Alkaline base catalysis

Either acid or base catalysis may be employed. Alkaline catalysts such as caustic soda or sodium methoxide give more rapid alcoholysis. With alkaline catalysts, increasing catalyst concentration, usually less than 1% in the case of sodium methoxide, will result in decreasing residual acetate content and this phenomenon is used as a method of controlling the degree of alcoholysis. Variations in reaction time provide only a secondary means of controlling the reaction. At 60°C the reaction may takes less than an hour but at 20°C complete hydrolysis may take up to 8 hours. 

A scheme depicting general base catalysis is shown in Fig. 7.2,b. Because the HO anion is more nucleophilic than any base-activated H20 molecule, intermolecular general base catalysis (Fig. 7.2,bl) is all but impossible in water, except for highly reactive esters (see below). In contrast, entropy may greatly facilitate intramolecular general base catalysis (Fig. 7.2,b2) under conditions of very low HO anion concentrations. Alkaline ester hydrolysis is a particular case of intermolecular nucleophilic attack (Fig. 7.2,cl). Intramolecular nucleophilic attacks (Fig. 7.2,c2) are reactions of cyclization-elimination to be discussed in Chapt. 8. 

Shackelford and co-workers studied the 1,2-addition of 2,2-dinitropropanol, 2,2,2-trinitroethanol, and 2-fluoro-2,2-dinitroethanol across the double bonds of vinyl ethers. These reactions are Lewis acid catalyzed because of the weak nucleophilic character of alcohols which contain two or three electron-withdrawing groups on the carbon p to the hydroxy functionality. Base catalysis is precluded since alkaline conditions lead to deformylation with the formation of formaldehyde and the nitronate salt. 

The dehydration of the enediols is a reaction subject to general acid-base catalysis. The deoxyaldosulose 7a has been isolated from 3-O-benzyl-D-glucose34 and from D-fructose35 after treatment with alkali, and from D-fructose35 and various Amadori products8 after treatment with acid. The most successful preparation of 7a has been by way of amine addition compounds an improved procedure has been reported.36 Compound 9a has been isolated as a product of the alkaline treatment of both cellobiose37 and maltose.38 The isolation of 10a has not been reported, but it has been synthetically39 prepared. 

Other kinetically allowed mechanistic models, i.e. hydroxide ion attack on the monoanion, can be rejected on the grounds that the required rate coefficients far exceed that found for alkaline hydrolysis of phosphate triesters. At pH > 9 two new reactions appear, one yielding a 1,6-a.nhydro sugar by nucleophilic attack through a five-membered transition state of the 1-alkoxide ion upon C-6 with expulsion of phosphate trianion. The second is apparently general-base catalysis by 1-alkoxide of water attack on C-6 or phosphorus through greater than six-membered cyclic transition states. 

Simpler evidence for the presence of a tetrahedral intermediate is adduced from a study of the kinetics of alkaline hydrolysis of amides such an anilides26-28, chloroacetamide30, N,N-diacylamines31, and urea32. The rate equations for these reactions contain both first- and second-order terms in hydroxide ion. A reasonable explanation is that the hydrolysis mechanism involves a tetrahedral intermediate, rather than that the second-order term is due to base catalysis of the addition of the hydroxide ion to the carbonyl group. Such a mechanism is... 

Stoichiometry (28) is followed under neutral or in alkaline aqueous conditions and (29) in concentrated mineral acids. In acid solution reaction (28) is powerfully inhibited and in the absence of general acids or bases the rate of hydrolysis is a function of pH. At pH >5.0 the reaction is first-order in OH but below this value there is a region where the rate of hydrolysis is largely independent of pH followed by a region where the rate falls as [H30+] increases. The kinetic data at various temperatures both with pure water and buffer solutions, the solvent isotope effect and the rate increase of the 4-chloro derivative ( 2-fold) are compatible with the interpretation of the hydrolysis in terms of two mechanisms. These are a dominant bimolecular reaction between hydroxide ion and acyl cyanide at pH >5.0 and a dominant water reaction at lower pH, the latter susceptible to general base catalysis and inhibition by acids. The data at pH <5.0 can be rationalised by a carbonyl addition intermediate and are compatible with a two-step, but not one-step, cyclic mechanism for hydration. Benzoyl cyanide is more reactive towards water than benzoyl fluoride, but less reactive than benzoyl chloride and anhydride, an unexpected result since HCN has a smaller dissociation constant than HF or RC02H. There are no grounds, however, to suspect that an ionisation mechanism is involved. 

Kinetic studies have been reported of the reactions of a series of 2-substituted-5-nitrothiophenes (substituent = Br, OMe, OPh, OC6H4-4-NO2) with secondary amines in room-temperature ionic liquids. The kinetic behaviour is similar to that of the corresponding reactions in methanol so that most reactions do not show base catalysis. The observation that reactivity is higher in the ionic liquids than in methanol (or benzene) is attributed to relatively poor solvation of the reagents by the ionic liquids. As in conventional solvents, 2-bromo-3-nitrothiophene shows higher reactivity than 2-bromo-5-nitrothiophene.42 Solvent effects on the kinetics of the alkaline hydrolysis of 2-phenylthio-3,5-dinitropyridine in aqueous organic solvents have been analysed.43... 

On the other hand, if Bronsted acidity is generated, it is possible to generate basicity by exchanging the protons with alkaline ions [12]. Specifically, Na-MCM-41 and Cs-MCM-41 catalysts exhibit satisfactory performance in base catalysis [40], Besides, there exists the option of setting up transition metals in the MMS walls with the purpose of developing catalytic redox properties that will be effective in selective oxidation. 

