994-29-6Relevant articles and documents
Quantitative Assessment of Solvent-Sorting Effects. 1. Menschutkin Reaction in Mixed Solvents
Abboud, Jose-Luis M.,Douhal, Abderrazzak,Arin, Maria Jesus,Diez, Maria Teresa,Homan, Hamid,Guiheneuf, Georges
, p. 214 - 220 (1989)
The second-order rate constant kapp for the reaction between (C2H5)3N and CH3I has beeen determined at 30.0 deg C in cyclohexane and in mixtures of cyclohexane with variable amounts (up to ca. 0.3 M) of the following cosolvents (S): N,N-dimethylacetamide, cyclohexanecarbonitrile, cyclohexyl methyl ketone, butanone, tetrahydrofuran, ethyl acetate, cyclohexyl chloride, methyl cyclohexanecarboxylate, cyclohexyl methyl ether, dibutyl ether, nitrobenzene, N,N-dimethylbenzamide, benzonitrile, acetophenone, benzophenone, methyl benzoate, diphenylmethane, anisole, chlorobenzene, fluorobenzene, 1,2-diphenylethane, triphenylmethane, benzene, 1,4-dichlorobenzene, toluene, and p-xylene.Within the limits of experimental error, the following have been found: (1) The activity coefficients of the reagents are practically unaffected by the added cosolvent. (2) For low cosolvent concentrations, kapp is related to the concentration of S by the equation kapp = k0 + kc, where k0 is the reaction rate in pure cyclohexane. (3) In all cases, the catalytic effect of S is quite large: it amounts to ca. 50percent of the lowering of the activation free energy of the reaction, observed on going from pure cyclohexane to pure S. (4) This major effect is largely underestimated by the Onsager-Kirkwood model. (5) The catalytic efficiency of aromatic cosolvents of low or zero dipolarity is over 1 order of magnitude larger than predicted by this model.This is traced to electrostatic interactions involving higher multipoles and to London forces. (6) Although a fraction of the catalytic effect can be attributed to a "general dielectric" contribution, these and other results strongly suggest that this reaction can proceed through a true termolecular channel.
A new synthesis of Entacapone and report on related studies
Harisha, Attimogae Shivamurthy,Nayak, Suresh Parameshwar,Pavan,Shridhara,Sundarraja Rao,Rajendra,Pari, Koteppa,Sivaramkrishnan,Guru Row,Nagarajan, Kuppuswamy
, p. 1977 - 1991 (2015/12/30)
A new synthesis of the catechol-O-methyltransferase (COMT) inhibitor, entacapone (E-isomer) has been achieved under mild conditions by amine-mediated demethylation of the precursor 2-Cyano-3-(3- hydroxy-4-methoxy-5-nitrophenyl) prop-2-eneamide, wherein the methoxyl group adjacent to a nitro group gets demethylated under nucleophilic attack. Similar demethylation was achieved on ethyl 2-cyano-3-(3, 4-dimethoxy-5-nitrophenyl) prop-2-enoate, 2-cyano-3-(3,4-dimethoxy-5-nitrophenyl)-N,N-diethylprop-2-enamide, ethyl 2-cyano-3-(3-hydroxy-4-methoxy-5-nitrophenyl) prop-2-enoate and ethyl 2-cyano-3-(4-methoxy-3-nitrophenyl) prop-2-enoate. The scope of demethylation has been studied. Analogues of ethyl 2-cyano-3-(3, 4-dimethoxy-5-nitrophenyl) prop-2-enoate wherein a methoxyl group is not adjacent to a NO 2 group are unaffected and phenolic derivatives yield the amine salts. Entacapone has been converted to salts with organic bases. The crystal structure of the isomer of entacapone (Z-isomer), a significant human metabolite of E-isomer has been established. NMR methods for deriving E and Z geometry and other similar molecules have been successfully established, mainly by studying the proton coupled 13C spectra. Preliminary studies reveal in vitro activity for some compounds against tuberculosis (TB) and dengue. [Figure not available: see fulltext.]
Quaternary ammonium ions can externally block voltage-gated K+ channels. Establishing a theoretical and experimental model that predicts KDS and the selectivity of K+ over Na+ ions
Wempe
, p. 63 - 78 (2007/10/03)
The physicochemical basis for the high ion selectivity of potassium channels is poorly understood. In the present studies, external blockade of cloned voltage-gated potassium channels with alkyl quaternary ammonium ions are analyzed from a model derived from theory and experimental data. Atomic mass units, electrostatic potential residing on the nitrogen atom, the COSMO van der Waals solvent accessible surface, the Onsager solvation model, and the isodensity PCM solvation model are computed at the semi-empirical and the ab initio levels of theory. A structure-activity relationship (SAR) exists between the calculated values and the experimentally obtained KD (mM). The SAR model gives us KD predictions and when K+ and Na+ are incorporated into the model, it dramatically predicts the selectivity of K+ over Na+ ions.
