One-pot synthesis of the derivatives of 2-cyclopent-2-en-1-one by SOCl 2/EtOH

Article abstract of DOI:10.3184/030823407X237803

A simple and efficient method for the synthesis of derivatives of cyclopent-2-en-1-one is presented. Aromatic aldehydes reacted with aliphatic ketones in the presence of thionyl chloride in anhydrous ethanol to give seven derivatives of 2-cyclopenten-1-one in one step with reasonable yields. The structures of the products were established.

Full text of DOI:10.3184/030823407X237803

JOURNAL OF CHEMICAL RESEARCH 2007
AUGUST, 461–463
RESEARCH PAPER 461
One-pot synthesis of the derivatives of 2-cyclopent-2-en-1-one by
SOCl2/EtOH
Zhiguo Hu* and Zhibing Dong
College of Chemistry and Environmental Science, Henan Normal University, Xinxiang, 453007, Henan, P. R. China
A simple and efficient method for the synthesis of derivatives of cyclopent-2-en-1-one is presented. Aromatic
aldehydes reacted with aliphatic ketones in the presence of thionyl chloride in anhydrous ethanol to give seven
derivatives of 2-cyclopenten-1-one in one step with reasonable yields. The structures of the products were
established.
Keywords: derivatives of 2-cyclopent-2-en-1-one, SOCl2/EtOH
Crossed aldol–condensation reactions are important synthetic
reactions for carbon–carbon bond formation.1 As classical
methods, they were performed in the presence of strong acids
or bases and many successful examples including transition
metal enolates as well as main group metal enolates have
been reported in the recent literature.2 However, traditional
acid- or base-catalysed reactions suffer from reverse
reactions, and a metal chloride was reported to promote the
self-condensation of ketones rather than the crossed aldol-
condensation.3 These methods generally resulted in mono-
or di-substituted α,β-unsaturated carbonyl compounds. It is
well known that the base-catalysed reaction of butanone with
benzaldehyde gave preferential reactions at C1 of the ketone,
while the acid-catalysed reaction occurred preferentially
at C3 of the ketone. Kenichi and Atsuchi4 reported the
synthesis of a regioselective compound condensed from
C1 of the ketone in the presence of Co2+–VP–MMA (in
a sealed tube, in vacuum). Chuit and Corriu5 synthesised
similar regioselective compounds by using tetraalkoxysilane
in the presence of fluoride ions. On the contrary, Nasser
and Kasemi6 used RuCl3 as the catalyst to synthesise the
other α,β-unsaturated carbonyl compound regioselectively
condensed from C1. Francis and Andrew7 once synthesised
methylanhydracetonebenzil through the condensation of
benzil and acetone under the influence of potassium hydroxide,
and benzylidenemethylanhydracetonebenzil was obtained
when methylanhydracetonebenzil reacted with benzaldehyde
under the influence of alcoholic potassium in the cold.
By the reaction of zirconium chloride catalysts (120–130°C,
12h),YukiandHashimoto8 synthesised2,3,4,5-tetrasubstituted
cyclopent-2-en-1-ones with low yield from the corresponding
ketones and aldehydes. Huang and coworkers9 synthesised
some derivatives of 2-cyclopenten-1-one in the presence of
TiCl4-2THF using Schlenk techniques. Based on the synthesis
of 1,3,5-triarylbenzene,10 asymmetric 1,3,5-triaryl-benzene,11
chalcones,12 α,α'-bis(substituted benzylidene) ketones,13
symmetric trisannelated benzenes14 and unsymmetric
trisannelated benzenes15 catalysed by SOCl2/EtOH, we
have developed this simple one-pot method for the crossed
condensation of aromatic aldehydes with aliphatic ketones.
Surprisingly, a series of new derivatives of cyclopent-2-
en-1-one were obtained in one step with reasonable yields
(Scheme 1).
