- Quantitative analysis of solvent effects in highly aqueous media. Application of the SWAG procedures and a critical appraisal of the additivity principle
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This paper describes a study on medium effects of 25 monohydric and polyhydric alcohols on the neutral hydrolysis of 1-benzoyl-3-phenyl-1,2,4-triazole in highly aqueous media. Dependences of pseudo-first-order rate constants on molality of added alcohol are quantitatively analyzed in terms of pairwise Gibbs energy interaction parameters for initial state and transition state. Additivity of pairwise group interaction parameters (SWAG procedure) is applied, and the validity of additivity is critically examined. Excellent additivity is observed in series of monohydric alcohols and vicinal diols. In series of polyhydric alcohols, group contributions to the observed rate effects, as expressed in pairwise group interaction parameters, are, however, strongly dependent on the position of hydroxyl groups in the alcohol. This (apparent) nonadditivity behavior is discussed in terms of the hydration characteristics of the cosolvents. The importance of hydration shell overlap in determining medium effects is supported by kinetic data in ternary 1-propanol-urea-water mixtures.
- Blokzijl,Engberts,Blandamer
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- General-base catalysed hydrolysis and nucleophilic substitution of activated amides in aqueous solutions
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The reactivity of 1-benzoyl-3-phenyl-1,2,4-triazole (1a) was studied in the presence of a range of weak bases in aqueous solution. A change in mechanism is observed from general-base catalysed hydrolysis to nucleophilic substitution and general-base catalysed nucleophilic substitution. A slight tendency is also observed for the more hydrophobic general bases to show higher reactivity towards 1a. Aspartame is an effective nucleophile, possibly because nucleophilic substitution is subject to intramolecular general-base catalysis. A general conclusion derived from the present results is that unexpected rate effects can only be rationalised provided that the detailed reaction mechanisms are well understood. Copyright
- Buurma, Niklaas J.,Blandamer, Michael J.,Engberts, Jan B.F.N.
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- Synthesis of novel 1,2,4-trizaole- and isoxazol(in)e-containing heterocycles
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A route for the regiospecific synthesis of 3-(triazol-3-yl)-1,2-isoxazol(in)e-5-yl-aryl derivatives has been developed by intermolecular 1,3-dipolar cycloaddition chemistry, and novel annulated compounds having triazole/isoxazole have been prepared by emp
- Franzen, Alicia K.,Marshall, William J.,Park, Kyung-Ho
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- Perturbation of SDS and CTAB Micelles by Complexation with Poly(ethylene oxide) and Poly(propylene oxide)
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Pseudo-first-order rate constants have been determined for the neutral hydrolysis of 1-benzoyl-3-phenyl-1,2,4-triazole in aqueous solutions in the presence of SDS and CTAB micelles and SDS-PEO, SDS-PPO, and CTAB-PPO mixed micelles.The micellar rate inhibition of the hydrolysis is clearly modified as a result of micelle-polymer complexation, the effects being rather specific for the nature of the surfactant and the polymer.The kinetic data were analyzed by a simple pseudophase model.The results revealed stabilization of the micelles by interaction with the polymer and polymer-induced microenvironmental changes at the micellar binding sites of the substrate.Results from conductivity measurements facilitated the interpretation of the kinetic data.
- Witte, Frank M.,Engberts, Jan B. F. N.
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- Association of Hydrotropes in Aqueous Solution Studied by Reaction Kinetics
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The effect of added hydrotropes on the rates of neutral hydrolysis for 1-benzoyl-3-phenyl-1,2,4-triazole 1 has been studied, together with the concentration dependence of the 1H NMR spectra of the hydrotropes in aqueous solution. Hydrotropes include sodium 4-alkylbenzenesulfonates 2a-e, sodium 4-methoxybenzenesulfonate 2f, sodium 4-hydroxybenzenesulfonate 2g, cesium benzenesulfonate 3, benzamidinium chloride 4, phenyltrimethylammonium bromide 5a, and benzyltrimethylammonium bromide 5b. All hydrotropes, except 2g, induce strong rate-retarding effects, indicative of strong interactions with 1 and of remarkably strong hydrophobic interactions between aromatic moieties. Most hydrotropes show neither spectroscopic nor kinetic evidence for cooperative aggregation in the concentration range studied, i.e., from 0 to 1.4 mol kg-1. Cooperative aggregation is absent because the Hydrophobic moieties are too small for hydrophobic interactions to overcome electrostatic repulsion. Lack of aggregation results in high availability of hydrophobic binding sites, thereby accounting for the high solubilizing power characteristic for hydrotropes. However, sodium 4-n-propylbenzenesulfonate 2d and sodium 4-n-butylbenzenesulfonate 2e show cooperative self-association forming highly dynamic loose micellar-type structures.
