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Studies on aminopyridines in aqueous solution by laser Raman spectroscopy
Spectrochimica Acto. Vol. 49A. Printed in Great Britain
0584-8539/93 gmo+o.cm @ 1992 Pergamon Press Ltd
No. 1, pp. 1-9.1993
Studies on aminopyridines in aqueous solution by laser Raman spectroscopy P. CARMONA* and M. MOLINA Instituto de Optica (CSIC) , Serrano 121, 28006Madrid,
Spain
and R. ESCOBAR Departamento
de Quimica Analftica, Fact&ad de Quimica, Universidad de Sevilla, 41012-Sevilla, Spain (Received 24 April 1992; accepted 27 May 1992)
Abstract-Raman spectra of 2-, 3-, 4-aminopyridine and 3,4_diaminopyridine in water solution are reported for the first time in the 4OOO-3OOcm-’ range. Vibrational assignments have been made for many of the observed frequencies on the basis of isotopic frequency shifts, depolarization ratios, group frequency considerations as well as comparison with accepted assignments for certain vibrational modes in other compounds with structural similarities. The Raman spectra of these monoaminopyridines can be interpreted as if the molecule of 4-aminopyridine possesses C,, symmetry and as if the 2- and 3-aminopyridine molecular species were planar, due to a low barrier to amino group inversion. The Raman spectra of 3,4_diaminopyridine, however, preclude any symmetry. This is probably due to the formation of intramolecular hydrogen bonds between the amino groups.
AMINOPYRIDINES are currently finding increasing applications for several reasons. Firstly, they represent a group of compounds used as reagents in analytical chemistry.
Secondly, some of them show anesthetic properties and have been used as drugs for certain brain diseases. In spite of these physiological applications and the consequent interest in their qualitative and quantitative characterization in aqueous solution, their Raman spectra have not been thoroughly investigated in the mid-spectral region. Thus, IR and Raman spectra (300-50 cm-‘) for charge-transfer complexes between aminopyridines and halogen elements were reported [l]. The far-IR vapour-phase spectra of aminopyridines between 600 and 50 cm-’ were also reported [2] in order to determine the amino inversion vibration in these compounds. On the other hand, polarized IR spectra of 4-aminopyridine hemiperchlorate single crystal were studied over the frequency range 3200-200 cm-’ [3] in connection with the assignment of the vibrations of NHN hydrogen bridges. The purpose of the present paper is to report for the first time the Raman spectra of 2-, 3- and 4-aminopyridines (2-AP, 3-AP and 4-AP) and 3,Cdiaminopyridine (3,CDAP) in water and heavy water solutions. A tentative assignment is given by referring to the isotopic frequency shifts and group frequency considerations as well as depolarization ratios. The correlation between Raman bands of these compounds and some vibrational modes of pyridine [4,5] and methylpyridines [6] is performed as a further aid to the spectral assignments.
EXPERIMENTAL 2-AP, 3-AP, aminopyridines solutions of 0.5 adequate basic
4-AP and 3,4-DAP were obtained from Merck and used as supplied. Deuterated were prepared by repeated exchanges with heavy water. Aminopyridine aqueous M were used for Raman spectroscopy. The pH of each solution was adjusted to an pH value in the range between 9.0 and 10.0 in order to prevent the formation of
* Author to whom correspondence
should be addressed.
P. CARMONAet al.
Fig. 1. Resonant
structures
for the monoaminopyridines 2-AP, 3-AP and 4-AP.
protonated aminopyridine molecules through hydrolysis. On the other hand, aqueous solutions of these compounds at pH near 7.0 were also studied. Sodium hydroxide and hydrochloric acid solutions were used for pH adjustments. The Raman spectra were recorded using a Jobin-Yvon Ramanor U-1000 spectrometer at 3 cm-’ resolution coupled to photon-counting electronics. The samples were excited with the 514.5 nm line of a Spectra Physics 165 argon ion laser at power of 200-400mW. Signals were fed to a computer for storage, display, plotting and processing, and the spectra were obtained from the average of at least five scans.
RESULTS AND DISCUSSION
It was demonstrated that the far-IR vapour-phase spectra of aminopyridines [2] (Fig. 1) are dominated by lines due to transitions in the inversion vibration of the -NH, group, which supports a possible pyramidal amino group structure. This pyramidal structure allows two locations for the amino groups with respect to the aromatic ring. For the first location the molecular plane of symmetry is perpendicular to the plane of the aromatic ring. In the second case it is the plane of the ring. The effect of the three-dimensional, spatial location of the amino groups on the vibrational spectra of aminopyridines allows us to find the real geometry in these molecules, In fact, if the molecular plane of symmetry is, for instance, the same as that of the aromatic ring the assumed molecular geometry of 2-AP, 3-AP, 4-AP and 3,4-DAP would belong to symmetry group C,, and consequently the Raman bands involving both the pyridine ring and amino group would belong either to the A’ or A” type of symmetry and would be polarized or depolarized, respectively. By contrast, in molecules without symmetry (C, point group) the Raman bands generated by vibrational modes where pyridine ring and amino group motions are coupled would be only polarized. It is to be noted, however, that although the plane of the amino group is not coincident with the ring plane of these molecules the barrier to inversion is in some cases so low [2] that for symmetry purposes the said molecules may be treated as if they were planar. In this connection the depolarization ratios permit us to find the true situation as described below.
