Mild synthesis of N -acylsulfenamides from arylamides and disulfides

Article abstract of DOI:10.1080/10426507.2015.1012670

An efficient and new method was developed to synthesize N-acylsulfenamides via NaH-promoted sulfenylation of benzamides with readily available disulfides under mild conditions. A series of N-acylsulfenamides were easily obtained in moderate to high yields. Moreover, the obtained N-acylsulfenamides were used as thiolating reagents in the synthesis of sulfenylpyrroles and 3-sulfenylbenzofurans.

Full text of DOI:10.1080/10426507.2015.1012670

Phosphorus, Sulfur, and Silicon and the Related Elements
ISSN: 1042-6507 (Print) 1563-5325 (Online) Journal homepage: http://www.tandfonline.com/loi/gpss20
Mild Synthesis of n-Acylsulfenamides from
Arylamides and Disulfides
Xing-Song Zhang & Xiao-Hong Zhang
To cite this article: Xing-Song Zhang & Xiao-Hong Zhang (2015): Mild Synthesis of n-
Acylsulfenamides from Arylamides and Disulfides, Phosphorus, Sulfur, and Silicon and the
Related Elements, DOI: 10.1080/10426507.2015.1012670
To link to this article: http://dx.doi.org/10.1080/10426507.2015.1012670
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Date: 20 September 2015, At: 12:42

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MILD SYNTHESIS OF N-ACYLSULFENAMIDES FROM ARYLAMIDES AND
DISULFIDES
Xing-Song Zhang, Xiao-Hong Zhang*
College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou 325035, China
*Author to whom correspondence should be addressed; E-Mail: kamenzxh@163.com
Abstract An efficient and new method was developed to synthesize N-acylsulfenamides via
NaH-promoted sulfenylation of benzamides with readily available disulfides under mild
conditions. A series of N-acylsulfenamides were easily obtained in moderate to high yields.
Moreover, the obtained N-acylsulfenamides were used as thiolating reagents in the synthesis of
sulfenylpyrroles and 3-sulfenylbenzofurans.
Keywords N-acyl sulfenamides, sulfenylation, thiolating reagents
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INTRODUCTION
Sulfenamide derivatives have aroused much interest because of their practical application
in biochemistry and pharmacological chemistry,1 including antibacterial agents,2 enzyme
inhibition,3 and as the prodrugs of carbamazepine,4 metformin5 or NH-acidic compounds.6
Moreover, sulfenamides were also potential precursors for the synthesis of numerous
pharmaceuticals and agrochemicals owing to their unique S-N bonds.7 For example,
N-(phenylthio)phthalimide,8 N-(phenylthio)succinimide9 and 1,2-benzisothiazolin-3-one10 were
used as versatile thiolating reagents in the synthesis of diverse sulfur-containing molecules.
However, only limited efficient methods have been reported for the synthesis of N-acyl
sulfenamides,11 possibly due to the difficult formation of S-N bonds. For example, to date
N-acylsulfenamides are usually obtained by the reaction of amides with the toxic and unstable
sulfenyl chlorides,12 which are generally prepared by chlorination of thiols or disulfides with
poisonous / corrosive chlorine gas (Scheme 1, eq. 1). An alternative method was the acylation of
not easily available arenesulfenamides using acyl chlorides as acylation reagent.13 However, a
sulfenyl chloride is also required for the synthesis of the arenesulfenamides (Scheme 1, eq. 2).14
It is well-known that the use of both sulfenyl chlorides and acyl chlorides, would inevitability
bring about environmental pollution.
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Therefore, the development of “green” and efficient strategies for the synthesis of
N-acylsulfenamides is highly desired. Based on the aforementioned synthetic methods and
considering the weak acidity of amides, we envisage that N-acylsulfenamides could be prepared
via the sulfenylation of benzamides with a disulfide with the aid of base. Fortunately, the
reaction proceeded smoothly to provide a series of N-acylsulfenamides in moderate to high
yields when using NaH as the base under mild conditions. The obtained N-acylsulfenamides can
also act as useful thiolating reagents to achieve diverse sulfur compounds. Herein, we describe
our results in detail.
