Characterization and comparative studies on conventional and microwave synthesis of some disulfides

Article abstract of DOI:10.1080/10426507.2013.769984

Some disulfide derivatives have been prepared by microwave assisted synthesis methodology from thiophthalimides(sulfenimides) and thiols in a modified microwave oven under reflux at 600 Watt in ethanol. Elucidation of the structures of the synthesized com

Full text of DOI:10.1080/10426507.2013.769984

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Phosphorus, Sulfur, and Silicon and the
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Characterization and Comparative
Studies on Conventional and Microwave
Synthesis of Some Disulfides
Nalan Turkoz Karakullukcu a , Hasan Yakan a , Seyhan Ozturk a &
Halil Kutuk a
a Chemistry Department, Faculty of Arts and Sciences , Ondokuz
Mayis University , Atakum , Samsun , Turkey
Accepted author version posted online: 05 Apr 2013.Published
online: 20 Sep 2013.
To cite this article: Nalan Turkoz Karakullukcu , Hasan Yakan , Seyhan Ozturk & Halil Kutuk (2013)
Characterization and Comparative Studies on Conventional and Microwave Synthesis of Some
Disulfides, Phosphorus, Sulfur, and Silicon and the Related Elements, 188:11, 1576-1583, DOI:
10.1080/10426507.2013.769984
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Phosphorus, Sulfur, and Silicon, 188:1576–1583, 2013
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426507.2013.769984
CHARACTERIZATION AND COMPARATIVE STUDIES
ON CONVENTIONAL AND MICROWAVE SYNTHESIS
OF SOME DISULFIDES
Nalan Turkoz Karakullukcu, Hasan Yakan, Seyhan Ozturk,
and Halil Kutuk
Chemistry Department, Faculty of Arts and Sciences, Ondokuz Mayis University,
Atakum, Samsun, Turkey
GRAPHICAL ABSTRACT
Abstract Some disulfide derivatives have been prepared by microwave assisted synthesis
methodology from thiophthalimides(sulfenimides) and thiols in a modified microwave oven
under reflux at 600 Watt in ethanol. Elucidation of the structures of the synthesized compounds
has been performed by IR, 1H NMR, and 13C NMR spectroscopic methods.
[Supplemental materials are available for this article. Go to the publisher’s online edition of
Phosphorus, Sulfur, and Silicon and the Related Elements for the following free supplemental
files: Additional figures]
Keywords Disulfides; cysteine; 2-mercaptobenzimidazole; 2-mercaptonicotinic acid; mi-
crowave heating
INTRODUCTION
Microwave heating has emerged as a powerful technique to promote a variety of
chemical reactions.1 High-speed microwave-assisted chemistry has attracted a consid-
erable amount of attention in recent years.2 Since the pioneering work of Gedye3 and
Giguere/Majetich4 in 1986, microwave irradiation has frequently been employed to accel-
erate organic chemical transformations for many organic reactions.
Received 25 May 2012; accepted 21 January 2013.
We would like to thank to the Ondokuz Mayis University (Grant No. F-391) for its financial support of this
work.
Address correspondence to Prof. Dr. Halil Kutuk, OMU Fen-Ed. Fakultesi, Kimya Bolumu, 55139 Atakum,
Samsun, Turkey. E-mail: hkutuk@omu.edu.tr
1576

