Proton, solvated abstraction

Reaction conditions can be modified to accelerate the rate of lithiation when necessary. Addition of tertiary amines, especially TMEDA, facilitates lithiation53 by coordination at the lithium and promoting dissociation of aggregated structures. Kinetic and spectroscopic evidence indicates that in the presence of TMEDA lithiation of methoxybenzene involves the solvated dimeric species (BuLi)2(TMEDA)2.54 The reaction shows an isotope effect for the o-hydrogcn, establishing that proton abstraction is rate determining.55 It is likely that there is a precomplexation between the methoxybenzene and organometallic dimer. 

To abstract a proton is to remove only the proton. The substantial extent of dissociation in Equation (6.11) helps explain why aqueous ammonia is more properly called ammonium hydroxide , NH4OH. We generate the solvated hydroxide ion OH (aq) by abstracting a proton from water. The OH (aq) ion in Equation (6.11) is chemically and physically identical to the solvated hydroxide ion generated by dissolving NaOH or KOH in water. 

H. C. Brown has suggested that steric factors are of primary and almost sole importance in determining the position of the double bond. According to Brown, Hofmann product predominates when a large leaving group makes it even more difficult for the base to abstract the more hindered protons.96 He has asserted that data similar to those of Table 7.12, which seem at first glance to be contrary to his theory, support it further He says that fluorine takes up more space in the transition state than iodine because fluorine is more solvated.97 However, the entropies of activation for Reaction 7.37 with X = F, Cl, Br, or I are all very similar therefore increased solvation of fluorine seems not to be the proper explanation for the preponderance of Hofmann product when X = F.98... 

The number of solvents that have been used in SrnI reactions is somewhat limited in scope, but this causes no practical difficulties. Characteristics that are required of a solvent for use in SrnI reactions are that it should dissolve both the organic substrate and the ionic alkali metal salt (M+Nu ), not have hydrogen atoms that can be readily abstracted by aryl radicals (c/. equation 13), not have protons which can be ionized by the bases (e.g. Nth- or Bu O" ions), or the basic nucleophiles (Nu ) and radical ions (RX -or RNu- ) involved in the reaction, and not undergo electron transfer reactions with the various intermediates in the reaction. In addition to these characteristics, the solvent should not absorb significantly in the wavelength range normally used in photostimulated processes (300-400 nm), should not react with solvated electrons and/or alkali metals in reactions stimulated by these species, and should not undergo reduction at the potentials employed in electrochemically promoted reactions, but should be sufficiently polar to facilitate electron transfer processes. 

Proton abstraction from a model carbon acid, hydroxyacetaldehyde, by formate anion has been examined theoretically for the gas phase and for aqueous solution.152 The reaction shows an early transition state, whereas its enzymatic equivalent has a late transition state. Solvation brings the transition state foiward. The factors that contribute to producing the later transition state in enzymes are discussed. 

Abstraction, hydrogen atom, from O—H bonds, 9, 127 Acid-base behaviour macroeycles and other concave structures, 30, 63 Acid-base properties of electronically excited states of organic molecules, 12, 131 Acid solutions, strong, spectroscopic observation of alkylcarbonium ions in, 4, 305 Acids, reactions of aliphatic diazo compounds with, 5, 331 Acids, strong aqueous, protonation and solvation in, 13, 83 Acids and bases, oxygen and nitrogen in aqueous solution, mechanisms of proton transfer between, 22, 113... 

In a polar solvent, heterolytic cleavage leading to proton abstraction is usually facilitated because of the favorable solvation energy of the proton, and cation radicals are ordinarily much more acidic than the corresponding neutral compounds. Table 1-5 combines acidity constants of organic compounds (AH) and their cation radicals (AH+ ) calculated for their solutions in dimethylsulfoxide (DMSO, a very polar solvent) at 25°C. 

It was shown that the rate of olefin production was dependent on the size of the metal cation (Li+, Na+, K+, Rb+, and Cs+) of the base. The increase in olefin production with an increase in cation size was explained as an increase in cation solvation by solvent with the larger cations, making t-butoxide a stronger base and thus increasing the rate of proton abstraction. Possibly these differences in cation solvation influence the reactivity of the carbanion intermediate for the conversion of benzothiophene and account for increased reactivity with the larger cation, potassium. 

In a similar way, it has been possible to form NH4 ions in the gas phase by reaction of the amide ion NH2 with formaldehyde (Kleingeld et al., 1983). In this case the proton abstraction (61a) from formaldehyde by NH2, which is a stronger base than OH-, is exothermic and results in the formation of HCO. This ion then transfers a hydride to ammonia in a subsequent ion/ molecule reaction (61b) to give NH4 and carbon monoxide. D-labelling experiments have proved that the hydride ion transferred to ammonia retains its identity so that the NH4 ion, like the H30 ion discussed above, can best be described as a hydride ion solvated by an ammonia molecule. This has also been confirmed recently both by photoelectron spectroscopy (Coe et al., 1985), where the NH4 ion was generated with a nozzle-ion source, and by theoretical calculations (Cardy et al., 1986 Cremer and Kraka, 1986 Kalcher et al., 1984 Squires, 1984). 

The mechanism of the Birch reduction (shown next) is similar to the sodium/liquid ammonia reduction of alkynes to fnmy-alkencs (Section 9-9C). A solution of sodium in liquid ammonia contains solvated electrons that can add to benzene, forming a radical anion. The strongly basic radical anion abstracts a proton from the alcohol in the solvent, giving a cyclohexadienyl radical. The radical quickly adds another solvated electron to form a cyclohexadienyl anion. Protonation of this anion gives the reduced product. 

If a hydrogen atom is abstracted from an alkane by an alkyl radical, both the initial and final state of the reaction involve neutral species and it is only the transition state where some limited charge separation can be assumed. In the case of a homolytic O—H bond fission, however, the initial state possesses a certain polarity and possible changes in polarity during the reaction depend on both the lifetime of the transition state and the nature of the attacking radical. If the unpaired electron is localized mainly on oxygen in the reactant radical, the polarity of the final state will be close to that of the initial state and any solvent effect will primarily depend on the solvation of the transition state. Solvent effects can then be expected since the electron and proton transfers are not synchronous. 

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