Aminopyridines in aqueous solution
3
Ring vibrations The ring stretching vibrations are very much prominent in the spectrum of pyridine and its derivatives and are highly characteristic of the aromatic ring itself. The benzene double degenerate vibration e,, (1596 cm-‘) consists of lateral dilation and contraction of the ring produced mainly by stretching and compressing of the bonds. On the removal of the degeneracy, the components of this vibration will appear separately. The Raman spectra of aminopyridines (Figs 2-5) show a pair of bands in the 1610-1590 and 1585-1540 cm-’ ranges which have been assigned as the components of the above mode (Table 1). In the spectra of 3-AP the spectral range of the higher frequency component of this vibrational mode is complicated by Fermi resonance between the v., fundamental and the combination tone vX+ v,,. For 3-AP in aqueous solution a Raman band occurs as a shoulder at 1597 cm-‘. The combination tone vX+ vY is expected at 1047 + 549= 1596 cm-‘, which suggests that the 1597 cm-’ band be assigned as a Fermi resonance enhanced tone. The Raman spectrum of 3-AP in heavy water supports this interpretation, for a shoulder appears at 1582 cm-’ and is assigned as vX+ vY= 1046+538= 1584 cm-‘. The IR spectra of benzene contain a double degenerated e,, (1485) mode. This is basically a ring deformation, since it involves both stretching and bending of the carbon bonds. Under reduced symmetry the two components appear separately which are active in both IR and Raman spectra. This pair of bands appearing in the Raman spectra of pyridine [2,7] at 1482 and 1439 cm-’ are assigned to coupled CC and CN stretching vibrations and can be correlated with the pairs of bands of aminopyridines in the 15201480 and 1450-1410cm-’ ranges (Table 1). Other Raman bands falling in the 1400-1050 cm-’ range involve pyridine ring and C-H in-plane motions, the number of visible bands in this range depending on the location of the amino groups in the pyridine ring. An intense and strongly polarized Raman band which in pyridine appears near 1000 cm-’ is characteristic of the ring breathing vibration [4,6-81. It was shown that this vibrational mode changes to a large amount depending on the mass, nature, number and
400
800
1200
1600
cm-’ Fig. 2. Raman spectra of 0.5 M 2-AP at (top) pH 9.0 and (bottom) pD 9.0.
4
P. CARMONAetal.
T Q)
4~
c¢
a~ g o9
¢¢
L'~
I
400
12i)0
800
1600
c m -1 Fig. 3. Raman spectra of 0.5 M 3-AP at (top) pH 9.0 and (bottom) pD 9.0.
1 4-~ .q,-0
¢¢ Q~
480
800
1200
1600
C m -! Fig. 4. Raman spectra of 0.5 M 4-AP at (top) pH 10.0 and (bottom) pD 10.0.
Aminopyridinesin aqueous sohtion
400
800
1200
5
1600
cm-’ Fig. 5. Raman spectra of 0.5 M 3,4-DAP at (top) pH 10.0 and (bottom) pD 10.0.
position of substituents [6, g-101. The frequency of the breathing vibration in aminopyridines depends, in fact, on the number and positions of amino group substituents, which should be considered at a time of choosing the key bands to be used in the analysis of these compounds in aqueous solution through Raman spectroscopy. There are, finally, three visible Raman bands stemming from vibrational modes involving pyridine ring deformation which appear in the 670-630, 570-540 and 425-380cm-’ ranges. These bands can be correlated with the ylg, ylo and ~27 vibrations of pyridine [4], respectively (Table 1). The presence of both polarized and depolarized Raman bands of 4-AP generated by vibrational modes which can be described in terms of vibrations in the plane of the pyridine ring coupled with amino group motions should be noted. In this connection one can mention, for instance, the depolarized and polarized bands appearing at 1271 cm-’ (v16) and 1607 cm-’ (vq) which shift to 1257 and 1612 cm-‘, respectively, on iV-deuteration (Table 1). This is consistent with a low barrier to inversion of the amino group [2] oriented in such a way that the molecular plane of symmetry is perpendicular to the plane of the pyridine ring, whereby 4-AP molecules may be treated as if they possess C,, symmetry. In fact, a pyramidal structure for the -NH, group with a high barrier to inversion would lead to a C, point group for 4-AP molecules, the molecular plane of symmetry being either perpendicular to the pyridine ring or coincident with it. If this were the true situation, the in-plane vibrations of pyridine ring coupled with amino group motions would originate Raman bands, all of them being either polarized or depolarized, depending on the parallel or perpendicular orientation of the molecular plane of symmetry with respect to the pyridine ring, respectively. However, the v4 and v16bands of 4-AP are polarized and depolarized, which supports the spectral treatment of 4-AP molecules as if they belong to the C2, point group, due to the low barrier to amino group inversion [2]. In fact, the lifetime of Raman scattering is of the order of 10-11-10-13s, whereas the amino inversion vibration in aminopyridines proceeds in the 10-13-10-14 time interval [2]. Raman spectroscopy, thus, cannot discern between two amino group inverted molecular structures of aminopyridines if these structures transform very quickly into each other due to sufficient thermal energy at room temperature. On the other hand, the band of the vn out-of-plane vibration is
