Benzilic acid, Table

Considering the formation of C02" on CdS-DMF, we successfully applied the CdS-DMF photocatalysis to the fixation of CO2 into benzophenone (BP), acetophenone (AP), and benzyl halides (BnCl and BtiBr) (Table 1). Four substrates gave benzilic acid, atrolactic acid, and phenylacetic acid as respective fixation products, with dimerized and hydrogenated products. Considering the mechanism proposed above, C02 formed through the same route as described therein should participate in the fixation reaction. 

Benzilic acid rearrangement is usually carried out by heating benzil derivatives and an alkali metal hydroxide in aqueous organic solvent. This reaction also proceeds efficiently in the solid state. For example, a mixture of finely powdered benzil (35a) (0.5 g, 2.38 mmol) and KOH (0.26 g, 4.76 mmol) was heated at 80 °C for 0.2 h, and the reaction mixture was mixed with 3N HCl (20 ml) to give benzilic acid (39a) as colorless needles (0.49 g, 90% yield) [13]. Since the product is collected simply by filtration, this method is very simple and economical. Similar treatment of benzil derivatives (35b-g) in the solid state also gave the corresponding benzilic acid (39b-g) in good yields (Table 15-8) [13],... 

Table 15-8. Yields of benzilic acid 39 produced by treatment of benzil bolo 35 with KOH at 80 C in the solid state.

Table 3.8 Basicity and Anticholinergic Activity of Substituted Aminoethyl Esters of Benzilic Acid...

The data in Table 4 also show that of the quinuclidine and diethylaminoethanol derivatives the benzilic acid esters (LXXII) and (IVp) are more potent than the corresponding diphenylpropionates (LXXI) and (IVo). Enhancement of anticholinergic activity is not accompanied by a parallel increase in toxicity (Table 5). The benzilic acid esters were somewhat more toxic than the diphenylpropionates. However, esters of 3-hydroxyquinuclidine did not differ substantially from the corresponding esters of 2-diethylaminoethanol in toxicity [only (IVo) being somewhat more toxic than (LXXI) on intravenous administration]. 

A range of reactions has been described. In Baeyer-Villiger oxidation of ketones with m-chloroperbenzoic acid the reaction proceeds significantly faster in the solid state than in solution. For example, when a mixture of a powdered ketone and two equivalents of the perbenzoic acid are reacted at room temperature, significantly improved yields were obtained with the solid state mixture than from solution. Values are given in Table 6.2. Similarly, the benzilic acid rearrangement proceeded faster as a solid state reaction than in solution. A typical procedure involved heating at 80°C... 

The reaction between aromatic 1,2-diamines and 1,2-diketones affords 2,3-disubstituted quinoxaline derivatives (see table below) " however, a number of hindered a-ketones fail to react. " Unsymmetrical diketones give mixtures of isomers whose ratio varies with the acidity of the medium in some examples. A mechanistic study of quinoxaline formation from benzene-1,2-diamine and benzil has been described." ... 

Before proceeding with a discussion of the effects of 3-qulnuclidlnyl benzilate, it may be worth while to look at the available information on the lethality of single doses of the benzlllc acid esters with which we are concerned. Table 1-2 is based on information supplied by Hoffman-LaRoche, Inc., the Sterllng-Wlnthrop Research Institute, and a number of investigators (36,173,176,178-189). 

The generality of the rearrangement is further illustrated by the reaction of 2,2 -furil with hydroxide ion in dry ether (Table 1). Likewise, 2,2 -pyridil is rearranged in hot methanol solution (40 min) to give the sodium salt of 2,2 -pyridilic acid (86%). Acidification, however, affords bis(2-pyridyl)methanol by decarboxylation since 2,2 -pyridilic acid (16) is structurally similar to a -keto acid. Benzilic rearrangement of 2,2 -pyridil with methanolic nickel(ll) and cobalt(II) acetates results in the formation of metal complexes of 2,2 -pyridilic acid (17 92%). A plausible mechanism is summarized in Scheme 4. Rearrangement is also observed with 2,2 -quinaldil, but benzil, 2,2 -furil or 1-phenyl-2-(2 -pyridyl)ethane-1,2-dione are not susceptible to these metal template reactions. 

Esters of 3-hydroxyquinuclidine with arylaliphatic acids, have proved by their central and peripheral cholinolytic activity to be more potent than related esters (diphenylpropionates, benzilates) of 2-diethylaminoethanol (Table 4) and 3-hydroxy-iV-methylpiperidine. 

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