Synthesis and photochemistry of novel 3,5-diacetyl-1,4-dihydropyridines. II [1]

Article abstract of DOI:10.1007/s00706-003-0139-5

In continuation of previous work some novel 3,5-diacetyl-1,4- dihydropyridine derivatives were synthesized and their photochemical behavior was studied under oxygen and argon atmosphere. Oxidation of the dihydropyridine ring and formation of pyridine derivatives was the result of the reaction. The presence of oxygen affects not only on the rate of oxidation, but also the formation of some unidentified by-products was observed on irradiation under this atmosphere. Springer-Verlag 2004.

Full text of DOI:10.1007/s00706-003-0139-5

Monatshefte f€ur Chemie 135, 833–838 (2004)
DOI 10.1007/s00706-003-0139-5
Synthesis and Photochemistry
of Novel 3,5-Diacetyl-1,4-
dihydropyridines. II [1]
1
2
Hamid R. Memarian1;ꢀ, Mohammad Bagheri , and Dietrich Dopp
¨
1
University of Isfahan, Faculty of Sciences, Department of Chemistry,
81746-73441 Isfahan, Iran
2
€
Institut f€ur Chemie, Gerhard Mercator-Universitat=GH Duisburg, D-47048
Duisburg, Germany
Received September 23, 2003; accepted September 29, 2003
Published online February 5, 2004 # Springer-Verlag 2004
Summary. In continuation of previous work some novel 3,5-diacetyl-1,4-dihydropyridine derivatives
were synthesized and their photochemical behavior was studied under oxygen and argon atmosphere.
Oxidation of the dihydropyridine ring and formation of pyridine derivatives was the result of the
reaction. The presence of oxygen affects not only on the rate of oxidation, but also the formation of
some unidentified by-products was observed on irradiation under this atmosphere.
Keywords. Aromatization; 1,4-Dihydropyridines; Heterocycles; Photochemistry; Photooxidation.
Introduction
Recently we have reported on the synthesis and photochemistry of novel 3,5-
diacetyl-1,4-dihydropyridines 1a–1e [1]. These results indicated that besides the
presence or absence of oxygen atmosphere, the type and nature of the 4-sub-
stituent has an effect on the rate or type of reaction. Two types of reactions
have been observed: oxidation with retention and with expulsion of the 4-
substituent.
Our experience with the photochemistry of 1,4-dihydropyridine-3,5-diesters,
known as Hantzsch esters [2], showed also such dependence of the reaction on
both factors [3, 4]. In continuation of our recent work, we synthesized some
other novel 3,5-diacetyl-1,4-dihydropyridines 1f–1l and investigated their photo-
chemical behavior under oxygen and argon atmosphere. The aim of this work
was to study the effect of various substituents in position 4 on the rate or type of
reaction.
ꢀ
Corresponding author. E-mail: memarian@sci.ui.ac.ir

834
H. R. Memarian et al.
Scheme 1
Results and Discussion
A 15 ꢁ 10ꢂ3 M solution of 1f–1l in chloroform was irradiated under oxygen and
argon atmosphere until total disappearance of starting material. The results are
summarized in Table 1.
As shown in Table 1, only the product with retention of the 4-substituent was
obtained under both atmospheres, except for 1f. In this case, reaction under oxygen
atmosphere resulted in the formation of an unidentified salt, may be the pyridinium
salt. This is supported by the fact, that the isolated yield of products is lower in the
reaction under oxygen atmosphere than under argon atmosphere. The presence of
oxygen could induce a radical reaction and formation of HCl in chloroform solu-
tion, which leads to the formation of the pyridinium salt. Therefore we should
obtain a higher yield of product in reaction under argon atmosphere. Another
interesting result is that the irradiation time under oxygen is shorter than under
argon atmosphere, except for 1h. This should be due to the involvement of the
triplet excited state of 1h and quenching of this excited state by the presence of
oxygen.
