Ester production

Nucleophile p Toluenesulfonate ester Product of nucleophilic substitution pi... 

Step 6 Deprotonation of the species formed m step 5 gives the neutral form of the ester product... 

The carbon-carbon bond forming potential inherent m the Claisen and Dieckmann reac tions has been extensively exploited m organic synthesis Subsequent transformations of the p keto ester products permit the synthesis of other functional groups One of these transformations converts p keto esters to ketones it is based on the fact that p keto acids (not esters ) undergo decarboxylation readily (Section 19 17) Indeed p keto acids and their corresponding carboxylate anions as well lose carbon dioxide so easily that they tend to decarboxylate under the conditions of their formation... 

Table 32. U.S. Trimellitic Anhydride Prices and TrimeUitate Ester Production...

Year Trimellitic anhydride price, /kg TrimeUitate ester production, 10 t/vr... 

Unlike simple, unhindered carbonyl compounds, the quinones do not yield bisulfite addition products, but undergo ring addition. Another significant carbonyl reaction is the addition of tertiary phosphites under anhydrous conditions (98). The ester product (99) is easily hydroly2ed, and the overall sequence produces excellent yields of hydroquinone monoethers. 

The principal method of siUcon ester production is described by Von Ebehnan s 1846 synthesis (21) ... 

Fig. 9. U.S. production of cellulose esters A, total cellulose esters production B, cellulose acetate flake C, other cellulose esters, ie, cellulose nitrate,...

In general, esters having equilibrium constants below unity are not prepared by direct interaction of alcohol and acid in these cases, the acid anhydrides or acid chlorides are used, since the equiUbrium favors the ester product. 

Use of Azeotropes to Remove Water. With the aliphatic alcohols and esters of medium volatility, a variety of azeotropes is encountered on distillation (see Distillation, azeotropic and extractive). Removal of these azeotropes from the esterification reaction mixture drives the equihbrium in favor of the ester product (39). 

Unreacted Starting Material S Intermolecular Reaction Product Keto Ester Product ... 

The Dieckmann condensation of diethyl adipate yields a keto-ester product. 

Chemists have estabhshed that a Dieckmann condensation will not succeed unless the final keto-ester product is deprotonated by a base. In our example, this would be a reaction between EtO" and the keto-ester (it is necessary, therefore, to use excess EtO ). What reaction products are generated by this proton transfer Obtain the energies of the reactants and products, and calculate the energy for this final proton transfer. Is this reaction thermodynamically favorable or unfavorable Does this step make the overall condensation reaction favorable or unfavorable ... 

The Hinsberg synthesis of thiophene derivatives describes the original condensation of diethyl thiodiglycolate and a-diketones under basic conditions which provides 3,4-disubstituted-thiophene-2,5-dicarboxylic acids upon hydrolysis of the crude ester product with aqueous acid. ... 

The 3-o-ch orophenvl-5-methvlisoxa2ole4-carboxylic acid, from which the acid chloride was prepared, was obtained by hydrolysis of the ester product of the reaction between o-chloro-benzohydroxamic chlorideand ethyl acetoacetate in methanolic sodium methoxide. Reaction with thionyl chloride gave the starting material. 

Loss of a proton and expulsion of H2O regenerates the acid catalyst and gives the ester product. 

Protonation of the enolate ion by addition of aqueous acid in a separate step yields the final /3-keto ester product. 

The mixed Claisen condensation of two different esters is similar to the mixed aldol condensation of two different aldehydes or ketones (Section 23.5). Mixed Claisen reactions are successful only when one of the two ester components has no a hydrogens and thus can t form an enolate ion. For example, ethyl benzoate and ethyl formate can t form enolate ions and thus can t serve as donors. They can, however, act as the electrophilic acceptor components in reactions with other ester anions to give mixed /3-keto ester products. 

The mechanism of the Dieckmann cyclization, shown in Figure 23.6, is the same as that of the Claisen condensation. One of the two ester groups is converted into an enolate ion, which then carries out a nucleophilic acyl substitution on the second ester group at the other end of the molecule. A cyclic /3-keto ester product results. 

Mechanism of the Dieckmann cyclization of a 1,7-diester to yield a cyclic /3-keto ester product. 

Dieckmann cyclization of diethyl 3-methylheptanedioate gives a mixture of two /3-keto ester products. What are their structures, and why is a mixture formed ... 

The Claisen reaction is a carbonyl condensation that occurs between two ester molecules and gives a /3-keto ester product. Mixed Claisen condensations... 

Step 4 of Figure 29.3 Chain Cleavage Acetyl CoA is split off from the chain in the final step of /3-oxidation, leaving an acyl CoA that is two carbon atoms shorter than the original. The reaction is catalyzed by /3-ketoacyl-CoA thiolase and is mechanistically the reverse of a Claisen condensation reaction (Section 23.7). In the forward direction, a Claisen condensation joins two esters together to form a /3-keto ester product. In the reverse direction, a retro-Claisen reaction splits a /3-keto ester (or /3-keto thioester) apart to form two esters (or two thioesters). 

Claisen condensation reaction (Section 23.7) The carbonyl condensation reaction of an ester to give a /3-keto ester product. 

Lipase-catalyzed methanolysis of racemic N-benzyloxycarbonyl (Cbz) amino acid trifluoroethyl esters carrying aliphatic side chains afforded the L-methyl esters and the D-trifluoromethyl esters (Figure 6.16). The released alcohol (CF3CH2OH) is a weak nucleophile that cannot attack the ester product. The nucleophilidty of the leaving group is depleted by the presence of an electron-withdrawing group [63]. 

The ability of enzymes to achieve the selective esterification of one enantiomer of an alcohol over the other has been exploited by coupling this process with the in situ metal-catalysed racemisation of the unreactive enantiomer. Marr and co-workers have used the rhodium and iridium NHC complexes 44 and 45 to racemise the unreacted enantiomer of substrate 7 [17]. In combination with a lipase enzyme (Novozyme 435), excellent enantioselectivities were obtained in the acetylation of alcohol 7 to give the ester product 43 (Scheme 11.11). A related dynamic kinetic resolution has been reported by Corberdn and Peris [18]. hi their chemistry, the aldehyde 46 is readily racemised and the iridium NHC catalyst 35 catalyses the reversible reduction of aldehyde 46 to give an alcohol which is acylated by an enzyme to give the ester 47 in reasonable enantiomeric excess. 

Oxidation Processes Scheidt and co-workers have employed cascade oxidation pathways from aUyhc or propargylic alcohols to afford unsaturated ester products 25. In situ oxidation of an unsaturated alcohol 21 to the enal 22 using MnO, ... 

This homoenolate methodology has been extended to the use of nitrones 170 as electrophiles [72]. Scheldt and co-workers have shown that enantiomerically enriched y-amino esters 172 can be prepared with excellent levels of stereocontrol from an enal 27 and a nitrone 170 using the NHC derived from triazolium salt 164 (Scheme 12.37). The oxazinone product 171, formally a result of a [3-1-3] cycloaddition, is cleaved to afford the y-amino ester product 172. The reaction shows broad substrate scope, as a range of substituted aryl nitrones containing electron donating and withdrawing substituents are tolerated, while the enal component is tolerant of both alkyl and aryl substituents. 

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