic calorimeter run shows three
228
‘10( 8C T
60
40
7a
20
3400
100
3000
2000
1500
1000
500
cm
lk Y
80 T 60
’
40
I6 20
Fig.
1.
TR spectra of the two discussed modifications of VII. la refers the modification stable below 56' C and lb to that stable above 56' C.
peaks. This means a transformation into another crystal structure at 56' instead of melting. The heats of transformations at 56', 75' and 115' are 9500 J/mole, 20800 J/mole and 17300 J/mole, respectively. The compound I shows a broad carbonyl band due to the two acidic groups of the molecule. Strong association exists between the molecules of compound VIII. There the two NH str. bands overlap and no resolution is possible.
229
The frequencies of the CO amide str. and the NH bending vibration of the substances mentioned until now, have not been discussed in detail, because in all oases they are about the same, the irregularities pointed out being excluded. The first of them, all.in all, seems to be somewhat (10 - 20 cm") lower than was to be expected, in comparison to values from the literature (1). The results obtained by investigations of the other class of substances (DPAA as the acidic component) are less numerous than those given &ove. Generally the NH group in these substances is taking part in the association. The CO amide group act as an acceptor of the NIIproton and shows a down shift of about IO cm-' in its str. frequency compared with the values of the conjugates of CPBA. According to this interpretation, the average NH bending wave number is 10 cm-' higher than in the case of the other class. !;re learn from the information given by the CC str. frequencies of the COO11groups, that nearly all substances are dimerized with the exception of the compounds IX end X. In IX the preponderant quantity of the oarboxylic group does not take psrt in association and in X the association due to the COOH dimerization is scarcely to be recognized. We cannot give an adequate explanation for the behaviour of the compound IX, and the spectrum of substance X may only be explained by really unusual disttibution of interaction. The high frequency of the CO part of the COO11group as well as that of its OH group argue clearly for non COOH dimeriaation, and the NH-CC amide association will be the only one acting. This interpretation is supported by the low str. frequencies of the associating groups; accompanied by the high value of the NR bending frequency. In contrast to the corresponding substanoe VIII in the spectrum of XI two clearly divided NH str. bands and also two CO amide bands can be seen. By comparison of this spectrum with that of the substance X we asslgn the lower frequency NH band to the glycyl group, whereas the other band (about 65 cm" higher) is due to the NH bond of the leuoyl group. This ,asslgnmentis
230 confirmed unambiguously by tsotoplc substitution 14N + I514in the leucyl .partof the molecule: In this case, the higher frequency NH band slightly changes its position to lower Wave numbers, whereas all other bands remain unaltered except one NH def, vibration. The greater half width of the lower wave number band is a clear indication at the taking part of the corresponding group In the association only. An analogous assignment should be made for the CO amide str. bands. The favourable steric conditions, which lead to the dominant appearance of the NH-OC association in substance X, are evidently altered by adding the leuoyl group, for tinthe speotrum of XI we find no free CC band of the COOH group. By means of the compounds XIII, XIV and XV, XVI we have checked the influence of configurative homogeneity upon the existence of interactions in the orystalline state. In XIII the COOR dimerization seems to be hindered, because we find two almost equally intense CO bands due to the COOH group, which appear between the positions characteristic for the free and the associated bands in the other cases. The NH-CC amide interactions behave regularly. However, comparing the spectra of XIII and XIV, the carboxylic CO absorptions of both substances a0 not coincide. Consequently, in XIII in no case are diastereoisomeric dimers of molecules of equal chirality formed, but they are always mixed from one R and one S molecule. As a consequence of the chiral homogeneity, which reduces the possibilities to arrange molecules In a crystal, the molecules of XIV are only less inclined to undergo association; accordingly, the CO band of the free COOH group is essentially more intense than that of the associated one. Additionally, In contrast to the usual behaviour of the DPRA conjugates, the NH group is free in this case. This conclusion can also be taken from the positions of the NIIbending and the CO amide str. vibration. Approximately the same relations have been found for the substances XV and XVI. In XV the NH group as well as the alooholio OH group as the main factors take part in the asso-
