Benzilic Acid Research Articles

The gas phase benzilic acid rearrangement

AbstractReaction of benzil with HO− in the chemical ionization source of a triple‐analyser mass spectrometer forms a [benzl + HO−] ion. This ion, upon collisional activation, gives a mass spectrum identical to that obtained from deprotonated benzilic acid under the same experimental conditions.

Kinetics and Mechanism of Osmium Tetroxide catalysed Oxidation of Benzilic Acid by Alkaline Hexacyanoferrate(III)

Kinetics and Mechanism of Osmium Tetroxide catalysed Oxidation of Benzilic Acid by Alkaline Hexacyanoferrate(III)

CHLOROSULFONATION OF SOME COMPOUNDS CONTAINING TWO PHENYL RINGS

Abstract Diphenylmethane (1) and dibenzyl (17) reacted with chlorosulphonic acid to give the corresponding p,p′-disulphonyl chlorides (2,18). However, attempted chlorosulfonations of α-chloro-, αα′-dichlorodiphenylmethane, stilbene and 1,4-diphenylbutadiene were unsuccessful. Diphenylacetic acid reacted with chlorosulfonic acid to give a mixture of 4,4′-dichlorosulfonyl-benzophenone (40) and α-chlorodiphenylmethane-4,4′-disulfonyl chloride (39). Benzilic acid (41) afforded 9-chlorofluorene-2,7-disulfonyl chloride (42), which with amines gave 3 different products according to the reaction conditions. Fluorene (53) and the 9-carboxylic acid (43) have been treated with chlorosulfonic acid. The various sulfonyl chlorides were converted into 43 derivatives for biocidal evaluation. Mechanistic interpretations for the reactions are included.

Enhanced photodecarboxylation efficiency of α-hydroxysubstituted arylacetic acids in aqueous solution

The photochemistry of several α-hydroxyarylacetic acids, including mandelic and benzilic acids, was studied in aqueous solution; these compounds photodecarboxylate, via α-hydroxyarylmethyl carbanions, with high quantum yields (≈ 0.2–0.7), to give the corresponding arylmethanols in high yield (> 50%), in contrast to the parent arylacetic acids, which typically have ≈ 0.01–0.03.

Potential cholinergic and anticholinergic compounds: Synthesis of 2,8-substituted 2,8-diazaspiro[4,5]decane-1,3-diones

Heating the ammonium salt of (4-carboxy-1-methyl-4-piperidinyl)acetic acid (XII) gave 8-methyl-2,8-diazaspiro[4,5]decane-1,3-dione (II) which was N-alkylated with 2-bromoethanol and 4-bromobutanol to give the alcohols III and V. Compound III was transformed to the chloro compound VI which was reacted with the sodium salt of hexahydrobenzilic acid to give the ester VII. Compound V was transformed to the 4-toluenesulfonic ester VIII which reacted with 1-(2-pyrimidinyl)piperazine and gave IX. 2-(2-Propyl)-2,8-diazaspiro[4,5]decane-1,3-dione (XVIII) was similarly transformed via XIX to XX which reacted with the sodium salts of diphenylacetic, benzilic, hexahydrobenzilic, and (2-oxo-1-pyrrolidinyl)acetic acid to give the esters XXI-XXIV. The esters VII and XXI-XXIV were transformed to the methiodides. The compounds prepared were tested in the lines of activity of the analogous "RS-86" (I) but proved inactive.

Synthesis of [11C]‐3‐quinuclidinylbenzilate (QNB)

AbstractA method is described by which 1.11 to 1.48 GBq (30 to 40 mCi) of [11C]QNB can be obtained from approximately 55.5 GBq (1.5 Ci) of 11CO2 in 40 minutes.The product, purified by HPLC chromatogaphy, is obtained with a specific activity of 18.5 to 33.3 GBq/μmol (500 to 900 mCi/μmol).Carbon‐11 labelling is performed in two stages: Formation of [11C]benzilic acid by carbonation by 11CO2 of the the pre‐prepared benzophenone dianion. Esterification of [11C]benzilic acid by 3‐quinuclidinol in the presence of carbonyldiimidazole.

Synthesis of 3‐quinuclidinol‐18O, benzilic‐d5 acid, and 3‐quinuclidinyl‐18O benzilate‐d5

AbstractIsotopically labeled analogs of 3‐quinuclidinol (Q), benzilic acid (BA), and 3‐quinuclidinyl benzilate (BZ), for use as internal standards for isotope dilution measurements and the labeled intermediates 3‐quinuclidinone and methyl benzilate used in their production, were synthesized. The isotopic purities of the 1‐azabicyclo[2.2.2]octan‐3‐18O‐ol, α‐hydroxy‐a‐phenyl‐d5‐benzeneacetic acid, and 3‐quinuclidinyl‐18O benzilate‐d5 were determined and the electron impact ionization mass spectrum was obtained for each.

