Potassium Fluoride-Alumina1


[7789-23-3]  · FK  · Potassium Fluoride-Alumina  · (MW 58.10) (Al2O3)

[1344-28-1]  · Al2O3  · Potassium Fluoride-Alumina  · (MW 101.96)

(demethylation and desilylation of phenol ethers;1,2 a solid base catalyst for elimination,3 addition,17 and condensation reactions3)

Form Supplied in: white powder.

Preparative Method: to a stirred solution of Potassium Fluoride (20 g) in water (150 mL) is added neutral Alumina (60-80 mesh, 30 g) in water (150 mL); after 30 min the water is then evaporated in a rotary evaporator at ~60 °C. When most of the water has been removed, the remaining mixture is heated to 140-150 °C and maintained at that temperature under vacuum (5 mmHg) for 6 h to give 50 g of KF-alumina reagent.

Handling, Storage, and Precautions: anhydrous KF-alumina is usually handled and used in dry N2 for best results, but in some cases a trace amount of water facilitates reactions. KF reacts with acid to form the toxic gas hydrogen fluoride. Use in a fume hood.

Deprotecting Reagent.

KF-alumina is an effective reagent for demethylation of methyl phenyl ethers. Heating various methyl phenyl ethers with KF-alumina at 210-215 °C gives phenols. Ethyl phenyl ethers, alkyl methyl ethers, and methylamines do not react with KF-alumina (eq 1).1 It is also used to remove t-butyldimethylsilyl groups from aryl ethers at rt, whereas benzyl t-butyldimethyl ethers and 2-(trimethylsilyl)ethoxymethyl ethers of phenols are stable to the reagent (eq 2).2

Use as a Base.

KF-alumina reagent is a stronger base than KF alone, and it is used as a solid base for eliminations,3 alkylations, additions, isomerizations,4,5 and condensations.3 These reactions can be carried out without any solvent, but addition of a trace amount of water facilitates some reactions, such as Wittig and Wittig-Horner reactions.6

Phenethyl bromides react with KF-alumina to give the corresponding alkenes in good yield. Vinyl bromides or dibromides afford alkynes. However, when simple alkyl halides are used as substrates, hydrolysis becomes the main reaction and alcohols are obtained along with the desired alkenes.3

KF-alumina promotes alkylations of amides, lactams, and N-heterocycles in MeCN or DME at rt.7 The alkylations occur exclusively at nitrogen atoms. In addition to simple acyclic amides, cyclic amides of various ring sizes are readily alkylated in excellent yields (eq 3). Methylation of uracil and xanthine derivatives is very effective (eq 4).7 Arylation of phenols, thiophenols, and anilines with fluorobenzonitriles is also achieved by using KF-alumina as a catalyst.8

1-Hydroxyalkane phosphonic esters are readily available from KF on alumina catalyzed addition of dialkyl phosphites to aldehydes or activated ketones.9 By using KF-g-alumina, the addition proceeds smoothly with nonactivated ketones such as dialkyl, diaryl, and aryl alkyl ketones at rt (eq 5).10 Reactions of nitroalkanes with aldehydes also occur to give 2-nitroalkanols.11 The reaction times are shorter than with alumina alone so that aromatic nitroalcohols are readily obtained without dehydration to nitroalkenes.

Michael addition proceeds readily at rt or below in the presence of catalytic amounts of KF-alumina.3,12 Aprotic solvents, such as THF and MeCN, are mostly used, in contrast to employment of KF alone as a catalyst in protic solvents.13 Secondary nitroalkanes readily add to a,b-unsaturated esters with KF on neutral alumina while primary nitroalkanes give byproducts resulting from multiple Michael additions.14 When basic alumina is used as the support, the side reaction can be avoided and the reaction proceeds well with a,b-unsaturated ketones and acrylate esters.14 With a,b-unsaturated a-cyano esters and a,b-unsaturated a-cyano nitriles, cyclopropane derivatives are formed (eq 6).15 On the other hand, reactions of secondary nitroalkanes with a,b-unsaturated keto esters and sulfones give dihydrofurans instead of cyclopropanes (eq 7).16 When primary nitroalkanes are used as Michael addition donors, the major products are furans along with dihydrofurans as byproducts (eq 8).16 The isoxazoline N-oxides are available from nitroalkenes (eq 9).16

KF-alumina is an efficient base for condensation of active methylene groups with carbonyl compounds. Reaction of various sulfones17 and phosphonates6 containing active methylene groups with aldehydes in the absence of solvent under microwave irradiation gave a,b-unsaturated sulfones and phosphonates, respectively (eqs 10 and 11). However, condensation of malononitrile and acetone gives a 2-azabicyclo[2.2.2]octane derivative in 92% yield; presumably the initial product is isopropylidenemalononitrile, which undergoes KF-alumina-catalyzed Michael addition and cyclization reactions to give the final cyclic product (eq 12).18 Even less acidic methylene compounds condense with aldehydes to afford alkenes (eq 13).19 Under similar conditions, trimethylsulfonium iodide6 or arsonium salts20 react with aldehydes to give epoxides (eq 14).

