Aminolysis of Benzyl 4-Pyridyl Carbonate in Acetonitrile: Effect of Modification of Leaving Group from 2-Pyridyloxide to 4-Pyridyloxide on Reactivity and Reaction Mechanism

Bae, Ae-Ri,Um, Ik-Hwan Korean Chemical Society 2012 Bulletin of the Korean Chemical Society Vol.33 No.8

A kinetic study is reported for nucleophilic substitution reactions of benzyl 4-pyridyl carbonate 6 with a series of alicyclic secondary amines in MeCN. The plot of pseudo-first-order rate constant ($k_{obsd}$) vs. [amine] curves upward, which is typical for reactions reported previously to proceed through a stepwise mechanism with two intermediates (i.e., a zwitterionic tetrahedral intermediate $T^{\pm}$ and its deprotonated form $T^-$). Dissection of $k_{obsd}$ into the second- and third-order rate constants (i.e., $Kk_2$ and $Kk_3$, respectively) reveals that $Kk_3$ is significantly larger than $Kk_2$, indicating that the reactions proceed mainly through the deprotonation pathway (i.e., the $k_3$ process) in a high [amine] region. This contrasts to the recent report that the corresponding aminolysis of benzyl 2-pyridyl carbonate 5 proceeds through a forced concerted mechanism. An intramolecular H-bonding interaction was suggested to force the reactions of 5 to proceed through a concerted mechanism, since it could accelerate the rate of leaving-group expulsion (i.e., an increase in $k_2$). However, such H-bonding interaction, which could increase $k_2$, is structurally impossible for the reactions of 6. Thus, presence or absence of an intramolecular H-bonding interaction has been suggested to be responsible for the contrasting reaction mechanisms (i.e., a forced concerted mechanism for the reaction of 5 vs. a stepwise mechanism with $T^{\pm}$ and $T^-$ as intermediates for that of 6).

Decomposition of Paraoxon and Parathion by Amines, HOO^- and OH^- Ions: Reaction Mechanism and Origin of the α-Effect

Bae, Ae-Ri,Lee, Jieun,Um, Ik-Hwan Korean Chemical Society 2013 Bulletin of the Korean Chemical Society Vol.34 No.1

The second-order rate constants have been measured spectrophotometrically for the reactions of paraoxon 1 and parathion 2 with a series of alicyclic secondary amines, $OH^-$ and $HOO^-$ ions in $H_2O$ at $25.0{\pm}0.1^{\circ}C$. A linear Br${\o}$nsted-type plot with ${\beta}_{nuc}$ = 0.40 was obtained for the reactions of 1 with amines and $OH^-$. The reaction has been concluded to proceed through a concerted mechanism. $HOO^-$ deviates positively from the linear Br${\o}$nsted-type plot, implying that the ${\alpha}$-effect is operative. The magnitude of the ${\alpha}$-effect ($k_{HOO^-}/k_{OH^-}$) was found to be ca. 55 for the reaction of 1 and 290 for that of parathion 2, indicating that $HOO^-$ is highly effective in decomposition of the toxic phosphorus compounds although it is over 4 $pK_a$ units less basic than $OH^-$. Among the theories suggested as origins of the ${\alpha}$-effect (e.g., TS stabilization through an intramolecular Hbonding interaction, solvent effect, and polarizability effect), polarizability effect appears to be the most important factor for the ${\alpha}$-effect in this study, since the polarizable $HOO^-$ exhibits a larger ${\alpha}$-effect for the reaction of the more polarizable substrate 2.

Kinetics and Reaction Mechanism of Aminolyses of Benzyl 2-Pyridyl Carbonate and t-Butyl 2-Pyridyl Carbonate in Acetonitrile

Bae, Ae-Ri,Um, Ik-Hwan Korean Chemical Society 2012 Bulletin of the Korean Chemical Society Vol.33 No.5

