A three-component reaction between azaarenes (phenanthridine, quinoline or isoquinoline), acetylenic esters and phenol derivatives

Article abstract of DOI:10.3184/174751911X13128171741972

Three component condensation reactions between azaarenes (phenanthridine, quinoline or isoquinoline) and acetylenic esters were undertaken in the presence of phenol derivatives (2,4-di-tert-butylphenol, 2,6-dimethylphenol, 4- methylphenol and 4-chloro-3,5

Full text of DOI:10.3184/174751911X13128171741972

JOURNAL OF CHEMICAL RESEARCH 2011
RESEARCH PAPER 437
AUGUST, 437–441
A three-component reaction between azaarenes (phenanthridine,
quinoline or isoquinoline), acetylenic esters and phenol derivatives
Mahmoud Nassiri*
Faculty of Marine Science, Chabahar Maritime University, PO Box 99717-56499, Chabahar, Iran
Three component condensation reactions between azaarenes (phenanthridine, quinoline or isoquinoline) and acety-
lenic esters were undertaken in the presence of phenol derivatives (2,4-di-tert-butylphenol, 2,6-dimethylphenol, 4-
methylphenol and 4-chloro-3,5-dimethylphenol) for generation of C-arylation in good yields. The reactions proceeded
smoothly at room temperature without using any catalyst.
Keywords: phenanthridine, isoquinoline, quinoline, acetylenic esters, phenol derivatives, C-arylation
Introduction
activities,15–17 including antifungal, antimicrobial and anti-
inflammatory.18 I now describe the reaction between azaarenes
(phenanthridine, quinoline and isoquinoline) and acetylenic
esters in the presence of phenol derivatives (see Scheme 1 and
Table 1).
Azaarenes are a group of substituted polycyclic aromatic
hydrocarbons (PAHs) where one carbon atom of the aromatic
ring is replaced by a nitrogen atom.1 They are found in
environmental matrices such as ambient air, lake and marine
sediment, and seawater. They are also found in stack gases
from coal combustion and automobile exhaust gases.2–5 The
isoquinoline skeleton is found in a large number of naturally
occurring and synthetic biologically active heterocyclic com-
pounds.6,7 These compounds exhibit sedative,8 antidepressant9
and antimicrobial activities.10Quinoline is a representative
nitrogen heterocyclic compounds that is commonly generated
by coking plants, pharmaceutical factories, and related
industries.11A number of biological activities have been
associated with quinoline-containing compounds such as
anti-flammatory, antimalarial, antibacterial, anticancer and
antiparasitic.12,13 Substituted phenanthridines are an important
class of heterocyclic compounds in material science14 and
in medicinal chemistry due to their significant biological
Results and discussion
The reaction between azaarenes (phenanthridine 1, isoquino-
line 5 or quinoline 9) and acetylenic esters 2, 6 or 10 as a
Michael acceptor19–24 was undertaken in the presence of phenol
derivatives (2,5-dimethylphenol, 2,4-di-tert-butylphenol, 4-
methylphenol and 4-chloro-3,5-dimethylphenol) at ambient
temperature (see Scheme 2 and Table 1). Reactions were car-
ried out by first mixing the phenanthridine, isoquinoline or
quinoline and phenol derivatives and then the acetylenic ester
was added slowly. The reactions proceeded smoothly in CH2Cl2
and then the whole reaction mixture solidified into yellow or
brown solid within a few hours. The 1H and 13C NMR spectra
Scheme 1
* Correspondent. E-mail: mdnassiri@yahoo.com

438 JOURNAL OF CHEMICAL RESEARCH 2011
