Substitution transesterification

Some esters of substituted alcohols have been synthesized by transesterification. Treatment of 4-methyl-5-thiazolecarboxylic acid (14) with 3-chloroethyldiethylamine in acetone in the presence of anhydrous potassium carbonate gives the desired ester (15) in good vield (60%) (Scheme 10) (163). 

Most large-scale industrial methacrylate processes are designed to produce methyl methacrylate or methacryhc acid. In some instances, simple alkyl alcohols, eg, ethanol, butanol, and isobutyl alcohol, maybe substituted for methanol to yield the higher alkyl methacrylates. In practice, these higher alkyl methacrylates are usually prepared from methacryhc acid by direct esterification or transesterification of methyl methacrylate with the desired alcohol. 

In contrast to the hydrolysis of prochiral esters performed in aqueous solutions, the enzymatic acylation of prochiral diols is usually carried out in an inert organic solvent such as hexane, ether, toluene, or ethyl acetate. In order to increase the reaction rate and the degree of conversion, activated esters such as vinyl carboxylates are often used as acylating agents. The vinyl alcohol formed as a result of transesterification tautomerizes to acetaldehyde, making the reaction practically irreversible. The presence of a bulky substituent in the 2-position helps the enzyme to discriminate between enantiotopic faces as a result the enzymatic acylation of prochiral 2-benzoxy-l,3-propanediol (34) proceeds with excellent selectivity (ee > 96%) (49). In the case of the 2-methyl substituted diol (33) the selectivity is only moderate (50). 

Lipase-catalyzed enantioselective transesterification of 0-substituted-l,2-diols is another practical route for the synthesis of P-blockers. Lipase PS suspended in toluene catalyzes the transesterification of (63) with vinyl acetate to give the (5)-ester in 43% yield and >98% ee (78). The desired product, optically pure (R)-ttitylglycidol, is then easily obtained by treating the ester with alcohoHc alkaU. Moreover, Pseudomonas Hpase catalyzes the acylation of oxazohdinone (64) with acetic anhydride in very good yield and selectivity (74). PPL-catalyzed transesterification of a number of /n j -norbomene derivatives proceeds in about 30% yield and 92% ee (79,80). 

NEW Green chemistry promotes environmentally sound chemistry. Passages in the text created in consultation with Michael Cann and new end-of-chapter exercises are accompanied by a (IT). Topics include ionic liquids (Chapter 5), supercritical C02 (Chapter 8), yttrium in paint (Chapter 12), chelates as a substitute for chlorine bleach (Chapter 16), and transesterification (Chapter 19). 

Cyclization of substituted phenylacetylene sequences afforded functionalized macrocycles that were amenable to subsequent manipulation. For example, transesterification of 42 with octanol in the presence of 18-crown-6 ether and potassium carbonate gave the corresponding ester in 85% yield (Scheme 13). The ester functionalities could be reduced by DIBALH to give the hydroxymethyl-substituted macrocycle (43) in 61 % yield. The low yield of this particular transformation is attributed to mechanical losses during purification, due to the highly polar nature of the product. Macrocycle 43 could then be treated with alkyl bromides to give a group of benzyl ether derivatized PAMs. 

Besides allylic substitution reactions it was also shown that [Fe(CO)3(NO)] 76 is catalytically active in transesterification reactions under neutral conditions (Scheme 24) [70]. Various activated acyl donors 97 can be used to give rise to the corresponding carboxylic esters 100 in good to excellent yields. This reaction proceeds in the absence of additional ligands in nonpolar solvents, for example, hexane. Mechanistically, the reaction is assumed to proceed via a Fe-acyl-complex 98 (Scheme 24). 