P. CAIWONA et al.
6
depolarized in 2-AP and 3-AP, which supports the idea that these molecules can be treated as if they were planar due to the low barrier to the inversion of the amino group. In 3,CDAP, however, all the Raman bands whose depolarization ratios could be measured are polarized. Perhaps the intramolecular hydrogen bond interactions between the two adjacent -NH2 groups lead to a higher barrier of amino group inversion, whereby a C, point group results in 3,4-DAP molecules. In fact, the repulsion between two hydrogen atoms from different amino groups in the molecule results in an orientation for each amino group which is different from that of the other in such a way that hydrogen bonding between them occurs. This obviously involves a C, point group for the 3,4-DAP molecules. Even if the barrier to amino group inversion were low the C, molecular structure would remain, on averaging through time, the amino group inverted structures. Amino group vibrations The characteristic frequency of the NH2 scissoring vibration is usually located in the 1650-1600 cm-’ range [3]. However, the presence of the 60H2 band does not allow us to unequivocally assign this vibrational mode. In addition, the shifting of the bands in the 1610-1500 cm-’ region on N-deuteration shows that the 6NH2 motion takes part in the vibrational modes falling in this region. On the other hand, a band near 1400 cm-’ in the polarized IR spectra of 4-aminopyridine hemiperchlorate crystals [3] was attributed to the NH2 rocking motion. This vibration may be involved in the v14 mode where the
Table 1. Raman frequencies (cm-‘) of aminopyridines in Hz0 and D20 solution*
Dz0
Hz0 2-AP 1629 sh
3-AP
4-AP
3,4-DAP
2-AP
1634 w
1637 w
1606mp
1625 w 1597 sh 159Omp
1607mp
1592mp
1570 m p 1486vwp
1546 vw 1488 w
1561 vw 1512 vw
1445vwp
1442 w
1442 vw dp
1586mp 1564m 1516~~ 1480bw 1440 vw 1444w 1430 vw p
1607m
1333 m p
1367 1346w wp
1337 w
1350 sh
1351 m
1314 sh 1261 m p
1310w 1271 w dp 1217mp
1328 w 1287 w 1198mp
1169sh 1258 m
1154wp 1131 w p 1048s~ 997sp
1287mp 1261 vw ll%mp 1138~~ 1088 vw 1047 vs p 1023sp
866 sh
871 sh
848vsp 82Ovwp 780vwdp 636wp 565mp 421 vw dp
842s~ 820 sh 636wp 549mp 385 w dp
3-AP
4-AP
3,4-DAP
Assignment7 6H,O, 8NH2 1047 + 549 v4 1046+ 538
1596m 1582 sh 1550~~ 1488~
16612m
1600s
1561 vw 1511~~
VI3
1430vw
1439vw
1574~ 1512~ 1427 w 1414w
1376 w 1346vw
1341 w
1354 w
vu
1170~ 1257~ 1220 m
1330 w 1190sh 1277 w 1183m
V~ VI4
1081 m 1052 m p
1152 w 1106m 1048 s 997vs
1311 w 1168~ 1250~~ 1192 m 1128vw 1112vw 1046~s 1025s
871vw
860w
876 vw
848vsp
775 vs p
828s
822 s
832 s
751 vs
666mdp 539mp 398 w dp
618mp 541wp 330 vw
781 vw 635 w 553 m 382 vw
761 vw 635 w 538 m 352vw
667m 529 m 361vw
v25 609m v19 503 w VI0 3OOvw vt7
1058 m p 1002 vs p
vC-NH2 %6
v6 VI7 V18
1057 m 1CKtO vs
1080sh 1066s 990vw 876 w 840W
vs v9 v21
6, v-ring + vC-NH,
Abbreviations: vs, very strong; s, strong; m, medium; w, weak; vw, very weak; sh, shoulder; b, broad; p, polarized; dp, depolarized. * Bands corresponding to Figs 2-5. t Numbering of the assigned vi bands according to Ref. [4].
Aminopyridines in aqueous
solution
7
pyridine ring also takes part, so it is also very difficult to unambigously identify this vibration in the Raman spectra of these aminopyridines. The C-NH2 stretching vibration usually appear around 1300 cm-’ [ll]. We have assigned this vibrational mode to bands falling in the 1350-1280 cm-’ range on the basis of isotopic frequency shifts (Table 1). The shifts of the K-NH, Raman band upon N-deuteration is accompanied by shifts of some bands falling in the 1400-llOOcm-’ region, which shows that these are coupled with the C-NH, motion. This seems to be also involved in the vibrational mode giving rise to the strong band located in the 850-750 cm-’ range as this band shifts to lower frequencies on N-deuteration. Moreover, it was shown previously [6,8] that in methylpyridines there is usually a polarized strong band in the 850-750 cm-’ range whose vibrational mode is described in terms of in-plane deformation of the pyridine ring as well as YC-C and vN-C vibrations coupled with the YC-CH~ motion. As the mass of the -CH, group is near that of the -NH, one, the strong polarized Raman band shown in the 850-750 cm-’ range of aminopyridines can be correlated with the polarized strong Raman band of methylpyridines in the same range. This seems to be supported by considering the frequency of this band from each aminopyridine and the resonant structures (Fig. 1) that are expected to be most important in the valence bond picture of aminopyridines. Thus, no reasonable resonance structure can put a negative charge on the ring nitrogen in 3-AP, so the double bond character of the external C-NH2 bond in this compound is lower than that of 2-AP and 4-AP. If the vC-NH, motion takes part in the vibrational mode of the polarized strong band appearing in the 850-750 cm-’ range, it is to be expected that the frequency of this band is higher in 