231
ciation (we cannot unambigously assign the groups to the frequencies), but the carboxylic groups interact only weakly with each other. As the one and only case, the CO amide band here soli.tsin two about equally intense and clearly resolved bands. This should be taken as distinct evidence for the interactj.onwith two different donors. Again we learn from comparison with the spectrum of XVI, that in XV molecules of equal configuration do not dimerize with each ether. Analo' gously to XIV the spectrum of XVI shows a free NII,and additionally, a free OH band. ISkewise as in XIV the free carboxylic CO band is relatively strong, but not as dominant as in the case of XIV, and therefore in XVI there may be slightly stronger interactions. Somewhat surprisfng indeed there remains the rather low str. frequency of the CC amide group, which may be perhaps explafned by an intermolecular interaction-with the carboxylio group. The melting points (of XIII, XIV, XV and XVI namely 144-146', 111-113°, 169-172' and 128-132°, respectively) of the substances discussed confirm the understandings obtained considering the spectra. On the other hand, we have investigated such systems as XVII, XVIII and XIX, also XX and XXI where only less signifioant differences in the IR spectra can be seen. Accordingly, in these cases the melting points of optically active and racemic substances (XVII, XVIII, XIX, XX and XXI, namely 144-147', 162-164', 154,156', 104-106~ and 109-113°, respectively) differ only by a few degrees from each other. hlakinga final survey at the variety of behaviour of the molecules in the crystals, we do not believe to be justified to derive from our investigations any structure-action relation, because the shapes of the molecules dissolved are scarcely similar to those, existing in the crystals. Therefore, we do not try to establish relations analogous to those given by hlesley(2) in the case of some barbiturates.
232
EXPERIA5ENTAL The synthesis of the substances used will be reported elsewhere (3). .Asan identification criterion the parent peak of the mass spectrum was always used. The crystnl.s have been obtained by crystalli.sntionfrom solutions. Be do not know, whether we have investigated in al.1 cases the most stable modifications. The IR measurements were performed using the IR 71 (Zeiss, Jena) and ?the Beckman IR 12. Usually KBr discs (3 mg substance in a disc of 20 mm diameter) were prepared nnd in some cases also nujol suspensions, to eliminate the possible influence of pressure. The molten substances have been recorded in capillary. The.concentration of the solutions investigated amounts to IO mg substance in 0.2 ml dioxan, using cells of 0.1 mm thickness. In few cases of low solubility saturated solutions have been used. The calorimetric work was done using the Perkin Elmer DSC-2.
Ye are indebted to Dr. A. Wiegeleben for performing the calorimetric investigations and to Dr. J. Shorter for making suggestions to the m,anusGript.
T,.J. Bellamy, The IR Spectra of Complex Molecules 2nd ed. Methuen & Co. Ltd., London 1958 2. R. J. Mesley, Spectrochim. Acta 26A (1970) 1427 3. A. Rolbe und H. R. Sohiitte,J. prakt. Chem., in preparation 1.
.'
IR
SPECTROSCOPIC
IN
~~IOLECULAR CRYSTALS
ALFRED
STUDY
OF
INTERMOLECULAR
OF AMINO
ACID
221
INTERACTIONS
COPJJUGRTES
KOLBE
Sektion Chemie aer Martin-Luther-UniversitBt 402 Halle, DDR ana ADELJ~EID KOLBE Institut fiirBioohemie der Pflanzen, 402 IIalle, Forschungszentrum fiirXlolekularbiologieuna Medizin, AdW der DDR (Received
15 December
1976)
ABSTRACT
The IR spectra of some crystalline amino acid conjugates of diphenylacetic acid and of p-chlorophenoxyisobutyric acid are investigated, paying special attention to those features of the spectra, which allow one to draw conclusions about the intermolecular interactions in the crystals. In most cases it is clearly to be recognized whether dimerization by associative linking of the carboxyl groups takes place or not and, more specifically, the amount of associated carboxylic groups can be estimated. The NH groups as well as the CO amide groups of the derivates of the diphenylacetic acid usually take part in the association, but in the other class they generally do not. In one case the existence of polymorphism has been discussed in terms of IR spectroscopic, X-ray, and calorimetric results. Special differences in the interaction behaviour are obtained, if one considers the spectra of some optically active substances and compares them with their racemic analogous. INTRODUCTION
