A synthesis of diethyl alkylsulfanylmethylmalonates catalyzed by KOH in an ionic liquid

Article abstract of DOI:10.1007/s00706-008-0064-8

1-Ethyl-3-methylimidazolium bromide was used as a green recyclable alternative to volatile organic solvents for KOH catalyzed three-component synthesis of diethyl alkylsulfanylmethylmalonates from aldehydes, diethyl malonate, and alkylthiols. Graphical Abstract: A synthesis of diethyl alkylsulfanylmethylmalonates catalyzed by KOH in an ionic liquid [Figure not available: see fulltext.]

Full text of DOI:10.1007/s00706-008-0064-8

Monatsh Chem (2009) 140:205–207
DOI 10.1007/s00706-008-0064-8
ORIGINAL PAPER
A synthesis of diethyl alkylsulfanylmethylmalonates
catalyzed by KOH in an ionic liquid
Issa Yavari Æ Rahimeh Hajinasiri Æ
S. Zahra Sayyed-Alangi
Received: 24 August 2008 / Accepted: 6 September 2008 / Published online: 15 October 2008
Ó Springer-Verlag 2008
Abstract 1-Ethyl-3-methylimidazolium bromide was
used as a green recyclable alternative to volatile organic
solvents for KOH catalyzed three-component synthesis of
diethyl alkylsulfanylmethylmalonates from aldehydes,
diethyl malonate, and alkylthiols.
carbon double bonds is a useful protocol in synthetic
organic chemistry [7, 8], and it is used extensively in the
synthesis of pharmaceutical intermediates, peptide ana-
logues, antibiotics, and other biologically active molecules
and drugs [9–11]. In the past few years, a number of
alternative procedures have been developed for the conju-
gate addition of amines to a,b-unsaturated nitriles and
carbonyl compounds. In particular, various Lewis-acid-
catalyzed reactions have been reported [12–16]. Recently,
there were also some reports of this reaction conducted in
Cu(acac)2/ionic liquid [17–19], water [20, 21], b-cyclo-
dextrin in water [22], cerium ammonium nitrate [23],
HClO4–SiO2 [24], and indium(III) chloride[25]. As part of
our current studies, on the development of in situ thia-
Michael addition, we wish to report a one-pot synthesis of
sulfanylmethylmalonates catalyzed by KOH.
Keywords Alkylmalonate ꢀ Alkylthiol ꢀ Ionic liquid
Introduction
Ionic liquids (ILs) have gained tremendous attention in the
last 15 years [1–3]. They are, among other uses, solvents
and are frequently fitted with attributes like ‘‘modern,’’
‘‘green,’’ ‘‘designable,’’ ‘‘non-volatile,’’ ‘‘non-coordinat-
ing,’’ etc., although it is increasingly recognized that none
of these labels should be used lightly. Nonetheless, many
chemical reactions have been attempted and successfully
performed in IL media, and oftentimes these systems show
interesting and peculiar features. However, considerable
work in IL chemistry is still based on trial-and-error rather
than fundamental understanding and rational design. To
rationalize the differences between ILs and molecular
solvents, it is important to understand their properties
[1–6].
Results and discussion
Thus, three-component reaction of aldehyde 1, diethyl
malonate 2, and alkyl thiols 3 catalyzed by KOH proceeds
smoothly in ionic liquid to produce diethyl alkylsulfa-
nylmethylmalonates 4 in good yields (Scheme 1).
1
The products were characterized based on their IR, H
The Michael reaction has been studied for more than
one century. The conjugate addition of amines to carbon–
NMR, and 13C NMR. The mass spectra of compounds 4a–f
displayed molecular ion peaks at appropriate m/z values.
The 1H NMR spectra of 4a–f exhibited characteristic
doublets for the vicinal CH protons. The proton-decoupled
13C NMR spectra of 4a–f showed resonances in agreement
with the proposed structures.
I. Yavari ꢀ R. Hajinasiri ꢀ S. Z. Sayyed-Alangi
Chemistry Department, Science and Research Campus,
Islamic Azad University, Ponak, Tehran, Iran
The following mechanism may be invoked for the for-
mation of compounds 4. Conceivably, the starting point of
reaction is formation of the Knoevenagel condensation
adduct 6 between diethyl malonate and aldehyde 1, which
I. Yavari (&) ꢀ S. Z. Sayyed-Alangi
Chemistry Department, Tarbiat Modares University,
PO Box 14115-175, Tehran, Iran
e-mail: yavarisa@modares.ac.ir
123