Table 1 Reaction between azaarenes with acetylenic esters in the presence of phenol derivatives
of the crude products clearly indicated the formation of com-
pounds 4a–b, 8c–e and 12f–g. No product other than 4a–b,
8c–e and 12f–g could be detected by NMR spectroscopy. The
structures of compounds 4a–b, 8c–e and 12f–g were confirmed
OCH2CH3 and δ = 2.28, 6H, s, 2Me, phenol), methylene
(δ = 4.21, 2H, q, 3JHH = 7.00 Hz, OCH2CH3), olefinic protons
(δ=5.51and8.22,2d,3JHH =13.6Hz,N-CH=CH-CO2CH2CH3),
a sharp line at δ = 6.69 ppm for the OH group, and also a sharp
line for methine proton (δ = 9.30 ppm, 1H, s, NCHC). Aro-
matic protons, along with multiplets at δ = 6.74–8.15 ppm for
the phenanthridine and phenol moiety. The 13C NMR spectrum
1
by elemental analyses, mass, IR, H NMR and 13C NMR
spectra. The 1H NMR 500 MHz spectrum of 4a exhibited two
3
signals identified as methyl (δ = 1.31, 3H, t, JHH = 7.00 Hz ,

JOURNAL OF CHEMICAL RESEARCH 2011 439
of 4a showed 26 distinct resonances in agreement with the
proposed structure. In addition, product 4a displayed 13C NMR
resonances at δ = 63.14, 109.35 and 123.90 ppm, respectively
for the NCHC, N-CH=CH-CO2CH2CH3, and N-CH=CH-
CO2CH2CH3 units.22–24 The carbonyl group resonance in the
13C NMR spectrum of 4a appear at δ = 168.35 ppm. The 1H and
13C NMR spectra of compounds 4b, 8c–e and 12f–g are similar
about 5.67–6.65 ppm, which is in agreement with the ( Z) con-
figuration25,26 for the vinyl moiety in 4b, 8d–e and 12f. (see
Scheme 2 and Table 1).
Briefly, I now describe a new method to access a novel class
of heterocyclic derivatives. The present procedure has the
advantage that not only is the reaction performed under neutral
conditions, but also the reactants can be mixed without any
prior activation or modification. It seems that, this procedure is
very useful to functionalise azaarenes in a one-pot operation.
1
to those of 4a. The H NMR of each of the isolated products
4b, 8d–e and 12f exhibited a N–C=CH proton signal at
Scheme 2

440 JOURNAL OF CHEMICAL RESEARCH 2011
72.98; H, 7.31; N, 2.85%. 1H NMR (500.1 MHz, CDCl3), δH 1.19 and
Experimental
1.45 (18H, 2s, 2OCMe3), 3.61 and 3.93 (6H, 2s, 2OMe), 5.35 (1H,
Melting points and IR spectra of all compounds were measured on an
Electrothermal 9100 apparatus and a Shimadzu IR-460 spectrometer,
respectively. The 1H and 13C NMR spectra were obtained with a Bruker
DRX-500 Avance instrument using CDCl3 as applied solvent and
TMS as internal standard at 500.1 and 125.8 MHz respectively.
In addition, the mass spectra were recorded on a GCMS-QP5050A
mass spectrometer operating at an ionisation potential of 70 eV.
Elemental analyses for C, H and N were performed using a Heraeus
CHN-O-Rapid analyser. All the chemicals used in this work were
purchased from Fluka (Buchs, Switzerland) and were used without
further purification.
3J
s, OH), 5.86 (1H, s, N–C=CH–CO2Me), 6.13 (1H, d,
= 7.8 Hz,
HH
3
N–CH=CH, isoquinoline), 6.47 (1H, s, NCHC), 6.57 (1H, d, JHH
=
7.8 Hz, N–CH=CH, isoquinoline), 7.03–8.52 (7Haro, m, isoquinoline
and phenol). 13C NMR (125.8 MHz, CDCl3), 30.35 and 31.52 (2CMe3),
34.23 and 34.35 (2CMe3), 51.01 and 52.32 (2CO2Me), 91.13 (NCHC),
105.84 (1C, N–C=CH–CO2Me), 122.97 and 123.57 (2C, isoquinoline
and phenol), 124.89 (1C, N–C=CH–CO2Me), 126.85, 127.46, 127.63,
128.81, 129.75, 130.47, 131.83, 134.90, 142.99 and 148.05 (12C,
isoquinoline and phenol), 166.38 and 169.45 (2C=O, ester).
