SPECTROSCOPIC STUDIES OF
ISOTOPICALLY
1177
SUBSTITUTED 2-PYRIDONES
the apparently complete separation of CO and COZ evolution on Graphon.12 The CO similarities support interconversion. All things considered, it appears that interconversion did not obscure the decompositions. Acknowledgment. We are very grateful to The
Robert A. Welch Foundation of Houston, Texas, whose generous support made this research possible. We wish to thank the Cabot Corporation for the Spheron-6. Fellowship support for M. T. C. by the Procter and Gamble Company is gratefully acknowledged.
Spectroscopic Studies of Isotopically Substituted 2-Pyridones by Robert A. Coburn A r m y Materials and Mechanics Research Center, Watertown, Massachusetts 02172
and Gerald 0.Dudek Department of Chemistry, Harvard University, Cambridge, Massachusetts 08198
(Received August 16, 1967)
The pmr spectrum of 2(1H)-pyridone-15N provides direct evidence, at low temperatures, of the pyridone form predominating over the hydroxypyridine tautomer by greater than 50: 1 in deuteriochloroform solution. The exchange of the enolisable proton appears to be unusually facile under these conditions. Infrared spectra of 2(1H)-pyridone-V, 2( 1s)-pyridone-1-d, 2 (1H)-pyridone-l-d-15N, 2 (1H)-pyridoneJ80, 2 (lH)-pyridone-l-d-’*O, 1-methyl-2( 1H)-pyridone-16N, and 1-methyl-2(lH)-pyridone-’*O in solution are reported. Isotopic spectral shifts suggest a revision of previous vibrational assignments and reveal unsuspected anomalous solvent and concentration effects. Implications bearing on molecular structure are discussed.
The infrared absorption spectra of 2-pyridones and secondary amides, in general, have presented a vexatious problem to those who would desire to obtain molecular bonding parameters from such data. Assignments of vibrations are hampered by strong intermolecular interactions as well as extensive coupling of vibrations.‘ A study of the infrared spectra of normal and isotopically substituted bensamides by Kniseley and coworkers2 gives an indication of the scope of spectral changes which can be produced in amides by changes in state and nitrogen-15 or deuterium substitution. In spite of this, the phase in which such spectra are recorded is often neglected. Important spectral changes occur with 2-pyridones when proceeding from the solid state3 (helix) to solutions with nonpolar solvents4 (dimer) and finally to polar solvents or high dilution in less-polar solvents such as chloroform (hydrogen-bonded monomer). The existence of 2-pyridone in the lactam form is supported by electronic absorption studies,6infrared studies,6ionization-constant determinations,’ and pmr data.s I n view of the classical aromatic properties of 2-pyridones, significant participation of resonance structures such as I1 and I11 have been invoked by a number of authors,@’
while othersedhave argued against a large contribution from them. The data desirous from infrared spectra
-
- 0-
Qo QoI I H
I
H
II
I
H
m
bearing on this facet of the molecular structure would (1) L. J. Bellamy, “The Infra-Red Spectra of Complex Molecules,” John Wiley and Sons, Inc., New York, N. Y.,1964,pp 203-233. (2) R. N. Kniseley, V. A. Fassel, E. L. Farquhar, and L. 8. Gray, Spectrochim. Acta, 18, 1217 (1962). (3) B. Penfold, Acta Cryst., 6, 591 (1953). (4) (a) M. H.Krackov, C. M. Lee, and H. G. Mautner, J. Am. Chem. SOC.,87, 892 (1965); (b) G. G.Hammes and H. 0. Spivey, ibid., 88, 1621 (1966). (5) H.Specker and H. Gawrosch, Ber., 75, 1338 (1942); V. I. Blienyukov and V. M. Reanikov, J. Gen. Chem, USSR, 25, 1735 (1955). (6) (a) P. Sensi and G. G. Gallo, Ann. Chim. (Rome), 44, 232 (1954); (b) A. Albert and E. Spinner, J. Chem. Soc., 1221 (1960); (c) A. R. Katriteky and R. A. Jones, ibid., 2947 (1960); (d) E. Spinner and J. C. B. White, {bid., Sect. E , 991 (1966). (7) A. Albert and J. N. Phillips, ibid., 1294 (1956). (8) J. A. Elvidge and L.IM. Jackman, ibid., 859 (1961). Volume 72, Number 4 April 1968
1178 provide information concerning the natures of the C-0, C-N, and, possibly, N-H bonds. We report here infrared and pmr studies of isotopically substituted 2-pyridones, vibrational assignments which differ from those previously proposed, and implications concerning molecular structure. Experimental Section 2-Pyridone was obtained from the Aldrich Chemical Co. and was purified by repetitive sublimation and dried over anhydrous phosphorus pentoxide. 2-PyridoneI6N was prepared according to the procedure of Stetten and Schoenheimerg from coumalic acid and ammonium chloride containing >95 atom yonitrogen-15 (Bio Rad Laboratories). 