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Base Catalysis (base + catalysis)
Kinds of Base Catalysis Selected AbstractsConcave Pyridines for Bifunctional Acid,Base Catalysis,EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 6 2007Timo Liebig Abstract Two bifunctional concave acid,base catalysts, 1 and 2, have been synthesized starting from 2,6-dibromopyridine (9) and 2,6-bis(,-alkenyloxy)phenylboronic acids 8 and 10 which end up as bridgeheads in final bimacrocycles 1 and 2. One bridgehead contained an additional substituent in the 4-position. The respective protected 4-hydroxymethyl-substituted phenylboronic acids 8 were synthesized from 4-bromo-3,5-dihydroxybenzoic acid (3) in five steps. 4-Unsubstituted boronic acid 10 and 4-substituted boronic acid 8 were then attached to 9 by subsequent Suzuki couplings to give tetra-,-alkenes 12. By ring-closing metathesis of 12, bimacrocyclic dienes 13 and 17 were formed. After deprotection of the 4-hydroxymethyl group of one bridgehead, a 3-hydroxybenzoate was coupled to 14 to give ester 15 which gave bifunctional acid,base catalyst 1 upon hydrolysis. Analogously, homologue 2 was synthesized, but before coupling the bimacrocycle to the benzoate, tetraene 14 was hydrogenated to 18. Acidic and basic centers in 1 (49,% from 9) and 2 (19,% from 9) are at least 5 Å apart.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007) [source] ChemInform Abstract: Highly Diastereoselective Aldol Additions of a Chiral Ethyl Ketone Enolate under Lewis Base Catalysis.CHEMINFORM, Issue 44 2001Scott E. Denmark Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source] Rational Design of Sterically and Electronically Easily Tunable Chiral Bisimidazolines and Their Applications in Dual Lewis Acid/Brønsted Base Catalysis for Highly Enantioselective Nitroaldol (Henry) ReactionsCHEMISTRY - A EUROPEAN JOURNAL, Issue 6 2007Kuoyan Ma Abstract A new addition to the rational design of sterically and electrically easily tunable chiral bis(imidazoline) ligands from chiral amino alcohols has been developed. Vast structural variation of chiral bis(imidazoline) ligands can be simply achieved by the choice of both the 1,2-amino alcohol and its N-1 R1 substituent. A small library of chiral bisimidazolines (1,a,h) has been constructed. The method has provided an easy and simplified route to a diverse set of air-stable and water-tolerant chiral bis(imidazoline) ligands on 10,g scales. The dual Lewis Acid/Brønsted base catalytic system generated from the (S)- 1,a/Cu(OTf)2 complex and Et3N was able to catalyze Henry reactions between aldehydes and nitromethane effectively at room temperature, and also to tolerate a wide scope of aldehydes with excellent enantiomeric excesses. Not only aromatic aldehydes but also aliphatic aldehydes afforded the nitroalcohol products, with enantiomeric excesses in the 93,98,% range. This dual catalytic system is among the most effective systems so far reported for the asymmetric parent Henry reactions. This work also represents the first members of the class of chiral bisimidazolines to have been demonstrated to achieve excellent enantioselectivities. [source] Reactions of Methyl Diazoacetate with (E)- and (Z)-1,2-Bis(trifluoromethyl)ethene-1,2-dicarbonitrile: Novel and Unanticipated Pathways,HELVETICA CHIMICA ACTA, Issue 1 2007Rolf Huisgen Abstract The cycloadditions of methyl diazoacetate to 2,3-bis(trifluoromethyl)fumaronitrile ((E)- BTE) and 2,3-bis(trifluoromethyl)maleonitrile ((Z)- BTE) furnish the 4,5-dihydro-1H -pyrazoles 13. The retention of dipolarophile configuration proceeds for (E)- BTE with >,99.93% and for (Z)- BTE with >,99.8% (CDCl3, 25°), suggesting concertedness. Base catalysis (1,4-diazabicyclo[2.2.2]octane (DABCO), proton sponge) converts the cycloadducts, trans - 13 and cis - 13, to a 94,:,6 equilibrium mixture (CDCl3, r.t.); the first step is N -deprotonation, since reaction with methyl fluorosulfonate affords the 4,5-dihydro-1-methyl-1H -pyrazoles. Competing with the cis/trans isomerization of 13 is the formation of a bis(dehydrofluoro) dimer (two diastereoisomers), the