RESULTS AND DISCUSSION
We began our study with the reaction between benzamide andh phenyl disulfide to explore
the optimal reaction conditions (Table 1). Benzamide was initially treated with NaH (1 equiv.) in
THF at room temperature for about 1 h, then phenyl disulfide (1.5 equiv.) was added and the
mixture was stirred for another 36 h, giving the aimed product N-(phenylthio)benzamide (3) in
30% yield (entry 1). We supposed that the low yield was caused by the low loading of NaH.
Therefore, the amount of NaH was increased to 2 and 3 equivalents, and the yields sharply
increased to 52% and 96%, respectively (entries 2-3). When 4 equivalents of NaH were used, no
obvious yield improvement was observed (entry 4). Subsequently, the loading of phenyl
disulfide was screened. We found that N-(phenylthio)benzamide was obtained in lower yields
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when we used 1.0 and 1.2 equivalents disulfide (entries 5-6). Besides, shortening the reaction
times to 24 h (12 h) also led to lower yields (entries 7-8). If benzamide, diphenyl disulfide and
NaH were added into the reaction system at the same time, only a 25% yield of
N-(phenylthio)benzamides was isolated (entry 3). The results showed that the sulfenylation
proceed via the base-deprotonation of benzamide to form the benzamide anion, which then
reacted with diphenyl disulfide to give the target molecules. Thus, the optimal condition was
finally identified as following: benzamide (1.0 equiv.) was initially treated with NaH (3 equiv.)
in THF (3.0 mL) at room temperature for 1 h, then diphenyl disulfide (1.5 equiv.) was added and
the mixture was stirred for another 36 h at room temperature.
With the optimal reaction conditions determined, the scope of disulfides was next investigated
(Table 2). As expected, various aryl disulfides worked well under the reaction conditions. A
range of functional groups, such as methyl, methoxy, fluoro, chloro, and nitro substituents were
tolerated in this sulfenylation procedure. Generally, electron-withdrawing groups on the phenyl
ring of disulfides were beneficial for the transformation, whereas electron-donating substituents
decreased the efficiency (products 4-12). For example, the disulfides with chloro, and nitro
groups gave the N-acylsulfenamides in more than 79 % yields (products 8-12), while disulfides
bearing methyl and methoxy moieties generated the corresponding products in less than 60%
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yields (products 4 and 5). To our delight, treatment of the 1,2-di(pyridin-2-yl)disulfide and
1,2-di(thiophen-2-yl)disulfide with benzamide also afforded the sulfenamides 13 and 14 in 41%
and 59 % yields, respectively.
Subsequently, a series of arylamides bearing different substituents on the phenyl groups
were evaluated. The results disclosed that the reaction seemed to be insensitive to the electronic
effects on the phenyl ring of the arylamides. For instance, both arylamides with
electron-donating substituents (such as methyl and methoxyl groups) and those bearing
electron-withdrawing groups (including fluoro, chloro and bromo) can furnish the desired
products 15-19, 22 in moderate to high yields. However, arylamides bearing strong
electron-withdrawing groups, such as NO2 and CF3, reacted with diphenyl disulfide to give
products 20 and 21 in lower yields of 40% and 37%, respectively. Gratifyingly, both
α-naphthamide and 2-iodobenzamide can undergo the reaction, providing the corresponding
N-acylsulfenamides 24 and 25 in 21% and 28% yields. It is noteworthy that the reaction
conditions are compatible with aliphatic amides. Cyclohexanecarboxamide and butyramide, for
instance, underwent the reaction with diphenyl disulfide to furnish the products 26, 27 in 38 %
and 42 % yields, respectively. Meanwhile, 4-methylbenzamide was also successfully reacted
with bis(2-chlorophenyl), bis(3,5-dichlorophenyl) and bis(4-nitrophenyl) disulfide, to afford the
compounds 28-29 in good yields.
