Surfactant-catalyzed addition of higher thiols to N-Aryl substituted maleimides

Article abstract of DOI:10.1080/00397911.2013.853192

The cationic-type surfactant-catalyzed conjugate addition reaction of long-alkyl-chained thiols with N-aryl-substituted maleimides in water as a green reaction medium afforded the corresponding thia-Michael adducts in moderate to good yields.

Full text of DOI:10.1080/00397911.2013.853192

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Surfactant-Catalyzed Addition of Higher
Thiols to N-Aryl Substituted Maleimides
A. Yıldırım a
a Department of Chemistry , Uludağ University , Bursa , Turkey
Accepted author version posted online: 08 Nov 2013.Published
online: 19 Mar 2014.
To cite this article: A. Yıldırım (2014) Surfactant-Catalyzed Addition of Higher Thiols to N-Aryl
Substituted Maleimides, Synthetic Communications: An International Journal for Rapid Communication
of Synthetic Organic Chemistry, 44:8, 1137-1141, DOI: 10.1080/00397911.2013.853192
To link to this article: http://dx.doi.org/10.1080/00397911.2013.853192
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Synthetic Communications®, 44: 1137–1141, 2014
Copyright © Taylor & Francis Group, LLC
ISSN: 0039-7911 print/1532-2432 online
DOI: 10.1080/00397911.2013.853192
SURFACTANT-CATALYZED ADDITION OF HIGHER
THIOLS TO N-ARYL SUBSTITUTED MALEIMIDES
A. Yıldırım
Department of Chemistry, Uludag˘ University, Bursa, Turkey
GRAPHICAL ABSTRACT
Abstract The cationic-type surfactant-catalyzed conjugate addition reaction of long-alkyl-
chained thiols with N-aryl-substituted maleimides in water as a green reaction medium
afforded the corresponding thia-Michael adducts in moderate to good yields.
[Supplementary materials are available for this article. Go to the publisher’s online
edition of Synthetic Communications® for the following free supplemental resource(s):
Full experimental and spectral details.]
Keywords Alkyl thiols; green chemistry; thia-Michael addition; water
INTRODUCTION
The Michael reaction is one of the most important ways to form C-C bonds. In
this reaction conjugate addition occurs between electron-poor olefins and C nucleo-
philes. The reaction of S nucleophiles (thiols) with polarized double bonds may be
represented as a thia-Michael type addition for the construction of the C-S bond.[1]
Numerous methods have been reported for the conjugated addition of thiols to polar-
ized double bonds through the activation of thiol nucleophiles by bases,[1] acids,[2,3]
or ionic liquid systems.[4–7] Most Michael adducts were obtained in toxic organic
Received September 14, 2013.
Address correspondence to A. Yıldırım, Department of Chemistry, Uludag˘ University, Bursa,
16059, Turkey. E-mail: yildirim@uludag.edu.tr
1137

1138
A. YILDIRIM
solvents.[8–10] Generally water alone is a poor solvent for the hydrophobic reagents.
Surface active agents are capable adequately dissolving these reagents in water by
micellar effects.
The solvent is the main component in many organic syntheses. It is used as the
reaction medium, as well as for the separation and purification of the reaction product.
There are many common organic solvents that have adverse health effects. Most of the
halogenated solvents and benzene are strongly carcinogenic. Therefore, knowledge of
alternative, greener solvents is important. Water has been successfully employed as a
versatile and alternative green solvent in a variety of organic reactions and synthesis
methodologies. Kumar et al. developed an efficient methodology for the addition of
thiols to N-aryl maleimides.[11] They have used only water-soluble 2-mercaptoethanol
and mono-halogenated aromatic thiols as nucleophiles. There are no prior stud-
ies in the literature related to Michael addition of long-hydrocarbon-chained alkyl
thiols to N-aryl maleimides in water. For instance, Jegelka and Plietker used only
1-hexadecanethiol as a nucleophile in benzene solvent.
This article describes a simple and efficient one-pot procedure for the addition
of higher aliphatic thiols to N-aryl-substituted maleimides using cetylpyridinium
bromide (CPB) or cetyl trimethylammonium bromide (CTAB) catalyst and water as
a green solvent under mild and neutral conditions. The reaction in this study pro-
ceeded efficiently at room temperature under micellar catalysis and adduct thus
obtained was isolated by simple vacuum filtration.
RESULTS AND DISCUSSION
The N-Aryl maleimides 1 used in this study were prepared by condensation of
maleic anhydride with different anilines in ether, followed by refluxing the obtained
maleamic acid in acetic anhydride and in the presence of fused sodium acetate to give
the corresponding maleimide. The selected alkyl thiols are insoluble in water. To facil-
itate their dispersion and to accelerate the reaction in water medium, CPB or CTAB
were used as catalyst (10% mmol/mmol). Cationic surfactant, particularly quaternary
ammonium bromide, in aqueous media has been proved to enhance the reactivity of
water-mediated organic reactions via the formation of micelles or vesicular cavities.[12]
As seen in Scheme 1, the addition reactions of the corresponding thiols in the pres-
ence of either CPB or CTAB proceeded with complete chemoselectivity and afforded
only the desired thia-Michael adducts in good yields.
The experimental results are summarized in Table 1. The surfactant CPB is more
soluble in water. Consequently in the presence of its catalytic activity the adducts
Scheme 1. Reaction conditions of thia-Michael addition.

