Aliphatic and Alicyclic Ketones

TABLE 5.3 Time (min) for the Hydrogenation of Ketones over Raney Nickel Catalyst Effects of Promoters 1  

Ketone None NaOH Et3N Pt+NaOH EtjN+Pt NaOH 

Nishimura prepared a platinized T-4 Raney nickel by platinizing and simultaneously leaching Raney alloy specifically, chloroplatinic acid solution, made alkaline with a small amount of sodium hydroxide, was added to a suspension of Raney alloy in water.91 The partly leached and platinized Raney alloy was then developed in water, forming a large quantity of bayerite. Partial loss in activity of Raney nickel, which may result on treatment with chloroplatinic acid, could be avoided in this way, and the platinized Raney nickel thus obtained showed a better activity than that platinized by the method of Delepine and Horeau in hydrogenation of typical organic compounds including ketones such as cyclohexanone and acetophenone. 

For hydrogenation of larger amounts of ketones and/or in hydrogenation with Ni-kieselguhr or copper-chromium oxide, use of higher temperatures and pressures is preferable as shown in eqs. 5.2996 and 5.30.7 

The rates, the products, and the stereochemistry of the hydrogenation of ketones over platinum metals may depend greatly on catalyst, solvent, and acidic or alkaline additive, impurities, as well as the structure of ketones. Breitner et al.97 studied the rates of hydrogenation of isobutyl methyl ketone, cyclohexanone, and cyclopentanone over 5% Pd-C, Pt-C, Rh-C, and Ru-C catalysts in various solvents (AcOH, H20, 0.5M aqueous NaOH, 0.5M aqueous HC1, MeOH, and EtOAc). Palladium was always not active irrespective of the solvents used. Over Pt-C all three ketones were hydrogenated most rapidly in H20 and 0.5M aqueous HC1, while in 0.5M aqueous NaOH only cyclohexanone was hydrogenated in a satisfactory rate. With Rh-C and Ru-C all the ketones were hydrogenated best in H20 and 0.5M aqueous NaOH, and the presence of HC1 depressed the rates of hydrogenation, especially for Ru-C. 

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With aliphatic and alicyclic ketones, it appears that trifluoroperoxyacetic acid is the reagent of choice. It reacts much faster than other... 

The Schmidt reaction of ketones works best with aliphatic and alicyclic ketones alkyl aryl ketones and diaryl ketones are considerably less reactive. The reaction is only seldom applied to aldehydes as starting materials. The hydrazoic acid used as reagent is usually prepared in situ by treatment of sodium azide with sulfuric acid. Hydrazoic acid is highly toxic, and can detonate upon contact with hot laboratory equipment. 

Aliphatic and alicyclic ketones condense with primary nitroalkanes under the influence of A,A-dimethylethylenediamine to yield ally lie nitro compounds as mixtures of geometrical isomers, e.g. equation 125408. 

The immense number of reductions performed on ketones dictates subdivision of this topic into reductions of aliphatic, alicyclic, aromatic and unsaturated ketones. However, since differences in behavior toward reduction are very small between aliphatic and alicyclic ketones the section on reductions of alicyclic ketones includes only specific examples due to stereochemistry of the ring systems. 

Yoshigama and Fuchigami have also reported that several dithioacetals of aliphatic and alicyclic ketones can be converted to their gem difluoro-derivatives in a similar manner. However, they found that with diphenyl dithioacetals only one C - S bond is cleaved to give the monofluoro- compound... 

Although true for many oximes of aliphatic and alicyclic ketones, the previous sequence is not absolute and can change depending on the reaction conditions and ketoxime type. Tetrabutylammonium hydroxide, for instance, which catalyzes fairly actively in the synthesis of 4,5,6,7-tetrahydroindole from cyclohexanon oxime and acetylene (79KGS197), turned out to be nearly inert with alkyl aryl ketoximes (78ZOR1733). 

A process for the selective preparation of NH-pyrrole from oximes of aliphatic and alicyclic ketones and acetylene in an autoclave under pressure (yield 70-80%) with DMSO containing up to 10% of water as a solvent (120-140°C, 1-2 hr, 10% KOH) has been developed (76MIP1). According to Mikhaleva and co-workers (79ZOR602), the pyrroles were obtained... 

No difficulty exists in the hydrogenations where aliphatic and alicyclic ketones are formed. Thus, acetylcyclohepetene was hydrogenated to acetylcycloheptane in 97% yield over Pd-C (eq. 3.63).235... 

Tetraalkyl- and tetraatyl-ethylene glycols (pinacols) are made by reduction of ketones with active metals such as sodium, magnesium, and aluminum. The reaction is only fair for aliphatic and alicyclic ketones. Acetone, methyl ethyl ketone, cyclopentanone, and cyclohexanone all give less than 0% yields of pinacols. Mixtures of ketones are reduced to unsymmetrical pinacols. An active zinc-copper couple has been employed in the reduction of several simple olefinic aldehydes to dieodiols, e.g., crotonaldehyde to dipropenyl glycol,... 

Finch has demonstrated that the sulfoximine approach is a viable alternative for fluoromethylenation (Scheme 12). The fluorosulfoximine (54) is deprotonated with LDA in THF and the aldehyde or ketone added to the anion. Conversion to the alkene is carried out with the standard aluminum amalgam procedure to yield a 1 1 mixture of ( )- and (Z)-alkenes (56). The reaction is very effective for aromatic and aliphatic aldehydes and aliphatic and alicyclic ketones, but, while aromatic and a,p-unsaturated ketones give good yiel of the addition adduct, the reductive elimination results in a variable amount of product formation. This method was tilled to the synthesis of prostaglandin 9-fluoromethylene (58 equation IS).- ... 

Clemmensen reaction. The Clemmensen method of reduction (1913) consists in refluxing a ketone with amalgamated zinc and hydrochloric acid. Acetophenone, for example, is reduced to ethylbenzene. The method is applicable to the reduction of most aromatic-aliphatic ketones to at least some aliphatic and alicyclic ketones, to the y-keto acids obtainable by Friedel-Crafts condensations with succinic anhydride (succinolylation), and to the cyclic ketones formed by intramolecular condensation. 

Conjugation of the carbonyl group with the electrons of the cyclopropyl ring is evident from the shifts of aliphatic and alicyclic ketones that have a three-membered ring a to the carbonyl group. 

The Leuckart-Wallach reaction was originally used in wide scope for the reaction of aliphatic and alicyclic ketones with ammonia and primary and secondary amines.1-5 In... 

Other researchers [50] deal that the use acid-base catalyst (ammonium salts acetates and trifluoroacetates of diethylammonium, morpholinimn, piperidinimn) promotes the creation of the Knoevenagel-Cope condensation product (X,P-imsaturated nitrile) and enhances the yield of final 2-aminothiophene. Ionic liquids used as solvents in combination with ethylenediammonium diacetate were shown to be very efficient in the case of the Gewald synthesis with aliphatic and alicyclic ketones with possibility of regeneration of used liquids [83]. 

A reaction of this type was first performed by Tafel in 1906 [6] and was investigated in detail in later work [7-11]. On the basis of the available data it can be asserted that mostly aliphatic and alicyclic ketones are susceptible to oi nometallic compound formation. 

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