N-[(Hexadecyloxy)sulfonylethyl]-N,N,N-trimethylammonium Fluorosulfate1

[66143-52-0]  · C21H46FNO6S2  · N-[(Hexadecyloxy)sulfonylethyl]-N,N,N-trimethylammonium Fluorosulfate  · (MW 491.81)

(alkyl transfer agent1,2)

Alternate Names: 2-[(hexadecyloxy)sulfonyl]-N,N,N-trimethylethanaminium fluorosulfate; hexadecyl [2]betylate fluorosulfate.

Physical Data: white solid.2

Solubility: sol H2O, MeOH, organic solvents (e.g. DME, toluene), two-phase H2O-organic solvent mixtures.2

Analysis of Reagent Purity: [2]betylates show a characteristic signal (typically a broad singlet) at ~3.7 ppm in the 1H NMR spectrum.2

Preparative Methods: [2]betylates (3) are prepared2 from alcohols by the sequence ROH -> (1) -> (2) -> (3) (eq 1). Vinylsulfonyl chloride is easily made by the action of 2,6-Lutidine or cold Triethylamine on 2-chloroethanesulfonyl chloride,3,4 which is obtained commercially or made from sodium 2-hydroxyethanesulfonate (sodium isethionate) and Thionyl Chloride with a catalytic amount of DMF.5

Handling, Storage, and Precautions: [2]betylates (3) are usually prepared as needed, but may be stored under dry conditions for extended periods.

Alkyl Transfer Intermediates.

Betylates [Me3+N(CH2)nSO2OR X-] are useful intermediates, enabling an alcohol to transfer its alkyl group to a variety of nucleophiles to form a wide array of products (eq 2). (The byproduct in these reactions is a betaine; hence the nickname betylate.)

Of the various betylates, those with n = 2 ([2]betylates) offer the most serviceable combination of ease of preparation and handling, and general reactivity under neutral or acidic conditions. [0]Betylates (n = 0) are extremely reactive and not usually isolated;6 [3]- and [4]betylates (n = 3, 4) are less conveniently made than [2]betylates, but can be used in much more basic media.2

The title compound and related alkyl [2]betylates react readily (rt, 0.5-24 h) with a wide variety of water-soluble nucleophiles (Sodium Azide, Sodium Thiocyanate, KBr, NaCl, KNO3, Thiourea, Na2SO3 and Sodium Thiosulfate), either in water or in such two-phase aqueous-organic mixtures as CH2Cl2-H2O, to give the alkyl transfer products (azide, thiocyanate, bromide, etc.) in fair to excellent yields. Other tested alkyl groups include butyl, 1-methylheptyl, 3-phenylpropyl, and docosyl.2

The nucleophile may be made the counterion of the betylate cation (by ion extraction or with an ion-exchange resin); the salt so obtained may lead to a substrate-reagent ion-pair (SRIP) reaction,2 as in eq 3. Nu- in eq 3 may be not only I-, SCN-, picrate, and formate, but also ClO4-, FSO3-, CF3SO3-, CH2=CHSO3-, etc., yielding the alkyl perchlorate, fluorosulfate, triflate, or vinylsulfonate in fair to excellent yields.2 SRIP reactions also take place with norbetylates (4), produced by addition of the conjugate acid of the nucleophile to the alkyl 2-(dimethylamino)ethanesulfonate (2).2

SRIP reactions at a chiral secondary center go with complete inversion of configuration. (S)-(+)-2-Iodooctane was obtained in high optical purity (i.e. without subsequent racemization by I-) from (R)-1-methylheptyl [2]betylate iodide.2 (R)-2-Octanol was converted into both (S)-2-bromooctane and (R)-2-bromooctane by the sequence shown in eq 4.2

The betylate procedure was found7 to be valuable for introducing the isobutyl group to make (5) (eq 5).

1. Fieser, M.; Danheiser, R. L.; Roush, W. R. FF 1981, 9, 211.
2. King, J. F.; Loosmore, S. M.; Aslam, M.; Lock, J. D.; McGarrity, M. J. JACS 1982, 104, 7108.
3. Rondestvedt, C., Jr. JACS 1954, 76, 1926.
4. Etienne, A.; Lonchambon, G.; Benard, C. BSF 1976, 483.
5. Le Berre, A.; Etienne, A.; Dumaitre, B. BSF 1970, 946.
6. King, J. F.; Lee, T. M. L. CJC 1981, 59, 356, 362.
7. King, J. F.; Tsang, G. T. Y.; Abdel-Malik, M. M.; Payne, N. C. JACS 1985, 107, 3224.

James F. King

The University of Western Ontario, London, Ontario, Canada

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