a-Diazo ketones and esters can be prepared by KF-alumina-catalyzed diazo transfer reactions of tosyl azide with the ketones or esters (eq 15).21

Condensations of active methylene compounds with carbon disulfide lead to ketene thioacetals under KF-alumina catalysis. Various a-keto, a-cyano, and a-carboxyl ketene thioacetals,22 as well as a-phosphonic ketene dithioacetals (eq 16),23 are available from the reaction of active methylene compounds with Carbon Disulfide, followed by methylation with Iodomethane. The dithioacetals are also directly obtained by reaction of the methylene compounds with 2 equiv of S-methyl methanesulfonothioate under microwave irradiation.24 a-Alkynic alcohols react with carbon disulfide to give 4-alkylidene-2-thione-1,3-oxathiolanes without solvent at rt (eq 17).25 The presence of solvent in the previous reaction causes side reactions.25 Aldehydes can be directly converted into the corresponding nitriles by treatment with carbon disulfide, KF-alumina, hydroxylamine, and HCl in one pot (eq 18).26 KF-alumina also promotes hydrolysis of nitriles into amides in refluxing butanol.27

Related Reagents.

Lithium Fluoride; Potassium Fluoride; Potassium Fluoride-Celite.

1. (a) Clark, J. H. CRV 1980, 80, 429. (b) Radhakrishna, A. S.; Prasad Rao, K. R. K.; Suri, S. K.; Sivaprakash, K.; Singh, B. B. SC 1991, 21, 379.
2. Schmittling, E. A.; Sawyer, J. S. TL 1991, 32, 7207.
3. Yamawaki, J.; Kawate, T.; Ando, T.; Hanafusa, T. BCJ 1983, 56, 1885.
4. Radhakrishna, A. S.; Suri, S. K.; Prasad Rao, K. R. K.; Sivaprakash, K.; Singh, B. B. SC 1990, 20, 345.
5. Bhujanga Rao, A. K. S.; Gundu Rao, C.; Singh, B. B. SC 1991, 21, 443.
6. Texier-Boullet, F.; Villemin, D.; Ricard, M.; Moison, H.; Foucaud, A. T 1985, 41, 1259.
7. Yamawaki, J.; Ando, T.; Hanafusa, T. CL 1981, 1143.
8. Schmittling, E. A.; Sawyer, J. S. JOC 1993, 58, 3229.
9. Texier-Boullet, F.; Foucaud, A. S 1982, 165, 916.
10. Texier-Boullet, F.; Lequitte, M. TL 1986, 27, 3515.
11. Mélot, J.; Texier-Boullet, F.; Foucaud, A. TL 1986, 27, 493.
12. Laszlo, P.; Pennetreau, P. TL 1985, 26, 2645.
13. Kambe, S.; Yasuda, H. BCJ 1966, 39, 2549.
14. Bergbreiter, D. E.; Lalonde, J. J. JOC 1987, 52, 1601.
15. Mélot, J. M.; Texier-Boullet, F.; Foucaud, A. S 1987, 364.
16. Mélot, J. M.; Texier-Boullet, F.; Foucaud, A. T 1988, 44, 2215.
17. Villemin, D.; Alloum, A. B. SC 1991, 21, 63.
18. Nakano, Y.; Niki, S.; Kinouchi, S.; Miyamae, H.; Igarashi, M. BCJ 1992, 65, 2934.
19. Villemin, D.; Ricard, M. TL 1984, 25, 1059.
20. Wang, W. B.; Shi, L. L.; Li, Z. Q.; Huang, Y. Z. TL 1991, 32, 3999.
21. Alloum, A. B.; Villemin, D. SC 1989, 19, 2567.
22. Villemin, D.; Alloum, A. B. S 1991, 301.
23. Villemin, D.; Thibault-Starzyk, F.; Esprimont, E. PS 1992, 70, 117.
24. Villemin, D.; Alloum, A. B.; Thibault-Starzyk, F. SC 1992, 22, 1359.
25. Villemin, D.; Alloum, A. B. SC 1992, 22, 1351.
26. Villemin, D.; Lalaoui, M.; Alloum, A. B. CI(L) 1991, 176.
27. Gundu Rao, C. SC 1982, 12, 177.

Qi Han & Hui-Yin Li

Du Pont Merck, Wilmington, DE, USA

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