HuagongsheHuagongshe Chemistry Print Report · For research reference only
Diethyl Malonate
DEM · DIETHYL PROPANEDIOATE · ETHYL MALONATE · MALONIC ESTER · MALONIC ACID DIETHYL ESTER · Diethyi malonate · FEMA 2375 · Diethyl malonat
Identifiers & Physical Properties
| CAS No. | 105-53-3 |
|---|---|
| Molecular formula | C7H12O4 |
| Average molar mass | 160.17 g/mol |
| Monoisotopic mass | 160.07355886 g/mol |
| SMILES | CCOC(=O)CC(=O)OCC |
| InChIKey | IYXGSMUGOJNHAZ-UHFFFAOYSA-N |
| PubChem CID | 7761 |
| ChEMBL | CHEMBL177114 |
| ChEBI | CHEBI:167785 |
| EC No. | 203-305-9 |
| DTXSID | DTXSID7021863 |
Chemical & Physical Properties
| XLogP | 1 |
|---|---|
| Topological polar surface area | 52.6 |
| Hydrogen bond donors | 0 |
| Hydrogen bond acceptors | 4 |
| Rotatable bonds | 6 |
| Heavy atoms | 11 |
| Formal charge | 0 |
| Complexity | 125 |
| Chemical classes | Other Classes -> Esters, OtherFlammable agents - 2nd degree |
| Cosmetics | Cosmetic ingredients (Diethyl Malonate) -> CIR (Cosmetic Ingredient Review) |
| SpringerMaterials Properties | Boiling point |
| Fragrances | Fragrance Ingredient (Diethyl malonate) -> IFRA transparency List |
| LogP (partition coefficient) | log Kow = 0.96 |
| Odor | Sweet ester odorSlightly aromatic, pleasant odorAroma of ripe fruit, peach, cut grass |
| Taste | Sweet and fruity taste with apple and pineapple nuances |
| Food additives | FLAVORING AGENT OR ADJUVANT -> FDA Substance added to food |
| Density | 1.0551 g/cu cm at 20 °CDensity (at 20 °C): 1.06 g/cm³Relative density of the vapour/air-mixture at 20 °C (air = 1): 1.001.053-1.0561.055 @ 20°C1.055 g/mL at 25 °C (lit.) |
| Flavoring agents | EU Flavoring substances |
| Viscosity | 1.86 centistokes at 25 °C |
| Color/Form | Colorless liquidClear, colorless liquid |
| Melting point | -51--50 °C (lit.) |
| Boiling point | 199 °C (lit.) |
| Vapor density | 5.52 (vs air) |
| Vapor pressure | 1 mm Hg ( 40 °C) |
| Refractive index | n20/D 1.413(lit.) |
| FEMA | 2375 | DIETHYL MALONATE |
| FLAVIS Number | 09.490 | Diethyl malonate |
| Flash point | 212 °F |
| Storage conditions | Store below +30°C. |
| Solubility | 20.8g/l (External MSDS)Miscible with ethyl alcohol, ether, chloroform and benzene. Slightly miscible with water. |
| pKa (acidity coefficient) | 13.5(at 25℃) |
| Physical state | Liquid |
| Color | colourless liquid |
| Biological source | synthetic |
| Odor type | fruity |
| Explosive limits | 0.8-12.8%(V) |
| Specific heat capacity | Cp(liquid): 1.78 J/(g·K), at 25℃ |
| Merck | 14,3823 |
| JECFA Number | 614 |
| BRN | 774687 |
| Henry's law constant | 3.9×100 mol/(m3Pa) at 25℃, Brockbank (2013) |
| Dielectric constant | 7.9(21℃) |
| Stability | Stable. Combustible. Incompatible with strong oxidizing agents, |
| Major applications | flavors and fragrances |
| Cosmetics Ingredients Functions | PERFUMING |
| Cosmetic Ingredient Review (CIR) | Diethyl malonate (105-53-3) |
| InChI | 1S/C7H12O4/c1-3-10-6(8)5-7(9)11-4-2/h3-5H2,1-2H3 |
| InChIKey | IYXGSMUGOJNHAZ-UHFFFAOYSA-N |
| SMILES | CCOC(=O)CC(=O)OCC |
| LogP (partition coefficient) | 0.96 at 20℃ |
| CAS DataBase Reference | 105-53-3(CAS DataBase Reference) |
| Substances Added to Food (formerly EAFUS) | DIETHYL MALONATE |
| EWG's Food Scores | 1 |
| FDA UNII | 53A58PA183 |
| NIST Chemistry Reference | Propanedioic acid, diethyl ester(105-53-3) |
| EPA Substance Registry System | Diethyl malonate (105-53-3) |
| UNSPSC Code | 12352108 |
| NACRES | NA.22 |
| GHS pictogram | GHS07 |
| Signal word | Warning |
| GHS hazard statements | H319 |
| GHS precautionary statements | P264-P280-P305+P351+P338-P337+P313 |
| Personal protective equipment (PPE) | Eyeshields, Gloves, multi-purpose combination respirator cartridge (US) |
| Hazard symbols | Xi |
| Risk statements (R) | 36/37/38-36 |
| Safety statements (S) | 24/25-26 |
| Water hazard class (WGK) | 1 |
| RTECS number | OO0700000 |
| Autoignition temperature | 435 °C DIN 51794 |
| Hazard Note | Irritant |
| TSCA inventory status | TSCA listed |
| Customs code | 29171910 |
| Storage class | 10 - Combustible liquids |
| Hazard class | Eye Irrit. 2 |
| Hazardous substances data | 105-53-3(Hazardous Substances Data) |
| Toxicity | LD50 orally in Rabbit: 15720 mg/kg LD50 dermal Rabbit > 16000 mg/kg |
| REACH registrations | Active |
Safety & Regulations
| GHS classification | This chemical does not meet GHS hazard criteria for 2.7% (69 of 2532) of reports.WarningH319 (96.9%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]P264+P265, P280, P305+P351+P338, and P337+P317 (click each P-code to see the statement)Aggregated GHS information provided per 2532 reports by companies from 18 notifications to the ECHA C&L Inventory. |
