Names | |
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IUPAC name Diethyl malonate [1] | |
Preferred IUPAC name Diethyl propanedioate | |
Other names Diethyl malonate | |
Identifiers | |
3D model (JSmol) | |
Abbreviations | DEM |
774687 | |
ChEBI | |
ChEMBL | |
ChemSpider | |
ECHA InfoCard | 100.003.006 |
EC Number |
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MeSH | Diethyl+malonate |
PubChem CID | |
RTECS number |
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UNII | |
CompTox Dashboard (EPA) | |
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Properties | |
C7H12O4 | |
Molar mass | 160.17 g/mol |
Appearance | colourless liquid |
Density | 1.05 g/cm3, liquid |
Melting point | −50 °C (−58 °F; 223 K) |
Boiling point | 199 °C (390 °F; 472 K) |
negligible | |
Acidity (pKa) | 14 16.37 (DMSO) [2] |
-92.6·10−6 cm3/mol | |
Structure | |
2.54 D (liquid) [3] | |
Thermochemistry | |
Heat capacity (C) | 285.0 J·mol−1·K−1 [3] |
Hazards | |
Occupational safety and health (OHS/OSH): | |
Main hazards | Harmful (X), Flammable (F) |
Flash point | 93 °C (199 °F; 366 K) [3] |
Safety data sheet (SDS) | Oxford University MSDS |
Related compounds | |
Related compounds | Dimethyl malonate Malonic acid |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). |
Diethyl malonate, also known as DEM, is the diethyl ester of malonic acid. It occurs naturally in grapes and strawberries as a colourless liquid with an apple-like odour, and is used in perfumes. It is also used to synthesize other compounds such as barbiturates, artificial flavourings, vitamin B1, and vitamin B6.
Malonic acid is a rather simple dicarboxylic acid, with two carboxyl groups close together. In forming diethyl malonate from malonic acid, the hydroxyl group (−OH) on both of the carboxyl groups is replaced by an ethoxy group (−OEt; −OCH2CH3). The methylene group (−CH2−) in the middle of the malonic part of the diethyl malonate molecule is neighboured by two carbonyl groups (−C(=O)−). [4]
The hydrogen atoms on the carbon adjacent to the carbonyl group in a molecule is significantly more acidic than hydrogen atoms on a carbon adjacent to alkyl groups (up to 30 orders of magnitude). (This is known as the α position with respect to the carbonyl.) The hydrogen atoms on a carbon adjacent to two carbonyl groups are even more acidic because the carbonyl groups help stabilize the carbanion resulting from the removal of a proton from the methylene group between them. The extent of resonance stabilization of this compound's conjugate base is suggested by the three resonance forms below:
Diethyl malonate is produced from the reaction of the sodium salt of chloroacetic acid with sodium cyanide, which produces the nitrile. This intermediate is then treated with ethanol in the presence of acid catalyst:
Alternatively, sodium chloroacetate undergoes carboxyesterification by treatment with carbon monoxide and ethanol:
Dicobalt octacarbonyl is employed as the catalyst. [5]
One of the principal uses of this compound is in the malonic ester synthesis. The carbanion (2) formed by reacting diethyl malonate (1) with a suitable base can be alkylated with a suitable electrophile. This alkylated 1,3-dicarbonyl compound (3) readily undergoes decarboxylation with loss of carbon dioxide, to give a substituted acetic acid (4):
In general, salts of the alkoxide anion whose alkyl part corresponds to the one used in the above alkylation are preferred as the base. The use of a conventional base may give base hydrolysis products – for example, sodium hydroxide would simply produce sodium malonate and the alcohol, while other alkoxide salts will cause scrambling by transesterification. Only the "same" alkoxide anion as the one that one used to alkylate the deprotonated active methylenic site will prevent both base hydrolysis and transesterification.
Like many other esters, this compound undergoes the Claisen ester condensations. The advantage of using this compound is that unwanted self-condensation reactions are avoided. Like other esters, this compound undergoes bromination at the alpha position. [6]
Diethyl malonate can be nitrosated with excess sodium nitrite in acetic acid to afford diethyl oximinomalonate, catalytic hydrogenolysis of which in ethanol over Pd/C affords diethyl aminomalonate (DEAM). DEAM can be acetylated to produce diethyl acetamidomalonate (useful in amino-acid synthesis), or can be added with 3-substituted 2,4-diketones to boiling acetic acid to afford in maximal yield variously substituted ethyl pyrrole-2-carboxylates of interest for porphyrin synthesis. [7]
Diethyl malonate is used in the preparation of several medicinally useful compounds including vigabatrin, phenylbutazone, nalidixic acid, and rebamipide. Several pesticides are also produced from diethylmalonate, including sethoxydim and the derivatives of 2-amino-4-chloro-6-methoxypyrimidine. [5]
In chemistry, an ester is a compound derived from an acid in which the hydrogen atom (H) of at least one acidic hydroxyl group of that acid is replaced by an organyl group. Analogues derived from oxygen replaced by other chalcogens belong to the ester category as well. According to some authors, organyl derivatives of acidic hydrogen of other acids are esters as well, but not according to the IUPAC.
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's diethyl ester. The name originates from the Greek word μᾶλον (malon) meaning 'apple'.
Ethyl acetate is the organic compound with the formula CH3CO2CH2CH3, simplified to C4H8O2. This colorless liquid has a characteristic sweet smell and is used in glues, nail polish removers, and in the decaffeination process of tea and coffee. Ethyl acetate is the ester of ethanol and acetic acid; it is manufactured on a large scale for use as a solvent.
