• Bulletin of the Korean Chemical Society
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• 제29권10호
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• pp.1911-1914
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• 2008

Second-order rate constants (kN) have been measured for Michael-type addition reactions of a series of alicyclic secondary amines to 1-phenyl-2-propyn-1-one (2) in MeCN at 25.0 ${\pm}$ 0.1 ${^{\circ}C}$. All the amines studied are less reactive in MeCN than in $H_2O$ although they are more basic in the aprotic solvent by 7-9 p$K_a$ units. The Bronsted-type plot is linear with $\beta_{nuc}$ = 0.40, which is slightly larger than that reported previously for the corresponding reactions in $H_2O$ ($\beta_{nuc}$ = 0.27). Product analysis has shown that only E-isomer is produced. Kinetic isotope effect is absent for the reactions of 2 with morpholine and deuterated morpholine (i.e., $k^H/k^D$ = 1.0). Thus, the reaction has been concluded to proceed through a stepwise mechanism, in which proton transfer occurs after the rate-determining step. The reaction has been suggested to proceed through a tighter transition state in MeCN than in H2O on the basis of the larger $\beta_{nuc}$ in the aprotic solvent. The nature of the transition state has been proposed to be responsible for the decreased reactivity in the aprotic solvent.

• Bulletin of the Korean Chemical Society
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• 제17권6호
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• pp.520-524
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• 1996

Solvolyses of phenyl chloroformate in water, D2O, CH3OD, 50% D2O-CH3OD, and in aqueous binary mixtures of acetone, ethanol and methanol are investigated at 25.0 ℃. Product selectivities are reported at 25 ℃ for a wide range of ethanol-water and methanol-water solvent compositions. The Grunwald-Winstein plots of first-order rate constants for phenyl chloroformate with YCl (based on 2-adamantyl chloride) show marked dispersions into three separate lines for the three aqueous mixtures with a small m value (m< 0.2) and a rate maximum for aqueous alcohol solvents. Third-order rate constants, kww, kaw, kwa and kaa were calculated from the observed kww and kaa values together with kaw and kwa calculated from the intercept and slope of the plot of 1/S vs. [alcohol]/[water]. The calculated rate constants, kcalc and mol % of ester agree satisfactorily with those of the observed rate constants, kobs and mol % of ester, supporting the stoichiometric solvation effect analysis. The kinetic solvent isotope effects determined in water and methanol are consistent with the proposed mechanism of the general base catalyzed and/or carbonyl addition for phenyl chloroformate solvolyses based on mass law and stoichiometric solvation effect studies.

• Bulletin of the Korean Chemical Society
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• 제24권9호
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• pp.1293-1302
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• 2003

Rate constants at various temperatures and activation parameters are reported for solvolyses of acyl chlorides (RCOCl), with R = Me, Et, i-Pr, t-Bu, cyclopentylmethyl, benzyl, thiophenylmethyl, 2-phenylethyl, diphenylmethyl, and phenylthiomethyl in 100% ethanol, 100% 2,2,2-trifluoroethanol (TFE), 80% v/v ethanol/ water and 97% w/w TFE/water. Additional rate constants for solvolyses with R = Me, t-Bu, and $PhCH_2$ are reported for TFE/water and TFE/ethanol mixtures, and for solvolyses with R = t-Bu, and PhCH2 are reported for 1,1,1,3,3,3-hexafluoropropan-2-ol/water mixtures, as well as selected kinetic solvent isotope effects (MeOH/MeOD and TFE). Taft plots show that electron withdrawing groups (EWG) decrease reactivity significantly in TFE, but increase reactivity slightly in ethanol. Correlation of solvent effects using the extended Grunwald-Winstein (GW) equation shows an increasing sensitivity to solvent nucleophilicity for EWG. The effect of solvent stoichiometry in assumed third order reactions is evaluated for TFE/ethanol mixtures, which do not fit well in GW plots for R = Me, and t-Bu, and it is proposed that one molecule of TFE may have a specific role as electrophile; in contrast, reactions of substrates containing an EWG can be explained by third order reactions in which one molecule of solvent (ethanol or TFE) acts as a nucleophile, and a molecule of ethanol acts as a general base catalyst. Isokinetic relationships are also investigated.

• Bulletin of the Korean Chemical Society
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• 제21권10호
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• pp.955-956
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• 2000

Solvolyses of methanesulfonyl chloride in water, $D^2O$, $CH^3OD$, and in aqueous binary mixtures of acetone, eth-anol and methanol are investigated at 25, 35 and $45^{\circ}C.$ The Grunwald-Winstein plot of first-order rate con-stants for the solvolytic react ion of methanesulfonyl chloride with YCl (based on 2-adamantyl chloride) shows marked dispersions into three separate lines for three aqueous mixtures with a small m value (m < 0.30), and shows a rate maximum for aqueous alcoholic solvents. Stoichiometric third-order rate constants, kww and kaa were calculated from the observed first-order rate constants and (kaw + kwa) was calculated from the kww and kaa values. The kinetic solvent isotope effects determined in water and methanol are consistent with the proposed mechanism of the general base catalyzed and/or SAN/SN2 reaction mechanism for methanesulfonyl chloride solvolyses based on mass law and stoichiometric solvation effect studies.