structure of which was elucidated by IR, 19F-NMR, and 13C-NMR spectroscopy. The reaction slows when DABCO is bound by HF, but F, as base keeps the conversion to 22 going and binds HF. The diazo group in 22 suggests a common intermediate for cis/trans isomerization of 13 and conversion to 22: reversible ring opening of N -deprotonated 13 provides 18, a derivative of methyl diazoacetate with a carbanionic substituent. Mechanistic comparison with the reaction of diazomethane and dimethyl 2,3-dicyanofumarate, a related tetra-acceptor-ethylene, brings to light unanticipated divergencies. [source] Nucleophilic heteroaromatic substitution: Kinetics of the reactions of nitropyridines with aliphatic amines in dipolar aprotic solventsINTERNATIONAL JOURNAL OF CHEMICAL KINETICS, Issue 3 2008Chukwuemeka Isanbor Rate data are reported for the reactions of 2-chloro-5-nitropyridine 2a, 2-chloro-3-nitropyridine 2b, and the corresponding 2-phenoxy derivatives 2c with n -butylamine, pyrrolidine and piperidine and 2d with n -butylamine and pyrrolidine in dimethyl sulfoxide (DMSO) as solvent. The same reactions in acetonitrile had been reported earlier (Crampton et al., Eur J Org Chem 2007, 1378,1383). Values in these solvents are compared with those of 2,4-dinitrochlorobenzene 3a, 2,6-dinitrochlorobenzene 3b, and the corresponding nitroactivated diphenyl ethers 3c and 3d. Reactions with n -butylamine in both solvents gave values of kobs, which increase linearly with amine concentration indicating that nucleophilic attack is rate limiting. The only exception is the reactions in acetonitrile with 2c where base catalysis was observed. Values of k1, the rate constant for the nucleophilic attack, decrease in the order pyrrolidine > piperidine > n -butylamine. In acetonitrile, kinetic data show that k/k ratios are more than unity while the inverse is the case in DMSO. With the phenoxy derivatives, substitution was the only process observed. Base catalysis detected in the reactions of the 1-phenoxy derivatives is attributed to rate-limiting deprotonation of the initially formed zwitterionic intermediate. Our results shed more light on fundamental aspects of activation, hydrogen bonding, and steric effects associated with an aza or a nitro group in the molecules investigated as it affects the nucleophilic aromatic substitution (SNAr) reaction pathways. © 2008 Wiley Periodicals, Inc. Int J Chem Kinet 40: 125,135, 2008 [source] The active site of hydroxynitrile lyase from Prunus amygdalus: Modeling studies provide new insights into the mechanism of cyanogenesisPROTEIN SCIENCE, Issue 2 2002Ingrid Dreveny Abstract The FAD-dependent hydroxynitrile lyase from almond (Prunus amygdalus, PaHNL) catalyzes the cleavage of R -mandelonitrile into benzaldehyde and hydrocyanic acid. Catalysis of the reverse reaction,the enantiospecific formation of ,-hydroxynitriles,is now widely utilized in organic syntheses as one of the few industrially relevant examples of enzyme-mediated C,C bond formation. Starting from the recently determined X-ray crystal structure, systematic docking calculations with the natural substrate were used to locate the active site of the enzyme and to identify amino acid residues involved in substrate binding and catalysis. Analysis of the modeled substrate complexes supports an enzymatic mechanism that includes the flavin cofactor as a mere "spectator" of the reaction and relies on general acid/base catalysis by the conserved His-497. Stabilization of the negative charge of the cyanide ion is accomplished by a pronounced positive electrostatic potential at the binding site. PaHNL activity requires the FAD cofactor to be bound in its oxidized form, and calculations of the pKa of enzyme-bound HCN showed that the observed inactivation upon cofactor reduction is largely caused by the reversal of the electrostatic potential within the active site. The suggested mechanism closely resembles the one proposed for the FAD-independent, and structurally unrelated HNL from Hevea brasiliensis. Although the actual amino acid residues involved in the catalytic cycle are completely