206
I. Yavari et al.
Scheme 1
[emim]Br
or
[bmim]CF3SO3
EtO2C
CO2Et
O
EtO2C
CO2 Et
+
+
RCH2 SH
Ar
SCH2R
Ar
H
KOH/EtOH
4a:Ar = C6H5
4b:Ar = C6H5
4c:Ar = 4-ClC6H4
4d:Ar = 4-ClC6H4
4e:Ar = 4-MeC6H4
4f:Ar = 2-Furyl
2
3a: R = CH2CO2Me
3b: R = 2-Furyl
1a: Ar = C6H5
R = CH2CO2Me
R = 2-Furyl
R = CH2CO2Me
1b: Ar = 4-ClC6H4
1c: Ar = 4-MeC6H4
1d: Ar = 2-Furyl
R = 2-Furyl
R = CH2CO2Me
R = CH2CO2Me
undergoes Michael addition by alkylthiol 3 to produce 4
(Scheme 2).
evaporated under reduced pressure to leave the crude
product, which was purified by column chromatography on
silica gel and eluted with a mixture of n-hexane:EtOAc
(3:1) to afford pure title compounds.
In conclusion, we report a novel transformation
involving diethyl malonate and aldehydes in the presence
of alkyl thiols in ionic liquid, which affords diethyl
alkylsulfanylmethylmalonates in good yields. The advan-
tage of the present procedure is that the reaction is
performed in green and environmentally benign media by
simple mixing of the starting materials.
Diethyl 2-{[(3-methoxy-3-oxopropyl)sulfanyl](phenyl)
methyl}malonate (4a, C18H24O6S)
ꢀ
Yellow oil; yield: 0.56 g (80%). IR (KBr): m = 1740
(C=O), 2980 (CH) cm-1. EI-MS: m/z = 354 (2, M?), 309
(5), 295 (35), 235 (80), 195 (85), 119 (90), 91 (45), 87
1
3
(100), 59 (35), 45 (35); H NMR: d = 0.95 (t, J = 7.1,
Me), 1.28 (t, J = 7.1, Me), 2.46–2.70 (m, 2CH2), 3.6 (s,
3
Experimental
3
OMe), 3.90 (q, J = 7.1, OCH2), 3.92 (d, J = 11.6, CH),
3
3
3
4.23 (q, J = 7.1, OCH2),4.47 (d, J = 11.6, CH), 7.24–
7.47 (m, 5 CH) ppm; 13C NMR: d = 13.5 (Me), 13.9 (Me),
26.4 (CH2), 34.3 (CH2), 48.9 (CH), 51.3 (OMe), 58.4 (CH),
61.4 (OCH2), 61.8 (OCH2), 127.9 (CH), 128.7 (2CH),
128.8 (2CH), 140.3 (C), 166.4 (C=O), 167.0 (C=O), 171.9
(C=O) ppm.
Compounds 1–3 and the ionic liquids were obtained from
Fluka and were used without further purification. M.p.:
Electrothermal-9100 apparatus. IR Spectra: Shimadzu IR-
1
460 spectrometer. H and 13C NMR spectra: Bruker DRX-
300 AVANCE instrument; in CDCl3 at 300 and 75 MHz; d
in ppm, J in Hz. EI-MS (70 eV): Finnigan-MAT-8430
mass spectrometer, in m/z. Elemental analyses (C, H, N)
were performed with a Heraeus CHN-O-Rapid analyzer.
The results agreed favorably with the calculated values.
Diethyl 2-{[(2-furylmethyl)sulfanyl](phenyl)methyl}
malonate (4b, C19H22O5S)
ꢀ
Yellow oil; yield: 0.60 g (83%). IR (KBr): m = 1755
(C=O), 2982 (CH) cm-1. EI-MS: m/z = 362 (2, M?), 317
General procedure for the preparation of compounds 4
(5), 250 (85), 202 (90), 113 (95), 91 (35), 81 (100), 45 (35);
1H NMR: d = 0.95 (t, J = 7.1, Me), 1.28 (t, J = 7.0,
Me), 3.58 (AB q, DmAB = 51 Hz, JAB = 14.7, SCH2), 3.90
(q, 3J = 7.1, OCH2), 3.95 (d, 3J = 11.5, CH), 4.18
3
3
To a stirred solution of 0.03 g KOH in 1 cm3 of EtOH and
2 cm3 of [emim]Br was added 0.34 g (2 mmol) of 2 and
2 mmol of aldehyde 1. After 5 min, 2 mmol of alkylthiol 3
was added. After completion of the reaction (0.5–2 h), as
indicated by TLC (EtOAc/n-hexane, 2:1), the products
were extracted with Et2O (2 9 10 cm3). The solvent was
3
3
(q, J = 7.0, OCH2), 4.50 (d, J = 11.5, CH), 6.21–6.23
(m, 1 CH), 6.35–6.37 (m, 1 CH), 7.27–7.47 (m, 6 CH)
ppm; 13C NMR: d = 13.5 (Me), 13.8 (Me), 27.8 (CH2),
48.43 (CH), 58.3 (CH), 61.4 (OCH2), 61.7 (OCH2), 108.0
Scheme 2
[emim]Br or [bmim]CF3 SO3
HO
EtO2C
Ar
CO2Et
[emim]OH or [bmim]OH
EtO2C
CO2Et
+ 2
+
3
1
4
_
_
H2 O
H
5
6
123