Extensive IR investigations have been performed on molecular arrangement and intermolecular interactions in the crystalline states of some conjugates of diphenylacetic acid (DPAA) and
222
or p-chlorophenoxyisobutyricacid (Ci'RA).The molten substances and the substances dissolved in dioxan give almost identical.spectra in the accessible spectral rnC;ions,but very sfmilar compounds, which differ only insignificantly in their chemical formulae by variation of the amino acid component, show substantial dif:ferencesin the spectra of the crystalline state. This phenomenon is to be discussed in terms of intermol.ecul.ar interactions. It is our intention, using the spectra and Some results of other methods ‘-, to characterize the dominant intermolecular actions for as many cases as possibl.e. RESlJJdSAL1 DISCUSSTOIJ Y/ehave paid special.attention to two regions of the IR spectra. The first one is that of the NH str. vibration (3000 3500 cm-') ,andthe second one is the region extending from 1500 to 1800 cm-'. There the amide b,a_nd II appears, which was proved without doubt by deuteration as due to the NE bending vibration. Further the amide band I (CO str. vibration of the amide group) and the str. vibration of the carbonyl group of the dfmer as well.as of the free carboxylic group absorb in this range. The IR spectra of the molten substances snd those of the dissolved ones behave in the interesting regions to a high degree similarly to each other. In both cases the re1ativel.y high frequencies of the carbonyl absorptions (1745
-1 the neighbourhood of 3500 cm . But because the behaviour of the HH and OR groups of molecules dissolved in dioxan is essentially determined by the interaction with the basic centers of the solvent molecules, which are acting as acceptors, a comparison of the spectra of the solution and the molt is not reasonable in this region. There risquite another finding, when we look at the spectra of the crystalline substances, recorded as K!!+discs, For the purpose of discussion, we have listed the substances, the positions of their bands and their assignments in table 1. The Hom,annumerals given in the table 1 ctreused as abbreviations for the names of the substances throughout the paper. In the high wave number region the spectra of the conjugates of I>PAAshow only EJIJ bands between 3260 and 3310 cm-1 - three exceptional cases are discussed below. The half width of these bands are about twice those of the corresponding bands i.nthe spectra of the derivates of CPBA, which absorb about IO0 cm-' higher. (Also here one exceptional finding is to be mentioned below.) In the CUBA case the NIIgroups may be considered as free ones. This assertion is based on the positions of the free and associated NH bands of CPBA isopropylamLae in CC14 solution, namely 3426 cm-1 and 334% cm-? , respectively. The associated band belongs to the intermolecular association NH-OC. 'Thisassignment has been confirmed by the NJ&?result, for the IJHproton of the substance just mentioned i.spart of the spin-spin coupling system, because its signal appears as a doublet, thus exclu'dinga NH-B association. Xvidcntly there is no association, too, between the NH group and the carboxylic group of the acid because in this case a shift of the NH str. frequency of about 250 - 300 cm-' would be expected. This can be checked by adding a small quantity of acetic acid to the solution of CPBA isopropylamide in CC14. Transfering these results to those of the DPM conjugates, we believe position and half width of their NH bands is due to NH-OC interaction. The slightly lower frequency of the
224 TABLE
1
List of investigated compounds The assignments and the positions (cm-I) of the bands, which are important for the discussion are given in the rows 3 - 6. The signs > ,>) , CM , < , and << refer to the relative intensities of the particular bands. br. means broad. 1510 . Conjugates of
"r&~i~e
C!;OAmi-
C=O dim. mon.
HII
I
CPBA DI,-Asparticacid 1536M 525 I ST,-Phenylalanine 1533 II III !j-Alanine 1540>1532 DL-d-Alanine IV 1544 DL-Serine V 1545 DkProllne VI Glycine stable VII 1555 below 560 C Glycine stable 1548 above 56O C VIII Glycyl-L-leucine 1535
IX X XI XII XIII XIV xv
DPAA DL-c+Alanine Glycine Glycyl-L-leucine DL-Nethionine DELeucine L-Leucine DZ-Serine
1547
1647
1735
1652 1634 1647 1652 159691635 1662
br. 3427)3361 1731 3373 1727 3427 1713>1736 3361 1705<<17443388 1738 1713 3300 br.
