For acidic substrates

Perhaps the most extensively studied catalytic reaction in acpreous solutions is the metal-ion catalysed hydrolysis of carboxylate esters, phosphate esters , phosphate diesters, amides and nittiles". Inspired by hydrolytic metalloenzymes, a multitude of different metal-ion complexes have been prepared and analysed with respect to their hydrolytic activity. Unfortunately, the exact mechanism by which these complexes operate is not completely clarified. The most important role of the catalyst is coordination of a hydroxide ion that is acting as a nucleophile. The extent of activation of tire substrate througji coordination to the Lewis-acidic metal centre is still unclear and probably varies from one substrate to another. For monodentate substrates this interaction is not very efficient. Only a few quantitative studies have been published. Chan et al. reported an equilibrium constant for coordination of the amide carbonyl group of... 

Mordant Dyes. MetaUizable azo dyes are appHed to wool by the method used for acid dyes and then treated with metal salts such as sodium chromate [7775-11-5] sodium dichromate [10588-01-9] and chromium fluoride [1488-42-5] to form the metal complex in situ. This treatment usually produces a bathochromic shift ia shade, decreases the solubUity of the coloring matter, and yields dyeiags with improved fastness properties. The chromium salts can be appHed to the substrate before dyeiag (chrome-mordant or chrome-bottom method), together with the dye ia a single bath procedure (metachrome process), or as a treatment after dyeiag (afterchrome process). 

As Olah et al. have reported (81JOC2706), iV-nltropyrazole in the presence of Lewis or Brpnsted acid catalysts is an effective nitrating agent for aromatic substrates. The greater lability of the N—NO2 bond in iV-nltropyrazole compared with aliphatic nltramines was discussed on the basis of its molecular structure as determined by X-ray crystallography. 

The introduction of the BDT group proceeds under these rather neutral conditions, and this may prove advantageous for acid-sensitive substrates. The BDT group can also be reduced with Raney nickel to a methyl group or with Bu3SnH to a 2-[(methylthio)phenylthio]methyl ether (MTPM ether)... 

Aryl and alkyl trimethylsilyl ethers can often be cleaved by refluxing in aqueous methanol, an advantage for acid- or base-sensitive substrates. The ethers are stable... 

The TBDMS ester can be converted directly to an acid chloride [DMF, (COCl)2, It, CH2CI2] and then converted to another ester, with different properties, by standard means. This procedure avoids the generation of HCl during the acid chloride formation and is thus suitable for acid-sensitive substrates. ... 

Taft began the LFER attack on steric effects as part of his separation of electronic and steric effects in aliphatic compounds, which is discussed in Section 7.3. For our present purposes we abstract from that treatment the portion relevant to aromatic substrates. Hammett p values for alkaline ester hydrolysis are in the range +2.2 to +2.8, whereas for acid ester hydrolysis p is close to zero (see Table 7-2). Taft, therefore, concluded that electronic effects of substituents are much greater in the alkaline than in the acid series and. in fact, that they are negligible in the acid series. This left the steric effect alone controlling relative reactivity in the acid series. A steric substituent constant was defined [by analogy with the definition of cr in Eq. (7-22)] by Eq. (7-43), where k is the rate constant for acid-catalyzed hydrolysis of an orr/to-substituted benzoate ester and k is the corresponding rate constant for the on/to-methyl ester note that CH3, not H, is the reference substituent. ... 

Correlations with o in carboxylic acid derivative reactions have been most successful for variations in the acyl portion, R in RCOX. Variation in the alkyl portion of esters, R in RCOOR, has not led to many good correlations, although use of relative rates of alkaline and acidic reactions, as in the defining relation, can generate linear correlations. The failure to achieve satisfactory correlations with cr for such substrates may be a consequence of the different steric effects of substituents in the acyl and alkyl locations. It has been shown that solvolysis rates of some acetates are related to the pA", of the leaving group, that is, of the parent alcohol. The pK of alcohols has been correlated with but this relationship... 

HgCl2, CaCO, MeCN, H2O. The calcium carbonate is used as an acid scavenger for acid-sensitive substrates. 

Me2C(OMe)2, DMF, pyridinium p-toluenesulfonate (PPTS). The use of PPTS for acid-catalyzed reactions has been quite successful and is particularly useful when TsOH is too strong an acid for the functionality in a given substrate. TBDMS groups are stable under these conditions. ... 

Aryl and alkyl trimethylsilyl ethers can often be cleaved by refluxing in aqueous methanol, an advantage for acid- or base-sensitive substrates. The ethers are stable to Grignard and Wittig reactions and to reduction with lithium aluminum hydride at —15°. Aryl -butyldimethylsilyl ethers and other sterically more demanding silyl ethers require acid- or fluoride ion-catalyzed hydrolysis for removal. Increased steric bulk also improves their stability to a much harsher set of conditions. An excellent review of the selective deprotection of alkyl silyl ethers and aryl silyl ethers has been published. ... 

Subsequent to the development of the (salen)Cr-catalyzed desymmetrization of meso-epoxides with azide (Scheme 7.3), Jacobsen discovered that the analogous (salen)Co(n) complex 6 promoted the enantioselective addition of benzoic acids to meso-epoxides to afford valuable monoprotected C2-symmetric diols (Scheme 7.15) [26], Under the reaction conditions, complex 6 served as a precatalyst for the (salen) Co(iii)-OBz complex, which was fonned in situ by aerobic oxidation. While the enantioselectivity was moderate for certain substrates, the high crystallinity of the products allowed access to enantiopure materials by simple recrystallization. 

Figure 5.1 A simplified diagram of glycolysis and the tricarboxylic acid (TCA) cycle showing the entry points for various substrates. indicates the two reactions specific to the giyoxyiate cycle. Compounds in boxes are potential substrates for entry into the TCA cycle, via acetyl CoA.

Very few optically active cyanohydrins, derived from ketones, are described in the literature. High diastcrcosclectivity is observed for the substrate-controlled addition of hydrocyanic acid to 17-oxosteroids27 and for the addition of trimethyl(2-propenyl)silane to optically active acyl cyanides28. The enantioselective hydrolysis of racemic ketone cyanohydrin esters with yeast cells of Pichia miso occurs with only moderate chemical yields20. 

In the first instance, acidity influences the acid-base equilibria of the reactants. The amine is a Bronsted base. Aniline, a typical substrate, has pKa = 4.6, which means that the protonation shown in Scheme 3-11 is almost complete under normal conditions of diazotization (pH < 1). The base is definitely a much better reagent than the anilinium ion for nitrosation because the latter is an electrophilic substitution. One expects — simply on the basis of the equilibrium shown in Scheme 3-11 — that the rate of diazotization should decrease linearly with increasing acid concentration or, at higher acidities, with the Hammett acidity function h0 (for acidity functions see Rochester, 1970 Cox and Yates, 1983). 

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