Potassium Hydroxide-Hexamethylphosphoric Triamide


[1310-58-3]  · HKO  · Potassium Hydroxide-Hexamethylphosphoric Triamide  · (MW 56.11) (HMPA)

[680-31-9]  · C6H18N3OP  · Potassium Hydroxide-Hexamethylphosphoric Triamide  · (MW 179.24)

(strongly basic; esterification of hindered acids; additions to alkynes; ketone oxidations)

Physical Data: see entries for Potassium Hydroxide and Hexamethylphosphoric Triamide.

Esterification of Hindered Carboxylic Acids.

Esters of hindered carboxylic acids, such as dialkyl and trialkyl acetic acids and mesitoic acid, were synthesized in high yields using alkyl halides, HMPA and EtOH as cosolvents, and KOH at 50 °C (eq 1). Esterifications were very rapid, near quantitative, and allowed the preparation of methyl and other alkyl esters.

Under these conditions, some dialkyl acetic acids were esterified to the methyl esters in 5 min with 98% conversion. The trialkyl acetic acid 2-methyl-2-propylpentanoic acid (1a) was quantitatively converted to the methyl ester (1b) in 30 min. Interestingly, the rate of reaction for the branched acid (1a) was about 5 times that of its straight chain analog, nonanoic acid. Mesitoic acid (2a) was esterified with Iodomethane in 20 min to give the methyl ester (2b) in 96% yield and with 2-iodooctane to give the 2-octyl ester (2c) in 80% yield in 2 h. The reaction was slower in the absence of HMPA as a cosolvent and gave significantly lower conversions.1

Additions to Acetylene.

Addition of H2S to acetylene in the superbasic medium of KOH/HMPA gave ethanethiol as the only product. Under these conditions, the initial addition product, the vinylthiol anion, was reduced to give the product (eq 2).2 The reaction in DMSO gave, among other products, divinyl sulfide.2

The reaction of elemental tellurium with acetylene in HMPA and KOH gave divinyl telluride in >50% yield (eq 3).2

Preparation of Divinyloxypropenes.

Divinyloxypropenes (3) and (4) were obtained from the reaction of glycerol with acetylene in HMPA in the presence of KOH under a pressure of 10 atm at 150-160 °C for 2 h (eq 4). The product mixture (~25% overall yield) contained cis- and trans-1,2-divinyloxypropenes (3) (11%) and 2,3-divinyloxypropene (4) (1%) in addition to 2-methyl-4-vinyloxymethyl-1,3-dioxolane (5) (~7%) and 2-vinyloxy-1,3-butadiene (6) (~5%).3 In the absence of HMPA the major reaction product was the 1,3-dioxolane (5) (33-66%), depending on the reaction conditions.4

Oxidation of Ketones.

Oxidations of acetophenone to benzoic acid (eq 5) and cyclic ketones to dicarboxylic acids (eq 6) were carried out with O2 in the presence of KOH (or NaOH) in HMPA. The use of HMPA was superior to hydroxylic solvents, water, DMF, or DMSO. Either KOH or NaOH was an equally effective base catalyst, but LiOH was extremely poor. In the oxidation of acetophenone, addition of water slowed down the rate of oxidation but minimized the side reactions arising from the ketone enolate, thus increasing the selectivity to acidic products. Yields were moderate to excellent.5

1. Pfeffer, P. E.; Foglia, T. A.; Barr, P. A.; Schmeltz, I.; Silbert, L. S. TL 1972, 4063.
2. Trofimov, B. A. RCR 1981, 50, 138.
3. Trofimov, B. A.; Malysheva, S. F.; Sigalov, M. V.; Vyalykh, E. P.; Kalabin, G. A. TL 1984, 25, 4257.
4. Shachat, N.; Schneider, H. J.; Nedwick, J. J.; Murdoch, G. C.; Bagnell, J. J. JOC 1961, 26, 3712.
5. Wallace, T. J.; Pobiner, H.; Schriesheim, A. JOC 1965, 30, 3768.

Ahmed F. Abdel-Magid

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

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