2-AP and 4-AP than in 3-AP, as indeed occurs. The fact that this band in 3,4-DAP is located even at lower frequency (775 cm-‘) than in the three aminopyridines can be explained by assuming the presence of two vibrational modes involving, respectively, the symmetric and antisymmetric motions of both C-NH, bonds, only the symmetric mode being very active in Raman. The great intensity of this band from these aminopyridines allows us to consider it as a potential key band to be used in the analysis of these compounds through Raman spectroscopy. The relative intensity of this band even increases at pH near 7.0 and appears practically at the same frequency with respect to higher pH (Figs 6-7), which means that this band can also be used for the analysis of these aminopyridines at physiological pH when used as drugs. Concerning the wagging NH2 mode, a band near 440 cm-’ was assigned to it in the polarized IR spectra of 4-aminopyridine hemiperchlorate single crystal [3]. This NH, wagging motion is probably involved in the ~27 mode of the compounds studied in this work, as shown by its shifting to lower frequencies on ZV-deuteration. The largest spectral changes in going from basic to neutral pH in the aminopyridine solutions correspond to 4-AP and 3,CDAP, which can be explained by considering that the p& values of 2-AP, 3-AP, 4-AP and 3,bDAP are 6.8,5.8, 9.1 and 8.3, respectively [12]. Therefore, protonation at the pyridine ring N atom of 4-AP and 3,CDAP must occur to a much greater extent at pH 7.0 than in 2-AP and 3-AP at the same pH. This may be the reason why some bands of the exocylic =N+H2 group of the amidinium ion, resulting from the protonation of the 4-AP form (II) (Fig. 1) at the ring nitrogen, are visible. In fact, the most prominent band above 1600 cm-’ in the Raman spectra of 4-AP at pH 7.0 appears at 1647 cm-’ (Fig. 6) for which there is no counterpart in its respective aqueous solution at basic pH. This band is attributable to exocylic C=N+ stretching, possibly mixed with the NH+H scissoring [13,14]. A similar band is also observed for 3,6DAP at neutral pH (Fig. 7) which is interpreted in the same way. The Raman spectra of 4-AP and 3,6DAP reveal, then, an increase of the contribution of the mesomeric amidinium forms (Fig. 1) in the structure of these aminopyridines on protonation. This is also reflected by the slight frequency increase of the polarized strong band (Figs 4-7) located in the 850-750 cm-’ range which seems to involve the exocyclic C-NH2 stretching motion to some extent, as described above. In conclusion, we report for the first time the Raman spectra of 2-AP, 3-AP, 4-AP and 3,4-DAP in aqueous solution whose bands have been assigned. Measurements of depolarization ratios reveal that the spectra of 4-AP can be interpreted as if its molecules
P. CARMONAet al.
cm-’ Fig. 6. Raman spectra of 0.5 M monoaminopyridines at pH7.0. bottom, 4-AP.
Top, 2-AP; middle, 3-AP;
possess C,, symmetry, which involves low barriers to amino group inversion as described previously [2]. On the other hand, the presence of some depolarized Raman bands from 2-AP and 3-AP supports the idea that the molecules of these two compounds behave in Raman spectroscopy as if they were planar, which may be also due to a low barrier to amino inversion. The Raman spectra of 3,4-DAP, however, are consistent with the absence of a plane of symmetry, probably due to intramolecular hydrogen bonding between both amino groups. Protonation of 4-AP and 3,4-DAP at pH 7.0 leads to an increase in the contribution of the mesomeric amidinium forms to the description of the electron distribution in these substances.
F
400
1200
800
1600
cm-’ Fig. 7. Raman spectrum of 0.5 M 3,4-DAP at pH 7.0.
Aminopyridines
in aqueous solution
9
Acknowledgement-The financial support (PB90-148) of the Direcci6n General de Investigacih Cientffica y T&nica is gratefully acknowledged.
REFERENCES [l] [2] [3] [4] [S] [6] [7] [8] [9] [lo] [ll] [12]
K. Sasaki, I. Kuwano and K. Aida, 1. Inorg. Nucl. Chem. 43, 485 (1981). R. A. Kydd, Spectrochim. Actu. 35A, 409 (1979). J. Baran, Z. Malarski, L. Sobczyk and E. Grech, Spectrochim. Actu 44A, 933 (1988). D. A. Long and E. L. Thomas, Trans. Faraday Sot. 59,783 (1%3). D. P. DiLella, J. Rumun Spectrosc. 9,239 (1980). J. A. Draeger, Spectrochim. Actu 39A, 809 (1983). D. P. DiLella and H. D. Stidham, J. Rumun Spectrosc. 9, 90 (1980). A. Y. Obaid and M. S. Soliman, Spectrochim. Actu 46A, 1779 (1990). J. K. Wilmshurst and H. J. Bernstein, Can. J. Chem. 35, 911 (1957). D. H. Whiffen and A. Stojiljkovic, Spectrochim. Actu 12A, 42 (1958). V. B. Singh, R. N. Singh and I. S. Singh, Spectrochim. Actu 22, 927 (1966). R. C. Weast, Handbook of Chemistry and Physics, 62nd Edn. Chemical Rubber Co., Boca Raton, Florida (1981). [13] L. J. Bellamy, The Infrared Spectra of Complex Molecules, Vol. 2, Chapman and Hall, London (1980). [14] S. Mansy, W. L. Peticolas and R. S. Tobias, Spectrochim. Actu 35A, 315 (1979).