1662
l713B1748
3370
1730
3425
1712<1740
3288
1640
1561
1626
1550>1560
1635
1670
1763>1702
3293
1717
3274
1519
lG65
1723
3344
1539
1657
1722M728
3312
3339
1511
1662
1695C1737
3314
1548<1552
1647wI652
1708>1717
3268>3358
>I725
XVI XVII xv111 XIX xx XXI XXII XXIII
L-Serine D-Phenylalanine DLPhenylalanine L-Phenylalanine DL-Aspartic acid L-Aspartic acid D-Alanine DL-Proline
1520 1548>1530 1539 1548 1544 "1535 1546
1645
1705>1737
3412
1655
1720
3290
3470
1660
1710
327733310
1653
1721
3257
1628>1650
1705
3290
1635<1652
1706<1725
3299<3349
164091668
1701
332OW3280
1622
1702
225
free NH band in the crystal compared with that of the dissolved substance arises from the change of state. The results given here are modified slightly in the following cases. The optically active compounds XIV and XVI show no interaotion between NH and OC, but their NH groups are free. The second exception, the substnnce XII, bearing a long chain, absorbs at about 3360 cm-1 , thus presenting a free NH band, in accordance with the extremely low NH bending -1 vibration at 1515 cm . The conjugates with combined amino acids (VIII and XI) show either broad unresolved NFIstr. bands, or possess clearly-divided two NH bands (XI). Another irregularity, now concerning the class of CI'BAconjugates, is the substance I, which shows a clearly free NH str. band at 3427 cm-' , besides an additional one at 3361 cm-', which is of low intensity. 17econclude from the intensities of both bands, that about IO - 15 ?Iof the molecules, with their NH bonds, either take part in an association or, less probable, exist in another conformation. In addition to the interaction between NH and CO amide there is the tendency of the carboxylic groups to form dimers. Information concerning this particular association we take -1 from the 1500 to 1800 cm region. In contrast to the rather uniform behaviour of the NH bands discussed above, the positions snd intensities of the bands in this range vary in part considerably. Therefore we believe it more reasonable to discuss the spectra one by one. Clearly in the CPBA conjugates the dimerieation of the carboxylic groups is the dominant effect. In the spectra of II end of III only associated oarboxylic groups can be seen, but in IV a part (> 50 5) of the carboxylic groups is free. In V the main quantity of carboxylic groups evidently does not dimerize. Probably this is caused by the involvement of the alcoholic OH group in the association. As can be demonstrated by Courtauld atomic models, this result can be understood only if the OH group of the alcohol and that one of the osrboxylio group are arranged side by side. In accordance to the
226
spectrum, in this case the ac:i.dfc CO groups arc free and the intermolecular interactions take place between the 011groups. Thus the associated mol.ecules‘arelinked always by two hydrogen bonds, but, under these ci.xcumst,ances, we believe the fosmation of dimers as a consequence of this interaction to be impr0babI.e;on the contrary,doubl.ebonded chains will exist. The compound VI also behaves somewhat irregularly. Since these molecules do not possess a NH bond, a NH bending vibration is absent also. The CC pert of the carboxylic group evidently acts only in very few oases as an acceptor, but a strong intramol.ecul,ar hydrogen bond can be recognized, formed between the amide carbonyl.group and the OH part of the carboxyl_j.c group. This effect i.saccompanied by a decrease of the amide band I -1 wave number by about 50 cm-' to a value I.owerthan 1600 cm , The sterl.cfavouring of such an internal.H bond is also demonstrated by atomic models. Probably the dimerization by assooiatj.onof the carboxylic groups in thj.scase is sterically hindered by the bulkiness of its neighbouring groups, which does not al.Lowthe carboxylic group to move out of the influence of the amide carbonyl group. This interpretation is supported by the spectrum of the molten substance. Just above the melting temperature, the band of the intramolecular H bonded CO amide group remaining at the original position given above can be seen, as well as a new band ne
227
which are obtained by crystallization from the solution, are completely associated. The association between the carboxyllc groups in this case is nn unusually strong one, if a broad -1 band (+,2 SY 300 cm-') of medium intensity near 2500 cm is correctly assipged as the carb0xy:Lj.c ~JHband. From atomic models we see, that the NH groups interact intramolecularly with the ri-electrons of the phenyl ring of CPBA. This Interpretation is also i.naccordance with slight variations of several vibration frequencies of the aromatic ring nenr 1000 cm-1 , when the spectra of different modificatLons are compared. The intramolecular IIbond between a NH grou? and 'li-electrons enforces a.relatively spherical ,arrangementof the molecule and its associate, too. Thus the low melting (or transformation) point of this modification may be understood vie I1 .