2-Pyridone failed to incorporate oxygen-18 when heated to 100" for 24 hr in 90 atom % oxygen-18 enriched water, with or without the presence of an acid catalyst. Therefore, 2-pyridone-180 was prepared from 2-aminopyridine in the following manner. Sodium nitrite (36 mg, 0.514 mmol) in 0.1 ml of 93.7 atom % oxygen-18 enriched water was slowly added to a solution of 2-aminopyridine (47 mg, 0.5 mmol) and fuming sulfuric acid, 30% SO3 (85 mg) in 0.4 ml of oxygen-18 enriched water which was cooled in an ice bath. The reaction mixture was allowed to stand for l/z hr a t 0" then for 2 hr a t room temperature. After refluxing for 3 hr, the cooled solution was neutralized with 10% sodium bicarbonate solution and the solvent was removed by distillation. Repeated extraction of the residue with chloroform and evaporation of the combined extracts gave crystals of 2-pyridone. Recrystallization from carbon tetrachloride and sublimation provided 23.7 mg (Soyo yield) of white crystals of 2-pyridone, identical in melting point and mixed melting point with that of an authentic sample. From the ratio of 97 to 95 (m/e) in the mass spectrum of this sample, the oxygen-18 content was found to be 67 atom %. Deuterated samples of 2-pyridone were obtained by repetitive treatment with a tenfold excess of >99.7 atom % deuterium enriched water followed by sublimation. Greater than 95 yo deuteration of the l-position was estimated from the 3600-2000-cm-' region of the infrared spectrum. The isotopically substituted N-methyl-2-pyridones were obtained from the correspondingly substituted 2-pyridones by treatment with a freshly distilled ethereal solution containing a fivefold excess of diazomethane. The reaction solution was maintained at 0" for 24 hr. Evaporation of solvent at reduced pressure and drying under vacuum yielded an oil which exhibited properties (tlc, ultraviolet absorption, etc.) identical to those of an authentic sample of N-methyl-2-pyridone.1° Presumably, any 2-methoxypyridine formed under these conditions" is lost during the workup, since it could not be detected in the ultraviolet spectrum or by chromatographic means. The Journal of Physical Chemistry
ROBERT A. COBURN AND GERALD 0. DUDEK Solvents were carefully dried before each determination, and only fresh solutions were used. I n the case of samples prepared for pmr studies, transfers of solids were conducted in a drybox and solvents distilled under nitrogen from their drying agents (anhydrous phosphorus pentoxide, in most cases) directly into sample tubes which were then degassed and sealed. Infrared spectra were recorded with a Cary-White Model 90 infrared spectrophotometer. The band width was set to 2.5 em-' or less and spectra recorded in triplicate where applicable. Determinations of frequency generally agreed within 1cm-'. Solutions were recorded in 0.2-mm sodium chloride, 0.5-mm potassium bromide, 0.02-mm calcium fluoride, and 0.2-mm Irtran compensated cells. Pmr spectra were recorded with a Varian A-60 spectrometer operating a t 60.00 MHz. The chemical shifts were determined by interpolating between side bands of tetramethylsilane (internal) generated by an audiooscillator continuously monitored by a frequency counter. The variable temperature probe was calibrated by measuring the shift between the resonances of methanol. The chemical shifts are accurate to iO.01 ppm, the spin couplings to *0.2 Hz, and the temperature to f1". Association studies were conducted using a Mechrolab Model 301A vapor-phase osmometer. Apparent molarities were determined for dry, alcohol-free chloroform solutions of 2-pyridone of known concentrations. Purified benzophenone in the same solvent was used to establish a calibration factor us. concentration curve. Concentrations in the range 0.07-0.005 m were studied. Results Table I contains the infrared data for 2-pyridone, 2-pyridone-'6N, and 2-pyridone-'*O0 Also indicated are solvent effects. The 4000-2000-cm-' region has been discussed at length by Bellamy and Rogasch12 and is not considered here. Deuteration of 2-pyridone was found to produce such extensive changes in the solution spectra that the infrared data for the deuterated normal, nitrogen-15, and oxygen-18 substituted 2-pyridones are listed separately in Table 11. Discussion No attempt will be made to provide a complete vibrational assignment, although a number of previous assignments are questionable. For instance, the 1477and 1443-em-' bands have been assigned t o skeletal stretching;6c however, the sensitivity of these bands t o changes in state, solvent, and isotopic substitution (they disappear entirely upon deuteration) render this (9) M. R. Stetten and R. Schoenheimer, J. Biol. Chem., 153, 113 (1944). (10) E,A. Prill and S. M. McElvain, "Organic Syntheses," Coll. Vol. 11,John Wiley and Sons, Inc., New York, N. Y.,1943,p 419. (11) N.Kornblum and G. P. Coffey, J . Org. Chem., 31, 3447 (1966). (12) L. J. Bellamy and P. E. Rogasch, PTOC.Roy. SOC.(London), A257, 98 (1960).
