Phenyl butyl ketone

Donohoe and co-workers reported the development of a rhodium-catalyzed reaction for the methylation of ketones (Scheme 15). In a typical example of this reaction, phenyl butyl ketone (0.3 mmol) was reacted with methanol (1.5 mL) in the presence of [Cp RhCl2]2 (5 mol%) combined with CS2CO3 (5 equiv) to give the corresponding methylated product in 98 % yield (Scheme 15) [144]. 

CixHi.KO Uethyl- [d -phenyl-butyl ]-keton-oxim 7 1177. 

Spectroscopic investigations of the lithium derivatives of cyclohexanone (V-phenylimine indicate that it exists as a dimer in toluene and that as a better donor solvent, THF, is added, equilibrium with a monomeric structure is established. The monomer is favored at high THF concentrations.110 A crystal structure determination was done on the lithiated A-phenylimine of methyl r-butyl ketone, and it was found to be a dimeric structure with the lithium cation positioned above the nitrogen and closer to the phenyl ring than to the (3-carbon of the imine anion.111 The structure, which indicates substantial ionic character, is shown in Figure 1.6. 

Early reports of the persistance of optical activity in nitro-substituted carbanions have since been shown to be erroneous.365 366 The treatment of optically active 2-nitrooctane with sodium ethoxide or hydroxide produces an optically inactive salt.366 Optically active 4-nitropentanoic acid racemizes and enolizes at the same rate in the presence of a base.368 Optically active phenyl sec-butyl ketone racemizes and undergoes deuterium exchange at the same rate in the presence of DQ<-)a 7 Of course this could conceivably be due to the tendency of the... 

This explanation (135) rationalizes the stereoselectivity trend in the phenyl alkyl ketone series, but it does not explain the anomalous result with phenyl f-butyl ketone, which would be predicted to give the highest optical yield on the basis of this model. 

TABLE 2. IR carbonyl wavenumber shifts" and equilibrium constants for the reactions of sec-BuIi with substituted phenyl sec-butyl ketones in cyclohexane at 25°C ... 

Fig. 1.3. Crystal structure of dimer of lithium derivative of TV-phenyl imine of methyl /-butyl ketone. (Reproduced with permission from Ref. 72. Copyright 1986 American Chemical Society.)...

If an aldehyde or ketone has an abstractable y hydrogen, Norrish Type I and Norrish Type II reactions are, of course, competitive. Aliphatic ketones, which have no a side chains (63), undergo exclusively Type II reaction in solution 97 but aliphatic t-butyl ketones (64), which can form a stable t-butyl radical on a cleavage, undergo predominantly Type I reaction.98 Phenyl aliphatic ketones (65) form Type I products much more slowly than 64. The probable reason is that the low triplet energy of 65 makes a cleavage of it almost a thermoneutral reaction, whereas a cleavage of 64 is exothermic by ca. 5 kcal."... 

Variations have been made in the activated system also. Higher homologues of butenone (e.g., l-penten-3-one, tert-butyl vinyl ketone) react 1n the same manner, as does phenyl vinyl ketone. The same variety of functional groups as shown before may be possible in the side chain of the ketone... 

Other hemiacetals which have been prepared include the methyl 8<9a>, ethyl 9b), and isopropyl hemiacetals 81) of tetramethylcyclopropanone, the phenyl, a- and (3-naphthyl hemiacetals of cyclopropanone 82>, and the benzyl hemiacetal of 2,3-di-f-butylcyclopropanone. 13> In the last case, the benzylic methylene protons display an AB pattern in the PMR spectrum indicating that the two Ybutyl groups are trans to one another. Although derivatization of this di-f-butyl ketone was possible, carbonyl addition may be hindered by steric factors as suggested by the lack of reaction of 2,2-diY-butylcyclopropanone with methanol. 55a>... 

