O-(Mesitylsulfonyl)hydroxylamine1

[36016-40-7]  · C9H13NO3S  · O-(Mesitylsulfonyl)hydroxylamine  · (MW 215.2)

(reagent for electrophilic aminations, NH2 transfer to nucleophiles)

Physical Data: mp 93-94 °C.1

Solubility: very sol diethyl ether, chloroform, dichloromethane, benzene, ethanol, THF; insol water and petroleum ether.

Analysis of Reagent Purity: IR (KCl) n(cm-1) 3340, 3250, 1600, 1350, 1190, 1180.1

Preparative Methods: to a solution of 89 g (330 mmol) O-(mesitylsulfonyl)acetohydroxamate (1) in dioxane is added with stirring 30 mL perchloric acid (70%) at 0 °C within 10 min, and then stirred for another 10 min. After about 20 mL of the acid has been added, the reaction mixture becomes pasty. The crude reaction mixture is poured into ice-water to give a white solid of O-(mesitylsulfonyl)hydroxylamine (2) (eq 1) which is collected, washed with cold water (500 mL), then with cold petroleum ether (300 mL), and dried by maintaining suction for about 1 h; yield 55-65 g (77-92%).1

The product should be stored in a refrigerator below 0 °C. Iodometric titration indicates that (2) thus prepared contains 20-30% water. It can be used for most applications. A further purification can be achieved by dissolution of a small amount in diethyl ether at room temperature and precipitation with petroleum ether.

Handling, Storage, and Precautions: caution: O-(mesitylsulfonyl)hydroxylamine (2) must be handled with care. A first report about a rapid decomposition when standing at room temperature appeared in 1977.2 After an explosion of (2) during storage below 0 °C,3 as suggested above,1 it is strongly recommended that (2) be prepared immediately prior to use, and that it not be stored.3

Reactions with Heteroaromatic Amines.

N-Amine salts of heteroaromatic amines have received wide attention as synthetic intermediates for heterocyclic compounds.4 The use of (2) in place of, e.g. Hydroxylamine-O-sulfonic Acid, has many advantages. The amination procedure is outlined in (eq 2) and the results for some representative heteroaromatic systems are summarized in Table 1.

Typical Procedure for N-Amination.

To an ice-cold solution of the amine (e.g. 1.00 mmol Pyridine) in dichloromethane (2 mL) is added dropwise a solution of (2) (1.00 mmol) in dichloromethane (2 mL). The reaction mixture is allowed to stand at 20 °C for 10 min. After addition of diethyl ether, the precipitated crystals are collected and recrystallized from methanol/ethyl acetate to give the N-aminopyridinium mesitylsulfonate (3); 235 mg yield (80%), mp 125-126 °C.1

Reactions with Tertiary Amines.

Reagent (2) aminates a variety of tertiary amines, including alkaloids, under very mild conditions to give the corresponding 1,1,1-trisubstituted hydrazonium salts in high yields.11 Some typical examples are listed in Table 2.

Reactions with Secondary Amines.

The formation of 1,1-disubstituted hydrazines with (2) occurs in lower yield than with hydroxylamine-O-sulfonic acid or Chloramine; another useful reagent is O-Mesitoylhydroxylamine (13),1,12 which gives (14) in 58% yield.

More interesting is the reaction between (2) and compounds of the type (15), which leads (probably via 16-18) to benzodiazepine derivatives such as (19) (eq 3).13

Reactions with the Anionic Nitrogen of Amides, Imides, and Pyrroles.

Reagent (2) is not a successful aminating reagent for these anionic species, with O-mesitoylhydroxylamine (13) being the more effective. Two examples, derived from their sodium salt, are (20) and (21).14,15

Reactions with Sulfides.

The reactions of sulfides with (2) provide the easiest and most efficient access to S-amine mesitylsulfonates (22) (eq 4). A few examples from a long list are collected in Table 3.16

With allyl sulfides, consecutive reactions of the S-amine mesitylsulfonates (23) lead, probably via the intermediate sulfilimines (24), to allylamines (25) (eq 5).1

Reactions with Sulfoxides.