Scheme 2

Novel 3,5-Diacetyl-1,4-dihydropyridines
835
Table 1. Irradiation of dihydropyridines 1f–1l under oxygen and argon atmosphere
O2
Ar
Product (yield=%)a
Time=hb
Product (yield=%)a
Time=hb
1f
1g
1h
1i
–
7
8
3f (60)
3g (92)
3h(94)
3i (85)
3j (90)
3k (90)
3l (81)
13.5
13.5
10
3g (85)
3h (86)
3i (82)
3j (85)
3k (61)
3l (50)
12
8
10
1j
1k
1l
8.25
10
26
11
12
49
a
b
Isolated yield; The irradiation times are given after total disappearance of the starting material
1
IR, H NMR, and UV data allowed the structural assignments of the photo-
products 3f–3l. A comparison of the IR spectra of educts and products showed the
disappearance of the NH band and a shift of the CO vibration to higher frequency
due to oxidation and aromatization of the ring, which cause a decrease in the
1
conjugation of the CO group with the C¼C bonds. H NMR spectra showed the
loss of the NH and C4–H signals and aromatization of ring. Due to the missing
conjugation of the CO group with the pyridine ring, the signals of the methyl
groups in positions 2 and 6 are shifted upfield and the protons of the acetyl groups
are shifted downfield in comparison with the starting materials. Also, a comparison
of the UV spectra did not show any strong absorption above 300 nm, which indi-
cates aromatization of the ring and formation of pyridine derivatives.
Experimental
All melting points were determined with a Stuart Scientific SMP 2. IR: Shimadzu IR-435; 1H NMR:
Bruker AW 80 (80 MHz); UV: Shimadzu UV-160; Mass spectra: Micromass Platform II: EI mode
(70 eV). Elemental analyses: Euro EA CHNS Analysator; the results agreed favourably with the
calculated values. Preparative thin layer chromatography (PLC) was carried out on 20ꢃ20cm2 plates
coated with a 1 mm layer of Merck silica gel PF254. Column chromatography: Merck silica gel 60, 70–
230 mesh ASTM.
All irradiations were performed using a 400W high-pressure Hg-vapour lamp from NARVA with
cooling of samples in Duran glass (ꢀ ꢄ 280 nm) by running cold H2O. Ar (99.99%) or O2 (99.99%)
was bubbled through the solutions during irradiation.
General Procedure for the Preparation of 3,5-Diacetyl-1,4-dihydropyridines
A mixture of 0.05 mol of freshly distilled acetyl acetone, 0.025mol of the corresponding aldehyde, and
30cm3 of conc. NH3 (in the case of 1f NH3 gas was used) in 15cm3 of C2H5OH was refluxed for the
time given. The solvent was evaporated, the precipitate was washed with cold diethyl ether, and
recrystallized from ethanol.
3,5-Diacetyl-2,4,6-trimethyl-1,4-dihydropyridine (1f, C12H17NO2)
Refluxed for 4 h, yield 32%, yellow crystals, mp 150–152ꢅC; IR (KBr): ꢁꢀ¼ 3280 (NH), 1665 (CO)
cmꢂ1; 1H NMR (CDCl3): ꢂ ¼ 0.9 (d, J ¼ 7.2 Hz, 4-CH3), 2.3 (s, 2- and 6-CH3, 3- and 5-COCH3), 3.8

836
H. R. Memarian et al.
(q, 4-H), 6.3 (brd s, NH) ppm; EI-MS: m=z (%) ¼ 208 [Mþþ1] (11), 207 [Mþ] (52), 192 [Mþ–CH3]
(100), 176 [Mþ–2CH3–H] (20), 164 [Mþ–CH3CO] (37), 150 [Mþ–CH3–CH2CO] (66), 149 [Mþ–
CH3–CH3CO] (65), 106 [Mþ–CH3–2CH3CO] (57), 43 [CH3COþ] (64); UV (CHCl3): ꢀ (log ") ¼ 368
(3.82), 250 (3.98) nm.