SPECTROSCOPIC
STUDIES OF
ISOTOPICALLY
Table I : Infrared Data for Normal, 16N, and
1179
SUBSTITUTED 2-PYRIDONES
180
2-Pyridone
Table 111: Infrared Data for Normal, and l80N-Methyl-2-pyridone
IKN,
-2-PyridonebV,
om -1
c
1682' 1658 1620
340 1200 335
1544 1477 1443 1374 1251 1228 1151 1097 1007' 991 922 845 767 723 611 558 51 1 494
140 96 104 32 88 26 60 12
Avc for
Avd for
16N
180
A"#'
-9 -2 -2, -5O
-7 -5 -3
-2 -7 (-14)h -4 (-23)h
-2 -5 -2
...
..
- 10
+I
... ...
-4
... -6
.,.
140 50 30 290 135 20 170 135 160
-7
$2
... ...
+I
...
Avo for d
- 15 - 10 - 40i
-7 -2 1604' -6
*.. ... ... ... ... ... ...
...
-4
... ... ...
$3
...
- 11
... ... ...
... ...
- 39
-2 -3
-3 -2 -4
... ,
.
-4
-4
' Data reported for carbon tetrachloride solution and, below 800 cm-1, for carbon disulfide solution. Solvent shift in dry, alcohol-free chloroform. ' Determined from carbon tetrachloride solution spectra for the first seven peaks, the remaining from carbon disulfide solution spectra. Determined by comparison of chloroform solution spectra. e See Table I1 for details. Shoulder. Broad peak at low concentrations. Solvent shift in aqueous solution. ' Value is approximate.
'
Table 11: Infrared D a t a for Normal, and 1 8 0 2-Pyridone-l-d -----2-Pyridone-di'--om -1
1667' 1658' 1648 1586 1575b 1539 1310 1156' 1148 980 964' 847
€
400 570 1000 730 150 120 30 110 150 70 75
ISN,
Au for 'ON
-4 -2 -2 -3 -4 15
-
... -7
... ...
1659 s 1599' m 1583 s 1541 m 1411 w 1384 w 1316 m 1290 w 1240 m 1182 w 1154 1051 m 876 m 844 m
-5
..,
I
N-Methyl2-~yridone,~ om-'
Av
for
180
... ... ...
- 14 - 17 *.. +2 -2
Data were determined from carbon tetrachloride solution spectra in all cases. Shoulder.
'
assignment doubtful, as already noted by Spinner and WhitesBd For the present study, interest is centered on the 2000-1000-~m-~region. The great difference between the solution spectra of 2-pyridone and 2-pyridone-d~is readily apparent. The
Av
for "N
Au
for
180
-2
-4
...
...
...
-11
-2 -3 -3 - 14
...
... ...
...
... ... ... ... ... ...
-3 -2
...
... ... *.. -5
-8
Datq were determined from chloroform solution spectra in all cases. Shoulder.
'
~
~~
~
latter bears a much greater resemblance to that of 2-pyridone in the solid state6dor N-methyl-Ppyridone. Undoubtedly, this is due to effects centered about the N-H bond. In the case of 2-pyridone itself, the 1658cm-l band varies from 1649-1641 cm-I in the solid state6d to 1673 cm-' in dilute solution in chloroform. Chloroform as a solvent is particularly interesting, since both dimer and monomer can be observed in the same medium. Vapor-phase osmometric measurements indicate that the per cent dimer varies from ca. 90 to 40% over the concentration range whose infrared spectrum can be determined conveniently, ie., 0.001-0.2 m. At low concentrations, the small shoulder at 1673 cm-I becomes equal in intensity to the 1656-cm-I peak (ca. 0.003 m). At concentrations below 0.001 m, the 1673cm-1 peak is the most prominent peak in the spectrum (the 1656-cm-1 peak decreases proportionately). In dimethyl sulfoxide, the higher frequency peak at 1668 cm-I is also the most intense. These results are in accord with the results of Bellamy and Rogasch,I3 who found that the 1659-cm-' band of N-methyl-Bpyridone varies from 1698 cm-I in the vapor state to 1658 cm-' in methylene iodide solution. On this basis, they assigned this band to the carbonyl stretching vibration. Although solvent effects on band frequency and intensity strongly support this contention for both 2-pyridone and its N-methyl derivative, the isotopic results reported here indicate an interesting alternative explanation. (See Table 111). Extensive coupling of carbonyl stretching, carboncarbon double bond stretching, carbon-nitrogen stretching, and nitrogen-hydrogen in-plane bending modes is (13) L. J. Bellamy and P. E. Rogasoh, Spectrochim. Acta, 16, 30 (1960).
