Glycine tert butyl ester hydrochloride is the hydrochloride salt of glycine tert-butyl ester, commonly used as an intermediate in organic synthesis and medicinal chemistry. Its properties, performance characteristics, and applications are detailed below:

I. Basic Properties

Physical Properties

Appearance: Typically a white to off-white crystalline powder, odorless or with a slight characteristic odor.

Solubility: Soluble in water, methanol, ethanol, and other polar organic solvents; poorly soluble in non-polar solvents such as ether and n-hexane, due to its polar salt structure.

Molecular Formula and Weight: C₆H₁₃NO₂·HCl, with a molecular weight of 167.63 (Glycine tert-butyl ester itself has the formula C₆H₁₃NO₂; it forms a stable salt upon combination with HCl).

Melting Point: Approximately 145–148°C (may vary slightly with purity); decomposition may occur at higher temperatures.

Chemical Properties

Stability: Relatively stable under dry, light-protected, and room temperature conditions. Under strongly basic conditions, the ester group is prone to hydrolysis, producing glycine and tert-butanol. It may undergo oxidation reactions when exposed to strong oxidizers, which should be avoided during storage.

Acidity: Due to the hydrochloride component, its aqueous solution is acidic (low pH).

Reactive Characteristics:

The ester group (-COO-tBu) exhibits typical ester reactivity and can undergo hydrolysis under acidic or basic catalysis, as well as transesterification.

The amino group, present as -NH₃⁺Cl⁻, can be deprotonated under basic conditions to form -NH₂, which can participate in nucleophilic substitution, condensation, or reactions with acid chlorides to form amides.

As an amino acid derivative, it is capable of participating in peptide bond formation and is widely used as an intermediate in peptide synthesis.

II. Performance Characteristics

High Reaction Selectivity: The tert-butyl ester group (-tBu) is a common protecting group for carboxyl groups. It is relatively stable under mildly acidic conditions but can be selectively removed under strong acidic conditions (e.g., trifluoroacetic acid, TFA), with minimal impact on other functional groups such as amines or hydroxyls. This enables controlled protection and deprotection in synthetic chemistry.

Excellent Water Solubility: Compared to the free form of glycine tert-butyl ester (which is more hydrophobic), the hydrochloride salt has greatly improved water solubility due to its ionic nature, making it suitable for aqueous-phase reactions and biologically compatible systems.

Ease of Handling: As a crystalline powder, it is easy to weigh, store, and transport. Its moderate chemical stability allows for convenient handling without requiring stringent storage conditions (sealed and light-protected under normal conditions is sufficient).

Biocompatibility Basis: As a glycine derivative, it retains structural similarity to natural amino acids, allowing for a basic level of biocompatibility in pharmaceutical intermediate synthesis. This facilitates subsequent structural modifications into biologically active compounds.

III. Applications

Organic Synthesis and Peptide Chemistry

Used as a carboxyl-protected glycine derivative in peptide synthesis. In both solid-phase and solution-phase peptide synthesis, protecting the carboxyl group of glycine prevents premature reactions with amino groups, enabling targeted peptide chain assembly. After the assembly, the tert-butyl ester group can be removed with trifluoroacetic acid to yield the desired peptide.

Utilized in the synthesis of complex organic molecules containing glycine moieties, such as heterocyclic compounds and pharmaceutical intermediates, by exploiting the reactivity of the ester group to introduce diverse structures.

Pharmaceutical Intermediates

Used in the synthesis of drugs containing glycine structures, such as anti-ulcer and antiviral agents. For instance, in the synthesis of some gastric mucosa protectants, it serves as a glycine donor and connects to other active groups via its ester, enhancing the drug’s stability and targeting.

Employed in the preparation of amino acid derivative drugs, where modifications to the amino or ester groups help adjust solubility, metabolic pathways, and biological activity.

Research and Analytical Applications

Acts as a standard or reagent in studies of amino acid metabolism and the mechanisms of ester hydrolysis reactions.

Used as a reference compound in chromatographic methods (e.g., HPLC) for method development or quantitative analysis of samples.

IV. Precautions

Store in a sealed, light-protected, dry environment to prevent moisture absorption and hydrolysis under alkaline conditions.

Avoid direct skin contact or inhalation of dust during handling. Use gloves and a dust mask. In case of accidental contact, rinse immediately with plenty of water.

 

Thanks to its unique protecting group properties, excellent reactivity, and ease of use, glycine tert-butyl ester hydrochloride is an important intermediate in organic synthesis, peptide chemistry, and pharmaceutical research, playing a key role in selective synthesis and structural modification.