Esters base-catalysed

The mechanism, of the base-catalysed acylation of ketones by esters probably involves several steps (compare acetoacetlc ester condensation see discussion prloi to Section 111,151) —... 

The main example of a category I indole synthesis is the Hemetsberger procedure for preparation of indole-2-carboxylate esters from ot-azidocinna-mates[l]. The procedure involves condensation of an aromatic aldehyde with an azidoacetate ester, followed by thermolysis of the resulting a-azidocinna-mate. The conditions used for the base-catalysed condensation are critical since the azidoacetate enolate can decompose by elimination of nitrogen. Conditions developed by Moody usually give good yields[2]. This involves slow addition of the aldehyde and 3-5 equiv. of the azide to a cold solution of sodium ethoxide. While the thermolysis might be viewed as a nitrene insertion reaction, it has been demonstrated that azirine intermediates can be isolated at intermediate temperatures[3]. 

Many of the compounds that undergo ready base-catalysed keto i enol prototropic changes, e.g. / -keto esters, l,3-(/ -) diketones, aliphatic nitro compounds, etc., form relatively stable carbanions, e.g. (25), that can often be isolated. Thus it is possible to obtain carbanions from the keto forms of the /J-keto ester (23a) and nitromethane (24a) and, under suitable conditions, to protonate them so as to obtain the pure enol forms (23b) and (24i>), respectively. It thus seems extremely probable that their interconversion follows the intermolecular pathway (a). The more acidic the substrate, i.e. the more stable the carbanion to which it gives rise, the greater the chance that prototropic interconversion will involve the carbanion as an intermediate. 

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... 

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) ... 

If we now look at the list of base-catalysed ester... 

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... 

The first evidence that an elimination-addition mechanism could be important in nucleophilic substitution reactions of alkanesulfonyl derivatives was provided by the observation (Truce et al., 1964 Truce and Campbell, 1966 King and Durst, 1964, 1965) that when alkanesulfonyl chlorides RCH2S02C1 were treated in the presence of an alcohol R OD with a tertiary amine (usually Et3N) the product was a sulfonate ester RCHDS020R with exactly one atom of deuterium on the carbon alpha to the sulfonyl group. Had the ester been formed by a base-catalysed direct substitution reaction of R OD with the sulfonyl chloride there would have been no deuterium at the er-position. Had the deuterium been incorporated by a separate exchange reaction, either of the sulfonyl chloride before its reaction to form the ester, or of the ester subsequent to its formation, then the amount of deuterium incorporated would not have been uniformly one atom of D per molecule. The observed results are only consistent with the elimination-addition mechanism involving a sulfene intermediate shown in (201). Subsequent kinetic studies... 

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. 

I Antanovics, GT Young. Amino-acids and peptides. Part XXV. The mechanism of the base-catalysed racemisation of the p-nitrophenyl esters of acylpeptides. J Chem Soc C 595, 1967. 

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... 

Symmetrical 5,5-dialkyl dithiocarbonates have been obtained by thermal rearrangement of the corresponding (9,5-dialkyl esters in the presence of Aliquat [43]. This procedure is not suitable for the preparation of unsymmetrical 5,5-dialkyl dithiocarbonates, as it has been reported that disproportionation of the products can lead to a mixture of the symmetrical and unsymmetrical esters. Alternatively, they can be prepared by a base-catalysed disproportionation of 5-alkyl-O-methyl dithiocarbonates [44] (Table 4.9). These methods for the synthesis of the 5,5-dialkyl esters are more convenient than the traditional procedures from the thiol and phosgene. 

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). 

Methylenesulphones are more acidic than the simple esters, ketones and cyano compounds and are more reactive with haloalkanes [e.g. 48-57] to yield precursors for the synthesis of aldehydes [53], ketones [53], esters [54] and 1,4-diketones [55] (Scheme 6.4). The early extractive alkylation methods have been superseded by solidtliquid phase-transfer catalytic methods [e.g. 58] and, combined with microwave irradiation, the reaction times are reduced dramatically [59]. The reactions appear to be somewhat sensitive to steric hindrance, as the methylenesulphones tend to be unreactive towards secondary haloalkanes and it has been reported that iodomethylsulphones cannot be dialkylated [49], although mono- and di-chloromethylsulphones are alkylated with no difficulty [48, 60] and methylenesulphones react with dihaloalkanes to yield cycloalkyl sulphones (Table 6.5 and 6.6). When the ratio of dihaloalkane to methylene sulphone is greater than 0.5 1, open chain systems are produced [48, 49]. Vinyl sulphones are obtained from the base-catalysed elimination of the halogen acid from the products of the alkylation of halomethylenesulphones [48]. 

Regio-control of the formation of benzoic esters of mixed benzoin derivatives results from the initial formation of the cyanhydrin benzoate (see Chapter 3). Subsequent base-catalysed hydrolysis of the esters produces the mixed benzoins (Scheme 6.20) [66]. 

With the exception of the parent compounds, where the Michael adducts are isolated, acrylic esters [see, e.g. 6,7,31,105,111 ] and nitriles [6,7], and vinyl ketones [26, 113, 115] generally yield the cyclopropanes (Table 7.6) under the standard Makosza conditions with chloroform. Mesityl oxide produces a trichlorocyclopropy-lpropyne in low yield (10%) [7]. When there is no substituent, other than the electron-withdrawing group at the a-position of the alkene, further reaction occurs with the trichloromethyl anion to produce spiro systems (35-48%) (Scheme 7.12) [7, 31]. Under analogous conditions, similar spiro systems are formed with a,p-unsaturated steroidal ketones [39]. Generally, bromoform produces cyclo adducts with all alkenes. Vinyl sulphones are converted into the dichlorocyclopropane derivatives either directly or via the base-catalysed cyclization of intermediate trichloromethyl deriva-... 

Dioxo-l,3-dioxanes ring-open under basic conditions. Cleavage of the 5,5-disubstituted derivatives in the presence of quininium or quinidinium alkoxides produces chiral malonic hemi-esters (ee 30-40%) in high yield [11]. The addition of cetyltrimethylammonium bromide promotes the base-catalysed cleavage of p-keto esters to form ketones under sonication [12]. 

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