Benzhydrol, reduction

Benzhydrol (Diphenylcarbinol), (C HJ,CH OH, from Bettzo-phenone. The Meerwem-Ponndorf-Verley Reductions. 

In addition to the reductive coupling reaction of ketones, certain alcohols can also be reductively coupled using active uranium. Benzhydrol is coupled by active uranium to give TPA as the only coupled product. No TPE is seen. Under similar conditions, no coupling of benzyl alcohol is seen. The chemistry of the active uranium is under continued investigation. 

An interesting example of hydrogenation with hydrogen in the absence of transition metal catalyst is reduction of benzophenone to benzhydrol with hydrogen in /er/-butyl alcohol containing potassium /er/-butoxide at 150-210° and 96-135 atm. Although the yields range from 47 to 98% the method is not practical because of its drastic conditions, and because of a cornucopia of more suitable reductions. 

If as surface active agent with the reduction of 2- and 4-acetylpyridine the optically active proton-donating alcaloids strychninium or brucinium are adsorbed at the cathode, relatively high yields of optically active alcohol (benzhydrol) are obtained (234, 235). 

Ashby and Yu31 have also investigated the reduction of benzophenone (to benzhydrol) by triisobutylaluminium in solvent ether. They suggest that a complex between the ketone and the trialkyl is formed rapidly and reversibly in a subsequent slow step the complex rearranges intramolecularly to yield Ph2CHO-AlBu 2 and isobutene. 

Cohen SG, Sherman W. Inhibition and quenching of the light induced reduction of benzophenone to benzopinacol and to benzhydrol. J Am Chem Soc 1963 85 1642-1647. 

Marcus treatment does not exclude a radical pathway in lithium dialkyl-amide reduction of benzophenone. It does, however, seem to be excluded (Newcomb and Burchill 1984a,b) by observations on the reductions of benzophenone by N-lithio-N-butyl-5-methyl-l-hex-4-enamine in THF containing HMPA. Benzophenone is reduced to diphenylmethanol in good yield, and the amine yields a mixture of the acyclic imines no cyclic amines, expected from radical cyclization of a putative aminyl radical, were detected. An alternative scheme (17) shown for the lithium diethylamide reduction, accounts for rapid formation of diphenylmethoxide, and for formation of benzophenone ketyl under these conditions. Its key features are retention of the fast hydride transfer, presumably via the six-centre cyclic array, for the formation of diphenylmethoxide (Kowaski et al., 1978) and the slow deprotonation of lithium benzhydrolate to a dianion which disproportion-ates rapidly with benzophenone yielding the ketyl. The mechanism demands that rates for ketyl formation are twice that for deprotonation of the lithium diphenylmethoxide, and, within experimental uncertainty, this is the case. 

Delorme and coworkers have published a stereoselective route that is effective with a wide range of amines, including those without a stereocenter on the amine (Scheme 8) [43]. Chiral reduction of the appropriate benzophe-none (as a chromium tricarbonyl complex) using Corey s oxazaborolidine approach afforded the benzhydrol with 91% ee. Treatment with tetrafluo-roboric acid followed by the piperazine gave the desired benzhydryl piperazine without any erosion of stereochemical purity after decomplexation. In addition to simplifying analogue synthesis, these two complementary routes provide a useful base for the future development of stereoselective manufacturing routes. 

A number of important synthetic processes involving mediated reactions of halides rather than direct electrochemical reduction have been reported. The reduction of aryl halides in the presence of alcohols with or without NH3 as a cosolvent leads to the oxidation of the alcohols to the carbonyl compounds. The reaction involves an electrocatalytic process mediated by electron transfer from the initially reduced aryl halide. Alcohols such as benzhydrol and 2-propanol are converted to their respective ketones, on a preparative scale163. The proposed mechanism is shown in Schemes 14 and 15. 

The electrochemical reduction of ketones in alkaline solution at lead cathodes gives the same products as the chemical reduction with sodium. amalgafn or with zinc dust and alkali the process is in many cases suitable for the preparation of benzhydrols. 

Rate Data for Reduction of Benzhydrol to Diphenylmethane Using 0.5 mole benzhydrol, 150 ml. of a benzene solution containing 7.8 g. dicobalt octacarbonyl, and an initial pressure of 3500 p.s.i. of 1 1 synthesis gas (1H2 1C0)... 

A kinetic study of the hydrogenation of benzhydrol to diphenyl-methane (Wender, Greenfield, Metlin, Markby and Orchin, 21) in different solvents showed that the rate decreased in the following order ethanol > benzene > cyclohexane. This is the solvent effect to be expected in a reaction with an ionic intermediate. Furthermore, the reduction is completely inhibited with pyridine as a solvent, a fact consistent with acid catalysis. 