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The successful synthesis of N-acylsulfenamides encouraged us to extend their application
as sulfur sources for other reactions. As we know, pyrroles15 and benzofurans16 are important
classes of heterocyles with naturally occurrence and biological activities. There are different
methods available in the literature for the synthesis of sulfenyl pyrroles17 and
3-sulfenylbenzofurans.18 Sulfenyl chlorides or thiols are commonly used as sulfenylating
reagents. But we wished to use N-acylsulfenamides as new sulfenylating reagents for the
synthesis of sulfenylpyrroles and 3-sulfenylbenzofurans. We found that 2-phenylthio-1H-pyrrole
(30) was obtained in high yield under mild conditions when 2 mol% of AlCl3 (Scheme 2, eq. 3)
was used as catalyst. Moreover, the electrophilic cyclisation of 2-alkynylanisoles with
N-(phenylthio)benzamide was accomplished well to give the target molecule 31 in 83% yield in
the presence of 1.0 equivalent of FeCl3 at low temperature (Scheme 2, eq. 4). The results
demonstrated that N-acylsulfenamides can act as efficient and new sulfur sources to provide a
series of sulfur-containing compounds.
CONCLUSION
In summary, we have developed an efficient and mild method for the synthesis of
N-acylsulfenamides via sulfenylation of carboxamides with readily available disulfides under
mild conditions. A series of N-acylsulfenamides with various groups can be obtained in moderate
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to high yields. Moreover, N-acylsulfenamides could be used as new thiolating reagents to access
to a variety of sulfur compounds, such as sulfenylpyrroles and 3-sulfenylbenzofurans.
EXPERIMENTAL
Materials and methods
Chemicals were either used as purchased or purified by standard techniques. NaH was used
as 60% dispersion in mineral oil. NMR spectroscopy was performed on a Bruker Avance-500
spectrometer operating at 500 MHz (1H NMR) and 125 MHz (13C NMR) using CDCl3 and
Actone-D6 as the solvent with tetramethylsilane (TMS) as an internal standard at room
temperature. The high resolution mass spectrometer was Waters Micromass GCT Premier (ESI).
Melting points were determined on a digital melting-point apparatus from Beijing TECH
Instrument CO. LTD and are uncorrected. All reactions are performed under air atmosphere.
Column chromatography was performed using EM Silica gel 60 (300-400 mesh).
Typical experimental procedure for NaH promoted sulfenylation of benzamides
with disulfide
The benzamide (0.2 mmol), NaH (3 equiv.) and dry THF (3 mL) were added to a two
necked flask in turn and stirred at room temperature for 1h. Then disulfide (1.5 equiv.) was
added into the mixture and stirred for another 36 h at room temperature. During the whole
reaction process, the system was kept turbid owing to the difficult solubility of NaH in THF.
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Then the resulting mixture was filtered and washed with EtOAc to give the solvent, which was
concentrated in vacuo and the residue was purified by flash column chromatography on a silica
gel to give the desired product.
2-(Phenylthio)-1H-pyrrole. Pyrrole (0.4 mmol), N-(phenylthio)benzamide (0.2 mmol), AlCl3
(2 mol%) and DMA (2 mL) were put in a two necked flask and stirred at 90 °C for 16 h and then
cooled to room temperature. The solution was extracted with EtOAc (3 x 10 mL) and the
combined organic extracts washed with brine (3 x 10 mL) before being dried over MgSO4 and
concentrated. The solvent was concentrated in vacuo and the residue was purified by flash
column chromatography on a silica gel to give the desired product.
2-Phenyl-3-(phenylthio)benzofuran. 1-Methoxy-2-(phenylethynyl)benzene (0.2 mmol),
N-(phenylthio)benzamide (1.2 equiv.), FeCl3 (1.0 equiv.) and CH2Cl2 (3 mL) were put in a two
necked flask in turn and stirred at 50 °C for 24 h, and then cooled to room temperature. The
solvent was concentrated in vacuo and the residue was purified by flash column chromatography
on silica gel to give the desired product.