The synthetically very important sulfoximines (28) are easily prepared from sulfoxides (26) and (2) via the S-aminosulfoxonium mesitylsulfonates (27) (eq 6). Some pertinent examples for the formation of (27) are given in Table 4.

Reactions with S,S-Acetals.

S,S-Acetals are readily dethioacetalized by (2). This is thus a method to cleave S,S-acetals from a,b-unsaturated ketones, ketones, and aldehydes (eq 7 and Table 5).19

The oxidation at sulfur with (2) is also achieved in the case of disulfides, thioketones, and thiols.1

Reactions with Phosphines.

Not surprisingly, (2) also aminates phosphines to give P-aminophosphonium salts such as (33) in very good yields (eq 8).1 Other electrophilic H2N transfer reagents aminate phosphines in a similar fashion.1

Reactions with Carbanions.

The amination of carbanions with (2) has also been investigated (eq 9).20 The a-amino diethyl phosphonoacetate (34) was formed in moderate yields. Most probably, the basic anion deprotonated (2) at least in part, which should lead to fast decomposition of the resulting nitrenoid. In a similar fashion, aminomalonitrile tosylate (35) has been formed via a simple procedure (eq 10).3

Amination of the enolate precursor to give 2-exo-amino-6-endo-(methylthio)-bicyclo[2.2.1]heptane-2-endo-carboxylic acid (36) in 38% yield has been described.21

Since early observations of electrophilic aminations of organoboranes with hydroxylamine-O-sulfonic acid or chloramine,22 it is not surprising that the reaction of R3B with (2) similarly gives primary amines, albeit under milder conditions. Some amines formed via di- or trialkylboranes are (37)-(39), shown with the corresponding alkenes (Scheme 1).23

There exists a variety of aminating reagents for carbanions which are much better than (2). An excellent review on this topic has been written20c (see also O-(Diphenylphosphinyl)hydroxylamine).

Reactions with Electrophiles.

Reagent (2) also reacts with electrophiles, although this chemistry is of minor importance. Thus reaction of (2) with ketones (40) leads to the corresponding oximes (41), which are intermediates for the Beckmann and Neber rearrangements (eq 11).24,25

With Schiff bases derived from aliphatic aldehydes (42) (aldimines), (2) forms diaziridines (43) (eq 12).1,26

If R1 is a phenyl group as in (44), phenylhydrazones are formed instead (eq 13).27

Finally, it has been reported that (2) also reacts with strongly electrophilic alkenes like (45) to give (46), which after treatment with base affords 1H-aziridines such as (47) (eq 14).28


