Photoinduced Aromatization of Unsymmetrically Substituted 1,4 ...

Photoinduced Aromatization of Unsymmetrically Substituted 

1,4-Dihydropyridines 

Hamid R. Memarian, a * Masumeh Abdoli-Senejani a and Dietrich Döpp b 

a University of Isfahan, Faculty of Science, Department of Chemistry, 81746-73441 Isfahan, Iran 

b Universität Duisburg-Essen, Organische Chemie, D-47057 Duisburg, Germany 

Irradiation of unsymmetrically substituted 1,4-dihydropyridines (1b-1j) while bubbling oxygen or argon 

through the solution resulted in aromatization to the corresponding pyridine derivatives (3b-3j). 

Compound 1a with 2-nitrophenyl substituent in 4-position undergoes elimination of water upon irradiation 

under both oxygen and argon atmospheres and formation of 3a with 2-nitrosophenyl substituent. On 

the other hand, irradiation of the compounds 1e, 1k and 1l with 4-hydroxy-3-methoxyphenyl, 5-methyl- 

2-furyl and 2-furyl substituent in this position, respectively, resulted in the expulsion of these substituents 

and formation of a pyridine derivative unsubstituted in position 4, namely compound 2. Chloroform as a 

solvent causes the photo-oxidation of these compounds by an electron transfer mechanism which is supported 

by the formation of dichloromethaneaccording to GC analysis and presence of acid (HCl) in the solution 

after irradiation. 

Keywords: Aromatization; 1,4-Dihydropyridines; Photochemistry; Photo-oxidation; Unsymmetrical 

substitution. 

INTRODUCTION 

1,4-Dihydropyridines are interesting compounds, especially 

because of their pharmaceutical activity. They also 

play an important role in synthetic, therapeutic and bioorganic 

chemistry. 1-4 The most interesting aspect of dihydropyridines 

can be attributed to the coenzyme reduced 

nicotinamide adenine dinucleotide (NADH). Due to their 

light sensitivity, many studies have been devoted to the 

photochemistry and photo-oxidation of symmetrical dihydropyridine 

drugs such as lacidipine, 5 nifedipine 6-10 and 

unsymmetrical dihydropyridine drugs such as amlodipine, 

11 nisoldipine, 12 nilvadipine 13 and nimodipine. 14 The 

purpose of these studies was to elucidate the effects of concentration, 

light intensity and pH on the photostability of 

the title compounds. A number of studies have also been 

devoted to the mechanism of photo-degradation and photooxidation 

of these compounds and, especially, the role of a 

4-substituent in the rate of reaction. 15-20 The importance of 

the oxidative reaction of these compounds is due to their 

similarity to the oxidative metabolism of these compounds 

with pharmaceutical activity in the liver to form pyridine 

derivatives, which become biologically inactive. 21,22 Hence, 

* Corresponding author. E-mail: memarian@sci.ui.ac.ir 

Journal of the Chinese Chemical Society, 2007, 54, 131-139 131 

a convenient method for the conversion of 1,4-dihydropyridines 

to pyridine derivatives is important for the investigation 

of their metabolism. 

In the course of our study on the chemistry of 1,4-dihydropyridines 

and especially photo-oxidation or photodehydrogenation 

of these compounds, we synthesized various 

1,4-dihydropyridine-3,5-diesters known as Hantzsch 

esters, 23 and 3,5-diacetyl-1,4-dihydropyridines and investigated 

their photochemical behavior by exposing them to 

UV-light in solution 24-27 or in the solid state. 28 We have also 

investigated photosensitized oxidation of these compounds 

using triplet dye-sensitizers for in situ generation of singlet 

oxygen as oxidant. 29 The aim of these works was to investigate 

the effect of the presence of the acetyl groups instead 

of the carboethoxy groups (ester groups), the nature of 4substituent 

on the dihydropyridine ring and also the presence 

or absence of oxygen atmosphere on the rate of oxidation. 

In continuation of our studies we were interested in 

synthesizing various unsymmetrically substituted 1,4-dihydopyridines 

in which a carboethoxy group (ester) and an 

acetyl group (keto) are located in 3- and 5-positions, respectively. 

30 Now we wish to report on the photochemical 

behavior of keto-ester dihydropyridines under oxygen and

132 J. Chin. Chem. Soc., Vol. 54, No. 1, 2007 Memarian et al. 

argon atmosphere. 

RESULTS AND DISCUSSION 

Irradiation (280 nm) of 15.10 -3 M solution of each 

of 1a-1l in chloroform by bubbling oxygen or argon through 

the solution was followed by thin layer chromatography 

(TLC) until the total disappearance of 1a-1l. The results are 

summarized in Table 1. 