In organic chemistry, the Michael reaction or Michael 1,4 addition is a reaction between a Michael donor and a Michael acceptor to produce a Michael adduct by creating a carbon-carbon bond at the acceptor's β-carbon. It belongs to the larger class of conjugate additions and is widely used for the mild formation of carbon-carbon bonds.
In organic chemistry, the Knoevenagel condensation reaction is a type of chemical reaction named after German chemist Emil Knoevenagel. It is a modification of the aldol condensation.
The Claisen condensation is a carbon–carbon bond forming reaction that occurs between two esters or one ester and another carbonyl compound in the presence of a strong base. The reaction produces a β-keto ester or a β-diketone. It is named after Rainer Ludwig Claisen, who first published his work on the reaction in 1887. The reaction has often been displaced by diketene-based chemistry, which affords acetoacetic esters.
Meldrum's acid or 2,2-dimethyl-1,3-dioxane-4,6-dione is an organic compound with formula C6H8O4. Its molecule has a heterocyclic core with four carbon and two oxygen atoms; the formula can also be written as [−O−(C 2)−O−(C=O)−(CH2)−(C=O)−].
The Knorr pyrrole synthesis is a widely used chemical reaction that synthesizes substituted pyrroles (3). The method involves the reaction of an α-amino-ketone (1) and a compound containing an electron-withdrawing group α to a carbonyl group (2).
Sodium ethoxide, also referred to as sodium ethanolate, is the ionic, organic compound with the formula CH3CH2ONa, C2H5ONa, or NaOEt. It is a white solid, although impure samples appear yellow or brown. It dissolves in polar solvents such as ethanol. It is commonly used as a strong base.
The organic compound ethyl acetoacetate (EAA) is the ethyl ester of acetoacetic acid. It is a colorless liquid. It is widely used as a chemical intermediate in the production of a wide variety of compounds. It is used as a flavoring for food.
Nucleophilic acyl substitution describes a class of substitution reactions involving nucleophiles and acyl compounds. In this type of reaction, a nucleophile – such as an alcohol, amine, or enolate – displaces the leaving group of an acyl derivative – such as an acid halide, anhydride, or ester. The resulting product is a carbonyl-containing compound in which the nucleophile has taken the place of the leaving group present in the original acyl derivative. Because acyl derivatives react with a wide variety of nucleophiles, and because the product can depend on the particular type of acyl derivative and nucleophile involved, nucleophilic acyl substitution reactions can be used to synthesize a variety of different products.
Triethyl orthoformate is an organic compound with the formula HC(OC2H5)3. This colorless volatile liquid, the ortho ester of formic acid, is commercially available. The industrial synthesis is from hydrogen cyanide and ethanol.
The malonic ester synthesis is a chemical reaction where diethyl malonate or another ester of malonic acid is alkylated at the carbon alpha to both carbonyl groups, and then converted to a substituted acetic acid.
Acetoacetic ester synthesis is a chemical reaction where ethyl acetoacetate is alkylated at the α-carbon to both carbonyl groups and then converted into a ketone, or more specifically an α-substituted acetone. This is very similar to malonic ester synthesis.
Potassium ethoxide, also known as potassium ethanolate, is an off-white or yellow powder with the chemical formula of C2H5KO. Potassium ethoxide contains an ethoxide ion, the conjugate base of ethanol, which makes this compounds strongly basic. It hydrolyzes to yield ethanol and potassium hydroxide.
Cyanoacetic acid is an organic compound. It is a white, hygroscopic solid. The compound contains two functional groups, a nitrile (−C≡N) and a carboxylic acid. It is a precursor to cyanoacrylates, components of adhesives.
Ethyl cyanoacetate is an organic compound that contains a carboxylate ester and a nitrile. It is a colourless liquid with a pleasant odor. This material is useful as a starting material for synthesis due to its variety of functional groups and chemical reactivity.
Diethyl phosphite is the organophosphorus compound with the formula (C2H5O)2P(O)H. It is a popular reagent for generating other organophosphorus compounds, exploiting the high reactivity of the P-H bond. Diethyl phosphite is a colorless liquid. The molecule is tetrahedral.
Diethyl oxomalonate is the diethyl ester of mesoxalic acid (ketomalonic acid), the simplest oxodicarboxylic acid and thus the first member (n = 0) of a homologous series HOOC–CO–(CH2)n–COOH with the higher homologues oxalacetic acid (n = 1), α-ketoglutaric acid (n = 2) and α-ketoadipic acid (n = 3) (the latter a metabolite of the amino acid lysine). Diethyl oxomalonate reacts because of its highly polarized keto group as electrophile in addition reactions and is a highly active reactant in pericyclic reactions such as the Diels-Alder reactions, cycloadditions or ene reactions. At humid air, mesoxalic acid diethyl ester reacts with water to give diethyl mesoxalate hydrate and the green-yellow oil are spontaneously converted to white crystals.
Diethyl acetamidomalonate (DEAM) is a derivative of malonic acid diethyl ester. Formally, it is derived through the acetylation of ester from the unstable aminomalonic acid. DEAM serves as a starting material for racemates including both, natural and unnatural α-amino acids or hydroxycarboxylic acids. It is also usable as a precursor in pharmaceutical formulations, particularly in the cases of active ingredients like fingolimod, which is used to treat multiple sclerosis.
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