different in the two enzymes, a common motif for the mechanism of cyanogenesis (general acid/base catalysis plus electrostatic stabilization of the cyanide ion) becomes evident. [source] Structures of mannose-6-phosphate isomerase from Salmonella typhimurium bound to metal atoms and substrate: implications for catalytic mechanismACTA CRYSTALLOGRAPHICA SECTION D, Issue 7 2009S. R. Sagurthi Mannose-6-phosphate isomerase (MPI) catalyzes the interconversion of mannose 6-phosphate and fructose 6-phosphate. X-ray crystal structures of MPI from Salmonella typhimurium in the apo form (with no metal bound) and in the holo form (with bound Zn2+) and two other structures with yttrium bound at an inhibitory site and complexed with Zn2+ and fructose 6-phosphate (F6P) were determined in order to gain insights into the structure and the isomerization mechanism. Isomerization involves acid/base catalysis with proton transfer between the C1 and C2 atoms of the substrate. His99, Lys132, His131 and Asp270 are close to the substrate and are likely to be the residues involved in proton transfer. The interactions observed at the active site suggest that the ring-opening step is probably catalyzed by His99 and Asp270. An active-site loop consisting of residues 130,133 undergoes conformational changes upon substrate binding. Zn2+ binding induces structural order in the loop consisting of residues 50,54. The metal atom appears to play a role in substrate binding and is probably also important for maintaining the architecture of the active site. Isomerization probably follows the previously suggested cis -enediol mechanism. [source] Nucleophilic heteroaromatic substitution: Kinetics of the reactions of nitropyridines with aliphatic amines in dipolar aprotic solventsINTERNATIONAL JOURNAL OF CHEMICAL KINETICS, Issue 3 2008Chukwuemeka Isanbor Rate data are reported for the reactions of 2-chloro-5-nitropyridine 2a, 2-chloro-3-nitropyridine 2b, and the corresponding 2-phenoxy derivatives 2c with n -butylamine, pyrrolidine and piperidine and 2d with n -butylamine and pyrrolidine in dimethyl sulfoxide (DMSO) as solvent. The same reactions in acetonitrile had been reported earlier (Crampton et al., Eur J Org Chem 2007, 1378,1383). Values in these solvents are compared with those of 2,4-dinitrochlorobenzene 3a, 2,6-dinitrochlorobenzene 3b, and the corresponding nitroactivated diphenyl ethers 3c and 3d. Reactions with n -butylamine in both solvents gave values of kobs, which increase linearly with amine concentration indicating that nucleophilic attack is rate limiting. The only exception is the reactions in acetonitrile with 2c where base catalysis was observed. Values of k1, the rate constant for the nucleophilic attack, decrease in the order pyrrolidine > piperidine > n -butylamine. In acetonitrile, kinetic data show that k/k ratios are more than unity while the inverse is the case in DMSO. With the phenoxy derivatives, substitution was the only process observed. Base catalysis detected in the reactions of the 1-phenoxy derivatives is attributed to rate-limiting deprotonation of the initially formed zwitterionic intermediate. Our results shed more light on fundamental aspects of activation, hydrogen bonding, and steric effects associated with an aza or a nitro group in the molecules investigated as it affects the nucleophilic aromatic substitution (SNAr) reaction pathways. © 2008 Wiley Periodicals, Inc. Int J Chem Kinet 40: 125,135, 2008 [source] Intramolecular general base catalysis exerted by the carboxilate group in the spontaneous dehydration of the carbinolamine formed from benzoylformic anion and hydroxylamine at early values of pHJOURNAL OF PHYSICAL ORGANIC CHEMISTRY, Issue 9 2007M. Calzadilla Abstract Data obtained from the reaction of oxime formation from benzoylformic anion lead to the suggestion that the spontaneous dehydration observed after pH,,,5.0, proceeds through a transition state in which an intramolecular general base catalysis is exerted by the carboxylate group. Copyright © 2007 John Wiley & Sons, Ltd. [source] Specific and non-specific solvent effects on aromatic