Since the aim of this study was (i). the investigation 

of photochemical behavior of these compounds, dependent 

on the type and nature of 4-substituent and (ii). to elucidate 

the effect of oxygen atmosphere on the rate of reactions, we 

have carried out simultaneously the photoreactions under 

both oxygen and argon atmospheres. Because of the similarity 

of the products obtained on irradiation under both atmospheres, 

the products obtained under an argon atmosphere 

have not been isolated, except for 1e, and the times 

of total oxidation are determined by TLC monitoring. For 

this purpose, we have taken the same volumes with equal 

concentration of each of the compounds in two different 

test tubes and irradiated them simultaneously and continuously 

by purging with a stream of either oxygen or argon 

until total disappearance of 1,4-dihydropyridines is observed 

by following the reaction by TLC. 

The observed fast reaction under oxygen atmosphere 

is an indication of the involvement of the excited singlet 

state of 1b, 1e, 1i, 1j, 1k and 1l in the reaction, since the excited 

singlet state could not be quenched by triplet oxygen. 

In the cases of 1a, 1c, 1d, 1f, 1g and 1h the excited triplet 

state should be involved in the reaction, since a faster pho- 

Scheme I 

Table 1. Irradiation of dihydropyridines 1a-1l under O2 and Ar 

O2 Ar 

Product (%) I 

Time (h) II 

Product (%) III 

Time (h) II 

1a 3a (60) 0.66 3a 0.33 

1b 3b (71) 5.5 3b 36 

1c 3c (72) 9 3c 3.75 

1d 3d (40) 6 3d 5.5 

1e 2 (20) 

3e (50) 

9 2 (18) 

3e (49) 

22 

1f 3f (84) 12.5 3f 8 

1g 3g (73) 5.5 3g 3 

1h 3h (67) 6 3h 4 

1i 3i (65) 7.5 3i 8.5 

1j 3j (80) 6 3j 15 

1k 2 (63) 1.5 2 5 

1l 2 (74) 2.25 2 5 

I II 

Isolated yield. Irradiation times refer to disappearance of the 

starting material. III The products have not been isolated except 

for 1e and identified only by TLC. 

to-oxidation has been observed by bubbling argon through 

the solution under irradiation. 

We have also investigated the effect of the nature of 

solvent on the rate of reaction. Whereas irradiation of only 

compound 1a in ethanol solution after 15 minutes led to the 

formation of compound 3a in 70% yield, other compounds 

were obtained unchanged even after 5-13 hours of irradiation 

in the same solvent. Therefore, we found that chloroform 

is a suitable solvent for our reaction. Owing to the formation 

of dichloromethane during the reaction, which has 

been proved by GC-analysis of the reaction mixture and by 

testing for acidity of the solution after irradiation (due to 

formation of HCl), we will propose an electron transfer

Photoinduced Aromatization of 1,4-Dihydropyridines J. Chin. Chem. Soc., Vol. 54, No. 1, 2007 133 

mechanism for this conversion, in which chloroform is involved 

in the reaction (Scheme II). According to the proposed 

mechanism, excited 1,4-dihydropyridine (PyH2*), 

especially 1b-1l, donates an electron to chloroform under 

formation of PyH2· + and CHCl3· . Elimination of HCl from 

both intermediates leads to the formation of a radical pair, 

namely hydropyridyl (PyH·) and dichloromethyl (·CHCl2) 

radicals. Hydrogen abstraction by ·CHCl2 radical completes 

the reaction by formation of the pyridine compound (Py) 

and dichloromethane. Other studies also have proposed 

this mechanism for the photo-oxidation of symmetrical 

1,4-dihydropyridines in CCl4 15 and CBrCl3 solutions. 17,20 

The interesting point in our study is the expulsion of 

the 4-substituent in the cases of 1e, 1k and 1l with a 4-hydroxy-3-methoxyphenyl, 

5-methyl-2-furyl and 2-furyl 

substituent, respectively, in the 4-position-. The loss of the 

C-4 substituent upon irradiation of Hantzsch esters has 

been reported earlier only in the case of carboxy groups, 31 

some heterocyclic groups, 25 and secondary alkyl and benzyl 

groups. 25 The expulsion of the 4-substituent has also 

been reported upon irradiation of diketo-dihydropyridines 

with 5-methyl-2-furyl and 2-furyl substituents in the 4 position. 

26 Thermal oxidation of Hantzsch esters with expulsion 

of benzylic and secondary alkyl substituents by various 

oxidants has also been cited. 26 Most of the product derived 

from 1d in our work is converted to an unidentified 

compound, which stays on the start line when separation is 

attempted by PLC and which we considered to be the pyridinium 

salt. However, shaking of this zone with NaOHsolution 

and extraction of the aqueous phase with CHCl3 

did not give any isolable product. 

