Methylcrotonate is a chemical compound, a synthetic aroma, the methyl ester of crotonic acid, an unsaturated fatty acid with four carbon atoms. It is primarily used as a chemical intermediate in the synthesis of various organic compounds and in some industrial applications, particularly in the production of fragrances due to its volatility and sweet, fruity aroma.

Chemical Composition and Structure

Methylcrotonate is an ester formed by the reaction of crotonic acid and methanol. Its chemical structure includes a crotonate group, which contains a double bond, attached to a methyl group (-CH₃). This configuration gives the compound its reactivity and volatile properties.

Physical Properties

It appears as a colorless or slightly yellowish liquid with a sweet and fruity odor. It is soluble in organic solvents like alcohols and oils but has low solubility in water. Due to its volatility, Methylcrotonate evaporates quickly, making it useful in fragrance applications.

Production Process

Methylcrotonate is produced through an esterification process, in which crotonic acid reacts with methanol in the presence of an acid catalyst. This chemical process results in the formation of the ester, which is then purified to obtain the final product.

The name describes the structure of the molecule:

• Methyl refers to a functional group derived from methane (CH₄). It consists of a carbon atom bonded to three hydrogen atoms (CH₃). In organic chemistry, a methyl group is often added to larger molecules.
• Crotonate or 'trans-2-butenoate' refers to a type of carboxylate ester derived from crotonic acid or trans-2-butenoic acid. The designation 'trans' refers to the geometric configuration of the molecule, indicating that the two carbon-containing groups are on opposite sides of the double bond. The '2' in '2-butenoate' indicates the position of the double bond in the butenoate group.

Description of raw materials used in production

• 3-methyl-2-butenoic acid - The starting carboxylic acid from which the ester is derived.
• Methanol - The alcohol that reacts with the carboxylic acid to form the ester.

The synthesis process takes place in different steps:

• Synthesis of Crotonic Acid: The first step in the production of methylcrotonate is the synthesis of crotonic acid, which can be obtained through various chemical routes, including aldol condensation between acetone and acetic acid or by dehydrating fatty acids.

• Esterification: Once crotonic acid is obtained, it undergoes an esterification process with methanol. This is achieved by heating crotonic acid with methanol in the presence of an acid catalyst, such as sulfuric acid, to promote the formation of methylcrotonate.

• Distillation: The produced methylcrotonate is then separated from the reactor through a distillation process. This step helps remove any impurities and unreacted solvents, resulting in a purer product.

• Purification: Further purification techniques, such as chromatography, may be employed to ensure high-quality methylcrotonate.

• Analysis and Packaging: Finally, methylcrotonate is analyzed to verify its purity and chemical composition. After analysis, it is packaged for distribution and use.

Methylcrotonate appears as a clear, colourless liquid.

Biotin-response Organicaciduria:

Methylcrotonate is associated with biotin-responsive organicacidemia. Patients with this condition excrete abnormal levels of metabolic intermediates, including beta-methylcrotonate.

The condition is linked to a deficiency in certain enzymes, including beta-methylcrotonyl-CoA carboxylase, after growth in biotin-limited culture medium.

Biosynthesis of Rubber:

There were studies on the incorporation of beta-hydroxy-beta-methylglutarate or beta-methylcrotonate into rubber. However, the results were inconclusive.

Leucine Catabolism in Pseudomonas putida:

The catabolism of leucine in Pseudomonas putida involves several enzymes. One of the intermediates in this pathway is 3-methylcrotonate.

The pathway for the oxidation of 3-methylcrotonate is induced by growth on isovalerate or 3-methylcrotonate.

Sporulation in Bacillus subtilis:

The fatty acid composition of Bacillus subtilis can be influenced by the presence of various precursors, including 3-methylcrotonate.

Cosmetics

It is a restricted ingredient as II/445 a Relevant Item in the Annexes of the European Cosmetics Regulation 1223/2009. Should not be used as a fragrance ingredient. Based on the sensitizing potential (Opdyke FCT 17,865(1979)). Replaces 3/78

Health and Safety Considerations

Safety in Use
Methylcrotonate is generally considered safe at the typical concentrations used in industrial and cosmetic formulations. However, due to its volatile and reactive nature, it should be handled carefully to avoid prolonged exposure or accidental inhalation, which may cause irritation to the respiratory system or eyes.

Allergic Reactions
Allergic reactions to Methylcrotonate are rare, but it is always advisable to perform a preliminary patch test to check for skin tolerance, especially if used in products that may come into contact with the skin or mucous membranes.

Toxicity and Carcinogenicity
There is no evidence to suggest that Methylcrotonate is carcinogenic or toxic at the concentrations typically used. However, as with any volatile chemical compound, prolonged exposure or inhalation of large amounts may cause irritation or temporary adverse effects.

Environmental and Safety Considerations
As a volatile compound, Methylcrotonate evaporates quickly in the environment. It does not pose significant risks of bioaccumulation, but it should be disposed of properly to avoid uncontrolled release into the environment. It is biodegradable, which reduces its ecological impact.

Regulatory Status
Methylcrotonate is regulated for industrial and cosmetic use, and its use is subject to chemical safety regulations that set maximum concentrations depending on the type of application. Regulatory authorities such as the European Union and the Food and Drug Administration (FDA) in the United States monitor its safe use.

Methylcrotonate  studies

• Molecular Formula  C₅H₈O₂
• Molecular Weight  100.117 g/mol
• CAS 18707-60-3  623-43-8
• EINECS 210-793-7

Synonyms:

• Methyl E-crotonate
• Methyl 2-butenoate
• Methyl trans-crotonate
• 2-Butenoic acid, methyl ester, (2E)-
• trans-2-Butenoic acid methyl ester
• Methyl trans-2-butenoate
• InChI=1/C5H8O2/c1-3-4-5(6)7-2/h3-4H,1-2H3/b4-3

References_____________________________________________________________________

(1) Ko Kyung-mok, Yoo Chan-joo, Ko Byung-rye e Lee Seok-ki. (2020). A study on simultaneous analysis of allergenic aroma substances in children's products using GC-MSD. Analytical sciences, 33(3), 134-142.

Abstract. Twenty-one allergy-induced aromatic material in children's products were analyzed using gas chromatography mass spectrometer(GC-MSD). The analytes were extracted using an automatic Soxhlet extractor, centrifuged for 10 minutes in a fast freezing centrifuge, and the supernatant was filtered with a syringe filter and then transferred into a 2 mL vial and injected in a split mode. In the established condition, the calibration curve showed linearity with a determination coefficient of 0.9981 or more. Sensitivity was 0.3145 ~ 1.6757, which showed a fairly wide range of sensitivity for each substance. The detection limit of the device was 0.0016 ~ 0.0423 ㎍/mL and the maximum detection limit was less than 0.05 ㎍/mL. The method detection limit ranged from 0.0030 ~ 0.0589 ㎍/mL. In addition, the limit of quantification ranged from 0.0096 to 0.1876 ㎍/mL, with precision ranging from 0.41 to 10.49 % and accuracy ranging from 83 to 116 %. The analytical method developed in this study was applied to commercial products.