- Buurma, Niklaas J.,Blandamer, Michael J.,Engberts, Jan B. F. N.
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- Stereochemical Aspects of Hydration of Carbohydrates in Aqueous Solutions. 2. Kinetic Medium Effects
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Rate constants for the hydrolysis of 1-benzoyl-3-phenyl-1,2,4-triazole in aqueous solutions of carbohydrates have been measured as a function of molality and nature of added mono- and disaccharides.The kinetic medium effects induced by the carbohydrates originate from hydration sphere overlap effects.The results are analyzed using the additivity principle and reveal specificity in the stereochemical aspects of hydration.The major effect determining the hydration of a monosaccharide appears to be the position of the OH(4) group in conjunction with OH(2).The positionof the carbonyl function and the number of equatorial groups present in the molecule are of minor importance.The experimentally obtained G(C) values, which are representative of the interaction between the carbohydrate and the initial state and activated complex for the hydrolysis reaction, show that the hydration of the carbohydrates is mainly determined by the methine moieties.The G(CHOH, endo) values obtained for the dominant conformers in solution point to similar conclusion.With an increase in compatibility of the carbohydrate molecule with the three-dimensional hydrogen-bond structure of water, the hydroxy groups become less important in determining carbohydrate-solute interactions.This might be important in molecular recognition, since under these conditions the carbohydrates are recognized as hydrophobic moieties.For disaccharides the medium effects are larger than expected on the basis of the medium effect of two monosaccharide subunits.We suggest that this is caused by a cooperativity effect, which makes the methine moieties even more dominant in governing the hydration characteristics.The G(C) values reveal that thetype of linkage in the disaccharide molecule hardly influences the kinetic medium effect.Only when one of the monosaccharide subunits has an axial OH(4) or when there is a 1-3 type of linkage between the moieties is a significantly different G(C) found.It is suggested that the compatibility of the carbohydrates with the three-dimensional hydrogen-bond structure of water largely depends on the compatibility of the next nearest neighbor oxygens of the carbohydrate molecule with the nearest or next nearest neighbor oxygens of liquid water.
- Galema, Saskia A.,Blandamer, Michael J.,Engberts, Jan B. F. N.
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- Liganding Functional Tyrosine Sites on Proteins Using Sulfur-Triazole Exchange Chemistry
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Tuning reactivity of sulfur electrophiles is key for advancing click chemistry and chemical probe discovery. To date, activation of the sulfur electrophile for protein modification has been ascribed principally to stabilization of a fluoride leaving group (LG) in covalent reactions of sulfonyl fluorides and arylfluorosulfates. We recently introduced sulfur-triazole exchange (SuTEx) chemistry to demonstrate the triazole as an effective LG for activating nucleophilic substitution reactions on tyrosine sites of proteins. Here, we probed tunability of SuTEx for fragment-based ligand discovery by modifying the adduct group (AG) and LG with functional groups of differing electron-donating and -withdrawing properties. We discovered the sulfur electrophile is highly sensitive to the position of modification (AG versus LG), which enabled both coarse and fine adjustments in solution and proteome activity. We applied these reactivity principles to identify a large fraction of tyrosine sites (～30%) on proteins (～44%) that can be liganded across >1500 probe-modified sites quantified by chemical proteomics. Our proteomic studies identified noncatalytic tyrosine and phosphotyrosine sites that can be liganded by SuTEx fragments with site specificity in lysates and live cells to disrupt protein function. Collectively, we describe SuTEx as a versatile covalent chemistry with broad applications for chemical proteomics and protein ligand discovery.