3,5-Diacetyl-2,6-dimethyl-4-phenyl-1,4-dihydropyridine (1g, C17H19NO2)
Refluxed for 3 h, yield 31%, yellow crystals, mp 169–170ꢅC; IR (KBr): ꢁꢀ¼ 3280 (NH), 1665 (CO)
cmꢂ1; 1H NMR (CDCl3): ꢂ ¼ 2.2 (s, 2- and 6-CH3), 2.25 (s, 3- and 5-COCH3), 5.05 (s, 4-H), 6.7 (brd s,
NH), 7.1 (s, C6H5) ppm; EI-MS: m=z (%) ¼ 270 [Mþþ1] (7), 269 [Mþ] (39), 268 [Mþ–H] (43), 254
[Mþ–CH3] (13), 226 [Mþ–CH3CO) (39), 192 [Mþ–C6H5–CH3CO–CH3] (16), 106 [Mþ–C6H5–
2CH3CO] (15), 43 [CH3COþ] (56); UV (CHCl3): ꢀ (log ") ¼ 367 (3.55), 254 (3.88) nm.
3,5-Diacetyl-4-(4-chlorophenyl)-2,6-dimethyl-1,4-dihydropyridine (1h, C17H18NO2Cl)
Refluxed for 3 h, yield 26%, yellow crystals, mp 140–141ꢅC; IR (KBr): ꢁꢀ¼ 3300 (NH), 1670 (CO)
cmꢂ1; 1H NMR (CDCl3): ꢂ ¼ 2.2 (s, 2- and 6-CH3), 2.3 (s, 3- and 5-COCH3), 5.2 (s, 4-H), 5.9 (brd s,
37
35
NH), 7.3 (s, C6H4) ppm; EI-MS: m=z (%) ¼ 305 [Mþ Cl] (67), 303 [Mþ Cl] (89), 288 [Mþ–CH3)
(75), 262 [Mþ(37Cl)–CH3CO] (73), 260 [Mþ(35Cl)–CH3CO] (89), 192 [Mþ–C6H4Cl] (100), 149
[Mþ–C6H4Cl–CH3CO] (81), 134 [Mþ–C6H4Cl–CH3CO–CH3] (88), 106 [Mþ–C6H4Cl–2CH3CO]
(72) 43 [CH3COþ] (81); UV (CHCl3): ꢀ (log ") ¼ 368 (3.79), 252 (4.14) nm.
3,5-Diacetyl-4-(2-methoxyphenyl)-2,6-dimethyl-1,4-dihydropyridine (1i, C18H21NO3)
Refluxed for 3.25h, yield 30%, yellow crystals, mp 172–173ꢅC; IR (KBr): ꢁꢀ¼ 3280 (NH), 1670 (CO)
1
cmꢂ1; H NMR (CDCl3): ꢂ ¼ 2.2 (s, 2- and 6-CH3, 3- and 5-COCH3), 3.75 (s, OCH3), 5.3 (s, 4-H),
6.1 (brd s, NH), 6.8–7.1 (m, C6H4) ppm; EI-MS: m=z (%) ¼ 300 [Mþþ1] (4), 299 [Mþ] (11), 297
[Mþ–2H] (16), 284 [Mþ–CH3] (110), 268 [Mþ–OCH3] (85), 192 [Mþ–C6H4OCH3] (100), 150 [Mþ–
C6H4OCH3–CH2CO] (61), 134 [Mþ–C6H4OCH3–CH3CO–CH3] (36), 107 [C6H4OCH3þ] (22), 43
[CH3COþ] (73); UV (CHCl3): ꢀ (log ") ¼ 348 (3.84), 252 (4.03) nm.
3,5-Diacetyl-4-(3-methoxyphenyl)-2,6-dimethyl-1,4-dihydropyridine (1j, C18H21NO3)
Refluxed for 3 h, yield 29%, yellow crystals, mp 196–198ꢅC; IR (KBr); ꢁꢀ¼ 3260 (NH), 1660 (CO)
cmꢂ1; 1H NMR (CDCl3): ꢂ ¼ 2.3 (s, 2- and 6-CH3), 2.4 (s, 3- and 5-COCH3), 3.8 (s, OCH3), 5.2 (s, 4-
H), 6.1 (brd s, NH), 6.7–7.3 (m, C6H4) ppm; EI-MS: m=z (%) ¼ 300 [Mþþ1] (50), 299 [Mþ] (82), 284
[Mþ–CH3] (64), 256 [Mþ–CH3CO] (83), 241 [Mþ–CH3CO–CH3] (16), 192 [Mþ–C6H4OCH3] (100),
149 [Mþ–C6H4OCH3–COCH3] (76), 134 [Mþ–C6H4OCH3–COCH3–CH3] (85), 106 [Mþ–
C6H4OCH3–2COCH3] (69), 92 [C6H4Oþ] (42), 43 [CH3COþ] (85); UV (CHCl3): ꢀ (log ") ¼ 366
(3.81), 252 (4.10) nm.