Results and discussion
A white crystalline compound was obtained when p-chloro-
benzaldehyde was condensed with butanone in the SOCl2/
EtOH system, and it was expected to be compound a
(Scheme 2) at first. But after checking its mass spectrum
(m/z: 439, M+), we found that 3 mol of p-chlorobenzaldehyde
condensed with 1 mol of butanone. The band at 1677 cm-1 in the
IR spectrum indicated a carbonyl in the structure, 1611 cm-1,
1641 cm-1 indicated a carbon–carbon double bond and
841 cm-1, 819 cm-1 suggested the existence of a p-substituted
1
aromatic ring. H NMR (CDCl3, ppm): 1.98(s, 3H, CH3),
5.06(s, 1H, CH), 6.90–7.34(m, 12H, Ar–H), 7.53(s, 1H, =CH);
13C NMR (CDCl3, ppm): 10.5, 51.4, 129.3, 129.4, 129.4,
129.8, 130.0, 131.9, 132.5, 133.1, 133.4, 133.5, 135.8, 136.1,
137.6, 137.9, 138.9, 164.8, 197.5. This showed the compound
had an unsaturated 5-membered ring which suggested e
(Scheme 2) as the structure. The structure could also be
O
O
SOCl2 /EtOH
reflux 2 h
Ar
+
Ar
CH
(CH ) CH
n-1
CHO H3 CC(CH2 )nCH3
2
3
Ar
Ar
b: n = 1, Ar = p-CH3O-C6H4
d: n = 1, Ar = C6H5
c: n = 1, Ar = p-CH3-C6H4
e: n = 1, Ar = p-Cl-C6H4
g: n = 2, Ar = C6H5
f: n = 1, Ar = m-NO2-C6H4
O
O
SOCl2/EtOH
reflux 2 h
Ph
CHO
+
Ph
Ph
h
Scheme 1 The synthesis of derivatives of cyclopent-2-en-1-one.
* Correspondent. E-mail: zhiguohu@yahoo.com
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462 JOURNAL OF CHEMICAL RESEARCH 2007
Table 2 The synthesis of derivatives of cyclopent-2-en-1-one
C1C6H4HC=CHCOC=CHC0H4C1
Entry
Product
M.p./°C
Yield/%
CH3
a
O
1
2
3
4
5
6
7
b
c
d
e
f
g
h
119–121
183–185
155–157
178–179
211–212
159–161
117–118
71
75
83
84
85
70
75
5
1
2
3
C1C6H4HC=
CH3
4
7
6
C1C6H4 C6H4C1
e
Conclusion
Scheme 2
In conclusion, we have developed a simple and general method
for the synthesis of the derivatives of cyclopent-2-en-1-one
(b, c, e, f, g are new compounds) in one step. The advantages
of this method are the cheap catalyst, short reaction times,
reasonable yields and simple manipulation.
confirmed by an HMQC spectrum (shown in Table 1,
see Scheme 2 e at the same time). Taking benzaldehyde
as the example of aromatic aldehydes (four substituted
benzaldehydes) to react with aliphatic ketones, and taking
butanone as the example of ketones (butanone, 2-pentanone,
3-pentanone) to react with aromatic aldehydes, we obtained
a series of compounds (b, c, d, f, g, h) which had similar
structures to compound e.
Experimental
Melting points were determined on the Kofler micro melting point
apparatus without correction. IR spectra were recorded on a PTS-40
1
IR spectrophotometer in KBr. H NMR (in CDCl3) and 13C NMR
During the course of the crossed-condesation reaction, self-
condensation of ketones was also observed as a side reaction.
In order to prevent this, thionyl chloride and the ketone were
dropped into the mixture of aldehyde and anhydrous ethanol.
High temperature increased the yield of the products. The
yield of the product d was only 65% when the reaction was
carried out at room temperature but the yield was 83% when
the reaction was refluxed. There was almost no product when
the system was cooled below 0°C (ice-salt cold bath). The
optimal reaction time was 2 hours and the optimal ratio of
SOCl2 to ketone was 2:1. Furthermore, we found that the
alcohol was indispensable in the catalyst system as well as
serving as reaction solvent. Other solvents such as toluene and
pyridine were also used, but only alcohols catalysed this aldol
reaction. There was no significant variation of yields between
using anhydrous CH3OH and anhydrous C2H5OH.
