Diethyl Malonate (105-53-3) Physical and Chemical Properties
Diethyl Malonate
A common malonate ester used as a C3 building block in fine chemical and pharmaceutical synthesis for formulation and organic synthesis workflows.
| CAS Number | 105-53-3 |
| Family | Malonate esters (diesters) |
| Typical Form | Colorless liquid |
| Common Grades | EP, FCC, JP, Reagent Grade, USP |
Diethyl malonate is a simple aliphatic diester — the diethyl ester of malonic (propanedioic) acid — belonging to the malonate ester structural class. The molecule contains two ester carbonyl groups flanking a methylene (—CH2—) unit; this activated methylene is the characteristic functional handle for enolate chemistry. Structurally it is neutral, moderately polar (topological polar surface area \(=52.6\)), and compact (\(\mathrm{C}7\mathrm{H}_4\), molecular weight \(160.17\)). Electronic features include two carbonyl π-systems (strong electron-withdrawing relative to the central methylene) and four hydrogen-bond acceptor sites (the two carbonyl oxygens and two ester oxygens), with no hydrogen-bond donors.}\mathrm{O
Chemically, diethyl malonate behaves as a readily enolizable ester: the central methylene hydrogen atoms are acidified relative to typical aliphatic C–H bonds and are deprotonated by common bases to give stabilized enolates used in C–C bond-forming reactions (alkylations, condensations, Michael additions). It is susceptible to hydrolysis (chemical and enzymatic) to give ethanol and malonic acid; hydrolysis rate increases under neutral-to-basic conditions and can be catalyzed by esterase-type enzymes. Physically it is a colorless, fruity-ester‑odour liquid with moderate volatility and limited water solubility compared with lower esters but good solubility in many organic solvents, which makes it a versatile intermediate and solvent/modifier in synthetic workflows.
Diethyl malonate is widely used industrially as a synthetic intermediate in the production of barbiturates, pharmaceuticals, agrochemicals, vitamins, dyes and fragrances, and is also employed as a flavoring/fragrance ingredient in low concentrations. Common commercial grades reported for this substance include: EP, FCC, JP, Reagent Grade, USP.
Basic Physical Properties
Density
Reported experimental densities at ambient temperature include:
- \(1.0551\ \mathrm{g}\,\mathrm{cm}^{-3}\) at \(20\,^\circ\mathrm{C}\).
- \(1.06\ \mathrm{g}\,\mathrm{cm}^{-3}\) (at \(20\,^\circ\mathrm{C}\)).
- A measured range \(1.053\text{–}1.056\ \mathrm{g}\,\mathrm{cm}^{-3}\).
These values are consistent with an oxygen-rich organic liquid whose molecular packing yields a density slightly above water at room temperature.
Melting Point
- Reported melting point: \(-50\,^\circ\mathrm{C}\).
No additional experimentally established solid‑state thermal phase data are available in the current data context.
Boiling Point
Reported boiling points:
- \(200\,^\circ\mathrm{C}\).
- \(199.00\text{ to }200.00\,^\circ\mathrm{C}\) at \(760.00\ \mathrm{mm Hg}\).
- \(199\,^\circ\mathrm{C}\) (alternate report).
The high normal boiling point reflects the molecular weight and intermolecular polar interactions associated with two ester groups.
Vapor Pressure
Available vapor pressure data:
- \(0.26\ \mathrm{mm Hg}\) (unspecified temperature).
- \(0.19\ \mathrm{mm Hg}\) at \(25\,^\circ\mathrm{C}\).
- Vapor pressure expressed in SI: \(36\ \mathrm{Pa}\) at \(25\,^\circ\mathrm{C}\).
The vapor pressure values indicate moderate volatility at ambient temperatures, consistent with observed atmospheric half‑life estimates for related esters.
Flash Point
Reported flash/ignition data:
- \(200\,^\circ\mathrm{F}\) (\(93\,^\circ\mathrm{C}\)) (open cup).
- \(85\,^\circ\mathrm{C}\) (closed cup).
Diethyl malonate is combustible; keep away from ignition sources and follow appropriate flammable‑liquid controls.