The molecules stretch themselves considerably, when this l.nternalIIbond is broken at 56', and the melting properties of the crys,talsformed now are also changed. Spectroscopically we find here free NH b,ands,besides a aonsiderable amount of free carboxylic CO bands. Ve cannot crystallize again the substance once molten. Analogously the substance that has been heated higher than 56' cannot be retransformed to the stable low temperature modification. This result is in accordance with the calorimetric ffndlng. In spi_teof a decreasing intermolecular interaction the melting point of the modification last mentioned is remarkably higher. This fact is t,akenas nn expression, that the molecules in this actual conformation are especially approIQ_ate for a special arrangement in the crystal. The extraordinarily unequal arr,angementsof the molecules in the dkfferent modifications are also to be recognized in the IR spectra (Fig. 1). Also Debye diagrams of both modifications differ strongly from each other. Xthout special discussion, the modification stable below 56' may be characterized as more highly ordered. Probably one lattj.ceconstant.remains unaltered in both modifications. In accordance with the results given here, an adiabatic calorimeter run shows three
228
‘10( 8C T
60
40
7a
20
3400
100
3000
2000
1500
1000
500
cm
lk Y
80 T 60
’
40
I6 20
Fig.
1.
TR spectra of the two discussed modifications of VII. la refers the modification stable below 56' C and lb to that stable above 56' C.
peaks. This means a transformation into another crystal structure at 56' instead of melting. The heats of transformations at 56', 75' and 115' are 9500 J/mole, 20800 J/mole and 17300 J/mole, respectively. The compound I shows a broad carbonyl band due to the two acidic groups of the molecule. Strong association exists between the molecules of compound VIII. There the two NH str. bands overlap and no resolution is possible.
229
The frequencies of the CO amide str. and the NH bending vibration of the substances mentioned until now, have not been discussed in detail, because in all oases they are about the same, the irregularities pointed out being excluded. The first of them, all.in all, seems to be somewhat (10 - 20 cm") lower than was to be expected, in comparison to values from the literature (1). The results obtained by investigations of the other class of substances (DPAA as the acidic component) are less numerous than those given &ove. Generally the NH group in these substances is taking part in the association. The CO amide group act as an acceptor of the NIIproton and shows a down shift of about IO cm-' in its str. frequency compared with the values of the conjugates of CPBA. According to this interpretation, the average NH bending wave number is 10 cm-' higher than in the case of the other class. !;re learn from the information given by the CC str. frequencies of the COO11groups, that nearly all substances are dimerized with the exception of the compounds IX end X. In IX the preponderant quantity of the oarboxylic group does not take psrt in association and in X the association due to the COOH dimerization is scarcely to be recognized. We cannot give an adequate explanation for the behaviour of the compound IX, and the spectrum of substance X may only be explained by really unusual disttibution of interaction. The high frequency of the CO part of the COO11group as well as that of its OH group argue clearly for non COOH dimeriaation, and the NH-CC amide association will be the only one acting. This interpretation is supported by the low str. frequencies of the associating groups; accompanied by the high value of the NR bending frequency. In contrast to the corresponding substanoe VIII in the spectrum of XI two clearly divided NH str. bands and also two CO amide bands can be seen. By comparison of this spectrum with that of the substance X we asslgn the lower frequency NH band to the glycyl group, whereas the other band (about 65 cm" higher) is due to the NH bond of the leuoyl group. This ,asslgnmentis