N-(Phenylthio)benzamide (3)13
N-(p-Tolylthio)benzamide (4)13
1
N-[(4-Methoxyphenyl)thio]benzamide (5). White solid, m. p. 104-106 °C. H NMR
([D6]acetone) δ 9.24 (s, 1H), 7.96 (d, J = 8.5 Hz, 2H), 7.59-7.55 (m, 1H), 7.50-7.46 (m, 4H),
6.93-6.90(m, 2H), 3.78 (s, 3H). 13C NMR ([D6]acetone) δ 169.1, 160.7, 134.9, 132.8, 131.5,
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130.9, 129.4, 128.6, 115.4, 55.7; HRMS (ESI): calcd. for C14H14NO2S+ ([M+H]+): 260.0740,
found: 260.0744.
N-[(2-Fluorophenyl)thio]benzamide (6). Yellow solid, m. p. 99-100 °C. 1H NMR
([D6]acetone) δ 9.23 (s, 1H), 8.04-8.03 (m, 2H), 8.03 (d, J = 1.5 Hz, 1H), 7.64-7.61 (m, 1H),
7.55-7.52 (m, 2H), 7.33-7.29 (m, 1H), 7.27-7.23 (m, 1H), 7.20-7.12 (m, 2H).13C NMR
([D6]acetone) δ 169.2, 158.6 (d, J = 240.0 Hz), 134.4, 133.2, 129.5, 128.8, 128.7 (d, J = 7.5 Hz),
127.7 (d, J = 16.3 Hz), 127.2 (d, J = 2.5 Hz), 125.8 (d, J=3.8 Hz), 116.2 (d, J=20.0 Hz); HRMS
(ESI): calcd. for C13H11FNOS+ ([M+H]+): 248.0540, found: 248.0544.
N-[(3-Fluorophenyl)thio]benzamide (7). White solid, m. p. 100-102 °C. 1H NMR
([D6]acetone) δ 9.39 (s,1H), 8.05-8.03 (m,2H), 7.65-7.61 (m, 1H), 7.55-7.52 (m, 2H), 7.40-7.35
(m, 1H), 7.12-7.10 (m, 1H), 7.05-7.03 (m, 1H), 6.95-6.91 (m, 1H). 13C NMR ([D6]acetone) δ
169.1, 164.0 (d, J = 245.0 Hz), 143.9 (d, J = 7.5 Hz), 134.4, 133.2, 131.6 (d, J = 8.8 Hz), 129.5,
128.8, 120.1 (d, J = 3.8 Hz), 113.4 (d, J = 21.3 Hz), 111.1 (d, J = 23.8 Hz); HRMS (ESI): calcd.
for C13H11FNOS+ ([M+H]+): 248.0540, found: 248.0539.
N-[(4-Chlorophenyl)thio]benzamide (8)13
1
N-[(2-Chlorophenyl)thio]benzamide (9). White solid, m. p. 129-131 °C. H NMR (CD3Cl)
δ 7.88 (d, J = 7.0 Hz, 2H), 7.60 (bs, 1H), 7.57-7.54 (m, 1H), 7.45-7.42 (m, 2H), 7.29-7.27 (m,
1H), 7.19-7.07 (m, 3H). 13C NMR ([D6]acetone). δ 169.1, 137.3, 133.0, 132.8, 129.7, 129.2,
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129.0, 127.8, 127.4, 127.2, 124.8; HRMS (ESI): calcd. for C13H11ClNOS+ ([M+H]+): 264.0244,
found: 264.0253.
