A facile method for the synthesis of 2-(3-aryl-2-cyanopropenoyl)-1- methylpyrrole catalysed by KF/Al2O3 with microwave irradiation

Article abstract of DOI:10.3184/174751911X13052910926808

Knoevenagel reaction of 2-cyanoacetylpyrrole with aromatic aldehydes afforded 2-(3-aryl-2-cyanopropenoyl)-1-methylpyrrole in 81-94% yields in ethanol catalysed by KF/Al₂O₃ under microwave irradiation. This method has the advantages o

Full text of DOI:10.3184/174751911X13052910926808

302 RESEARCH PAPER
MAY, 302–303
JOURNAL OF CHEMICAL RESEARCH 2011
A facile method for the synthesis of 2-(3-aryl-2-cyanopropenoyl)-1-
methylpyrrole catalysed by KF/Al2O3 with microwave irradiation
Guo-Liang Feng*, Hong-Li Zhang, Li-Jun Geng and Yu-Mei Zhang
School of Science, Hebei University of Science andTechnology, Yuhua Road, Shijiazhuang 050018, P. R. China
Knoevenagel reaction of 2-cyanoacetylpyrrole with aromatic aldehydes afforded 2-(3-aryl-2-cyanopropenoyl)-1-
methylpyrrole in 81–94% yields in ethanol catalysed by KF/Al2O3 under microwave irradiation. This method has the
advantages of simplicity, good yields and low costs.
Keywords: 2-(3-aryl-2-cyanopropenoyl)-1-methylpyrrole derivatives, 2-cyanoacetylpyrrole, aromatic aldehydes, microwave
irradiation, KF/Al2O3
The Knoevenagel condensation as carbon–carbon bond form-
ing reaction is one of the well-known reactions in organic
chemistry owing to synthesis of important compounds for
coumarin derivatives,1 perfumes,2 pharmaceuticals,3 fine
chemicals4 and polymers.5 It is the condensation of aldehydes
with active methylene group compounds in organic solvents in
the presence of basic sites6–9 such as primary, secondary or
tertiary amine and ammonium salts, amino acids, dimethyl-
aminopyridine and potassium fluoride mixture. Lewis acid,10
zeolites11 and other heterogeneous catalysts12 have also been
employed to catalyse the reaction. Also this reaction has been
carried in aqueous medium using catalysts like diammonium
hydrogen phosphate and 12-tungstophosphoric acid.
Recently, the use of solid supported reagents in organic syn-
thesis has received considerable attention due to their friendly
nature and unique properties, such as enhanced reactivity,
selectivity, mild conditions, avoidance of cumbersome aque-
ous work-up and decreased solvent handling issues, etc. KF/
Al2O3 is a widely used solid supported reagent for catalysis of
a variety of reactions. Due to its strongly basic nature it has
been used as a replacement for organic bases in a number of
organic reactions.13–16
In this report, we describe a simple and economical reaction
of aromatic aldeheydes 1 with 2-cyanoacetylpyrrole17 2 cata-
lysed by KF (40% by weight)/Al2O3 in dry ethanol under
microwave irradiation. (Scheme 1 and Table 1).
It should be noted that in the absence of catalyst lower yields
of product were observed even with prolonged reaction time.
For example, entry 2 without catalyst after 30 minutes only
46% yield of product was obtained in ethanol under micro-
wave irradiation, whereas 93% yield was obtained with cata-
lyst for 10 minutes. The reaction worked better in ethanol than
in methanol, which may be due to its higher boiling tempera-
ture than that of methanol. In addition, we applied the synthe-
sis of 3b in ethanol under classical heating conditions. After
refluxing for 1 h, the desired product 3b was obtained in 66%
yield. However, under microwave irradiation condition, the
yield of 3b was up to 93% (Table 1, entry 2). Therefore, micro-
wave irradiation exhibited several advantages over the conven-
tional heating by significantly reducing the reaction times and
improving the reaction yields.