- Brulet, Jeffrey W.,Borne, Adam L.,Yuan, Kun,Libby, Adam H.,Hsu, Ku-Lung
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p. 8270 - 8280
(2020/05/25)
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- Design, synthesis, and biological activity of novel tetrahydropyrazolopyridone derivatives as FXa inhibitors with potent anticoagulant activity
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A series of novel tetrahydropyrazolopyridone derivatives containing 1,3,4-triazole, triazolylmethyl, and partially saturated heterocyclic moieties as P2 binding element was designed, synthesized, and evaluated in vitro for anticoagulant activity in human and rabbit plasma. All compounds showed moderate to significant potency, and compounds 15b, 15c, 20b, 20c, and 22b were further examined for their inhibitory activity against human FXa in vitro. While compounds 15c and 22b were tested for rat venous thrombosis in vivo. The most promising compound 15c, with an IC50 (FXa) value of 0.14?μM and 98% inhibition rate, warranted further investigation as an FXa inhibitor.
- Sun, Xiaoqing,Hong, Zexin,Liu, Moyi,Guo, Su,Yang, Di,Wang, Yong,Lan, Tian,Gao, Linyu,Qi, Hongxia,Gong, Ping,Liu, Yajing
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p. 2800 - 2810
(2017/04/18)
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- A new, high-yield synthesis of 3-aryl-1,2,4-triazoles
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A convenient new synthetic approach to 3-aryl-1,2,4-triazoles has been developed. Chloralamides were obtained by high yield reactions between benzamides and chloral hydrate. These reacted with a phosphorus pentachloride/phosphorus oxychloride mixture unde
- Guirado, Antonio,López-Caracena, Libertad,López-Sánchez, José I.,Sandoval, José,Vera, María,Bautista, Delia,Gálvez, Jesús
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p. 8055 - 8060
(2016/11/19)
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- PDE10 MODULATORS
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The present invention relates to compounds of formula (I) wherein R1, R2, R3, R5, W, X, X1, Y, Y1, Z and Z1 are as defined in the description and in the claims, as well as physiologically acceptable salts thereof. These compounds inhibit PDE10A and can be used in the treatment of CNS disorders such as schizophrenia, Alzheimer's disease, and Parkinson's disease.
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Paragraph 0239
(2013/03/26)
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- PDE10 MODULATORS
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The present invention relates to compounds of formula (I) wherein R1, R2, R3, R5, W, X, X1, Y, Y1, Z and Z1 are as defined in the description and in the claims, as well as physiologically acceptable salts thereof. These compounds inhibit PDE10A and can be used as medicaments.
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Page/Page column 42
(2013/03/26)
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- Heterocyclic compounds as inhibitors of factor VIIa
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The present invention relates generally to compounds that inhibit serine proteases. In particular it is directed to novel heterocyclic compounds, or a stereoisomer or pharmaceutically acceptable salt, solvate, or prodrug form thereof, which are useful as selective inhibitors of serine protease enzymes of the coagulation cascade; for example thrombin, factor VIIa, factor Xa, factor XIa, factor IXa, and/or plasma kallikrein. In particular, it relates to compounds that are factor VIIa inhibitors. This invention also relates to pharmaceutical compositions comprising these compounds and methods of using the same.
