N,N-Dimethyl-O-(methylsulfonyl)hydroxylamine1

[75812-61-2]  · C3H9NO3S  · N,N-Dimethyl-O-(methylsulfonyl)hydroxylamine  · (MW 139.20)

(reagent for electrophilic aminations, Me2N transfers to nucleophiles)

Physical Data: mp 33-35 °C.2

Solubility: sol THF, diethyl ether; very sol CHCl3, CH2Cl2.2

Analysis of Reagent Purity: 1H NMR (CDCl3) (ppm) 2.90 (s, 6 H, Me2N), 3.08 (s, 3 H, MeSO2).2

Preparative Methods: to a solution of 29.3 g (300 mmol) N,N-dimethylhydroxylamine hydrochloride and 35.6 g (300 mmol) Methanesulfonyl Chloride in 360 mL CH2Cl2 is added dropwise under stirring at -20 °C a solution of 60.7 g (600 mmol) Triethylamine in 240 mL CH2Cl2. After stirring for 30 min at 0 °C the reaction mixture is poured into ice water, the organic phase is extracted another two times with ice water and then dried over MgSO4 at 0 °C. After removal of the solvent at 0 °C the noncrystalline residue is dissolved in 60 mL diethyl ether. On standing at -30 °C, N,N-dimethyl-O-(methylsulfonyl)hydroxylamine (1) crystallizes in colorless needles which are separated in a cooled frit. After one (or two) recrystallization(s) from diethyl ether between 21.9 and 26.4 g (53-63%) (1) are isolated.3,4 In a similar fashion the following compounds have been prepared and used in electrophilic amination reactions: N,N-dimethyl-O-(phenylsulfonyl)hydroxylamine, mp 18-19 °C;2b,3 N,N-diethyl-O-(mesitylsulfonyl)hydroxylamine, mp 103-104 °C;2b,3 N,N-diethyl-O-(phenylsulfonyl)hydroxylamine, mp 46-47 °C;2b N,N-diethyl-O-(mesitylsulfonyl)hydroxylamine, mp 68-69 °C;2b,3 N-(O-phenylsulfonyl)hydroxypiperidine, mp 57-58 °C;2b N-(O-mesitylsulfonyl)hydroxypiperidine, mp 50-51 °C;2b N-(O-mesitylsulfonyl)hydroxypyrrolidine, mp 23-24 °C.2b

Handling, Storage, and Precautions: reagents for electrophilic aminations with N,N-dimethyl(dialkyl) functionality like (1) are much more stable than their NH2 analogs. Thus the pure compound (1) can be stored at -30 °C for at least 1 year.2,3 Impure (1) (and related compounds), however, may decompose at rt,2,3 as also reported for N,N-diethyl-O-(mesitylsulfonyl)hydroxylamine.5

Electrophilic Aminations.

N,N-Dimethyl-O-(methylsulfonyl)hydroxylamine (1) reacts with organometallic compounds RM to give N,N-dimethylamines (2) (eq 1). N,N-Dimethylamines prepared via eq 1 from RM and (1) together with a specification of RM are shown in (3)-(19).

As can be seen from the structures shown, N,N-dimethyl-O-(methylsulfonyl)hydroxylamine (1) aminates alkyl Grignard compounds (to give 3) and aryl Grignard compounds (to give 4) with moderate yields. The same is true for benzylic anion type carbon atoms (5-9). Compounds (10) and (11) are formed from the corresponding malonates, while (12)-(16) are derived from (ester)enolates, although with aryl-stabilized anionic carbon atoms. Metalated cyanides lead to (17)-(19).

Related amination reactions of organometallic compounds RM have been performed with N,N-dimethyl-O-(mesitylsulfonyl)hydroxylamine (20),3 N,N-dimethyl-O-(phenylsulfonyl)hydroxylamine (21),3 and N,N-dimethyl-O-(p-tolylsulfonyl)hydroxylamine (22).4a Structures (23)-(26) provide examples of N,N-dimethylamines formed by reactions of RM with the mesitylsulfonyl species (20).3,6

N,N-Dimethylamines of strained hydrocarbons like (23) and especially (24) are otherwise not easily accessible. The same is true for the cyclononatetraenylamine (26).6 N,N-Dimethyl-O-(p-tolylsulfonyl)hydroxylamine (22) is reported to react with Phenylmagnesium Bromide and cyclohexylmagnesium bromide to give the corresponding N,N-dimethylamines in 54% and 14% yield, respectively.4a For further and comparable electrophilic amination reactions with transfer of a Me2N group to give, for example, (27)-(29), see N,N-Dimethyl-O-(diphenylphosphinyl)hydroxylamine.

Disadvantages.

Normal enolates are not aminated by (1), (20), (21), or (22), probably because of a b-elimination of MeSO3H initiated by deprotonation at one of the N-methyl groups.4a a-Lithiated sulfones like (30) are aminated to give (31) (eq 2); however, the reaction does not stop there. Rather, the a-aminosulfone (31) leads with unreacted (30) to the b-aminosulfone (32) (eq 3). Without the phenyl substituent at the anionic carbon atom, only the cuprate (33) gives (34) (eq 4).2b

The corresponding Li compound deprotonates (1) (or 20-22). With the dibenzylamine reagent (35), amination of RLi is not observed because of the comparatively fast b-elimination to give (36) due to the rather acidic benzylic hydrogen atoms (eq 5).4b

Reactions with organometallic compounds in which iodide I- is present (e.g. in Grignard reagents of the type RMgI) should be avoided because I- reduces (1); a similar reaction is not observed with Cl- and Br- containing organometallic compounds.


1. Erdik, E.; Ay, M. CRV 1989, 89, 1947.
2. (a) Niebner, M., Diploma Thesis, Universität Marburg, 1980. (b) Bernheim, M. Ph.D. Thesis, Universität München, 1981.
3. Boche, G.; Mayer, N.; Bernheim, M.; Wagner, K. AG(E) 1978, 17, 687.
4. Other syntheses of O-sulfonylhydroxylamines. (a) N,N-Dimethyl-O-(p-tolylsulfonyl)hydroxylamine: Barton, D. H. R.; Bould, L.; Clive, D. L. J.; Magnus, P. D.; Hase, T. JCS(C) 1971, 2204. (b) N,N-Dibenzyl-O-(p-tolylsulfonyl)hydroxylamine: Sheradsky, T.; Itzhak, N. JCS(P1) 1986, 13. See also: (c) Tamura, Y.; Minamikawa, J.; Sumoto, K.; Fujii, S.; Ikeda, M. JOC 1973, 38, 1239. (d) Carpino, L. A. JACS 1960, 82, 3133. (e) Carpino, L. A. JOC 1964, 29, 2820.
5. Abraham, T.; Curran, D. T 1982, 38, 1019.
6. Boche, G.; Bernheim, M.; Lawaldt, D.; Ruisinger, B. TL 1979, 4285.

Gernot Boche

Philipps-Universität Marburg, Germany



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