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effective stabilization. Measurements in the polymer which consider both excited carbonyl and singlet oxygen quenching are now needed to completely characterize the behavior of stabilizers.
Acknowledgment. We wish to thank R. P. Hendrix for performing many of the quenching experiments and Professor R. S. Becker of the University of Houston for many helpful suggestions.
2,4,6-Trisubs titu ted Pyridines. Synthesis, Fluorescence, and Scintillator Properties1' Maria del Carmen G. Barrio, Jorge R. Barrio, Graham Walker, Armando Novelli,lb and Nelson J. Leonard"
Contribution f r o m the Facultad de Farmacia y Bioquimica, Universidad de Buenos Aires, Buenos Aires, Argentina, and the Roger Adams Laboratory, School of Chemical Sciences, University of Illinois, Urbana, Illinois 61801. Received December 9, 1972 Abstract: The synthesis of 2,4,6-trisubstituted pyridines from chalcones and formamide, under the conditions of the Leuckart reaction, is described. In contrast to 2,4,6-triphenylpyridine, which yields 2,4,6-tricyclohexylpiperidine on catalytic hydrogenation with platinum in acetic acid, 2,6-diphenyl-4-(p-methoxyphenyl)pyridineand 2,6di(p-methoxyphenyl)-4-phenylpyridineyield 2,6-dicyc1ohexy1-4-(-methoxypheny1)pyridine and 4-cyclohexyl-2,6di(p-methoxyphenyl)pyridine, respectively. Physical and chemical evidence firmly established the proposed structures. The ultraviolet absorption and fluorescence excitation and emission spectra of the substituted pyridines synthesized showed structure and pH dependence. Most of the compounds showed extremely high fluorescence M . Initial studies have demonstrated that intensity, being readily visible at concentrations even below 1 X certain 2,4,6-triaryl substituted pyridines show promising potential as scintillators that will allow liquid scintillation counting to be carried out at high efficiency in strongly acidic solution.
A
convenient and relatively simple procedure for the preparation of 2,4,6-triarylpyridines has been developed during the course of attempts to synthesize 1,3-diarylallylamines. The starting materials for this synthesis are the commercially available or easily accessible chalcones (1). The reaction of chalcones (1) with formamide under conditions of the Leuckart reaction2 (Scheme I) yielded 2,4,6-triarylpyridines (2) as the major products. The overall yields, in the range of 30-33%, were good compared with those obtained by other routes. The spectroscopic properties of certain of the 2,4,6-trisubstituted pyridines are of interest, particularly the high degree of fluorescence and the efficiency of liquid scintillation counting in strongly acidic solution. Previously, 2,4,6-triarylpyridines have been prepared by the condensation of 1,5-diketones with formamide-formic acid3 and by other synthetic procedures including the Chichibabin method. 4-7 Following this procedure, the yields of single products are low because of the formation of mixtures of pyridines and various b y - p r o d ~ c t s . ~Formamide has proved t o be a versatile agent in heterocyclic syntheses,*-'O in (1) (a) The synthetic methodology described in this article was initiated at the University of Buenos Aires under the guidance of Professor Armando Novelli. (b) Deceased. (2) M . L. Moore, Org. React., 5, 301 (1949). (3) F. Chubb, A. S. Hay, and R. B. Sandin, J. Amer. Chem. Soc., 75, 6042 (1953). (4) W. Dilthey, J. Prukt. Chem., 102, 209 (1921). (5) R. Lombard and J. P. Stephan, Bull. Soc. Chim. Fr., 1458 (1958). (6) W. Zecher and F. Krohnke, Chem. Ber., 94,690 (1961). (7) R. L. Frank and R. P. Seven, J. Amer. Chem. Soc., 71, 2629 (1949), and references therein. (8) H. Bredereck, R. Gompper, H. G. v. Schuh, and G. Theilig, Angew. Chem., 71, 753 (1959).
the Leuckart reaction with aldehydes and ketones, l1-I7 and in addition reactions to olefins in the presence of ultraviolet or peroxides. The course of the reaction of the chalcones (1) with the product mixture resulting from heating ammonium carbonate and formic acid in ca. 1 :2 molar proportion, or with excess formamide-ammonium formate, is complicated because of the combined functionality in l . Formamide alone during 6 hr at 180-190" did not produce appreciable triarylpyridine from chalcone IC. The structures of the products formed in the general condensation reaction, 1 +- 2 (Scheme I), were established by elemental analysis, nmr spectra, and positive compari25n26
(9) H. Bredereck, R. Gompper, H. G. v. Schuh, and G. Theilig, Newer Methods Prep. Org. Chem., 3,241 (1964). (10) H. W. Gibson, Chem. Reu., 69,673 (1969). (11) P. A. S. Smith and A. J. Macdonald, J. Amer. Chem. Soc., 72, 1037 (1950). (12) W . H. Davies and M. A. T . Rogers,J. Chem. Soc., 126 (1944). (13) M. Mousseron, R. Jacquier, and R. Zagdoun, Bull. SOC.Chim. Fr., 197 (1952). (14) V . Komarov, E. A. Chernikova, and G. V. Komarov, Zh. Fiz. Khim., 36, 540 (1962); Chem. Abstr., 57, 1605 (1962). (15) A. N. Kost and I. I. Grandberg, Zh. Obshch. Khim., 25, 1432 (1955); Chem. Absrr., 50, 4800 (1956). (16) D. S . Noyce and F. W. Bachelor, J . Amer. Chem. Soc., 74, 4577 (1952). (17) A. Chatterjee and R. Raychaudhuri, J . Org. Chem., 33, 2546 (1968). (18) D. Elad, Proc. Chem. Soc., London, 225 (1962). (19) D. Elad, Chem. Ind. (London), 362 (1962). (20) D. Elad and J. Rokach, J . Org. Chem., 29,1855 (1964). (21) D. Elad and J. Rokach, ibid., 30,3361 (1965). (22) D. Elad and J. Rokach, J . Chem. Soc., 800 (1965). (23) D. Elad, Angew. Chem., Int. Ed. Engl., 5 , 2 5 5 (1966). (24) M. Fish and G. Ourisson, Bull. Soc. Chim. Fr., 1325 (1966). (25) A. Rieche, E. Schmitz, and E. Gruendemann, Z. Chem., 4, 177 (1964). (26) A. Rieche, E. Schmitz, and E. Gruendemann, Angew. Chem., 73, 621 (1961).