IR (Table 2), 1 H NMR (Table 3) and UV data (Table 

4) gave useful information on the structural assignment of 

Scheme II 

Table 2. Comparison of the IR spectra I (/cm -1 ) 1a-1l with 

those of 3a-3j 

1 NH CO2C2H5 COCH3 3 CO2C2H5 COCH3 a 3333 1675 1655 a II 

1723 1705 

b 3289 1700 1645 b 1724 1710 

c 3333 1675 1662 c 1724 1688 

d 3264 1675 1643 d 1740 1726 

e 3291 1677 1640 e 1724 1702 

f 3300 1663 1640 f 1724 1700 

g 3341 1700 1654 g 1724 1697 

h 3290 1692 1648 h 1724 1694 

i 3033 1691 1662 i 1724 1705 

j 3162 1643 1632 j 1737 1722 

k 3307 1691 1646 2 1724 1691 

l 3231 1676 1660 2 1724 1691 

I 

The spectra have been taken as KBr disc, except for 3d which 

has been taken in CHCl3-solution. II The absorption at 1551 cm -1 

indicated the presence of a NO-group. 

the photoproducts 2 and 3a-3j. 

A comparison of the IR spectra showed the disappearance 

of the NH band and also the shift of both CO vibrations 

to higher frequency due to the aromatization of the 

ring, which changes the role of the ring from enamine-like 

in 1 to acceptor-like in 3. Comparison of the 1 H NMR spectra 

indicated the loss of the signals for NH and also for the 

substituent in position 4 because of the expulsion of this 

substituent upon photo-oxidation of 1e, 1k and 1l with formation 

of the identical product 2. In this case, 4-H appears 

in the aromatic region at 8.53 ppm. In the 1 H NMR spectra 

of photoproducts containing the 4-substituent, the loss of 

NH and 4-H resonances was observed. Owing to aromatization 

of the ring and diminished conjugation of the C-C 

double bonds with both CO groups, the methyl protons in


Table 3. Structurally relevant 1 H NMR chemical shifts ( values) of 1a-1j in comparison with 3a-3j 

1 4-H N-H 2-CH3 6-CH3 3-CH2CH3 3-CH2CH3 5-COCH3 3 4-H 2-CH3 6-CH3 3-CH2CH3 3-CH2CH3 5-COCH3 a 5.88 5.79 2.32 2.36 1.26 4.04, 4.24 2.37 a - 2.63 2.04 0.81 

2.70 

b 5.20 5.99 2.24 2.38 1.33 4.21 2.43 b - 2.59 2.07 1.05 4.11 2.67 

c 5.02 5.71 2.21 2.33 1.35 4.24 2.42 c - 2.54 1.95 1.04 4.11 2.62 

d 5.35 6.07 2.26 2.34 1.39 4.28 2.42 d - 2.52 2.03 1.09 4.16 2.60 

e 4.99 5.70 2.20 2.32 1.35 4.22 2.41 e - 2.55 1.97 1.05 4.12 2.63 

f 5.05 5.87 2.20 2.32 1.33 4.21 2.40 f - 2.54 1.92 0.92 4.04 2.64 

g 5.03 5.84 2.20 2.33 1.33 4.20 2.40 g - 2.55 1.99 1.02 4.09 2.64 

h 5.02 5.87 2.20 2.31 1.34 4.22 2.40 h - 2.55 1.94 0.99 4.08 2.63 

i 5.08 6.69 2.23 2.35 1.31 4.19 2.39 i - 2.58 2.04 1.09 4.09 2.67 

j 5.11 6.06 2.22 2.36 1.33 4.21 2.42 j - 2.58 2.05 0.98 4.07 2.67 

k 5.14 5.86 2.24 2.36 1.34 4.22, 4.29 2.37 2 8.53 2.80 2.65 1.45 4.44 2.88 

l 5.20 6.08 2.34 2.36 1.33 4.24 2.36 2 8.53 2.80 2.65 1.45 4.44 2.88 

1 Appears as two quartets. 

Table 4. Comparison of the UV-absorption [max (nm)] of the starting materials 1a-1j with 

those of photoproducts 3a-3j in methanol solution 

1 max (log ) 3 max (log ) 

a 250 (4.22), 366 (3.72) a 219 (sh, 4.39), 279 (4.10), 310 (3.90) 

b 245 (4.04), 369 (3.49) b 211 (4.27), 259 (sh, 3.91) 

c 230 (4.26), 369 (3.88) c 223 (sh, 4.32), 275 (3.98) 

d 238 (4.15), 363 (3.80) d 224 (4.32), 281 (4.14) 

e 231 (4.18), 370 (3.88) e 223 (4.20), 276 (3.83), 296 (3.79) 

f 247 (3.91), 370 (3.63) f 222 (4.54), 269 (sh, 4.05) 

g 245 (4.20), 369 (3.82) g 225 (4.43), 269 (sh, 4.14), 307 (sh, 3.44) 

h 249 (4.16), 371 (3.94) h 213 (sh, 4.52), 264 (4.26) 

i 243 (4.39), 370 (3.95) i 209 (3.97), 266 (3.75) 

j 242 (4.65), 370 (4.21) j 212 (4.20), 268 (3.67) 

k 239 (4.06), 362 (3.80) 2 218 (4.20), 242 (4.05), 275 (3.77) 

l 244 (4.34), 361 (4.09) 2 218 (4.20), 242 (4.05), 275 (3.77) 

