Benzilic acid esters

As is not uncommon in homologous series, close homologues sometimes showed anomalous behaviour, e.g., of the benzilic acid esters with the following basic components —... 

A variant is represented by the benzilic ester rearrangement, where an alkoxide is used as nucleophile. The alkoxide should not be sensitive towards oxidation. The reaction product is the corresponding benzilic acid ester 5 ... 

Benzil acid esters 95a and 95b, investigated on the isolated heart of the frog, are both relative potent anticholinergic compounds. 

Representative LD3q8 of Benzilic Acid Esters in Laboratory Animals... 

It is prepared by the eondensation of two moleeules of benzaldehyde with sodium cyanide to get benzoin, which on treatment with nitric acid or cupric sulphate forms benzil. In the presence of sodium ethoxide, benzil in hot condition yields benzilic acid ester, (a) The latter on condensation with urea in the presence of sodium ethoxide give rise to phenytoin the enol-form of which on neutralization with sodium hydroxide ultimately results into the formation of phenytoin sodium. 

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]. 

Intensity (ordinate) and duration (dbscisse) of hyperactivity induced by Aprophen-1 (Compound LXXI), Benactizine -II (Compound LXXII), Aprolidine - III (Compound I Vo) and Benzilic acid ester of 3-hydroxyquinuclidine -IV (Compound IVp). All drugs injected intra-... 

According to Morpurgo [181] the central anticholinergic compounds reduce catalepsia induced in rats by phenothiazine derivatives. In our experiments [182] catalepsia was induced in rats by compazine [5 mg/kg intraperitoneally]. In these conditions also the esters of 3-hydroxyquinuclidine were shown to be more active than the corresponding esters of 2-diethylaminoethanol, and the benzilic acid esters were shown to be more active than the diphenylpropionic acid esters (Fig. 2). The benzilic acid ester of 3-hydroxyquinuclidine (IVp) appeared to be the most potent. When the compound was administered intraperitoneally at a dose of... 

Benzilic acid rearrangement Benzoin reaction (condensation) Blanc chloromethylation reaction Bouveault-Blanc reduction Bucherer hydantoin synthesis Bucherer reaction Cannizzaro reaction Claisen aldoi condensation Claisen condensation Claisen-Schmidt reaction. Clemmensen reduction Darzens glycidic ester condensation Diazoamino-aminoazo rearrangement Dieckmann reaction Diels-Alder reaction Doebner reaction Erlenmeyer azlactone synthesis Fischer indole synthesis Fischer-Speior esterification Friedel-Crafts reaction... 

A mixture containing 8 g (0.06 mol) of N-methyl-3-chloro-piperidine and 13.6 g (0.06 mol) of benzilic acid in 50 cc of anhydrous isopropyl alcohol was refluxed for 3 days the isopropyl alcohol was removed by distillation in vacuo, the residue treated with dilute aqueous hydrochloric acid and the aqueous acid mixture extracted repeatedly with ether. The aqueous phase was separated, made strongly alkaline with 20% aqueous sodium hydroxide and extracted with ether. The ether extracts were dried with potassium carbonate and distilled the product was collected at 175° to 176°C (0.03 mm), yield 11.5 g (59%). The ester base thus prepared was then dissolved in 75 cc of isopropyl alcohol and 3.4 g (0.037 mol) methyl bromide added. The reaction mixture was allowed to stand at 30°C for 2 days and the product isolated by filtration, yield, 13 g (87%), MP 228° to 229°C dec. 

Therapeutic Function Anticholinergic, antiulcer Chemical Name Benzilic acid, 2i3iperidinoethyl ester ethobromide Common Name Piperilate ethyl bromide Structural Formula /= ... 

Due to excellent yields, mild reaction conditions, and a fast reaction rate, the azolide method is well suited to the synthesis of isotopically labeled esters, even ones with very short half-lives, just as it is always useful for the esterification of sensitive carboxylic acids, alcohols, and phenols under mild conditions. An example is provided by the synthesis of [nC]-quinuclidinyl benzilate prepared from benzilic acid, CDI, and nC-labeled quinuclidinol.[147]... 

Benzidine, N,N -diethyl-, 36, 21 Benzidine dihydrochloride, 36, 22 Bcnzil, 34, 42 Benzil dihydrazone, 34, 42 Benzilic acid, 33, 37 2-Benzimidazolethiol, 30, 56 l,2-Benzo-3,4-dihydrocarbazole, 30, 91 Benzofuran, 3-methyl, 33, 43 Benzofurazan oxide, 31,14, 15 37,1 Benzoguanamine, 33,13 Benzoic acid, 32, 94 37, 21 Benzoic acid, -acetyl-, methyl ester, 32, 81... 

Chemical name Benzilic acid, 2a-tropanyl ester... 

Mepenzolate Mepenzolate, 3-[(hydroxydiphenylacetyl)oxy]-l,1-dimethyl piperidinium bromide (14.1.13), is synthesized by esterification of benzilic acid with l-methyl-3-chloropiperidine and subsequent reaction of the resulting ester (14.1.12) with methyl bromide [14,15]. 

---