We also found that the electronic nature of substrates had a
marked effect on the reaction. The results of the condensation
reactions are shown in Table 2. Strong electron-withdrawing
groups on the aromatic rings led to increased yields (entries
4 and 5), while electron-donating groups decreased the yield
(entries 1 and 2). And with the increase of the carbon chain
of the aliphatic ketone, the yield of the products decreased
(entries 6 and 7).
As for the mechanism, we believe that the condensation
in our reaction is not catalysed by HCl. Robert et al.16 once
reported the synthesis of triarylbenzenes by HCl with low
yield (26%) under the action of anhydrous HCl for 18 days
and we reported the synthesis of triarylbenzenes in the
presence of thionyl chloride in anhydrous ethanol with high
yield 85% (only within 1 hour).10 Moreover, Elmorsy et al.17
reported the mechanism of the condensation of acetophenone
by SiCl4/EtOH which went through the silyl enol ether of the
ketone. We believe therefore, that the reaction proceeds via
the reaction of the enol sulfite ester of ketones and that the
byproduct HCl may accelerate the reaction.
(in CDCl3) spectra were measured using TMS as internal standard
on a BRUKER 250 AC NMR spectrometer. The mass spectra were
measured on an Agilent GC–MS spectrometer. The high-resolution
mass spectra (ESI–HRMS) were determined on an Ion Spec (7.0 T)
spectrometer.
Synthesis of compound (d): a typical experimental procedure
Thionyl chloride (8.8 ml, 0.12 mol) and butanone (5.4 ml, 0.06 mol)
were dropped synchronously into a stirred mixture of the benzaldehyde
(24.2 ml, 0.24 mol) and anhydrous ethanol (14.6 ml, 0.25 mol). The
mixture was refluxed for 2 hours and then saturated aqueous Na2CO3
was added and the mixture was filtered. The solid was washed
successively with ethanol, water, anhydrous ethanol and di ethyl ether.
Compound spectroscopic data (b): M.p. 119–121°C; 1H NMR
(CDCl3, ppm): 2.02(s, 3H, CH3), 3.64(s, 3H, OCH3), 3.75(s, 3H,
OCH3), 3.79(s, 3H, OCH3), 5.06(s, 1H, CH), 6.60–7.41(m, 12H, Ar–
H), 7.50(s, 1H, =CH); IR (KBr, cm-1): 2835, 1640, 1640, 1610, 1463,
1350, 1178, 1034, 831, 578, 563; HRMS(m/z): Calcd. For C28H27O4
[M+ + H]: 427.1915. Found: 427.1919.
1
(c): M.p. 183–185°C; H NMR (CDCl3, ppm): 2.01(s, 3H, CH3),
2.15(s, 3H, CH3), 2.28(s, 3H, CH3), 2.31(s, 3H, CH3), 5.15(s, 1H,
CH), 6.86–7.36(m, 12H, Ar–H), 7.52(s, 1H, =CH); IR (KBr, cm-1):
3033, 1680, 1641, 1604, 1345, 832; HRMS(m/z): Calcd. For C28H27O
[M+ + H]: 379.2056. Found: 379.2062.
(d): M.p. 155–157°C (m.p.9 150–152°C); 1H NMR (CDCl3, ppm):
2.04(s, 3H, CH3), 5.19(s, 1H, CH), 7.02–7.45(m, 15H, Ar–H), 7.61(s,
1H, =CH); IR (KBr, cm-1): 2919, 2850, 1679, 1641, 1611, 1447,
1343, 1130, 770, 703, 689; 563; HRMS(m/z): Calcd. For C25H21O
[M+ + H]: 337.1587. Found: 337.1581.
1
(e): M.p. 178–179°C; H NMR (CDCl3, ppm): 1.98(s, 3H, CH3),
5.06(s, 1H, CH), 6.90–7.34(m, 12H, Ar–H), 7.53(s, 1H, =CH); 13C
NMR (CDCl3, ppm): 10.5, 51.4, 129.3, 129.4, 129.4, 129.8, 130.0,
131.9, 132.5, 133.1, 133.4, 133.5, 135.8, 136.1, 137.6, 137.9, 138.9,
164.8, 197.5; IR (KBr, cm-1): 1677, 1641, 1611, 1491, 1341, 1091,
1011, 841, 819, 770, 515; HRMS(m/z): Calcd. For C25H1635Cl3O
[M+–H]: 437.0272. Found: 437.0267(100%), 439.0237(96.53%).