2- and 6-positions are shifted to opposite directions. The 

anisotropy effect 32 of the carbonyl group of the COCH3 

moiety in a planar pyridine ring causes a shift of the 6-CH3 

resonance to upper field. Since the resonance of the oxygen 

atom of the ethoxy group with CO moiety of the carboethoxy 

group, the anisotropy effect of the carbonyl moiety is 

not efficient, and 2-CH3 is shifted downfield. Such phenomena 

have been observed in the 1 H NMR of the dihydropyridine-diesters 

25 and diketo-dihydropyridines. 26 Conjugation 

of the acetyl carbonyl with the acceptor pyridine 

causes a downfield shift of the resonance of the acetyl 

group. Whereas the 1 H NMR spectra of 1g showed a multiplet 

centered at 7.24 for the p-chlorophenyl ring, due to 

conversion to the pyridine ring in 3g, the electron withdrawing 

character of the pyridine ring causes a downfield 

shift of the aromatic protons to 7.23 ppm (3- and 5-H) and 

7.43 ppm (2- and 6-H), which appear as a doublet of dou- 

1 3.89 1 

blets. Comparison of the UV-spectra of 2 and 3a-3j with 

those of 1a-1l indicated a hypsochromic shift of the absorption 

of the photoproducts from 370 to 300 nm, which is 

characteristic of the pyridine ring. 

Another interesting facet of this work is the result obtained 

on irradiation of 1a (with a 2-nitrophenyl group in 

4-position) under both oxygen and argon atmospheres. Our 

results indicate that irradiation of 1a under both atmospheres 

yields 3a (with a 2-nitrosophenyl substituent in position 

4) with loss of one molecule of water. Berson and 

Brown had reported earlier that upon irradiation of 3,5-diacetyl-2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine 

an internal disproportionation of this compound occurs 

with loss of one molecule of water and formation of 

4-(2-nitrosophenyl)pyridine. 33 Another study has shown 

that the result of the photolysis of dimethyl 2,6-dimethyl- 

4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate


is dependent on the conditions applied and gives dimethyl 

2,6-dimethyl-4-(2-nitrophenyl)pyridine-3,5-dicarboxylate 

under UV-light, whereas by using day light only the 

corresponding nitroso compound has been obtained. 9 We 

had observed earlier that the absence of oxygen atmosphere 

is required for the formation of the nitroso compound. 24 

Whereas irradiation of diethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate 

(diethyl 

ester analogue of Nifedipine) gives diethyl 2,6-dimethyl- 

4-(2-nitrosophenyl)pyridine-3,5-dicarboxylate under argon 

atmosphere, the corresponding nitro derivative is formed 

upon irradiation under oxygen. In our new study, the data 

of IR, 1 H NMR, UV and mass spectroscopy but also from 

CHN-analysis, support the formation of 3a. In the IR spectra 

of 3a, the presence of one band at 1551 cm -1 points to a 

NO group, whereas the bands at 1533 and 1353 cm -1 in the 

IR spectra of 3b indicate the presence of the NO2 group. A 

better evidence of formation of 3a (o-nitrosophenyl compound) 

and 3b (m-nitrophenyl compound) is drawn from 

the comparison of their 1 H NMR spectra with those of their 

precursors, namely, 1a and 1b. Owing to aromatization of 

1,4-dihydropyridine ring and loss of a chiral center at C-4 

of the unsymmetrical dihydropyridines, the diastereotopic 

character of the methylene group of CO2CH2CH3 moiety is 

lost and the resonance of the methylene protons appears as 

a quartet. But in the case of 3a, the presence of the noncoplanar 

unsymmetrical NO group at C-2 of the phenyl 

ring, the methylene protons become diastereotopic again 

and appear as a quartet of quartets. Fig. 1 clearly shows this 

Fig. 1. Expanded CH3CH2O resonances of 1a, 3a, 1b 

and 3b. 

situation in the expanded part of the 1 H NMR spectra for 

the CH2 group in 1a, 3a, 1b and 3b. 

Our recent study concerning photochemistry of diacetyl-1,4-dihydropyridines 

prompted us to investigate the 

effect of the presence of the acetyl and carboethoxy groups 

in positions 3 and 5, respectively, on the rate of photo-oxidation. 

Therefore, we have taken the same concentration 

of some unsymmetrical 1,4-dihydropyridines 1a,b,d,e,f, 

h,k, symmetrical 3,5-diacetyl-1,4-dihydropyridines 4a,b, 

d,e,f,h,k and symmetrical 1,4-dihydropyridine-3,5-diesters 

5a,b,d,e,f,h,k in three different test tubes in CHCl3 solution 

and irradiated them simultaneously under oxygen atmosphere 

until their disappearance. The results are summarized 

in Table 5. 