Volume 71,Number 4 April 1968
1180 apparent. The results of this intermixing of vibrations can be seen in the first six bands listed in Table I. As with secondary amides, V C O , V C N , and ~ N would H be expected to be ~ o u p l e d . ' ~It can be noted that when 8" is removed by deuteration or methylation, the lSN isotopic effect on the high-frequency bands decreases. At the same time, the 15Xisotopic shift of 10 cm-' on what must be predominantly Y C N , occurring at 1290 cm-', increases to 14 and 15 cm-' for the 1316 and 1310-cm-' bands of X-methyl and N-deuterio-2-pyridone, respectively. The latter isotopic shifts compare favorably with a shift of 21 cm-' calculated for an isolated carbonnitrogen stretching vibation. The conclusion is that upon removal of coupling between vco and V C N is considerably reduced. Therefore, in the deuterated or methylated 2-pyridones, bands in the 1400-2000cm-' region represent largely a mixture of vco and YCC'S. Oxygen-18 substitution was employed to determine the extent of this coupling and identity of vibrations. A completely isolated carbon-oxygen stretching vibration can be calculated to produce an oxygen-18 isotopic shift of 41 cm-l. Typical observed shifts are: 20-24 cm-' for benzamide,lb 27 cm-' for benzoic acid in chloroform, l6 and 31 cm-l for 2,4-dimethyl-3-pentanone. l7 As expected, in 2-pyridone itself both the 1650 and 1620 1544-cm-l bands exhibit oxygen-18 sensitivity. I n the case of the simplified systems of the N-substituted 2-pyridones, the lower frequency strong-intensity band exhibits the primary isotopic eflect. This appears to be another instance where the application of the concept of group frequencies would be entirely misleading. l8 The higher frequency band exhibits solvent effects associated with a polar oscillator, while the lower frequency band exhibits the greater sensitivity toward isotopic substitution within that same group. Certainly, one would expect a polar group vibration coupled to a nonpolar group vibration to produce an observable solvent effect, The unexpected result is the extent to which the solvent and isotope effects appear predominantly in one or the other of the two bands. The unperturbed carbonyl stretching frequency in N-substituted 2-pyridones would lie somewhere between the 1650 and 1580-cm-' bands. Correction for an electronegativity effect from the neighboring nitrogen on the carbonyl frequency would further favor a lower carbon-oxygen bond order and a greater participation of resonance forms I1 and I11 than would be implied by a heretofore accepted 1650-cm-l carbonyl stretching frequency. Conversely, similar coupling in the 4-pyridones would lead to an upward revision of the carbonyl stretching frequency, since the lower frequency band has previously been assigned to the carbonyl stretching mode.13
+
Proton Magnetic Resonance Studies Pmr studies of a number of types of compounds have The Journal of Physical Chemistry
ROBERT A. COBURN AND GERALD 0. DUDEK shown that 15N-substitutioncan be used to advantage in studying exchange processes in nitrogenous systems. l9 Substitution of the 15Nnucleus with its spin of l/z and a 15N-H coupling constant of 90 Hz in place of the 14N nucleus with its quadrupole broadening allows the convenient study of exchange processes.20
0-0 I
0
OF
N
H I
Iv
The lactam form of 2-pyridone (I) has been estimated from ionization-constant studies to predominate by 340:l over its lactim tautomer (IV) in aqueous solution.' Intramolecular proton exchange between nitrogen-15 and oxygen, if slow, would allow the observation of the 'W-H coupled doublet and the 0-H singlet of I and IV, respectively. The relative intensities of these signals would provide a measure of the above equilibrium. More likely, the exchange is rapid.lgb In that case, the magnitude of the observed 15N-H coupling constant would provide an indication of the relative amounts of the two forms involved.lgb
Results The enolizable proton of 2-pyridone-15N was found t o resonate at 6 13.60 f 0.01 ppm in carbon tetrachloride, deuteriochloroform, and methylene chloride. In dimethyl sulfoxide, pyridine, and acetone-&, the chemical shifts were 6 = 11.47, 12.72, and 13.17 ppm, respectively. I n all cases, a singlet was observed at room temperature, even though the solvents and samples were rigorously purified and dried. Under similar conditions, the multiplet of the hydroxylic proton of ethanol could easily be resolved. Cooling, in the case of deuteriochloroform solution, resulted in the broadening of this signal until the co2". The SO-Hz alescence point was reached at -46 'EN-H coupling constant was observed at -56". In methylene chloride, the coalescence point was -74 2" and the 90-Hz splitting was achieved a t -84".