0584-8539/93 gmo+o.cm @ 1992 Pergamon Press Ltd
No. 1, pp. 1-9.1993
Studies on aminopyridines in aqueous solution by laser Raman spectroscopy P. CARMONA* and M. MOLINA Instituto de Optica (CSIC) , Serrano 121, 28006Madrid,
Spain
and R. ESCOBAR Departamento
de Quimica Analftica, Fact&ad de Quimica, Universidad de Sevilla, 41012-Sevilla, Spain (Received 24 April 1992; accepted 27 May 1992)
Abstract-Raman spectra of 2-, 3-, 4-aminopyridine and 3,4_diaminopyridine in water solution are reported for the first time in the 4OOO-3OOcm-’ range. Vibrational assignments have been made for many of the observed frequencies on the basis of isotopic frequency shifts, depolarization ratios, group frequency considerations as well as comparison with accepted assignments for certain vibrational modes in other compounds with structural similarities. The Raman spectra of these monoaminopyridines can be interpreted as if the molecule of 4-aminopyridine possesses C,, symmetry and as if the 2- and 3-aminopyridine molecular species were planar, due to a low barrier to amino group inversion. The Raman spectra of 3,4_diaminopyridine, however, preclude any symmetry. This is probably due to the formation of intramolecular hydrogen bonds between the amino groups.
AMINOPYRIDINES are currently finding increasing applications for several reasons. Firstly, they represent a group of compounds used as reagents in analytical chemistry.
Secondly, some of them show anesthetic properties and have been used as drugs for certain brain diseases. In spite of these physiological applications and the consequent interest in their qualitative and quantitative characterization in aqueous solution, their Raman spectra have not been thoroughly investigated in the mid-spectral region. Thus, IR and Raman spectra (300-50 cm-‘) for charge-transfer complexes between aminopyridines and halogen elements were reported [l]. The far-IR vapour-phase spectra of aminopyridines between 600 and 50 cm-’ were also reported [2] in order to determine the amino inversion vibration in these compounds. On the other hand, polarized IR spectra of 4-aminopyridine hemiperchlorate single crystal were studied over the frequency range 3200-200 cm-’ [3] in connection with the assignment of the vibrations of NHN hydrogen bridges. The purpose of the present paper is to report for the first time the Raman spectra of 2-, 3- and 4-aminopyridines (2-AP, 3-AP and 4-AP) and 3,Cdiaminopyridine (3,CDAP) in water and heavy water solutions. A tentative assignment is given by referring to the isotopic frequency shifts and group frequency considerations as well as depolarization ratios. The correlation between Raman bands of these compounds and some vibrational modes of pyridine [4,5] and methylpyridines [6] is performed as a further aid to the spectral assignments.
EXPERIMENTAL 2-AP, 3-AP, aminopyridines solutions of 0.5 adequate basic
4-AP and 3,4-DAP were obtained from Merck and used as supplied. Deuterated were prepared by repeated exchanges with heavy water. Aminopyridine aqueous M were used for Raman spectroscopy. The pH of each solution was adjusted to an pH value in the range between 9.0 and 10.0 in order to prevent the formation of
* Author to whom correspondence
should be addressed.
P. CARMONAet al.
Fig. 1. Resonant
structures
for the monoaminopyridines 2-AP, 3-AP and 4-AP.
protonated aminopyridine molecules through hydrolysis. On the other hand, aqueous solutions of these compounds at pH near 7.0 were also studied. Sodium hydroxide and hydrochloric acid solutions were used for pH adjustments. The Raman spectra were recorded using a Jobin-Yvon Ramanor U-1000 spectrometer at 3 cm-’ resolution coupled to photon-counting electronics. The samples were excited with the 514.5 nm line of a Spectra Physics 165 argon ion laser at power of 200-400mW. Signals were fed to a computer for storage, display, plotting and processing, and the spectra were obtained from the average of at least five scans.
RESULTS AND DISCUSSION
It was demonstrated that the far-IR vapour-phase spectra of aminopyridines [2] (Fig. 1) are dominated by lines due to transitions in the inversion vibration of the -NH, group, which supports a possible pyramidal amino group structure. This pyramidal structure allows two locations for the amino groups with respect to the aromatic ring. For the first location the molecular plane of symmetry is perpendicular to the plane of the aromatic ring. In the second case it is the plane of the ring. The effect of the three-dimensional, spatial location of the amino groups on the vibrational spectra of aminopyridines allows us to find the real geometry in these molecules, In fact, if the molecular plane of symmetry is, for instance, the same as that of the aromatic ring the assumed molecular geometry of 2-AP, 3-AP, 4-AP and 3,4-DAP would belong to symmetry group C,, and consequently the Raman bands involving both the pyridine ring and amino group would belong either to the A’ or A” type of symmetry and would be polarized or depolarized, respectively. By contrast, in molecules without symmetry (C, point group) the Raman bands generated by vibrational modes where pyridine ring and amino group motions are coupled would be only polarized. It is to be noted, however, that although the plane of the amino group is not coincident with the ring plane of these molecules the barrier to inversion is in some cases so low [2] that for symmetry purposes the said molecules may be treated as if they were planar. In this connection the depolarization ratios permit us to find the true situation as described below.