SYNTHESIS OF SOME DISULFIDES
1577
The microwave-assisted synthesis offers considerable advantages over conventional
heating because of rapid heating and substantial rate enhancements of a wide range of
organic reactions.5 The increasing demand of clean and efficient chemical synthesis makes
solvent-free reactions requisite which give a more eco-friendly approach required from
both economic and environmental standpoints.6 Microwave heating has been shown to
dramatically reduce reaction times, increase product yields, and enhance product purities
by reducing unwanted side reactions compared to conventional heating methods.5,7
Recently, in the literature many studies have been reported for microwave assisted
synthesis of disulfides,8 N-arylsulfonyl imines,9 1,2,4-triazol-5-one derivatives,10 bicyclic
thiazolo-pyrimidine and pyrimido-thiazine derivatives,11 N-bromosulfonamides,12 1,2,4-
benzothiadiazines,13 benzothiazole,14 and tetrathiomolybdate.15
Disulfides are found in numerous natural products and biologically significant func-
tional materials. For example, diallyl disulfide is the active constituent of garlic and the
antibacterial disulfide monoxide is also present in alicin.16 Some disulfides have antitu-
mor activity.17 Similarly, compounds having disulfide bonds play a vital role in living
organisms.18
Disulfides are also key intermediates in a wide variety of organic synthetic pro-
cesses. Industrially, disulfides find wide application as vulcanizing agents for rubbers and
elastomers, giving them excellent tensile strength.19 We now report that some disulfide
derivates are obtained with microwave heating.
RESULTS AND DISCUSSION
Disulfide derivatives were synthesized by treating thiophthalimides 1 with thiols
2–4 by using microwave irradiation, as described in Scheme 1. Microwave reactions were
carried out under reflux in ethanol as solvent at 600 Watt power output. Thiophthalimides
were prepared according to the literature.20
By using 600 W (2450 MHz, a wavelength of 12.2 cm and an energy of 0.94 J/mol)
microwave irradiation, 5–7a, b were obtained under reflux in ethanol. In fact, these products
could not be obtained under classical heating, even after prolonged heating session.
Elucidation of the structures of the synthesized compounds was in accordance with
the proposed structures. Comparison of the IR spectra at each step clearly indicated the
formation of disulfides, generally by the disappearance of the C O stretching band at
about 1741 cm−1 and the S N stretching band at about 1071 cm−1 in sulfenimides, and the
appearance of a new S S band at about 525 cm−1 in disulfides. The current experimental
results for reaction times, yields, decomposition points, and Rf values are summarized in
Table 1.
1
The characteristic IR vibrations, and H NMR, and 13C NMR chemical shifts are
given in Tables 2, and 3, respectively. The spectra are in agreement with the structures of
the synthesized disulfides. Related experimental results are collated in Table 4.
The conventional mechanism for the synthesis of disulfides is shown in Scheme 2.22
CONCLUSIONS
In this study, the microwave-assisted synthesis method has been compared with
the classical method. The synthesis of some disulfides which is not possible by classical
heating methods may be obtained only by using 600 W microwave irradiation with reflux in
ethanol. The notable advantages of this method are easy and quick work-up, no undesirable

1578
N. T. KARAKULLUKCU ET AL.
Scheme 1
by-products occur. This study describes a successful approach for the synthesis of some
disulfides using a modified microwave oven. Discovered advantages of using microwaves
over traditional heating methods for performing an organic reaction included better yields,
shorter reaction times, reduction of by-products, and no thermal decomposition of products.7
EXPERIMENTAL
All raw materials and solvents were purchased from Aldrich and Merck Chemical
Company and were used without further purification. IR spectra were recorded on a Bruker
Vertex 80v spectrophotometer. 1H NMR and 13C NMR spectra were determined in DMSO-
d6 at 400 MHz in an Avence II NMR spectrometer and in CDCl3 at 200 MHz in a BRUKER
AC 200NMR spectrometer using TMS as the internal standard. Melting points were mea-
sured with a Gallenkamp electrothermal apparatus and are uncorrected. Reactions were
monitored by thin-layer chromatography (TLC) on Merck plates. The disulfide derivatives
Table 1 The reaction time, yields, decomposition points, and Rf values for the
synthesized disulfides under microwave irradiation (600 W)
Compounds
Time (min.)
Yield (%)
◦C
∗Rf
5a
5b
6a
6b
7a
7b
120
145
70
90
220
245
63
58
43
48
45
55
222
220
Oil
172
177
148
0.33
0.35
0.31
0.30
0.29
0.28
∗Solvent conditions: mixture of n-butanol, acetic acid, and water (4:1:1).