Formula 1 

The data shown in Table 5 indicate that the nature of 

the 4-substituent plays an important role on the rate of 

aromatization of the dihydropyridine ring. The presence of 

acetyl or carboethoxy groups makes the dihydropyridines 4 

and 5 behave slightly different in this reaction, but in the 

cases of unsymmetrical 1,4-dihydropyridines 1a,b,d,e,h,k 

the photolysis times required are a little shorter than for the 

corresponding diester or diketo compounds. Thus, unsymmetrical 

1,4-dihydropyridines 1 appear to have a slightly 

higher light sensitivity in comparison with their symmetrical 

analogues 4 and 5. 

EXPERIMENTAL SECTION 

Melting points were determined using a Stuart Scientific 

SMP2 capillary apparatus and are uncorrected. IR 

spectra were recorded using KBr pellets (unless otherwise 

stated) on a Philips PU 9716. 1 H NMR spectra were recorded 

on a Bruker DRX-500 (500 MHz) spectrometer in 

CDCl3 with TMS as internal standard. They are reported as 

follows: Chemical shifts , [multiplicity, number of protons, 

coupling constants J (Hz), and assignment]. Mass-


Table 5. Irradiation of various dihydropyridines in CHCl3 under oxygen atmosphere 

Time of total oxidation (h) 

Unsymmetrical 1,43,5-Diacetyl-1,41,4-Dihydropyridinesdihydropyridinesdihydropyridines 

3,5-diester 

1a 0.66 4a 0.66 5a 0.75 

1b 5.5 4b 6 5b 6.5 

1d 6 4d 6 5d 9 

1e 9 4e 9.75 5e 19 

1f 12.5 4f 11 5f 21 

1h 6 4h 8.5 5h 9 

1k 1.5 4k 2.5 5k 3.5 

spectra were obtained on a Sisonn, TRIO 1000, EI-mode at 

70 eV. The elemental analyses were measured on a Euro EA- 

CHNS analyzer. UV spectra were measured on a Shimadzu 

UV-160 spectrometer. Preparative layer chromatography 

(PLC) was carried out on 20 × 20 cm 2 plates, coated with a 

1 mm layer of Merck silica gel PF254, prepared by applying 

the silica as slurry and drying in air. All irradiations were 

performed using a 400 W high-pressure lamp from NARVA 

with cooling of samples in Duran glass ( 280 nm) by 

running cold water. Argon (99%) or oxygen (99%) was 

bubbled through the solutions during irradiation. 

General procedure for the irradiation of dihydropyridines 

(1a-1l) 

A 15.10 -3 M solution of 1a-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. 

Ethyl 5-acetyl-2,6-dimethylpyridine-3-carboxylate (2) 

PLC (petroleum ether/ethyl acetate, 3:1). m.p. 35-36 

C. UV (MeOH) max [nm] (log ): 275 (3.77), 242 (4.05), 

218 (4.20); IR max: 1724 (CO2C2H5), 1691 (COCH3)cm -1 ; 

1 H NMR : 1.45 (t, 3H,J= 7.13 Hz, CO2CH2CH3), 2.65 (s, 

3H, 6-CH3), 2.80 (s, 3H, 2-CH3), 2.88 (s, 3H, COCH3), 4.44 

(q, 2H, J = 7.12 Hz, CO2CH2CH3), 8.53 ppm (s, 1H, 4-H); 

MS m/z (rel. int. %): 221 [M + ] (36), 206 [M + -CH3] (100), 

178 [M + - COCH3] (21), 176 [M + -CH3CH2O] (20), 160 

[M + -CH3CH2OH-CH3] (5), 150 [M + -COCH3 -C2H4] 

(16), 106 [M + -CO2CH2CH3 - COCH2] (25), 43 [CH3CO + ] 

(47); Anal. Calcd. for C12H15NO3 (221.26): C, 65.14; H, 

6.83; N, 6.33; O, 21.69. Found: C, 65.16; H, 6.88; N, 6.31. 

Ethyl 5-acetyl-2,6-dimethyl-4-(2-nitrosophenyl)pyridine-3-carboxylate 

(3a) 

Recrystallized from ethyl acetate. m.p. 94-97 C. UV 

(MeOH) max [nm] (log ): 310 (3.90), 279 (4.10), 219 (sh, 

4.39); IR max: 1723 (CO2C2H5), 1705 (COCH3), 1551 (NO) 

cm -1 ; 1 H NMR : 0.81 (t, 3H, 3 J = 7.13 Hz, CO2CH2CH3), 

2.04 (s, 3H, 6-CH3), 2.63 (s, 3H, 2-CH3), 2.70 (s, 3H, 

COCH3), 3.89 (qq, 2H, J = 7.07 Hz, CO2CH2CH3), 6.52 (d, 

1H, J = 8.04 Hz, 6-H), 7.50 (mc, 1H, 4-H), 7.58 (d, 1H, 

3-H, J = 7.58 Hz), 7.78 ppm (mc, 1H, 5-H); MS m/z (rel. 

int. %): 327 [M + +1] (3), 284 [M + - COCH2] (100), 267 [M + 

-NO-CH2CH3] (20), 253 [M + -CO2CH2CH3] (27), 239 

[M + -CH3CHO - COCH3] (33), 237 [M + -CH3CH2OH - 

COCH3] (14), 211 [M + - COCH2 -CO2CH2CH3] (7), 193 

[M + -H2O - COCH2 -CO2CH2CH3] (15), 192 [M + - 

C6H4NO-C2H4] (11), 43 [CH3CO + ] (90); Anal. Calcd. for 

C18H18N2O4 (326.36): C, 66.25; H, 5.56; N, 8.58; O, 19.61. 