Aminopyridines in aqueous solution
3
Ring vibrations The ring stretching vibrations are very much prominent in the spectrum of pyridine and its derivatives and are highly characteristic of the aromatic ring itself. The benzene double degenerate vibration e,, (1596 cm-‘) consists of lateral dilation and contraction of the ring produced mainly by stretching and compressing of the bonds. On the removal of the degeneracy, the components of this vibration will appear separately. The Raman spectra of aminopyridines (Figs 2-5) show a pair of bands in the 1610-1590 and 1585-1540 cm-’ ranges which have been assigned as the components of the above mode (Table 1). In the spectra of 3-AP the spectral range of the higher frequency component of this vibrational mode is complicated by Fermi resonance between the v., fundamental and the combination tone vX+ v,,. For 3-AP in aqueous solution a Raman band occurs as a shoulder at 1597 cm-‘. The combination tone vX+ vY is expected at 1047 + 549= 1596 cm-‘, which suggests that the 1597 cm-’ band be assigned as a Fermi resonance enhanced tone. The Raman spectrum of 3-AP in heavy water supports this interpretation, for a shoulder appears at 1582 cm-’ and is assigned as vX+ vY= 1046+538= 1584 cm-‘. The IR spectra of benzene contain a double degenerated e,, (1485) mode. This is basically a ring deformation, since it involves both stretching and bending of the carbon bonds. Under reduced symmetry the two components appear separately which are active in both IR and Raman spectra. This pair of bands appearing in the Raman spectra of pyridine [2,7] at 1482 and 1439 cm-’ are assigned to coupled CC and CN stretching vibrations and can be correlated with the pairs of bands of aminopyridines in the 15201480 and 1450-1410cm-’ ranges (Table 1). Other Raman bands falling in the 1400-1050 cm-’ range involve pyridine ring and C-H in-plane motions, the number of visible bands in this range depending on the location of the amino groups in the pyridine ring. An intense and strongly polarized Raman band which in pyridine appears near 1000 cm-’ is characteristic of the ring breathing vibration [4,6-81. It was shown that this vibrational mode changes to a large amount depending on the mass, nature, number and
400
800
1200
1600
cm-’ Fig. 2. Raman spectra of 0.5 M 2-AP at (top) pH 9.0 and (bottom) pD 9.0.
4
P. CARMONAetal.
T Q)
4~
c¢
a~ g o9
¢¢
L'~
I
400
12i)0
800
1600
c m -1 Fig. 3. Raman spectra of 0.5 M 3-AP at (top) pH 9.0 and (bottom) pD 9.0.
1 4-~ .q,-0
¢¢ Q~
480
800
1200
1600
C m -! Fig. 4. Raman spectra of 0.5 M 4-AP at (top) pH 10.0 and (bottom) pD 10.0.
Aminopyridinesin aqueous sohtion
400
800
1200
5
1600
cm-’ Fig. 5. Raman spectra of 0.5 M 3,4-DAP at (top) pH 10.0 and (bottom) pD 10.0.
position of substituents [6, g-101. The frequency of the breathing vibration in aminopyridines depends, in fact, on the number and positions of amino group substituents, which should be considered at a time of choosing the key bands to be used in the analysis of these compounds in aqueous solution through Raman spectroscopy. There are, finally, three visible Raman bands stemming from vibrational modes involving pyridine ring deformation which appear in the 670-630, 570-540 and 425-380cm-’ ranges. These bands can be correlated with the ylg, ylo and ~27 vibrations of pyridine [4], respectively (Table 1). The presence of both polarized and depolarized Raman bands of 4-AP generated by vibrational modes which can be described in terms of vibrations in the plane of the pyridine ring coupled with amino group motions should be noted. In this connection one can mention, for instance, the depolarized and polarized bands appearing at 1271 cm-’ (v16) and 1607 cm-’ (vq) which shift to 1257 and 1612 cm-‘, respectively, on iV-deuteration (Table 1). This is consistent with a low barrier to inversion of the amino group [2] oriented in such a way that the molecular plane of symmetry is perpendicular to the plane of the pyridine ring, whereby 4-AP molecules may be treated as if they possess C,, symmetry. In fact, a pyramidal structure for the -NH, group with a high barrier to inversion would lead to a C, point group for 4-AP molecules, the molecular plane of symmetry being either perpendicular to the pyridine ring or coincident with it. If this were the true situation, the in-plane vibrations of pyridine ring coupled with amino group motions would originate Raman bands, all of them being either polarized or depolarized, depending on the parallel or perpendicular orientation of the molecular plane of symmetry with respect to the pyridine ring, respectively. However, the v4 and v16bands of 4-AP are polarized and depolarized, which supports the spectral treatment of 4-AP molecules as if they belong to the C2, point group, due to the low barrier to amino group inversion [2]. In fact, the lifetime of Raman scattering is of the order of 10-11-10-13s, whereas the amino inversion vibration in aminopyridines proceeds in the 10-13-10-14 time interval [2]. Raman spectroscopy, thus, cannot discern between two amino group inverted molecular structures of aminopyridines if these structures transform very quickly into each other due to sufficient thermal energy at room temperature. On the other hand, the band of the vn out-of-plane vibration is