|---|---|
| Regulatory information | Chemical: Propanedioic acid, diethyl esterRegulation (EC) No 1831/2003 (amended)Propanedioic acid, 1,3-diethyl ester is listed on the EPA's Chemical Data Reporting (CDR) system. Manufacturers and importers of Propanedioic acid, 1,3-diethyl ester are required to report information about their production and use of this chemical to the EPA under the Toxic Substances Control Act (TSCA). (40 eCFR Part 711)Status: Active Update: 06-04-2023 https://echa.europa.eu/registration-dossier/-/registered-dossier/5774Diethyl malonate: Does not have an individual approval but may be used under an appropriate group standardThe New Jersey Worker and Community Right to Know Act requires public and private employers to provide information about hazardous substances at their workplaces. (N.J.S.A. 34:5A-1 et. seq.) |
| Fire hazards | Combustible. Gives off irritating or toxic fumes (or gases) in a fire. Heating will cause rise in pressure with risk of bursting. |
| Fire potential | Combustible liquid when exposed to heat or flame. |
| Hazards summary | A slight to moderate eye irritant based on animal studies[eChemPortal: SIDSUNEP] A mild skin irritant based on animal studies[MSDSonline] |
| Chemical Dangers | It reacts with strong oxidants. This generates fire and explosion hazard. |
| NFPA Hazard Classification | 1 - Materials that, under emergency conditions, can cause significant irritation.2 - Materials that must be moderately heated or exposed to relatively high ambient temperatures before ignition can occur. Materials would not under normal conditions form hazardous atmospheres with air, but under high ambient temperatures or under moderate heating could release vapor in sufficient quantities to produce hazardous atmospheres with air.0 - Materials that in themselves are normally stable, even under fire conditions. |
| Hazard Classes and Categories | Eye Irrit. 2A (96.9%)Flammable liquids - Category 4Flammable agents - 2nd degree |
| Explosive Limits and Potential | Explosive limits , vol% in air: 0.8 - 12.8 |
| Skin, Eye, and Respiratory Irritations | Eye irritation in rabbits: moderately irritating.A skin irritant. |
| Critical Temperature and Pressure | Critical temperature: 653 K (estimated)Critical pressure: 2780 kPa (estimated) |
| Hazardous Reactivities and Incompatibilities | Conditions to avoid: Heat, flames and sparks. Incompatible materials: Acids, Bases, Oxidizing agents, Reducing agentscan react with oxidizing materials. |
| Fire fighting | Use carbon dioxide, dry powder, water spray, foam. In case of fire: keep drums, etc., cool by spraying with water. |
| First aid measures | Fresh air, rest. Seek medical attention if you feel unwell.Rinse and then wash skin with water and soap.First rinse with plenty of water for several minutes (remove contact lenses if easily possible), then refer for medical attention.Give one or two glasses of water to drink. Seek medical attention if you feel unwell. |
| Safe storage | Separated from strong oxidants. Ventilation along the floor. Store in an area without drain or sewer access. |
| Fire fighting procedures | Water may be used to blanket fire.To fight fire, use water to blanket fire, foam, CO2, dry chemical.Extinguishing media: Suitable extinguishing media Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide. Advice for firefighters: Wear self-contained breathing apparatus for firefighting if necessary. Further information: Use water spray to cool unopened containers. |
| Storage conditions | Keep container tightly closed in a dry and well-ventilated place. |
| Cleanup methods | ACCIDENTAL RELEASE MEASURESPersonal precautions, protective equipment and emergency procedures: Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Remove all sources of ignition. Beware of vapors accumulating to form explosive concentrations. Vapors can accumulate in low areas. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Discharge into the environment must be avoided. Methods and materials for containment and cleaning up: Contain spillage, and then collect with an electrically protected vacuum cleaner or by wet-brushing and place in container for disposal according to local regulations. Keep in suitable, closed containers for disposal. |
