Alcohols acid-base equilibria

Sn2 reactions with anionic nucleophiles fall into this class, and observations are generally in accord with the qualitative prediction. Unusual effects may be seen in solvents of low dielectric constant where ion pairing is extensive, and we have already commented on the enhanced nucleophilic reactivity of anionic nucleophiles in dipolar aprotic solvents owing to their relative desolvation in these solvents. Another important class of ion-molecule reaction is the hydroxide-catalyzed hydrolysis of neutral esters and amides. Because these reactions are carried out in hydroxy lie solvents, the general medium effect is confounded with the acid-base equilibria of the mixed solvent lyate species. (This same problem occurs with Sn2 reactions in hydroxylic solvents.) This equilibrium is established in alcohol-water mixtures ... 

The acid-catalysed hydrolysis of an ester is the reverse reaction of the Fischer esterification. Addition of excess water drives the equilibrium towards the acid and alcohol formation. The base-catalysed hydrolysis of esters is also known as saponification, and this does not involve the equilibrium process observed for the Fischer esterification. 

R = R = Me) which are obtained by photooxidation of the corresponding olefin.72 The acid-induced cyclization of the same alcohols has been used they are prepared from coumarins 87,88,185,186 or by base-promoted elimination from epoxides (50).150,164 The acid-catalyzed equilibrium between these alcohols and the corresponding... 

An alternative and more generally used oxidation method employs chromic acid. This process is an exception to our general theme, because here the alcohol is transformed to a carbonyl group by removal of electron density from oxygen rather than from carbon. The first step has been shown to be a rapid equilibrium between the alcohol and its chromate ester, followed by rate-determining decomposition of the ester in the manner shown in Scheme 7.42 It will be noted that the species eliminated from the carbon that becomes the carbonyl carbon is a Lewis acid, not a Lewis base. 

Use eq. 7.48 as a guide. The equilibrium lies on the side of the weakest acid (the alcohol) and the weakest base (the thiolate salt). 

In the substrates, special attention has been devoted to zeolites and fullerenes [34, 38, 39, 44], in the reactions to acid-base equilibria and the influence of hardness and softness on both sides of the equilibrium (acidity of carboxylic acids [45], alkyl [46] and halogenated alcohols [47], hydrides [48] and recently hydrofullerenes [49], basicity of amines [50, 51] and proton affinities of amino acids [52]). For reviews of these studies, see [18, 53, 54],... 

Reactions were studied under the pseudo first-order condition of [substrate] much greater than [initial dihydroflavin]. Under these conditions, the reactions are characterized by a burst in the production of Flox followed by a much slower rate of Flox formation until completion of reaction. The initial burst is provided by the competition between parallel pseudo first-order Reactions a and b of Scheme 3. These convert dihydroflavin and carbonyl compound to an equilibrium mixture of carbinolamine and imine (Reaction a), and to Flox and alcohol (Reaction b), respectively. The slower production of Flox, following the initial burst, occurs by the conversion of carbinolamine back to reduced flavin and substrate and, more importantly, by the disproportionation of product Flox with carbinolamine (Reaction c followed by d). Reactions c and d constitute an autocatalysis by oxidized flavin of the conversion of carbinolamine back to starting dihydroflavin and substrate. In the course of these studies, the contribution of acid-base catalysis to the reactions of Scheme 3 were determined. The significant feature to be pointed out here is that carbinolamine does not undergo an elimination reaction to yield Flox and lactic acid (Equation 25). The carbinolamine (N(5)-covalent adduct) is formed in a... 

The alkoxide doesn t have to be made first, though, because alcohols dissolved in basic solution are at least partly deprotonated to give alkoxide anions. How much alkoxide is present depends on the pH of the solution and therefore the pKa of the base (Chapter 8), but even a tiny amount is acceptable because once this has added it will be replaced by more alkoxide in acid-base equilibrium with the alcohol. In this example, allyl alcohol adds to pent-2-enal, catalysed by sodium-hydroxide in the presence of a buffer. 

On the other hand, if HA is an uncharged acid z = — V, e.g. CH3—CO2H), the right-hand side of Eq. (4-10) involves the sum of two reciprocal radii (zha = 0) and a strong influence of the relative permittivity on the ionization equilibrium is expected. Because in acid/base reactions of this charge type, neutral molecules are converted into anions and cations, which attract each other, reaction (4-5) will shift to the right with an increase in relative permittivity of the solvent in which HA is dissolved. Ionization increases when increases. This rule is qualitatively verifiable for water and alcohols as... 

Organic solvents influence the ionization constants of weak acids or bases in several ways (note that they influence the analytes and the buffer as well). Concerning ionization equilibria, an important solvent property is the basicity (in comparison to water), which reflects the interaction with the proton. From the most common solvents, the lower alcohols and acetonitrile are less basic than water. Dimethyl sulfoxide is clearly more basic. However, stabilization of all particles involved in the acido-basic equilibrium is decisive for the pKa shift as well. For neutral acids of type HA, the particles are the free, molecular acid, and the anion, A . In the equilibrium of bases, B, stabilization of B and its conjugated acid, HB, takes place. As most solvents have a lower stabilization ability toward anions (compared to water), they shift the pK values of adds of type HA to higher values in general. No such clear direction of the change is found for the pK values of bases however, they undergo less pronounced shifts. 