3,5-Diacetyl-4-(4-methoxyphenyl)-2,6-dimethyl-1,4-dihydropyridine (1k, C18H21NO3)
Refluxed for 7 h, yield 33%, yellow crystals, mp 175–176ꢅC; IR (KBr): ꢁꢀ¼ 3300 (NH), 1660 (CO)
cmꢂ1; 1H NMR (CDCl3): ꢂ ¼ 2.2 (s, 2- and 6-CH3), 2.25 (s, 3- and 5-COCH3), 3.7 (s, OCH3), 5.0 (s, 4-
H), 6.5 (brd s, NH), 6.7–7.15 (m, C6H4) ppm; EI-MS: m=z (%) ¼ 300 [Mþþ1] (9), 299 [Mþ] (45), 298
[Mþ–H] (56), 284 [Mþ–CH3] (19), 256 [Mþ–CH3CO] (63), 240 [Mþ–CH3CO–CH3–H] (23), 192
[Mþ–C6H4OCH3] (100), 149 [Mþ–C6H5OCH3–CH3CO] (20), 106 [Mþ–C6H5–2CH3CO] (15), 43
[CH3COþ] (12); UV (CHCl3): ꢀ (log "): 368 (3.66), 253 (4.13) nm.

Novel 3,5-Diacetyl-1,4-dihydropyridines
837
3,5-Diacetyl-4-(3-nitrophenyl)-2,6-dimethyl-1,4-dihydropyridine (1l, C17H18N2O4)
Refluxed for 2.75 h, yield 45%, yellow crystals, mp 210–211ꢅC; IR (KBr): ꢁꢀ¼ 3300 (NH), 1670
1
(CO) cmꢂ1; H NMR (CDCl3): ꢂ ¼ 2.25 (s, 2- and 6-CH3), 2.4 (s, 3- and 5-COCH3), 5.25 (s, 4-H),
6.35 (brd s, NH) 7.2–8.0 (m, C6H4) ppm; EI-MS: m=z (%) ¼ 314 [Mþ] (4), 297 [Mþ–OH] (17), 271
[Mþ–CH3CO] (17), 192 [Mþ–C6H4NO2] (100), 149 [Mþ–C6H4NO2–CH3CO] (16), 134 [Mþ–
C6H4NO2–CH3CO–CH3] (13), 43 [CH3COþ] (65); UV (CHCI3): ꢀ (log ") ¼ 348 (3.74), 254
(4.31) nm.
General Procedure for the Irradiation of Dihydropyridines
A 0.015 M solution of 1f–1l in chloroform was irradiated under Ar or O2 atmosphere until total
disappearance of dihydropyridines was observed (TLC; the corresponding irradiation times are given
in Table 1). When the reaction was complete, the product was purified by chromatography.
3,5-Diacetyl-2,4,6-trimethylpyridine (3f, C12H15NO2)
Column chromatography, petroleum ether=ethyl acetate (3=2), yield 60%, white crystals, mp 58–59ꢅC;
IR (KBr): ꢁꢀ¼ 1700 (CO) cmꢂ1; 1H NMR (CDCl3): ꢂ ¼ 2.05 (s, 4-CH3), 2.35 (s, 2- and 6-CH3), 2.4 (s,
3- and 5-COCH3) ppm; EI-MS: m=z (%) ¼ 205 [Mþ] (10), 190 [Mþ–CH3] (24), 162 [Mþ–CH3CO]
(8), 147 [Mþ–CH3–CH3CO] (2), 120 [Mþ–CH3CO–CH2CO] (21), 105 [Mþ–CH3CO–CH2CO–CH3]
(5), 44 [CH3COHþ] (100), 43 [CH3COþ] (64); UV (CHCl3): ꢀ (log "): 272 (3.51) nm.