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Page/Page column 33
(2008/06/13)
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- The nature of the micellar Stern region as studied by reaction kinetics. 2
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The nature of rate-retarding effects of cationic micelles on the water-catalyzed hydrolyses of a series of para-substituted 1-benzoyl-1,2,4-triazoles (1a-f) and 1-benzoyl-3-phenyl-1,2,4-triazole (2) has been studied using kinetic methods. A comparison is drawn between medium effects in the micellar Stern region and in model solutions for the micellar Stern region. Simple model solutions involving concentrated aqueous solutions of a small ionic molecule resembling the surfactant headgroup, as reported before, were improved. New model solutions for alkyltrimethylammonium bromide micelles contain both tetramethylammonium bromide (TMAB), mimicking micellar headgroups, and 1-propanol, mimicking hydrophobic tails. The rate-retarding effect of micelles on the hydrolysis of 1a-f and 2 is caused by the high concentration of headgroups as well as by hydrophobic tails in the Stern region where 1a-f and 2 bind to the micelle. Individual contributions of these interactions are quantified. Rate-retarding effects found for different probes, with different sensitivities for interactions as they occur when the probe binds to the micellar Stern region, as well as the micellar Stern region's micropolarity as reported by the ET(30) probe, are satisfactorily reproduced by new model solutions containing both TMAB and 1-propanol.
- Buurma, Niklaas J.,Serena, Paola,Blandamer, Michael J.,Engberts, Jan B. F. N.
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p. 3899 - 3906
(2007/10/03)
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- Thermal rearrangement of allyl substituted unsymmetric 4H-1,2,4-triazoles to the corresponding 1H-1,2,4-triazoles
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A series of neat 4-(2-alkenyl) substituted 5-methyl-3-phenyl-4H-1,2,4- triazoles were thermolyzed at 320°C producing a rearrangement products, of which the regioisomeric 1- and 2-substituted triazoles were the main products. The group migrations were rationalized in terms of consecutive S N2-type reactions. This mechanism was supported by a study of the alkylations of the triazoles which gave similar product mixtures. 4-(2-alkenyl) substituted 3-phenyl-4H-1,2,4-triazoles, on the other hand, gave predominantly elimination products.
- Jorgensen, Kare B.,Olsen, Ragnhild B.,Carlsen, Per H.J.
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p. 481 - 495
(2007/10/03)
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- Pairwise Gibbs energies of interaction involving N-alkyl-2- pyrrolidinones and related compounds in aqueous solution obtained from kinetic medium effects
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Kinetic solvent effects of N-alkyl-2-pyrrolidinones and structurally related compounds on the water-catalyzed hydrolysis reactions of p- methoxyphenyl dichloroacetate (MPDA), 1-benzoyl-3-phenyl-1,2,4-triazole (BPhT), and 1-benzoyl-1,2,4-triazole (BT) in highly dilute aqueous solutions at pH 4 and 298.15 K have been determined by UV/vis spectroscopy. Using a thermodynamic description of solute-solute interactions in aqueous solutions, the kinetic results have been analyzed in terms of pairwise Gibbs energy interaction parameters: G(c) values. These are negative, indicating that hydrophobic interactions in the initial state dominate the medium effects. The interaction parameters increase in the order MPDABT>BPhT. However, when differences in reactivity and transition state effects are taken into account, it appears that BPhT is more successful in establishing hydrophobic interactions with the cosolutes than are MPDA and BT. Using the SWAG-approach for additivity of group interactions, additivity is observed for the first three consecutive CH2 groups in the cosolute in all three hydrolysis reactions. Larger alkyl substituents cause larger retardations than anticipated on basis of this additivity. The results are explained by intramolecular destructive overlap of the polar hydration shell of the amide functionality and the apolar (hydrophobic) hydration shell of the alkyl group, which extends to the third CH2 group in the N-alkyl group of the cosolute molecule. The inner apolar groups, therefore, have a reduced apparent hydrophobicity. More remote CH2 groups develop independent hydrophobic hydration shells. The effect of the position of a CH2 group in the cosolute molecule is also considered. Kinetic solvent effects with structurally related esters show that amide-amide, ester-ester, and amide- ester group interactions affect the transition state in different ways. Finally, the effects of PVP polymers on the three hydrolysis reactions have been examined. The data presented enhance the understanding of pairwise hydrophobic interactions in aqueous solutions. In addition the results provide insights into the interactions between hydrophobic and hydrophilic hydration shells as well as into the energetics of amide hydration and interactions involving amides in aqueous solution, both playing important roles in protein stabilization.
- Apperloo, Joke J.,Streefland, Lisette,Engberts, Jan B. F. N.,Blandamer, Michael J.
