Methyl 2-amino-2-methylpropanoate hydrochloride
[CAS# 15028-41-8]

Identification

• Classification: Organic raw materials >> Carboxylic compounds and derivatives >> Salt of carboxylic acid ester and its derivatives
• Name: Methyl 2-amino-2-methylpropanoate hydrochloride
• Synonyms: 2-Aminoisobutyric acid methyl ester hydrochloride
• Protein Sequence: X
• Molecular Formula: C₅H₁₁NO₂^.HCl
• Molecular Weight: 153.61
• CAS Registry Number: 15028-41-8
• EC Number: 864-887-3
• SMILES: CC(C)(C(=O)OC)N.Cl

Properties

• Melting point: 185 ºC (Decomposes) (Expl.)

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H315-H319-H335
• Precautionary Statements: P261-P264-P264+P265-P271-P280-P302+P352-P304+P340-P305+P351+P338-P319-P321-P332+P317-P337+P317-P362+P364-P403+P233-P405-P501

Hazard Classification

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

Discovory and Applicatios

Methyl 2-amino-2-methylpropanoate hydrochloride is a chemically defined compound belonging to the class of amino acid esters and their salts. Its molecular formula is C₅H₁₂ClNO₂, and the compound consists of a methyl ester derivative of 2-amino-2-methylpropanoic acid (commonly known as α-aminoisobutyric acid) paired with a hydrochloride counterion. This compound combines the ester functionality with an amino group, which is protonated to form the hydrochloride salt, enhancing its solubility and stability.

The parent amino acid, 2-amino-2-methylpropanoic acid, is a non-proteinogenic amino acid featuring a tertiary α-carbon substituted with two methyl groups, conferring steric hindrance and distinctive chemical behavior. The methyl ester modification converts the carboxylic acid into a methyl ester group (–COOCH₃), often employed to improve lipophilicity and membrane permeability in pharmaceutical contexts. Formation of the hydrochloride salt involves protonation of the amino group, resulting in a positively charged ammonium ion balanced by a chloride ion, which generally improves aqueous solubility and facilitates handling.

Synthesis of methyl 2-amino-2-methylpropanoate hydrochloride is typically carried out by esterification of 2-amino-2-methylpropanoic acid with methanol in the presence of an acid catalyst such as hydrochloric acid or sulfuric acid. The reaction proceeds via Fischer esterification, producing the methyl ester. Subsequent treatment with hydrochloric acid ensures the formation of the hydrochloride salt, stabilizing the amino group and yielding a crystalline solid suitable for storage and application.

Chemically, the compound exhibits typical behaviors of amino acid esters and their salts. The protonated amino group can participate in acid-base reactions and hydrogen bonding, while the ester moiety is susceptible to hydrolysis under acidic or basic conditions, regenerating the free acid. The presence of steric hindrance around the α-carbon influences reactivity and biological interactions, often leading to distinct properties compared to common amino acids.

Applications of methyl 2-amino-2-methylpropanoate hydrochloride primarily reside in organic synthesis and medicinal chemistry. It serves as an important building block or intermediate in the preparation of peptides, peptidomimetics, and other bioactive compounds. The compound’s structural features contribute to conformational constraints when incorporated into peptides, potentially enhancing stability or modifying biological activity. Moreover, the hydrochloride salt form facilitates handling in aqueous environments and formulation in pharmaceutical preparations.

In addition, this compound can be employed in asymmetric synthesis as a chiral auxiliary or ligand precursor due to its amino acid origin, supporting stereoselective reactions. Its ester functionality enables further chemical modifications such as amidation or reduction to corresponding alcohols, expanding its utility in synthetic pathways.

Characterization of methyl 2-amino-2-methylpropanoate hydrochloride is routinely performed using analytical techniques. Proton nuclear magnetic resonance (²H NMR) spectroscopy identifies characteristic signals from methyl groups, methine protons adjacent to amino and ester functions, and ammonium protons. Carbon-13 NMR confirms ester and aliphatic carbons. Infrared (IR) spectroscopy reveals absorption bands associated with the ester carbonyl stretch near 1740 cm⁻¹, N–H stretching vibrations, and salt formation effects. Elemental analysis and mass spectrometry provide molecular weight confirmation and purity assessment.

Physically, the compound typically appears as a white to off-white crystalline solid, exhibiting good stability under standard storage conditions. It is highly soluble in water and polar organic solvents such as methanol and ethanol, reflecting its ionic and polar nature.

In summary, methyl 2-amino-2-methylpropanoate hydrochloride is a stable amino acid ester salt with significant relevance in organic synthesis and pharmaceutical research. Its ester and protonated amino functionalities afford it versatile chemical reactivity and biological applicability, making it a valuable intermediate and reagent in the preparation of bioactive molecules and peptide-based compounds.

References

2015. Synthesis of the First Representatives of Spiro-1λ6-isothiazolidine-1,1,4-triones. Synthesis, 46(12).
DOI: 10.1055/s-0034-1380434