title: Kinetic studies of cyclisations of 2'-hydroxychalcones and derivatives

authors: Old, Kenneth Barry

abstract: The rates of cyclisation of various 2'-hydroxychalcones to the equilibrium mixture of chalcone and flavanone have been determined over the pH range in which the chalcones undergo ionisation. The compounds studied were 2'-hydroxy-, 2'-hydroxy-5', 6'-benzo-, 2',4'-dihydroxy-, 2'-hydroxy-4'-methoxy-, 2'-hydroxy-6'-methoxy-, and 2'-hydroxy-4', 6'-dimethylchalcone. In each case the observed first order rate constant has been fitted to a theoretical pH-rate profile based on the equation
kₒbₛ = kfCH + k’fC⁻ + k’’ {OH⁻} 
where k is the rate constant for the cyclisation of neutral chalcone (fCH is the fraction of neutral chalcone), k' is the rate constant for the cyclisation of the ionised chalcone (fC⁻ is the fraction of ionised chalcone), and k" is a measure of the rate in the reverse reaction. The expression implies that the reaction in the forward direction can proceed from neutral or ionised chalcone, and in the reverse direction through the reaction of flavanone with hydroxide ion. In all cases the forward reaction of the ionised chalcone (k') is very much faster than that of the neutral species (k). Weak catalysis by some buffer species has been detected but the origin of this catalysis has not been pursued in detail. Comparisons are made between the forward and reverse rate constants for the different chalcones in order to see how they are affected by different A-ring substituents. It is observed that electron releasing groups at the 4'- or 6'- positions decrease the rate. This diminution in the observed rate is particularly pronounced with 6'-substituents, and is considered as possibly due to the steric and/or electrostatic interaction of this substituent with the carbonyl group an interaction that could force the carbonyl group to lie out of the plane of the A-ring thereby changing rates of reactions by electronic or steric effects.
The first kinetic study of the reactivity of a 2'-hydroxychalcone epoxide is reported. The variation of the rate of cyclisation of the parent epoxide, 2'-hydroxychalcone epoxide, to 3-hydroxyflavanone in water, over the range pH 1 - 6.5, is shown to be consistent with the rate equation.
Rate = 0.235 [Epoxide]{H⁺} + 1.85 x 10⁶ [Expoxide] {OH⁻} mol 1⁻¹s⁻¹
This shows the epoxide to be very unstable at or above neutral pH, and suggests that such compounds, if they do occur, as has often been suggested, as intermediates in flavanoid biosynthesis would probably be very difficult to isolate. Their detection under the basic conditions of either the Algar-Flynn-Oyamada oxidation of 2'-hydroxychalcones, or the formation of aurones from certain 2'-hydroxychalcone dibromides, both reactions in which they have been suggested as intermediates, would be equally unlikely : based on a suggested mechanism, the parent epoxide of this study can be predicted to have a half-life at pH 10 of the order of a few milliseconds.
The first determination of the ratio of E- and Z-2'-hydroxy-α-bromochalcones formed directly from a 2'-hydroxychalcone dibromide is described. Combined kinetic and spectrophotometric measurements give the yield (%) of E- and Z-2'-hydroxy-α-bromochalcone as 35 ± 2 and 63 ± 8 respectively for the reaction of erythro-2'-hydroxychalcone dibromide in 4:1 ethanol-water buffered at pH 7.88 with N-ethylmorpholine. Direct cyclisation of the dibromo compound, if it occurs at all, is only a very minor route to 3-bromoflavanone. The lack of any detected dependence buffer concentrations of the rate constants or of the proportions of the E- and Z-isomers formed suggest, an E1cв mechanism rather than an E2. However, with the particular elimination involved (i.e. a double bond being formed α, β to a carbonyl group) there is precedence for small catalysis by N-alkylmorpholines and therefore, it is not certain that the lack of measurable buffer catalysis does in fact mean a total lack of catalysis. Further, if the elimination is in fact by an E1cв type mechanism, a carbanion is not necessarily involved, as the elimination could proceed from the phenolate ion as conjugate base, the phenoxide group acting in place of an external base. An El mechanism is excluded on kinetic grounds.