1. (a) Tamura, Y.; Minamikawa, J.; Ikeda, M. S 1977, 1. (b) Krause, J. G. S 1972, 140.
2. Ning, R. Y. Chem. Eng. News 1973, 51 (Dec. 17), 36.
3. Taylor, E. C.; Sun, J. H. S 1980, 801.
4. Timpe, H. J. Adv. Heterocycl. Chem. 1974, 17, 213.
5. Tamura, Y.; Miki, Y.; Sumida, Y.; Ikeda, M. JCS(P1) 1973, 2580.
6. (a) Tamura, Y.; Miki, Y.; Ikeda, M. JHC 1973, 10, 447. (b) Eichenberger, Th.; Balli, H. HCA 1986, 69, 1521.
7. (a) Tamura, Y.; Miki, Y.; Minamikawa, J.; Ikeda, M. JHC 1974, 11, 675. (b) Tamura, Y.; Miki, Y.; Ikeda, M. JHC 1975, 12, 119. (c) Tamura, Y.; Miki, Y.; Nakamura, K.; Ikeda, M. JHC 1976, 13, 23.
8. (a) Tamura, Y.; Hayashi, H.; Minamikawa, J.; Ikeda, M. CI(L) 1973, 952. (b) Tamura, Y.; Hayashi, H.; Minamikawa, J.; Ikeda, M. JHC 1974, 11, 781. (c) Tamura, Y.; Hayashi, H.; Ikeda, M. JHC 1975, 12, 819.
9. Tamura, Y.; Hayashi, H.; Ikeda, M. S 1974, 126.
10. (a) Wiemer, D. F.; Leonard, N. J. JOC 1974, 39, 3438. (b) Kos, N. J.; Jongejan, H.; Van der Plas, H. C.; van Veldhuizen, A. RTC 1985, 104, 302. (c) Frankowski, A. T 1986, 1511. (d) Streith, J.; Tschamber, T.; Wolff, G. LA 1983, 1374.
11. (a) Tamura, Y.; Minamikawa, J.; Kita, Y.; Kim, J. H.; Ikeda, M. T 1973, 29, 1063. (b) Fennhoff, G.; Heesing, A. CB 1989, 122, 1153.
12. Carpino, L. A. JACS 1960, 82, 3133.
13. (a) Tamura, Y.; Minamikawa, J.; Matsushima, H.; Ikeda; M. S 1973, 159. (b) Back, T. G.; Barton, D. H. R. JCS(P1) 1977, 924.
14. (a) Carpino, L. A. JOC 1965, 30, 736. (b) Carpino, L. A.; Padykula, R. E.; Barr, D. E.; Hall, F. H.; Krause, J. G.; Dufresne, R. F.; Thoman, C. J. JOC 1988, 53, 2565.
15. (a) Carpino, L. A. JOC 1965, 30, 321. (b) Liu, K.-C.; Shih, B.-J.; Hu, M.-K. JHC 1987, 24, 1729.
16. (a) Tamura, Y.; Matsushima, H.; Minamikawa, J.; Ikeda, M. T 1975, 31, 3035. (b) Franek, W.; Claus, P. K. M 1990, 121, 539. (c) Young, P. R.; Reid, K. J. JOC 1987, 52, 2695.
17. Tamura, Y.; Sumoto, K.; Minamikawa, J.; Ikeda, M. TL 1972, 4137.
18. Johnson, C. R.; Kirchhoff, R. A.; Corkins, H. G. JOC 1974, 39, 2458.
19. Tamura, Y.; Sumoto, K.; Fujii, S.; Satoh, H; Ikeda, M. S 1973, 312.
20. (a) Scopes, D. I. C.; Kluge, A. F.; Edwards, J. A. JOC 1977, 42, 376. (b) Erdik, E. Commun. Fac. Sci. Univ. Ankara, Ser. B 1980, 26, 83. (c) Erdik, E.; Ay, M. CVR 1989, 89, 1947.
21. Glass, R. S.; Hojjatie, M.; Sabahi, M.; Steffen, L. K.; Wilson, G. S. JOC 1990, 55, 3797.
22. (a) Brown, H. C.; Heydkamp, W. R.; Breuer, E.; Murphy, W. S. JACS 1964, 86, 3565. (b) Rathke, M. W.; Inoue, N.; Varma, K. R.; Brown, H. C. JACS 1966, 88, 2870.
23. Tamura, Y.; Minamikawa, J.; Fujii, S.; Ikeda, M. S 1974, 196.
24. Tamura, Y.; Fujiwara, H.; Sumoto, K.; Ikeda, M.; Kita, Y. S 1973, 215.
25. Luh, T. Y.; Chow, H. F.; Leung, W. Y.; Tam, S. W. T 1985, 41, 519.
26. Makhova, N. N.; Petukhova, V. Yu.; Khmel'nitskii, L. I. IZV 1982, 2107; BAU 1982, 1858.
27. Tamura, Y.; Hayashi, H.; Nishimura, Y.; Ikeda, M. JHC 1975, 12, 225.
28. Métra, P.; Hamelin, J. CC 1980, 1038.

Gernot Boche

Philipps-Universität Marburg, Germany



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