• Bulletin of the Korean Chemical Society
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• 제19권9호
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• pp.968-973
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• 1998

Solvolyses of para-substituted phenyl chloroformates in water, $D_2O,\;CH_3OD$, 50% $D_2O-CH_3OD$, and in aqueous binary mixtures of acetone, ethanol, methanol are investigated at 25.0 ℃. Product selectivities are reported for a wide range of ethanol-water and methanol-water solvent compositions. These data are interpreted using the Grunwald-Winstein relationship, Hammett equation, and quantum mechanical model. Grunwald-Winstein plots of the first-order rate constants for phenyl chloroformates with $Y_{Cl}$ (based on 1-adamantyl chloride) show marked dispersions into three separate curves for the three aqueous mixtures with a small m value and a rate maximum for aqueous alcohol solvents. To account for these results, third-order rate constants, $k_{ww},\;k_{aw},\;k_{wa}$, and $k_{aa}$ were calculated from the observed $k_{ww}\;and\;k_{aa}$ values together with $k_{aw}\;and\;k_{wa}$ calculated from the computer fit. The kinetic solvent isotope effects determined in water and methanol are consistent with the proposed mechanism of the general base catalyzed carbonyl addition-elimination for para-substituted phenyl chloroformates solvolyses based on mass law and stoichiometric salvation effect studies. This study has shown that the quantum mechanical model predicts transition state variation correctly for $S_N2\;like\;S_AN$ reaction mechanism of para-substituted phenyl chloroformates.

• Bulletin of the Korean Chemical Society
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• 제23권1호
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• pp.123-131
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• 2002

Solvolyses rate constant of 1- and 2- naphthoyl chlorides (1 and 2) are reported for aqueous binary mixtures with methanol, ethanol, fluorinated alcohol, acetonitrile and dioxane. Kinetic solvent isotope effects (KISE) in methanol and product selectivities (S) of 2-naphthoyl chloride (2) in alcohol-water are also reported. Dispersions in Grunwald-Winstein correlations $(r{\leq}0.901)$ are discussed by multiple regression analysis incorporating ionizing power $(Y_{Cl})$ scale and rate-rate profiles. Major causes for these phenomena are investigated as an aromatic ring solvation effects, in conjunction with weakly nucleophilic solvation effects ($S_N2$ character), for solvolyses of 1 and for solvolyses of 2, as dual reaction channels, described as $S_N1$-$S_N2$ and $S_AN$-$S_N2$ processes. Distinct border lines between the two pathways are derived from solvolyses rates of 2 in 18 solvent using the results of $log(k/k_o)=mY_{Cl}+lN_T+hI$ plot with values of 1.13 for m, 0.37 for l and 0.15 for h value in 5 aqueous fluorinated alcohol mixtures. Using rate-product correlation, the validity of a third order model based on a general base catalyzed by solvent and contribution from these rate constants, $k_{aa},\;k_{aw}$ and $k_{aw}$, are investigated for $S_AN$-$S_N2$ solvolyses of 2 favored in more rich alcohol media and gradual addition of water to alcohol solvent shows a great shift away from stoichiometric solvation to predominantly medium effects. Rate-rate correlation between solvolyses of 2 and trimethyl acetylchloride (5) with alkyl group in the 29 aqueous solvent mixtures shows appreciable linearity (slope = 0.84, r = 0.987), caused by the same pathway ($S_N1$-$S_N2$ process), even if this correlation coincides with appreciable dispersion (different solvation effect).

• Bulletin of the Korean Chemical Society
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• 제30권9호
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• pp.1939-1945
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• 2009

Kinetic investigations on the oxidation of pyrazine and four 2-substituted pyrazines viz., 2-methylpyrazine, 2-ethylpyrazine, 2-methoxypyrazine and 2-aminopyrazine by bromamine-B (BAB) to the respective N-oxides have been studied in HCl$O_4$ medium at 303 K. The reactions show identical kinetics being first-order each in $[BAB]_o\;and\;[pyrazine]_o$, and a fractional- order dependence on $[H^+]$. Effect of ionic strength of the medium and addition of benzenesulfonamide or halide ions showed no significant effect on the reaction rate. The dielectric effect is positive. The solvent isotope effect was studied using $D_2$O. The reaction has been studied at different temperatures and activation parameters for the composite reaction have been evaluated from the Arrhenius plots. The reaction showed 1:1 stoichiometry and the oxidation products of pyrazines were characterized as their respective N-oxides. Under comparable experimental conditions, the oxidation rate of pyrazines increased in the order: 2-aminopyrazine > 2-methoxypyrazine > 2-ethylpyrazine > 2-methylpyrazine > pyrazine. The rates correlate with the Hammett $\sigma$ relationship and the reaction constant $\rho$ was found to be -0.8, indicating that electron donating centres enhance the rate of reaction. An isokinetic temperature of $\beta$ = 333 K, indicated that the reaction was enthalpy controlled. A mechanism consistent with the experimental results has been proposed in which the rate determining step is the formation of an intermediate complex between the substrate and the diprotonated species of the oxidant. The related rate law in consistent with observed results has been deduced.