| Disposal methods | SRP: Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air qualitypotential migration in air, soil or watereffects on animal, aquatic and plant lifeand conformance with environmental and public health regulations. If it is possible or reasonable use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity or environmental contamination.Product: This combustible material may be burned in a chemical incinerator equipped with an afterburner and scrubber. Offer surplus and non-recyclable solutions to a licensed disposal company. Contaminated packaging: Dispose of as unused product. |
| Spillage disposal | Personal protection: filter respirator for organic gases and vapours adapted to the airborne concentration of the substance. Do NOT let this chemical enter the environment. Collect leaking liquid in sealable containers. Absorb remaining liquid in sand or inert absorbent. Then store and dispose of according to local regulations. |
| Preventive Measures | Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.Avoid inhalation of vapor or mist. Keep away from sources of ignition - No smoking. Take measures to prevent the build up of electrostatic charge.ACCIDENTAL RELEASE MEASURESPersonal precautions, protective equipment and emergency procedures: Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Remove all sources of ignition. Beware of vapors accumulating to form explosive concentrations. Vapors can accumulate in low areas. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Discharge into the environment must be avoided.Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and at the end of workday.SRP: The scientific literature for the use of contact lenses by industrial workers is inconsistent. The benefits or detrimental effects of wearing contact lenses depend not only upon the substance, but also on factors including the form of the substance, characteristics and duration of the exposure, the uses of other eye protection equipment, and the hygiene of the lenses. However, there may be individual substances whose irritating or corrosive properties are such that the wearing of contact lenses would be harmful to the eye. In those specific cases, contact lenses should not be worn. In any event, the usual eye protection equipment should be worn even when contact lenses are in place. |
| Eye Prevention | Wear safety goggles. |
| Fire Prevention | NO open flames. |
| Inhalation Risk | Evaporation at 20 °C is negligiblea nuisance-causing concentration of airborne particles can, however, be reached quickly when dispersed. |
| Interactions | Because it inhibits dehydrochlorinase activity, diethyl malonate (10-40 ppm) increased the toxicity of DDT (2 ppm) to DDT-resistant mosquitoes Culex fatinans. |
| Ecotoxicity values | EC50Species: Pimephales promelas (Fathead Minnow) age 33 days, length 14 mm, weight 0.036 gConditions: freshwater, flow through, 25.4 °C (23.5-27.7 °C), pH 7.42 (7.35-7.45), hardness 44.0 mg/L CaCO3, alkalinity 45.0 mg/L CaCO3, dissolved oxygen 87.6 mg/L (73.7-102 mg/L)Concentration: 20900 ug/L for 24 hrEffect: behavior, loss of equilibrium /99% purity/Concentration: 15600 ug/L for 48 hrLC50Concentration: 23500 ug/L for 24 hr /99% purity/Concentration: 16600 ug/L for 48 hr /99% purity/For more Ecotoxicity Values (Complete) data for Diethyl malonate (7 total), please visit the HSDB record page. |
| Environmental fate | TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 10(SRC), determined from a structure estimation method(2), indicates that diethyl malonate is expected to have very high mobility in soil(SRC). Volatilization of diethyl malonate from moist soil surfaces may occur(SRC) given an estimated Henry's Law constant of 2.0X10-6 atm-cu m/mole(SRC), derived from its vapor pressure, 0.19 mm Hg(3), and water solubility, 2.0X10+4 mg/L(4). In chemical stimulant studies simulating chemical warfare agents, diethyl malonate deposited to dry soil and foliar surfaces was rapidly lost through volatilization processes with observed half-lives on soil of about 2 hours (fast) to 5-16 hours (residual material)(4)foliar half-lives ranged from 1 to 242 hours(5). Two screening studies found diethyl malonate to be readily biodegradable(6,7). An 86% of theoretical BOD in two weeks using activated sludge in the Japanese MITI test(6) suggests that biodegradation is an important environmental fate process in soil(SRC).AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 10(SRC), determined from a structure estimation method(2), indicates that diethyl malonate