1
N-[(3-Chlorophenyl)thio]benzamide (10). White solid, m. p. 130-131 °C. H NMR
([D6]acetone) δ 9.29 (s, 1H), 8.08-8.06 (m, 2H), 7.66-7.63 (m, 1H), 7.56-7.53 (m, 2H), 7.40-7.38
13
(m, 1H), 7.32-7.29 (m, 1H), 7.20-7.16 (m, 2H). C NMR ([D6]acetone) δ 169.1, 139.3, 134.3,
133.1, 130.2, 129.5, 128.8, 128.4, 127.9, 127.3, 124.4; HRMS (ESI): calcd. for C13H11ClNOS+
([M+H]+): 264.0244, found: 264.0253.
1
N-[(3,5-Dichlorophenyl)thio]benzamide (11). White solid, m. p. 129-131 °C. H NMR
([D6]acetone) δ 9.44(s, 1H), 8.06-8.05 (m, 2H), 7.66-7.63 (m, 1H), 7.56-7.53 (m, 2H), 7.26-7.25
(m, 3H). 13C NMR ([D6]acetone). δ 169.0, 145.6, 136.1, 134.0, 133.4, 129.6, 128.9, 126.3, 122.3;
HRMS (ESI): calcd. for C13H10Cl2NOS+ ([M+H]+): 297.9855, found: 297.9869.
N-[(4-Nitrophenyl)thio]benzamide (12).[13] Yellow solid, m. p. 144-146 °C. 1H NMR
([D6]acetone) δ 8.15 (d, J = 9.0 Hz, 2H), 7.91 (d, J = 7.5 Hz, 2H), 7.64-7.61 (m, 1H), 7.53-7.50
(m, 3H), 7.30 (d, J = 9.0 Hz, 2H). 13C NMR ([D6]acetone) δ 168.7, 148.3, 146.1, 133.3, 132.5,
129.2, 127.9, 124.4, 123.0; HRMS (ESI): calcd. for C13H11N2O3S+ ([M+H]+): 275.0485, found:
275.0502.
N-(Pyridin-2-ylthio)benzamide (13). Yellow solid, m. p. 67-69 °C. 1H NMR ([D6]acetone) δ
9.34 (s, 1H), 8.41-8.39 (m, 1H), 8.08-8.06 (m, 2H), 7.71-7.68 (m, 1H), 7.67-7.62 (m, 1H),
7.57-7.53 (m, 2H), 7.23-7.21 (m, 1H) 7.12-7.09 (m, 1H). 13C NMR ([D6]acetone) δ 169.0, 163.1,
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150.1 137.8, 134.6, 133.1, 129.5, 128.8, 120.9, 117.8; HRMS (ESI): calcd. for C12H11N2OS+
([M+H]+): 231.0587, found: 231.0592.
N-(Thiophen-2-ylthio)benzamide (14). White solid, m.p. 168-169 °C. 1H NMR
([D6]acetone) δ 9.31 (s, 1H), 7.10 (d, J = 7.0 Hz, 2H), 7.66-7.65 (m, 1H), 7.57-7.54 (m, 1H),
7.48-7.45 (m, 2H), 7.44-7.43 (m, 1H), 7.06-7.04 (m, 1H). 13C NMR ([D6]acetone) δ 168.7,
+
137.9, 136.3, 134.7, 133.2, 132.9, 129.4, 128.6, 128.2; HRMS (ESI): calcd. for C11H10NOS2
([M+H]+): 236.0198, found: 236.0199.
4-Methyl-N-(phenylthio)benzamide (15). White solid, m. p. 140-142 °C. 1H NMR
([D6]acetone) δ 9.22 (s, 1H), 7.93 (d, J = 8.5 Hz, 2H), 7.33-7.28 (m, 6H), 7.19-7.16 (m, 1H), 2.40
13
(s, 3H). C NMR ([D6]acetone) δ 169.0, 143.6, 141.0, 131.8, 130.0, 129.8, 128.8, 126.9, 124.9,
21.4; HRMS (ESI): calcd. for C14H14NOS+ ([M+H]+): 244.0791, found: 244.0799.