SYNTHESIS OF SOME DISULFIDES
1579
Scheme 2
5–7a, b were synthesized under microwave irradiation (600 W) by using a domestic mi-
crowave (BOSCH HMT 812 C) oven that was modified by fitting a reflux system and an
internal camera was used for all synthesis as shown in Figure 1.23
Table 2 The characteristic IR vibrations (cm−1) data for the synthesized compounds
Compounds
υC
(Arom.)
υS
υC
υ
υC
υ
υC
O
H
S
H
NH
N
OH
5a
5b
6a
6b
7a
7b
3033
625
2950—2870
—
2915–2860
—
2919–2863
—
3200
1509
1505
—
—
1552
1551
—
—
—
—
1590
1582
1675
1596
3030
3019
3050
3055
3057
620
618
684
643
684
3220
∗
∗
3300–2710
3420–2550
3155
—
—
3151
∗NH band was under the OH band.

1580
N. T. KARAKULLUKCU ET AL.
Table 3 1H NMR and 13C NMR chemical shifts spectral data for synthesized compounds
Chemical Shifts (δ), ppm
s: singlet d: doublet t: triplet dd: doublet of doublets
DMSO-d6 and CDCl3 signals are shown at 2.54 and 7.26 ppm for 1H NMR and 39.50 and 77.2 ppm in 13
C
NMR, respectively.21
Compounds
1H NMR
13C-NMR
5a
2.06 (3H, s, –CH3); 5.00 (1H, s, –NH); 7.26–7.29
(2H, d); 7.36–7.38 (2H, d); 7.51–7.58 (2H; dd, J
= 7.46 Hz); 7.75–7.84 (2H, dd, J = 9.14 Hz)
5,02 (1H, s, -NH); 7,14–7,19 (1H, dd, J = 6.58 Hz);
7,28–7,31 (2H; dd, J = 6.12 Hz); 7,35–7,38 (2H;
dd, J = 6.26 Hz); 7,50–7,61 (2H; dd, J =
8.98 Hz); 7,77–7,87 (2H, dd, 8.76 Hz)
21.0, 124.8, 125.0, 128.5, 129.1,
130.5, 130.7, 137.9, 138.7
5b
114.5, 123.3, 125.6, 129.1, 129.4,
135.4, 138.1, 140.5
6a
6b
2.06 (2H, s, –NH2); 2.42 (3H, s, –CH3); 2.81–2.91
(2H, d); 3.33–3.51 (1H, t); 7.71–7.79 (2H, d);
8.11–8.18 (2H, d); 11.33 (1H, s, -OH)
22.2, 46.8, 56.9, 127.7, 128.0, 129.9,
136.2, 176.3
2.00 (2H, s, –NH2); 3.17–3.21 (2H, d); 3.78–3.83
(1H, t); 7.04–7.08 (1H, dd, J = 7.67 Hz);
7.10–7.15 (2H, dd, J = 7.83 Hz); 7.18–7.24 (2H,
dd, J = 9.45 Hz); 11.30 (1H, s, –OH)
45.6, 56.9, 126.5, 129.3, 129.4,
133.2, 176.3
7a
7b
2.06 (3H, s, -CH3); 7.09–7.15 (2H, d); 7.33–7.37
(2H, d); 7.71–7.88 (1H, dd, J = 9.64 Hz);
8.26–8.28 (1H, dd, J = 6.47 Hz); 8.50–8.64 (1H,
dd, J = 8.66 Hz); 13.89 (1H, s, –OH)
21.1, 121.7, 123.3, 128.8, 130.0,
133.0, 137.2, 139.8, 153.0, 167.1,
180.3
7.02–7.05 (1H, dd, J = 6.62 Hz); 7.12–7.17 (2H, dd,
J = 7.78 Hz); 7.19–7.22 (2H, dd, J = 7.82 Hz);
7.43–7.45 (1H, dd, J = 6.22 Hz); 8.22–8.25 (1H,
dd, J = 7.34 Hz); 8.69–8.71 (1H, dd, J =
6.12 Hz); 11.80 (1H, s, –OH)
122.1, 123.5, 125.6, 129.1, 129.4,
135.2, 138.4, 151.2, 170.8, 179.7
Synthesis of Substituted Thiophthalimides
N-(p-Methylphenylthio)phthalimide 1a, p-Methylthiophenol (2.60 g, 21 mmol), and
phthalimide (2.94 g, 20 mmol) were dissolved in hot pyridine-acetonitrile (18 mL, 4:5
mixture), and the resulting solution was cooled to room temperature with continuous
stirring. A solution of bromine (3.79 g, 1.22 mL, 24 mmol) in acetonitrile (10 mL) was
then added dropwise over 30 min. After a further period of 2 h, methanol (40 mL) was
added dropwise over 30 min. The products were cooled in an ice-water bath for 30 min, and
then the product 1a was filtered as a pale yellow powder. The product was recrystallized
from methanol. Yield: 81%, m.p. 202–204◦C (lit.24 204–205◦C); found C, 67.60; H, 4.28;
N, 5.28; S, 11.88; calc. for C15H11NO2S C, 66.89; H, 4.12; N, 5.20; S, 11.91%; 1H NMR
(CDCl3): δ = 2.32 (CH3, 3H, s), 7.11–7.16 (2H, d), 7.57–7.62 (2H, d), 7.73–7.80 (2H, dd
J = 7.86 Hz), 7.87–7.93 (2H, dd J = 8.24 Hz); and 13C NMR (CDCl3): δ = 21.2, 123.9,
129.9, 131.3, 131.9, 132.6, 134.5, 140.3, and 167.7.
N-(Phenylthio)phthalimide 1b, Thiophenol (2.31 g, 21 mmol), and phthalimide
(2.94 g, 20 mmol) were dissolved in hot pyridine-acetonitrile (18 mL, 4:5 mixture) and
the resulting solution was cooled to room temperature with continuous stirring. A solution
of bromine (3.79 g, 1.22 mL, 24 mmol) in acetonitrile (10 mL) was then added dropwise
over 30 min. After a further period of 2 h, methanol (40 mL) was added dropwise over
30 min. The products were cooled in an ice-water bath for 30 min, and then the product 1b

