Diethyl Malonate, Ethyl malonate, Diethyl Propanedioate, Dicarbethoxy Methane, DEM, 105-53-3

DIETHYL MALONATE (DEM) 

Chemical Name: Diethyl Malonate (DEM)
CAS Number: 105-53-3
Molecular Formula: C₇H₁₂O₄
Molecular Weight: ~160 g/mol
Chemical Class: Diester, organic compound, malonic ester

SECTION 1: PRODUCT IDENTIFICATION AND CHEMICAL IDENTITY

PRODUCT DESCRIPTION AND EXPLANATION:

Diethyl Malonate (DEM) is a diester of malonic acid and ethanol, widely recognized as a versatile "building block" in organic synthesis . It is a colorless liquid with a characteristic fruity, apple-like odor . Its molecular structure features an active methylene group (-CH₂-) positioned between two ester groups, which is the key to its exceptional reactivity and utility in a wide range of synthetic applications.

DEM is one of the most important chemical intermediates in the industry . It serves as a cornerstone precursor in the synthesis of barbiturates , and is also crucial in the production of vitamin B1 and B6 derivatives, non-steroidal anti-inflammatory drugs, agrochemicals, and various flavor and fragrance compounds . Its high reactivity allows it to participate in classic reactions such as the Knoevenagel condensation and Michael addition . Due to its widespread use, it has a global production volume in the range of 100–1000 metric tons per year .

SECTION 2: PHYSICAL AND CHEMICAL PROPERTIES

SOLUBILITY PROFILE:

PHYSICAL AND CHEMICAL PROPERTIES EXPLANATION:

Diethyl Malonate is a clear, colorless liquid at room temperature, known for its pleasant, fruity, apple-like odor . It has a density of ~1.055 g/cm³, making it denser than water . Its boiling point is approximately 199°C, and its flash point is around 90-93°C, classifying it as a combustible liquid .

DEM is slightly soluble in water (~20.8 g/L at 20°C) but is miscible with most common organic solvents such as ethanol, ether, and acetone . Its low vapor pressure of 0.36 hPa at 25°C indicates low volatility, while its Log P value of ~0.96 suggests a low potential for bioaccumulation .

SECTION 3: CHEMICAL PROPERTIES AND REACTIONS

CHEMICAL PROPERTIES EXPLANATION:

The exceptional utility of Diethyl Malonate in organic synthesis stems from the reactivity of its active methylene group (-CH₂-) positioned between two electron-withdrawing ester groups. This arrangement makes the methylene hydrogens acidic (pKa ~13) and susceptible to abstraction by bases, generating a highly nucleophilic enolate ion .

This enolate can undergo a diverse range of reactions:

• Alkylation and Acylation: It can be alkylated or acylated to form mono- or di-substituted malonic esters, which are key intermediates in the synthesis of substituted acetic acids and various pharmaceuticals .

• Knoevenagel Condensation: It readily reacts with aldehydes or ketones in the presence of a base to form α,β-unsaturated esters .

• Hydrolysis and Decarboxylation: Upon hydrolysis, DEM yields malonic acid, which readily decarboxylates upon heating to produce acetic acid derivatives. This "malonic ester synthesis" is a classic method for preparing substituted acetic acids .

SECTION 4: FUNCTIONAL PROPERTIES

FUNCTIONAL PROPERTIES EXPLANATION:

Diethyl Malonate's primary functional role is that of a versatile reagent and building block in chemical synthesis . Its value lies in its ability to form C-C bonds under mild conditions, making it an essential tool for building complex molecules. In pharmaceutical synthesis, it is a cornerstone precursor for barbiturate drugs . It also serves as a key intermediate in the synthesis of vitamin B1 and B6 derivatives, as well as various non-steroidal anti-inflammatory agents . Beyond pharmaceuticals, it is used in the creation of agrochemicals  and is a building block for artificial flavorings and perfumes . Its suitability for polymer synthesis and other in fine chemical applications is also documented .

SECTION 5: APPLICATION AREAS AND INDUSTRIAL USES

5.1. Pharmaceutical Synthesis (Primary Application)

5.2. Aroma and Fragrance Chemicals

5.3. Fine Chemical Synthesis

APPLICATION AREAS EXPLANATION:

Pharmaceutical Synthesis: DEM is an indispensable reagent in the pharmaceutical industry. Its primary application is as a building block for barbiturate drugs, where it reacts with urea derivatives to form the core barbituric acid ring structure . Additionally, it is a crucial intermediate in the synthesis of vitamins (B1, B6), various NSAIDs, and other active pharmaceutical ingredients .

Aroma and Fragrance Chemicals: Owing to its fruity odor profile, DEM is used directly or as a precursor in the synthesis of artificial flavorings and perfumes . The RIFM (Research Institute for Fragrance Materials) has conducted safety assessments confirming its safe use in fragrance applications .

Fine Chemical Synthesis: Beyond pharmaceuticals and flavorings, DEM is a versatile intermediate for agrochemicals , organic pigments , and a range of specialty chemicals. Its participation in classic reactions like the Knoevenagel condensation makes it a staple in research and development laboratories .