ChemInform Abstract: Evaluation of Some Arylhydrazones (III) of Benzilic Acid Hydrazide (II) as Antimicrobial Agents.

ChemInformVolume 20, Issue 2 Heterocyclic Compounds ChemInform Abstract: Evaluation of Some Arylhydrazones (III) of Benzilic Acid Hydrazide (II) as Antimicrobial Agents. S. ROLLAS, S. ROLLAS Fac. Pharm., Marmara Univ., 80200 Istanbul, TurkeySearch for more papers by this authorS. + BUEYUEKTIMKIN, S. + BUEYUEKTIMKIN Fac. Pharm., Marmara Univ., 80200 Istanbul, TurkeySearch for more papers by this authorN. + BUEYUEKTIMKIN, N. + BUEYUEKTIMKIN Fac. Pharm., Marmara Univ., 80200 Istanbul, TurkeySearch for more papers by this authorM. + UELGEN, M. + UELGEN Fac. Pharm., Marmara Univ., 80200 Istanbul, TurkeySearch for more papers by this authorE. YEMNI, E. YEMNI Fac. Pharm., Marmara Univ., 80200 Istanbul, TurkeySearch for more papers by this author S. ROLLAS, S. ROLLAS Fac. Pharm., Marmara Univ., 80200 Istanbul, TurkeySearch for more papers by this authorS. + BUEYUEKTIMKIN, S. + BUEYUEKTIMKIN Fac. Pharm., Marmara Univ., 80200 Istanbul, TurkeySearch for more papers by this authorN. + BUEYUEKTIMKIN, N. + BUEYUEKTIMKIN Fac. Pharm., Marmara Univ., 80200 Istanbul, TurkeySearch for more papers by this authorM. + UELGEN, M. + UELGEN Fac. Pharm., Marmara Univ., 80200 Istanbul, TurkeySearch for more papers by this authorE. YEMNI, E. YEMNI Fac. Pharm., Marmara Univ., 80200 Istanbul, TurkeySearch for more papers by this author First published: January 10, 1989 https://doi.org/10.1002/chin.198902184Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume20, Issue2January 10, 1989 RelatedInformation

Simultaneous determination of tungsten and molybdenum in sea water by catalytic current polarography after preconcentration on a resin column

The simultaneous determination of tungsten and molybdenum in sea water is based on preconcentration by column extraction with 7-(1-vinyl-3,3,5,5-tetramethylhexyl)-8-quinolinol (Kelex- 100) resin, and measurement of the polarographic catalytic currents obtained in a solution of chlorate, benzilic acid and 2-methyl-8-quinolinol. When the concentration factor is 50, the detection limits are 2.4 pM for tungsten and 17 pM for molybdenum (for a signal-to-noise ratio of 3). The precision of the determination is ca. 10% for 67 pM tungsten and ca. 5% for 106 nM molybdenum in sea water ( n=4). Results for sea water and other natural waters are presented.

Pharmacokinetic studies of propiverine hydrochloride (2). Metabolism in rats after single oral administration of P-4.

Biotransformation of propiverine hydrochloride [1-methyl-4-piperidyl diphenylpropoxyacetate hydrochloride, P-4] was studied in rats after oral administration of P-4.1. The presence of nine metabolites of P-4 was found in the urine and the bile after oral administration ; they were identified based on a 1H-NMR and Mass spectra by direct comparison with authentic compounds.2. Portal plasma concentration of unchanged drug after oral administrati on of 14C-P-4 was 4 ?? 16 times higher than in peripheral plasma, indicating the presence of the hepatic first pass effect.3. After oral administration of 14C-P-4, 1-methyl-4-piperidyl benzilate N-oxide [DPr-P-4 (N → O)] was mainly excreted to the urine, unidentified polar metabolites, benzilic acid [BA], diphenyl-1-(2-hydroxy) propoxyacetic acid [ω-1-OH-Pr-BA], 2, 2-diphenyl-5-methyl-1, 4-dioxan-3-one [ω1-OH-Pr-BA(L)], 1-methyl-4-piperidyl diphenyl-(2-carboxy) ethoxyacetate [ω-COOH-P-4] were excreted to the bile.4. Conjugates (glucuronide and sulfate) accounting for only 3 ?? 4 % of administered dose were detected in the urine and bile.

A mechanistic study of the FK-506 tricarbonyl system rearrangement: Synthesis of C.9 Labeled FK-506

Hydroxide mediated benzilic acid rearrangement of a C.9- 13C labeled FK-506 derivative gave 97% rearrangement thru a C.8→C.10 acyl shift mechanism.

