Acylation ester condensation

Reactions of the Carboxyl Group. Ester and amide formation may be mentioned first one H atom of an alcohol or an amine is replaced by the acyl group. But C-acylation ( ester condensation in organic chemistry) is also known, along with the reverse reaction, thioclastic cleavage ... 

The acetoacetic ester condensation (involving the acylation of an ester by an ester) is a special case of a more general reaction term the Claisen condensation. The latter is the condensation between a carboxylic ester and an ester (or ketone or nitrile) containing an a-hydrogen atom in the presence of a base (sodium, sodium alkoxide, sodamide, sodium triphenylmethide, etc.). If R—H is the compound containing the a- or active hydrogen atom, the Claisen condensation may be written ... 

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) —... 

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). 

Claisen ester condensation, 6, 279 Thiazolecarboxylic acid chlorides reactions, 6, 279-280 Thiazolecarboxylic acid hydrazides synthesis, 6, 280 Thiazolecarboxylic acids acidity, 6, 279 decarboxylation, 6, 279 reactions, S, 92 6, 274 Thiazole-2-carboxylic acids decarboxylation, S, 92 Thiazole-4-carboxylic acids stability, S, 92 Thiazole-5-carboxylic acids decarboxylation, S, 92 Thiazole-4,5-dicarboxylic acid, 2-amino-diethyl ester reduction, 6, 279 Thiazole-4,5-dicarboxylic acids diethyl ester saponification, 6, 279 Thiazolediones diazo coupling, 5, 59 Thiazoles, 6, 235-331 ab initio calculations, 6, 236 acidity, S, 49 acylation, 6, 256 alkylation, S, 58, 73 6, 253, 256 analytical uses, 6, 328 antifogging agents... 

Harrison et al. have demonstrated that bis-acyl glycoluril derivatives 84 undergo efficient Claisen ester condensation, as exemplified in Equation (18) to yield /3-ketoamide derivatives 85. A kinetic study is also presented which indicates clean, bimolecular kinetics and short half lives for the intermediates <2002CJC517>. 

Conversely, ester condensation reactions join acyl groups from CoA derivatives to Schiff bases derived from glycine or serine. Succinyl-CoA is the acyl donor... 

Figure 13.50 outlines how esters in general (not shown) and especially lactones (shown) can be prepared for a one-step aldol condensation with an aldehyde they are exposed to a mixed ( crossed ) Claisen condensation with formic acid methyl ester (cf. Figure 13.59, first line). Like all Claisen condensations (Section 13.5.1), this also first leads to the formation of the enolate of the acylated ester. Unlike other Claisen condensations, this enolate is isolated. 

Fig. 13.60. Crossed ester condensation via acylation of a quantitatively prepared ester enolate. Three equivalents of ester enolate must be employed because the acylating ester contains a free OH group with an acidic H atom one for the deprotonation of the OH group of the substrate, one for the substitution of the MeO group, and one for the transformation of the C,H-acidic substitution product into an enolate.

A different cyclization leads to the flavones and anthocyanidins. Reaction of the stable enol from a 1,3-diketone with the thiol ester as electrophile results in acylation at carbon in the manner of the Claisen ester condensation (Chapter 28) with loss of CoASH and the formation of a trihydroxyben-zene ring. 

The first step is the Claisen ester condensation of two molecules of acetyl CoA, one acting as an enol and the other as an electrophilic acylating agent to give acetoacetyl CoA. We saw the same reaction in the biosynthesis of the pyrrolidine alkaloids earlier in this chapter. 

If the acylating ester is capable of undergoing self-condensation in the presence of sodium ethoxide, sodium triphenylmethide is substituted for the latter. An example is the reaction of acetonitrile with ethyl -butyrate to give n-butyrylacetonitrile (52%). ... 

The over-all yields (R equals w-C,-Q, -C , and -C ) from the esters vary from 55% to 78%. Certain heterocyclic ketones, namely, 8-acetyl-quinoline and /3-acetylpyridine, have been prepared through a mixed ester condensation. (3) If acetoacetic ester is acylated in the form of its sodium enolate and carefully hydrolyzed, a new /3-keto ester is formed. Alkylation of this keto ester followed by hydrolysis gives ketones of the type RCOCH,R. ... 

The acylation of RLi or RMgBr by nitriles (cyanides) is an effective way to make ketones (Chapr and here we see the cyanide version of an intramolecular Claisen ester condensation. One cy-makes an enolate , which attacks the other. The resulting imine tautomerizes to the coni. . enamino nitrile. 

O. R. 1-9, C. R. Hauser and B. E. Hudson, Jr., The Acctoacetic Ester Condensation and Related Reactions lV-4, S. M. McElvain, The Acyloins 11-4, W. S. Johnson, The Formation of Cyclic Ketones by Intramolecular Acylation VIII-2, D. A. Shirley, The Synthesis of Ketones from Acid Chlorides and Organometallic Compounds of Magnesium, Zinc, and Cadmium. ... 

Tritylpotassium. (CeHslaCK (deep red). In one method the reagent is prepared by reaction of triphenylmethane with potassium in liquid ammonia and replacement of the ammonia by ether to give a suspension of the reagent and provide a medium suitable for acylations, alkylations, and carbonations. Tritylsodium also can be prepared from triphenylmethane in the same way, but it is destroyed when the ammonia is replaced by ether the preparation of an ethereal solution from trityl chloride and sodium takes considerably longer than the preparation of tritylpotassium from triphenylmethane. Moreover, triphenylmethane is recoverable in good yield from a condensation in a form suitable for reuse. Typical reactions utilizing tritylpotassium are an ester condensation (1 ), an acylation (2 ), an alkylation (3 ), and a carbonylation (4 ). 

Likewise, the mechanism of nucleophilic addition to the carbonyl group of aldehydes and ketones described in Chapter 17 sets the stage for aldol condensation in Chapter 18, esterification of carboxylic acids in Chapter 19, nucleophilic acyl substitution in Chapter 20, and ester condensation in Chapter 21. 

Further persuasive evidence in support of the expectation that the mechanism of the ECH-catalyzed reaction involves an Elcb mechanism with a stabilized thioester enolate anion intermediate is obtained from the membership of ECH in the mechanistically diverse enoyl-CoA hydratase superfamily [70]. Such superfamilies are derived from a common ancestor by divergent evolution the members of these share a partial reaction, usually formation of a common intermediate, e.g., an enolate anion. The reactions catalyzed by members of the enoyl-CoA hydratase superfamily (almost) always utilize acyl esters of CoA as substrates the reactions invariably can be rationalized with mechanisms that involve the formation of a thioester enolate anion intermediate, e.g., 1,3-proton transfer, 1,5-proton transfer, Dieckman and reverse Dieckman condensations, and yS-decarboxylation. Although mechanisms with thioester enolate anion intermediates are plausible for each of these reactions, as in the ECH-catalyzed reaction, evidence for their existence on the reaction coordinate is circumstantial because the intermediates do not accumulate, thereby avoiding spectroscopic detection. 

For /f-oxo esters, condensations with pyrimidine-4,6-diamines237 and -2,4,6-triamines238 539,540,569 are realised upon heating in iV-methylpyrrolidonc or diphenyl ether. The observed orientation is the consequence of the first step being an acylation of the 6-amino group by the ester, the subsequent cyclization yielding the 7-oxo compounds 16. 

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