Carboxylic esters, acetoacetic

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 ... 

One route to o-nitrobenzyl ketones is by acylation of carbon nucleophiles by o-nitrophenylacetyl chloride. This reaction has been applied to such nucleophiles as diethyl malonatc[l], methyl acetoacetate[2], Meldrum s acid[3] and enamines[4]. The procedure given below for ethyl indole-2-acetate is a good example of this methodology. Acylation of u-nitrobenzyl anions, as illustrated by the reaction with diethyl oxalate in the classic Reissert procedure for preparing indolc-2-carboxylate esters[5], is another route to o-nitrobenzyl ketones. The o-nitrophenyl enamines generated in the first step of the Leimgruber-Batcho synthesis (see Section 2.1) are also potential substrates for C-acylation[6,7], Deformylation and reduction leads to 2-sub-stituted indoles. 

Carboxylic esters 1 that have an a-hydrogen can undergo a condensation reaction upon treatment with a strong base to yield a /3-keto ester 2. This reaction is called the Claisen ester condensation or acetoacetic ester condensation, the corresponding intramolecular reaction is called the Dieckmann condensation ... 

It is obvious that many carboxylic acids of the formulas RCH2COOH and RR CHCOOH can be synthesized by this method (for some other ways of preparing such acids, see 10-106, 10-108, and 10-109). Another important example is the acetoacetic ester synthesis, in which Z is COOEt and Z is COCH3. In this case the product can be decarboxylated with acid or dilute base (12-38) to give a ketone or cleaved with concentrated base (12-41) to give a carboxylic ester and a salt of acetic acid ... 

The alkylation of activated halogen compounds is one of several reactions of trialkylboranes developed by Brown (see also 15-16,15-25,18-31-18-40, etc.). These compounds are extremely versatile and can be used for the preparation of many types of compounds. In this reaction, for example, an alkene (through the BR3 prepared from it) can be coupled to a ketone, a nitrile, a carboxylic ester, or a sulfonyl derivative. Note that this is still another indirect way to alkylate a ketone (see 10-105) or a carboxylic acid (see 10-106), and provides an additional alternative to the malonic ester and acetoacetic ester syntheses (10-104). 

The Mechanism of the Ethyl Acetoacetate Synthesis—Before the tautomerism of ethyl acetoacetate is discussed we must consider the mechanism of its formation, which for decades has been the subject of lively discussion and was conclusively explained only in recent years (Scheibler). It has been found that even the C=0-group of the simple carboxylic esters, although in other respects inferior in activity to the true carbonyl group, can be enolised by alkali metals. Thus ethyl acetate is converted by potassium into the potassium salt of the tautomeric enol with evolution of hydrogen ... 

Plant. In plants, mevinphos is hydrolyzed to phosphoric acid dimethyl ester, phosphoric acid, and other less toxic compounds (Hartley and Kidd, 1987). In one day, the compound is almost completely degraded in plants (Cremlyn, 1991). Casida et al. (1956) proposed two degradative pathways of mevinphos in bean plants and cabbage. In the first degradative pathway, cleavage of the vinyl phosphate bond affords methylacetoacetate and acetoacetic acid, which may be precursors to the formation of the end products dimethyl phosphoric acid, methanol, acetone, and carbon dioxide. In the other degradative pathway, direct hydrolysis of the carboxylic ester would yield vinyl phosphates as intermediates. The half-life of mevinphos in bean plants was 0.5 d (Casida et ah, 1956). In alfalfa, the half-life was 17 h (Huddelston and Gyrisco, 1961). 

Molecules in which the enolic double bond is in conjugation with another double bond. Some of these are shown in Table 2.1. As the table shows, carboxylic esters have a much smaller enolic content than ketones. In molecules like acetoacetic ester, the enol is also stabilized by internal hydrogen bonding, which is unavailable to the keto form ... 

Keywords ethyl acetoacetate, o-phenylendianiine, acid cleavage, decarboxylation, carboxylic ester... 

Among procedures for the synthesis of 1,7-naphthyridines, four-component condensation of l-benzyl-3-hydroxy-5-piperidone 101 with 2,3-dichloro-6-fluorobenz-aldehyde, acetoacetic esters and ammonium acetate giving rise to 1,4,5,6,7-hexahydro-l,7-naphtyridin-5-one-3-carboxylic esters 102 attracts attention due to its simplicity. The compounds 102 and their N-debenzylation products 103 exhibit hypotensive activity (1985USP4596873, 1985USP4618678). 

The compound containing the active methylene group is first converted in tetrahydrofuran solution into its sodium salt by means of sodium hydride, then a two- to three-fold excess of acetone cyanohydrin nitrate is added and the whole is boiled for 2 h under reflux. Substituted acetoacetic and malonic esters thus give good yields of a-nitro carboxylic esters. 

DONORS. Acetoacetates Aldehydes Carboxylic esters Cyanoacetates Ketones Malonates Nitriles Nitro compounds and Sulfones. 

Acetoacetic ester s. a. / -Keto-carboxylic acid esters Acetoacetic esters... 

In 1991, Wright et al. reported a procedure for the preparation of substituted 1-benzyl-1//-1,2,3-triazoles 21 and 23 from benzyl azides 20 under very mild conditions (Scheme 4.7) [9]. Benzyl azides 20 reacted with active methylene compounds in DMSO induced by potassium carbonate at 35-40 C to give 1-benzyl-1//-1,2,3-triazoles 21 and 23 usually in good yield. Acetonitrile derivatives 10 gave 5-amino-l-benzyl-l//-l,2,3-triazoles 21, whereas diethyl malonate gave 5-hydroxy-l-benzyl-l//-l,2,3-triazoles. l//-l,2,3-Triazole-4-carboxylate esters and l//-l,2,3-triazole-4-ketones were obtained from ethyl acetoacetate and P-diketones, respectively. Benzyl methyl ketone reacted to give a 5-methyl-4-phenyl-l//-l,2,3-triazole, but acetone and acetophenone failed to react. Other active methylene compounds that did not react under these reaction conditions included ethyl cyanoacetate, ethyl fluoroacetate, and ethyl nitroacetate. 

By the ketonic hydrolysis of substituted acetoacetic esters this is brought about by the action of dilute alkali in the cold, followed by acidification and boiling. The free substituted acetoacetic acid is produced, which readily undergoes decarboxylation (since it has a carboxyl and a carbonyl group on the same carbon atom) to give a ketone, for example ... 

Section 21 7 The malonic ester synthesis is related to the acetoacetic ester synthesis Alkyl halides (RX) are converted to carboxylic acids of the type RCH2COOH by reaction with the enolate ion derived from diethyl mal onate followed by saponification and decarboxylation... 

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