A convenient synthesis of 2-methoxycarbonyl-5-iodobenzene sulfonamide

Article abstract of DOI:10.14233/ajchem.2017.20627

A convenient and concise synthesis of 2-methyl-5-nitrobenzene sulfonamide can be achieved by sulfochlorination and ammoniation with p-nitrotoluene as raw materials for an 81.2 % yield. 6-Aminosaccharin can be produced via oxidation and reduction in a 64.3

Full text of DOI:10.14233/ajchem.2017.20627

Asian Journal of Chemistry; Vol. 29, No. 7 (2017), 1622-1624
A
SIAN
J
OURNAL OF HEMISTRY
C
https://doi.org/10.14233/ajchem.2017.20627
A Convenient Synthesis of 2-Methoxycarbonyl-5-iodobenzene Sulfonamide
†
†
*
XINHONG CAI , QIULU CHEN , JING GUAN, SHUNZE GONG, HAO FU and DEFENG XU
School of Pharmaceutical Engineering and Life Sciences, Changzhou University, Changzhou 213164, Jiangsu Province, P.R. China
†These authors are co-first author
*
Corresponding author: Fax: +86 519 86334598; Tel: +86 519 85281008; E-mail: markxu@cczu.edu.cn
Received: 6 March 2017;
Accepted: 26 April 2017;
Published online: 13 May 2017;
AJC-18406
A convenient and concise synthesis of 2-methyl-5-nitrobenzene sulfonamide can be achieved by sulfochlorination and ammoniation with
p-nitrotoluene as raw materials for an 81.2 % yield. 6-Aminosaccharin can be produced via oxidation and reduction in a 64.3 % yield and
then the iodination using potassium iodide can afford 6-iodosaccharin with a 70.8 % yield. 2-Methoxycarbonyl-5-iodobenzene sulfonamide
can be produced via esterification in a 94.1 % yield.
Keywords: 2-Methyl-5-nitrobenzene sulfonamide, Sulfochlorination, Ammoniation, Oxidation, Iodination, Esterification.
potassium permanganate and environment friendly hydroge-
nation reduction reaction using aluminum-nickel alloy catalyst
in good yield. A convenient and most practical approach to
the synthesis of 2-methoxycarbonyl-5-iodobenzene sulfona-
mide (7) involved sulfochlorination, ammoniation, oxidation,
reduction and iodination reactions.
INTRODUCTION
The sulfonylurea herbicides with extremely high effect,
low poison, low cost and other characteristics got the extensive
expansion application quickly after the development, which
was one of the important milestones of the agrochemical
development history [1]. Iodosulfuron-methyl (1) was a sulfo-
nylurea postemergence herbicide. Iodosulfuron-methyl-
sodium was an active ingredient of the Alister Grande 190
OD herbicide manufactured by Bayer Crop Science, which
was registered for use in Poland in 2008. Iodosulfuron-methyl
can affect the activity of the acetolactate synthase (ALS)
enzyme, leading to plant deformation and death, growth
retardation and chlorosis [2-4]. It usually existed in the forma-
tion of methyl ester and sodium salt in the application and
mainly applied to variety of gramineous weeds and broad-
leaved weeds that grow in spring and winter wheat, durum
wheat and triticale [5,6]. The herbicide was safe for the cereal
crops and has no influence on succeeding crops. 2-methoxy-
carbonyl-5-iodobenzene sulfonamide (7) and 2-amino-4-
methoxy-6-methyl-1,3,5-triazine were two key intermediates
of iodosulfuron-methyl.
COOCH3
OCH3
N
H
I
SO NH
N
N
2
N
O
OCH3
Structure of Iodosulfuron-methyl (
1)
EXPERIMENTAL
Reagents and solvents were obtained from commercial
suppliers and were used without further purification.All melting
points were determined on a XT34 binocular microscope
(Beijing Tech Instrument Co., China) and were not corrected.
1
H NMR spectra were recorded on Mercuryplus 400 (300 MHz)
Several syntheses of 2-methoxycarbonyl-5-iodobenzene
sulfonamide had been reported in the literature [7]. Diao reported
the raw material was not easy to get and high cost [8]. Wang et
al. reported to use the hyper-toxic potassium dichromate and
iron powder [9]. A large quantity of iron mud pollution was
produced in the iron powder reduction. This paper reported a
convenient and efficient synthesis of 2-methoxycarbonyl-5-
iodobenzene sulfonamide (7) utilizing a non-toxic oxidant
spectrometer, chemical shifts (δ) were reported in parts per
million relative to tetramethylsilane. Chemical shifts were
reported in parts per million relative to the solvent resonance
as the internal standard (CDCl , δ = 7.16 ppm). Analytical
3
TLC and column chromatography were performed on silica
gel GF254 and silica gel H60, respectively.
2-Methyl-5-nitrobenzene sulfonamide (3): To a mixture
of p-nitrotoluene (27.4g, 0.20 mol) in 1,2-dichloroethane (120

