Mechanisms of base catalysis

The reactive intermediate in a base catalyzed reaction is the deproto-nated substrate. Deprotonation of an alcohol or phenol leads to the formation of an anion which is a stronger nucleophile than the substrate itself. This is of particular interest if the anion may undergo an intramolecular substitution. An example of such a mechanism is the base catalyzed formation of an epoxide 

Another interesting possibility for the second step involves the reversal of a carbonyl addition. Examples are the dehydration of a gem-dihydroxy compound (hydrate of carbonyl compound) 

Amines are weaker acids than alcohols. On the other hand, they are strong nucleophiles even if they are not deprotonated. One of the relatively few mechanisms known which involves proton abstraction from a NH bond is the decomposition of nitramide 

The acidity of CH bonds in alkanes is extremely low. Deprotonation by bases is possible only if strongly activating groups are present as in chloroform, for example. The anion of chloroform decomposes in a series of consecutive steps 

CH bonds in alpha position to carbonyl, sulfonyl, or nitro groups may undergo slow hydrogen isotope exchange with a hydroxylic solvent in the presence of a strong base. In another method of measurement of the deprotonation rate, a reagent (bromine or iodine) is added which reacts 

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In contrast, the rate constant of a mechanism of base catalysis involving a fast preequilibrium... 

In originally considering the 5 3 mechanism, involving base catalysis, Bennett, Brand, James, Saunders and Williams were trying to account for the small increase in nitrating power which accompanies the addition of water, up to about 10%, to sulphuric acid. The dilution increases the concentration of the bisulphate ion, which was believed to be the base involved (along with molecular sulphuric acid itself). The correct explanation of the effect has already been given ( 2.3.2). 

Similar treatments of base catalysis are left as an exercise (Problem 10-13). There is for specific base catalysis an additional mechanism, known as nucleophilic catalysis. 

A detailed mechanism of ORR catalysis for electrode-adsorbed complexes was proposed (Fig. 18.20) [Boulatov et al., 2002 Boulatov, 2004], based on determination of the following ... 

Bob s research interests and knowledge across chemistry were great. Throughout his career he retained an interest in biomimetic chemistry, specifically the study of metal ion-promoted reactions and reactions of molecules activated by metal ion coordination. His early interests in carbohydrate chemistry inspired him to study metal ion catalysis of both peptide formation and hydrolysis as well as studies in inorganic reaction mechanisms. He was particularly interested in the mechanisms of base-catalyzed hydrolysis within metal complexes and the development of the so-called dissociative conjugate-base (DCB) mechanism for base-catalyzed substitution reactions at inert d6 metal ions such as Co(III). 

Some of the most important evidence for the two-step mechanism comes from studies of base catalysis, in this regard, reactions involving primary and secondary amines have played a central role1-5. The initially formed cx-adduct, 1, is zwitterionic and contains an acidic proton, which can be removed by a base which may be the nucleophile itself. Conversion of 1 to products can then occur via the uncatalysed k2 pathway or via the base-catalysed hl pathway. The influence of Brpnsted base catalysis, the experimental observation of 1,1- and 1,3-cr-adducts, the sensitivity of the system to medium effects, are some experimental evidence of the mechanism depicted in equation 1. 

In the preceding sections throughout this chapter, several aspects of the influence of the nucleophile on the rates of the different reaction steps and/or mechanisms involved in ANS with amines have been discussed. One of the most outstanding features and most widely studied phenomena is the observation or the absence of base catalysis and, somewhat related with this subject, is the occurrence of a first, second or third order in amine kinetic law. 

Fig. 7.2. a) The most common mechanism of base-catalyzed ester hydrolysis, namely specific base catalysis (HCT catalysis) with tetrahedral intermediate and acyl cleavage. Not shown here are an W mechanism with alkyl cleavage observed with some tertiary alkyl esters, and an 5n2 mechanism with alkyl cleavage sometimes observed with primary alkyl esters, particularly methyl esters, b) Schematic mechanism of general base catalysis in ester hydrolysis. Intermolecular catalysis (bl) and intramolecular catalysis (b2). c) The base-catalyzed hydrolysis of esters is but a particular case of nucleophilic attack. Intermolecular (cl) and intramolecular (c2). d) Spontaneous (uncatalyzed) hydrolysis. This becomes possible when the R moiety is... 

