Potassium fluoride on alumina

The preparation of oxazolines from p-hydroxy amides and SOCI2 via the corresponding p-chloro amides under basic conditions is well known and has been discussed earlier. Potassium fluoride on alumina has been reported as a mild alternative to the aqueous or alcoholic bases that are commonly used. The reaction is typically carried out in acetonitrile or tetramethylene sulfone and moderate to good yields of oxazolines and oxazines can be obtained as shown in Scheme 8.29. 

Lately, a number of papers have dealt with microwave-assisted reactions on palladium-doped A1203. Villemin reported on Stifle, Suzuki, Heck and Trost—Tsuji reactions where potassium fluoride on alumina was used as the base26. The reactions were carried out without solvent or stabilising phosphine ligands in single-mode reactors. The Stifle reactions were noteworthy as the toxic organotin residue remained adsorbed on the solid support, thus allowing a simplified work-up procedure for the otherwise unpleasant, and toxic, stannous by-products. Both the Stifle and the Suzuki reactions could be performed under air. Furthermore, it was noted that with experiments where the... 

The same author also found the combination of potassium fluoride on alumina to be the most efficient in the phenylation reaction of aroyl chlorides. Five different bases and different power outputs were screened to find the optimal conditions31 (Scheme 2.5). 

A similar reaction was reported by Kabalka et al. where ligandless and solvent-free Suzuki couplings were performed with potassium fluoride on alumina. This reaction is very interesting as the catalyst used was palladium powder, the least expensive form of palladium available32. The authors demonstrated the simplicity of the procedure by efficient isolation of the biaryl products via a simple filtration. This could be done as the palladium catalyst remains adsorbed on the alumina surface. A small amount of water in the matrix was beneficial for the outcome of the reactions. Recycling of the catalyst was possible by adding fresh potassium fluoride to the palladium/alumina surface and the catalytic system remained effective at least through six reaction cycles (Scheme 2.6). 

To a solution of sulfone 1 (5 mmol) in the minimum of dichloromethane, aldehyde 2 (5 mmol) and potassium fluoride on alumina (3 g) were added. The solvent was evaporated in vacuo with a rotary evaporator. The resulting solid was placed in a open Pyrex Erlenmeyer flask (25 mL) and was irradiated in a micro-wave oven (280 W, 5 min). 

Hydrolysis with powdered potassium hydroxide or potassium fluoride on alumina in r-butyl alcohol converts nitriles to amides without further hydrolysis to carboxlic acids. Under similar conditions, addition of alkyl halides gives iV-alkylcarboxyamides. Less drastic acidic or basic hydrolysis conditions involve disproportionation of alkaline hydrogen peroxide with concomitant hydration of the nitrile (equation 21). 

Ben Alloum, A., Villemin, D. Potassium fluoride on alumina an easy preparation of diazo carbonyl compounds. Synth. Common. 1989, 19, 2567-2571. 

Alloum, A.B., and Villemin, D., Potassium fluoride on alumina. An easy preparation of diazocarbonyl compounds, Synth. Commun., 19, 2567, 1989. 

Amino-3-cyano-thiophenes or 2-amino-thiophene-3-esters result from this route, generally conducted as a one-pot process, involving a ketone that has an a-methylene, ethyl cyanoacetate or malononitrile, sulfur, and morpholine. Various improvements to the original procedure include using microwave irradiation on solid snpport, or with potassium fluoride on alumina as the base, or solvent-free,and using morpho-lininm acetate in excess morpholine for aryl alkyl ketones. 

Potassium fluoride on alumina is sometimes used as a base.23 It may be that the fluoride ion displaces some surface hydroxyl from the alumina to produce some potassium hydroxide. Lithium chloride, bromide, and iodide on silica... 

Potassium fluoride on alumina is a solid base.69 (It forms potassium hydroxide by exchange of fluoride for hydroxyl groups on the surface of the alumina.) An example of its use is given by Reaction 6.21.70 It has also been used without solvent in the Tishchenko reaction of benzaldehyde to give benzyl benzoate if 94% yield.71 Potassium fluoride on an aluminum phosphate molecular sieve was a weaker base in the isomerization of 1 -butene.72... 

This method and its modified version utilising potassium fluoride-on-alumina and 18-crown-6 represents an efficient alternative to the copper catalysed Ullmann synthesis [151]. 

The desulfonylation of N-sulfonyl tetrahydroisoquinolines 63 with potassium fluoride on alumina under the action of microwave irradiation enables the selective synthesis of 3,4-dihydroisoquinolines 64 and isoquinolines 65 (Scheme 5.18) [62]. 

A few interesting papers have appeared with ligandless and solvent-free Suzuki-Miyaura reactions using cheap palladium powder and potassium fluoride on alumina. The catalysts have been recycled and used through several reaction cycles and the products were collected by a simple filtration, adding to the preparative ease of the method [35]. Potassium fluoride on alumina has also been used in the solvent-free synthesis of unsymmetrical ketones, with good results [36, 37]. 

Phenylisoxazolin-5-one condenses with aromatic aldehydes in the absence of a solvent in the presence of potassium fluoride on alumina under microwave irradiation to yield 4-(arylmethylene) derivatives 14 (93SC16). 

Bauchat et al have carried out reactions of MBH acetates with carbanions generated from a 1,3-diketone, methyl cyanoacetate or nitroalkane by treatment with potassium carbonate or potassium fluoride on alumina to provide trisubstituted olefins 182 and 183 with ( )-selectivity. These products were subsequently transformed into useful y-lactones 184 and 8-lactones 185, respectively (Scheme 3.73). 

The yield for and jS increases in passing from LiF to KF. This fact can be associated with increasing basicity of the solid supports not with an appreciable template effect for which the maximum yield should be observed when NaF on alumina was employed. Potassium fluoride on alumina turned out to be the most efficient in the synthesis of... 

Desilylation of silyl ethers by potassium fluoride on alumina, in fact an SN2 attack of the fluoride anion at a silicon atom, is improved in many cases by sonication and proves to be selective for protected phenolic groups. 156 An example is given in Eq. 63 and in Qi. 9, p. 357 (see also p. 129). 

Add 0.0573 g (0.24 mmol) of 4-iodoanisole, 0.0120 g of palladium black powder, 0.1460 g of 40% potassium fluoride on alumina (Aldrich Chemical Co. 316385), 0.0317 g triphenylphosphine, 0.0410 g of cuprous iodide, 1 mL of 95% ethanol, and 70 /jlL of 1-pentyne to a standard microwave tube (12 mL). Add a stir bar recommended by the manufacturers of the microwave reactor. Cap the microwave tube secmely with one of the caps supplied by the manufacturer of the microwave unit. 

This conversion is generally achieved by converting the aldehyde into oxime followed by its dehydration by a variety of reagents. One pot synthesis has also been developed , but these methods suffer from a number of drawbacks. In the microwave assisted reaction, the aldehyde is converted into oxime by reaction with hydroxylamine hydrochloride and potassium fluoride on alumina... 

An exception to the otherwise general use of an organic base is the employment of potassium fluoride on alumina with microwave heating [55]. A range of cyclic ketones, p-keto-esters and aldehydes were used successfully - an example is shown in Scheme 34. 

---