P. CAIWONA et al.
6
depolarized in 2-AP and 3-AP, which supports the idea that these molecules can be treated as if they were planar due to the low barrier to the inversion of the amino group. In 3,CDAP, however, all the Raman bands whose depolarization ratios could be measured are polarized. Perhaps the intramolecular hydrogen bond interactions between the two adjacent -NH2 groups lead to a higher barrier of amino group inversion, whereby a C, point group results in 3,4-DAP molecules. In fact, the repulsion between two hydrogen atoms from different amino groups in the molecule results in an orientation for each amino group which is different from that of the other in such a way that hydrogen bonding between them occurs. This obviously involves a C, point group for the 3,4-DAP molecules. Even if the barrier to amino group inversion were low the C, molecular structure would remain, on averaging through time, the amino group inverted structures. Amino group vibrations The characteristic frequency of the NH2 scissoring vibration is usually located in the 1650-1600 cm-’ range [3]. However, the presence of the 60H2 band does not allow us to unequivocally assign this vibrational mode. In addition, the shifting of the bands in the 1610-1500 cm-’ region on N-deuteration shows that the 6NH2 motion takes part in the vibrational modes falling in this region. On the other hand, a band near 1400 cm-’ in the polarized IR spectra of 4-aminopyridine hemiperchlorate crystals [3] was attributed to the NH2 rocking motion. This vibration may be involved in the v14 mode where the
Table 1. Raman frequencies (cm-‘) of aminopyridines in Hz0 and D20 solution*
Dz0
Hz0 2-AP 1629 sh
3-AP
4-AP
3,4-DAP
2-AP
1634 w
1637 w
1606mp
1625 w 1597 sh 159Omp
1607mp
1592mp
1570 m p 1486vwp
1546 vw 1488 w
1561 vw 1512 vw
1445vwp
1442 w
1442 vw dp
1586mp 1564m 1516~~ 1480bw 1440 vw 1444w 1430 vw p
1607m
1333 m p
1367 1346w wp
1337 w
1350 sh
1351 m
1314 sh 1261 m p
1310w 1271 w dp 1217mp
1328 w 1287 w 1198mp
1169sh 1258 m
1154wp 1131 w p 1048s~ 997sp
1287mp 1261 vw ll%mp 1138~~ 1088 vw 1047 vs p 1023sp
866 sh
871 sh
848vsp 82Ovwp 780vwdp 636wp 565mp 421 vw dp
842s~ 820 sh 636wp 549mp 385 w dp
3-AP
4-AP
3,4-DAP
Assignment7 6H,O, 8NH2 1047 + 549 v4 1046+ 538
1596m 1582 sh 1550~~ 1488~
16612m
1600s
1561 vw 1511~~
VI3
1430vw
1439vw
1574~ 1512~ 1427 w 1414w
1376 w 1346vw
1341 w
1354 w
vu
1170~ 1257~ 1220 m
1330 w 1190sh 1277 w 1183m
V~ VI4
1081 m 1052 m p
1152 w 1106m 1048 s 997vs
1311 w 1168~ 1250~~ 1192 m 1128vw 1112vw 1046~s 1025s
871vw
860w
876 vw
848vsp
775 vs p
828s
822 s
832 s
751 vs
666mdp 539mp 398 w dp
618mp 541wp 330 vw
781 vw 635 w 553 m 382 vw
761 vw 635 w 538 m 352vw
667m 529 m 361vw
v25 609m v19 503 w VI0 3OOvw vt7
1058 m p 1002 vs p
vC-NH2 %6
v6 VI7 V18
1057 m 1CKtO vs
1080sh 1066s 990vw 876 w 840W
vs v9 v21
6, v-ring + vC-NH,
Abbreviations: vs, very strong; s, strong; m, medium; w, weak; vw, very weak; sh, shoulder; b, broad; p, polarized; dp, depolarized. * Bands corresponding to Figs 2-5. t Numbering of the assigned vi bands according to Ref. [4].
Aminopyridines in aqueous
solution
7
pyridine ring also takes part, so it is also very difficult to unambigously identify this vibration in the Raman spectra of these aminopyridines. The C-NH2 stretching vibration usually appear around 1300 cm-’ [ll]. We have assigned this vibrational mode to bands falling in the 1350-1280 cm-’ range on the basis of isotopic frequency shifts (Table 1). The shifts of the K-NH, Raman band upon N-deuteration is accompanied by shifts of some bands falling in the 1400-llOOcm-’ region, which shows that these are coupled with the C-NH, motion. This seems to be also involved in the vibrational mode giving rise to the strong band located in the 850-750 cm-’ range as this band shifts to lower frequencies on N-deuteration. Moreover, it was shown previously [6,8] that in methylpyridines there is usually a polarized strong band in the 850-750 cm-’ range whose vibrational mode is described in terms of in-plane deformation of the pyridine ring as well as YC-C and vN-C vibrations coupled with the YC-CH~ motion. As the mass of the -CH, group is near that of the -NH, one, the strong polarized Raman band shown in the 850-750 cm-’ range of aminopyridines can be correlated with the polarized strong Raman band of methylpyridines in the same range. This seems to be supported by considering the frequency of this band from each aminopyridine and the resonant structures (Fig. 1) that are expected to be most important in the valence bond picture of aminopyridines. Thus, no reasonable resonance structure can put a negative charge on the ring nitrogen in 3-AP, so the double bond character of the external C-NH2 bond in this compound is lower than that of 2-AP and 4-AP. If the vC-NH, motion takes part in the vibrational mode of the polarized strong band appearing in the 850-750 cm-’ range, it is to be expected that the frequency of this band is higher