Benzhydrol, preparation

In the following preparation to illustrate the Meen.vein-Pormdorf-Verley reduc tion, a solution of benzophenone in isopropanol is rapidly reduced in the presence of aluminium isopropoxide to benzhydrol (CaHs)2CO (C Hj)jCH OH. It is clear that the aluminium isopropoxide must take some essential part in this reaction, for benzophenone when dissolved even in cold isopropanol with a trace of acetic acid is reduced to tetraphenylethyleneglycol (p. 150). 

Several analogs bearing different substituents on the aromatic rings are accessible by essentially the same route. The. ippropriate benzhydrol (4) is first prepared by reaction of an... 

Diphenylmethyl vinyl ether has also been prepared from benzhydrol and acetylene (ethyne) under high-pressure conditions.3 In the described method, which is an adaptation of the procedure ofWeinstock and Boekelheide,4 improved yields of the alkene are obtained by using more convenient experimental conditions. 

Tractable polymers can be prepared when amino and anhydride functions are not located on the same aromatic ring, and different strategies were employed to obtain soluble polymer. AB benzhydrol imide was prepared by polycondensation of 4-(3-amino-l-hydroxymethylene) phtlialic acid monomethyl ester in NMP. The polymer soluble in NMP has been used as adhesive and coating.56 A second approach was based on an ether imide structure. AB aminophenylether phthalic acids (Fig. 5.34) were prepared by a multistep synthesis from bisphenols.155 The products are stable as hydrochloride, and the polycondensation takes place by activation with triphenylphosphite. The polymers are soluble in an aprotic polar... 

A slightly more complex Scheme is required for preparation of an antihistaminic agent bearing a secondary amine, e. g., tofenacin (32). In the synthesis of tofenacin, alkylation of the benzhydrol (29) with ethyl bromoacetate affords the alkoxy ester (30) saponification followed by conversion to the methylamide gives (31), which is reduced with lithium aluminum hydride to complete the synthesis of 32. 10... 

Oxidation of Potassium Peroxide. Determination of Potassium Superoxide. Potassium peroxide was prepared by the addition of a tert-butyl alcohol solution of 90% hydrogen peroxide to potassium tert-butoxide in DMSO or tert-butyl alcohol. Oxygen absorption was followed in the standard manner (20). Analysis of solid precipitates for potassium superoxide followed exactly the method of Seyb and Kleinberg (23). Potassium superoxide formed in the oxidation of benzhydrol was determined in a 15-ml. aliquot of the oxidation solution. To this aliquot 10 ml. of diethyl phthlate was added to prevent freezing of the solution. The mixture was cooled to 0°C., and 10 ml. of acetic acid-diethyl phthlate (4 to 1) added over a period of 30 minutes with stirring. The volume of the evolved oxygen was measured. 

A series of benzhydryl azides have been reported to be prepared from the benzhydrols in trichloroacetic acid using hydrogen azide. 

Thus, reaction of equimolar amounts of 2-phenyl-2,2"-spirobis(l,3,2-benzodioxaphosphole) (3a) 6) and benzhydrol under anhydrous conditions in boiling acetonitrile gave l-benzhy-drylacetamide (40%), bis(benzhydryl)ether (30%) and 2-phenyl-1,3, 2-benzodioxaphosphole (4) which was identified by spectroscopic comparison with an authentic sample prepared from phenylphosphonic dichloride and catechol (10). 

The role of the miscibility of semi-IPN components on the mechanical properties has been discussed. The linear bisnadimide was a benzhydrol bisnadimide (Fig. 33). Three polyimides prepared from the same diamine and three different dianhydrides (Fig. 37) were used as linear components. The blends were cured up to 300 °C in a similar fashion to the bisnadimide alone. The results for the blend containing 20% by weight of linear polymers are summarized in Table 9. The non-miscible character of the components gives a phase segregation leading to the best toughness [121]. 

