Phenylsulfonylnitromethane

[21272-85-5]  · C7H7NO4S  · Phenylsulfonylnitromethane  · (MW 201.22)

(precursor for a-nitro sulfones;1 precursor for phenylsulfonylnitrile oxide for 1,3-dipolar cycloadditions2)

Physical Data: mp 78-79 °C; pKa 5.69 (MeOH-H2O, 50:50).3

Solubility: insol water; sol CH2Cl2, hot alcohol. Sodium salt (1) sparingly sol DMSO but not THF; lithium salt (2) sol THF.

Form Supplied in: white crystalline solid.

Analysis of Reagent Purity: analytical TLC (CH2Cl2 elution) should give one spot, Rf 0.35; a possible impurity is 1,3-bis(phenylsulfonyl)-1,3-dinitropropane, Rf 0.1, which can be removed by sublimation.

Preparative Methods: Nitromethane, Sodium Benzenesulfinate, and Iodine are added sequentially to a cold (0-5 °C) DMF solution of Sodium Methoxide. The reagent can be converted to NaO2N=CHSO2Ph (1) and LiO2N=CHSO2Ph (2) using NaOMe and LiOMe, respectively.1

Handling, Storage, and Precautions: indefinitely stable; the nitronate salts (1) and (2) can be stored dry without decomposition for several weeks but, like all nitronate salts, they are explosive: (2) vigorously decomposes above 150 °C.

Alkylation Reactions.

The reagent can be C-monoalkylated via its nitronate salts (1) and (2). a-Nitro sulfones were obtained by reaction of (1) with a variety of benzyl halides and primary alkyl iodides (eq 1).1,4 a-Nitro sulfones were similarly obtained by reaction of (2) with allylic acetates in the presence of Pd0 catalysts (eqs 2 and 3).1,5 High regioselectivity for the less hindered carbon of the p-allylpalladium intermediate was typically observed. Displacement of the acetate usually occurs with net retention.6

C,C-Dialkylates were not formed in the alkylation reactions owing to congestion at the monoalkylated a-nitro sulfone center. However, internal O-alkylation can occur,1,7 subsequent to C-alkylation, affording cyclic nitronic esters (eq 4) which can be deoxygenated to provide 3-phenylsulfonyl-4,5-dihydroisoxazoles. The reagent has also been used to prepare a-nitro sulfones by Michael addition to 3-buten-2-one.4a a-Nitro sulfones can be converted to carboxylic acids,1,5 desulfonated nitro compounds,1,4a,8 and nitriles.1

Cycloaddition Reactions.

The reagent is used to make three precursors for generation of the 1,3-dipole benzenesulfonyl cyanide N-oxide (PhSO2C&tbond;+N-O-). The first precursor, N-hydroxy-1-phenylsulfonylmethanimidoyl bromide (3), is obtained from the reagent by sequential bromination, methylation, and mild thermolysis (eq 5).2a Bromooxime (3) is preferred because it gives the nitrile oxide most cleanly.

However, nitronic ester (4), which has been known to explode, is a more easily obtained precursor: the reagent is simply methylated using diazomethane.2b,10 The reagent also reacts with nitric acid to provide bis(phenylsulfonyl)furazan 2-oxide (5), which is a third nitrile oxide precursor.9,2c

Any of these precursors, for example (3), can be used to generate the nitrile oxide which then reacts in situ with a wide variety of alkenes to give 3-phenylsulfonyl-4,5-dihydroisoxazoles (eq 6).2,10,11

The alkene configuration is retained in the dihydroisoxazole and regioselectivity is high for monosubstituted, gem-disubstituted, and trisubstituted alkenes. Conditions for generation of the nitrile oxide vary: (3) requires mild base2a or Silver(I) Nitrate,2b while nitronic ester (4) requires strong base2b or strong acid,12 and (5) requires heating (140 °C).2c The phenylsulfonyl group of the dihydroisoxazoles can be replaced using a variety of nucleophiles including organolithium reagents and sodium methoxide.13,7 Reductive cleavage using 2% Sodium Amalgam14 or Hexacarbonylmolybdenum7 affords cis-b-hydroxynitriles, and this is the most general route to these compounds (eq 7).

Related Reagents.

(Phenylthio)nitromethane.


1. Wade, P. A.; Hinney, H. R.; Amin, N. V.; Vail, P. D.; Morrow, S. D.; Hardinger, S. A.; Saft, M. S. JOC 1981, 46, 765.
2. (a) Wade, P. A.; Hinney, H. R. JACS 1979, 101, 1319. (b) Wade, P. A.; Pillay, M. K. JOC 1981, 46, 5425. (c) Whitney, R. A.; Nicholas, E. S. TL 1981, 22, 3371.
3. Bordwell, F. G.; Bartmess, J. E. JOC 1978, 43, 3101.
4. (a) Park, K. K.; Lee, C. W.; Choi, S. Y. JCS(P1) 1992, 601. (b) The reagent can also be used directly for alkylations in the presence of the phase transfer agent TEBA: El-Khawaga, A. M.; Ismail, M. T.; Abdel-Wahab, A.-M. A. G 1982, 112, 235.
5. Trost, B. M.; Kuo, G.-H.; Benneche, T. JACS 1988, 110, 621.
6. Trost, B. M.; Verhoeven, T. R. JACS 1980, 102, 4730. For an example of retention using lithium salt (2), see: Schink, H. E.; Bäckvall, J.-E. JOC 1992, 57, 1588.
7. Trost, B. M.; Li, L.; Guile, S. D. JACS 1992, 114, 8745.
8. (a) Chen, J.; Tanner, D. D. JOC 1988, 53, 3897. (b) Suzuki, H.; Takaoka, K.; Osuka, A. BCJ 1985 58, 1067.
9. Kelley, J. L.; McLean, E. W.; Williard, K. F. JHC 1977, 14, 1415.
10. Nordmann, R.; Graff, P.; Maurer, R.; Gähwiler, B. H. JMC 1985, 28, 1109.
11. Taylor, M. D.; Himmelsbach, R. J.; Kornberg, B. E.; Quin, J., III; Lunney, E.; Michel, A. JOC 1989, 54, 5585.
12. Wade, P. A.; Amin, N. V.; Yen, H.-K.; Price, D. T.; Huhn, G. F. JOC 1984, 49, 4595.
13. Wade, P. A.; Yen, H.-K.; Hardinger, S. A.; Pillay, M. K.; Amin, N. V.; Vail, P. D.; Morrow, S. D. JOC 1983, 48, 1796.
14. Wade, P. A.; Bereznak, J. F. JOC 1987, 52, 2973.

Peter A. Wade

Drexel University, Philadelphia, PA, USA



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