1
4-Methoxy-N-(phenylthio)benzamide (16). White solid, m. p. 131-133 °C. H NMR
([D6]acetone) δ 9.15 (s, 1H), 8.03-8.01 (m, 2H), 7.33-7.30 (m, 2H), 7.28-7.27 (m, 2H), 7.19-7.15
13
(m, 1H), 7.05-7.03 (m, 2H), 3.88 (s, 3H). C NMR ([D6]acetone) δ 168.4, 163.9, 141.2, 130.8,
129.8, 126.8, 126.7, 124.9, 114.7, 55.9; HRMS (ESI): calcd. for C14H14NO2S+ ([M+H]+):
260.0740, found: 260.0745.
4-Fluoro-N-(phenylthio)benzamide (17). Yellow solid, m. p. 124-126 °C.1H NMR
([D6]acetone) δ 9.33 (s, 1H), 8.12-8.10 (m, 2H), 7.35-7.27 (m, 6H), 7.21-7.17 (m, 1H). 13C NMR
([D6]acetone) δ 168.1, 166.0 (d, J = 248.8 Hz), 140.7, 131.5(d, J = 8.8 Hz), 131.0 (d, J = 2.5 Hz)
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129.8, 127.0, 125.2, 116.4 (d, J = 21.3 Hz); HRMS (ESI): calcd. for C13H11FNOS+ ([M+H]+):
248.0540, found: 248.0542.
4-Chloro-N-(phenylthio)benzamide (18). White solid, m. p. 159-161 °C.1H NMR
([D6]acetone) δ 9.38 (s, 1H), 8.03 (d, J = 8.5 Hz, 2H), 7.57-7.55 (m, 2H), 7.34-7.30 (m, 4H),
13
7.21-7.38 ( m, 1H). C NMR ([D6]acetone) δ 168.2, 140.6, 138.9, 133.3, 130.6, 129.9, 129.6,
127.1, 125.3; HRMS (ESI): calcd. for C13H11ClNOS+ ([M+H]+): 264.0244, found: 264.0253.
1
4-Bromo-N-(phenylthio)benzamide (19). Yellow solid, m. p. 163-164 °C. H NMR
([D6]acetone) δ 9.39 (s, 1H), 7.96 (d, J = 8.5 Hz, 2H), 7.72-7.71 (m, 2H), 7.35-7.30 (m, 4H),
13
7.21-7.17 ( m, 1H). C NMR ([D6]acetone) δ 168.3, 140.5, 133.7, 132.6, 130.7, 129.8, 127.2,
127.1, 125.2; HRMS (ESI): calcd. for C13H11BrNOS+ ([M+H]+): 307.9739, found: 307.9754.
4-Nitro-N-(phenylthio)benzamide (20). Yellow solid, m. p. 146-147 °C. 1H NMR
([D6]acetone) δ 9.63 (s, 1H), 8.37 (d, J = 8.5 Hz, 2H), 8.25 (d, J = 8.0 Hz, 2H), 7.36-7.35 ( m,
4H), 7.23-7.20 (m, 1H). 13C NMR ([D6]acetone) δ 167.9, 151.0, 140.2, 140.1, 130.2, 129.9,
127.4, 125.6, 124.6; HRMS (ESI): calcd. for C13H11N2O3S+ ([M+H]+): 275.0485, found:
275.0502.
1
N-(Phenylthio)-4-(trifluoromethyl)benzamide (21). Yellow solid, m. p. 175-176 °C. H
NMR ([D6]acetone) δ 9.55 (s, 1H), 8.22 (d, J = 8.0 Hz, 2H), 7.88 (d, J=8.0 Hz, 2H), 7.35-7.34
(m, 4H), 7.22-7.19 (m, 1H). 13C NMR ([D6]acetone) δ 168.3, 140.3, 138.3, 133.8 (q, J = 32.5
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Hz), 129.9, 129.6, 127.2, 126.5 (q, J= 3.8 Hz), 127.1 (q, J = 270 Hz), 125.4; HRMS (ESI): calcd.
for C14H11F3NOS+ ([M+H]+): 298.0508, found: 298.0510.
