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Molbank 2006, M502 |
3-[(Phenylsulfonyl)methyl]aniline hydrochloride
Daniel G. Grohmann and
Bruce A. Hathaway*
Department of Chemistry, MS
6400, One University Plaza, Southeast Missouri State University, Cape
Girardeau, MO, USA,
Tel. 001 573-651-2370, e-mail: [email protected]
*Author to whom correspondence
should be addressed
Received: 6 July 2006 / Accepted: 1 August 2006 /
Published: 1 September 2006
Keywords: nitro, amine, reduction.
In the course of our work
to prepare inhibitors of the enzyme dihydrofolate reductase, we desired to
prepare sulfone analogues of some previously reported sulfides [1, 2]. The
previously reported nitrosulfone [3] was not able to be reduced to the amine by
using catalytic hydrogenation with a palladium on carbon catalyst, with tin and
hydrochloric acid [4], or with iron and acetic acid in ethanol [5]. Therefore,
the nitrosulfone, 1, was converted
into the acetamide, 2, using iron in
acetic acid [5]. The acetamide, 2,
was hydrolyzed to the desired aniline, 3,
using concentrated hydrochloric acid and ethanol. Unfortunately for us, the
aniline was not able to be converted into the desired triazine by the reported
procedure [2].
In round bottom flask 1-nitro-3-[(phenylsulfonyl)methyl]benzene, 1 (2.453 g, 8.85 mmoles), iron filings (2.019 g, 36.2 mmoles), and 25 mL of concentrated acetic acid were combined and refluxed overnight. After allowing the flask to cool, 200 mL of water and 100 mL of dichloromethane were added to the mixture. The unreacted iron was then removed by vacuum filtration. The aqueous and organic layers were separated, and the aqueous layer was extracted two more times with 45 mL portions of dichloromethane. The organic extracts were combined and dried with anhydrous magnesium sulfate. The dichloromethane was removed by using the rotavap. A yellow, viscous liquid was collected. After this liquid was allowed to stand for a couple of days, it solidified forming a tan solid, to yield 2.438 g (8.43 mmoles) of 3-[(phenylsulfonyl)methyl]acetanilide, 2. The percent yield for the reaction was 96%.
Melting Point: 121-123oC
IR (cm-1): 3280, 1661, 1593, 1300, 1161,
1152, 1083, 798, 777, 765, 698, 687.
1H-NMR (300 MHz,
DMSO-d6): ¦Ä=
10.0 (1H, singlet), 7.7 (3H,
multiplet), 7.6 (3H, multiplet), 7.5 (1H, singlet), 7.2 (1H, triplet, J = 7.7
Hz), 6.7 (1H, doublet, J = 7.7 Hz), 4.6 (2H, singlet), 2.0 (3H, singlet).
13C-NMR (75 MHz, DMSO-d6): ¦Ä= 168.3, 139.3, 138.4, 133.7, 129.1, 128.9, 128.4, 127.9, 125.6, 121.3,
118.9, 60.7, 23.9.
GC-MS [E.I., m/z (relative intensity)]: 148 (100), 106
(60), 77 (20), 77(16), 289 (M+, 14).
In a round bottom flask
3-[(phenylsulfonyl)methyl)acetanilide, 2
(1.003 g, 3.47 mmoles), 5 mL of 95% ethanol, and 6 mL of concentrated
hydrochloric acid were combined and refluxed for 24 hours. The amide dissolved in the hot ethanol
forming a yellow solution. After
about 1 hour, a precipitate began to form.
The reaction mixture was allowed to cool, and the precipitate was
collected by vacuum filtration. The
precipitate was washed with three portions of cold 95% ethanol to yield 0.893 g
(3.15 mmoles) of 3-[(phenylsulfonyl)methyl]aniline hydrochloride, 3, was collected. The percent yield of the reaction was
91%.
Melting Point: 260 oC (decomposed)
IR (cm-1): 2879 (br), 1536, 1311, 1294,
1134, 1083, 765, 751, 720, 682.
1H-NMR (300 MHz,
DMSO-d6): ¦Ä=
10.2 (3H, broad singlet), 7.7 (3H,
multiplet), 7.6 (2H, multiplet), 7.3 (2H, multiplet), 7.2 (1H, singlet), 7.0
(1H, doublet, J = 7.1 Hz), 4.8 (2H, singlet).
13C-NMR (75 MHz, DMSO-d6): ¦Ä= 138.3, 133.9, 132.9, 130.3, 129.9, 129.5, 129.2, 127.9, 124.8, 122.7, 59.9.
GC-MS [E.I., m/z (relative intensity), free base]: 106
(100), 77 (26), 247 (M+, 18), 79 (16), 183 (12).
Acknowledgment
The authors thank the
Grants and Research Funding Committee of Southeast Missouri State University
for financial support.
References:
1. Selassie, C. D., Guo, Z.-r., Hansch, C., Khwaja, T. A., and Pentacost, S. A Comparison of the Inhibition of Growth of Methotrexate-Resistant and -Sensitive Leukemia Cells in Culture by Triazines. Evidence of a New Mechanism of Cell Resistance to Methotrexate. J. Med. Chem. 1982, 25. 157-161.
2. Hansch, C., Hathaway, B. A., Guo, Z.-r., Selassie, C. D., Dietrich, S. W., Blaney, J. M., Langridge, R., Volz, K. W., and Kaufman, B. T. Crystallography, QSAR, and Molecular Graphics in a Comparative Analysis of the Inhibition of Dihydrofolate Reductase from Chicken Liver and L. casei by 4,6-Diamino-1,2-dihydro-2,2-dimethyl-1-(x-phenyl)-s-triazines. J. Med. Chem. 1984, 27, 129-143.
3. Grohmann, D. G. and Hathaway, B. A. 1-Nitro-3-[(phenylsulfonyl)methyl]benzene Molecules 2006, Mxxx.
4. Jones, A.G. The Selective Reduction of
5. Owsley, D. C.; Bloomfield, J. J. The Reduction of Nitroarenes with Iron/Acetic Acid. Synthesis. 1977, 118-120.
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