In this study, the structures of the compounds 3a–m were
1
fully supported by IR, H NMR and elementary analysis as
demonstrated for compound 3a as follows: the IR spectral
Scheme 1
Table 1 Synthesis of compounds 3a–m catalysed by KF/Al2O3 under microwave irradiation
Entry
Ar
Producta
Time/min
Yield/%b
M. p. /°C
1
2
C6H5
3a
3b
3c
3d
3e
3f
3g
3h
3i
10
10
10
10
10
10
10
12
12
12
12
10
91
93
92
94
90
92
90
88
83
82
81
90
71 °C
81–82 °C
113 °C
4-CH3C6H4
3
2,4-(CH3)2C6H3
3,4-(CH3)2C6H3
4-N(CH3)2C6H4
2-CH3OC6H4
3,4-(CH=CH-CH=CH)C6H3
4-PhCH2C6H4
2,4-Cl2C6H3
4
84–85 °C
192–193 °C
135 °C
132–133 °C
80–81 °C
137–138 °C
147–148 °C
170–171 °C
103–104 °C
5
6
7
8
9
10
11
12
3-NO2C6H4
4-NO2C6H4
3j
3k
3l
13
3m
10
94
241–242 °C
a The products were characterised by 1H NMR, IR and elementary analysis.
b Isolated yield.
* Correspondent. E-mail: fgl197012@163.com

JOURNAL OF CHEMICAL RESEARCH 2011 303
analysis of 3a showed two peaks at 1633 cm−1 which cor-
respond to the carbonlys. The peak at 2210 cm−1 correspond to
the CN. In the 1H NMR spectrum of 3a, the –NCH3 protons of
the pyrrole exhibited a singlet at δ 3.98.
In conclusion, we have demonstrated the efficiency for
the synthesis of 2-(3-aryl-2-cyanopropenoyl)-1-methylpyrrole
derivatives involving Knoevenagel condensation of 2-cyano-
acetylpyrrole with aromatic aldehydes in ethanol catalysed by
KF/Al2O3 under microwave irradiation. High efficiency and
short reaction time were the advantages of this protocol.
(dd, 1H, J = 1.5 Hz and J = 4.0 Hz), 6.98 (t, 1H, J = 1.5 Hz), 6.24 (dd,
1H, J = 2.5 Hz and J = 4.5 Hz), 4.00 (s, 3H). IR (KBr) ν 3109, 2973,
2209, 1640, 1545, 1459, 1408, 1377 cm−1. Anal. Calcd for C19H14N2O:
C, 79.70; H, 4.93; N, 9.78. Found: C, 79.79; H, 4.87; N, 9.69%.
3h: 1H NMR (500 MHz, CDCl3): δ (ppm) 7.97 (d, 4H, J = 2.0 Hz),
7.68–7.65 (m, 2H), 7.54–7.50 (m, 4H), 6.96 (dd, 1H, J = 1.5 Hz and
J = 4.5 Hz), 6.92 (t, 1H, J = 1.5 Hz), 6.19 (dd, 1H, J = 2.5 Hz and
J = 4.5 Hz), 3.95 (s, 3H), 3.87 (s, 2H). IR (KBr) ν 3112, 2215, 1633,
1580, 1559, 1458, 1373 cm−1. Anal. Calcd for C22H18N2O: C, 80.96;
H, 5.56; N, 8.58. Found: C, 80.87; H, 5.65; N, 8.66%.
3i: 1H NMR (500 MHz, CDCl3): δ (ppm) 8.36 (s, 1H), 8.20 (d, 1H,
J = 8.5 Hz), 7.53 (d, 1H, J = 2.0 Hz), 7.41 (d, 1H, J = 8.5 Hz), 7.34
(dd, 1H, J = 1.5 Hz and J = 4.5 Hz), 7.00 (t, 1H, J = 2.0 Hz), 6.24 (dd,
1H, J = 2.5 Hz and J = 4.0 Hz), 3.99 (s, 3H). IR (KBr) ν 3110, 2216,
1630, 1600, 1556, 1458, 1342 cm−1. Anal. Calcd for C15H10Cl2N2O: C,
59.04; H, 3.30; N, 9.18. Found: C, 59.10; H, 3.32; N, 9.25%.
3j: 1H NMR (500 MHz, CDCl3): δ (ppm) 8.70 (s, 1H), 8.41 (d, 1H,
J = 8.0 Hz), 8.39–8.37 (m, 1H), 8.11 (s, 1H), 7.73 (t, 1H, J = 8.0 Hz),
7.40 (dd, 1H, J = 1.5 Hz and J = 4.0 Hz), 7.01 (t, 1H, J = 1.5 Hz), 6.26
(dd, 1H, J = 2.5 Hz and J = 4.0 Hz), 4.00 (s, 3H). IR (KBr) ν 3109,
2215, 1635, 1599, 1515, 1456, 1338 cm−1.Anal. Calcd for C15H11N3O3:
C, 64.05; H, 3.94; N, 14.94. Found: C, 64.11; H, 3.86; N, 14.98%.