In a variation of this method, isolation of the benzhydrol derivative is not required. The methane base undergoes oxidative condensation in the presence of acid with the same or a different arylamine directly to the dye. New fuchsine [3248-91-7], Cl Basic Violet 2 (16), is prepared by condensation of two moles of o-toluidine with formaldehyde in nitrobenzene in the presence of iron salts to give the corresponding substituted diphenylmethane base. This base is also not isolated, but undergoes an oxidative condensation with another mole of <> t olu idme to produce the dye. 

F-labelled benzhydrols 100 have been synthesized120 by the method of Sugasawa and coworkers121. Four different anilinochloroboranes have been prepared and coupled with [18F]-2-fluorobenzaldehyde in 70-90% yield after 10 minutes. The products 100 have been used to produce the corresponding [18F]-l,4-benzodiazepine-2-ones122. 

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. 

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. 

Hypochlorites are very good oxidizers of alcohols and are frequently selective enough to oxidize secondary alcohols in preference to primary alcohols see equations 288-291). Solutions of sodium hypochlorite in acetic acid react exothermically with secondary alcohols within minutes [693]. Calcium hypochlorite in the presence of an ion exchanger (IRA 900) oxidizes secondary alcohols at room temperature in yields of 60-98% [76 5]. Tetrabutylammonium hypochlorite, prepared in situ from 10% aqueous sodium hypochlorite and a 5% dichloromethane solution of tetrabutylammonium bisulfate, oxidizes 9-fluorenol to fluorenone in 92% yield and benzhydrol to benzophenone in 82% yield at room temperature in 35 and 150 min, respectively [692]. Cyclohexanol is oxidized to cyclohexanone by teit-butyl hypochlorite in carbon tetrachloride in the presence of pyridine. The exothermic reaction must be carried out with due precautions [709]. 

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. 

Formation and Cleavage of Ethers in Acidic Media. When alcohols are treated with acids, dehydration (p. 105) or etherification often occurs. Diethyl ether, for example, is prepared commercially by passing ethanol into a mixture of sulfuric acid and alcohol maintained at 140°. By modifying this method somewhat, satisfactory yields of certain mixed ethers have been obtained.4 In other instances etherification proceeds extremely readily. Triphenylcarbinol is etherified by boiling with methanol5 (unless it is carefully freed of traces of acid),6 and benzhydrol is reported to form dibenzhydryl ether by refluxing it with water.7 Again, traces of acid are probably responsible for reaction. 

Preparation. Hiis stable, crystalline white solid is readily prepared as shown, starting with the condensation of benzhydrol and methyl chlorothiolcarbonate to produce the ester (1). The crude ester is treated in ether with hydrazine in methanol to form the hydrazide (2) and this is converted into the azide (3) by reaction with nitrous acid. 

Reduction. Ketones are reduced to secondary alcohols when refluxed in a mixture of potassium hydroxide and ethylene glycol for 24 hours.1 Thus benzo-phenone was reduced to benzhydrol in 92.7% yield. This unexpected reduction was discovered in an attempt to isomerize 3-enearlier methods for preparation of (3) and (4). 

However, various attempts to prepare compound (41) by condensation of compound (40) with 3,4,5-trimethoxybenzoic acid gave poor results, although a method employing Nafion-H (ref. 51) and polyphosphoric acid ester (ref. 52) afforded compound (41) in low yield (below 30 %) accompanied with a by-product (42). Compound (42) was identified by comparison with an authentic sample, which was synthesized by the condensation of 2-methoxy-3,4-methylenedioxy-benzaldehyde and 3,4,5-trimethoxy-1 -bromobenzene followed by oxidation of the resulting benzhydrol. Moreover, the condensation of compound (4 1 ) with diethyl succinate to give compound (43) in the next step was unsuccessful. 

The preparation of benzhydrol from benzophenone is described as an example of reduction of an aromatic ketone 325... 

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