1
(f): M.p. 211–212°C; H NMR (CDCl3, ppm): 2.14(s, 3H, CH3),
5.47(s, 1H, CH), 7.28(s, 1H, =CH), 7.30–8.21(m, 12H, Ar–H); IR
(KBr, cm-1): 1696, 1622, 1535, 1351, 827, 810, 719; HRMS(m/z):
Calcd. For C25H16O7N3 [M+-H]: 470.0994. Found: 470.0990.
1
(g): M.p. 159–161°C; H NMR (CDCl3, ppm): 1.13(t, 3H, CH3,
J = 7.6 Hz), 2.24(m, 2H, CH2), 5.09(s, 1H, CH), 6.70–7.41(m,
Table 1 NMR spectroscopic data of compound e (CDCl3, δ in ppm)
Position of carbons
1H NMR(δ, mult.)
13C NMR (δ, mult.)
HMQC(1H–13C)
1
2
3
4
5
6
7
7.53 (s, 1H)
No H
131.4 (s)
Between 129.3-138.9
197.5 (s)
Between 129.3-138.9
10.5 (s)
relative
not found
not found
not found
relative
not found
relative
No H
No H
1.98 (s, 3H)
No H
164.8 (s)
51.4 (s)
5.06 (s, 1H)
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JOURNAL OF CHEMICAL RESEARCH 2007 463
15H, Ar–H), 7.58(s, 1H, =CH); IR (KBr, cm-1): 3033, 2976, 1679,
1641, 1610, 1355, 1140, 752, 700; HRMS(m/z): Calcd. For C26H23O
[M+ + H]: 351.1743. Found: 351.1750.
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K. Asakawa and H. Yamamoto, J. Am. Chem. Soc., 1999, 121, 892.
T. Nakano, S. Irifune, A. Umano, Y. Ishii and M. Ogawa, J. Org. Chem.,
1987, 52, 2239.
W. Kenichi and I. Atsushi, Bull. Chem. Soc. Jpn, 1982, 55, 3208.
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I. Nasser and F. Kazemi, Tetrahedron, 1998, 54, 9475.
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X.C. Tao, R.Z. Liu, Q.H. Meng, Y.Y. Zhao, Y.B. Zhou and J.L. Huang,
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3
(h): M.p. 117–118°C (m.p8. 116–117°C); 1H NMR (CDCl3,
ppm):1.35(d, 3H, J = 7.6 Hz, CH3), 2.02(s, 3H, CH3), 2.40(m, 1H,
CH–CH3), 3.97 (m, 1H, CH–Ph), 7.06–7.36 (m, 10H, Ar–H); IR
(KBr, cm-1): 3062, 2976, 2867, 1693, 1626, 1498, 1342, 755, 725,
699; Mass (m/z,%): 262(M+, 100).
4
5
6
7
8
9
Received 5 June 2007; accepted 2 August 2007
Paper 07/4685 doi: 10.3184/030823407X237803
10 Z.G. Hu, J. Liu, G.A. Li and Z.B. Dong, J. Chem. Res., 2003, 778.
11 Z.G. Hu, J. Liu, G.A. Li, Z.B. Dong and W. Li, J. Chin. Chem. Soc., 2004,
581.
12 Z.G. Hu, J. Liu, Z.B. Dong, L.L. Guo, D. Wang and P.L. Zeng, J. Chem.
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13 Z.G. Hu, J. Liu, P.L. Zeng and Z.B. Dong, J. Chem. Res., 2004, 55.
14 Z.G. Hu and Z.B. Dong, J. Chem. Res., 2005, 603.
15 Z.G. Hu and Z.B. Dong, J. Chem. Res., 2005, 252.
16 E.L. Robert, J.D. Elmer and M.N. Nancy, J. Am. Chem. Soc., 1953, 75,
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