Vol. 29, No. 7 (2017)
A Convenient Synthesis of 2-Methoxycarbonyl-5-iodobenzene Sulfonamide 1623
mL) was heated to 50 °C, chlorosulfonic acid (35.4 g, 0.3
mol) was added drop-wise with stirring for over 30 min. The
mixture was heated to 60 °C for 6 h. Ice water (500 mL) was
added at the end of the reaction with stirring. The aqueous
mixture was extracted three times with 1,2-dichloromethane
(d, J = 2.2 Hz, 2H), 6.97 (d, J = 2.2 Hz, 2H), 7.62 (s, 1H),
7.64 (s, 1H), 9.8 (1H, br, NH).
6-Iodosaccharin (6): 6-Aminosaccharin (5, 19.8 g, 0.10
mol), acetic acid (150 mL), water (30 mL) and concentrated
hydrochloric acid (30 mL) were mixed together and cooled to
-5 °C, then the sodium nitrite (8.4 g, 0.12 mol) and water (50
mL) were added drop-wise with stirring at 0 °C for 1 h. The
potassium iodide (16.6 g, 0.10 mol) was dissolved in water
(100 mL) was added drop-wise and the reaction mixture was
heated to 50 °C for 1 h. In the end of reaction, the mixture was
cooled to room temperature, filtrated and washed with water,
recrystallized from ethyl alcohol to give bronzing solid 6-
(
75 mL), 25 % ammonium hydroxide (25 mL, 0.33 mol) was
added drop-wise combined the organic layers at 10 °C, the
mixture was heated to 40 °C for 2 h. The reaction mixture was
concentrated under reduced pressure in the end of the reaction.
The crude residue was taken up in water (80 mL) and filtered,
washed with water to afford off-white solid 3 (35.1 g, 81.2 %
1
yield), m.p.: 183.2-184.8 °C (lit. [10] m.p.: 183-185 °C) H
NMR (CDCl
NH ), 7.55 (1H, d, J = 8.4 Hz), 8.26 (1H, d, J = 8.4 Hz), 8.82
1H, s).
-Nitrosaccharin (4): 2-Methyl-5-nitrobenzene sulfona-
mide (3, 26.1 g, 0.10 mol), benzyl triethyl ammonium chloride
TEBA) (1.2 g, 5.2 mmol) and water (250 mL) were mixed
together and heated to 95 °C. The potassium permanganate
3
, 300 MHz) δ, ppm: 2.78 (3H, s), 7.24 (2H, s,
iodosaccharin (6, 21.9 g, 70.8 % yield), m.p.: 224.6 -227.5 °C
1
2
(lit. [13] m.p.: 224-226 °C). H NMR (CDCl
3
) δ, ppm: 7.73
(
(d, J = 8.0 Hz, 1H), 8.19 (d, J = 8.0 Hz, 1H), 8.24 (s, 1H),
10.2(1H, br, NH).
6
2-Methoxycarbonyl-5-iodobenzene sulfonamide (7):
6-Iodosaccharin (6, 31.0 g, 0.10 mol) was dissolved in methanol
(200 mL), concentrated sulfuric acid (2 mL) was added drop-
wise with stirring, the mixture was heated under reflux for
6 h. The mixture was cooled to room temperature. In the end
of reaction, the methanol was removed and the residue was
taken up in sodium hydrogen carbonate saturated aqueous (120
mL) to adjust pH 8, filtered and washed with water, recrysta-
llized from methanol to afford 2-methoxycarbonyl-5-iodo-
benzene sulfonamide 7 (32.1g, 94.1 % yield), m.p.: 175-179