Found: C, 66.14; H, 5.54; N, 8.50. 

Ethyl 5-acetyl-2,6-dimethyl-4-(3-nitrophenyl)pyridine- 

3-carboxylate (3b) 


C. UV (MeOH) max [nm] (log ): 259 (sh, 3.91); 211 

(4.27); IR max: 1724 (CO2C2H5), 1710 (COCH3), 1533 and 

1353 (NO2) cm -1 ; 1 H NMR : 1.05 (t, 3H, J = 7.13 Hz, 

CO2CH2CH3), 2.07 (s, 3H, 6-CH3), 2.59 (s, 3H, 2-CH3), 

2.67 (s, 3H, COCH3), 4.11 (q, 2H, J = 7.11 Hz, CO2CH2CH3), 

7.65 (mc, 2H, 5-H and 6-H), 8.21 (s, 1H, 2-H), 8.33 ppm 

(dd, 1H, J = 7.85 Hz and 1.53 Hz, 4-H); MS m/z (rel. int. 

%): 342 [M + ] (28), 327 [M + -CH3] (99), 325 [M + - OH] 

(49), 299 [M + - COCH3] (23), 281 [M + -CH3 -NO2] (29), 

43 [CH3CO + ] (100); Anal. Calcd. for C18H18N2O5 (342.35): 

C, 63.15; H, 5.30; N, 8.18; O, 23.37. Found: C, 63.15; H, 

5.33; N, 8.10.


Ethyl 5-acetyl-4-(3,4-dimethoxyphenyl)-2,6-dimethylpyridine-3-carboxylate 

(3c) 

PLC (petroleum ether/ethyl acetate, 5:2). m.p. 110- 

112 C. UV (MeOH) max [nm] (log ): 275 (3.98), 223 (sh, 

4.32); IR max: 1724 (CO2C2H5), 1688 (COCH3) cm -1 ; 1 H 

NMR : 1.04 (t, 3H, J = 7.13 Hz, CO2CH2CH3), 1.95 (s, 3H, 

6-CH3), 2.54 (s, 3H, 2-CH3), 2.62 (s, 3H, COCH3), 3.88 (s, 

3H, OCH3), 3.94 (s, 3H, OCH3), 4.11 (q, 2H, J = 7.14 Hz, 

CO2CH2CH3), 6.81 (d, 1H, J = 1.97 Hz, 2-H), 6.85 (dd, 1H, 

J = 8.19 Hz and 2.00 Hz, 6-H), 6.92 ppm (d, 1H, J = 8.24 

Hz, 5-H); MS m/z (rel. int. %): 357 [M + ] (100), 342 [M + - 

CH3] (4), 328 [M + -CH2CH3] (2), 315 [M + -COCH2] (4), 

314 [M + - COCH3] (2), 296 [M + -CH3 -CH3CH2OH] (70), 

270 [M + - COCH3 -CH3CHO] (6), 268 [M + -CH3CO - 

CH3CH2OH] (9), 43 [CH3CO + ] (31); Anal. Calcd. for 

C20H23NO5 (357.41): C, 67.21; H, 6.49; N, 3.92; O, 22.38. 

Found: C, 67.22; H, 6.50; N, 3.86. 

Ethyl 5-acetyl-2,6-dimethyl-4-(2-thienyl)pyridine-3carboxylate 

(3d) 

PLC (petroleum ether/ethyl acetate, 3:1). Viscose oil. 

UV (MeOH) max [nm] (log ): 281 (4.14), 224 (4.32). IR 

(CHCl3) max: 1740 (CO2C2H5), 1726 (COCH3) cm -1 ; 1 H 


6-CH3), 2.52 (s, 3H, 2-CH3), 2.60 (s, 3H, COCH3), 4.16 (q, 

2H, J = 7.11 Hz, CO2CH2CH3), 7.05 (d, 1H, J = 3.54 Hz, 

3-H), 7.09 (mc, 1H, 4-H), 7.47 ppm (d, 1H, J = 5.06 Hz, 

5-H); MS m/z (rel. int. %): 303 [M + ] (95), 288 [M + -CH3] 

(34), 274 [M + -CH2CH3] (10), 260 [M + - COCH3] (100), 

242 [M + -C2H5OH-CH3] (75), 230 [M + -CO2CH2CH3] 

(16), 216 [M + - COCH3 -CH3CHO] (23), 83 [C4H3S + ] (22). 

