937. The cumulative effect of substituents in an aromatic nucleus on reactions of the side-chain: the effect of the chlorine as substituent on the reaction of benzoyl chlorides with aniline, on the alkaline hydrolysis of ethyl benzoates, and on the ionisation of benzoic acids

Carba analogs of normuramic acid, i.e., 3-(benzyl 2-acetamido-2,3-dideoxy-4,6-O-isopropylidene-α-D-glucopyranosid-3-yl)propanoic acid derivatives (nitrile or esters) 3a-3c were prepared by addition of radicals generated from benzyl 2-acetamido-2-deoxy-4,6-O-isopropylidene-3-O-[(methylsulfanyl)thiocarbonyl]- (2a) or -3-O-(phenoxythiocarbonyl)-α-D-glucopyranoside (2b) with Bu3SnH to acrylonitrile or acryl esters. Alkaline hydrolysis of ethyl ester 3c afforded 3-(benzyl 2-acetamido-2,3-dideoxy-4,6-O-isopropylidene-α-D-glucopyranosid-3-yl)propanoic acid (5). Coupling of acid 5 with L-2-aminobutanoyl-D-isoglutamine benzyl ester trifluoroacetate and subsequent deprotection of the intermediate 6 furnished N-[3-(2-acetamido-2,3-dideoxy-α-D-glucopyranosid-3-yl)propanoyl]-L-2-aminobutanoyl-D-isoglutamine (7).

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Kinetic study of hydrolysis of benzoates. part xxvii. ortho substituent effect in alkaline hydrolysis of phenyl esters of substituted benzoic acids in aqueous Bu4NBr

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc2008019 ◽

2009 ◽

Vol 74 (1) ◽

pp. 29-42 ◽

Cited By ~ 9

Author(s):

Vilve Nummert ◽

Mare Piirsalu ◽

Signe Vahur ◽

Oksana Travnikova ◽

Ilmar A. Koppel

Keyword(s):

Alkaline Hydrolysis ◽

Rate Constants ◽

Pure Water ◽

Substituent Effects ◽

Benzoic Acids ◽

Resonance Effects ◽

The Media ◽

Substituted Benzoic Acids ◽

Hydrolysis Of ◽

Ortho Substituent

The second-order rate constants k (in dm3 mol–1 s–1) for alkaline hydrolysis of phenyl esters of meta-, para- and ortho-substituted benzoic acids, X-C6H4CO2C6H5, have been measured spectrophotometrically in aqueous 0.5 and 2.25 M Bu4NBr at 25 °C. The substituent effects for para and meta derivatives were described using the Hammett relationship. For the ortho derivatives the Charton equation was used. For ortho-substituted esters two steric scales were involved: the EsB and the Charton steric (υ) constants. When going from pure water to aqueous 0.5 and 2.25 M Bu4NBr, the meta and para polar effects, the ortho inductive and resonance effects in alkaline hydrolysis of phenyl esters of substituted benzoic acids, became stronger nearly to the same extent as found for alkaline hydrolysis of C6H5CO2C6H4-X. The steric term of ortho-substituted esters was almost independent of the media considered. The rate constants of alkaline hydrolysis of ortho-, meta- and para-substituted phenyl benzoates (X-C6H4CO2C6H5, C6H5CO2C6H4-X) and alkyl benzoates, C6H5CO2R, in water, 0.5 and 2.25 M Bu4NBr were correlated with the corresponding IR stretching frequencies of carbonyl group, (ΔνCO)X.