nucleophilic substitution.JOURNAL OF PHYSICAL ORGANIC CHEMISTRY, Issue 5 20026-dinitrobenzene, Kinetics of the reaction of 1-fluoro-, homopiperidine in binary solvent mixtures Abstract This paper presents a comparative study of the solvent effects on the kinetics of the reactions between 1-fluoro-2,6-dinitrobenzene and hexahydro-1H -azepine in ethyl acetate,+,chloroform or acetonitrile and acetonitrile,+,chloroform binary solvent mixtures. The purpose was to asses the contribution of each molecular-microscopic solvent property to the overall solvation effect of the reaction critical state. The influence of the dipolarity/polarizability, hydrogen-bond donor acidity and hydrogen-bond acceptor basicity of the solvent mixtures on the reaction rate was analyzed by the application of the multiparametric approach of Kamlet, Abboud and Taft. The evaluation of the correlation coefficients shows that the solvation effects are dominated by the non-specific interactions. Moreover, the incidence of the hydrogen-bond acceptor solvent ability is more important than that corresponding to the hydrogen-bond donor character, except for the reactions that manifest kinetic retarding effects. The influence of the solvation effects on the base catalysis was analyzed, describing the response patterns of the partial rate coefficients to the mixture composition and also to each solvent property. The application of a preferential solvation model to the kinetic results yields information on the preferential solvation of the reaction critical state by any of the pure solvents, or by the hydrogen-bonded complexed media. Copyright © 2002 John Wiley & Sons, Ltd. [source] Alteration of the Diastereoselectivity of 3-Methylaspartate Ammonia Lyase by Using Structure-Based MutagenesisCHEMBIOCHEM, Issue 13 2009Hans Raj Abstract 3-Methylaspartate ammonia-lyase (MAL) catalyzes the reversible amination of mesaconate to give both (2S,3S)-3-methylaspartic acid and (2S,3R)-3-methylaspartic acid as products. The deamination mechanism of MAL is likely to involve general base catalysis, in which a catalytic base abstracts the C3 proton of the respective stereoisomer to generate an enolate anion intermediate that is stabilized by coordination to the essential active-site MgII ion. The crystal structure of MAL in complex with (2S,3S)-3-methylaspartic acid suggests that Lys331 is the only candidate in the vicinity that can function as a general base catalyst. The structure of the complex further suggests that two other residues, His194 and Gln329, are responsible for binding the C4 carboxylate group of (2S,3S)-3-methylaspartic acid, and hence are likely candidates to assist the MgII ion in stabilizing the enolate anion intermediate. In this study, the importance of Lys331, His194, and Gln329 for the activity and stereoselectivity of MAL was investigated by site-directed mutagenesis. His194 and Gln329 were replaced with either an alanine or arginine, whereas Lys331 was mutated to a glycine, alanine, glutamine, arginine, or histidine. The properties of the mutant proteins were investigated by circular dichroism (CD) spectroscopy, kinetic analysis, and 1H NMR spectroscopy. The CD spectra of all mutants were comparable to that of wild-type MAL, and this indicates that these mutations did not result in any major conformational changes. Kinetic studies demonstrated that the mutations have a profound effect on the values of kcat and kcat/KM; this implicates Lys331, His194 and Gln329 as mechanistically important. The 1H NMR spectra of the amination and deamination reactions catalyzed by the mutant enzymes K331A, H194A, and Q329A showed that these mutants have strongly enhanced diastereoselectivities. In the amination direction, they catalyze the conversion of mesaconate to yield only (2S,3S)-3-methylaspartic acid, with no detectable formation of (2S,3R)-3-methylaspartic acid. The results are discussed in terms of a mechanism in which Lys331, His194, and Gln329 are involved in positioning the substrate and in formation and stabilization of the enolate anion intermediate. [source] | |||||||||||||||||||