Diethyl 2-[1-(3,5-di-tert-butyl-2-hydroxyphenyl)isoquinolin-2(1H)-yl]
maleate (8e): Brown powder, yield 91%, 0.46g, m.p. 115–117 °C, IR
(νmax, cm−1): 1632 and 1741 (C=O), 3240 (OH). MS, m/z (%) = 505
(M, 7), 460 (M-OEt, 41), 432 (M-CO2Et, 24), 300 (M-C14H21O, 67),
205 (C14H21O, 19), 129 (C9H7N, 100) . Anal. Calcd for C31H39NO5
(505.65): C, 73.64; H, 7.77; N, 2.77. Found: C, 73.50; H, 7.85; N,
2.86%. 1H NMR (500.1 MHz, CDCl3), δH 1.15 (3H, t, 3JHH = 7.0 Hz,
OCH2CH3), 1.28 (9H, s, CMe3), 1.33 (3H, t, 3JHH = 7.0 Hz, OCH2CH3),
1.40 (9H, s, CMe3), 4.28 (4H, m, 2ABX3system, 2OCH2CH3), 5.39
General procedure
Ethyl-(2E)-3-[6-(4-hydroxy-3,5-dimethylphenyl)phenanthridin-5(6H)-yl]
acrylate (4a): To a magnetically stirred solution of phenanthridine
(0.18 g, 1 mmol) and 2,6-dimethylphenol (0.12 g, 1 mmol) in CH2Cl2
(10 mL) was added, dropwise, a mixture of ethyl propiolate (1 mmol)
in CH2Cl2 (5 mL) at –10°C over 10 min. After 5 hours stirring at ambi-
ent temperature, the whole reaction mixture solidified into a brown
solid, the solvent was then removed under reduced pressure and prod-
uct washed with cold diethyl ether (2×5 mL). Then the product was
recrystallised from a mixture of acetonitrile and acetone. Brown
powder, yield 88%, 0.35g, m.p. 88–90 °C, IR (νmax, cm−1): 1740 (C=O),
3200 (OH). MS, m/z (%) = 399 (M, 9), 370 (M-Et, 83), 326 (M-CO2Et,
37), 179 (C13H9N, 100). Anal. Calcd for C26H25NO3 (399.49): C, 78.17;
H, 6.31; N, 3.50. Found: C, 78.01; H, 6.39; N, 3.61%. 1H NMR (500.1
(1H, s, OH), 5.74 (1H, s, N–C=CH–CO2CH2CH3), 6.12 (1H, d, 3JHH
=
7.2 Hz, N–CH=CH, isoquinoline), 6.24 (1H,s, NCHC), 6.41 (1H, d,
3JHH = 7.2 Hz, N–CH=CH, isoquinoline), 6.66–8.55 (7Haro, m, iso-
quinoline and phenol). 13C NMR (125.8 MHz, CDCl3), 13.87 and
14.20 (2OCH2CH3), 27.68 and 29.03 (2CMe3), 56.80 and 57.11
(2OCH2CH3), 63.17 (NCHC), 94.45 (1C, N–C=CH–CO2CH2CH3),
122.35 and 122.49 (2C, isoquinoline and phenol), 123.18 (1C, N–
C=CH–CO2CH2CH3), 125.10, 126.31, 127.37, 128.21, 128.39, 129.53,
130.11, 131.34, 133.60, 143.19, 145.56 and 151.36 (12C, isoquinoline
and phenol), 169.17 and 171.65 (2C=O, ester).
Dimethyl 2-[2-(2-hydroxy-5-methylphenyl)quinolin-1(2H)-yl]
maleate (12f): Brown powder, yield 92%, 0.35g, m.p. 102–104 °C, IR
(νmax, cm−1): 1634 and 1729 (C=O), 3180 (OH). MS, m/z (%) = 379
(M, 8), 320 (M-CO2Me, 40), 272 (M-C7H7O, 54), 261 (M-2CO2Me,
32), 143 (C6H7O4, 26), 129 (C9H7N, 100), 107 (C7H7O, 18). Anal.
