Acylation with esters

The sugar alkaloid colchicoside and its synthetic sulfur analog thiocol-chicoside were acylated with esters of trifluoroethanol and with isopro-penylacetate in pyridine in the presence of the enzyme subtilisin from Bacillus subtilis (132). The 13C-NMR spectra of the ester alkaloids, which... 

Dimethyl-188 and 2,6-dimethylpyrazine react very similarly to methylpyrazine. Thus, 2,6-dimethylpyrazine can be converted into a monoanion with sodamide in liquid ammonia which can be condensed with aldehydes and ketones,179 acylated with esters,181 and alkylated with alkyl halides181 to give the corresponding 2-methyl-6-substituted pyrazines. Acylation under suitable conditions also yields diacylated derivatives. Thus, when 2,6-dimethylpyrazine, sodamide, and ethyl benzoate are reacted in 1 3 2 molecular proportion, 38% 2,6-diphen-acylpyrazine (35) and 25% 2-methyl-6-phenacylpyrazine (36) is obtained. From the preparative point of view it is better to form the diacyl derivative by the further acylation of the monoacyl derivative rather than by direct diacylation.187... 

In the presence of sodium ethoxide, nitriles having reactive a methylene groups may be acylated with esters to form /S-keto nitriles. The method is general and is illustrated by the reaction of alkyl cyanides, where R is C, to with ethyl benzoate to form the corresponding alkylbenzoyl-... 

Lateral metallation at C-2(a) of l-/ftt-butoxycarbonyl-2-methylimidazoline 709 (Scheme 173) with r f-BuLi results in the formation of a bright yellow lithiated intermediate that reacts with alkyl halides, diphenyldiselenide, and phosphoryl chlorides to give 710. In the case of reaction with esters, the conjugated ketones 711 are formed <2000T2061>. In the case of acylation with esters, conjugated enamino-ketones were the tautomer isolated. Further alkylation is also possible under similar conditions, to give 712. 

Y-Oxo sulfone acetals can be acylated with esters giving, after reductive desulfonylation, a convenient route to y-keto aldehydes or 1,4-diketones (Scheme 67). The intermolecular acylation of a-sulfonyl carbanions was also used to synthesize 7-butyrolactones. ... 

Ketones are acylated with esters in a similar manner. The product is a 1,3-diketone. Again, with intermolecular condensations, the reaction is especially important with nonenolizable esters such as diethyl carbonate, diethyl oxalate, and ethyl formate. And again, the reaction is driven to completion by deprotonation of the very acidic 1,3-dicarbonyl product. 

Similarly the carbanion (XI) need not have been derived from an ester. Methyl ketones in the presence of sodamide23 can be acylated with, esters to give /3-diketones of the type RCOCHoCOR. The mechanism appears to be ... 

Lithiation of l-aryl-17/-imidazoles followed by quenching with electrophiles provided a route to 1,2-diaryl, l-aryl-2-cycloalkyl- and l-aryl-2-heterocycle-substituted imidazoles <05H(65)2721>. Isoprene-catalyzed lithiation of imidazole provided a synthetic route to 2-(hydroxyalkyl)- and 2-(aminoalkyl)imidazoles <05X11148>. 2-Lithiobenzimidazoles were efficiently acylated with esters, lactones and lactams <05TL5081>. 

Lithium derivatives of these sulfones can be alkylated with alkyl halides or epoxides,28 and acylated with esters to give the ketones 95 from which the sulfonyl group can be removed with aluminium amalgam Deprotection and cyclisation provides a synthesis of cyclopentenones 98 (cf. chapter 6).26... 

The most typical type of hydrolase-catalyzed stereoselective reactions under continuous-flow conditions is KR. Continuous-flow KRs were performed on racemic acids by direct esterification with alcohols [100-102, 108, 109] or on racemic amines by acylation with esters (Figure 9.7 and Table 9.5) [110-114]. However, the most frequent so far is the continuous-flow KR of racemic primary... 

The acylation of ketones with esters an example of the Clalsen condensation is generally effected with a basic reagent, such as sodium ethoxide, sodium, sodamide or sodium hy dride. Thus acetone and ethyl acetate condense in the presence of sodium ethoxide to yield acetylacetone ... 

Chiral 2-oxazolidones are useful recyclable auxiliaries for carboxylic acids in highly enantioselective aldol type reactions via the boron enolates derived from N-propionyl-2-oxazolidones (D.A. Evans, 1981). Two reagents exhibiting opposite enantioselectivity ate prepared from (S)-valinol and from (lS,2R)-norephedrine by cyclization with COClj or diethyl carbonate and subsequent lithiation and acylation with propionyl chloride at — 78°C. En-olization with dibutylboryl triflate forms the (Z)-enolates (>99% Z) which react with aldehydes at low temperature. The pure (2S,3R) and (2R,3S) acids or methyl esters are isolated in a 70% yield after mild solvolysis. 