1
3,5-Difluoro-N-(phenylthio)benzamide (22). White solid, m. p. 106-107 °C. H NMR
([D6]acetone) δ 9.45 (s, 1H), 7.65 (d, J = 8.5 Hz, 2H), 7.34-7.33 (m, 4H), 7.31-7.29 (m, 1H),
7.23-7.19 (m, 1H). 13C NMR ([D6]acetone) δ 167.0, 163.8 (dd, J = 246.3, 11.3 Hz), 140.1,
138.0(t, J = 8.4 Hz), 129.9, 127.3, 125.6, 112.1 (dd, J = 20.0, 6.3 Hz), 108.2 (t, J = 25.0 Hz);
HRMS (ESI): calcd. for C13H10F2NOS+ ([M+H]+): 266.0446, found: 266.0453.
1
2-Chloro-6-nitro-N-(phenylthio)benzamide (23). Yellow solid, m. p. 169-170 °C. H
NMR (CD3)2SO) δ 10.42 (s, 1H), 8.24 (d, J = 9.0 Hz, 1H), 8.05-8.03 (m, 1H), 7.79-7.76 (m, 1H),
7.44-7.38 (m, 4H), 7.27-7.23 (m, 1H). 13C NMR [(CD3)2SO] δ 169.9, 165.5, 146.4, 138.4, 135.8,
131.9, 131.7, 128.9, 126.5, 124.8, 123.6; HRMS: calcd. for C13H10ClN2O3S+ ([M+H]+):
309.0095, found: 309.0103.
1
N-(Phenylthio)-1-naphthamide (24). White solid, m. p. 121-123 °C. H NMR (CDCl3) δ
8.29 (s, 1H), 7.97 (d, J = 8.0 Hz, 1H), 7.89-7.88 (m, 1H), 7.70-7.69 (m, 1H), 7.58-7.53 (m, 3H),
7.49-7.45 (m, 3H), 7.37-7.34 (m, 2H), 7.24-7.23 (m, 1H). 13C NMR (CDCl3) δ 170.7, 138.5,
133.7, 131.7, 130.1, 129.6, 129.2, 128.4, 127.6, 127.3, 126.7, 126.2, 125.5, 125.2, 124.6; HRMS
(ESI): calcd. for C17H14NOS+ ([M+H]+): 280.0791, found: 280.0792.
2-Iodo-N-(phenylthio)benzamide (25). White solid, m. p. 127-129 °C. 1H NMR (
[D6]acetone) δ 9.12 (s, 1H), 7.96 (d, J = 8.0 Hz, 1H), 7.53-7.46 (m, 4H), 7.38 (t, J = 8.0 Hz, 2H),
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13
7.26-7.22 ( m, 2H). C NMR ([D6]acetone) δ 171.3, 143.0, 140.8, 140.3, 132.3, 129.8, 129.2,
129.1, 127.3, 125.8, 92.9; HRMS (ESI): calcd. for C13H11INOS+ ([M+H]+): 355.9601, found:
355.9616.
1
N-(Phenylthio)cyclohexanecarboxamide (26). White solid, m. p. 119-121 °C. H NMR
(CDCl3) δ 7.81 (s, 1H), 7.21 (t, J = 7.5 Hz, 2H), 7.14-7.09 (m, 3H), 2.35-2.30 (m, 1H), 1.82-1.79
(m, 2H), 1.70-1.68 (m, 2H), 1.60-1.59 (m, 1H), 1.47-1.40 (m, 2H), 1.21-1.11 (m, 3H). 13C NMR
(CDCl3) δ 178.7, 139.3, 128.8, 126.2, 124.6, 45.5, 29.7, 25.6, 25.5; HRMS (ESI): calcd. for
C13H18NOS+ ([M+H]+): 236.1104, found: 236.1101.