Calcd for C22H21NO5 (379.40): C, 69.65; H, 5.58; N, 3.69. Found:
C, 69.69; H, 5.65; N, 3.81%. 1H NMR (500.1 MHz, CDCl3), δH 2.29
(3H, s, Me), 3.66 and 3.72 (6H, 2s, 2OMe), 5.39 (1H, s, OH), 5.67
(1H, s, N–C=CH–CO2Me), 6.55 (1H, s, NCHC), 6.61–8.33 (10Haro,
m, quinoline and phenol). 13C NMR (125.8 MHz, CDCl3), δC 14.15
(Me), 51.83 and 52.11 (2OMe), 67.31 (NCHC), 73.97 (N–C=CH–
CO2CH3), 114.12., 115.15, 116.15, 118.43, 121.07 and 121.13 (6C,
quinoline and phenol), 124.14 (N–C=CH–CO2CH3), 125.86, 126.48,
128.96, 130.30, 141.67 and 151.80 (8C, quinoline and phenol), 167.53
and 169.80 (2C=O, ester).
3
MHz, CDCl3), δH 1.31 (3H, t, JHH = 7.00 Hz, OCH2CH3), 2.28 (6H,
3
s, 2CH3, phenol), 4.21 (2H, q, JHH = 7.00 Hz, OCH2CH3), 5.51 (1H,
3
d, JHH = 13.6 Hz, N–CH=CH–CO2Et), 6.69 (1H, s, OH), 6.74–8.15
(11Haro, phenanthridine and phenol), 8.22 (1H, d, 3JHH = 13.6 Hz, N–
CH=CH–CO2Et), 9.30 (1H, s, NCHC). 13C NMR (125.8 MHz, CDCl3),
13.30 (OCH2CH3), 28.17 (2CH3), 58.29 (OCH2CH3), 63.14 (NCHC),
109.35 (N–C=CH–CO2CH2CH3), 123.90 (N–C=CH–CO2CH2CH3),
124.80, 127.37, 127.45, 127.90, 128.13, 128.56, 129.00, 129.17,
131.29, 131.82, 132.02, 133.41, 135.31, 141.07 and 152.60 (18C,
phenanthridine and phenol), 168.35 (C=O, ester).
Diethyl 2-[6-(4-hydroxy-3,5-dimethylphenyl)phenanthridin-5(6H)-yl]
maleate (4b): Yellow powder, yield 91%, 0.43g, m.p. 92–94 °C, IR
(νmax, cm−1): 1720 and 1654 (C=O), 3280 (OH). MS, m/z (%) = 471
(M, 12), 426 (M-OEt, 46), 398 (M-CO2Et, 71), 350 (M-C8H9O, 100),
179 (C13H9N, 86), 121 (C8H9O, 25). Anal. Calcd for C29H29NO5
(471.55): C, 73.87; H, 6.20; N, 2.97. Found: C, 73.98; H, 6.11;
N, 3.09%. 1H NMR (500.1 MHz, CDCl3), δH 0.79 and 0.98 (6H, 2t,
3JHH = 7.1 Hz, 2OCH2CH3), 2.35 (6H, s, 2Me, phenol), 3.70 and 3.81
(4H, 2m, 2ABX3system, 2OCH2CH3), 5.29 (1H, s, OH), 6.65 (1H,
s, N–C=CH–CO2CH2CH3), 6.72–8.08 (10Haro, m, phenanthridine and
phenol).13C NMR (125.8 MHz, CDCl3), 14.13 and 14.73 (2OCH2CH3),
27.50 (2CH3, phenol), 57.12 and 60.51(2OCH2CH3), 65.13 (NCHC),
120.20 (1C, N–C=CH–CO2CH2CH3), 123.19 (1C, N–C=CH–
CO2C(CH3)3), 123.59, 123.91, 124.26, 124,36, 125.75, 127.11, 127.36,
127.94, 128.34, 128.53, 129.71, 130.25, 141.61, 144.31, 151.89 and
152. 80 (18Caro, phenanthridine and phenol), 165.82 and 167.70
(2C=O, ester).
