The malonic ester synthesis is a

chemical reaction A chemical reaction is a process that leads to the chemical transformation of one set of chemical substances to another. Classically, chemical reactions encompass changes that only involve the positions of electrons in the forming and breaking ...

where diethyl malonate or another

ester In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides ...

malonic acid Malonic acid (IUPAC systematic name: propanedioic acid) is a dicarboxylic acid with structure CH2(COOH)2. The ionized form of malonic acid, as well as its esters and salts, are known as malonates. For example, diethyl malonate is malonic acid' ...

is alkylated at the carbon

alpha Alpha (uppercase , lowercase ; grc, ἄλφα, ''álpha'', or ell, άλφα, álfa) is the first letter of the Greek alphabet. In the system of Greek numerals, it has a value of one. Alpha is derived from the Phoenician letter aleph , whi ...

(directly adjacent) to both

carbonyl In organic chemistry, a carbonyl group is a functional group composed of a carbon atom double-bonded to an oxygen atom: C=O. It is common to several classes of organic compounds, as part of many larger functional groups. A compound containi ...

groups, and then converted to a substituted

acetic acid Acetic acid , systematically named ethanoic acid , is an acidic, colourless liquid and organic compound with the chemical formula (also written as , , or ). Vinegar is at least 4% acetic acid by volume, making acetic acid the main componen ...

. The major drawback of malonic ester synthesis is that the alkylation stage can also produce dialkylated structures. This makes separation of products difficult and yields lower. :

Mechanism

The carbons alpha to

carbonyl group In organic chemistry, a carbonyl group is a functional group composed of a carbon atom double-bonded to an oxygen atom: C=O. It is common to several classes of organic compounds, as part of many larger functional groups. A compound containi ...

s can be deprotonated by a strong base. The carbanion formed can undergo

nucleophilic substitution In chemistry, a nucleophilic substitution is a class of chemical reactions in which an electron-rich chemical species (known as a nucleophile) replaces a functional group within another electron-deficient molecule (known as the electrophile). The ...

on the alkyl halide, to give the alkylated compound. On heating, the di-ester undergoes thermal decarboxylation, yielding an acetic acid substituted by the appropriate R group. Thus, the malonic ester can be thought of being equivalent to the ⁻CH₂COOH

synthon In retrosynthetic analysis, a synthon is a hypothetical unit within a target molecule that represents a potential starting reagent in the retroactive synthesis of that target molecule. The term was coined in 1967 by E. J. Corey. He noted in 1 ...

. The esters chosen are usually the same as the base used, i.e. ethyl esters with sodium ethoxide. This is to prevent scrambling by

transesterification In organic chemistry, transesterification is the process of exchanging the organic group R″ of an ester with the organic group R' of an alcohol. These reactions are often catalyzed by the addition of an acid or base catalyst. The reaction ca ...

Variations

Dialkylation

The ester may be dialkylated if

deprotonation Deprotonation (or dehydronation) is the removal (transfer) of a proton (or hydron, or hydrogen cation), (H+) from a Brønsted–Lowry acid in an acid–base reaction.Henry Jakubowski, Biochemistry Online Chapter 2A3, https://employees.csbsju. ...

and alkylation are repeated before the addition of aqueous acid.

Cycloalkylcarboxylic acid synthesis

Intramolecular malonic ester synthesis occurs when reacted with a dihalide. This reaction is also called the Perkin alicyclic synthesis (see:

alicyclic compound In organic chemistry, an alicyclic compound contains one or more all-carbon rings which may be either saturated or unsaturated, but do not have aromatic character. Alicyclic compounds may have one or more aliphatic side chains attached. The s ...

) after investigator William Henry Perkin, Jr.''Ueber die Einwirkung von Trimethylenbromid auf Acetessigäther, Benzoylessigäther und Malonsäureäther'' W. H. Perkin Jun.

Berichte der deutschen chemischen Gesellschaft ''Chemische Berichte'' (usually abbreviated as ''Ber.'' or ''Chem. Ber.'') was a German-language scientific journal of all disciplines of chemistry founded in 1868. It was one of the oldest scientific journals in chemistry, until it merged with ...

Volume 16 Issue 2, Pages 1787–97 1883

Application

In the manufacture of medicines, malonic ester is used for the synthesis of

barbiturates Barbiturates are a class of depressant drugs that are chemically derived from barbituric acid. They are effective when used medically as anxiolytics, hypnotics, and anticonvulsants, but have physical and psychological addiction potential as we ...

, as well as sedatives and anticonvulsants. Used in organic synthesis. Аs a flavoring agent in the food industry.

References