1
N-(Phenylthio)butyramide (27). White solid, m. p. 50-52 °C. H NMR (CDCl3) δ 8.05 (s,
1H), 7.22-7.19 (m, 2H), 7.15-7.14 (m, 2H), 7.12-7.09 (m, 1H), 2.27 (t, J = 7.5 Hz, 2H), 1.64-1.58
13
(m, 2H), 0.85 (t, J = 7.5 Hz, 3H). C NMR (CDCl3) δ 176.0, 139.1, 128.8, 126.3, 124.8, 38.3,
19.1, 13.6; HRMS (ESI): calcd. for C10H14NOS+ ([M+H]+): 196.0791, found: 196.0781.
N-[(3,5-Dichlorophenyl)thio]-4-methylbenzamide (28). Yellow solid, m. p. 118-120 °C.
1H NMR ([D6]acetone) δ 9.40 (s, 1H), 7.95 (d, J = 8.0 Hz, 2H), 7.34 (d, J = 8.0 Hz, 2H), 7.24 (t,
13
J = 2.0 Hz, 1H), 7.22 (d, J = 2.0 Hz, 2H), 2.41 (s, 3H). C NMR ([D6]acetone) δ 168.9, 145.8,
144.0, 136.1, 131.2, 130.2, 128.9, 126.2, 122.2, 21.5; HRMS (ESI): calcd. for C14H12Cl2NOS+
([M+H]+): 312.0011, found: 312.0023.
1
4-Methyl-N-[(4-nitrophenyl)thio]benzamide (29). Yellow solid, m. p. 145-147 °C. H
NMR ([D6]acetone) δ 9.45 (s, 1H), 8.18 (d, J = 9.0 Hz, 2H), 7.97 (d, J = 8.0 Hz, 2H), 7.45 (d, J =
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9.0 Hz, 2H), 7.36 (d, J = 8.0 Hz, 2H), 2.42 (s, 3H). 13C NMR ([D6]acetone) δ 168.9, 150.9,
146.5, 144.1, 131.2, 130.2, 129.0, 124.9, 123.4, 21.5; HRMS (ESI): calcd. for C14H13N2O3S+
([M+H]+): 289.0641, found: 289.0648.
2-(Phenylthio)-1H-pyrrole (30).[17c]
2-Phenyl-3-(phenylthio)benzofuran (31).[18a]
ACKNOWLEDGMENTS
The authors thank the National Natural Science Foundation of China (No. 21302144 and No.
21272177).
SUPPLEMENTARY DATA
Supplementary data associated with this article can be found online.
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Table 1 Optimization of the reaction conditions a
Entry
NaH (eq)
Disulfide (eq)
Time (h)
36
Yield (%)b
1
2
3
4
5
6
7
8
1
2
3
4
3
3
3
3
1.5
1.5
1.5
1.5
1.0
1.2
1.5
1.5
30
52
36
36
95, 25c
96
36
36
80
36
85
24
84
12
72
a
the mixture of benzamide 1a (0.2 mmol) and NaH was stirred in THF (3 mL) for 1 h, then
b
diphenyl disulfide 2a was added and stirred for another indicated time at room temperature.
isolated yield. c benzamide, phenyl disulfide and NaH were added into the reaction system at the
same time.
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Table 2. The synthesis of N-acyl sulfenamides from the reaction of benzamides with disulfides a,
b
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O
O
O
NO2
F
S
S
S
S
N
Ph
N
H
Ph
Ph
N
Ph
H
H
Cl
F
22
23
, 72 %
24
, 63 %
, 21 %
O
O
O
S
S
N
Ph
N
H
N
Ph
H
H
I
25
26
, 38
%
27,
42 %
, 28 %
O
O
S
Cl
S
N
N
H
H
H3C
28, 93 %
H3C
NO2
Cl
29, 79 %
a the mixture of amide 1 (0.2 mmol), NaH (3 equiv.) was stirred in THF (3 mL) for 1
h, then disulfide 2 (1.5 equiv.) was added and stirred for another 36 h at room
temperature. b isolated yield.
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Scheme 1 The common processes for the synthesis of N-acylsulfenamides
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Scheme 2 The application of N-(phenylthio)benzamide as new thiolation reagent
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