text: Kinetic studies of cyclisations of 2'-hydroxychalcones and derivatives The rates of cyclisation of various 2'-hydroxychalcones to the equilibrium mixture of chalcone and flavanone have been determined over the pH range in which the chalcones undergo ionisation. The compounds studied were 2'-hydroxy-, 2'-hydroxy-5', 6'-benzo-, 2',4'-dihydroxy-, 2'-hydroxy-4'-methoxy-, 2'-hydroxy-6'-methoxy-, and 2'-hydroxy-4', 6'-dimethylchalcone. In each case the observed first order rate constant has been fitted to a theoretical pH-rate profile based on the equation
kₒbₛ = kfCH + k’fC⁻ + k’’ {OH⁻} 
where k is the rate constant for the cyclisation of neutral chalcone (fCH is the fraction of neutral chalcone), k' is the rate constant for the cyclisation of the ionised chalcone (fC⁻ is the fraction of ionised chalcone), and k" is a measure of the rate in the reverse reaction. The expression implies that the reaction in the forward direction can proceed from neutral or ionised chalcone, and in the reverse direction through the reaction of flavanone with hydroxide ion. In all cases the forward reaction of the ionised chalcone (k') is very much faster than that of the neutral species (k). Weak catalysis by some buffer species has been detected but the origin of this catalysis has not been pursued in detail. Comparisons are made between the forward and reverse rate constants for the different chalcones in order to see how they are affected by different A-ring substituents. It is observed that electron releasing groups at the 4'- or 6'- positions decrease the rate. This diminution in the observed rate is particularly pronounced with 6'-substituents, and is considered as possibly due to the steric and/or electrostatic interaction of this substituent with the carbonyl group an interaction that could force the carbonyl group to lie out of the plane of the A-ring thereby changing rates of reactions by electronic or steric effects.
The first kinetic study of the reactivity of a 2'-hydroxychalcone epoxide is reported. The variation of the rate of cyclisation of the parent epoxide, 2'-hydroxychalcone epoxide, to 3-hydroxyflavanone in water, over the range pH 1 - 6.5, is shown to be consistent with the rate equation.
Rate = 0.235 [Epoxide]{H⁺} + 1.85 x 10⁶ [Expoxide] {OH⁻} mol 1⁻¹s⁻¹
This shows the epoxide to be very unstable at or above neutral pH, and suggests that such compounds, if they do occur, as has often been suggested, as intermediates in flavanoid biosynthesis would probably be very difficult to isolate. Their detection under the basic conditions of either the Algar-Flynn-Oyamada oxidation of 2'-hydroxychalcones, or the formation of aurones from certain 2'-hydroxychalcone dibromides, both reactions in which they have been suggested as intermediates, would be equally unlikely : based on a suggested mechanism, the parent epoxide of this study can be predicted to have a half-life at pH 10 of the order of a few milliseconds.
The first determination of the ratio of E- and Z-2'-hydroxy-α-bromochalcones formed directly from a 2'-hydroxychalcone dibromide is described. Combined kinetic and spectrophotometric measurements give the yield (%) of E- and Z-2'-hydroxy-α-bromochalcone as 35 ± 2 and 63 ± 8 respectively for the reaction of erythro-2'-hydroxychalcone dibromide in 4:1 ethanol-water buffered at pH 7.88 with N-ethylmorpholine. Direct cyclisation of the dibromo compound, if it occurs at all, is only a very minor route to 3-bromoflavanone. The lack of any detected dependence buffer concentrations of the rate constants or of the proportions of the E- and Z-isomers formed suggest, an E1cв mechanism rather than an E2. However, with the particular elimination involved (i.e. a double bond being formed α, β to a carbonyl group) there is precedence for small catalysis by N-alkylmorpholines and therefore, it is not certain that the lack of measurable buffer catalysis does in fact mean a total lack of catalysis. Further, if the elimination is in fact by an E1cв type mechanism, a carbanion is not necessarily involved, as the elimination could proceed from the phenolate ion as conjugate base, the phenoxide group acting in place of an external base. An El mechanism is excluded on kinetic grounds.

year: 1980

title: Work-based Learning: A New Higher Education? [Book Review]

authors: Piercy, Gemma Louise

subjects: book review

abstract: This article reviews the book: “Work-based Learning: A New Higher Education?”, edited by D. Boud & N. Solomon.

text: Work-based Learning: A New Higher Education? [Book Review] This article reviews the book: “Work-based Learning: A New Higher Education?”, edited by D. Boud & N. Solomon.

year: 2002

title: Hoea Te Waka ki Uta: Critical Kaupapa Māori Research and Mormon Studies Moving Forward

authors: Simon, Hemopereki

abstract: The following is a reflective commentary on the place of Critical Indigenous Studies, with a focus on Kaupapa Māori Research, within Mormon Studies. Specifically, the piece explores the following questions: What does Kaupapa Māori Research look like when engaging in Mormon Studies? What positionality needs to be taken by Kaupapa Māori researchers and Critical Indigenous scholars when engaging in Mormon Studies? What are the main areas Critical Indigenous scholars and Kaupapa Māori scholars should engage when tackling issues around Mormonism? These questions are important in light of the growing importance of the cultural renaissance in Te Ao Māori and the rise of Kaupapa Māori Research.

text: Hoea Te Waka ki Uta: Critical Kaupapa Māori Research and Mormon Studies Moving Forward The following is a reflective commentary on the place of Critical Indigenous Studies, with a focus on Kaupapa Māori Research, within Mormon Studies. Specifically, the piece explores the following questions: What does Kaupapa Māori Research look like when engaging in Mormon Studies? What positionality needs to be taken by Kaupapa Māori researchers and Critical Indigenous scholars when engaging in Mormon Studies? What are the main areas Critical Indigenous scholars and Kaupapa Māori scholars should engage when tackling issues around Mormonism? These questions are important in light of the growing importance of the cultural renaissance in Te Ao Māori and the rise of Kaupapa Māori Research.

year: 2021