Ethyl 5-acetyl-4-(4-hydroxy-3-methoxyphenyl)-2,6-dimethylpyridine-3-carboxylate 

(3e) 

PLC (petroleum ether/ethyl acetate, 3:2). m.p. 114- 

115 C. UV (MeOH) max [nm] (log ): 296 (3.79), 276 

(3.83), 223 (4.20); IR max: 3162 (OH), 1724 (CO2C2H5), 

1702 (COCH3) cm -1 ; 1 HNMR: 1.05(t,3H,J =7.11Hz, 

CO2CH2CH3), 1.97 (s, 3H, 6-CH3), 2.55 (s, 3H, 2-CH3), 

2.63 (s, 3H, COCH3), 3.90 (s, 3H, 3-OCH3), 4.12 (q, 2H, J 

= 7.12 Hz, CO2CH2CH3), 5.84 (s, 1H, 4-OH), 6.78 (d, 1H, 

2-H, 4 J = 1.87 Hz), 6.82 (dd, 1H, J = 8.10 Hz and 1.89 Hz, 

6-H), 6.98 ppm (d, 1H, J = 8.08 Hz, 5-H); MS m/z (rel. int. 

%): 343 [M + ] (100), 328 [M + -CH3] (2), 314 [M + - 

CH2CH3] (3), 300 [M + - COCH3] (4), 298 [M + - OCH2CH3] 

(8), 282 [M + -OH-CH3CHO] (73), 270 [M + -CO2CH2CH3] 

(7), 268 [M + -CH3CHO - OCH3] (19), 254 [M + - COCH3 - 

CH3CH2OH] (6), 43 [CH3CO + ] (41); Anal. Calcd. for 

C19H21NO5 (343.38): C, 66.46; H, 6.16; N, 4.08; O, 23.30. 

Found: C, 66.58; H, 6.20; N, 4.04. 

Ethyl 5-acetyl-2,6-dimethyl-4-phenylpyridine-3-carboxylate 

(3f) 


C. UV (MeOH) max [nm] (log ): 269 (sh, 4.05), 222 

(4.54); IR max: 1724 (CO2C2H5), 1700 (COCH3) cm -1 ; 1 H 


6-CH3), 2.54 (s, 3H, 2-CH3), 2.64 (s, 3H, COCH3), 4.04 (q, 

2H, J = 7.11 Hz, CO2CH2CH3), 7.27 (mc, 2H, m-H), 7.42 

ppm (mc, 3H, o and p-H); MS m/z (rel. int. %): 297 [M + ] 

(50), 282 [M + -CH3] (22), 268 [M + -CH2CH3] (6), 254 [M + 

- COCH3] (35), 236 [M + -CH3CH2OH-CH3] (100), 224 

[M + -CO2CH2CH3] (6), 210 [M + -COCH3 -CH3CHO] 

(12), 43 [COCH3 + ] (53); Anal. Calcd. for C18H19NO3 

(297.36): C, 72.71; H, 6.44; N, 4.71; O, 16.14. Found: C, 

72.00; H, 6.41; N, 4.47. 

Ethyl 5-acetyl-4-(4-chlorophenyl)-2,6-dimethylpyridine-3-carboxylate 

(3g) 


C. UV (MeOH) max [nm] (log ): 307 (sh, 3.44), 269 (sh, 

4.14), 225 (4.43); IR max: 1724 (CO2C2H5), 1697 (COCH3) 

cm -1 ; 1 H NMR : 1.02 (t, 3H, J = 7.15 Hz, CO2CH2CH3), 

1.99 (s, 3H, 6-CH3), 2.55 (s, 3H, 2-CH3), 2.64 (s, 3H, 

COCH3), 4.09 (q, 2H, J = 7.13 Hz, CO2CH2CH3), 7.23 (dd, 

2H, J = 6.59 Hz and 1.86 Hz, 3-H and 5-H), 7.43 ppm (dd, 

2H, J = 6.60 Hz and 1.85 Hz, 2-H and 6-H); MS m/z (rel. 

int. %): 331 [M + ] (53), 316 [M + -CH3] (53), 302 [M + - 

CH2CH3] (8), 288, [M + - COCH3] (44), 272 [M + -CH3CHO 

-CH3] (34), 270 [M + -CH3CH2OH-CH3] (75), 258 [M + - 

CO2CH2CH3] (9), 244 [M + -COCH3 -CH3CHO] (23), 43 

[CH3CO + ] (100); Anal. Calcd. for C18H18ClNO3 (331.80): 

C, 65.16; H, 5.47; N, 4.22; O, 14.47; Cl, 10.68. Found: C, 

65.70; H, 5.54; N, 4.09. 