3k: 1H NMR (500 MHz, CDCl3): δ (ppm) 8.36–8.34 (m, 2H), 8.14–
8.10 (m, 3H), 7.40 (dd, 1H, J = 1.5 Hz and J = 4.5 Hz), 7.02 (t, 1H,
J = 1.5 Hz), 6.26 (dd, 1H, J = 2.5 Hz and J = 4.0 Hz), 4.00 (s, 3H). IR
(KBr) ν 3111, 2218, 1633, 1600, 1516, 1458, 1343 cm−1. Anal. Calcd
for C15H11N3O3: C, 64.05; H, 3.94; N, 14.94. Found: C, 64.11; H, 3.95;
N, 14.87%.
Experimental
Melting points were recorded on an electrothermal digital melting
1
point apparatus and uncorrected. H NMR spectra were determined
on a Varian VXP-500s spectrometer using CDCl3 as solvent and tetra-
methylsilane (TMS) as internal reference. IR Spectra was obtained
on a Nicolet FT-IR 6700 spectrophotometer using KBr pellets.
Elementary analyses were performed by a Carlo-Erba EA1110
CNNO-S analyser. Microwave reactions were carried out in a
Xianghu XH-100B microwave oven.
The mixture of 1 (1 mmol), 2 (0.15 g, 1 mmol), KF/Al2O3 (0.02 g)
and anhydrous C2H5OH (10 mL) were irradiated for the appropriate
number of minutes at 80 °C. After complete conversion as indicated
by TLC, the solvent was then removed under reduced pressure and
extracted with dichloromethane, washed with cool water (3×10 mL)
and the organic layer dried over MgSO4 and concentrated under
reduced pressure. The crude product was chromatographed on silica
gel (200–300 mesh) using a mixture of petroleum ether and dichloro-
methane as eluent to afford the pure product 3a–m.
3l: 1H NMR (500 MHz, CDCl3): δ (ppm) 8.00 (s, 1H), 7.73 (d, 1H,
J = 1.5 Hz), 7.45 (dd, 1H, J = 1.0 Hz and J = 4.5 Hz), 7.42 (d, 1H, J =
3.5 Hz), 6.94 (s, 1H), 6.65 (dd, 1H, J = 1.5 Hz and J = 4.0 Hz), 6.21–
6.22 (m, 1H), 3.96 (s, 3H). IR (KBr) ν 3108, 2919, 2207, 1643, 1601,
1533, 1460, 1379 cm−1. Anal. Calcd for C13H10N2O2: C, 69.02; H, 4.46;
N, 12.38. Found: C, 69.11; H, 4.45; N, 12.32%.
3a: 1H NMR (500 MHz, CDCl3): δ (ppm) 8.09 (s, 1H), 8.00–7.98
(m, 2H), 7.54–7.49 (m, 3H), 7.37 (dd, 1H, J = 1.5 Hz and J = 4.0 Hz),
6.97 (d, 1H, J = 1.5 Hz), 6.23 (dd, 1H, J = 2.5 Hz and J = 4.0 Hz), 3.98
(s, 3H). IR (KBr) ν 3112, 2210, 1633, 1578, 1561, 1458, 1446, 1401,
1370 cm−1. Anal. Calcd for C15H12N2O: C, 76.25; H, 5.12; N, 11.86.
Found: C, 76.31; H, 5.08; N, 11.94%.
1
3m: H NMR (500 MHz, CDCl3): δ (ppm) 9.02 (s, 1H), 8.72 (s,
1H), 8.68 (s, 1H), 7.84 (d, 1H, J = 7.0 Hz), 7.49 (dd, 1H, J = 1.5 Hz
and J = 7.5 Hz), 7.45 (dd, 1H, J = 1.5 Hz and J = 4.0 Hz), 7.36–7.30
(m, 2H), 6.93 (t, 1H, J = 1.5 Hz), 6.23 (dd, 1H, J = 2.5 Hz and J = 4.0
Hz), 4.00 (s, 3H). IR (KBr) ν 3281, 2212, 1613, 1588, 1560, 1504,
1459, 1412, 1330 cm−1. Anal. Calcd for C17H13N3O: C, 74.17; H, 4.76;
N, 15.26. Found: C, 74.13; H, 4.85; N, 15.35%.