Cydopentane reagents used in synthesis are usually derived from cyclopentanone (R.A. Ellison, 1973). Classically they are made by base-catalyzed intramolecular aldol or ester condensations (see also p. 55). An important example is 2-methylcydopentane-l,3-dione. It is synthesized by intramolecular acylation of diethyl propionylsucdnate dianion followed by saponification and decarboxylation. This cyclization only worked with potassium t-butoxide in boiling xylene (R. Bucourt, 1965). Faster routes to this diketone start with succinic acid or its anhydride. A Friedel-Crafts acylation with 2-acetoxy-2-butene in nitrobenzene or with pro-pionyl chloride in nitromethane leads to acylated adducts, which are deacylated in aqueous acids (V.J. Grenda, 1967 L.E. Schick, 1969). A new promising route to substituted cyclopent-2-enones makes use of intermediate 5-nitro-l,3-diones (D. Seebach, 1977). 

Alkyl- and arylmercury(II) halides are used for the ketone formation[402]. When active methylene compounds. such as /f-keto esters or malonates are used instead of alcohols, acylated / -keto esters and malonates 546 are produced, For this reaction, dppf is a good ligand[403]. The intramolecular version of the reaction proceeds by trapping the acylpalladium intermediate with eno-late to give five- and six-membered rings smoothly. Formation of 547 by intramolecular trapping with malonate is an example[404]. 

Another o-aminobenzyl anion equivalent is generated by treatment of A-trimethylsilyl-o-toluidinc with 2.2 eq. of n-butyllithium. Acylation of this intermediate with esters gives indoles[2]. This route, for example, was used to prepare 6.2D, a precursor of the alkaloid cinchonamine. 

The reaction of ammonia and amines with esters follows the same general mech anistic course as other nucleophilic acyl substitution reactions (Figure 20 6) A tetrahe dral intermediate is formed m the first stage of the process and dissociates m the second stage... 

Section 20 7 Esters occur naturally or are prepared from alcohols by Fischer estenfi cation or by acylation with acyl chlorides or acid anhydrides (see Table 20 3)... 

Reaction with esters of strong acids, such as formates or oxalates, yields the acyl derivatives of ethyleneimine dimer (238,239). 

Liquid crystal polyesters are made by a different route. Because they are phenoHc esters, they cannot be made by direct ester exchange between a diphenol and a lower dialkyl ester due to unfavorable reactivities. The usual method is the so-called reverse ester exchange or acidolysis reaction (96) where the phenoHc hydroxyl groups are acylated with a lower aHphatic acid anhydride, eg, acetic or propionic anhydride, and the acetate or propionate ester is heated with an aromatic dicarboxyHc acid, sometimes in the presence of a catalyst. The phenoHc polyester forms readily as the volatile lower acid distills from the reaction mixture. Many Hquid crystal polymers are derived formally from hydroxyacids (97,98) and thein acetates readily undergo self-condensation in the melt, stoichiometric balance being automatically obtained. 

Similar ester carboxylate group containing polymeric titanate esters are obtained by the reaction of titanoxanes with carboxyUc acids (26), by reaction of a tetraalkyl titanate with a carboxyUc acid and 1—2 moles of water (27), or by reacting a polymeric metal acylate with a higher boiling carboxyUc acid and removing the lower boiling carboxyUc acid by distillation (28). 

Unprotected racemic amines can be resolved by enantioselective acylations with activated esters (110,111). This approach is based on the discovery that enantioselectivity of some enzymes strongly depends on the nature of the reaction medium. For example, the enantioselectivity factor (defined as the ratio of the initial rates for (3)- and (R)-isomers) of subtiHsin in the acylation of CX-methyl-ben zyl amine with tritiuoroethyl butyrate varies from 0.95 in toluene to 7.7 in 3-methyl-3-pentanol (110). The latter solvent has been used for enantioselective resolutions of a number of racemic amines (110). 

Ester hydrolysis is the most studied and best understood of all nucleophilic acyl substitutions. Esters are fairly stable in neutral aqueous media but are cleaved when heated with water in the presence of strong acids or bases. The hydrolysis of esters in dilute aqueous acid is the reverse of the Eischer esterification (Sections 15.8 and 19.14) ... 

In their original communication on the alkylation and acylation of enamines, Stork et al. (3) had reported that the pyrrolidine enamine of cyclohexanone underwent monoacylation with acid chlorides. For example, the acylation with benzoyl chloride led to monobenzoylcyclohexanone. However, Hunig and Lendle (33) found that treatment of the morpholine enamine of cyclopentanone with 2 moles of propionyl chloride followed by acid hydrolysis gave the enol ester (56), which was proposed to have arisen from the intermediate (55). 

Stereochemical positioning of a functional group, relative to a separate enamine moiety in the same molecule, can be done in such a manner that a simple intramolecular alkylation or acylation will cause cyclization. Such intramolecular cycloalkylations with alkyl halides have been reported 107,108). Inftamolecular cycloacylations of enamines with esters 109, 110,110a) and with nitriles 110a,l 11,111a) have also been observed. 

The Gould-Jacobs reaction is a sequence of the following reactions (1) condensation of an arylamine 1 with either alkoxy methylenemalonic ester or acyl malonic ester 2 providing the anilidomethylenemalonic ester 3 (2) cyclization of 3 to the 4-hydroxy-3-carboalkoxyquinoline 4 (3) saponification to form acid 5, and (4) decarboxylation to give the 4-hydroxyquinoline 6. All steps of this process will be described herein with emphasis on the formation of intermediates like 3 and 4. 

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