is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is expected(3) based upon an estimated Henry's Law constant of 2.0X10-6 atm-cu m/mole(SRC), derived from its vapor pressure, 0.19 mm Hg(4), and water solubility, 2.0X10+4 mg/L(5). Using this Henry's Law constant and an estimation method(3), volatilization half-lives for a model river and model lake are 23 and 173 days, respectively(SRC). According to a classification scheme(6), an estimated BCF of 3(SRC), from its log Kow of 0.96(7) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Two screening studies found diethyl malonate to be readily biodegradable(8,9). An 86% of theoretical BOD in two weeks using activated sludge in the Japanese MITI test(8) suggests that biodegradation is an important environmental fate process in water(SRC). Diethyl malonate hydrolyzes readily in neutral and alkaline water, but slowly in acidic water(10). Respective hydrolysis half-lives at pH 4, pH7 and pH 9 are <10% after 5 days (50 °C), 137.5 hr (25 °C) and <2.4 hr (50 °C)(10).ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), diethyl malonate, which has a vapor pressure of 0.19 mm Hg at 25 °C(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase diethyl malonate is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC)the half-life for this reaction in air is estimated to be 3.1 days(SRC), calculated from its rate constant of 3.4X10-12 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Diethyl malonate contains chromophores that absorb at wavelengths >290 nm(4) and, therefore, may be susceptible to direct photolysis by sunlight(SRC). |
| Food survey values | Diethyl malonate is reported found in pineapple, bilberry, Cape gooseberry, cognac, malt whiskey, apple brandy, grape brandy port cider, sherry, and red wine, white and strawberry wines. It is used as a flavor additive in alcoholic beverages, baked goods, frozen dairy, gelatins, puddings, hard candy, non-alcoholic beverages and soft candy(1). |
| Toxicity summary | Safe in the present practices of use and concentration. Ingredient, concentration, and use information are available in documents discoverable at https://cir-reports.cir-safety.orgIDENTIFICATION AND USE: Diethyl malonate is used in chemical synthesis. It is also used in food, beverages, and in fragrances. HUMAN STUDIES: A maximization test was reported in 23 volunteers. 4% of the test substance in petrolatum produced no sensitization reactions. Tested at 4% in petrolatum it produced no irritation after a 48-hr closed-patch test on human subjects. ANIMAL STUDIES: Diethyl malonate causes moderate irritation to rabbit's eyes and is non-irritating to rabbit's skin. Application of 0.005 mL of undiluted diethyl malonate to the rabbit cornea caused severe burning. Diethyl malonate fed to rats for 90 days at more than 100 times the equivalent of the human daily dietary intake (averaging 35.93 mg/kg bw per day for males and 41.14 mg/kg bw per day for females) had no adverse effects. The maximum time for inhalation of the concentrated vapor of diethyl malonate by rats without deaths was found to be 8 hr. Mutagenicity test in Salmonella typhimurium TA98, TA 100, TA 1535, TA 1537, TA 1538 was negative with and without activation at concentrations of 8, 40, 200, 1000, 5000 ug/plate 5000 ug/plate (maximal concentration). |
| Average Daily Intake | Diethyl malonate average daily intake = 0.006101 mg/kg/day(1). |
| Signs and Symptoms | Cough.Redness.No acute symptoms expected. |
| Ongoing Test Status | EPA has released the Interactive Chemical Safety for Sustainability (iCSS) Dashboard. The iCSS Dashboard provides an interactive tool to explore rapid, automated (or in vitro high-throughput) chemical screening data generated by the Toxicity Forecaster (ToxCast) project and the federal Toxicity Testing in the 21st century (Tox21) collaboration. /The title compound was tested by ToxCast and/or Tox21 assays/[USEPAICSS Dashboard ApplicationAvailable from, as of August 9, 2018: http://actor.epa.gov/dashboard/] |
| ICSC Environmental Data | The substance is harmful to aquatic organisms. |
| Soil Adsorption/Mobility | Using a structure estimation method based on molecular connectivity indices(1), the Koc of diethyl malonate can be estimated to be 10(SRC). According to a classification scheme(2), this estimated Koc value suggests that diethyl malonate is expected to have very high mobility in soil(SRC). |