Second-order rate constants ($k_N$) have been measured spectrophotometrically for the reactions of benzyl 2-pyridyl carbonate $\mathbf{3}$ and $t$-butyl 2-pyridyl carbonate $\mathbf{3}$ with a series of alicyclic secondary amines in MeCN at $25.0{\pm}0.1^{\circ}C$. Substrate $\mathbf{4}$ is much less reactive than $\mathbf{3}$ and the steric hindrance exerted by the bulky $t$-Bu group in $\mathbf{4}$ has been attributed to its decreased reactivity. The Br${\o}$nsted-type plots for the reactions of $\mathbf{3}$ and $\mathbf{4}$ are linear with ${\beta}_{nuc}=0.57$ and 0.45, respectively. Thus, the reactions have been concluded to proceed through a concerted mechanism, although the current reactions were expected to proceed through a stepwise mechanism with a zwitterionic tetrahedral intermediate $T^{\pm}$. It has been proposed that the rate of leaving-group expulsion is accelerated by the intramolecular H-bonding interaction in $T^{\pm}$ and the "push" provided by the RO group through the resonance interaction. Thus, the enhanced nucleofugality forces the reactions to proceed through a concerted mechanism. The reactivity-selectivity principle (RSP) is not applicable to the current reaction systems, since the reaction of the less reactive $\mathbf{4}$ results in a smaller ${\beta}_{nuc}$ than that of the more reactive $\mathbf{3}$. Steric hindrance exerted by the bulky $t$-Bu group in $\mathbf{4}$ has been suggested to be responsible for the failure of the RSP.

Kinetic Study on Aminolysis of 4-Pyridyl X-Substituted Benzoates: Effect of Substituent X on Reactivity and Reaction Mechanism

이종팔,Ae Ri Bae,엄익환 대한화학회 2011 Bulletin of the Korean Chemical Society Vol.32 No.6

A kinetic study is reported for nucleophilic substitution reactions of 4-pyridyl X-substituted benzoates 7a-e with a series of alicyclic secondary amines in H_2O. The Brønsted-type plot for the reactions of 4-pyridyl benzoate 7c is linear with β_(nuc) = 0.71. The corresponding reactions of 2-pyridyl benzoate 6, which is less reactive than 7c, resulted in also a linear Brønsted-type plot with β_(nuc) = 0.77. The fact that the more reactive 7c results in a smaller β_(nuc) value appears to be in accord with the reactivity-selectivity principle. The aminolysis of 7c has been suggested to proceed through a stepwise mechanism in which breakdown of the intermediate is the rate-determining step (RDS). The Hammett plot for the reactions of 7a-e with piperidine consists of two intersecting straight lines, i.e., ρX = 1.47 for substrates possessing an electron-donating group (EDG) and ρX =0.91 for those possessing an electron-withdrawing group (EWG). In contrast, the corresponding Yukawa-Tsuno plot exhibits excellent linear correlation with ρX = 0.79 and r = 0.56. Thus, it has been concluded that the nonlinear Hammett plot is not due to a change in the RDS but is caused by stabilization of the ground state of the substrates possessing an EDG through resonance interaction between the EDG and the C=O bond of the substrates.

The α-Effect in Nucleophilic Substitution Reactions of Y-Substituted-Phenyl Diphenylphosphinates with HOO− and OH−

홍효정,Ae Ri Bae,엄익환 대한화학회 2013 Bulletin of the Korean Chemical Society Vol.34 No.8

Second-order rate constants (kHOO−) for the nucleophilic substitution reactions of Y-substituted-phenyl diphenylphosphinates (4a-4i) with HOO− in H2O have been measured spectrophotometrically. The α-nucleophile HOO− is 10-70 times more reactive than the reference nucleophile OH− although the former is ca. 4 pKa units less basic than the latter, indicating the α-effect is operative. The Brønsted-type plot for the reactions of 4a-4i with HOO– is linear with βlg = –0.51, a typical βlg value for reactions which were reported to proceed through a concerted mechanism. The Yukawa-Tsuno plot is also linear with ρ = 1.40 and r = 0.47, indicating that a negative charge develops partially on the O atom of the leaving group, which can be delocalized to the substituent Y through resonance interactions. Thus, the reactions have been proposed to proceed through a concerted mechanism. The magnitude of the α-effect (i.e., the kHOO−/kHO− ratio) decreases linearly as the leaving-group basicity increases. It has been concluded that solvation effect is not solely responsible for the α- effect found in this study but the transition-state stabilization through an intramolecular H-bonding interaction is also responsible for the α-effect.