Barrio, et al. 1 2,4,6-Triarylpyridines: Fluorescence and Scintillation
4892
addition of ferric chloride or sparging the reaction mixture with air was without apparent effect on the yield. No evidence of pyridine mixtures was detected in the isolated product, suggesting that the most useful aspect of the present method is that competitive reactions can be avoided. The structures of the catalytic reduction products 3a-c formed from 2a-c by the action of hydrogen and OCHS I
Q /--, /'
\ '\
', 3c
\\ \ \ \ \\ \\ \
360
380
400
420
440
460
500
480
WAVELENGTH
520
540
560
I nm I
Figure 1. Top panel: electronic absorption spectra (230-440 nm) of 2c in ethanol (-) and in 0.05 N HCI in 50z ethanol (------). Bottom panel: molecular fluorescence emission spectra of 2c i n the same solvents. Scheme I
HCOh'H,
h
HCOONH,
%0
\
/
R'
R'
1
R=R'=H b. R = OCH : R'= H c. R = H, R = OCH,
-2
a,
son of the physical properties with those previously described for the particular 2,4,6-triarylpyridines. The positions of the substituents in 2b and 2c define the precursor units: an intact chalcone accounting for the 2, 3, and 4 carbons of the pyridine and the acetophenone moiety of another chalcone accounting for the 5 and 6 carbons. The formal rationalization of the product formation involves a reverse aldol reaction of the a,B-unsaturated ketone, a Michael-type addition, condensation with formamide, and dehydrogenation by hydrogen transfer?' or disproportionation. The (27) M. Weiss [J. Amer. Chem. SOC.,74, 200 (195211 isolated 2,4,6triphenylpyridine and benzylacetophenone (low yield) from the reaction
Journal of the American Chemical Society
95:15
OCH,
platinum oxide in acetic acid solution were established by analyses, ultraviolet, infrared, nmr, and mass spectra. For example, the catalytic hydrogenation of 2,6-di(p-methoxyphenyl)-4-phenylpyridine(2c) resulted in the absorption of 3 mol equiv of hydrogen. The ir spectrum showed the disappearance of bands at 698, 763, and 775 cm-l, corresponding to the monosubstituted benzene ring. No change was observed in the aromatic band at 833 cm-', characteristic of disub~ t i t u t i o n . ? ~The nmr spectrum of 2c in CDCls included a multiplet centered at 6 7.50 that was replaced by a new, broad resonance (1 1 H) centered at 6 1.60 for 3c. The P-pyridine hydrogens appeared as a sharp singlet at 6 7.74 in 212, shifted to 6 7.10 in 312, and the AB pattern of doublets at 6 7.15 and 8.16, J = 9.0 Hz, indicative of the meta and ortho hydrogens of the p methoxyphenyl rings, respectively, was shifted to 6 6.70 and 7.75 in the conversion. The molecular ion peak at inje 373 confirmed the extent of the reduction process and the assignment of the product as 4-cyclohexyl-2,6-di(p-methoxyphenyl)pyridine. Similarly, 2,6diphenyl-4-(p-methoxyphenyl)pyridine (2b) underwent reduction in the rings lacking methoxyl to give 2,6dicyclohexyl-4-(p-methoxyphenyl)pyridine (3b). 2,4,6Triphenylpyridine (2a) underwent complete reduction to 2,4,6-tricyclohexylpiperidine (3a), mp 153', under our conditions, whereas Overhoff and Wibaut 30 observed the formation of 2,4,6-tricyclohexylpyridine, mp 47", by catalytic reduction in ethanol and HCl. The spectral evidence which established structure 3a included an ultraviolet spectrum devoid of maxima between 210 and 360 nm, an ir spectrum indicating the between benzaldehyde and acetophenone in ammonium acetate and glacial acetic acid. (28) Dihydropyridines are known to disproportionate to form pyridine and piperidine derivatives; see M. Scholtz, Ber., 30, 2295 (1897); I