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Kinetic Study of Hydrolysis of Benzoates. Part XXV. Ortho Substituent Effect in Alkaline Hydrolysis of Phenyl Esters of Substituted Benzoic Acids in Water

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc20060107 ◽

2006 ◽

Vol 71 (1) ◽

pp. 107-128 ◽

Cited By ~ 16

Author(s):

Vilve Nummert ◽

Mare Piirsalu ◽

Vahur Mäemets ◽

Ilmar Koppel

Keyword(s):

Acid Hydrolysis ◽

Alkaline Hydrolysis ◽

Substituent Effect ◽

Ethyl Esters ◽

Benzoic Acids ◽

Neat Water ◽

Substituted Benzoic Acids ◽

Hydrolysis Of Esters ◽

Hydrolysis Of

The second-order rate constants k2 for alkaline hydrolysis of phenyl esters of meta-, para- and ortho-substituted benzoic acids, X-C6H4CO2C6H5 (X = H, 3-Cl, 3-NO2, 3-CH3, 4-NO2, 4-Cl, 4-F, 4-CH3, 4-OCH3, 4-NH2, 2-NO2, 2-CN, 2-F, 2-Cl, 2-Br, 2-I, 2-CH3, 2-OCH3, 2-CF3, 2-NH2), and of substituted phenyl esters of benzoic acid, C6H5CO2C6H4-X (X = 2-I, 2-CF3, 2-C(CH3)3, 4-Cl, 4-CH3, 4-OCH3, 4-NH2), have been measured spectrophotometrically in water at 25 °C. The substituent effect in alkaline hydrolysis of phenyl esters of para-substituted benzoic acids, similar to that for ethyl esters of para-substituted benzoic acids, was found to be precisely described by the Hammett relationship (ρ = 1.7 in water). The log k value for alkaline hydrolysis of phenyl and ethyl esters of meta-, para- and ortho-substituted benzoic acids, X-C6H4CO2R, was nicely correlated with log km,p,ortho = log ko + (ρ)m,pσ + (ρI)orthoσI + (ρ°R)orthoσ°R + δorthoEsB where σ, σI, σ°R are the Hammett polar, Taft inductive and Taft resonance (σ°R = σ° - σI) substituent constants, respectively. EsB is the steric scale for ortho substituents calculated on the basis of the log k values for the acid hydrolysis of ortho- substituted phenyl benzoates in water owing to the ortho substituent in the phenyl of phenyl benzoates. In water, the main factors responsible for changes in the ortho substituent effect in alkaline hydrolysis of phenyl and ethyl esters of ortho-substituted benzoic acids, X-C6H4CO2R, were found to be the inductive and steric factors while the role of the resonance term was negligible ((ρ°R)ortho ca. 0.3). In alkaline hydrolysis of substituted benzoates in neat water, the ortho inductive effect appeared to be 1.5 times and steric influence 2.7 times higher than the corresponding influences from the ortho position in the phenyl of phenyl benzoates. The contributions of the steric effects in alkaline hydrolysis of esters of ortho-substituted benzoic acids was found to be approximately the same as in acid hydrolysis of esters of ortho-substituted benzoic and acid esterification of ortho-substituted benzoic acids.

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Prediction of ortho substituent effect in alkaline hydrolysis of phenyl esters of substituted benzoic acids in aqueous acetonitrile

Open Chemistry ◽

10.2478/s11532-013-0321-5 ◽

2013 ◽

Vol 11 (12) ◽

pp. 1964-1975 ◽

Cited By ~ 1

Author(s):

Vilve Nummert ◽

Mare Piirsalu ◽

Ilmar Koppel

Keyword(s):