9,9′-anthril (di-9-anthrylethanedione)

9,9′-Anthril has been synthesized both from 9-anthryllithium/oxalyl chloride at −78 °C, and from methyl 9-anthrilate by a reverse benzilic acid rearrangement. Anthril isomerizes by Diels-Alder reaction. Reduction gives 9,9′-anthroin and hydro-9,9′-anthroin.

Chemistry of FK-506: Benzilic acid rearrangement of the tricarbonyl system

Treatment of FK-506 with aqueous hydroxide results in a benzilic acid rearrangement of the C.8–C.10 tricarbonyl portion of the molecule. A corrected structure for a previously reported degradation product as well as oxidative decar☐ylation of rearranged FK-506 is presented.

Mode of inhibitory action of propiverine hydrochloride on the micturition movements of the bladder in dogs

Propiverine hydrochloride (P-4) is a new derivative of benzilic acid. The effect of P-4 on the vesico-detrusor reflex (corresponding to the first reflex of Barrington) in anesthetized or decerebrated dogs was studied to elucidate the mode of action of the drug. When bladder contraction was induced by electrical stimulation of the distal ending of the pelvic nerve under the bilateral pelvic nerve and hypogastric nerve transection, P-4 (2, 5 and 10 mg/kg, i.v.) significantly inhibited the contraction. A similar effect was also observed following intravenous administration of flavoxate (10 and 20 mg/kg), verapamil (1 mg/kg) or propantheline (2 mg/kg), while thiopental (4 mg/kg, i.v.) had no significant effect. When the bladder was filled under the bilateral pelvic nerve and hypogastric nerve transection, an increase of afferent impulses from the distal ending of a pelvic vesical branch was observed. P-4 (10 mg/kg, i.v.) had no effect on the afferent impulses. When the central endings of the pelvic vesical branches were electrically stimulated, reflex discharges were noted from a pelvic vesical branch on the contralateral side. Thiopental (2 and 4 mg/kg, i.v.) markedly decreased the reflex discharge, whereas P-4 (10 mg/kg, i.v.) caused no such inhibition. These findings suggest that the inhibition of the vesico-detrusor reflex by P-4 may result from its inhibitory action on the efferent terminal of the pelvic nerve.

Synthesis by benzilic acid rearrangement of the 2-oxo-3-pyrroline dimeric alkaloid of Mercurialis leiocarpa

The 2-oxo-3-pyrroline dimer, 3,3′-bis(1,1′-dimethyl-2,2′-dioxo-4,4′-dimethoxy-5,5′-dihydroxy-5,5′-dimethoxycarbonyl-3-pyrroline), present in Mercurialis leiocarpa has been synthesized.

頻尿改善剤Ｐｒｏｐｉｖｅｒｉｎｅ ｈｙｄｒｏｃｈｌｏｒｉｄｅのイヌの生体位ぼうこう機能に対する作用

Propiverine hydrochloride (P-4) is a new derivative of benzilic acid. The effect of P-4 on the function of the bladder in anesthetized dogs was studied in comparison with flavoxate, which is clinically used for the treatment of pollakiuria. P-4 (4 mg/kg, i.v.) caused a significant increase in maximum vesical volume (Vmax), which was estimated by a cystometrogram. A similar effect was also observed following intravenous administration of verapamil (1 mg/kg), while flavoxate (4 mg/kg, i.v.) caused no significant changes in Vmax. P-4 significantly decreased the frequency of rhythmic bladder contractions at doses higher than 1 mg/kg, i.v., whereas flavoxate first revealed a significant decrease at 4 mg/kg, i.v. Thus the inhibitory effect of P-4 on the micturition movements of the bladder is more potent than that of flavoxate. These findings indicate that P-4 is a useful drug for the treatment of pollakiuria.

ChemInform Abstract: Diphenylacetic Acid from Benzilic Acid: An Ecologically and Economically Improved Procedure.

AbstractBenzilic acid (I) is dimerized in the presence of p‐toluenesulfonic acid under azeotropic removal of water, yielding the cyclic diester (II).