230 confirmed unambiguously by tsotoplc substitution 14N + I514in the leucyl .partof the molecule: In this case, the higher frequency NH band slightly changes its position to lower Wave numbers, whereas all other bands remain unaltered except one NH def, vibration. The greater half width of the lower wave number band is a clear indication at the taking part of the corresponding group In the association only. An analogous assignment should be made for the CO amide str. bands. The favourable steric conditions, which lead to the dominant appearance of the NH-OC association in substance X, are evidently altered by adding the leuoyl group, for tinthe speotrum of XI we find no free CC band of the COOH group. By means of the compounds XIII, XIV and XV, XVI we have checked the influence of configurative homogeneity upon the existence of interactions in the orystalline state. In XIII the COOR dimerization seems to be hindered, because we find two almost equally intense CO bands due to the COOH group, which appear between the positions characteristic for the free and the associated bands in the other cases. The NH-CC amide interactions behave regularly. However, comparing the spectra of XIII and XIV, the carboxylic CO absorptions of both substances a0 not coincide. Consequently, in XIII in no case are diastereoisomeric dimers of molecules of equal chirality formed, but they are always mixed from one R and one S molecule. As a consequence of the chiral homogeneity, which reduces the possibilities to arrange molecules In a crystal, the molecules of XIV are only less inclined to undergo association; accordingly, the CO band of the free COOH group is essentially more intense than that of the associated one. Additionally, In contrast to the usual behaviour of the DPRA conjugates, the NH group is free in this case. This conclusion can also be taken from the positions of the NIIbending and the CO amide str. vibration. Approximately the same relations have been found for the substances XV and XVI. In XV the NH group as well as the alooholio OH group as the main factors take part in the asso-
231
ciation (we cannot unambigously assign the groups to the frequencies), but the carboxylic groups interact only weakly with each other. As the one and only case, the CO amide band here soli.tsin two about equally intense and clearly resolved bands. This should be taken as distinct evidence for the interactj.onwith two different donors. Again we learn from comparison with the spectrum of XVI, that in XV molecules of equal configuration do not dimerize with each ether. Analo' gously to XIV the spectrum of XVI shows a free NII,and additionally, a free OH band. ISkewise as in XIV the free carboxylic CO band is relatively strong, but not as dominant as in the case of XIV, and therefore in XVI there may be slightly stronger interactions. Somewhat surprisfng indeed there remains the rather low str. frequency of the CC amide group, which may be perhaps explafned by an intermolecular interaction-with the carboxylio group. The melting points (of XIII, XIV, XV and XVI namely 144-146', 111-113°, 169-172' and 128-132°, respectively) of the substances discussed confirm the understandings obtained considering the spectra. On the other hand, we have investigated such systems as XVII, XVIII and XIX, also XX and XXI where only less signifioant differences in the IR spectra can be seen. Accordingly, in these cases the melting points of optically active and racemic substances (XVII, XVIII, XIX, XX and XXI, namely 144-147', 162-164', 154,156', 104-106~ and 109-113°, respectively) differ only by a few degrees from each other. hlakinga final survey at the variety of behaviour of the molecules in the crystals, we do not believe to be justified to derive from our investigations any structure-action relation, because the shapes of the molecules dissolved are scarcely similar to those, existing in the crystals. Therefore, we do not try to establish relations analogous to those given by hlesley(2) in the case of some barbiturates.
232
EXPERIA5ENTAL The synthesis of the substances used will be reported elsewhere (3). .Asan identification criterion the parent peak of the mass spectrum was always used. The crystnl.s have been obtained by crystalli.sntionfrom solutions. Be do not know, whether we have investigated in al.1 cases the most stable modifications. The IR measurements were performed using the IR 71 (Zeiss, Jena) and ?the Beckman IR 12. Usually KBr discs (3 mg substance in a disc of 20 mm diameter) were prepared nnd in some cases also nujol suspensions, to eliminate the possible influence of pressure. The molten substances have been recorded in capillary. The.concentration of the solutions investigated amounts to IO mg substance in 0.2 ml dioxan, using cells of 0.1 mm thickness. In few cases of low solubility saturated solutions have been used. The calorimetric work was done using the Perkin Elmer DSC-2.
Ye are indebted to Dr. A. Wiegeleben for performing the calorimetric investigations and to Dr. J. Shorter for making suggestions to the m,anusGript.
T,.J. Bellamy, The IR Spectra of Complex Molecules 2nd ed. Methuen & Co. Ltd., London 1958 2. R. J. Mesley, Spectrochim. Acta 26A (1970) 1427 3. A. Rolbe und H. R. Sohiitte,J. prakt. Chem., in preparation 1.
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