3,5-Diacetyl-2,6-dimethyl-4-phenylpyridine (3g, C17H17NO2)
PLC, petroleum ether=ethyl acetate (5=3), yield 85%, mp 185–186ꢅC; IR (KBr): ꢁꢀ¼ 1690 (CO) cmꢂ1
;
1H NMR (CDCl3): ꢂ ¼ 1.8 (s, 2- and 6-CH3), 2.5 (s, 3- and 5-COCH3), 7.1–7.6 (m, C6H5) ppm; EI-
MS: m=z (%) ¼ 268 [Mþþ1] (8), 267 [Mþ] (39), 252 [Mþ–CH3] (47), 224 [Mþ–CH3CO] (9), 210
[Mþ–CH2CO–CH3] (63), 209 [Mþ–CH3CO–CH3] (4), 191 [Mþ–C6H5] (2), 181 [Mþ–2CH3CO] (5),
167 [Mþ–CH3CO–CH2CO–CH3] (12), 43 [CH3COþ] (100); UV (CHCl3): ꢀ (log "): 252 (3.96) nm.
3,5-Diacetyl-4-(4-chlorophenyl)-2,6-dimethylpyridine (3h, C17H16NO2Cl)
The solvent was evaporated and the residue was washed with cold ethanol, yield 86%, mp 174–175ꢅC;
1
IR (KBr): ꢁꢀ¼ 1695 (CO) cmꢂ1; H NMR (CDCl3): ꢂ ¼ 1.95 (s, 2- and 6-CH3), 2.6 (s, 3- and 5-
COCH3), 7.1–7.5 (m, C6H4) ppm; EI-MS: m=z (%) ¼ 303 [Mþ Cl] (83), 301 [Mþ35Cl] (97), 288
37
[Mþ(37Cl)–CH3] (88), 286 [Mþ(35Cl)–CH3] (98), 260 [Mþ(37Cl)–CH3CO] (16), 258 [Mþ(35Cl)–
CH3CO] (46), 246 [Mþ(37Cl)–CH2CO–CH3] (79), 244 [Mþ(35Cl)–CH2CO–CH3] (94), 163 [Mþ–
35
C6H4Cl–CH3CO] (16), 139 (100), 113 [C6H437Cl] (36), 111 [C6H4 Cl] (8), 43 [CH3COþ] (86); UV
(CHCl3): ꢀ (log ") ¼ 248 (4.24) nm.
3,5-Diacetyl-4-(2-methoxyphenyl)-2,6-dimethylpyridine (3i, C18H19NO3)
Column chromatography, petroleum ether=ethyl acetate (3=2), yield 82%, white crystals, mp 142–
143ꢅC; IR (KBr): ꢁꢀ¼ 1695 (CO) cmꢂ1; 1H NMR (CDCl3): ꢂ ¼ 1.9 (s, 2- and 6-CH3), 2.5 (s, 3- and 5-
COCH3), 3.7 (s, OCH3), 6.8–7.4 (m, C6H4) ppm; EI-MS: m=z (%) ¼ 298 [Mþþ1] (15), 297 [Mþ] (45),
282 [Mþ–CH3] (24), 267 [Mþ–2CH3] (10), 266 [Mþ–CH3O] (39), 264 [Mþ–CH3OH–H] (30), 249
[Mþ–CH3OH–H–CH3] (24), 224 [Mþ–CH3CO–2CH3] (28), 196 [Mþ–2CH3CO–CH3] (16), 132
þ
[Mþ–C6H5OCH3–CH3CO–CH3] (15), 57 [CH2COCH3 ] (100), 44 [CH3COHþ] (67), 43 [CH3COþ]
(88); UV (CHCl3): ꢀ (log ") ¼ 250 (3.82) nm.

