Potassium Hydroxide

KOH

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

(very strong alkali; reacts readily with acids; used in nucleophilic substitution reactions, addition reactions, and basic hydrolysis reactions; occasionally employed as a catalyst for aldol-type reactions; ethanolic solution (alcoholic KOH) is traditionally used in dehydrohalogenation of halides)

Physical Data: mp 361 °C; d 2.044 g cm-3.

Solubility: sol 0.9 part water, 0.6 part boiling water, or 3 parts ethanol; its dissolution in water is exothermic.

Form Supplied in: white lumps, rods, or pellets; commercially available pellets contain 85-88% KOH and 10-15% water.

Handling, Storage, and Precautions: toxic (oral-rat: LD50: 365 mg kg-1). Corrosive. Harmful if swallowed, inhaled, or absorbed through skin. Material is extremely destructive to tissue of the mucous membranes and upper respiratory tract. Inhalation may be fatal. Do not breathe dust. Avoid contact with eyes, skin, and clothing. Store in a cool dry place. Extremely hygroscopic. Wash thoroughly after handling.1

Incompatible with acids, acid chlorides, acid anhydrides, and aluminum metal. Absorbs moisture and CO2 from air.

Elimination Reactions.

Alcoholic KOH is the most frequently used base for dehydrohalogenation of alkyl halides in the synthesis of alkenes.2 Some representative examples showing the use of KOH in elimination reactions are listed here.

Preparation of Diphenylacetylene.

Diphenylacetylene was prepared via the dehydrohalogenation of stilbene dibromide. The dibromide was heated at reflux temperature with KOH in absolute ethanol for 24 h. After workup and recrystallization, a 66-69% yield of pure diphenylacetylene was obtained (eq 1).3

An alternative procedure for the synthesis of diphenylacetylene used the quaternary enammonium salt of deoxybenzoin via a Hofmann elimination reaction. Thus treatment of the methylated pyrrolidine enamine of deoxybenzoin (1) with 40% aq KOH at reflux afforded an 86% yield of diphenylacetylene (eq 2). The reaction was not as successful with other enamines.4

Preparation of Muconic Acid.

Muconic acid (1,3-butadiene-1,4-dicarboxylic acid) (3) was prepared by dehydrohalogenation and hydrolysis of diethyl a,d-dibromoadipate (2) upon heating with KOH in MeOH at reflux (eq 3). The acid was obtained in 37-43% yield.5

Synthesis of Coumarilic Acid.

2-Benzofurancarboxylic acid (coumarilic acid) (5) was prepared from coumarin dibromide (4) by the action of alcoholic KOH (eq 4). The product was isolated, after acidification, in 82-88% yield.6

Hydrolysis of Hindered Esters.

A solid-liquid phase-transfer catalysis system without organic solvents was developed for the hydrolysis of hindered esters such as mesitoic esters. The system consists of powdered KOH and 2% Aliquat 336 (methyltrioctylammonium chloride). The best results were obtained with 5 mol equiv of powdered KOH + 2% Aliquat 336 at 85 °C for 5 h (eq 5).7

Hydrolysis of Nitriles to Amides.

Several nitriles were chemoselectively hydrolyzed to the corresponding amides when heated at reflux in t-butyl alcohol containing powdered solid KOH. Thus benzonitrile was converted to benzamide in 94% yield when refluxed in t-BuOH containing powdered KOH for 20 min (eq 6). The amides were not further hydrolyzed to the carboxylic acids under these conditions; this was explained by the formation of an insoluble K salt which thus precluded further nucleophilic attack. The use of MeOH as a solvent resulted in a lower yield and more hydrolysis to the carboxylic acid.8

Formation of Hydroxamic Acids from Ethyl Benzoate.

Potassium benzohydroxamate was prepared in 60% yield by treatment of ethyl benzoate with hydroxylamine in the presence of KOH in MeOH. The K salt was converted to benzohydroxamic acid with dil AcOH (eq 7).9

Reduction of Aromatic Aldehydes via Crossed Cannizzaro Reaction.

Certain benzyl alcohols were prepared from the corresponding aromatic aldehydes via the crossed Cannizzaro reaction with formaldehyde and KOH in 80-90% yield.10 Thus the reaction of p-tolualdehyde with formalin and KOH in methanol at 60-70 °C gave about 80% yield of p-methylbenzyl alcohol (eq 8).11

Intramolecular Aldol Reactions.