SECTION 6: ADVANTAGES

• Versatile Building Block: Highly reactive active methylene group allows for a wide range of chemical transformations .

• Core Pharmaceutical Intermediate: Essential for the synthesis of barbiturates, vitamins, and various APIs .

• Fruity Odor Profile: Pleasant, apple-like odor makes it suitable for flavor and fragrance applications .

• Well-Established Reagent: A classic and reliable reagent in organic synthesis, widely available and well-characterized .

• High Purity: Commercially available in high purity grades (≥98%, ≥99%) for sensitive applications .

SECTION 7: QUALITY STANDARDS AND SPECIFICATIONS

QUALITY STANDARDS EXPLANATION:

Diethyl Malonate is manufactured to high purity standards, typically ≥98% or ≥99% as determined by gas chromatography . Key quality parameters include density, refractive index, and IR spectrum for identity confirmation . Low water content and acid number are indicative of product stability and minimal hydrolysis .

SECTION 8: SAFETY AND TOXICOLOGY

SAFETY AND TOXICOLOGY EXPLANATION:

Diethyl Malonate is considered a hazardous substance due to its irritant properties and flammability . It can cause skin and serious eye irritation, and may trigger an allergic skin reaction . The oral LD50 in rats is approximately 15,794 mg/kg . It is not considered mutagenic . The RIFM safety assessments classify it under Cramer Class I, indicating a low order of toxicity, and conclude that it does not present a concern for genotoxicity .

Safety Precautions:

• Inhalation: Avoid inhalation of vapors or mist. Use in well-ventilated areas .

• Skin Contact: Wash with plenty of water and soap upon skin contact. Remove contaminated clothing .

• Eye Contact: Rinse immediately with plenty of water for at least 15 minutes. Get medical attention if symptoms occur .

• Ingestion: Do NOT induce vomiting. Rinse mouth. Seek medical attention if large amount is swallowed .

• PPE Recommendations: Wear protective gloves (e.g., nitrile), chemical safety goggles, and protective clothing .

• Hygiene Measures: Avoid contact with skin, eyes, and clothing. Wash hands before breaks and after work .

• Fire: Combustible liquid. Keep away from heat, sparks, and open flames. Use CO₂, dry chemical, or foam for extinction .

SECTION 9: TRANSPORT INFORMATION

TRANSPORT INFORMATION EXPLANATION:

Transport regulations for Diethyl Malonate may vary . While some sources indicate it is not classified as dangerous goods for transport under certain regulations , its combustibility (flash point 90-93°C) may subject it to specific transport controls for flammable liquids in many jurisdictions . It is not classified as a marine pollutant . In case of transport, refer to the appropriate regulations and consult the Safety Data Sheet for specific guidance.

SECTION 10: REGULATORY INFORMATION

REGULATORY INFORMATION EXPLANATION:

Diethyl Malonate is a widely used industrial chemical and is listed on the chemical inventories of all major markets, including the EU (REACH), USA (TSCA), China, Japan, Korea, and Australia . It is subject to the standard regulations for chemical handling, labeling, and transport (e.g., GHS, ADR) due to its hazardous nature .

SECTION 11: STORAGE AND HANDLING

STORAGE AND HANDLING EXPLANATION:

Diethyl Malonate should be stored in a cool, dry, and well-ventilated area, ideally at 2-30°C . Containers must be kept tightly closed to prevent contamination and evaporation . Protect from incompatible materials, particularly acids, bases, reducing agents, and strong oxidizing agents . Due to its combustible nature, it must be kept away from sources of ignition, heat, sparks, and open flames . Adequate ventilation is necessary, and precautionary measures against static electricity should be taken during handling .

SECTION 12: FIRE FIGHTING MEASURES

FIRE FIGHTING MEASURES EXPLANATION:

Diethyl Malonate is a combustible liquid with a flash point of 90-93°C . It can form explosive mixtures with air upon intense heating, and containers may explode if exposed to fire . Use CO₂, dry chemical, or foam to extinguish fires; water spray can be used to cool containers . Firefighters must wear self-contained breathing apparatus (SCBA) and full protective gear. Incompatible materials include acids, bases, and strong oxidizing agents .

SECTION 13: ACCIDENTAL RELEASE MEASURES

ACCIDENTAL RELEASE MEASURES EXPLANATION:

In case of a spill, immediately wear appropriate PPE and ensure the area is well-ventilated . Remove all sources of ignition as the product is combustible. Prevent the spilled liquid from entering drains, sewers, or water bodies . The liquid can be contained and absorbed using an inert material like sand or a universal binder. The absorbed material should be collected in a suitable, closed container for proper disposal according to local regulations .

SECTION 14: FIRST AID MEASURES

FIRST AID MEASURES EXPLANATION:

Standard first aid measures for chemical exposure should be applied for Diethyl Malonate:

• Inhalation: Move the affected person to fresh air immediately. If breathing stops, provide artificial respiration. Seek medical attention if symptoms such as headache, dizziness, or nausea occur .