An additional interesting fact uncovered by the kinetic study of the hydrogenation of benzhydrol (Wender, Greenfield, Metlin, Markby and Orchin, 21) is the accelerating effect of small quantities of metallic copper. The addition of copper to the reaction mixture increased the rate of reduction about tenfold. The exact significance of this fact which probably involves the ability of copper to act as an electron donor, Cu°—> Cu+ + 1(e), is yet to be explained. 

Baeger-Villiger reaction, 311 Barbiturates, 358 Base peak in ms. 248 Bases, soft and hard. 121 Basicity and structure. 43 Basic Red. 428 Beckmann rearrangement. 406 Benzene, resonance structure. 192 structure, 189 Benzenonium ion, 205 Benzhydrol, 269 Benzidine rearrangement. 422 Benzyne. 217 Bicydic compounds. 162 Birch reduction, 200 Bischler-Napieralski reaction, 460 Boat and chair forms. 168 Boiling point, influences on, 212 Bond dissociation, 37 Bond order, 17 Bond stretching. 233 Bonding orbitals, 14 Bredt s rule. 168 Bromonium ion. 100 BrOnsted. 42... 

Reduction of aromatic ketones. It has been generally assumed that metal ammonia reduction of aromatic ketones leads to alcohols, mainly because benzo-phenone (1) is reduced to diphenylmcthanol (2, benzhydrol) by sodium in liquid ammonia. However, Hall and co-workers report that aromatic ketones are reduced,... 

Reduction of ketones. Saturated and conjugated ketones can be reduced by the reagent to alcohols, probably by a mechanism similar to electrochemical reduction (as illustrated for acetophenone in scheme I). In some cases, ptnacols are formed as well. Thus acetophenone is reduced to the alcohol (45 % yield) and the pinacol (45% yield). Generally the alcohol is the predominant product. For example, benzophenonc is reduced to benzhydrol in 98 % yield. a,)3-Unsaturated ketones are reduced to saturated alcohols. Reduction of camphor gives predominantly the exo-alcohol note that reduction with sodium in alcohol or with potassium, in the presence of graphite (not intercalated), gives predominantly the endo-alcohol. 

Compound 639 also promotes the photo induced reduction of ketones whereas 2-(2 -hydroxyphenyl)-l,3-dimethyl-benzimidazoline 640 promotes benzpinacol formation (Scheme 153) <2005JOC9632>. Photoinduced single electron transfer (SET) followed by regiospecific proton transfer (PT) led to the formation of either benzhydrol or benzpinacol, depending on the 2-aryl substituent. 

Benzophenone can be converted into benzhydrol in nearly quantitative yield by following the procedure outlined above for the preparation of benzopinacol, modified by addition of a very small piece of sodium (5 mg) instead of the acetic acid. The reaction is complete when, after exposure to sunlight, the greenish-blue color disappears. To obtain the benzhydrol the solution is diluted with water, acidified, and evaporated. Benzopinacol is produced as before by photochemical reduction, but it is at once cleaved by the sodium alkoxide. The benzophenone formed by cleavage is converted into more benzopinacol, cleaved, and eventually consumed. 

Barium manganate, prepared from potassium manganate and barium chloride [5JJ] or by the reduction of potassium permanganate with potassium iodide in the presence of barium chloride and sodium hydfoxide [5J2], is used for the quantitative oxidation of benzhydrol to benzophenone. The reaction mixture is refluxed in benzene for 0.5-2 h [SJ5]. The result is comparable with and even better than that of oxidation with manganese dioxide [250, 525]. 

Sillion et al [47] prepared polyimides containing benzhydrol groups by using the reduction product of benzophenonetetracarboxylic acid dimethyl ester shown below. 

Although the addition of t-BuMgCl to benzophenone had been reported [43] to yield 63% of the expected tertiary alcohol, 1,1-diphenyl-2,2-dimethyl-1-propanol, diphenyl-t-butylcarbinol (no reduction products, such as benzhydrol and benzopinacol, were found then), it was shown that besides the normal addition to the carbon-oxygen double bond, 1,2-addition and also 1,6-addition had taken place, leading to the formation of an alkyldihydrobenzophenone [44] (Scheme 9) ... 

Apart from these SET reactions, solvent effects in reactions of organomagnesium reagents with carbonyl compounds have been studied rather extensively. The reaction of ethylmagnesium bromide with benzophenone (Scheme 15) in diethyl ether yields 94% of the expected addition reaction product, 1,1-diphenyl-1-propanol, and 6% benzhydrol, resulting from a reduction reaction of the Grignard reagent [36]. In tetrahydrofuran this reaction yields 21 and 77%. respectively, of both products. 

The production of diphenylmethyl trimethylgermane in 44% yield is reported from the reductive germylation of benzhydrol with trimethylchlorogermane, magnesium, and HMPT [80]. 

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