838
H. R. Memarian et al.: Novel 3,5-Diacetyl-1,4-dihydropyridines
3,5-Diacetyl-4-(3-methoxyphenyl)-2,6-dimethylpyridine (3j, C18H19NO3)
Column chromatography, petroleum ether=ethyl acetate (3=1), yield 85%, white crystals, mp 111–
113ꢅC; IR (KBr): ꢁꢀ¼ 1690 (CO) cmꢂ1; 1H NMR (CDCl3): ꢂ ¼ 1.9 (s, 2- and 6-CH3), 2.6 (s, 3- and 5-
COCH3), 3.8 (s, OCH3), 6.7–7.6 (m, C6H4) ppm; EI-MS: m=z (%) ¼ 299 [Mþþ2] (13), 298 [Mþþ1]
(66), 297 [Mþ] (83), 282 [Mþ–CH3] (76), 264 [Mþ–CH3OH–H] (81), 254 [Mþ–CH3CO] (63), 240
[Mþ–CH2O–CH3] (84), 211 [Mþ–2CH3CO] (29), 197 [Mþ–CH3CO–CH2CO–CH3] (61), 196 [Mþ–
2CH3CO–CH3] (37), 132 [Mþ–C6H5OCH3–CH3CO–CH3] (100), 44 [CH3COHþ] (67), 43 [CH3COþ)
(88); UV (CHCl3): ꢀ (log ") ¼ 249 (3.71) nm.
3,5-Diacetyl-4-(4-methoxyphenyl)-2,6-dimethylpyridine (3k, C18H19NO3)
PLC, petroleum ether=ethyl acetate (5=2), yield 61%, white crystals, mp 164–165ꢅC; IR (KBr):
1
ꢁꢀ¼ 1700 (CO) cmꢂ1; H NMR (CDCl3): ꢂ ¼ 1.85 (s, 2- and 6-CH3), 2.45 (s, 3- and 5-COCH3),
3.8 (s, OCH3), 6.8–7.2 (m, C6H4) ppm; EI-MS: m=z (%) ¼ 298 [Mþþ1] (66), 297 [Mþ] (100), 282
[Mþ–CH3] (96), 266 [Mþ–CH3O] (8), 264 [Mþ–CH3OH–H] (45), 254 [Mþ–CH3O] (44), 240 [Mþ–
CH2O–CH3] (94), 211 [Mþ–2CH3CO] (18), 196 [Mþ–2CH3CO–CH3] (23), 132 [Mþ–C6H5OCH3–
þ
CH3CO–CH3] (21), 57 ½CH2COCH3 ꢆ (11), 44 [CH3COHþ] (13), 43 [CH3COþ] (66); UV (CHCl3):
ꢀ (log ") ¼ 274 (4.08) nm.
3,5-Diacetyl-4-(3-nitrophenyl)-2,6-dimethylpyridine (3l, C17H16N2O4)
PLC, petroleum ether=ethyl acetate (3=2), yield 50%, mp 126–127ꢅC; IR (KBr): ꢁꢀ¼ 1700 (CO) cmꢂ1
;
1H NMR (CDCl3): ꢂ ¼ 1.9 (s, 2- and 6-CH3), 2.5 (s, 3- and 5-COCH3), 7.5–8.2 (m, C6H4) ppm; EI-
MS: m=z (%) ¼ 313 [Mþþ1] (7), 312 [Mþ] (30), 297 [Mþ–CH3] (91), 295 [Mþ–OH] (90), 294 [Mþ–
H2O] (5), 282 [Mþ–NO] (6), 269 [Mþ–CH3O] (6), 266 [Mþ–NO2] (9), 251 [Mþ–NO2–CH3] (8), 236
[Mþ–NO2–2CH3] (37), 223 [Mþ–NO2–COCH3] (19), 208 [Mþ–NO2–COCH3–CH3] (17), 165 [Mþ–
NO2–2COCH3–CH3] (11), 44 [CH3COHþ] (16), 43 [CH3COþ] (83), 42 [CH2COþ] (100); UV
(CHCl3): ꢀ (log ") ¼ 253 (4.06) nm.
Acknowledgments
We are grateful to the Isfahan University Research Council for partial support to this work. H. R.
Memarian is indebted to the German Academic Exchange Service (DAAD) for a scholarship during
July–August 2002.
References
€
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[2] Hantzsch A (1882) Justus Liebigs Ann Chem 215: 1
[3] Memarian HR, Sadeghi MM, Aliyan H (1998) Indian J Chem 37B: 219
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