Alkaline Hydrolysis ◽

Rate Constants ◽

Substituent Effect ◽

Substituent Effects ◽

Benzoic Acids ◽

Aqueous Acetonitrile ◽

Substituent Constants ◽

Substituted Benzoic Acids ◽

Hydrolysis Of ◽

Ortho Substituent

AbstractThe second-order rate constants k for the alkaline hydrolysis of phenyl esters of meta-, para- and ortho-substituted benzoic acids, X-C6H4CO2C6H5, in aqueous 50.9% acetonitrile have been measured spectrophotometrically at 25°C. The log k values for meta and para derivatives correlated well with the Hammett σm,p substituent constants. The log k values for ortho-substituted phenyl benzoates showed good correlations with the Charton equation, containing the inductive, σI, resonance, σ○ R, and steric, E s B, and Charton υ substituent constants. For ortho derivatives the predicted (log k X)calc values were calculated with equation (log k ortho)calc = (log k H AN)exp + 0.059 + 2.19σI + 0.304σ○ R + 2.79E s B − 0.0164ΔEσI — 0.0854ΔEσ○ R, where DE is the solvent electrophilicity, ΔE = E AN — E H20 = −5.84 for aqueous 50.9% acetonitrile. The predicted (log k X)calc values for phenyl ortho-, meta- and para-substituted benzoates in aqueous 50.9% acetonitrile at 25°C precisely coincided with the experimental log k values determined in the present work.The substituent effects from the benzoyl moiety and aryl moiety were compared by correlating the log k values for the alkaline hydrolysis of phenyl esters of substituted benzoic acids, X-C6H4CO2C6H5, in various media with the corresponding log k values for substituted phenyl benzoates, C6H5CO2C6H4-X.

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The Effect of Substituents and alpha,beta-Unsaturation on the Alkaline Hydrolysis of alpha,beta-Unsaturated Aliphatic Esters.

Acta Chemica Scandinavica ◽

10.3891/acta.chem.scand.09-1492 ◽

1955 ◽

Vol 9 ◽

pp. 1492-1497 ◽

Cited By ~ 9

Author(s):

Eero A. Halonen ◽

Ivan Larsen ◽

Rolf Gmelin ◽

Harald Prydz

Keyword(s):

Alkaline Hydrolysis ◽

Effect Of Substituents ◽

Aliphatic Esters ◽

Alpha Beta ◽

Hydrolysis Of

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Synthesis and In Vitro Biological Evaluation of β,γ-Methano Analogues of Methotrexate and Aminopterin

Pteridines ◽

10.1515/pteridines.1990.2.3.133 ◽

1990 ◽

Vol 2 (3) ◽

pp. 133-139 ◽

Cited By ~ 2

Author(s):

Andre Rosowsky ◽

Ronald A. Forsch ◽

Richard G. Moran ◽

James H. Freisheim

Keyword(s):

Alkaline Hydrolysis ◽

Cyclopropane Ring ◽

Biological Evaluation ◽

Side Chain ◽

Activity Data ◽

Folylpolyglutamate Synthetase ◽

Conformationally Restricted ◽

Diastereomer Mixture ◽

Hydrolysis Of

Summaryβ,γ-Methano derivatives of methotrexate (MTX) and aminopterin (AMT) were synthesized with the aim of assessing the effect of this side-chain modification on dihydrofolate reductase (OHFR) inhibition, folylpolyglutamate synthetase (FPGS) inhibition, and tumor cell growth inhibition. Mixed carboxylic-carbonic anhydride (MCA) coupling of 4-amino-4-deoxy-N10-methylpteroic acid (mAPA) and dimethyl trans-α-(2-carboxycyclopropyl) glycinate, followed by alkaline hydrolysis, afforded N-( 4-amino-4-deoxy-N10-methylpteroyl)-α-( trans-2-carboxycyclopropyl)glycine (β,γ-methanoMTX) as a mixture of the four possible diastereomers with trans substitution on the cyclopropane ring. N-(4-Amino-4-deoxypteroyl)-trans-α.-(2-carboxycyclopropyl) glycine (β,γ-methanoAMT) , also as a diastereomer mixture, was obtained from 4-amino-4-deoxy-N10 - formylpteroic acid (fAPA) and dimethyl trans-α-(2-carboxycyclopropyl)-glycinate by MCA coupling and alkaline hydrolysis of the ester and N10-formyl groups. β,γ-MethanoMTX and β,γ-methanoAMT may be viewed as MTX and AMT analogues with a conformationally restricted side chain. In vitro biological activity data for these novel compounds support the view that the active site of DHFR, already known for its ability to tolerate modification of the γ-carboxyl group of MTX and AMT, can likewise accommodate substitution on the β- and γ-carbons.

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