These findings are compatible with a mechanism of intramolecular catalysis for both acyl migration and hydrolysis, as proposed in Fig. 8.5. Also, the possibility that both reactions share a common intermediate is emphasized. Reactions a and b in Fig. 8.5 involve a first step of deprotonation, in agreement with the observed specific base catalysis. Intramolecular nucleophilic attack (Reactions c and d) generates a tetrahedral intermediate that can result in acyl migration or hydrolysis (Reaction e). 

The valuable and versatile study was conducted by the group of Bosnich [143]. The defined nature and amounts of by-products in the reaction mixture allowed to judge about the possible mechanism of the catalysis. It was proved that the aldohzation and allylation reactions proceed with the evolution of TMS salt that is itself a strong Lewis acid and can catalyze the reaction in high rate (Scheme 52). The possible sources of the TMS salt production in the reaction medium were investigated. The utilization of a hindered base suppressed the influence of the silyl salt, and the rate of the reaction was dramatically diminished. This consequence was considered to confirm that the TMS salt can catalyze the reaction even in the undetectable quantities of 10 mol. 

Weyl (9) has also outlined a picture of the mechanism of heterogeneous catalysis, which is similar to the schemes proposed by the above authors. His suggestions, based on the quanticule theory of Fajans (10), also result in a qualitative description. 

The hydrolysis of the more reactive carboxylic esters is catalyzed by a wide range of oxyanions. The mechanism proposed for the neutral hydrolysis of esters on p. 158 involves two molecules of water, one as a nucleophile and one as a general base. In principle an oxyanion or other nucleophile can replace either of these molecules, and both general base and nucleophilic catalysis of ester hydrolysis are well-known. The detailed mechanism of nucleophilic catalysis depends, to some extent, on the type of anion concerned, but the differences occur at a relatively late stage in the reaction, and the similarities are sufficient to allow generalizations about oxyanion reactions as a class. Some of the differences are not normally kinetically significant, and are best mentioned briefly at this point. 

Comprehensive discussions are to be found in (a) M. L. Bender, Mechanisms of Homogeneous Catalysis from Protons to Proteins, Wiley, New York, 1971 (b) W. P. Jencks, Catalysis in Chemistry and Enzymology, McGraw-Hill, New York, 1969 (c) M. L. Bender, Ckem. Rev., 60, 53 (1960). For more specialized treatments of particular aspects, see (d) W. P. Jencks, Chem. Rev., 72, 705 (1972), general acid-base catalysis (e) S. L. Johnson, Advan. Phys. Org. Chem., 5,237 (1967), ester hydrolysis (f) L. P. Hammett, Physical Organic Chemistry, 2nd ed., McGraw-Hill, New York, 1970, chap. 10, acid—base catalysis. 

At the present time, commercial isomerization processes based on enzymic catalysis are predominant, so only brief mention will be made of some of the nonenzymic processes that have been considered for commercialization in the past. Probably the major reasons for the current commercial use of enzymic rather than nonenzymic systems are that the nonenzymic systems so far developed result in products having one or more of the following defects too much ash, color, acid, off-flavor, a content of D-mannose or D-psicose, and high ratios of D-glucose to D-fructose. Probably, further advances in our understanding of the isomerization reaction and the mechanisms of the catalysis will lead to more efficient, nonenzymic processes that could replace the enzymic-isomerization systems now used commercially. 

Survey of mechanisms of acid—base catalyzed reactions 5.1 MECHANISMS OF ACID CATALYSIS... 

The pattern of base catalysis of reactions with amine nucleophiles provides additional evidence. These reactions are catalyzed by bases only when a relatively poor leaving group (e.g., OR) is present (not Cl or Br) and only when relatively bulky amines are nucleophiles. Bases could not catalyze step 1, but if amines are nucleophiles, bases can catalyze step 2. Base catalysis is found precisely in those cases where the amine moiety cleaves easily but X does not, so that k i is large and step 2 is rate determining. This is evidence for the S Ar mechanism because it implies two steps. Furthermore, in cases where bases are catalysts, they catalyze only at... 

The exact mechanism of enzyme catalysis as well as the structural and energetic aspects of substrate and inhibitor binding have been studied with the aid of molecular modeling, based on the complex of Neu5Ac with influenza virus A/Tokyo/3/67 neuraminidase (Scheme 16.4) [74c]. 

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