Thia-MICHAEL ADDITION OF FATTY THIOLS
1139
Table 1. Aqueous thia-Michael addition in the presence of 10% mmol/mmol
CTAB or CPB
Entry
R
Thiol (n)
Adduct
Yielda
Yieldb
1
2
3
4
5
6
7
8
9
H
10
10
10
14
14
14
16
16
16
2a
2b
2c
2d
2e
2f
2g
2h
2i
85
84
78
80
85
86
79
92
84
98
89
97
95
98
86
82
82
91
p-OCH3
p-Br
H
p-OCH3
p-Br
H
p-OCH3
p-Br
aYield in the presence of CTAB after crystallization.
bYield in the presence of CPB after crystallization.
were obtained with slightly great yields than in the presence of catalytic activity of
CTAB. Known surfactants, like those used in this study, form a normal-phase micelle
in water, and the hydrophobic interior part of this micelle acts as a reaction realization
center. It provides an excellent reaction medium for Michael addition reaction by dis-
solving the water-insoluble N-aryl maleimides and higher thiols (Fig. 1). No reaction
occurs in the absence of CTAB and CPB. Because the long-chain thiols are practically
insoluble in water without the assistance of the surface active agents, it seems difficult
Figure 1. Possible addition mechanism via synchronous four-membered cyclic transition state.

1140
A. YILDIRIM
for the reaction to proceed through an ionic mechanism. Nonionic reaction in this
hydrophobic interior probably proceeds via a synchronous four-membered cyclic
transition state (Fig. 1).[12–13]
As a result we can conclude that the thia-Michael addition reaction proceeded
efficiently under milder and greener reaction conditions.
EXPERIMENTAL
Instrumentation and Materials
All reagents and solvents were purchased from either Merck or Sigma-Aldrich
and used without further purification. Thin-layer chromatography (TLC) was per-
formed using silica gel (60 F254, Merck, Darmstadt, Germany) plates. Melting points
were recorded on a Büchi melting point B-540 apparatus (Büchi Labortechnik AG in
Flawil, Switzerland). The NMR spectra were measured using a Varian Mercury Plus
spectrometer (400MHz) (Varian Inc., California, USA) in CDCl3 using telramethyl-
silane (TMS) as an internal standard. Chemical shifts (δ) are reported in parts per
million (ppm) and J values in hertz.
Typical Experimental Procedure for the Preparation
of Thia-Michael Adducts
To a 100-mL round-bottom flask containing (40mL) of distilled water, were
added CTAB or CPB (10mmol%) and stirred at room temperature. To this mix-
ture 1-dodecanethiol (0.35g, 1.56mmol) was added in one portion, followed by
N-phenylmaleimide (1) (0.3g, 1.56mmol) added portionwise. Stirring was continued
for an additional 1 h at room temperature. As the reaction completed (monitored
by thin-layer chromatography, TLC) the precipitated product was collected by vac-
uum filtration and dried at room temperature. Thereafter it was crystallized from
ethanol/ethyl acetate as a white crystalline solid.
SUPPORTING INFORMATION
Structural characterization data and NMR spectra are available online.
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