2-Methyl-2-phenylpropionic acid
[CAS# 826-55-1]

Identification

• Classification: Pharmaceutical intermediate >> Heterocyclic compound intermediate >> Pyrimidine compound >> Carboxylic acid
• Name: 2-Methyl-2-phenylpropionic acid
• Synonyms: alpha,alpha-Dimethylphenylacetic acid
• Molecular Formula: C₁₀H₁₂O₂
• Molecular Weight: 164.20
• CAS Registry Number: 826-55-1
• EC Number: 212-556-3
• SMILES: CC(C)(C1=CC=CC=C1)C(=O)O

Properties

• Solubility: Insoluble (water) (Expl.)
• Density: 1.1±0.1 g/cm³, Calc.^*
• Melting point: 80-82 ºC (Expl.)
• Index of Refraction: 1.525, Calc.^*
• Boiling Point: 270.5±9.0 ºC (760 mmHg), Calc.^*, 146.5 ºC (Expl.)
• Flash Point: 167.7±13.9 ºC, Calc.^*

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H315-H319
• Precautionary Statements: P264-P264+P265-P280-P302+P352-P305+P351+P338-P321-P332+P317-P337+P317-P362+P364

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Skin irritation	Skin Irrit.	2	H315
Eye irritation	Eye Irrit.	2	H319
Specific target organ toxicity - single exposure	STOT SE	3	H335

Discovory and Applicatios

2-Methyl-2-phenylpropionic acid, also known as alpha-methylphenylacetic acid, is an aromatic alpha-substituted carboxylic acid. It has a diverse range of applications, especially in the fields of pharmaceuticals, fine chemicals, and organic synthesis. This compound plays a significant role due to its ability to serve as a precursor to various complex molecules, making it a versatile building block in the chemical industry.

The discovery of 2-Methyl-2-phenylpropionic acid dates back to the early 20th century, where its synthesis was initially developed as part of efforts to create more efficient synthetic pathways for aromatic acids. The compound's structure, which consists of a phenyl group attached to a branched methylated propionic acid backbone, lends itself well to various chemical reactions and transformations. The introduction of the methyl group at the alpha position stabilizes the molecule and increases its reactivity, making it a valuable intermediate in synthetic chemistry.

One of the major applications of 2-Methyl-2-phenylpropionic acid is in the pharmaceutical industry. It is used in the synthesis of non-steroidal anti-inflammatory drugs (NSAIDs), most notably in the production of ibuprofen. Ibuprofen, one of the most widely used pain relievers globally, is synthesized via the Friedel-Crafts acylation of 2-methyl-2-phenylpropionic acid with isobutylbenzene. This reaction serves as a key step in the industrial-scale production of ibuprofen, which is used to alleviate pain, reduce inflammation, and lower fever.

In addition to its pharmaceutical applications, 2-Methyl-2-phenylpropionic acid is employed in the production of various fine chemicals. It serves as an important intermediate in the synthesis of specialty esters, which are used in flavors, fragrances, and other consumer products. The compound's structure and functional groups allow for a variety of chemical transformations, including esterification and decarboxylation reactions, which are central to the creation of more complex molecules.

Furthermore, 2-Methyl-2-phenylpropionic acid is used in organic synthesis for the production of chiral compounds. Its chiral nature, which arises from the asymmetry of the alpha-carbon, makes it a valuable precursor in the creation of optically active molecules, which have significant applications in drug development, agrochemicals, and other high-value chemical products. The ability to use this compound as a starting material in asymmetric synthesis has made it a staple in the field of medicinal chemistry.

In the cosmetic industry, derivatives of 2-Methyl-2-phenylpropionic acid are sometimes used in formulations aimed at skin care, particularly in products that need to exhibit anti-inflammatory properties. The anti-inflammatory nature of compounds derived from this substance can contribute to formulations intended for sensitive skin or products designed to treat conditions like acne or rosacea.

Overall, 2-Methyl-2-phenylpropionic acid's discovery and applications span across multiple industries, particularly in the production of pharmaceuticals and fine chemicals. Its role as a key building block in the synthesis of widely used compounds like ibuprofen highlights its importance in the field of chemical manufacturing.

References

2024. Metallaphotoredox catalysis for sp3 C-H functionalizations through single-electron transfer. Nature Catalysis, 7(9).
DOI: 10.1038/s41929-024-01215-3

2021. Catalytic and non-catalytic amidation of carboxylic acid substrates. Molecular Diversity, 25(3).
DOI: 10.1007/s11030-021-10252-0

2010. High-performance liquid chromatography/mass spectrometric and proton nuclear magnetic resonance spectroscopic studies of the transacylation and hydrolysis of the acyl glucuronides of a series of phenylacetic acids in buffer and human plasma. Rapid communications in mass spectrometry : RCM, 24(9).
DOI: 10.1002/rcm.4740