Aluminum isopropoxide in isopropyl alcohol

One of the chemoselective and mild reactions for the reduction of aldehydes and ketones to primary and secondary alcohols, respectively, is the Meerwein-Ponndorf-Verley (MPV) reduction. The lifeblood reagent in this reaction is aluminum isopropoxide in isopropyl alcohol. In MPV reaction mechanism, after coordination of carbonyl oxygen to the aluminum center, the critical step is the hydride transfer from the a-position of the isopropoxide ligand to the carbonyl carbon atom through a six-mem-bered ring transition state, 37. Then in the next step, an aluminum adduct is formed by the coordination of reduced carbonyl and oxidized alcohol (supplied from the reaction solvent) to aluminum atom. The last step is the exchange of produced alcohol with solvent and detachment of oxidized alcohol which is drastically slow. This requires nearly stoichiometric quantities of aluminum alkoxide as catalyst to prevent reverse Oppenauer oxidation reaction and also to increase the time of reaction to reach complete conversion. Therefore, accelerating this reaction with the use of similar catalysts is always the subject of interest for some researchers. 

Reduction of ketimines.1 Reduction of N-cyclohexylideneaniline (1) with aluminum isopropoxide and isopropyl alcohol (Meerwein-Ponndorf reduction, 1, 35-36) results in N-isopropylaniline as the major product (equation I). However, if... 

Experiments with deuterated optically active primary amyl alcohol, fluorenone, and sodium ethoxide, for example, showed a direct transfer of hydrogen from the hydroxyl carbon to the carbonyl carbon atom without intervention of the solvent.41 We should expect that, like all carbonyl additions, hydride addition reactions would be acid-catalyzed. Apparently, in aluminum isopropoxide and isopropyl alcohol the optimum acid strength of the solution has been reached. Some alkoxide ions... 

Sabina ketone (XXIV)26 and the esters of chelidonic acid (XXV)6 are reported not to be reduced by aluminum isopropoxide in boiling isopropyl alcohol solution. Apparently no attempts have been made to... 

Further Reduction to a Hydrocarbon. In the reduction of benzo-phenone with aluminum ethoxide the formation of 7% of diphenyl-methane was observed. When benzohydrol was treated with aluminum ethoxide under the same conditions, 28% reduction to diphenylmethane occurred.12 In these reactions acetic acid, rather than acetaldehyde,-was formed from the ethoxide. Aluminum isopropoxide does not give this type of undesirable reaction with this reagent, pure benzohydrol is easily obtained in 100% yield from benzophenone.6 37 However, one case of reduction of a ketone to the hydrocarbon has been observed with aluminum isopropoxide.17 When 9, 9-dimethylanthrone-10 (XU) was reduced in xylene solution, rather than in isopropyl alcohol, to avoid formation of the ether (see p. 190), the hydrocarbon XUII was formed in 65% yield. The reduction in either xylene or isopropyl alcohol was very slow, requiring two days for completion. 

The aluminum isopropoxide is prepared by dissolving cleaned amalgamated aluminum in anhydrous isopropyl alcohol. Although the resulting solution is dark because of suspended particles, in many cases it may be used for the reduction without purification.6 This procedure is often convenient where single reductions are to be carried out with ketones which are known to be reduced satisfactorily in this manner (see tables at end of chapter). However, with aldehydes or ketones which are new or not readily available, or with those which are known to give anomalous results with unpurified reagent, it is advisable to use distilled aluminum isopropoxide, either as the solid or as a molar solution in isopropyl alcohol. 

The benzene is removed at atmospheric pressure, and the residue is distilled under reduced pressure from a 50-cc. Claisen flask. The fraction boiling at 89-91°/7 mm. consists of colorless benzyl alcohol weight 19 g. (89%). A small amount of higher-boiling material, benzyl benzoate, remains in the flask (with a 200% excess of aluminum isopropoxide in 200 cc. of isopropyl alcohol, the yield dropped to 65% and a larger high-boiling fraction resulted). 

Unless otherwise stated, the reduction was carried out with aluminum isopropoxide in boding isopropyl alcohol solution. C refers to clarified but undistilled aluminum isopropoxide) D, to distilled reagent and U, to an untreated solution of the aikoxide (see p. 199)... 