*
*
(14) T. Miyazawa, T. Shimanouchi, and S. Mizushima, J . Chem. Phys., 29, 611 (1958). (15) S.Pinchas, D. Samuel, and M. Weiss-Broday, J . Chem. Soc., 1688 (1961). (16) S. Pinchas, D. Samuel, and M. Weiss-Broday, (bid., 2382 (1961). (17) G. J. Karabatsos, J. Org. Chem., 25, 315 (1960). (18).Randall, et al., used 16N spectral shifts to indicate the inadmsability of using the group-frequency concept in the case of tertiary amides and their complexes, E. W. Randall, C. M. S. Yoder, and J. J. Zuckerman, Inorg. Chem., 5, 2240 (1966). (19) (a) B. Sunners, L. H. Piette, and W. G. Schneider, Can. J . Chem., 38, 681 (1960); (b) G. 0. Dudek and E. P. Dudek, J . A m . Chem. Soc., 85, 694 (1963); 86, 4283 (1964); 88,2407 (1966); (0) G. 0. Dudek and E. P. Dudek, Chem. Commun., 464 (1965). (20)W. B. Monis and H. S.Gutowsky, J . Chem. Phys., 38, 1155 (1963).
SPECTROSCOPIC STUDIES OF ISOTOPICALLY
1181
SUBSTITUTED 2-PYRIDONES
Limited solubility or solvent solidification precluded similar observations in other solvents. As a check against the presence of water or other impurities, four different samples of 2-pyridone-16N were each subjected to a different sequence of recrystallizations from different solvents. The samples were sublimed after each recrystallization and protected from the atmosphere during transfers. Both alcohol-free chloroform and deuteriochloroform were used as solvents and were dried and distilled directly into the sample tubes. The observed coalescence point for the four samples agreed within experimental error ( *2O).
Discussion The unusually low field resonance of the enolizable proton is evidence of the very strong hydrogen bond existing in the dimer of 2-pyridone. I n fact, 2-pyridone forms one of the most stable hydrogen-bonded dimers known (excluding zwitterion structure^).^^ This is a consequence of the significant contribution of chargeseparated forms I1 and I11 to the resonance structure. The signal for the enolizable proton, appearing as a single peak of varying width depending upon solvent and temperature, can be interpreted in two ways. Either lactim IV predominates by >50:1 over lactam I or the proton in question is exchanging intermolecularly very rapidly, thereby being completely decoupled. The convincing ultraviolet spectral evidence5J1supporting the lactam structure in a wide variety of solvents argues against the first explanation.
Rapid intermolecular proton exchange could occur within the dimer followed by dissociation and re-association with different monomers, since the latter process has been shown to occur very r a ~ i d l y . ~ bAnother mechanism would be ionization and exchange through anionic or cationic forms. The faster exchange was observed, however, in the less polar solvent where the concentration of monomer would be expected to be smaller and ionic structures less favored. Despite the precautions taken, the catalysis of this exchange by some unknown agent cannot be excluded. Nevertheless, the possibility of exchange occurring within the dimer is interesting, since Cannon22 proposed the increased probability of proton transfer across the hydrogen bond in the vibrationally excited state. Bellamy and Rogasch12offered infrared spectral i n d i m tions of this possibility in 2-pyridone. Apparently this type of exchange does not occur in a similar system, 2-hydroxyquinoline, which also has been found to exist in the lactam form, since coupling was detected between the 14Nnucleus and a low-field proton.23 At very low temperatures, the observed lBN-H coupling of 90 Hz is good evidence that the relative amount of lactim IV is below 20ja.lgb (21) 3-Hydroxyisoquinoline is an example of a similar system in which ultraviolet studies have revealed the presence of both lactam and lactim forms depending upon the solvent: D. A. Evans, G. F. Smith, and M. A. Wahid, J. Chem. Soc., Sect B , 590 (1967). (22) C. G. Cannon, Speectrochim. Acta, 10, 341 (1958). (23) P. Hampson and A. Mathias, Chem. Commun., 371 (1967).
Volume 72,Number 4
April I968