Antidepressant-Like Effects of <i>Vaccinium bracteatum</i> in Chronic Restraint Stress Mice: Functional Actions and Mechanism Explorations

Oh, Dool-Ri,Kim, Yujin,Choi, Eun-Jin,Jung, Myung-A,Oh, Kyo-Nyeo,Hong, Ji-Ae,Bae, Donghyuck,Kim, Kwangsu,Kang, Huwon,Kim, Jaeyong,Kim, Young Ran,Cho, Seung Sik,Choi, Chul-Young World Scientific Publishing Company 2018 The American journal of Chinese medicine Vol.46 No.2

<P>The fruit of <I>Vaccinium bracteatum</I> Thunb. (VBF) is commonly known as the oriental blueberry in Korea. The aim of this study was to evaluate the antidepressant-like effects of water VBF extract (VBFW) in a mouse model of chronic restraint stress (CRS) and to identify the underlying mechanisms of its action. The behavioral effects of VBFW were assessed in the forced swim test (FST) and open field test (OFT). The levels of serum corticosterone (CORT), brain monoamines, in addition to the extracellular signal-regulated kinases (ERKs)/protein kinase B (Akt) signaling pathway were evaluated. VBFW treatment significantly reduced the immobility time and increased swimming time in FST without altering the locomotor activity in unstressed mice. Furthermore, CRS mice treated with VBFW exhibited a significantly decreased immobility time in FST and serum CORT, increased locomotor activity in OFT, and enhanced brain monoamine neurotransmitters. Similarly, VBFW significantly upregulated the ERKs/Akt signaling pathway in the hippocampus and PFC. In addition, VBFW may reverse CORT-induced cell death by enhancing cyclic AMP-responsive element-binding protein expression through the up-regulation of ERKs/Akt signaling pathways. In addition, VBFW showed the strong antagonistic effect of the 5-HT<TEX>$ _{2\text{A}}$</TEX> receptor by inhibiting 5-HT-induced intracellular Ca<TEX>$ ^{2+}$</TEX> and ERK1/2 phosphorylation. Our study provides evidence that antidepressant-like effects of VBFW might be mediated by the regulation of monoaminergic systems and glucocorticoids, which is possibly associated with neuroprotective effects and antagonism of 5-HT<TEX>$ _{2\text{A}}$</TEX> receptor.</P>

A Kinetic Study on Aminolysis of 2-Pyridyl X-Substituted Benzoates: Effect of Changing Leaving Group from 4-Nitrophenolate to 2-Pyridinolate on Reactivity and Mechanism

Lee, Jong-Pal,Bae, Ae-Ri,Im, Li-Ra,Um, Ik-Hwan Korean Chemical Society 2010 Bulletin of the Korean Chemical Society Vol.31 No.12

Second-order rate constants ($k_N$) have been measured spectrophotometrically for nucleophilic substitution reactions of 2-pyridyl X-substituted benzoates 8a-e with a series of alicyclic secondary amines in $H_2O$ at $25.0{\pm}0.1^{\circ}C$. The $k_N$ values for the reactions of 8a-e are slightly smaller than the corresponding reactions of 4-nitrophenyl X-substituted benzoates 1a-e (e.g., $kN^{1a-e}/k_N^{8a-e}$ = 1.1 ~ 3.1), although 2-pyridinolate in 8a-e is ca. 4.5 $pK_a$ units more basic than 4-nitrophenolate in 1a-e. The Br$\o$nsted-type plot for the aminolysis of 8c (X = H) is linear with $\beta_{nuc}$ = 0.77 and $R^2$ = 0.991 (Figure 1), which is typical for reactions reported previously to proceed through a stepwise mechanism with breakdown of a zwitterionic tetrahedral intermediate $T^{\pm}$ being the rate-determining step (RDS), e.g., aminolysis of 4-nitrophenyl benzoate 1c. The Hammett plot for the reactions of 8a-e with piperidine consists of two intersecting straight lines (Figure 2), i.e., $\rho$ = 1.71 for substrates possessing an electron-donating group (EDG) while $\rho$ = 0.86 for those bearing an electron-withdrawing group (EWG). Traditionally, such a nonlinear Hammett plot has been interpreted as a change in RDS upon changing substituent X in the benzoyl moiety. However, it has been proposed that the nonlinear Hammett is not due to a change in RDS since the corresponding Yukawa-Tsuno plot exhibits excellent linear correlation with $\rho$ = 0.85 and r = 0.62 ($R^2$ = 0.995, Figure 3). Stabilization of substrates 8a-e in the ground state has been concluded to be responsible for the nonlinear Hammett plot.

