- A directing group-assisted ruthenium-catalyzed approach to access: Meta -nitrated phenols
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meta-Selective C-H nitration of phenol derivatives was developed using a Ru-catalyzed σ-activation strategy. Cu(NO3)2·3H2O was employed as the nitrating source, whereas Ru3(CO)12 was found to be the most suitable metal catalyst for the protocol. Mechanistic studies suggested involvement of an ortho-CAr-H metal intermediate, which promoted meta-electrophilic aromatic substitution and silver-assisted free-radical pathway.
- Sasmal, Sheuli,Sinha, Soumya Kumar,Lahiri, Goutam Kumar,Maiti, Debabrata
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supporting information
p. 7100 - 7103
(2020/07/14)
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- NITRATION
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The present invention relates to a process for preparing a nitrated compound, comprising the step of reacting a compound (A) comprising at least one substituted or unsubstituted aromatic or heteroaromatic ring, wherein said heteroaromatic ring comprises at least one heteroatom selected from the group consisting of oxygen, sulfur, phosphor, selenium and nitrogen, with a compound of formula (I) wherein Y is selected from the group consisting of hydrogen and nitro.
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Page/Page column 36; 46; 44; 71
(2020/05/28)
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- Probing synergy between two catalytic strategies in the glycoside hydrolase O-GlcNAcase using multiple linear free energy relationships
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Human O-GlcNAcase plays an important role in regulating the post-translational modification of serine and threonine residues with β-O-linked N-acetylglucosamine monosaccharide unit (O-GlcNAc). The mechanism of O-GlcNAcase involves nucleophilic participation of the 2-acetamido group of the substrate to displace a glycosidically linked leaving group. The tolerance of this enzyme for variation in substrate structure has enabled us to characterize O-GlcNAcase transition states using several series of substrates to generate multiple simultaneous free-energy relationships. Patterns revealing changes in mechanism, transition state, and rate-determining step upon concomitant variation of both nucleophilic strength and leaving group abilities are observed. The observed changes in mechanism reflect the roles played by the enzymic general acid and the catalytic nucleophile. Significantly, these results illustrate how the enzyme synergistically harnesses both modes of catalysis; a feature that eludes many small molecule models of catalysis. These studies also suggest the kinetic significance of an oxocarbenium ion intermediate in the O-GlcNAcase-catalyzed hydrolysis of glucosaminides, probing the limits of what may be learned using nonatomistic investigations of enzymic transition-state structure and offering general insights into how the superfamily of retaining glycoside hydrolases act as efficient catalysts.
- Greig, Ian R.,Macauley, Matthew S.,Williams, Ian H.,Vocadlo, David J.
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supporting information; experimental part
p. 13415 - 13422
(2010/01/16)
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- Catalysis and inhibition of ester hydrolysis in the presence of resorcinarene hosts functionalized with dimethylamino groups
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Complexation and catalysis of two calixresorcinarene (RES) derivatives with nucleophilic N,N-dimethylamino functions attached to their upper rims in the hydrolysis of carboxylate and sulfonate esters of 4-nitrophenol and 2,4-dinitrophenol have been investigated. Rate constants obey the complexation equation: kobs = kb × Ks + k c[Host]/Ks + [Host] Values of the dissociation constant (Ks) of the complexes are within the range exhibited by other systems such as cyclodextrins-ester complexes. The reactions of sulfonate esters only exhibit inhibition by the macrocyclic hosts. The reactions of the carboxylate esters exhibit catalysis and inhibition depending on the pH of the system. It is proposed that the dimethylamino function in RES3 and RES5 behaves as a nucleophile to form a reactive acylammonium species which subsequently decomposes and regenerates the catalytic amine. In the reaction of substituted phenyl acetates with RES3 the effective charge on the leaving oxygen in the complexed state (+0.88) is slightly more positive than that in the free ester (+0.70). The effective charge on the leaving oxygen in the transition structure is substantially more positive (+0.04 units) than in a model intramolecular reaction of tertiary dimethylamines with aryl esters (-0.53 units). The influence of the host on the reaction in the complex includes an electronic component which is ascribed to solvation of the transition structure of the rate-limiting step by water molecules located within the cavity of the host. It is suggested that this solvation is stronger than that occurring in the transition state for the model intramolecular reaction. Copyright