Besides chalcones, other types of a,p-unsaturated carbonyls affording five-membered S-heterocycles were cinnamaldehyde, 12, and the a,p-unsaturated methyl ketone 13 and phenyl ketones 14 and 15. However, another phenyl ketone, 16, substituted at the a position or tertiary butyl ketone 17 failed to yield S-heterocycles. 

The butylated /J-ketoester C of Figure 13.26 is not the final synthetic target of the acetoacetic ester synthesis of methyl ketones. In that context, the /J-ketoester C is converted into the corresponding /J-ketocarhoxylic acid via acid-catalyzed hydrolysis (Figure 13.27 for the mechanism, see Figure 6.22). This /i-ketocarboxylic acid is then heated either in the same pot or after isolation to effect decarboxylation. The /f-ketocarboxylic acid decarboxylates via a cyclic six-membered transition state in which three valence electron pairs are shifted at the same time. The reaction product is an enol, which isomerizes immediately to a ketone (to phenyl methyl ketone in the specific example shown). 

Trimethylsilyl ethers of the ends from acetone, tern-butyl methyl ketone, cyclopentanone, cyclohexanone, 2-decalone, phenyl methyl ketone... 

A review of the literature to 1942 lists 137 condensations involving aldehydes and ketones. Trioxymethylene serves as a source of formal dehyde. In addition-to the compounds listed, condensations of 2 pente nal, ° o-tolualdehyde, methyl ethyl ketone, diethyl ketone, methyl hexyl ketone, cyclopentanone, and phenyl t-butyl ketone are noteworthy. 

The Sn2 mechanism is ruled out for reaction between the tertiary halide, r-BuBr, and radical anions derived from the more easialy reduced compounds cinnamonitrile (9) ethyl cinnamate (12a), methyl styryl ketone (23a), and phenyl styryl ketone (20a). Reduction of the activated alkenes in the presence of an excess of r-BuBr leads to mixtures of products where a r-Bu group has been introduced in a- or j0-position or in the phenyl ring. For 9 and 12a small amounts of butylated hydrodimers were obtained in addition, and for the enone 23a formation of the unsaturated alcohol with introduction of the /-Bu group at C-1 was a major product [192]. In this case the mechanism is unambiguously reduction of the activated alkene followed by electron transfer to r-BuBr concerted with halide cleavage, in... 

Here, too, the kinetics show the rate of halogenation to be independent of halogen concentration, but dependent upon ketone concentration and, this time, acid concentration. Here, too, we find the remarkable identity of rate constants for apparently different reactions fpr bromination and iodination of acetone, and exchange of its hydrogens for deuterium for iodination and racemization of phenyl sec-butyl ketone. 

Problem 21.9 (a) In the acid-catalyzed dehydration of alcohols (Sec. 5.20), what is the base involved (b) In the base-catalyzed racemization and hydrogen exchange of phenyl jec-butyl ketone (Problem 21.5, p. 707), what is the acid involved ... 

Preparation of Monomers. Methyl vinyl ketone (MVK) was obtained from Pfizer Chemical Division, New York, and distilled to remove the inhibitor. Methyl isopropenyl ketone (MIPK) was prepared by the aldol condensation of methyl ethyl ketone and formaldehyde, according to the method of Landau and Irany 0. The major impurity in this monomer is ethyl vinyl ketone (5. The monomer was redistilled before use. 3 Ethyl 3 buten 2 one (EB) was prepared by the aldol condensation of methyl propyl ketone and formaldehyde. Ethyl vinyl ketone (EVK) was prepared by a Grignard synthesis of the alcohol, followed by oxidation to the ketone. t-Butyl vinyl ketone (tBVK) was prepared from pinacolone and formaldehyde by the method of Cologne (9). Phenyl vinyl ketone (PVK) was prepared fay the dehydrochlorlnatlon of 0 cbloro propiophenone (Eastman Kodak). Phenyl isopropenyl ketone (PPK) was prepared by the Mannich reaction using propiophenone, formaldehyde and dimethylamine HCl. 

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