Determination of 3-quinuclidinyl benzilate in urine

The compound 3-quinuclidinyl benzilate (BZ) is a potent muscarinic cholinergic antagonist that can produce incapacitation at very small doses [1,2]. As such it can be used as a powerful psychochemical warfare agent. In response to the scheduled destruction of U.S. military stockpiles of BZ and the increased potential for worker exposure, our laboratory has developed a specific confirmatory test for human exposure to BZ. The test determines the amount of the parent compound in the urine as well as the two major metabolites, quinuclidinol (Q) and benzilic acid (BA) which are formed by hydrolysis as shown in figure 1. Previous work in our laboratory demonstrated that BA and Q could be determined in urine at their target concentration of 5 ng/mL as based on a proposed acceptable exposure level. The work described here demonstrates the recovery of the parent compound from urine at its target level and the incorporation of this method into an overall test for exposure to BZ. Only a small percentage of unmetabolized BZ is expected to be found in the urine of exposed persons. Estimates based on the proposed acceptable exposure level require detection limits for BZ in urine of 0.5 ng/mL. Because of the complexity of the urine matrix and the variation of urine from one individual to the next, the measurement of BZ in urine at this level presents a challenging analytical problem. A method using solid phase extraction and isotope dilution GC/MS was developed to measure BZ in urine. In the procedure, a 20 mL urine sample is made basic and the BZ is removed by solid phase extraction onto a C1 g sample preparation column. The column is washed with water and a 40% acetonitrile solution and the BZ is eluted with methanol. The eluent is blown to dryness and reconstituted in a derivatizing agent to form the trimethylsilyl derivative for analysis by GC/MS. Measurements are performed using single ion monitoring for the fragment ion (C6 H5 )2COTMS' at m/z 255 and the analogous ion from the isotopically labeled internal standard (3-quinuclidinyl-' 8 O-benzilate-d 5) at m/z 260. We have been able to determine BZ in urine at concentrations less than 0.5 ng/mL. Figure 2 depicts an ion chromatogram showing detection of BZ as its TMS derivative at 0.5 ng/mL. This method was incorporated into the overall test for exposure to BZ which determines the concentration of BZ, BA, and Q in urine. The test was validated by looking at eight different urine samples which were divided into subsamples, some spiked with known concentrations of the analytes and others left blank. Of the 18 subsamples that were analyzed for BZ, BA, and Q, nine were spiked at or just below the target concentration level, five at approximately 10 times the target level, and four were blank. The subsamples spiked at 10 times the target level were to provide information for urine samples with concentration levels that would be expected in the event of an actual exposure. The blank urine samples provided information regarding background interferences with the test over several different urines. The results of the validation test on these samples are summarized graphically in figure 3. For all three analytes we considered the measured values close to the spiked levels. Based on the established target levels no false positives occurred for any of the three analytes in any of the four blank urines. For samples spiked near the target levels no measured value was less than 80% of the spiked value. On this basis, no false negatives were apparent. The imprecisions in the method with regard to GC/MS measurement, sample preparation, and urine-to-urine variability were more or less evenly distributed and the imprecision of a single measurement was about 15%.

ChemInform Abstract: An MNDO SCF‐MO Study of the Mechanism of the Benzilic Acid and Related Rearrangements

Mechanisms for the benzilic acid and related rearrangements have been studied using the MNDO SCF-MO method. The barriers to concerted closed shell [1,2] migration of a substituent R in the initially formed intermediate (2) were found to display a much smaller range of values than is commonly found in rearrangements involving cations or radicals. Both the formation of (2) and its subsequent rearrangement are predicted to be enhanced if either R or the non-migrating group X bears electron-withdrawing substituents. The calculated hydrogen isotope effect and the Bell tunnelling correction for the rearrangement of glyoxal are both significantly larger than for the analogous hydride transfer in the Cannizzaro reaction of formaldehyde. Alternative open shell pathways involving intramolecular single-electron-transfers (SET) to the carbonyl group are relatively high in energy if the non-migrating substituent X is not capable of stabilising an adjacent radical centre (i.e. X = H), but are much more favourable for e.g. the case of X = phenyl. When R bears an electron-withdrawing substituent, electron-transfer to this group is favoured. We suggest on this basis that an SET mechanism may explain the migration of hydrogen rather phenyl in the reaction of phenylglyoxal. Electron-transfer is also favoured for the rearrangement of benzoin to benzilic acid itself, and is predicted to result in the formation of low-energy cyclic intermediates. Intervention of a counter-ion was modelled with Li(H2O)2+ co-ordinating to two oxygen atoms during migration. The migratory barriers were actually increased as a result, and it is suggested that the role of the counter-ion in non-polar solvents is to alter the pre-equilibrium in favour of the intermediate (2).

AN EQUILIBRIUM BETWEEN SPIROPHOSPHORANIC AND TETRACOORDINATED PHOSPHORUS COMPOUNDS HAVING THE PHOSPHORUS-BORON BOND

Abstract A new adduct was isolated from the reaction of borane-dimethyl-sulfide complex and conjugate bases of spirophosphorane prepared from benzilic acid. In solution, it exists as equilibrium between a spirophosphorane and a tetracoordinated phosphorus compound bearing a phosphorus-boron bond.