- Cevasco, Giorgio,Thea, Sergio,Vigo, Daniele,Williams, Andrew,Zaman, Flora
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p. 630 - 636
(2008/02/08)
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- Kinetics and mechanism of base-catalysed degradations of substituted aryl-N-hydroxycarbamates, their N-methyl and N-phenyl analogues
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The kinetics and mechanism of the degradation reactions of substituted phenyl N-hydroxycarbamates and their N-methyl and N-phenyl analogues have been studied at pseudo-first-order reaction conditions in aqueous buffers and sodium hydroxide solutions at 20°C and 60°C and at I = 1 mol·1 -1. The dependence of log kobs on pH for phenyl N-hydroxycarbamates at pH 13 is linear with the unit slope; at pH 10-12 log kobs is pH independent. The Bronsted coefficient βlg is about -1 (pH 7-13) and -1.53 (pH > 13) indicating that the degradation reaction of phenyl N-hydroxycarbamates follows an ElcB mechanism giving the corresponding phenol/phenolate and HO-N=C=O. The latter species undergoes further decomposition to give carbonate, nitrogen and ammonia as final products. In contrast to the phenyl N-hydroxycarbamates the N-methyl derivatives at pH 7-9 undergo degradation to the corresponding phenol/phenolate, carbonate and methylamine via a concerted mechanism (βlg is about - 0.75). The only exception is 4-nitrophenyl N-hydroxy-N-methylcarbamate in which the predominant break down pathway proceeds via the Smiles rearrangement to give sodium N-methyl-(4-nitrophenoxy)carbamate. At pH > 9 the reaction of N-hydroxy-N-methylcarbamates is kinetically complex: the dependence of absorbance on time is not exponential and it proceeds as a consecutive two-step reaction. N-Hydroxy-N-phenylcarbamate under the same conditions undergoes degradation to phenol, carbonate, aniline and azoxybenzene.
- Beier, Petr,Mindl, Jaromir,Sterba, Vojeslav,Hanusek, Jiri
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p. 562 - 569
(2007/10/03)
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- Kinetics and mechanism of the aminolysis of ethyl aryl carbonates in acetonitrile
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The aminolysis reactions of ethyl aryl carbonates with benzylamines in acetonitrile at 25.0°C are investigated. The base-catalyzed path, k2, disappears when strong nucleophiles (X = p-CH3O and p-CH3) react with a substrate activated by a strong nucleofuge (Z = p-NO2). The large magnitude of ρ(x) (-1.7 to -2.5), ρ(z) (3.4 to 4.3), and ρ(xz) (1.4) values, and relatively large k(H)/k(D) (1.6 to 1.8) found for the uncatalyzed path (k1) can be accounted for in terms of a stepwise mechanism with rate-limiting expulsion of the phenoxide leaving group. The catalyzed process (k2) is characterized by the much smaller magnitude of ρ(x) (-1.0 to -1.7), ρ(z) (0.4 to 0.7), and ρ(xz) (0.2), the larger k(H)/k(D) (2.1 to 2.5) values, and the lower ΔH(+) values (1.8-1.9 kcal mol-1) than those of the uncatalyzed process (k1) with large negative ΔS(+) values (-65 to -67 cal K-1 mol- 1). These results are consistent with four- and six-centered transition states for the two processes, k1 and k2, respectively.
- Koh, Han Joong,Lee, Ji-Won,Lee, Hai Whang,Lee, Ikchoon
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p. 710 - 716
(2007/10/03)
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- Transfer of a positively charged acyl group between substituted phenolate ion nucleophiles: The Bronsted β for the calibrating equilibrium for N-methylisonicotinyl (4-carbonyl-N-methylpyridinium) transfer
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Rate constants have been measured for the reaction of substituted phenolate ions with aryl acetate esters and with aryl N-methylisonicotinate esters? in aqueous solution. A new method is demonstrated for determining βeq for group transfer from 4-nitrophenyl esters; it employs the rate constant for the reaction of 2,6-difluorophenolate ion with substituted phenyl ester as a surrogate for the reactivity of the 4-nitrophenolate ion and yields βeq = 1.55 for the N-methylisonicotinyl transfer reaction. The Bronsted-type plot of the rate constant for phenolate ion attack on 4-nitrophenyl N-methylisonicotinate is linear over a range of pKa values from 5.5 to 10 and provides good evidence for a concerted displacement mechanism for this reaction. The reactivity of the N-methylisonicorinate esters to phenolate ions is some 300 times larger than that of the corresponding acetate esters but the larger βnuc value (0.90 compared with 0.74) suggests a 'later' transition structure. Calibration of the β values with the corresponding βeq gives a Leffler αnuc = 0.58 and 0.42 for N-methylisonicotinate and acetate respectively, which contrasts with the order expected from reactivity-selectivity. The tighter transition structure indicated by comparison of these α values is explained by a less favourable acylium ion in the case of the N-methylisonicotinyl transfer reaction.