On the other hand, adding alcohol to a solution of an acid or base in a solvent possessing acidic or basic characteristics less pronounced than those of the alcohol will disturb the acid-base equilibrium radically. 

Since water is a much stronger base than alcohol, all hydrogen ions remain in the form of H2OH+ even after the addition of alcohol to an aqueous solution. Alcohol can, however, displace the acid-base equilibrium in aqueous solutions and this influence which alcohol exerts upon the color of an indicator depends not only upon the nature of the indicator but also upon the kind of acid-base system found in the solution. 

The extent of the ionization step depends on the relative strength of the conjugate acid-conjugate base pairs. The amphiprotic properties of the solvent have an essential effect on the equilibrium constant of this reaction step. The extent of the dissociation step is influenced by the polarity of the solvent, increasing with the dielectric constant of the solvent. In water, all products of acid-base reactions of moderate to low concentrations are essentially completely dissociated into solvated ions (Pecsok et al., 1976). The dissociation step is suppressed by addition or substitution with cosolvents of lower polarity, e.g., alcohols in aqueous formulations. The ion-pair aggregates may have absorption spectra different from the dissociated species. Thus, the amphiprotic properties and polarity (expressed as the dielectric constant) of the solvent are essential for the acid-base equilibrium of the drug and thus the absorption spectrum of the compound. This subject is further discussed in Section 14.2.3. 

A less plausible, but nevertheless not entirely unreasonable mechanism, which could account for these results would invoke an acid form for the OH radical which is not scavenged by ethyl alcohol. There is evidence (12) that this residual yield increases with decreasing pH in both the H202 photolysis and gamma radiolysis of RNO solutions which is not compatible with the above mechanism unless there is some acid-base equilibrium involving either the RN02H or C2H4OH radicals. 

Alcohols are very weak acids and bases, slightly weaker than water. The extremely weak acidity of alcohol is evidenced by the negligible degree of reaction with a strong base such as NaOH. The equilibrium for the reaction... 

The catalytic properties of these reduced species have been actively studied by Gillard and co-workers. Among other things, they have shown that H2 also initiates Delepine s reaction of [RhClj] ", that Oj dramatically impedes the catalyst, and that halide substitution at trans-[Rhpy4Cl2] (equation 167) is also catalyzed by primary and secondary alcohols. Consistent with the pseudo acid-base equilibrium (equation 164), the rate of catalyzed halide substitution is pH dependent, with little catalytic activity occurring in acidic solutions. There is an induction period for the reaction (the more alcohol in the solution the shorter the period), suggesting that deoxygenation of the solution must occur before the reduced catalyst can be effective. 

The solvent can alter an acid-base equilibrium not only through the acid or basic character of the solvent itself, but also by its dielectric effect and its capacity to solvate the different species which participate in the process. Whilst the acid or basic force of a substance in the gas phase is an intrinsic characteristic of the substance, in solution this force is also a reflection of the acid or basic character of the solvent and of the actual process of solvat-ation. For this reason the scales of acidity or basicity in solution are clearly different from those corresponding to the gas phase. Thus, toluene is more acid than water in the gas phase but less acid in solution. These differences between the scales of intrinsic acidity-basicity and in solution have an evident repercussion on the order of acidity of some series of chemical substances. Thus, the order of acidity of the aliphatic alcohols becomes inverted on passing from the gas phase to solution ... 

In Section 6.2.5, alcohols were seen to be amphoteric. This section is simply a reminder that alcohols react as bases. In the presence of the strong acid HCl, alcohols such as ethanol (12), methanol, or butanol will react to form an oxonium ion, 13, from ethanol. Oxonium ions such as 13 are rather strong acids, and the Kg for this reaction generally lies to the left. In an aqueous solvent, water may stabilize the ions and separate them, which will influence the position of the equilibrium. In general, oxonium ions are transient and highly reactive species. 

Common organic acids are carboxylic acids, sulfonic acids, and alcohols. Carboxylic acids are more acidic than alcohols, but sulfonic acids are more acidic than carboxylic acids 10, 42, 68. The equilibrium constant for an acid-base reaction that involves organic acids is the same as any other acid-base reaction, K, where = products/reactants, and pK = -log K 1, 39, 40. 

Ethanol has about the same acidity as water. Higher-molecular-weight, water-soluble alcohols are slightly weaker acids than water. Thus, although alcohols have some acidity, they are not strong enough acids to react with weak bases such as sodium bicarbonate or sodium carbonate. (At this point, it would be wise to review Section 4.4, which discusses the position of equilibrium in acid-base reactions.)... 

As discussed in this chapter, enolate anions are formed when a carbonyl compound containing an a-hydrogen is treated with a base such as hydroxide or an alkoxide. We noted earlier that a-hydrogens normally are considerably less acidic than water or alcohols, so the position of equilibrium in this acid-base reaction greatly favors the reactants rather than enolate products. 

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