Chemical Properties
Solubility and Phase Behavior
Quantitative and qualitative solubility data:
- Water solubility: \(20\ \mathrm{g}\,\mathrm{L}^{-1}\) at \(20\,^\circ\mathrm{C}\) (moderate).
- \(23.2\ \mathrm{mg}\,\mathrm{mL}^{-1}\) at \(37\,^\circ\mathrm{C}\) (equivalent to \(\sim23.2\ \mathrm{g}\,\mathrm{L}^{-1}\)).
- Miscible/soluble in ethanol and diethyl ether; very soluble in acetone and benzene; soluble in chloroform; soluble in many fixed oils and propylene glycol; reported as insoluble in glycerin and mineral oil at \(200\,^\circ\mathrm{C}\) in one source.
Taken together, diethyl malonate is moderately water‑soluble and highly soluble in common organic solvents, which facilitates its handling as a reagent and intermediate in homogeneous organic reactions and formulations.
Reactivity and Stability
- Hydrolysis: chemical and enzymatic hydrolysis yields ethanol and malonic acid; hydrolysis is accelerated under neutral-to-basic conditions. Enzymes such as adipose‑tissue lipase and proteases (e.g., alpha‑chymotrypsin to monoester) can catalyze this transformation.
- Incompatibilities: reacts with oxidizing materials; avoid contact with strong acids, strong bases, and strong reducing agents under uncontrolled conditions.
- Thermal decomposition: on heating to decomposition emits carbon oxides and acrid/irritating fumes. Reported autoignition temperature: \(435\,^\circ\mathrm{C}\).
- Stability: described as stable under recommended storage conditions (cool, dry, ventilated, tightly closed container).
Reactivity with bases (enolate formation) is the basis for its primary synthetic utility; hydrolysis must be controlled in processes where the ester functionality must be preserved.
Thermodynamic Data
Standard Enthalpies and Heat Capacity
- Heat (enthalpy) of vaporization: \(64.7\ \mathrm{kJ}\,\mathrm{mol}^{-1}\).
No experimentally established values for the standard enthalpy of formation or isobaric heat capacity (\(C_p\)) are available in the current data context.
Molecular Parameters
Molecular Weight and Formula
- Molecular formula: C7H12O4.
- Molecular weight: \(160.17\).
LogP and Polarity
- Reported log octanol–water partition coefficient: \( \log K_{ow}=0.96\).
- Computed XLogP3: \(1\).
- Topological polar surface area (TPSA): \(52.6\ \text{Å}^2\).
These values indicate moderate lipophilicity; the molecule partitions weakly to lipophilic phases but remains sufficiently polar to be soluble in polar organic solvents and moderately soluble in water.
Structural Features
- SMILES: CCOC(=O)CC(=O)OCC
- InChI: InChI=1S/C7H12O4/c1-3-10-6(8)5-7(9)11-4-2/h3-5H2,1-2H3
- InChIKey: IYXGSMUGOJNHAZ-UHFFFAOYSA-N
Key structural attributes: two ethyl ester substituents on a central propanedioate backbone; an activated methylene (acidified α‑CH2) between two electron‑withdrawing carbonyls that enables enolate formation and subsequent C–C bond formation reactions.
Additional computed descriptors:
- Exact/monoisotopic mass: \(160.07355886\).
- Hydrogen-bond donors: \(0\).
- Hydrogen-bond acceptors: \(4\).
- Rotatable bond count: \(6\).
- Heavy atom count: \(11\).
Identifiers and Synonyms
Registry Numbers and Codes
- CAS Number: 105-53-3
- European Community (EC) Number: 203-305-9
- UNII: 53A58PA183
- ChEBI: CHEBI:167785
- ChEMBL: CHEMBL177114
- DSSTox Substance ID: DTXSID7021863
- FEMA Number: 2375
- HMDB: HMDB0029573
- ICSC Number: 1739
- JECFA Number: 614
- InChIKey: IYXGSMUGOJNHAZ-UHFFFAOYSA-N
- SMILES: CCOC(=O)CC(=O)OCC
Synonyms and Structural Names
Common synonyms and systematic names found in the chemical nomenclature pool:
- Diethyl malonate
- Diethyl propanedioate
- Ethyl malonate
- Malonic acid, diethyl ester
- Propanedioic acid, diethyl ester
- Malonic ester
- Carbethoxyacetic ester
- Dicarbethoxymethane
(Several additional vendor and historical synonyms exist; the list above gives the principal names and structural variants.)