Electronic Nature of Substituent X Governs Reaction Mechanism in Aminolysis of 4-Pyridyl X-Substituted-Benzoates in Acetonitrile

Um, Ik-Hwan,Bae, Ae Ri American Chemical Society 2012 Journal of organic chemistry Vol.77 No.13

<P>A kinetic study is reported for aminolysis of 4-pyridyl X-substituted-benzoates <B>5a</B>–<B>i</B>. Plots of pseudo-first-order rate constants (<I>k</I><SUB>obsd</SUB>) vs [amine] curve upward for the reactions of substrates possessing a strong electron-withdrawing group in the benzoyl moiety (<B>5a</B>–<B>d</B>) but are linear for the reactions of those bearing an electron-donating group (<B>5e</B>–<B>i</B>), indicating that the electronic nature of substituent X governs the reaction mechanism. The <I>k</I><SUB>1</SUB><I>k</I><SUB>2</SUB>/<I>k</I><SUB>–1</SUB> and <I>k</I><SUB>1</SUB><I>k</I><SUB>3</SUB>/<I>k</I><SUB>–1</SUB> values were calculated from the intercept and slope of the linear plots of <I>k</I><SUB>obsd</SUB>/[amine] vs [amine], respectively. The Hammett plot for <I>k</I><SUB>1</SUB><I>k</I><SUB>2</SUB>/<I>k</I><SUB>–1</SUB> consists of two intersecting straight lines, while the Yukawa–Tsuno plot exhibits an excellent linear correlation with ρ<SUB>X</SUB> = 0.41 and <I>r</I> = 1.58, implying that the nonlinear Hammett plot is not due to a change in rate-determining step but is caused by stabilization of substrates possessing an electron-donating group through resonance interactions. The small ρ<SUB>X</SUB> suggests that the <I>k</I><SUB>2</SUB>/<I>k</I><SUB>–1</SUB> ratio is little influenced by the nature of substituent X. The Brønsted-type plots for aminolysis of 4-pyridyl 3,5-dinitrobenzoate 5a are linear with β<SUB>nuc</SUB> = 0.98 and 0.79 for <I>k</I><SUB>1</SUB><I>k</I><SUB>2</SUB>/<I>k</I><SUB>–1</SUB> and <I>k</I><SUB>1</SUB><I>k</I><SUB>3</SUB>/<I>k</I><SUB>–1</SUB>, respectively. The effect of amine basicity on the microscopic rate constants is also discussed.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/joceah/2012/joceah.2012.77.issue-13/jo300961y/production/images/medium/jo-2012-00961y_0007.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/jo300961y'>ACS Electronic Supporting Info</A></P>

Change in Physicochemical and Microbiological Qualities of Hanwoo Beef under Different Freezing and Thawing Conditions

Ho Hyun Chun,Ae Ri Han,Eun Ji Choi,Young Bae Chung 한국식품영양과학회 2015 한국식품영양과학회 학술대회발표집 Vol.2015 No.8

A Kinetic Study on Aminolysis of 2-Pyridyl X-Substituted Benzoates: Effect of Changing Leaving Group from 4-Nitrophenolate to 2-Pyridinolate

Jong Pal Lee,Ae Ri Bae,Li-Ra Im,Ik-Hwan Um 대한화학회 2010 Bulletin of the Korean Chemical Society Vol.31 No.12

Second-order rate constants (kN) have been measured pectrophotometrically for nucleophilic substitution reactions of 2-pyridyl X-substituted benzoates 8a-e with a series of alicyclic secondary amines in H2O at 25.0 ± 0.1 ℃. The kN values for the reactions of 8a-e are slightly smaller than the corresponding reactions of 4-nitrophenyl X-substituted benzoates 1a-e (e.g., kN 1a-e/kN 8a-e = 1.1 ~ 3.1), although 2-pyridinolate in 8a-e is ca. 4.5 pKa units more basic than 4-nitrophenolate in 1a-e. The Brønsted-type plot for the aminolysis of 8c (X = H) is linear with βnuc = 0.77 and R2 = 0.991 (Figure 1), which is typical for reactions reported previously to proceed through a stepwise mechanism with breakdown of a zwitterionic tetrahedral intermediate T± being the rate-determining step (RDS), e.g., aminolysis of 4-nitrophenyl benzoate 1c. The Hammett plot for the reactions of 8a-e with piperidine consists of two intersecting straight lines (Figure 2), i.e., ρ = 1.71 for substrates possessing an electron-donating group (EDG) while ρ = 0.86 for those bearing an electron-withdrawing group (EWG). Traditionally, such a nonlinear Hammett plot has been interpreted as a change in RDS upon changing substituent X in the benzoyl moiety. However, it has been proposed that the nonlinear Hammett is not due to a change in RDS since the corresponding Yukawa-Tsuno plot exhibits excellent linear correlation with ρ = 0.85 and r = 0.62 (R2 = 0.995, Figure 3). Stabilization of substrates 8a-e in the ground state has been concluded to be responsible for the nonlinear Hammett plot.