in 2-AP and 4-AP than in 3-AP, as indeed occurs. The fact that this band in 3,4-DAP is located even at lower frequency (775 cm-‘) than in the three aminopyridines can be explained by assuming the presence of two vibrational modes involving, respectively, the symmetric and antisymmetric motions of both C-NH, bonds, only the symmetric mode being very active in Raman. The great intensity of this band from these aminopyridines allows us to consider it as a potential key band to be used in the analysis of these compounds through Raman spectroscopy. The relative intensity of this band even increases at pH near 7.0 and appears practically at the same frequency with respect to higher pH (Figs 6-7), which means that this band can also be used for the analysis of these aminopyridines at physiological pH when used as drugs. Concerning the wagging NH2 mode, a band near 440 cm-’ was assigned to it in the polarized IR spectra of 4-aminopyridine hemiperchlorate single crystal [3]. This NH, wagging motion is probably involved in the ~27 mode of the compounds studied in this work, as shown by its shifting to lower frequencies on ZV-deuteration. The largest spectral changes in going from basic to neutral pH in the aminopyridine solutions correspond to 4-AP and 3,CDAP, which can be explained by considering that the p& values of 2-AP, 3-AP, 4-AP and 3,bDAP are 6.8,5.8, 9.1 and 8.3, respectively [12]. Therefore, protonation at the pyridine ring N atom of 4-AP and 3,CDAP must occur to a much greater extent at pH 7.0 than in 2-AP and 3-AP at the same pH. This may be the reason why some bands of the exocylic =N+H2 group of the amidinium ion, resulting from the protonation of the 4-AP form (II) (Fig. 1) at the ring nitrogen, are visible. In fact, the most prominent band above 1600 cm-’ in the Raman spectra of 4-AP at pH 7.0 appears at 1647 cm-’ (Fig. 6) for which there is no counterpart in its respective aqueous solution at basic pH. This band is attributable to exocylic C=N+ stretching, possibly mixed with the NH+H scissoring [13,14]. A similar band is also observed for 3,6DAP at neutral pH (Fig. 7) which is interpreted in the same way. The Raman spectra of 4-AP and 3,6DAP reveal, then, an increase of the contribution of the mesomeric amidinium forms (Fig. 1) in the structure of these aminopyridines on protonation. This is also reflected by the slight frequency increase of the polarized strong band (Figs 4-7) located in the 850-750 cm-’ range which seems to involve the exocyclic C-NH2 stretching motion to some extent, as described above. In conclusion, we report for the first time the Raman spectra of 2-AP, 3-AP, 4-AP and 3,4-DAP in aqueous solution whose bands have been assigned. Measurements of depolarization ratios reveal that the spectra of 4-AP can be interpreted as if its molecules
P. CARMONAet al.
cm-’ Fig. 6. Raman spectra of 0.5 M monoaminopyridines at pH7.0. bottom, 4-AP.
Top, 2-AP; middle, 3-AP;
possess C,, symmetry, which involves low barriers to amino group inversion as described previously [2]. On the other hand, the presence of some depolarized Raman bands from 2-AP and 3-AP supports the idea that the molecules of these two compounds behave in Raman spectroscopy as if they were planar, which may be also due to a low barrier to amino inversion. The Raman spectra of 3,4-DAP, however, are consistent with the absence of a plane of symmetry, probably due to intramolecular hydrogen bonding between both amino groups. Protonation of 4-AP and 3,4-DAP at pH 7.0 leads to an increase in the contribution of the mesomeric amidinium forms to the description of the electron distribution in these substances.
F
400
1200
800
1600
cm-’ Fig. 7. Raman spectrum of 0.5 M 3,4-DAP at pH 7.0.
Aminopyridines
in aqueous solution
9
Acknowledgement-The financial support (PB90-148) of the Direcci6n General de Investigacih Cientffica y T&nica is gratefully acknowledged.
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K. Sasaki, I. Kuwano and K. Aida, 1. Inorg. Nucl. Chem. 43, 485 (1981). R. A. Kydd, Spectrochim. Actu. 35A, 409 (1979). J. Baran, Z. Malarski, L. Sobczyk and E. Grech, Spectrochim. Actu 44A, 933 (1988). D. A. Long and E. L. Thomas, Trans. Faraday Sot. 59,783 (1%3). D. P. DiLella, J. Rumun Spectrosc. 9,239 (1980). J. A. Draeger, Spectrochim. Actu 39A, 809 (1983). D. P. DiLella and H. D. Stidham, J. Rumun Spectrosc. 9, 90 (1980). A. Y. Obaid and M. S. Soliman, Spectrochim. Actu 46A, 1779 (1990). J. K. Wilmshurst and H. J. Bernstein, Can. J. Chem. 35, 911 (1957). D. H. Whiffen and A. Stojiljkovic, Spectrochim. Actu 12A, 42 (1958). V. B. Singh, R. N. Singh and I. S. Singh, Spectrochim. Actu 22, 927 (1966). R. C. Weast, Handbook of Chemistry and Physics, 62nd Edn. Chemical Rubber Co., Boca Raton, Florida (1981). [13] L. J. Bellamy, The Infrared Spectra of Complex Molecules, Vol. 2, Chapman and Hall, London (1980). [14] S. Mansy, W. L. Peticolas and R. S. Tobias, Spectrochim. Actu 35A, 315 (1979).