- Colthurst, Matthew J.,Nanni, Matilde,Williams, Andrew
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p. 2285 - 2291
(2007/10/03)
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- Concerted displacement mechanism at trigonal carbon: the aminolysis of 4-aryloxy-2,6-dimethoxy-1,3,5-triazines
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4-Aryloxy-1,3,5-triazines undergo bimolecular nucleophilic displacement reactions with amines and pyridines to yield the 4-substituted triazine and aryloxide ion.Rate constants in aqueous solution for the bimolecular reaction of morpholine and 4-dimethylaminopyridine with the title ethers obey the Hammett ? evaluation with Hammett ρlg values 1.65 and 0.82, respectively.Comparison of the ρlg values with the Hammett ρeq for the equilibrium constants indicates that build-up of effective charge on the departing ether oxygen in the transition structures is less than half of that for complete bond fission.Rate constants for the reaction of substituted pyridines with the 4-nitro- and 3,4-dinitro-phenyl ethers obey Broensted equations with exponents βnuc of 0.68 and 1.06, respectively.The build-up of effective charge in bond formation is greater than half of that expected for complete bond formation.Variation in βnuc and ρlg as a function of leaving group and nucleophile structure, respectively, is consistent with substantial coupling between bond forming and bond breaking.The ratio of the Leffler exponents in the pyridinolysis reactions, αnuc/αlg, is greater than unity, consistent with an imbalance between bond fission and bond formation and indicating an accumulation of negative charge in the heteroaromatic nucleus in the transition structure 29percent of that expected for adduct formation.
- Shakes, Janice,Raymond, Christel,Rettura, Donatella,Williams, Andrew
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p. 1553 - 1558
(2007/10/03)
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- Stepwise versus concerted mechanisms at trigonal carbon: Transfer of the 1,3,5-triazinyl group between aryl oxide ions in aqueous solution
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Displacements of 4-nitrophenolate ions from 2-(4-nitrophenoxy)-4,6-dimethoxy-1,3,5-triazine by substituted phenolate ions in aqueous solution obey a linear Br?nsted-type equation, log kArO = 0.951pKa - 10.98, over a range of pKa values greater than and less than the pKa of the leaving phenol. The absence of curvature is consistent with a mechanism involving a single transition state. This conclusion is supported by the existence of cross-correlation effects (Pxy = 0.0561) on βnuc of the pKa of the leaving group and on β1g of the pKa of the nucleophile on β1g. The value of βeq, the Br?nsted selectivity for transfer of the triazinyl function between phenolate ions, is calculated from the Br?nsted data to be 1.48. The identity reaction of 3,4-dinitrophenolate ion with the (3,4-dinitrophenoxy)triazine is calculated to have a Kreevoy-Albery τ value of 1.04, indicating that in this case changes in effective charge on entering and leaving ligands are approximately balanced.
- Renfrew, A. Hunter M.,Rettura, Donatella,Taylor, John A.,Whitmore, James M. J.,Williams, Andrew
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p. 5484 - 5491
(2007/10/02)
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- AN ALTERNATIVE METHOD FOR SYNTHESIS OF THE CC-1065 PHARMACOPHORE, 1,2,7,7a-TETRAHYDROCYCLOPROPINDOL-4-ONE
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The synthesis of the CC-1065 pharmacophore, 2-(1-methylpyrrole-2-carbonyl)-1,2,7,7a-tetrahydrocyclopropindol-4-one (17), is described.The methods reported here provide an alternative route for the synthesis of compounds possessing the biologically
- Wang, Yugiang,Lown, J. William
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p. 1399 - 1410
(2007/10/02)
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- 4H-1-benzopyran-4-one derivative or its salt, process for producing the same and pharmaceutical composition comprising the same as active ingredient
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This invention relates to a 4H-1-benzopyran-4-one derivative represented by the formula: STR1 or a salt thereof, a process for producing the same and a pharmaceutical composition comprising the same as active ingredient.
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- Stereoelectronic factors influencing the biological activity and DNA interaction of synthetic antitumor agents modeled on CC-1065
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The synthesis, physicochemical properties, and biological activities of a series of novel spiro cyclopropyl compounds, modeled on the potent antitumor antibiotic CC-1065 (1), are described. Many of these synthetic analogues are significantly more effectiv
- Warpehoski,Gebhard,Kelly,Krueger,Li,McGovren,Prairie,Wicnienski,Wierenga
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p. 590 - 603
(2007/10/02)
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