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p. 411 - 418
(2007/10/03)
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- A Practical Synthesis of 5-Substituted Tetrazoles.
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Nitrosation of N-formyl amidrazones 8a-g with sodium nitrite - aqueous hydrochloric acid gives tetrazoles 10a-g in good yields.
- Boivin, Jean,Husinec, Suren,Zard, Samir Z.
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p. 11737 - 11742
(2007/10/02)
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- Remarkably Distinctive Recognition of α-Alanine and α-Phenylalanine during the Water-Catalyzed Hydrolysis of an Activated Amide
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The rate of the water-catalyzed hydrolysis of three activated amides in aqueous solution is significantly retarded by small amounts of α-phenylalanine as compared with the rate acceleration induced by other common α-amino acids not containing a benzyl group in their side chain.These contrasting effects emphasize the large hydrophobicity of α-phenylalanine and are of relevance for a better quantitative understanding of protein folding and molecular recognition processes involving proteins.
- Streefland, Lisette,Blandamer, Michael J.,Engberts, Jan B. F. N.
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p. 5769 - 5771
(2007/10/02)
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- Kinetics of Uncatalysed Hydrolysis of 1-Benzoyl-3-phenyl-1,2,4-triazole and p-Methoxyphenyl Dichloroethanoate in Aqueous Solution Containing Ureas, Carboxamides, Sulfonamides, Sulfones and Sulfoxides
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Rate contants are reported for the hydrolysis of 1-benzoyl-3-phenyl-1,2,4-triazole and p-methoxyphenyl dichloroethanoate in aqueous solutions containing formamide, acetamide, propionamide, isobutyramide, N-methylformamide, N,N-dimethylformamide, n-butyramide, N-methylacetamide, N,N-dimethylacetamide, urea, 1,3-dimethylurea, 1,1,3,3-tetramethylurea, methanesulfonamide, N-methylmethanesulfonamide, dimethylsulfonamide, dimethyl sulfone, tetramethylene sulfone, diethyl sulfone, DMSO, tetramethylene sulfoxide or diethyl sulfoxide.The data are analysed to yield quantitiesdefined as G(c) which describe Gibbs energies for substrate added solute interactions.The G(c) parameters are used to calculate group interaction parameters.Trends in derived G(c) parameters can be understood in terms of additivity of group interactions following the patern described by Savage and Wood for pairwise solute-solute interactions in aqueous solutions.
- Kerstholt, Rene P. V.,Engberts, Jan B. F. N.,Blandamer, Michael J.
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- Kinetics of Neutral Hydrolysis of 1-Benzoyl-3-phenyl-1,2,4-triazole in Highly Aqueous Media: Analysis of Effects of Added Ethanol and Propan-1-ol in terms of Pairwise Group Interaction Parameters
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Over the range 288.15 T/K 333.15, the first-order rate constant for the neutral hydrolysis of 1-benzoyl-3-phenyl-1,2,4-triazole in aqueous solutions (pH ca. 4) decreases when either ethanol or propan-1-ol is added.The kinetic data are analysed in terms of (a) the dependence of rate constant on temperature at fixed molality of added alcohol, and (b) the dependence of rate constant on molality of added alcohol at fixed temperature.In the latter case, the analysis leads to Gibbs energy interaction parameters which are assigned to group interaction parameters G(CH) and G(OH) for methine and hydroxy groups respectively.G(CH) is negative and G(OH) is positive, the corresponding enthalpic pairwise group interaction parameters having the opposite sign.This pattern is consistent with a more dramatic effect of added alcohol on the initial than on the transition state for the water-catalysed hydrolysis of the activated amide.
- Benak, Harm,Engberts, Jan B. F. N.,Blandamer, Michael J.
