Thiazolidine-4-carboxylic acid
[CAS 444-27-9]

Identification

• Classification: API >> Antineoplastic agents
• Name: Thiazolidine-4-carboxylic acid
• Synonyms: 1,3-Thiazolidine-4-carboxylic acid
• Molecular Formula: C₄H₇NO₂S
• Molecular Weight: 133.17
• Protein Sequence: X
• CAS Registry Number: 444-27-9
• EC Number: 207-146-6
• SMILES: C1C(NCS1)C(=O)O

Properties

• Density: 1.4±0.1 g/cm³ Calc.^*
• Melting point: 195 °C (Expl.)
• Boiling point: 350.3±37.0 °C 760 mmHg (Calc.)^*
• Flash point: 165.7±26.5 °C (Calc.)^*
• Index of refraction: 1.566 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H302-H319
• Safety Statements: P264-P264+P265-P270-P280-P301+P317-P305+P351+P338-P330-P337+P317-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	4	H302
Eye irritation	Eye Irrit.	2	H319
Specific target organ toxicity - single exposure	STOT SE	3	H335
Skin irritation	Skin Irrit.	2	H315
Eye irritation	Eye Irrit.	2A	H319
Acute toxicity	Acute Tox.	3	H301

Discovery and Applications

Thiazolidine-4-carboxylic acid is a saturated five-membered heterocyclic compound containing one sulfur atom and one nitrogen atom in the ring, with a carboxylic acid substituent at the 4-position. It belongs to the broader family of thiazolidine derivatives, which are structurally related to cysteine-derived cyclic adducts and are commonly encountered in amino acid chemistry and heterocyclic synthesis.

The thiazolidine ring system is formed by the cyclization of an amino thiol with a carbonyl compound, typically through a condensation reaction between a cysteine-type amino acid and an aldehyde. This reaction produces a stable five-membered ring containing both sulfur and nitrogen heteroatoms. Thiazolidines are often considered important intermediates in sulfur-containing amino acid chemistry and can serve as protective or transient forms of aldehydes in synthetic transformations.

In thiazolidine-4-carboxylic acid, the carboxylic acid group is attached to the carbon at position 4 of the heterocyclic ring. This functional group introduces significant polarity and allows the compound to participate in acid–base equilibria in aqueous solution. The carboxylic acid can be deprotonated to form a carboxylate anion, increasing water solubility and enabling ionic interactions in biological or chemical environments.

The heterocyclic ring contains both sulfur and nitrogen atoms, which impart distinct electronic and chemical properties. The sulfur atom contributes polarizability and weak basic character, while the nitrogen atom provides a site for protonation and hydrogen bonding. Together, these heteroatoms influence the stability and reactivity of the ring system, as well as its ability to coordinate metal ions in certain chemical contexts.

Because the ring is saturated, thiazolidine-4-carboxylic acid is non-aromatic and adopts flexible, puckered conformations to minimize steric strain. This conformational flexibility distinguishes it from aromatic heterocycles such as thiazoles and affects its physical and chemical behavior, including hydrogen bonding patterns and crystal packing in the solid state.

Thiazolidine derivatives are often studied in relation to amino acid chemistry and biochemical transformations. In biological systems, thiazolidine formation can occur as a reversible reaction between cysteine residues and aldehydes, making these structures relevant in the study of protein modification and small-molecule adduct formation. Thiazolidine-4-carboxylic acid itself can be viewed as a stabilized cyclic derivative of amino acid-like building blocks.

From a physicochemical perspective, the compound is expected to be highly polar due to the presence of both a carboxylic acid group and heteroatoms within the ring. It can engage in extensive hydrogen bonding interactions, both as a donor and acceptor, which typically leads to relatively high melting points and good solubility in polar solvents, particularly under basic conditions where the carboxylic acid is deprotonated.

The carboxylic acid functionality also provides a versatile synthetic handle. It can undergo standard transformations such as esterification, amidation, or conversion to activated derivatives like acid chlorides, enabling incorporation into larger molecular frameworks. The heterocyclic core can also participate in further functionalization depending on reaction conditions.

In coordination chemistry, thiazolidine derivatives may act as ligands through nitrogen and sulfur donor atoms, although the carboxylate group often dominates metal-binding interactions when deprotonated. This combination of donor sites can lead to diverse coordination modes in metal complexes.

Overall, thiazolidine-4-carboxylic acid is a saturated sulfur–nitrogen heterocycle bearing a carboxylic acid substituent, characterized by high polarity, conformational flexibility, and versatile chemical reactivity. Its significance lies in its relationship to amino acid-derived heterocycles and its utility as a building block and intermediate in organic and bioorganic chemistry.

References

2026. Bitter Bean (Parkia speciosa) Aqueous Extract: A Potential Natural Compound Agent Against Mammary Carcinoma in BALB/c Mice. Revista Brasileira de Farmacognosia.
DOI: 10.1007/s43450-025-00715-y

2026. Multifunction medical printing of cotton by Egyptian eco-friendly seaweeds using their synergistic interaction of polyphenolics: in-vitro and computational drug approach. Discover Applied Sciences.
DOI: 10.1007/s42452-025-08175-8

2018. Thermokinetic profile of NDM-1 and its inhibition by small carboxylic acids. Bioscience Reports.
URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5897741