Malonic ester synthesis of substituted acetic acids

Malonic Ester Synthesis of Substituted Acetic Acids... 

A MECHANISM FOR THE REACTION ] The Malonic Ester Synthesis of Substituted Acetic Acids 840... 

Synthesis of substituted acetic acid via malonic ester Malonic ester is an ester formed by reacting an alcohol with malonic acid (propanedicarboxylic acid). Following is the structure of diethyl malonate ... 

Synthesis of substituted acetic acids via acetoacetic ester... 146 Synthesis of substituted acetic acid via malonic ester. .. 150 a halo acids, a hydroxy acids, and a, (3 unsaturated acids.. .153... 

SYNTHESIS OF SUBSTITUTED ACETIC ACIDS THE MALONIC ESTER SYNTHESIS... 

MALONIC ESTER SYNTHESIS OF R-SUBSTITUTED ACETIC ACIDS,... 

The malonic ester synthesis makes substituted derivatives of acetic acid. Malonic ester (diethyl malonate) is alkylated or acylated on the more acidic carbon that is a to both carbonyl groups, and the resulting derivative is hydrolyzed and allowed to decarboxylate. 

MALONIC ESTER SYNTHESIS OF R-SUBSTITUTED ACETIC ACIDS, RCH2COOH OR R(R ) CHCOOH (R could R)... 

The malonic ester synthesis makes substituted derivatives of acetic acid. Malonic... 

The synthetic importance of the malonic ester synthesis follows from the fact that the substituted malonic ester can easily be hydrolyzed, and subsequently decarboxylates to yield a substituted acetic acid 9. This route to substituted acetic acids is an important method in organic synthesis ... 

Malonic esters have two ester groups, each of which may react as in the acetoacetic ester synthesis due to their similar structure (see the preceding section). The malonic ester synthesis provides a method for preparing a substituted acetic acid. Figure 15-14 shows the structure of one type of malonic ester. Figure 15-15 outlines the basic malonic ester synthesis. May repeat in that figure refers to the reaction with a second molecule of RX (or R X). 

The product of a malonic ester synthesis is a substituted acetic acid, with the substituent being the group used to alkylate malonic ester. In effect, the second carboxyl group is temporary, allowing the ester to be easily deprotonated and alkylated. Hydrolysis and decarboxylation remove the temporary carboxyl group, leaving the substituted acetic acid. 

The malonic ester synthesis converts a primary or secondary alkyl halide into a carboxylic acid with two more carbons (a substituted acetic acid). Identify the component that originates from malonic ester (the acid component). The rest of the molecule comes from the alkyl halide, which should be primary or methyl. 

Certain acid derivatives are capable of reactions involving intermediate carbanions. The malonic ester synthesis is used to synthesize substituted acetic acids. The reaction involves abstraction of... 

Hell-Volhard-Zelinsky (HVZ) reaction Reaction of a carboxylic acid with Br2 and PBr3 to give an a-bromo acyl bromide, often hydrolyzed to an a-bromo acid. (p. 1051) malonic ester synthesis Alkylation or acylation of malonic ester (diethyl malonate), followed by hydrolysis and decarboxylation, to give substituted acetic acids, (p. 1076)... 

Two specific j8-dicarbonyl compounds have had broad use in organic synthesis. These are acetoacetic ester (ethyl acetoacetate, ethyl 3-oxobutanoate), which can be used to make substituted acetone derivatives, and diethyl malonate (diethyl 1,3-propanedicarboxylic acid), which can be used to make substituted acetic acid derivatives. We shall consider syntheses involving ethyl acetoacetate and diethyl malonate in the upcoming sections of this chapter. 

When this reaction is carried out on the parent diethyl malonate, acetic acid results, and the process is of no practical synthetic utility. As with the synthesis of ketones starting from P-keto esters, this process is far more usefiil when combined with the alkylation reaction. One or two alkylations of malonic ester give substituted diesters that can be hydrolyzed and decarboxylated to give carboxylic acids (Fig. 19.62). Substituted acetic acids are potential sources of esters, acid halides, and any other compound that can be made from a carboxylic acid. 

What is needed in the synthesis of C is a two-carbon nucleophile (or its equivalent) which is less basic titan an enolate so elimination is not competitive. If product C is recognized as an acetic acid derivative, then the following analysis can be made. A malonate ion used as the carbon nucleophile is much less basic than a simple ester enolate and hence undergoes substitution readily but does not promote elimination effectively, particularly in secondary systems. 

More recently. Prelog (194) has described an ingenious synthesis of quinuclidine, also adapted to the preparation of 2-ethylquinuclidine (195), which empiloys tetrahydropyranol (CLII) (196) as starting material. The substance was first converted into the corresponding benzene-sulfonyl derivative (CLIII), which was then treated with sodiomalonic ester. Hydrolysis and decarboxylation of the resulting substituted malonate afforded tetrahydropyranyl-4-acetic acid (CLIV). Bouveault... 

The introduction of a p-oxazilinyl substituent into the aromatic ring of the arylacetal anions (23) stabilizes the anions and allows them to be used as acyl anion equivalents. Bis(ethylthio)acetic acid is a new a-keto-acid synthon. Its dianion reacts with a variety of electrophiles, including aziridines, to give substituted a-keto-acids in fair to excellent yields after deprotection. In two syntheses of /8-keto-acids, R COCl is used as the source of the acyl group. In the first synthesis the dianion of the ethyl ester of malonic acid reacts with R COCl to give... 

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