For the delicate transesterification of a p-Lactam intermediate (for carbacephalosphorin skeleton), where originally hydrolysis of methyl ester was done homogeneously and then formation of the benzyl (or substituted benzyl) ester was done separately, Doecke et al. (1991) have devised a mild and efficient methodology using PTC. A dual use of a PT catalyst, Bu4NBr, in one pot was made in a CH2CI2 - H2O system. In the first step 5N NaOH was used, then the pH was adjusted to 7.2 to 7.8 and subsequently benzyl (or substituted benzyl) bromide was added. 

The effect of an ally lie hydroxy group was first observed in divinylglycol (1,5-hexadiene-cA-3,4-diol and 1.5-hexadiene-/raw.v-3,4-diol). It was shown that the hydroxy substitutions directed the addition of the osmium tetraoxide to syn addition, so that the cA-diol yielded allitol (all cA-hexaol) and the iraws-diol yielded mannitol42. The oxidation of the dienol 35 yielded a lactone ring 36 by cA-dihydroxylation and transesterification... 

It was found that decomposition is in part due to transesterification and that substitution increases stability. The effect of gamma radiation on aspirin has been described.184 The pH stability profile of aspirin according to Edwards has been made the subject of a student experiment.185... 

Historically, the thermal transesterification of (-)-ethyl p-toluene-sulfinate 224 with n-butanol affording (+)-n-butyl p-toluenesulfinate 225 described by Phillips in 1925 (100) is the first nucleophilic substitution reaction at chiral sulfur involving a Walden-type inversion. The evidence for inversion of configuration in this reaction was based on the assumption that both (-)-esters 224 and 225 obtained from the kinetic resolution have the same configuration. 

One of the best examples of the utility of enzymatic synthesis in catalyzing reactions that cannot be accomplished by any other route is the synthesis of substituted oxazolidine diesters. The oxazolidine ring is extremely water sensitive, the oxazolidine rapidly reverting back to the alkanolamine and aldehyde in the presence of water. Bis-oxazolidines have been used as hardeners for polymer coatings but the diester based on the hydroxyethyl oxazolidine and adipic acid cannot be synthesized directly with chemical catalysis because of the rapid rate of reaction of the oxazolidine ring with either the water from the esterification or the alcohol from transesterification. ... 

Under the general term of substitution, we will deal with several transformations in which two molecules of reactants form the product and in which a new C—C or C—O bond or bonds are formed by replacing a C—H bond or another C—O bond. Aldol condensation, esterification, or transesterification and the formation of ethers from alcohols fall into this broad category. We also will include in this section addition to multiple C—C bonds. The published LFERs are summarized in Table III (2, 72-76). 

Vegetable oils have the potential to substitute a fraction of petroleum distillates and petroleum-based petrochemicals in the near future. Possible acceptable converting processes of vegetable oils into reusable products are transesterification, solvent extraction, cracking and pyrolysis. Pyrolysis has received a significant amount of interest as this gives products of better quality compared to any other thermochemical process. The liquid fuel produced from vegetable oil pyrolysis has similar chemical components to conventional petroleum diesel fuel. 

A 50% functionalization evokes the interesting question, bearing in mind facile transesterification, of how the fluoroalkyl chains will be distributed over the molecules and how they will be distributed on one particular molecule This question has been examined in detail for dendrimers of the poly(propyleneimine) type functionalized with stearic acid [33]. It was proven that the compositional heterogeneity (distribution of degree of substitution) is random, but the positional heterogeneity (spatial distribution of the substituents over the dendrimer molecule) is not random. However, due to flexibility, no particular effect of the spatial distribution can be observed. Unlike the dendrimers, we expect the hyperbranched polyesteramides to be stiffer, so that spatial distribution could lead to interesting effects if the molecule were composed of a functionalized side and a non-func-tionalized side (Fig. 28), as shown possible for dendrimers via a convergent synthesis [34]. 