3b: 1H NMR (500 MHz, CDCl3): δ (ppm) 8.07 (s, 1H), 7.90 (d, 2H,
J = 8.5 Hz), 7.36 (dd, 1H, J = 1.5 Hz and J = 4.5 Hz), 7.31 (d, 2H, J =
8.5 Hz), 6.95 (t, 1H, J = 2.0 Hz), 6.20 (dd, 1H, J = 2.0 Hz and J = 4.5
Hz), 3.98 (s, 3H), 2.44 (s, 3H). IR (KBr) ν 3110, 2207, 1638, 1578,
1560, 1456, 1406, 1372 cm−1. Anal. Calcd for C16H14N2O: C, 76.78;
H, 5.64; N, 11.19. Found: C, 76.86; H, 5.70; N, 11.13%.
This work was financially supported by the Research Founda-
tion of Hebei University of Science and Technology.
3c: 1H NMR (500 MHz, CDCl3): δ (ppm) 8.36 (s, 1H), 8.20 (d, 1H,
J = 8.0 Hz), 7.36 (dd, 1H, J = 1.5 Hz and J = 4.0 Hz), 7.15 (d, 1H, J =
8.0 Hz), 7.15 (s, 1H), 6.96 (t, 1H, J = 1.5 Hz), 6.22 (dd, 1H, J = 2.5 Hz
and J = 4.5 Hz), 3.99 (s, 3H), 2.40 (s, 3H), 2.38 (s, 3H). IR (KBr) ν
3111, 2208, 1628, 1582, 1558, 1458, 1371 cm−1. Anal. Calcd for
C17H16N2O: C, 77.25; H, 6.10; N, 10.60. Found: C, 77.26; H, 6.15; N,
10.52%.
Received 4 March 2011; accepted 25 April 2011
Paper 1100608 doi: 10.3184/174751911X13052910926808
Published online: 1 June 2011
3d: 1H NMR (500 MHz, CDCl3): δ (ppm) 8.04 (s, 1H), 7.79 (d, 1H,
J = 8.0 Hz), 7.76 (s, 1H), 7.35 (dd, 1H, J = 1.5 Hz and J = 4.0 Hz),
7.26 (d, 1H, J = 7.5 Hz), 6.95 (t, 1H, J = 1.5 Hz), 6.21 (dd, 1H, J = 2.5
Hz and J = 4.5 Hz), 3.97 (s, 3H), 2.34 (s, 3H), 2.33 (s, 3H). IR (KBr)
ν 3108, 2210, 1632, 1585, 1561, 1460, 1410, 1364 cm−1. Anal. Calcd
for C17H16N2O: C, 77.25; H, 6.10; N, 10.60. Found: C, 77.20; H, 6.14;
N, 10.51%.
References
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3e: H NMR (500 MHz, CDCl3): δ (ppm) 8.07 (s, 1H), 7.99 (dd,
2H, J = 1.5 Hz and J = 7.5 Hz), 7.37 (dd, 1H, J = 1.5 Hz and J = 4.0
Hz), 6.89 (t, 1H, J = 1.5 Hz), 6.71 (d, 2H, J = 7.5 Hz), 6.19 (dd, 1H,
J = 2.5 Hz and J = 4.0 Hz), 3.96 (s, 3H), 3.11 (s, 6H). IR (KBr) ν 3104,
2918, 2201, 1633, 1610, 1557, 1523, 1458, 1371 cm−1. Anal. Calcd
for C17H17N3O: C, 73.10; H, 6.13; N, 15.04. Found: C, 73.19; H, 6.17;
N, 15.08%.
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3f: 1H NMR (500 MHz, CDCl3): δ (ppm) 8.56 (s, 1H), 8.30 (dd, 1H,
J = 1.5 Hz and J = 8.0 Hz), 7.52–7.48 (m, 1H), 7.31 (dd, 1H, J = 1.5
Hz and J = 4.0 Hz), 7.08 (t, 1H, J = 7.5 Hz), 6.97–6.95 (m, 2H), 6.21
(dd, 1H, J = 2.5 Hz and J = 4.0 Hz), 3.98 (s, 3H), 3.89 (s, 3H). IR
(KBr) ν 3115, 2917, 2223, 1624, 1602, 1587, 1485, 1470, 1412, 1329
cm−1. Anal. Calcd for C16H14N2O2: C, 72.16; H, 5.30; N, 10.52. Found:
C, 72.21; H, 5.37; N, 10.48%.
9
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8.20 (dd, 1H, J = 1.5 Hz and J = 8.5 Hz), 7.96–7.93 (m, 2H), 7.89 (d,
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