Frank Hibbert

Hydrogen Bonding and Chemical Reactivity

Publisher Summary This chapter discusses the hydrogen bonding, which has been recognized as the single most important intermolecular interaction, The chapter presents the hypothesis that there are three kinds of hydrogen bond: weak, strong, and very strong. These are determined by the shape of the potential energy well and the respective positions of hydrogen and deuterium within the well, which can be used to provide information about the well that applies in a particular example. The role of hydrogen bonding in catalysis has been discussed, although mainly in terms of the salicylate ion as a leaving group. With its strong intramolecular hydrogen bond playing an essential part in the reaction mechanism, it seems likely that this will herald other systems where the role of a strong hydrogen bond may serve as the key step in a catalytic process.

Mechanisms of Proton Transfer between Oxygen and Nitrogen Acids and Bases in Aqueous Solution

Publisher Summary This chapter reviews that acid and base catalysis of a chemical reaction involves the assistance by acid or base of a particular proton-transfer step in the reaction. Many enzyme catalyzed reactions involve proton transfer from an oxygen or nitrogen centre at some stage in the mechanism and often the role of the enzyme is to facilitate a proton transfer by acid or base catalysis. Proton transfer at one site in the substrate assists formation and/or rupture of chemical bonds at another site in the substrate. It discusses that an increasing number of categories of proton transfer of oxygen and nitrogen acids are being discovered that do not fit this simple picture and many of these more complex proton transfers have been proposed as components of multi-step mechanisms. In a sense, the more complex proton transfers are of greater chemical interest than processes controlled by the rate of encounter between reactant molecules. The chapter highlights that the presence of an intramolecular hydrogen bond in an acid considerably modifies the acid–base behavior and rates of proton transfer are different from the diffusion-limited values.

Glowing jellyfish, luminescence and a molecule called coelenterazine

Luminescence has assumed an important role in analytical biochemistry and molecular biology as an extremely sensitive method for determining the concentration of specific ions and molecules. The luminescent system of the jellyfish Aequorea victoria consists of the photoprotein aequorin, which contains the molecule coelenterazine as a prosthetic group and shows considerable potential in this area.

Exceptional basic strength of 1,8-bis(dimethylamino)- and 1,8-bis(diethylamino)-2,7-dimethoxynaphthalenes: kinetic and equilibrium studies of the ionisation of the protonated amines in Me2SO–H2O mixtures with hydroxide ion

Exceptionally high pKa values of 16.1 and 16.3 have been obtained for 1,8-bis(dimethylamino)- and 1,8-bis(diethylamino)-2,7-dimethoxynaphthalene respectively from measurements of the equilibrium between the protonated amines and hydroxide ion in Me2SO–H2O mixtures. These values make the amines more basic by four pKa units than 1,8-bis(dimethylamino)naphthalene. This may be a result of an increase in strain in the free amines and of a strengthening of the intramolecular hydrogen bond in the protonated amines. Proton transfer from protonated 1,8-bis(dimethylamino)-2,7-dimethoxynaphthalene to hydroxide ion in 35%(v/v) Me2SO–H2O occurs in the millisecond range (kOH– 110 dm3 mol–1 s–1) but for 1,8-bis(diethylamino)-2,7-dimethoxynaphthalene the reaction is extremely slow with half-lives in the range of minutes in 50%(v/v) Me2SO–H2O (kOH– 0.18 dm3 mol–1 s–1). The steady increase in the rate coefficient for proton transfer from protonated 1,8-bis(diethylamino)-2,7-dimethoxynaphthalene to hydroxide ion over the solvent range 50–90%(v/v) Me2SO–H2O is due to a weakening of the intramolecular hydrogen bond in the protonated amine.

Kinetic and equilibrium studies of the protonation of meso-tetraphenylporphyrin in dimethyl sulphoxide–water

The equilibrium between meso-tetraphenylporphyrin (B) and its diprotonated form (BH22+) has been studied spectrophotometrically in 98, 90, and 80% Me2SO–H2O (v/v). Visible spectra of solutions of the porphyrin containing varying concentrations of hydrochloric acid show good isosbestic points. The equilibrium involves the free base and the diprotonated species; the monoprotonated porphyrin (BH+) is not present in sufficiently high concentrations to be detected. The position of equilibrium and the rates of equilibration between B and BH22+ have been measured in 95, 90, and 85% Me2SO–H2O (v/v). The reaction is slow, with relaxation times (measured by the temperature-jump method) in the range 40–5 000 µs. Values of the rate coefficient for proton removal by water from BH22+ to give BH+ were obtained for each solvent mixture from the acid dependence of the reciprocal relaxation time. In comparison with other proton transfers from nitrogen acids, proton transfer from the diprotonated form of meso-tetraphenylporphyrin is exceptionally slow. This may arise because the reaction is strongly disfavoured thermodynamically; other possible factors are discussed.

Rates of proton transfer from protonated 1,8-bis(dimethylamino)- and 1,8-bis(diethylamino)-naphthalene to hydroxide ion in 20% and 30%(v/v) dimethyl sulphoxide–water

The conjugate acids of 1,8-bis(dimethylamino) naphthalene and 1,8-bis(diethylamino) naphthalene are intramolecularly hydrogen-bonded, and proton transfers to hydroxide ion in 30%(v/v) dimethyl sulphoxide–water occur slowly, with rate coefficients (kOH–) 6.1 ± 105 and 1.6 ± 104 I mol–1 s–1, respectively. Substitution of ethyl groups for methyl groups in 1,8-bis(dimethylamino)naphthalene has a larger effect on the rate of proton transfer than on the equilibrium constant, and this unusual observation is considered in terms of a two-step mechanism for proton removal from the protonated amines.