| Natural Pollution Sources | Diethyl malonate is reportedly found in pineapple, bilberry, Cape gooseberrys, grapes and strawberries(1). Diethyl malonate is present in guava fruit, melon, concord grape, pineapple, and blackberry(2). The related diester (dimethyl malonate) occurs in pineapple, bananas and blackberries(3). |
| Human Toxicity Excerpts | /HUMAN EXPOSURE STUDIES/ Tested at 4% in petrolatum it produced no irritation after a 48-hr closed-patch test on human subjects./HUMAN EXPOSURE STUDIES/ A maximization test was reported in 23 volunteers. 4% of the test substance in petrolatum produced no sensitization reactions. |
| Personal protective equipment (PPE) | Eyeshields, Gloves, multi-purpose combination respirator cartridge (US) |
| Water hazard class (WGK) | 1 |
| TSCA inventory status | TSCA listed |
| RTECS number | OO0700000 |
| Customs code | 29171910 |
| Toxicity | LD50 orally in Rabbit: 15720 mg/kg LD50 dermal Rabbit > 16000 mg/kg |
| Risk statements (R) | 36/37/38-36 |
| Signal word | Warning |
| GHS pictogram | GHS07 |
| Hazard symbols | Xi |
| hazard_note | Irritant |
| Safety statements (S) | 24/25-26 |
| Storage class | 10 - Combustible liquids |
| GHS hazard statements | H319 |
| REACH registrations | Active |
| Hazard class | Eye Irrit. 2 |
| Autoignition temperature | 435 °C DIN 51794 |
| GHS precautionary statements | P264-P280-P305+P351+P338-P337+P313 |
| Hazardous substances data | 105-53-3(Hazardous Substances Data) |
Applications & Uses
Description
As an organic compound, diethyl malonate belongs to the diethyl ester of malonic acid, which is present naturally in guava fruits, melons, grapes, pineapples, blackberries and strawberries as a colorless liquid with an apple-like odor. It is a flavor ingredient commonly found in perfumes, artificial flavorings, alcoholic beverages, various wines and spirits due to its natural pleasant odor. It is also used as an essential intermediate in the syntheses of numerous pharmaceuticals, such as barbiturates, vitamins B1 and B6, non-steroidal anti-inflammatory agents. Besides, diethyl malonate is also involved in organic synthesis of other compounds, such as alpha-aryl malonates, mono-substituted and di-substituted acetic acid. And it can react with benzaldehyde for the production of diethyl benzylidenemalonate in Knoevenagel condensation reaction.
Description
Diethyl malonate is a diester derivative of malonic acid, a dicarboxylic acid with two carboxyl groups (-COO-) separated by one methylene group (-CH2-). Diethyl malonate is formed by the replacement of the hydroxyl groups (-OH) of malonic acid with ethoxy groups (-OCH2CH3). The hydrogen atoms on the methylene carbon between the two carboxyl groups make this compound acidic. Because of its unique structure, diethyl malonate is reactive and functions as a reagent for organic synthesis and to make products such as barbiturates, pigments, and agrochemicals. Volatile esters are known to have fruity scents and are often used as fragrances and flavorings. Diethyl malonate is a volatile diester that occurs naturally in fruits such as grapes, strawberries, guava, melon, pineapple, and blackberries.
Occurrence
Reported found in pineapple, bilberry, Cape gooseberry, cognac, malt whiskey, apple brandy, grape brandy, port, cider, sherry and red, white, strawberry and bilberry wines.
Uses
Diethyl Malonate occurs naturally in grapes and strawberries. It is used in the preparation of barbiturates, artificial flavourings, vitamin B1, and vitamin B6 as well as in perfumes.
Uses
manufacture of barbiturates.
Uses
Diethyl malonate is used in organic synthesis for the preparation of alpha-aryl malonates, mono-substituted and di-substituted acetic acid, barbiturates and artificial flavorings. It is also involved in the synthesis of pharmaceuticals like chloroquine, butazolidin and barbital. It acts as intermediate in the synthesis of vitamin B1, vitamin B6, non-steroidal anti-inflammatory agents agrochemicals and perfumes. In Knoevenagel condensation reaction, it reacts with benzaldehyde to get diethyl benzylidenemalonate.
General Description
Diethyl malonate is diethyl ester of malonic acid. Acylation of diethyl malonate using magnesium chloride and triethylamine is reported. K2CO3-catalyzed 1,4-addition reaction of diethyl malonate with various substituted 1,2-allenic ketones yields polyfunctionalized β,γ-unsaturated enones.
Preparation & Synthesis
Preparation
Reacting chloroacetic acid to cyanoacetic acid using sodium cyanide and subsequent saponification; malonic acid is finally esterified by azeotropic distillation with ethanol in benzene