Ethyl 5-acetyl-2,6-dimethyl-4-(p-toluyl)pyridine-3-carboxylate 

(3h) 


C. UV (MeOH) max [nm] (log ): 264 (4.26), 213 (sh, 

4.52). IR max: 1724 (CO2C2H5), 1694 (COCH3) cm -1 ; 1 H 


6-CH3), 2.42 (s, 3H, 4-CH3), 2.55 (s, 3H, 2-CH3), 2.63 (s, 

3H, COCH3), 4.08 (q, 2H, J = 7.11 Hz, CO2CH2CH3), 7.16 

(d, 2H, J = 8.03 Hz, 3-H and 5-H), 7.24 ppm (d, 2H, J =


8.06 Hz, 2-H and 6-H); MS m/z (rel. int. %): 311 [M + ] 

(65), 296 [M + -CH3] (25), 282 [M + -CH2CH3] (11), 268 

[M + - COCH3] (16), 250 [M + -CH3CH2OH-CH3] (100), 

238 [M + -CO2CH2CH3] (6), 224 [M + - COCH3 -CH3CHO] 

(20), 43 [CH3CO + ] (49); Anal. Calcd. for C19H21NO3 

(311.38): C, 73.29; H, 6.80; N, 4.50; O, 15.41. Found: C, 

73.22; H, 6.81; N, 4.46. 

Ethyl 5-acetyl-2,6-dimethyl-4-(3-pyridyl)pyridine-3carboxylate 

(3i) 


C. UV (MeOH) max [nm] (log ): 266 (3.75), 209 (3.97). 

IR max: 1724 (CO2C2H5), 1705 (COCH3)cm -1 ; 1 H NMR : 

1.09 (t, 3H, J = 7.13 Hz, CO2CH2CH3), 2.04 (s, 3H, 6-CH3), 

2.58 (s, 3H, 2-CH3), 2.67 (s, 3H, COCH3), 4.09 (q, 2H, J = 

7.05 Hz, CO2CH2CH3), 7.40 (dd, 1H, J = 7.58 Hz and 4.90 

Hz, 5-H), 7.63 (d, 1H, J = 7.87 Hz, 4-H), 8.56 (s, 1H, 6- 

H), 8.71 ppm (br s, 1H, 2-H); MS m/z (rel. int. %): 298 

[M + ] (21), 283 [M + -CH3] (100), 269 [M + -CH2CH3] (7), 

256 [M + - COCH2] (27), 255 [M + - COCH3] (24), 237 [M + - 

CH3CH2OH-CH3] (13), 227 [M + - COCH3 -C2H4] (17), 

182 [M + -CO2CH2CH3 - COCH3] (4), 43 [CH3CO + ] (39); 

Anal. Calcd. for C17H18N2O3 (298.34): C, 68.44; H, 6.08; 

N, 9.39; O, 16.09. Found: C, 67.96; H, 6.17; N, 8.73. 

Ethyl 5-acetyl-2,6-dimethyl-4-(4-pyridyl)pyridine-3carboxylate 

(3j) 


C. UV (MeOH) max [nm] (log ): 268 (3.67), 212 (4.20); 

IR max: 1737 (CO2C2H5), 1722 (COCH3)cm -1 ; 1 H NMR : 

0.98 (t, 3H, J = 7.10 Hz, CO2CH2CH3), 2.05 (s, 3H, 6-CH3), 

2.58 (s, 3H, 2-CH3), 2.67 (s, 3H, COCH3), 4.07 (q, 2H, J = 

7.07 Hz, CO2CH2CH3), 7.26 (d, 2H, J = 5.41 Hz, 3-H and 

5-H), 8.72 ppm (d, 2H, J =4.03Hz,2-H and 6-H); MS 

m/z (rel. int. %): 298 [M + ] (37), 283 [M + -CH3] (100), 270 

[M + -C2H4] (5), 269 [M + -CH2CH3] (5), 255 [M + - COCH3] 

(23), 237 [M + -CH3 -CH3CH2OH] (16), 227 [M + - COCH3 

-C2H4] (12), 182 [M + -COCH3 -CO2CH2CH3] (5), 43 

[CH3CO + ] (38); Anal. Calcd. for C17H18N2O3 (298.34): C, 

68.44; H, 6.08; N, 9.39; O, 16.09. Found: C, 68.71; H, 6.18; 

N, 8.65. 

CONCLUSIONS 

Photo-induced electron transfer oxidation of unsymmetrically 

substituted 1,4-dihydropyridines in chloroform 

solution resulted in the oxidation of ring and the formation 

of the corresponding pyridine derivatives. The effect of 

4-substituent has influenced the rate of reaction under oxygen 

or argon atmosphere, and it explained the extent of the 

light sensitivity of these compounds depending on the type 

and nature of 4-substituent. Because of the completion of 

the reaction, the products can be isolated by simple chromatography 

methods. 

ACKNOWLEDGEMENTS 

We thank the Office of Graduate Studies of the University 

of Isfahan for financial support. 

Received April 28, 2006. 

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