Base-catalysed hydrolysis

The resulting oligonucleotide is often of surprising purity as judged by analytic HPLC or electrophoresis, and up to 30 mg of a deoxyeicosanucleotide (20-base DNA) can be routinely obtained. Nevertheless small amounts of short sequences, resulting from capping and from base-catalysed hydrolysis, must always be removed by quick gel filtration, repeated ethanol precipitation from water (desalting), reverse-phase HPLC, gel electrophoresis, and other standard methods. 

Another competing cyclisation during peptide synthesis is the formation of aspartimides from aspartic acid residues [15]. This problem is common with the aspartic acid-glycine sequence in the peptide backbone and can take place under both acidic and basic conditions (Fig. 9). In the acid-catalysed aspartimide formation, subsequent hydrolysis of the imide-containing peptide leads to a mixture of the desired peptide and a (3-peptide. The side-chain carboxyl group of this (3-peptide will become a part of the new peptide backbone. In the base-catalysed aspartimide formation, the presence of piperidine used during Fmoc group deprotection results in the formation of peptide piperidines. 

A system of parallel reactions as shown in Fig. 5.3-9 was studied by Paul et at. (1992). The reactions are an acid-base neutralization and a base-catalysed hydrolysis of product (C). The labile compound (Q is in solution in an organic solvent, and aqueous NaOH is added to raise the pH from 2 to 7. Enolization occurs under basic conditions and is accompanied by irreversible decomposition (ring opening), which is not shown in the figure. The system was studied in the laboratory using the 6-Iitre reactor shown in Fig. 5.3-10. 

The addition of H20 (hydrolysis) may be both acid- and base-catalysed ... 

The initial product is an amide (197), but this also undergoes ready acid- or base-catalysed hydrolysis (see above), and the actual reaction product is often the carboxylic acid, RC02H, or its anion. 

Another early example of Hammett s is shown in Fig. 13.2, which represents a plot of log k for base-catalysed hydrolysis of a group of ethyl esters (3) against log K for ionisation in water of the corresponding carboxylic acids (2). Judged... 

A reason for such non-conformity on the part of o-substituted benzene, and of aliphatic, derivatives is not far to seek. Thus for the base-catalysed hydrolysis (p. 238) of the esters (3) in Figs 13.2 and... 

Having thus obtained a range of substituent constant, trx> values it is now possible to use them to calculate the value of p, the reaction constant, in [6] for any further reactions in which we may be interested this is often done graphically. Thus to evaluate p for, say, the base-catalysed hydrolysis of m- and p-substituted ethyl 2-arylethanoates (4) we would, from kinetic measurements (or from... 

This is borne out by a comparison of the rates of base-catalysed hydrolysis (cf. p. 238) of m-N02 (5), and of m-Me (6), substituted ethyl benzoates with that of the unsubstituted ester a reaction in which the slow, and hence rate-limiting, step is initial attack on the ester by eOH (p. 239) ... 

To evaluate r for other reactions, we can obtain p for the reaction by measuring kx values for m -substituted compounds only, and then measure kx for p-substituted compounds where the values of graphical methods. Thus for the base-catalysed hydrolysis of p-substituted phenoxytriethylsilanes... 

The simplest possible use that can be made of the Hammett equation is to calculate k or K for a specific reaction of a specific compound, where this information is not available in the literature, or indeed where the actual compound has not even been prepared yet. Thus it is known that the base-catalysed hydrolysis of ethyl m -nitrobenzoate is 63-5 times as fast as the hydrolysis of the corresponding unsubstituted ester under parallel conditions what then will be the comparable rate for base-catalysed hydrolysis of ethyl p-methoxybenzoate under the same conditions Looking at the table of [Pg.374]

The p value for base-catalysed hydrolysis (+2-51) is +ve and quite large, reflecting the development of not inconsiderable -ve charge at the reaction centre in the rate-limiting step—attack on this centre by OH (step CD in the BAC2 pathway). By contrast, the p value for acid-catalysed hydrolysis (+0-03) is very nearly zero which means, of course, that the rate of this hydrolysis does not vary significantly from one ester to another, no matter what the m- or... 

If we now extend our consideration of base-catalysed (BAC2), and acid-catalysed (Aac2), hydrolysis to esters in general, including aliphatic ones (RC02Et), we see that there is a close similarity between the transition states (42b or 42a) for the rate-limiting step in each of the two pathways they are both tetrahedral and differ... 