The reduction of an aldehyde or ketone by this equilibrium reaction is readily accomplished by removal of the acetone as it is formed. In are-view of the literature to 1943, experimental conditions and limitations of the reaction have been discussed. Aluminum isopropoxide is superior to other metallic alkoxides that have been used. Yields are better, and the technique for determining the completion of the reaction is simpler. Procedures for the preparation of the reagent are described. A solution made by dissolving amalgamated aluminum in isopropyl alcohol is used directly, or the aluminum isopropoxide is purified by distillation. Best results are obtained when molecular amounts of the alkoxide are used. 

To a solution of aluminum isopropoxide (p. 7) in isopropyl alcohol, prepared from 47 g. (2.0 gram atoms) of aluminum, there are added 210 g. (3.0 moles) of crotonaldehyde (b.p. 102-103°) and 11. of isopropyl alcohol. The mixture is heated at a bath temperature of 110° for 8-9 hours, and some of the solvent plus the acetone formed in the reaction is distilled slowly through an 80-cm. Vigreux column. The temperature of the vapor is 60-70°. The remaining solvent is... 

The classical Meerwein-Ponndorf-Verley (MPV) process, named after the independent originators, can be illustrated by the reduction of crotonaldehyde (43) by aluminum isopropoxide (44) in isopropyl alcohol (equation 24). Aluminum isopropoxide transfers hydride reversibly to a carbonyl acceptor. Acetone is formed as a volatile side product, which can be removed during reaction. The reaction of equation (24) is forced even further to the right by the use of excess isopropyl alcohol. MPV reactions have been reviewed.In the Oppenauer variant of this reaction an alcohol is oxidized to a ketone, and acetone is used as hydride acceptor in the presence of a strong base like r-butoxide. This reaction was originally developed for the selective oxidation of sterols. The synthetic aspects of this procedure have also been reviewed. ... 

Ketotetrahydrochrysene (XXII) does not undergo reduction with aluminum isopropoxide in boiling isopropyl alcohol but can be reduced to the carbinol in 76% yield by substituting toluene as the solvent. Although no reduction of l-menthen-4-one-3 (XXHI) occurs in isopropyl alcohol solution, substitution of the hi er-boiling isobutyl alcohol results in an 84% yield of stereoisomeric carbinols. 

Mills and coworkers (37) performed a series of MPV reductions of cyclic ketones to the corresponding epimeric mixtures of alcohols using aluminum isopropoxide as the catalyst in isopropyl alcohol. A summary of their results is given in Table 2. They conclude that the predominant influence in these reductions pertinent to the cis/trans ratio of the resulting epimeric alcohol mixtures is the degree of steric hindrance of the carbonyl moiety. They also separately investigated (38) a series of MPV reductions of aldehydes and unstable ketones where slow, drop-wise addition of the carbonyl substrate to the reactions inproved the yields. 

Solutions of aluminum isopropoxide in cumene and diethylsilanediol in isopropyl alcohol were blended to give the desired ratios of silicon to aluminum. Water was added in excess of that required to hydrolyze the aluminum isopropoxide to aluminum hydroxide. The solution was distilled to remove the isopropyl alcohol and water, leaving a clear solution of reaction product in the cumene. When diethylsilanediol was omitted, the aluminum hydroxide precipitated and the decanted cumene solution contained no compound of aluminum. 

Alumina catalysts studied by the temperature-programmed desorption technique were prepared mainly by precipitating with ammonia aluminum hydroxide gel from an aluminum nitrate solution (2). The gel thus prepared was dried at 110° overnight and stored. Before use the catalyst was treated with air for 2 hours at 600° and evacuated in the reactor at the same temperature for more than 60 hours, until no more water condensed in the trap T (Fig. 1) during the evacuation. An alumina catalyst was also prepared by the hydrolysis of purified aluminum isopropoxide dissolved in isopropyl alcohol. This catalyst was dried and activated in the same manner as described above. In the... 

The decalinols A and B can be equilibrated using aluminum isopropoxide in 2-propanol (isopropyl alcohol) containing a small amount of acetone. 

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