Methyl (2E)-3-[2-(3-chloro-6-hydroxy-2,4-dimethylphenyl)quinolin-
1(2H)-yl]acrylate (12g): Brown powder, yield 89%, 0.33g, m.p. 140–
142 °C, IR (νmax, cm−1): 1732 (C=O), 3385 (OH). MS, m/z (%) = 369
(M, 8), 354 (M-Me, 50), 338 (M-OMe, 12), 310 (M-CO2Me, 14), 129
(C9H7N, 100), 120 (C8H8O, 39).Anal. Calcd for C21H20ClNO3 (369.89):
1
C, 68.19; H, 5.45; N, 3.78. Found: C, 68.19; H, 5.46; N, 3.74%. H
NMR (500.1 MHz, CDCl3), δH 2.27 and 2.36 (6H, 2Me, phenol), 3.80
3J
(3H, OMe), 5.30 (1H,d,
= 13. 3 Hz, N-CH=CH–CO2Me), 6.59
HH
(1H, s, OH), 6.83 (1H, s, NCHC), 6.98–8.24 (8Haro. quinoline and
phenol), 8.28 (1H, d, 3JHH = 13.3 Hz, N–CH=CH–CO2Me). 13C NMR
(125.8 MHz, CDCl3), 15.11 (Me), 51.31 (OMe), 65.48 (NCHC), 79.31
(1C, N–CH=CH–CO2Me), 114.95, 117.37, 117.60, 118.69, 120.57
and 122.85 (6C, quinoline and phenol), 123.28 (1C, N–CH=CH–
CO2Me), 125.16, 127.31, 128.42, 132.96, 141.38, 143.19 and 152.13
(8C, quinoline and phenol), 169.99 (C=O, ester).
Methyl-(2E) 3-[1-(3,5-di-tert-butyl-2-hydroxyphenyl]isoquinolin-
2(1H)-yl)acrylate (8c): Brown powder, yield 90%, 0.38g, m.p. 113–
115 °C, IR (νmax, cm−1): 1646 (C=O), 3197 (OH). MS, m/z (%) = 419
(M, 6), 388 (M-OMe, 63), 360 (M-CO2Me, 47), 214 (M-C14H21O, 17),
205 (C14H21O, 25), 129 (C9H7N, 73), 85 (C4H5O2, 41). Anal. Calcd for
C27H33NO3 (419.56): C, 77.30; H, 7.93; N, 3.34. Found: C, 77.10;
H, 8.06; N, 3.30%. 1H NMR (500.1 MHz, CDCl3), δH 1.12 and 1.35
3
(18H, 2s, 2CMe3), 3.83 (3H, s, OMe), 5.63 (1H, d, JHH = 13.4 Hz,
N–CH=CH–CO2Me), 5.76 (1H, s, OH), 6.63 (1H, s, NCHC), 6.95–
8.65 (9Haro, m, isoquinoline and phenol). 13C NMR (125.8 MHz,
CDCl3), δC 27.34 (2CMe3), 33.91 and 34.18 (2CMe3), 51.76 (2OCH3),
57.14 (NCHC), 93.16 (N–CH=CH–CO2Me), 123.14 (N–CH=CH–
CO2Me), 125.15, 125.55, 126.32, 126.83, 127.20, 127.91, 128.38,
128.45, 129.35 132.46, 133.11, 141.71, 142.45 and 152.51 (14C,
isoquinoline and phenol), 166.51 (C=O, ester).
We gratefully acknowledge financial support from the Research
Council of the Chabahar Maritime University.
Received 4 May 2011; accepted 12 July 2011
Paper 1100683 doi: 10.3184/174751911X13128171741972
Published online: 29 August 2011
Dimethyl 2-[1-(3,5-di-tert-butyl-2-hydroxyphenyl)isoquinolin-2(1H)-yl]
maleate (8d): Brown powder, yield 94%, 0.45g, m.p. 96–98 °C, IR
(νmax, cm−1): 1783 and 1722 (C=O), 3230 (OH). MS, m/z (%) = 477
(M, 6), 446 (M-OMe, 40), 418 (M-CO2Me, 50), 359 (M-2CO2Me,
48), 272 (M-C14H21O, 15), 205 (C14H21O, 22), 129 (C9H7N, 100). Anal.
Calcd for C29H35NO5 (477.59): C, 72.93; H, 7.38; N, 2.93. Found: C,
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