Benzhydrol synthesis

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... 

Substrates include benzyl (2 g) and cinnamyl (2.7 g) alcohols to acids cyclopentanol (1 g), benzhydrol (3.9 g), benzoin (4 g), pantolactone (2.6 g) to ketones (RuCy TCCA/( Bu N)Br/aq. Kj(C03)/CH3CN) (Fig. 2.14) [25] [[2-[2-hydroxypropyl) amino]-l,2-dioxoethyl]amino]acetic acid ethyl ester (6.21 kg) to [(l,2-dioxo-2-oxopropyl)amino]ethyl)amino] acetic acid ethyl ester, part of the industrial-scale synthesis of thrombin inhibitor (RuCyaq. Na(BrOj)/CH3CN) [166] (H-)-dihydroc-holesterol (8 g) to cholest-3-one (RuO /aq. K(10 )/(BTEAC)/CHCl3) [308] ... 

A structurally very simple carboxylic acid, modafinil (62-4), increases alertness and inhibits narcolepsy as a result of its activity as a cerebral ai-adrenergic agonist. The short synthesis begins with the reaction of benzhydrol proper (62-1) with chloroacetic... 

T. Yokozawa, and R. Noyori, Selective hydrogenation of benzophenones to benzhydrols. Asymmetric synthesis of unsymmetrical diarylmethanols, Org. Lett. 2000a, 2, 659-662. 

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. 

When pure phenylacetaldehyde was treated under the conditions that resulted in the conversion of benzyl alcohol to toluene and 2-phenyl-ethanol, the phenylacetaldehyde polymerized and no identifiable reaction products were secured. More information on this matter was obtained with the substituted benzyl alcohol, benzhydrol. Benzhydrol, on treatment with synthesis gas, gives an almost quantitative yield of diphenyl-methane. The hydrocarbon may be formed by decarbonylation of the intermediate diphenylacetaldehyde, or by direct hydrogenolysis of the alcohol ... 

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)... 

Benzhydrol added to the cathode chamber of a divided cell containing tetra- -butyl-ammonium perchlorate in extra-pure DMF (pre-electrolyzed between a Pt-anode and a Hg-pool cathode at —1.9V until the background current fell to ca, 1 mA), O2 bubbled through the mixture, and electrolysis continued at —1.0 V until 5 F/mol. passed (terminal current 15 mA) benzophenone. Y 80%. F.e.s. M. Singh, R.A. Misra, Synthesis 1989, 403-4. 

Oxo compds. from alcohols. Ba(Mn04)2 added to a soln. of benzhydrol in acetonitrile, and the mixture refluxed for 1 h - benzophenone. Y 99%. Ba(Mn04)2 is a mild, stable oxidant, efficiently oxidizing prim, and sec. alcohols in aprotic media, whilst leaving double bonds unaffected sec. benzylic hydroxyl groups are oxidized more rapidly than non-benzylic hydroxy groups. F.e., also oxidation of (3-hydroxyketones, and preparation of disulfides from mercaptans, s. H. Firouzabadi et al.. Synthesis 1989, 378-80. 

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