Ir-catalyzed allylic substitutions employing allylic alcohols as substrates and diethyl malonate as pronucleophile were first reported by Takeuchi and coworkers [11]. Here, the substitution step was found to be preceded by OH activation via transesterification to a malonic ester derivative. The asymmetric alkylation of cinnamic alcohol was similarly accomplished by Helmchen and colleagues, using a PHOX ligand and the procedure described in Section 9.2.3 [19]. 

Metal-catalyzed allylic substitution reactions have been a mainstay of synthetic chemistry because of their ability to proceed irreversibly and with high selectivity [42]. It is also feasible, however, to produce analogous systems that are completely reversible and nonselective, or ideally situated for use in DCC. These are essentially metal-catalyzed transesterification reactions, with the added feature of potentially providing stereochemical scrambling (and selection) as well as constitutional variation. An early example of this was provided in 2000 by Kaiser and Sanders [43]. In the absence of a template, reaction of diallyl diacetate 22 with a dicarboxylic acid in the presence of catalytic Pd(0) produced a negligible amount of the cycfized compound 23 (Fig. 1.9). However, when templated with 1,3-bis(4-pyridyl) benzene, yield of the cyclic structure increased to roughly 10%, independent of the dicarboxylic acid used. 

The next step is not immediately obvious. The generation of an ethyl ester from a lactone can be accommodated by transesterification (we might alternatively consider esterification of the free hydroxyacid). The incorporation of chlorine where we effectively had the alcohol part of the lactone leads us to nucleophilic substitution. That it can be SnI is a consequence of the tertiary site. Cyclopropane ring formation from an Sn2 reaction in which an enolate anion displaces a halide should be deducible from the structural relationships and basic conditions. 

We have also investigated the properties of several of our nanostructured catalysts as solid acids in reactions such as the dehydration of alcohols and transesterification reactions [99]. One of the best examples of atomically dispersed solid acid catalysts is aluminosilicates [100]. When aluminium is substituted into silicate frameworks and remains isolated from other A1 centers it can behave as a strong acid site [101]. 

In the absence of primary alcohols, secondary alcohols participate in transesterification reactions to provide good yields for most alcohols. No significant electronic effect is observed when electron-releasing and electron-withdrawing substitutents on aromatic secondary alcohols (Table 22, entries 2-4). A steric effect is observed with cyclohexanol derivatives. Increasing the a-substituent from hydrogen to methyl or teri-butyl dramatically decreases efficiency of transesterifi-... 

A proposed mechanism for this transformation, provided in Scheme 42, is based on the identification of alcohol-carbene complexes by Movassaghi and Schmidt. Mesityl substituted imidazolinylidine carbene acts as a Brpnsted base as transesterification occurs to produce LXVII. Upon O N acyl transfer, the observed product is formed. The evidence provided for this mechanism includes the control experiment in which LXVII is resubjected to the reaction conditions and proceeds with amide formation. A similar mechanism has recently been reported in a theoretical study of transesterification by Hu and co-workers [139], In light of this work, it seems reasonable to suggest a similar that mechanism is operative in the transesterification reactions discussed throughout this section. 

Suzuki and co-workers first published on the topic of enantioselective transesterification in 2004 [140, 141]. This process exploits C -symmetric imidazolium salts with various substitutions. When vinyl propionate 281 acts as the acyl donor, ester 282 is isolated in 68% ee at 19% conversion, corresponding to an s value of 6.1 (Eq. 27). 

As shown in previous sections, NHCs promote acyl transfer in transesterification reactions. In a similar manner, O C acyl transfer can be achieved with substrates such as 351 in the presence of 0.9 mol% of triazolium pre-catalyst 353 and KHMDS (Scheme 53). Moderate yields are obtained by varying substitution of the oxazole from R = Me, Ph, t-Bu, and t-Pr [171], Deprotonation of the triazolium salt followed by nucleophilic addition to the carbonate moiety of the oxazole results in enolate intermediate LXXXIII and activated carboxylate LXXXIV. Enolate addition and regeneration of the active catalyst provides quaternary stereocenters 352. 

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