T.S. for base-catalysed T.S. for acid-catalysed hydrolysis (BAC2) hydrolysis (Aac2)... 

Looking back at one of our earliest examples—Fig. 13.3 (p. 361) in which log K for the ionisation of ArC02H is plotted against log k for the base-catalysed hydrolysis of ArC02Et—the straight line implies that there is also a linear relationship between the AG° values for the former reaction and the AG+ values for the latter. Such a straight line relationship between these two series of AG terms is to be expected only if, for each series, one or other of the following conditions is satisfied ... 

Thin sol gel ORMOSIL-zirconia films successfully inhibit magnesium corrosion (Figure 4.11). The film obtained by combining sol-gel monomers phenyltrimethoxysilane (PTMOS) and zirconium(iv) tetra-1-propoxide (ZrTPO) exhibits superior corrosion inhibition as compared with other films,13 while the ZrTPO-based film alone does not show significant corrosion inhibition, and the PTMOS-based film provides only moderate protection. The films are prepared by the traditional acid-or base-catalysed hydrolysis and condensation, depositing first the PTMOS film followed by the ZrTPO-based film. 

Intramolecular general base catalysed reactions (Section II, Tables E-G) present less difficulty. A classification similar to that of Table I is used, but since the electrophilic centre of interest is always a proton substantial differences between different general bases are not expected. This section (unlike Section I, which contains exclusively unimolecular reactions) contains mostly bimolecular reactions (e.g. the hydrolysis of aspirin [4]). Where these are hydrolysis reactions, calculation of the EM still involves comparison of a first order with a second order rate constant, because the order with respect to solvent is not measurable. The intermolecular processes involved are in fact termolecular reactions (e.g. [5]), and in those cases where solvent is not involved directly in the reaction, as in the general base catalysed aminolysis of esters, the calculation of the EM requires the comparison of second and third order rate constants. 

Capon and Ghosh, 1966. No appropriate reference intermolecular reaction rate has been measured for an aryl benzoate. The reference used is the intramolecular general base-catalysed hydrolysis of salicyl salicylate (Kemp and Thibault, 1969) which has fchyd = 2.89 x 10-6 s-1 in water at 30°. If the EM is assumed to be the same as for aspirin (13 M) this corresponds to an intermolecular reaction of an aryl benzoate catalysed by benzoate with k2 = 2.22 x 10-7 dm3 mol-1 s 1. The correction from the pA"-value of salicyl salicylate (3.6) to the pA", of the substrate uses / = 0.5 (cf. 0.52 for the aspirin reaction). The temperature sensitivity is also taken to be equal to that of the aspirin reaction... 

Addition of P—H bonds to unsaturated systems also continues to be used as a route to heterocyclic systems. Thus base-catalysed cyclization of the phosphine (32) [prepared by the addition of methyl methacrylate (2 moles) to phenylphosphine], followed by subsequent hydrolysis and decarboxylation, affords the phosphorinanone (33). The phosphorinanone system is also directly accessible by the addition of phenylphosphine to divinyl ketones.28 The radical-initiated addition of phenylphosphine to dialkynyl systems (34) gives the heterocyclohexadienes (35).29 80 The stereochemistry of the addition of phenylphosphine to cyclo-octa-2,7-dienone to give... 

In base-catalysed hydrolysis, compound (93 R1 = R2 = Ph) behaves differently to (93 R1 = Me or Ph, R2 = OMe) not only with respect to reaction rate but also... 

The acid-catalysed hydrolysis of phosphinic esters (158) is relatively insensitive to the substituent (R = Me, Et, Pr1, or Bu1) attached to phosphorus this contrasts with the base-catalysed process.126 The acid hydrolysis of the phosphinic esters (159) (see Organophosphorus Chemistry , Vol. 7, p. 129 for the base hydrolysis) takes place with alkyl-oxygen fission in an SnI process.127... 

As indicated above, the traditional base-catalysed hydrolysis of 0,5-dialkyl thio-carbonates for the synthesis of thiols is generally unsatisfactory, as oxidation leads to the formation of disulphides. Under phase-transfer conditions, the procedure produces thioethers to the virtual exclusion of the thiols, as a result of the slow release of the thiolate anions in the presence of the electrophilic ester. However, a simple modification of the reaction conditions provides an efficient one-pot reaction [50] from haloalkanes (Table 4.15) via the intermediate formation of the thermally labile (9-/ert-butyl-5-alkyl dithiocarbonates (Scheme 4.8). 

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