KINETICS AND MECHANISM OF THE ADDITION OF WATER AND RING-OPENING OF 2-METHYL- AND 2-ARYL-4H-3,1-BENZOXAZINES TO 2-AMINOBENZYL ESTERS IN THE ACIDIC PH RANGE ; CHANGE IN RATE-LIMITING STEP WITH BUFFER CONCENTRATION AND EVIDENCE FOR A TETRAHEDRAL CARBONYL ADDITION INTERMEDIATE

The observed rate coefficients for the reaction of 2-methyl-, 2-phenyl- and 2-(4-nitrophenyl)-4H-3,1-benzoxazines to give the corresponding 2-aminobenzyl esters increase as the pH is lowered and reach a constant plateau value at pH 2–4 depending on the substituent. The plateau region corresponds to complete conversion of the benzoxazine to the protonated benzoxazine (SH+) which is the reactive species. Values of pKSH+ calculated by fitting the appropriate rate expression to the rate–pH profile and the pKSH+ values measured spectrophotometrically before significant reaction to the ester has taken place are in good agreement. For each benzoxazine the observed rate coefficients show a rectilinear dependence on buffer concentration. A mechanism is proposed involving addition of water to the protonated benzoxazine to give a cyclic tetrahedral carbonyl addition intermediate. At low buffer concentrations, buffer catalysed collapse of the intermediate to product is rate-limiting and the reaction is first order in buffer. At high buffer concentrations, collapse of the intermediate to product is rapid and addition of water to the protonated benzoxazine to give the intermediate is rate-limiting.

Acid–base properties of highly substituted diaminonaphthalenes

The kinetic and equilibrium acid-base behaviour of four new highly hindered diaminonaphthalenes has been studied in aqueous solution or in Me2SO–H2O mixtures containing hydroxide ion. In concentrated aqueous sodium hydroxide solutions, 1,8-bis(dimethylamino)-2,7-diethoxynaphthalene and 1,8-bis(diethylamino)-2,7-diethoxynaphthalene are almost fully protonated and aqueous pKa values of 16.1 and 15.9, respectively, have been measured from comparative studies with other diaminonaphthalenes in 60%(v/v) Me2SO–H2O. Studies of the protonation of 1,8-dimorpholino-2,7-dimethoxynaphthalene (pKa 13.0) and 1,8-dimorpholino-2,7-diethoxynaphthalene (pKa 12.5) were made in aqueous sodium hydroxide. The reversible acid-base reactions of the diaminonaphthalenes in the presence of hydroxide ion occur slowly. For example the approach to an equilibrium mixture of the protonated and unprotonated forms of 1,8-bis(diethylamino)-2,7-diethoxynaphthalene in 60%(v/v) Me2SO–H2O with 0.01 mol dm–3 NaOH occurs with a half-life of 8s. It is found that 2- and 7-substituents have large effects in increasing the basicity and decreasing the rates of proton transfer and this is due in part to an increase in strain in the amines and in the transition state for proton transfer.

Cyclic imine formation by intramolecular nucleophilic addition and elimination between an amino group and amide carbonyl; rate–pH profile for the reaction of 1-amino-8-trifluoroacetylaminonaphthalene to 2-trifluoromethylperimidine

The kinetics of the cyclisation of 1-amino-8-trifluoroacetylaminonaphthalene to 2-trifluoromethylperimidine have been studied in the range pH 0.6–13 in 70%(v/v) Me2SO–H2O in the presence of buffers and in solutions of hydrochloric acid. The first-order rate coefficient (k) obtained in the presence of hydrochloric acid or determined by extrapolation of the observed rate coefficient in buffers to zero buffer concentration gives a pH dependence with two plateau regions. The results are explained by assuming that reaction of 1-amino-8-trifluoroacetylaminonaphthalene occurs by spontaneous and hydronium-ion catalysed pathways and that forms of the amide in which the amide group is ionised or the amino group is protonated are unreactive. The rate–pH profile is fitted by the expression k=K1(k0+kH[H3O+])[H3O+]/(K1K2+K1[H3O+]+[H3O+]2) in which K1 is the acid dissociation constant of the protonated amino group in protonated 1-amino-8-trifluoroacetylaminonaphthalene and K2 is the acid dissociation constant of the amide group in 1-amino-8-trifluoroacetylaminonaphthalene. The rate coefficients kO and kH refer, respectively, to spontaneous and hydronium-ion catalysed cyclisation pathways. Catalysis by buffer acids is also observed. The mechanism of the reaction involves intramolecular addition of the amino group in 1-amino-8-trifluoroacetylaminonaphthalene to the amide carbonyl followed by elimination of water.

1,1,1-Trifluoropropan-2-one and 1,1,1-trifluoropentane-2,4-dione in hydrogen bromide–dibromodifluoromethane; evidence for the formation of α-bromo alcohols

N.m.r. analysis of solutions of 1,1,1-trifluoropropan-2-one (TFP) and 1,1,1-trifluoropentane-2,4-dione (TFPD) in the strong acid system HBr–CBr2F2 shows the formation of the 2-bromo alcohol analogues of TFP and TFPD at temperatures below 250 K. In the latter system equilibrium constants for the formation of the bromo alcohol at various temperatures and acid ratios have been measured, from which the enthalpy of formation, ΔH°=–25.2 kJ mol–1, has been calculated. 1,1,1,5,5,5-Hexafluoropentane-2,4-dione (HFPD) does not react to form a bromo alcohol.