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p. 2035 - 2038
(2007/10/02)
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- A potassium amide induced ring transformation of 1,2,4-triazines into 1,2,4-triazoles and 1,3,5-triazines
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5-Phenyl- and 3,5-diphenyl-1,2,4-triazine, when treated with potassium amide in liquid ammonia, are converted into a mixture of phenyl derivatives of 1,2,4-triazole and amino-1,3,5-triazines. The ring contraction of the 1,2,4-triazine ring into the 1,2,4-triazole ring has been explained by an initial addition of the amide ion to C-6, ring opening by fission of the N1-C6 bond and ring closure (ANRORC-mechanism). The transformation of the 1,2,4-triazine ring into the 1,3,5-triazine ring has been studied by means of 15N-labeled potassium amide. It was found that the nitrogen of the amide ion becomes one of the ring nitrogen atoms in the 1,3,5-triazine ring and that the exocyclic amino group is imlabeled. Based on these 15N-labeling studies, it is proposed that this ring transformation starts with an initial addition of the amide ion to C-5, ring opening between C-5 and C-6, a dehydrogenative rearrangement of the open-chain intermediate 1-amino-2,4,5-triazahexatriene into 1-amino-4-cyano-2,4-diaza-1,3-butadiene, and ring closure.
- Rykowski,Van Der Plas
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- Water-Catalyzed Amide Hydrolysis in Dilute Aqueous Carbohydrate Solutions
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Rates and thermodynamics activation parameters were determined for the water-catalyzed hydrolysis of the activated amide bond in three 1-acyl-1,2,4-triazoles of different hydrophobicity by using dilute aqueous solutions of simple carbohydrates as the reaction medium.The solutions show thermodynamically almost ideal behavior.It appears that the kinetic medium effects, and, in particular, the changes in ΔS. are largely determined by carbohydrate-induced alterations in the three-dimensional hydrogen-bond network of water.The specific, hydration model for carbohydrates, developed by Franks and his associates, appears to provide a key to the understanding of the carbohydrate medium effects on the hydrolytic model reaction
- Nusselder, Jan Jaap H.,Engberts, Jan B. F. N.
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p. 3159 - 3162
(2007/10/02)
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- Water-Catalyzed Hydrolysis of 1-Acyl-1,2,4-triazoles in the Presence of Surfactant-Polymer Mixed Micelles. Substrate Dependence of the Effect of Polymer on the Micellar Inhibition
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The water-catalyzed hydrolysis of 1-benzoyl-1,2,4-triazole (1) is inhibited by SDS micelles.Addition of poly(vinylalcohol)-poly(vinyl acetate) copolymers (17percent and 26percent acetate, respectively) leads to a decreased inhibition.As supported by conductivity measurements, the rate effects are attributed to the formation of SDS-copolymer mixed micelles.Ultrafiltration experiments indicate increased binding of the substrate to the mixed micelles.Therefore the copolymer-induced rate accelerations can be best reconciled with an increase in the micropolarity at the substrate binding sites in the mixed micelles relative to unperturbed SDS micelles.With the aid of a computer, all kinetic data can be fitted into a kinetic scheme assuming hydrolysis of 1 in bulk water and in SDS and SDS-copolymer micellar pseudophases.Hydrolysis in SDS-poly(N-vinylpyrrolidone) (PVP) mixed micelles at low SDS concentrations (3-10 mM) was studied with the more hydrophobic substrate 3-phenyl-1-benzoyl-1,2,4-triazole (3).Now the SDS-induced inhibition is further increased by the polymer.Kinetic analysis shows that 3 is less strongly bound to mixed SDS-PVP micelles than to SDS micelles but that the rate constants in both micellar pseudophases are rather similar.It is argued that the different behavior of 1 and 3 in the mixed micelles primarily reflects the large propensity of 3 for stabilization by hydrophobic interactions.
- Fadnavis, Nitin W.,Berg, Henk-Jan van den,Engberts, Jan B. F. N.
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- Kinetics of Neutral Hydrolysis of Two 1-Acyl-1,2,4-triazoles in Binary Aqueous Mixtures: A Critique of the Evans and Polanyi Proposals Concerning Isochoric Activation Parameters
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Kinetic data are reported for hydrolysis of two 1-acyl-1,2,4-triazoles in water and two isodielectric mixtures which belong to different classes of aqueous mixtures.Trends in isothermal and isobaric activation parameters are examined in light of both solute-solvent interactions.Comments by Evans and Polanyi concerning an isochoric constraint are considered.Attention is drawn to the difficulties of satisfying the original criteria and to the possibility of using the internal pressure of the solvent as a way of satisfying in part the requirements of the Evans-Polanyi formalism.