Treatment of several substituted 5-keto-2-hexenals (6) with KOH (2-3 equiv) in anhyd MeOH at rt for 2-3 h resulted in intramolecular aldol condensation reactions which led to the formation of the substituted phenols (7) in 74-100% yields (eq 9). Other catalysts including pyrrolidinium acetate, pyridinium tosylate, and BF3.Et2O were ineffective.12

Hydroxydeamination of Primary Amines.

Treatment of 1-substituted 1-tosylhydrazines (8) with KOH in refluxing ethanol in the presence of atmospheric oxygen afforded the corresponding alcohols (9) in high yields (eq 10). The reaction is believed to proceed via the hydroperoxide (10), since it was the major isolated product at rt. When the hydroperoxide was subjected to the typical reaction conditions, the corresponding alcohol (9) was obtained in excellent yield, with ethanol presumably acting as the reductant. The procedure provides a convenient route for replacement of the nitrogen of a primary amine by a hydroxy group. The sequence includes the conversion of the primary amine into the corresponding p-toluenesulfonamide followed by N-amination using Chloramine or O-(Mesitylsulfonyl)hydroxylamine to form the tosylhydrazine.13

Reactions with Alkyl Halides.

The alkali hydroxides including KOH are very effective in nucleophilic substitution reactions of alkyl halides. Aq KOH is traditionally used to convert alkyl halides to alcohols.14 Occasionally, it is used to convert gem-dihalides to ketones and trihalomethyl compounds to carboxylic acids.15

Reactions with Trichloromethyl Derivatives.

Treatment of a trichloromethyl derivative with KOH usually gives the corresponding carboxylic acid, e.g. 1,1-bis(p-chlorophenyl)-2,2,2-trichloroethane (11) was converted to bis(p-chlorophenyl)acetic acid (12) in 69-73% yield when reacted with KOH in aq diethylene glycol at 134-137 °C (eq 11).15

Substituted 1,1,1-trichloromethyl-2-ols [(trichloromethyl)carbinols] react with methanolic KOH to form substituted a-methoxyacetic acids (15b) in excellent yields if the substituent group is aryl, alkyl or dialkyl, or vinyl. The reaction fails with ethynylcarbinols. The reaction works equally well if methanol is replaced by ethanol or other alcohols. In a proposed mechanism, the (trichloromethyl)carbinol (13) is converted in situ to the dichloro epoxide (14). The epoxide is opened by methanol to give (15a) which is converted to the acid (15b) under the reaction conditions and workup (eq 12).16

Preparation of (Trichloromethyl)carbinols.

Several (trichloromethyl)carbinols were synthesized in very good yields from aldehydes or ketones upon treatment with CHCl3 in DMF in the presence of methanolic KOH (eq 13). The MeOH/DMF mixture provided a homogeneous reaction that permitted facile product formation at low temperature and was superior to using either solvent alone.17

Oxidation of Aromatic Compounds.

2,3-Dimethyltetrahydroanthraquinone (16) was dehydrogenated to 2,3-dimethylanthraquinone (17) upon treatment with ethanolic KOH and air for 24 h (eq 14). The product was isolated in 94-96%.18

Benzylation of Aromatic Primary Amines.

Heating a mixture of a primary aromatic amine and benzyl alcohol in the presence of KOH at a temperature between 250-280 °C (eq 15) gave the corresponding N-benzyl aromatic amine in high yield.19 For example, heating a mixture of 2-aminopyridine (1 equiv) and benzyl alcohol (1.4 equiv) to 250 °C in the presence of a catalytic amount of KOH (0.14 equiv) afforded 2-(benzylamino)pyridine in 98-99% yield.20

Reductive Benzylation of Aromatic Nitro Compounds.

Treatment of various aromatic nitro compounds with excess benzylamine and KOH at 225-260 °C, while removing the water generated, resulted in the formation of N-benzyl aromatic amines in low yields (11-51%). Under these conditions the nitro compound was first reduced to the aniline, which was benzylated according to the previous reference (eq 16).21

Conversion of Lactones into Benzyloxy Carboxylic Acids.

Treatment of lactones with benzyl chlorides and powdered KOH in dry toluene at reflux temperature resulted in their conversion to the corresponding benzyloxy carboxylic acids.22 The reaction was used to prepare g-, d-, and ε-benzyloxy or p-methoxybenzyloxy carboxylic acids from the appropriate lactones (eq 17).23

Rearrangement.

The substituted 4-hydroxycyclohexanone (18) rearranged partially to the isomeric compound (19) when heated with KOH in 35:1 t-BuOH-H2O at reflux (eq 18). The reaction was reversible and the ratio of (18):(19) at equilibrium was 65:35. The rearrangement was explained by a base-induced transannular 1,4-hydride shift.24

Epimerization of meso-Hydrobenzoins.

