Bahrami et al.
JOCArticle
SCHEME 4
(4 ꢀ 5 mL), and the extract dried with anhydrous MgSO4. The
filtrate was evaporated under vacuum to afford the analytically
pure product. All of the products are known compounds
and characterized easily by comparison with authentic samples
(1H NMR, 13C NMR, mp).
General Procedure for the Synthesis of Sulfonamides. A mix-
ture of thiol compound (2 mmol), H2O2 (30%, 6 mmol, 0.6 mL),
and SOCl2 (2 mmol, 0.14 mL) was stirred in CH3CN at 25 °C for
an appropriate time. After completion of the reaction as in-
dicated by TLC, a solution of amine (2 mmol) in pyridine (1 mL)
was added to the reaction mixture. The resulting mixture was
stirred at room temperature until TLC showed complete dis-
appearance of starting material (Table 3) and then acidified with
2 N HCl solution and extracted with EtOAc. The organic layer
was washed with H2O and brine and dried over MgSO4. The
filtrate was evaporated, and the corresponding pure sulfonam-
ide was obtained as a crystalline solid. Recrystallization from a
mixture of ethanol and water affords analytically pure product.
Spectral and analytical data for new compounds follow.
N-2-Chlorophenyl-4-methylbenzenesulfonamide. mp=105 °C.
1H NMR (200 MHz, CDCl3): δ 2.36 (s, 3H), 6.98-7.07 (m, 2H),
7.18-7.26 (m, 4H), 7.63-7.67 (m, 3H). 13C NMR (50 MHz,
CDCl3): δ 22, 122.8, 125.5, 126.3, 127.7, 128.3, 129.8, 130.1,
133.9, 136.3, 144.7. Anal. Calcd for C13H12NSO2Cl: C, 55.42; H,
4.26; N, 4.97; S, 11.36. Found: C, 55.06; H, 4.38; N, 4.86; S,
10.85.
We report a practical synthesis of sulfonamides starting
from thiols (1 mmol), amines (1 mmol) in the presence of
30% H2O2 (3 mmol), SOCl2 (1 mmol), and pyridine (0.5 mL).
The route for the synthesis of sulfonamides is shown in
Scheme 4.
Using optimized reaction conditions, the reaction of
structurally and electronically diverse thiols and amines
was examined. The results, which are summarized in
Table 3, indicate that all the reactions proceeded efficiently
and the desired sulfonamides were obtained in excellent
yields in fast reaction times with high purity (monitored by
NMR spectroscopy). Aryl thiols carrying either electron-
donating or electron-withdrawing substituents reacted very
well to give the corresponding sulfonamides with equal
efficiency. Also, aryl amines appeared to be insensitive to
substitution. Primary and secondary alkyl amines and also
ammonia undergo this reaction with equal efficiency.
For example, N-cyclohexyl-4-methylbenzenesulfonamide is
produced in 98% yield (Table 3, entry 3), N,N-diethyl-
benzenesulfonamide in 96% yield (Table 3, entry 11), and
4-methylbenzenesulfonamide in 97% yield (Table 3, entry 9).
Moreover, the reaction of 2-mercaptobenzimidazole with 4-
bromoaniline, contrary to our expectation, gives excellent
yield of product (Table 3, entry 8). It is noteworthy that the
rapidity of the reaction permits formation of the correspond-
ing heterocyclic sulfonamide.
N-Cyclohexyl-4-bromobenzenesulfonamide. mp = 100 °C. 1H
NMR (200 MHz, CDCl3): δ 1.15 (m, 5H), 1.53-1.74 (m, 5H),
3.10 (m, 1H), 4.96 (d, 1H, J = 7.5 Hz, NH), 7.63 (d, 2H, J =
8 Hz), 7.75 (d, 2H, J = 8 Hz). 13C NMR (50 MHz, CDCl3): δ
24.6, 25, 33.8, 52.7, 127.3, 128.5, 132.3, 140.6. Anal. Calcd for
C12H16NSO2Br: C, 45.28; H, 5.03; N, 4.40; S, 10.06. Found: C,
45.25; H, 5.01; N, 4.23; S, 9.77.
N-3-Nitrophenyl-4-bromobenzenesulfonamide. mp = 118-
1
120 °C. H NMR (200 MHz, CDCl3): δ 7.17-7.74 (m, 7H),
7.86-8.00 (m, 2H). 13C NMR (50 MHz, CDCl3): δ 115.4, 120.2,
126.4, 128.8, 129.1, 130.6, 132.9, 137.4, 137.6, 148.8. Anal. Calcd
for C12H9N2SO2Br: C, 44.31; H, 2.76; N, 8.61; S, 9.85. Found:
C, 43.65; H, 2.68; N, 8.53; S, 9.50.
Conclusion
In summary, H2O2-SOCl2 is an extremely efficient re-
agent system for the conversion of thiols to sulfonyl chlor-
ides. Furthermore, a novel one-pot conversion of thiols to
sulfonamides has been developed. The advantages are ex-
cellent yields, the cheapness and availability of the reagents,
easy and clean workup, extremely fast reaction, high che-
moselectivity, and operation at room temperature. This
methodology also overcomes the formation of unwanted
byproduct, thus, we believe that the present methodology
opens new possibilities for medicinal chemistry and material
sciences and could be an important addition to the existing
methodologies.
N-4-Chlorophenyl-2-naphthalenesulfonamide. mp = 115 °C.
1H NMR (200 MHz, CDCl3): δ 7.12 (d, 2H, J = 8.9 Hz), 7.25 (d,
2H, J = 8.9 Hz), 7.57-8.13 (m, 6H), 8.43 (d, 1H, J = 1.3 Hz),
10.56 (s, 1H, NH). 13C NMR (50 MHz, CDCl3): δ 122, 122.3,
128.2, 128.3, 128.5, 128.6, 129.5, 129.6, 129.7, 130, 132, 134.7,
136.6, 137.1. Anal. Calcd for C16H12NSO2Cl: C, 60.48; H, 3.78;
N, 4.41; S, 10.07. Found: C, 60.31; H, 3.87; N, 4.14; S, 9.88.
N-4-Bromophenyl-2-benzimidazolesulfonamide. mp = 156-
158 °C. 1H NMR (200 MHz, CDCl3): δ 7.57-7.65 (m, 5H), 8.07
(d, 2H, J = 9 Hz), 8.17 (d, 2H, J = 9 Hz). 13C NMR (50 MHz,
CDCl3): δ 123.6, 123.9, 126.5, 127.2, 132, 132, 142.6, 147.1.
Anal. Calcd for C13H10N3SO2Br: C, 44.32; H, 2.84; N, 11.93; S,
9.09. Found: C, 44.03; H, 2.51; N, 11.62; S, 8.72.
Experimental Section
Acknowledgment. We are thankful to the Razi University
Research Council for partial support of this work.
General Procedure for Oxidative Chlorination of Thiols. A
mixture of thiol compound (2 mmol), 30% H2O2 (6 mmol,
0.6 mL), and SOCl2 (2 mmol, 0.14 mL) was stirred in CH3CN at
25 °C for the time indicated in Table 2. After completion of the
reaction as indicated by TLC, the reaction mixture was
quenched by adding water (10 mL), extracted with ethyl acetate
Supporting Information Available: Complete experimental
procedures and relevant spectra (1H NMR and 13C NMR
spectra) for some compounds. This material is available free
J. Org. Chem. Vol. 74, No. 24, 2009 9291