A synthesis of diethyl alkylsulfanylmethylmalonates
207
(CH), 110.8 (CH), 127.9 (CH), 128.6 (2CH), 128.9 (2CH),
139.8 (C), 142.7 (CH), 151.7 (C), 166.4 (C=O), 166.9
(C=O) ppm.
Diethyl 2-{2-furyl[(2-methoxy-2-oxopropyl)sulfanyl]
methyl}malonate (4f, C16H22O7S)
ꢀ
Yellow oil; yield: 0.61 g (85%). IR (KBr): m = 1756
(C=O), 2982 (CH) cm-1. EI-MS: m/z = 358 (2, M?), 313
(5), 239 (75), 199 (75), 119 (80), 87 (100), 81 (95), 59 (65),
45 (75), 29 (100), 15 (70); 1H NMR: d = 1.10 (t, 3J = 7.0,
Me), 1.28 (t, 3J = 7.0, Me), 2.44–2.74 (m, 2 CH2), 3.58 (s,
Diethyl 2-{(4-chlorophenyl)[3-methoxy-3-oxopropyl)
sulfanyl]methyl}malonate (4c, C18H23 ClO6S)
ꢀ
Yellow oil; yield: 0.60 g (75%). IR (KBr): m = 1752
(C=O), 2980 (CH) cm-1. EI-MS: m/z = 402 (2, M?), 357
(5), 343 (25), 283 (80), 243 (85), 119 (95), 87 (100), 91
3
3
OMe), 4.00 (d, J = 11.5, CH), 4.04 (q, J = 7.0, OCH2),
3
3
4.21 (q, J = 7.0, OCH2), 4.56 (d, J = 11.5, CH), 6.35–
6.39 (m, 2 CH), 7.21 (d, 3J = 7.0, 2CH), 7.49 (d,
3J = 10.9, CH) ppm; 13C NMR: d = 13.7 (Me), 13.8
(Me), 26.2 (CH2), 34.5 (CH2), 41.8 (CH), 51.3 (OMe), 56.4
(CH), 61.7 (OCH2), 61.9 (OCH2), 107.9 (CH), 110.8 (CH),
142.7 (CH), 157.4 (C), 166.4 (C=O), 166.7.1 (C=O), 171.9
(C=O) ppm.
1
3
(50), 59 (45), 45 (35); H NMR: d = 0.99 (t, J = 7.1,
Me), 1.28 (t, J = 7.0, Me), 2.56–2.66 (m, 2CH2), 3.58 (s,
3
3
3
OMe), 3.91 (q, J = 7.1, OCH2), 3.95 (d, J = 11.5, CH),
4.23 (q, 3J = 7.0, OCH2), 4.48 (d, 3J = 11.5, CH), 7.21 (d,
3
3J = 7.0, 2CH), 7.48 (d, J = 7.0, 2CH) ppm; 13C NMR:
d = 13.6 (Me), 13.9 (Me), 26.5 (CH2), 34.22 (CH2), 48.1
(CH), 51.3 (OMe), 58.2 (CH), 61.6 (OCH2), 61.9(OCH2),
128.7 (2CH), 130.6 (2CH), 133.1 (C), 139.5 (C), 166.3
(C=O), 166.9 (C=O), 171.9 (C=O) ppm.
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ꢀ
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