Diethyl malonate

Diethyl malonate

Names
IUPAC name Diethyl malonate[1]
Preferred IUPAC name Diethyl propanedioate
Other names Diethyl malonate
Identifiers
CAS Number	105-53-3 Y
3D model (JSmol)	Interactive image
Abbreviations	DEM
Beilstein Reference	774687
ChEBI	CHEBI:391281 N
ChEMBL	ChEMBL177114 Y
ChemSpider	13863636 Y
ECHA InfoCard	100.003.006
EC Number	203-305-9
MeSH	Diethyl+malonate
PubChem CID	7761
RTECS number	OO0700000
UNII	53A58PA183 Y
CompTox Dashboard (EPA)	DTXSID7021863
InChI InChI=1S/C7H12O4/c1-3-10-6(8)5-7(9)11-4-2/h3-5H2,1-2H3 Y Key: IYXGSMUGOJNHAZ-UHFFFAOYSA-N Y InChI=1/C7H12O4/c1-3-10-6(8)5-7(9)11-4-2/h3-5H2,1-2H3 Key: IYXGSMUGOJNHAZ-UHFFFAOYAC
SMILES O=C(OCC)CC(=O)OCC
Properties
Chemical formula	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)
Solubility in water	negligible
Acidity (pKa)	14 16.37 (DMSO)[2]
Magnetic susceptibility (χ)	-92.6·10−6 cm3/mol
Structure
Dipole moment	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). N verify (what is YN ?) Infobox references

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:

ClCH₂CO₂Na + NaCN → NCCH₂CO₂Na + NaCl

NCCH₂CO₂Na + 2 C₂H₅OH + 2 HCl → C₂H₅O₂CCH₂CO₂C₂H₅ + NH₄Cl + NaCl

Alternatively, sodium chloroacetate undergoes carboxyesterification by treatment with carbon monoxide and ethanol:

ClCH₂CO₂Na + CO + 2 C₂H₅OH → C₂H₅O₂CCH₂CO₂C₂H₅ + NaCl

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]