(±)-Hydrobenzoin (21) was obtained in 64% yield by heating either erythro- or threo-3-phenylglyceric acid (20a) with KOH to 160 °C under reduced pressure. Under these conditions the (±)-diastereomer of hydrobenzoin is the thermodynamically more stable isomer. Thus applying the reaction to meso-hydrobenzoin (20b) gave the pure (±)-isomer in 90% yield in a few minutes (eq 19). Lower conversion (70%) was obtained with Potassium metal in refluxing toluene, and an attempt to use NaOH was unsuccessful. The KOH epimerization was applied successfully to certain other substituted meso- and erythro-hydrobenzoins.25

Huang-Minlon Modification of the Wolff-Kishner Reduction.

The use of KOH was introduced as a substitute for metallic Sodium or Sodium Methoxide in Wolff-Kishner reductions of ketones. This modification allowed the use of Hydrazine hydrate and made the procedure simpler and economical.26

Removal of 2-Hydroxypropyl Group in p-Ethynylbenzoic Acid Synthesis.

Potassium p-ethynylbenzoate (23) was obtained from 4-[4-(methoxycarbonyl)phenyl]-2-methyl-3-butyn-2-ol (22) in 98.5% yield and 99% purity upon heating at reflux in BuOH and 4 equiv of KOH (or NaOH) for 10 min (eq 20). The salt was precipitated from solution as it was formed.27

Related Reagents.

Potassium Hydroxide-Alumina; Potassium Hydroxide-Carbon Tetrachloride; Potassium Hydroxide-18-Crown-6; Potassium Hydroxide-Dimethyl Sulfoxide; Potassium Hydroxide-Hexamethylphosphoric Triamide.


1. For complete safety data on KOH, see: The Sigma-Aldrich Library of Chemical Safety Data; Lenga, R. E., Ed.; Sigma-Aldrich: Milwaukee, WI, 1985; p 1535C.
2. March, J. In Advanced Organic Chemistry. Reactions, Mechanisms, and Structure, 4th ed.; Wiley: New York, 1992; p 1023.
3. Smith, L. I.; Falkof, M. M. OSC 1955, 3, 350.
4. Hendrickson, J. B.; Sufrin, J. R. TL 1973, 1513.
5. Guha, P. C.; Sankaran, D. K. OSC 1955, 3, 623.
6. Fuson, R. C.; Kneisley, J. W.; Kaiser, E. W. OSC 1955, 3, 209.
7. Loupy, A.; Pedoussaut, M.; Sansoulet, J. JOC 1986, 51, 740.
8. Hall, J. H.; Gisler, M. JOC 1976, 41, 3769.
9. (a) Hauser, C. R.; Renfrow, Jr., W. B. OSC 1943, 2, 67. (b) Renfrow, Jr., W. B.; Hauser, C. R. JACS 1937, 59, 2308.
10. Davidson, D.; Weiss, M. OSC 1943, 2, 590.
11. Davidson, D.; Bogert, M. T. JACS 1935, 57, 905.
12. Tius, M. A.; Thurkauf, A.; Truesdell, J. W. TL 1982, 23, 2823.
13. Guziec, Jr., F. S.; Wei, D. TL 1992, 33, 7465.
14. Ref. 2, p 370.
15. Grummitt, O.; Buck, A.; Egan, R. OSC 1955, 3, 270.
16. Reeve, W.; Steckel, T. F. CJC 1980, 58, 2784 and references therein.
17. Wyvratt, J. M.; Hazen, G. G.; Wienstock, L. M. JOC 1987, 52, 944.
18. Allen, C. F. H.; Bell, A. OSC 1955, 3, 310.
19. Sprinzak, Y. JACS 1956, 78, 3207.
20. Sprinzak, Y. OSC 1963, 4, 91.
21. Miyano, S.; Abe, N.; Uno, A. CPB 1966, 14, 731.
22. Eyre, D. H.; Harrison, J. W.; Lythgoe, B. JCS(C) 1967, 452.
23. Hoye, T. R.; Kurth, M. J.; Lo, V. TL 1981, 22, 815.
24. Warnhoff, E. W. CC 1976, 517.
25. Collet, A. S 1973, 664.
26. Huang-Minlon JACS 1946, 68, 2487.
27. Melissaris, A. P.; Litt, M. H. JOC 1992, 57, 6998.

Ahmed F. Abdel-Magid

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



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