Potassium Hydroxide-Dimethyl Sulfoxide

KOH-Me2SO
(KOH)

[1310-58-3]  · HKO  · Potassium Hydroxide-Dimethyl Sulfoxide  · (MW 56.11) (DMSO)

[67-68-5]  · C2H6OS  · Potassium Hydroxide-Dimethyl Sulfoxide  · (MW 78.15)

(very strong base; low nucleophilicity due to low solubility which allows only surface reactivity2)

Physical Data: see entries for Potassium Hydroxide and Dimethyl Sulfoxide; KOH/DMSO has pKa of 27 or higher.1

Alkylation of Amides, Phenols, Alcohols, and Acids.

A variety of carboxamides were alkylated with primary alkyl halides using KOH in DMSO to give the N-alkyl amides (eq 1) in 54-90% yield. Most reactions were carried out at rt, but in some cases heating to 90 °C was required.3 Similar conditions were applied to alcohols, phenols, and acids to form ethers and esters.4 The procedure applies to MeI and all primary halides. Secondary alkyl halides show evidence of competitive dehydrohalogenation, while tertiary halides do not give any alkylation products. The procedure was applied to the N- and O-permethylation of peptides.4 It was also applied to the methylation of hydroxypyridines in 39-78% yield.5 In all the above cases, the substrate and alkyl halide were added to powdered KOH in DMSO and stirred at rt. It was unnecessary to use especially dry DMSO or to protect the reaction mixture from atmospheric moisture.

N-Alkylation of Indoles and Pyrroles.

N-Alkyl indoles and pyrroles were prepared in high yields (85-95%) by reaction of indoles and pyrroles with primary alkyl halides in DMSO and powdered KOH at rt (eq 2). The yields were lower with secondary halides (60% for N-isopropylindole), while tertiary halides gave no alkylation products.6

Alkylation of Ketones.

Ketones can be permethylated with Iodomethane in DMSO containing solid KOH. Cyclobutanone, cyclopentanone, and indanone gave the corresponding tetramethyl ketones in 49, 90, and 75% yields, respectively. All reagents can be used without drying and KOH can be used as pellets or as a powder.2

Synthesis of O-Arylhydroxylamines.

Reaction of tricarbonylchromium complexes of aryl halides (1) with N-t-butoxycarbonylhydroxylamine (2) in DMSO and powdered KOH under N2 at rt resulted in the nucleophilic substitution of the Cl to give the corresponding tricarbonyl[(t-butoxycarbonylaminoxy)arene]chromium complexes (3) (eq 3). Consecutive I2 treatment and acid hydrolysis gave the O-arylhydroxylamines in high overall yields.7

Hydroxylation of Ketones.

Treatment of the ketone (4) with KOH in warm DMSO in the presence of O2 followed by the in situ reduction of the intermediate hydroperoxide with dithionite gave (5) as a 1:1 mixture of diastereomers (eq 4).8

Synthesis of (E)-b-(Benzyloxy)styrenes from Benzyl Alcohols.

(E)-b-(Benzyloxy)styrenes (7) were obtained from the reaction of benzyl alcohols (6) with KOH/DMSO (eq 5) in 56-92% yields. This result was explained by an initial oxidation to the benzaldehyde followed by a condensation with DMSO anion to form intermediate (8). Subsequent addition of benzyloxide anion to (8) and elimination of MeSO- gives the product (7). The incorporation of the DMSO carbon was confirmed by 2H and 13C labelling. The methyl styryl sulfoxide intermediate (8) was independently synthesized and converted into (7) under identical reaction conditions.9

Preparation of N-Vinylpyrroles.

The reaction of ketoximes having at least one a-CH2 group with acetylene in DMSO/KOH at 80-120 °C under atmospheric pressure gave N-vinylpyrroles in average yields of 70-80% via an intermediate pyrrole (eq 6). The conditions are also suitable for N-vinylation of pyrroles and other NH heterocycles in good yields.1b


1. For discussions of the behavior of KOH in polar aprotic solvents see (a) Jolly, W. L. J. Chem. Educ. 1967, 44, 304. (b) Trofimov, B. A. RCR 1981, 50, 138 and references therein.
2. Langhals, E.; Langhals, H. T 1990, 31, 859 and references therein.
3. Isele, G. L.; Lüttringhaus, A. S 1971, 266.
4. Johnstone, R. A. W.; Rose, M. E. T 1979, 35, 2169.
5. Finkentey, C.; Langhals, E.; Langhals, H. CB 1983, 116, 2394.
6. Heaney, H.; Ley, S. V. JCS(P1) 1973, 499.
7. Baldoli, C.; Del Buttero, P.; Licandro, E.; Maiorana, S. S 1988, 344.
8. Sorgi, K. L.; Maryanoff, C. A.; McComsey, D. F.; Graden, D. W.; Maryanoff, B. E. JACS 1990, 112, 3567.
9. Langhals, H.; Julia, M.; Uguen, D. LA 1982, 2216.

Ahmed F. Abdel-Magid

The R. W. Johnson Pharmaceutical Research Institute, Spring House, PA, USA



Copyright 1995-2000 by John Wiley & Sons, Ltd. All rights reserved.