°C (lit. [14] m.p.: 176-177 °C).
(
(
(
15.7 g, 0.1 mmol) was added in batches and then added water
50 mL) finally. The reaction mixture was heated to 95 °C for
8
h. The reaction residue was filtered and washed with hot
water (80 mL) twice, the solution was acidified with concen-
trated hydrochloric acid to pH 2. A white solid was filtered off
and recrystallized from ethyl alcohol to give 6-nitrosaccharin
(
4, 16.3 g, 71.4 % yield), m.p.: 205.5-206.9 °C (lit. [11,12]
1
m.p.: 212-214 °C). H NMR (DMSO-d
.93 (1H, d, J = 8.4 Hz), 8.41 (1H, dd, J = 1.6, 2.1 Hz), 8.47
1H, s), 10.6 (1H, br, NH).
-Aminosaccharin (5): 6-Nitrosaccharin (4, 22.8 g, 0.10
6
, 300 MHz) δ, ppm:
7
(
RESULTS AND DISCUSSION
6
Recently studied using the sulfonylurea class of herbicides
and a key intermediate 2-methoxycarbonyl-5-iodobenzene
sulfonamide (7), showed that the efficient synthesis of 6-
aminosaccharin (5) with 6-nitrosaccharin (4) in the presence
of aluminum-nickel alloy catalyst afforded 2-methoxycarbonyl-
5-iodobenzene sulfonamide in very high yields, meantime,
the optimization of the synthetic conditions for 6-nitrosaccharin
was conducted.
mol) dissolved in ethyl acetate (120 mL), in the presence of
aluminum-nickel alloy catalyst (3.0 g), the theoretical amount
of hydrogen had been injected for 4 h under pressure 2.5 MPa.
The aluminum-nickel alloy catalyst was collected by filtration
in the end of reaction. The reaction mixture was concentrated
under reduced pressure, then recrystallized from ethyl alcohol
to give the pure pale yellow solid 6-aminosaccharin (5, 18.1 g,
9
0.1 % yield), m.p.: 181-184 °C (lit. [12] m.p.: 180-185 °C).
Potassium dichromate is a hyper-toxic oxidant, which had
limited use in the world. Generally, non-toxic or environ-
1
H NMR (DMSO-d
6
) δ, ppm: 6.85 (d, J = 2.2 Hz, 1H), 6.92
CH3
CH3
O
SO NH
a
2
2
c
b
NH
S
(81.2%)
(71.4%)
O N
2
(90.1%)
O
O
NO2
NO2
2
4
3
O
O
COOCH3
d
e
NH
NH
S
S
(70.8%)
I
(94.1%)
H N
O
2
I
SO NH
2 2
O
O
O
7
6
5
3
a. HSO Cl. NH3
b. KMnO . TEBA/H O
4
2
c. H . Ni-Al
2
d.NaNO /HAc. KI
e. CH OH. H SO
3 2 4
2
Scheme-I: Synthesis of 2-methoxycarbonyl-5-iodobenzene sulfonamide

1
624 Cai et al.
Asian J. Chem.
mentally friendly oxidant for manufacture should be used.
Although potassium permanganate was lower than potassium
dichromate in the performance of oxidation, it was a non-toxic
oxidant. Potassium permanganate was selected as an oxidant
and it was found that the phase translation catalytic benzyl
triethyl ammonium chloride could improve the yield of
ACKNOWLEDGEMENTS
This project is supported by the Introduction Talent Fund
of Changzhou University, China.
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