Industrial and Commercial Applications
Representative Uses and Industry Sectors
Diethyl malonate is used as a chemical intermediate across multiple sectors:
- Pharmaceutical manufacture (notably in syntheses leading to barbiturates and other active scaffolds).
- Agrochemical intermediates.
- Production of vitamins, dyes, and specialty organic chemicals.
- Flavor and fragrance ingredient in low concentrations (FEMA flavoring profile: apple).
- Solvent or co‑solvent role in formulations and reaction media where moderate polarity and ester functionality are acceptable.
Reported commercial activity includes routine manufacture and use in the basic organic chemical and specialty chemical manufacturing sectors.
Role in Synthesis or Formulations
The central synthetic utility of diethyl malonate stems from its activated methylene: deprotonation produces malonate enolates which undergo alkylation, condensation (Knoevenagel), Michael additions, and related C–C bond-forming processes. It is commonly applied in:
- Alkylation sequences to construct substituted acetates and carboxylic acid derivatives following hydrolysis and decarboxylation.
- Knoevenagel condensations to produce benzylidenemalonates and related conjugated systems.
- Laboratory and process syntheses where controlled enolate chemistry is required to introduce two‑carbon fragments or to generate substituted malonates for subsequent transformations.
If a concise application summary is required for a particular formulation or process, selection is typically based on the reactivity profile described above.
Safety and Handling Overview
Acute and Occupational Toxicity
- LD50 (rat, oral): \(15\ \mathrm{g}\,\mathrm{kg}^{-1}\) (also reported as \(15,794\ \mathrm{mg}\,\mathrm{kg}^{-1}\)).
- LD50 (mouse, oral): \(6400\ \mathrm{mg}\,\mathrm{kg}^{-1}\).
- LD50 (rabbit, dermal): \(>5\ \mathrm{g}\,\mathrm{kg}^{-1}\).
- LD50 (guinea pig, dermal): \(>10\ \mathrm{mL}\,\mathrm{kg}^{-1}\).
Hazard classifications and acute effects reported:
- Eye irritant: can cause serious eye irritation (GHS hazard H319; moderate to severe corneal effects reported in animal tests).
- Skin: mild skin irritation reported in some studies.
- Inhalation: coughing and respiratory irritation reported at elevated exposures; vapour concentrations can accumulate in low areas.
- Environmental acute hazard: harmful to aquatic life (acute aquatic toxicity studies report LC/EC values in the tens of mg·L^-1 range for fish).
First‑aid and emergency measures (summary):
- Inhalation: move to fresh air and seek medical attention if symptoms persist.
- Skin contact: rinse and wash with water and soap; remove contaminated clothing.
- Eye contact: flush eyes with water for several minutes and seek medical attention.
- Ingestion: do not induce vomiting; dilute with water if patient is conscious and seek medical attention.
Storage and Handling Considerations
- Storage: keep containers tightly closed in a dry, well‑ventilated place; store separated from strong oxidizing agents. Ventilation at floor level is advised because vapors are heavier than air in some reports.
- Handling: avoid breathing vapors, mists or aerosols; use local exhaust ventilation and eliminate ignition sources; take measures to prevent electrostatic charge accumulation.
- Personal protective equipment: safety goggles/face shield, chemical-resistant gloves, and impervious clothing. For respiratory protection, use appropriate cartridges or supplied‑air devices when engineering controls are insufficient.
- Fire response: use water spray, alcohol‑resistant foam, dry chemical, or carbon dioxide; heating can cause pressure rise and risk of container rupture. Decomposition yields carbon oxides and irritating fumes — use self‑contained breathing apparatus for firefighters if necessary.
Disposal and spill response: - Prevent release to sewers and the environment. Collect liquid spills into suitable containers; absorb residual liquid with inert material and dispose of according to local regulations. For disposal, incineration in a chemical incinerator with afterburner and scrubber is an appropriate option where permitted.
For detailed regulatory, transport, and product‑specific hazard information, consult the product Safety Data Sheet (SDS) and applicable local regulations.