- Haak, Jan R.,Engberts, Jan B. F. N.,Blandamer, Michael J.
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p. 6031 - 6035
(2007/10/02)
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- Effect of Poly(methacrylic acid) Hypercoils on the Neutral and Acid-Catalyzed Hydrolyses of 1-Acyl-1,2,4-triazoles in Aqueous Solution
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Rates and thermodynamic activation parameters have been measured for the neutral and acid-catalyzed hydrolyses of the 1-acyl-1,2,4-triazoles 1-3 in the presence of atactic poly(methacrylic acid) (at-PMAA).Under the employed reaction conditions at-PMAA resides in a coiled, compact conformation.The rates of hydrolysis of the relatively hydrophilic 1-acetyl- (1) and 1-benzoyl-1,2,4-triazole (2) are only little affected by the presence of the polymer.By contrast, the hydrolysis of the hydrophobic 1-benzoyl-3-phenyl-1,2,4-triazole (3) is effectively inhibited as a result of binding of 3 to hydrophobic microdomains within the at-PMAA hypercoil.Only small rate retardations are found for the hydrolysis of 3 in the presence of poly(acrylic acid).The effect of at-PMAA concentration on the rates of hydrolysis of 3 can be described in terms of a kinetic scheme that is essentially a variant of Michaelis-Menten enzyme kinetic formalism.In the presence of at-PMAA, ΔH(excit.) and ΔS(excit.) for the neutral hydrolysis of 3 undergo large and partly compensatory changes, the retardations being dominated by the increase of ΔH(excit.).These findings are interpreted by assuming reduced hydration of the dipolar transition state for hydrolysis in the relatively "dry" hydrophobic microdomains.Comparable results were obtained for the HCl-catalyzed hydrolysis of 3.The inhibitory effect of at-PMAA on this reaction is attenuated in the presence of urea, presumably because of destabilization of the compact conformation of the polymer.
- Jager, Jan,Engberts, Jan B. F. N.
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p. 1474 - 1478
(2007/10/02)
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- PREPARATION OF 3- AND 3,5-SUBSTITUTED 1,2,4-TRIAZOLES
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Ethyl 1,2,4-triazole-3-carboxylate (V), its 5-methyl and 5-phenyl derivatives (V and VI, respectively), 3-methyl-1,2,4-triazole (VIII), 3-phenyl-1,2,4-triazole (IX), 3,5-dimethyl-1,2,4-triazole (X), 3,5-diphenyl-1,2,4-triazole (XI) and 3-phenyl-5-methyl-1,2,4-triazole (XII) were prepared in 40-70percent yields by thermal cyclization of acylamidrazones III.
- Vanek, Tomas,Velkova, Vlasta,Gut, Jiri
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p. 2492 - 2495
(2007/10/02)
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- Water- and hydroxide-ion-catalyzed hydrolysis of 1-acyl-1,2,4-triazoles in mixed aqueous solvents. The effect of substrate hydrophobicity
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The solvent dependence of the enthalpies and entropies of activation for the title reaction in water-rich t-BuOH-H2O responds to the hydrophobicity of the substrate.
- Karzijn, Willem,Engberts, Jan B. F. N.
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p. 513 - 515
(2007/10/02)
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- SYNTHESIS OF TRIAZOLES AND OXADIAZOLES FROM 2-ARYL-3-PHENYL-4-IMINO-5-CYANO-3,4-DIHYDROPYRIMIDINES
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2-Aryl-3-phenyl-4-imino-5-cyano-3,4-dihydropyrimidines I were transformed to 1,2,4-triazoles II,IV and 1,2,4-oxadiazoles III by treatment with hydrazine, arylhydrazines or hydroxylamine in yields up to 90percent.
- Robev, Stefan K.
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p. 2903 - 2906
(2007/10/02)
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