[60595-16-6]  · C7H7NO2S  · (Phenylthio)nitromethane  · (MW 169.22)

(precursor for 1-nitro-1-phenylthioalkenes,2 furans,3 bicyclic b-lactams,4 and amino acids5)

Alternate Name: nitro(phenylthio)methane

Physical Data: bp 85-95 °C/0.05 mmHg;6 n23D 1.5785;7 pKa (DMSO) 11.9.7

Solubility: insol cold H2O; sol CH2Cl2, benzene, THF.

Analysis of Reagent Purity: 1H NMR: 5.45 (s, 2H) and 7.25-7.5 ppm (m, 5H).6

Preparative Method: most conveniently prepared by reaction of the sodium salt of Nitromethane with Benzenesulfenyl Chloride.6,8

Handling, Storage, and Precautions: may be stored essentially unchanged in a freezer at -25 °C; unpleasant odor; best handled in a well-ventilated hood; any spillage may be cleaned up with commercial bleach.

Nitroalkene Synthesis.

Henry reaction of (phenylthio)nitromethane with aldehydes followed by dehydration has been used to prepare (Z)-1-nitro-1-phenylthioalkenes.2-5 Potassium t-Butoxide-catalyzed addition and dehydration via mesylation (eq 1), or direct condensation catalyzed by piperidinium acetate (eq 2),9 are the methods of choice. Henry reaction can be also carried out by reaction of the nitroalkene dianion with aldehydes.8,10,11 The adducts of cyclic ketones and (phenylthio)nitromethane undergo ring expansion to provide 2-(phenylthio)cycloalkanones on Aluminum Chloride-mediated denitration.11

1-Nitro-1-phenylthioalkenes (1), on reaction with t-Butyl Hydroperoxide, are converted into epoxides and these species react with nucleophiles (halide salts, Boron Trifluoride Etherate, Trifluoroacetic Acid, MsOH) to provide a-substituted phenylthio esters (eq 3).9 Alternatively, Michael addition of nucleophiles (alkoxides, Phth-, Ts-, malonate) to 1-nitro-1-phenylthioalkenes and ozonolysis of the intermediate nitronate gave similar adducts (eq 4), including a-amino and a-hydroxy acid derivatives.2

(Phenylthio)nitromethane is useful in polyoxin synthesis.5,12 A ribose nitroalkene (2), derived from (phenylthio)nitromethane and the corresponding aldehyde (93%), was found to react with opposite stereochemical biases with potassium trimethylsilanoate (eq 5) and Phthalimide (eq 6) followed by ozonolysis. The hydroxy acid (eq 5) was further transformed into polyoxin C.

Synthesis of Heterocycles.

1-Nitro-1-phenylthiopropene is an excellent reagent for the synthesis of furanoterpenoids.3,13 Condensation with b-diketones and sulfoxide elimination gave ligularone and isoligularone, respectively (eq 7). The methods were also used to prepare curzerenone, epicurzerenone, and pyrocurzerenone.

Nitroalkenes derived from b-lactam aldehydes may be converted into diverse bicyclic b-lactams via intramolecular Michael addition and ozonolysis (eq 8). The method is appropriate for penam, carbapenam, carbacephem, and oxapenam arrays.4 In some cases, (benzyloxy)nitromethane is a superior reagent.14 This Michael addition-oxidation strategy is also useful for the synthesis of tetrahydrofuran (eq 9) and -pyran systems.15

(Phenylthio)nitromethane has been dehydrated and the resultant phenylthionitrile oxide trapped with alkenes to provide isoxazolines (eq 10).16 These compounds are convenient precursors for 3-(phenylsulfonyl)isoxazolines (see Phenylsulfonylnitromethane) and b-hydroxy ketones. The cycloaddition-ring contraction of ynamines with 1-nitro-1-phenylthioalkenes has been used to prepare cyclic nitrones (eq 11).17

The Michael addition of (phenylthio)nitromethane to a steroidal enone and nitro displacement (eq 12) has been employed in the stereoselective 16-methylation of corticosteroids.18

1. Barrett, A. G. M. CSR 1991, 20, 95.
2. (a) Barrett, A. G. M.; Graboski, G. G.; Russell, M. A. JOC 1986, 51, 1012. (b) Banks, B. J.; Barrett, A. G. M.; Russell, M. A. CC 1984, 670.
3. (a) Miyashita, M.; Kumazawa, T.; Yoshikoshi, A. JOC 1980, 45, 2945. (b) Miyashita, M.; Kumazawa, T.; Yoshikoshi, A. CC 1978, 362.
4. (a) Barrett, A. G. M.; Graboski, G. G.; Sabat, M.; Taylor, S. J. JOC 1987, 52, 4693. (b) Barrett, A. G. M.; Graboski, G. G.; Russell, M. A. JOC 1985, 50, 2603.
5. Barrett, A. G. M.; Lebold, S. A. JOC 1990, 55, 3853.
6. Barrett, A. G. M.; Dhanak, D.; Graboski, G. G.; Taylor, S. J. OS 1989, 68, 8.
7. (a) Bordwell, F. G.; Bares, J. E.; Bartmess, J. E.; Druker, G. E.; Gerhold, J.; McCollum, G. J.; Van Der Puy, M.; Vanier, N. R.; Matthews, W. S. JOC 1977, 42, 326. (b) Bordwell, F. G.; Bartmess, J. E. JOC 1978, 43, 3101.
8. Seebach, D.; Lehr, F. HCA 1979, 62, 2239.
9. (a) Ashwell, M.; Jackson, R. F. W. CC 1988, 282. (b) Ashwell, M.; Jackson, R. F. W.; Kirk, J. M.; T 1990, 46, 7429.
10. Lehr, F.; Gonnermann, J.; Seebach, D. HCA 1979, 62, 2258.
11. Kim, S.; Park, J. H. CL 1988, 1323.
12. Barrett, A. G. M.; Weipert, P. D.; Dhanak, D.; Husa, R. K.; Lebold, S. A. JACS 1991, 113, 9820.
13. (a) Miyashita, M.; Kumazawa, T.; Yoshikoshi, A. Tennen Yuki Kago Butsu Toronki Koen Yoshishu 1978, 21, 472 (CA 1979, 90, 168 757j). (b) Miyashita, M.; Kumazawa, T.; Yoshikoshi, A. JOC 1984, 49, 3728. (c) Miyashita, M.; Kumazawa, T.; Yoshikoshi, A. CL 1981, 593; 1979, 163.
14. (a) Barrett, A. G. M.; Cheng, M.-C.; Spilling, C. D.; Taylor, S. J. JOC 1989, 54, 992. (b) Barrett, A. G. M.; Cheng, M.-C.; Sakdarat, S.; Spilling, C. D.; Taylor, S. J. TL 1989, 30, 2349. (c) Barrett, A. G. M.; Sakdarat, S. JOC 1990, 55, 5110.
15. Barrett, A. G. M.; Flygare, J. A.; Spilling, C. D. JOC 1989, 54, 4723.
16. (a) Curran, D. P.; Chao, J.-C. JOC 1988, 53, 5369. (b) Harada, K.; Kaji, E.; Zen, S. NKK 1981, 1195.
17. Van Eijk, P. J. S. S.; Overkempe, C.; Trompenaars, W. P.; Reinhoudt, D. N.; Manninen, L. M.; VanHummel, G. J.; Harkema, S. RTC 1988, 107, 27.
18. Boivin, J.; Chauvet, C.; Zard, S. Z. TL 1992, 33, 4913.

Anthony G. M. Barrett

Imperial College of Science, Technology and Medicine, London, UK

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