• Skin Contact: Immediately wash the contaminated skin with plenty of water and soap for at least 15 minutes. Remove any contaminated clothing and wash before reuse. Seek medical attention if irritation or an allergic reaction develops .

• Eye Contact: Rinse eyes with plenty of water for at least 15 minutes, occasionally lifting the upper and lower eyelids. Remove contact lenses if present and easy to do. Seek immediate medical attention .

• Ingestion: Do NOT induce vomiting. Rinse the mouth with water. If the person is conscious, give them water to drink. Seek immediate medical attention .

SECTION 15: RAW MATERIALS AND DOWNSTREAM PRODUCTS

15.1. Raw Materials (Upstream)

15.2. Downstream Products

SECTION 16: INDUSTRY COMPATIBILITY AND USAGE VOLUMES

SECTION 17: DIETHYL MALONATE vs DIMETHYL MALONATE COMPARISON

COMPARISON EXPLANATION:

Diethyl Malonate and Dimethyl Malonate are both malonic esters with nearly identical chemical reactivity due to the active methylene group. Their primary difference lies in the alcohol moiety (ethyl vs. methyl), which influences their physical properties such as boiling point and solubility. Diethyl Malonate (the ethyl ester) is often preferred in certain pharmaceutical and industrial applications due to its established use, availability, and sometimes cost-effectiveness.

SECTION 18: DERIVATIVES AND RELATED COMPOUNDS

SECTION 19: SUMMARY AND CRITICAL NOTES

SUMMARY:

Diethyl Malonate (DEM, CAS 105-53-3) is a widely used chemical intermediate and versatile building block in organic synthesis . It is a colorless liquid with a characteristic fruity, apple-like odor . Its molecular weight is ~160.17 g/mol, density is ~1.055 g/cm³, and boiling point is 199°C . It is slightly soluble in water and miscible with most organic solvents .

The compound's high reactivity is due to its active methylene group, making it essential for reactions like Knoevenagel condensation, Michael addition, and alkylation . It is a cornerstone precursor in the synthesis of barbiturates , vitamins B1 and B6 derivatives , various pharmaceuticals, and agrochemicals . It is also used to produce artificial flavorings and perfumes .

Diethyl Malonate is classified as a hazardous substance with flammable and irritant properties . It should be stored in a cool, dry, well-ventilated area, protected from heat and ignition sources . It is subject to regulations for hazardous materials handling and transport.

Basic Properties:

Main Application Areas:

Key Safety Points:

• HAZARDOUS SUBSTANCE: Classified as hazardous; GHS07 exclamation mark .

• IRRITANT: Causes skin and serious eye irritation; may cause allergic skin reaction .

• COMBUSTIBLE LIQUID: Flammable liquid category 4; keep away from heat, sparks, and open flames .

• STORAGE: Store in cool, dry, well-ventilated area; keep container tightly closed .

• PPE RECOMMENDED: Wear protective gloves, chemical safety goggles, and protective clothing .

• INCOMPATIBLE: Acids, bases, reducing agents, strong oxidizing agents .

• GLOBAL PRODUCTION: 100-1000 metric tons per year .

CRITICAL NOTES:

1. Versatile Building Block: Diethyl Malonate is a classic and extremely versatile reagent in organic chemistry due to its active methylene group, which can undergo a wide variety of reactions including alkylation, acylation, and condensation .

2. Pharmaceutical Industry: It is a cornerstone intermediate in the manufacture of barbiturate drugs and is essential for the synthesis of vitamins B1 and B6 derivatives, as well as numerous non-steroidal anti-inflammatory drugs (NSAIDs) and antimalarial agents .

3. Flavor and Fragrance: DEM contributes to the synthesis of artificial flavorings and perfumes, leveraging its pleasant fruity, apple-like odor profile .

4. Classic Reactions: It is a key reagent in classic organic reactions, notably the Knoevenagel condensation for producing α,β-unsaturated esters, and the malonic ester synthesis for preparing substituted acetic acids .

5. Safety and Handling: Although considered of low toxicity (Cramer Class I) , DEM is an irritant to skin and eyes, and may act as a skin sensitizer . It is also a combustible liquid . Appropriate PPE, including gloves and safety goggles, must always be worn when handling this chemical.

6. Storage and Stability: It is chemically stable under standard ambient conditions but is sensitive to moisture and incompatible with strong acids, bases, and oxidizing agents . The container must be kept tightly closed and stored in a cool, dry place to prevent hydrolysis and degradation.

7. Occurrence: Diethyl Malonate has been reported to occur naturally in small quantities in various fruits and beverages, including grapes, wine, pineapple, and whisky .

IMPORTANT DISCLAIMER: This Technical Data Sheet (TDS) is for informational purposes only and is prepared based on available technical data. The information provided is believed to be accurate. However, the user is solely responsible for determining the product's suitability for their specific applications and for complying with all applicable local, national and international regulations and safety requirements. For complete safety, storage, handling, transport, waste and regulatory compliance information, please refer to the official Safety Data Sheet (SDS/MSDS) provided by the manufacturer/supplier. Users are obligated to test the product in their own processes and applications. All occupational health and safety rules must be observed when working with Diethyl Malonate.