SYNTHESIS OF SOME DISULFIDES
1581
Table 4 Comparison of microwave and classical heating for synthesized compounds
Classical heating
Yield (%)
—
Microwave heating
Yield (%)
Compounds
Time (min.)
React. cond.
Time (min.)
React. cond.
5a
5b
6a
6b
7a
7b
—
—
—
—
—
—
a
a
a
a
a
a
—
120
—
145
—
70
—
90
—
—
63
—
58
—
43
—
48
—
45
—
55
b, c, d
e
b, c, d
e
—
—
—
—
—
b, c, d
e
b, c, d
e
b, c, d
e
220
—
245
b, c, d
e
aReflux in EtOH.
bWith ethanol (neat) at 360 W.
cWith reflux in ethanol at 360 W.
dWith ethanol (neat) at 600 W.
eWith reflux in ethanol at 600 W.
Note. “-” indicates the reactions could not synthesized by both conventional and microwave methods.
Figure 1 A modified domestic microwave oven23
.

1582
N. T. KARAKULLUKCU ET AL.
1
was filtered as white crystals. Yield: 84%, m.p. 161–163◦C (lit.25 160–161◦C); H NMR
(CDCl3): δ = 7.23–7.93 (arom-H, 9H,m); 13C NMR (CDCl3): δ = 124.0, 129.3, 130.9,
131.9, 134.7, 134.9, and 167.7.
Synthesis of Substituted Disulfides
General process–microwave method. A mixture of thiophthalimide
(5.00 mmol) and thiol (5.00 mmol) were ground thoroughly and then transferred to a
flask. The mixture was refluxed in ethanol (15 mL) and was irradiated in a microwave
oven at 600 W. The reaction mixture was monitored throughout the experiment with a
TLC on silica gel with a mixture of n-butanol, acetic acid, and water (4:1:1) as eluents, to
determine whether or not the reaction had terminated. When the reaction was finished, hot
water added, stirred, and filtered. Since phthalimide dissolves in hot water, disulfide was
separated from phthalimide and recrystallized by using ethanol or acetone.
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