• Bulletin of the Korean Chemical Society
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• 제33권11호
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• pp.3544-3550
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• 2012

Cetrizine dihydrochloride (CTZH) is widely used as an anti-allergic drug. Sodium N-bromo-p-toluenesulfonamide or bromamine-T (BAT) is the bromine analogue of chloramine-T (CAT) and is found to be a better oxidizing agent than CAT. In the present research, the kinetics of oxidation of CTZH with BAT in acid and alkaline media was studied at 313 K. The experimental rate laws obtained are: -d[BAT]/dt=$k[BAT][CTZH]^{0.80}[H^+]^{-0.48}$ in acid medium and -d[BAT]/dt=$k[BAT][CTZH]^{0.48}[OH^-]^{0.52}[PTS]^{-0.40}$ in alkaline medium where PTS is p-toluenesulfonamide. Activation parameters and reaction constants were evaluated. The solvent isotope effect was studied using $D_2O$. The dielectric effect is positive. The stoichiometry of the reaction was found to be 1:1 and the oxidation products were identified as 4-chlorobenzophenone and (2-piperazin-1-yl-ethoxy)-acetic acid in both media. The rate of oxidation of CTZH is faster in acid medium. Suitable mechanisms and related rate laws have been worked out.

• 생명과학회지
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• 제12권1호
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• pp.32-42
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• 2002

합성된 hexanoylthiocholine을 기질로 하여 butyrylcholinesterase와의 반응을 연구하였다. 기질의 농도 변화에 따른 초기반응속도 관찰을 통해 아실기의 탄소수가 증가함에 따라 반응성은 감소하나 $K_{m}$ 값은 0.140(mM)으로 더 강한 ES 복합체를 형성함을 알 수 있었다. Hexanoylthio-choline의 촉매화된 acetylcholinesterase 가수분해에 대한 pH-V/K profile에서 p $K_{a}$ 값 4.974$\pm$0.02을 얻었다. 이는 최근 문헌의 보고와 상통하는 것으로 p $K_{a}$ =6.2~6.4를 갖는 잔류물의 기본형에 활성이 의존하는 것으로부터 하나의 잔류물 또는 p $K_{a}$ =4.7~5.0을 갖는 잔류물들의 촉매작용으로 계통적인 자리밀림을 보여준다. 이는 촉매화된 BChE의 활성영역 esteratic site 주변에 긴 사슬 아실기의 가수분해에 관여하는 새로운 활성영역이 존재함을 밝히는 증거이다. 분자 조형은 기질의 아실기의 탄소수에 따라 acetylcholinesterase에 의해 표현되어지는 반응과정의 변화의 합리성을 제공한다. 본 연구에서는 한국과학기술원 도핑컨트롤센터와 연계하여 acetylcholinesterase와 기질인 acylthiocholine과의 입체적으로 둘러싸인 acyl-binding site를 분자 조형하고자 노력 중에 있다.

• Bulletin of the Korean Chemical Society
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• 제24권1호
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• pp.65-69
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• 2003

The kinetic and chemical mechanisms of AChE-catalyzed hydrolysis of short-chain thiocholine esters are relatively well documented. Up to propanoylthiocholine (PrTCh) the chemical mechanism is general acid-base catalysis by the active site catalytic triad. The chemical mechanism for the enzyme-catalyzed butyrylthiocholine(BuTCh) hydrolysis shifts to a parallel mechanism in which general base catalysis by E199 of direct water attack to the carbonyl carbon of the substrate. [Selwood, T., et al. J. Am. Chem. Soc. 1993, 115, 10477- 10482] The long chain thiocholine esters such as hexanoylthiocholine (HexTCh), heptanoylthiocholine (HepTCh), and octanoylthiocholine (OcTCh) are hydrolyzed by electric eel acetylcholinesterase (AChE). The kinetic parameters are determined to show that these compounds have a lower Michaelis constant than BuTCh and the pH-rate profile showed that the mechanism is similar to that of BuTCh hydrolysis. The solvent isotope effect and proton inventory of AChE-catalyzed hydrolysis of HexTCh showed that one proton transfer is involved in the transition state of the acylation stage. The relationship between the dipole moment and the Michaelis constant of the long chain thiocholine esters showed that the dipole moment is the most important factor for the binding of a substrate to the enzyme active site.