Exchange of hydrogen in alkaline solution was reported by Franke and M5nch and subsequently confirmed but attributed to exchange of phosphite formed by alkaline decomposition. A study by proton nmr methods reports simple first-order dependence on the concentrations of HjPOJ and OD. At 25°C and H = 2.0, the rate parameters are k = (6.0+0.7)10 l.mole . sec ( a = 18.9 0.5 kcal.mole ). Reaction of D2POJ and OH has k = (1.92 0.1)10 l.mole sec ( a = 18.7 kcal.mole ). It is suggested that there may be general base catalysis, from qualitative observations of the effect of phosphate. 

The decrease of the first wave of phenyl vinyl ketone with time was used for the evaluation of the rate constant. Since hydroxide ions were always present in excess, it was possible to compute the rate constants at a given concentration according to a first-order rate equation. Rate constants obtained in this way were found to be proportional to hydroxide concentration, giving no indication of a reaction with the solvent or general base catalysis. The cleavage of phenyl vinyl ketone in alkaline media is thus first order in ketone and first order in hydroxide ion. The occurrence of dimerization and polymerization in the rate-determining step was therefore excluded. The simplest reaction scheme is given in (14) ... 

The rate equation for the alkaline hydrolysis of amides such as urea (Lynn, 1965), anilides (Biechler and Taft, 1957 Bender and Thomas, 1961a Mader, 1965 Schowen and Zuorick, 1966), chloroacetamide (Bruylants and K zdy, 1960) andN,N-diacylamines (Behme and Cordes, 1964), is known to contain both first- and second-order terms in hydroxide. It is highly improbable that the term which is second-order in hydroxide is due to base-catalysis of the addition of hydroxide ion to the carbonyl carbon, because of the low acidity of hydroxide. 

Fig. 10. Rates of imidazole-catalyzed ester hydrolysis as a function of the rate of alkaline hydrolysis nucleophilic reactions of acetates, general base catalysis of acetates, a general base catalysis of methyl and ethyl esters, o (ionic strength 1-0 25°). Trifluoroethyl acetate measured with N-methylimidazole. From Kirsch and Jencks (1964a). Reproduced with permission of the American Chemical Society. (> = NOAc = acetoxime acetate).

The autoxidation of phenols is slow in neutral and, especially, in acid solution but becomes very noticeable in alkaline solutions. This base catalysis of phenol oxidation is of course due to the conversion of the neutral phenols to the phenolate ions, which are more easily oxidized by the oxidant Ox (equation 18) than their conjugate acids. 

The essential feature of base catalysis is formation of carbanions. Compared to acid catalysts, solid base catalysts are not as widely used commercially, but can be active for alkylation, condensation (oligomerization), isomerization, and dehydrohalogenation. Common base catalysts are alkali metal oxides, carbonates, and hydroxides, as well as alkaline earth metal oxides. 

Diesters of quinquevalent phosphorus are normally difficult to hydrolyse further. 4-Nitrophenyl quinolin-8-yl phosphate exhibits a pH-rate profile that has a plateau extending well into the alkaline region, consistent with the idea of intramolecular nucleophilic catalysis via cyclization [as in (60)] rather than a mechanism based upon general base catalysis. ... 

A dehydration of this type has actually been observed as a side reaction of a Lobry de Bruyn-Alberda van Ekenstein transformation in a very simple system. Thus, in experiments with the DL-glycerose-l,3-dihy-droxy-2-propanone isomerization in acetate, formate, and trimethylacetate buffers, pyruvaldehyde appeared in the reaction mixtures. (The formation of pyruvaldehyde from l,3-dihydroxy-2-propanone- and dl-glycerose-mineral acid mixtures had been observed much earlier.) Since these experiments in acidic buffers established that this reaction is subject to general acid and base catalysis, pyruvaldehyde must be formed in alkaline mixtures also. The results of Wohl s and Evans and Hass s experiments with DL-glycerose in alkaline solutions containing phenyl-hydrazine, in which pyruvaldehyde phenylosazone was isolated, support this view. 

Deoxyglycosuloses (45) have been regarded as being products of a side reaction of the Lobry de Bruyn-Alberda van Ekenstein transformation. The transformation is subject to general, acid-base catalysis and, although it proceeds most rapidly in alkaline solution, it also takes place under neutral and acidic conditions. The Lobry de Bruyn-Alberda van Ekenstein transformation consists of the interconversion of two epimeric aldoses through the intermediate enediol (43) or its anion, and, where R = H, the 2-ketose also enters into the equilibrium. 

Since lysinoalanine is so readily formed by the treatment of protein with base, ornithinoalanine (Figure 7) also should be found in the hydrolysates of alkali-treated proteins, if only ornithine were a constituent amino acid of proteins. Ornithinoalanine may indeed become such a constituent amino acid of proteins. The alkaline conditions to which proteins are exposed provide the base catalysis required for the hydrolysis of the guanido group of arginine (Figure 8) and the formation of ornithine. The presence of ornithine in alkali-treated proteins was shown... 

One might expect that diazotization of aliphatic amines under alkaline conditions or in the presence of strong proton acceptors used for general base catalysis might also yield diazoalkanes. This alternative route, however, has not been successful so far, as shown by the experiments of Maltz et al. (1971), who nitrosated amines with disodium pentacyanonitrosyl ferrate (Fe[CN]5NO Na2 ) at pH up to 12.7 (see Sect. 2.3). 

Apart from protein sequence and structure, temperature, pH, and the type of buffers can all influence the deamidation and isoaspartate formation. The effect of temperature on the deamidation reaction rate generally follows the Arrhenius law. Deamidation activation energies around 21-22kcalmoH have been reported for two model peptides under alkaline conditions [19, 20]. The deamidation is also subject to general acid/base catalysis, as evidenced by an increase in deamidation rate with an increase in buffer concentration [2]. 

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