Tetrahydro pyrrole
[CAS# 123-75-1]

Identification

• Classification: Flavors and spices >> Synthetic spice >> Lactone and oxygen-containing heterocyclic compound >> Thiazole, thiophene and pyridine
• Name: Tetrahydro pyrrole
• Synonyms: Pyrrolidine
• Molecular Formula: C₄H₉N
• Molecular Weight: 71.12
• CAS Registry Number: 123-75-1
• EC Number: 204-648-7
• FEMA: 3523
• SMILES: C1CCNC1

Properties

• Density: 0.8$+/-$0.1 g/cm³ Calc.^*, 0.856 g/mL (Expl.)
• Melting point: -63 $degree$C (Expl.)
• Boiling point: 89.5$+/-$8.0 $degree$C 760 mmHg (Calc.)^*, 87 - 88 $degree$C (Expl.)
• Flash point: 2.8 $degree$C (Calc.)^*, 2 $degree$C (Expl.)
• Solubility: Soluble in alcohol, ether, chloroform. Miscible with water (Expl.)
• Index of refraction: 1.428 (Calc.)^*, 1.443 (Expl.)

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

Safety Data

• Hazard Symbols: GHS02;GHS05;GHS07 DangerGHS02
• Risk Statements: H225-H302-H314-H318-H332
• Safety Statements: P210-P233-P240-P241-P242-P243-P260-P261-P264-P264+P265-P270-P271-P280-P301+P317-P301+P330+P331-P302+P361+P354-P303+P361+P353-P304+P340-P305+P354+P338-P316-P317-P321-P330-P363-P370+P378-P403+P235-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	4	H332
Acute toxicity	Acute Tox.	4	H302
Skin corrosion	Skin Corr.	1A	H314
Flammable liquids	Flam. Liq.	2	H225
Serious eye damage	Eye Dam.	1	H318
Skin corrosion	Skin Corr.	1B	H314
Acute toxicity	Acute Tox.	4	H312
Acute toxicity	Acute Tox.	3	H301
Acute toxicity	Acute Tox.	3	H331
Specific target organ toxicity - single exposure	STOT SE	2	H371
Substances or mixtures corrosive to metals	Met. Corr.	1	H290
Chronic hazardous to the aquatic environment	Aquatic Chronic	3	H412

• Transport Information: UN 1922

Discovery and Applications

Tetrahydropyrrole, more commonly known as pyrrolidine, is a saturated five-membered nitrogen-containing heterocycle with the molecular formula C₄H₉N. It can be viewed as the fully hydrogenated derivative of pyrrole, in which the aromaticity of the ring has been lost and replaced by a flexible, saturated structure. This compound has been known since the nineteenth century and has become an important building block in organic chemistry, pharmaceuticals, and industrial applications.

The molecular structure of tetrahydropyrrole consists of a five-membered ring containing four carbon atoms and one nitrogen atom. Unlike pyrrole, which is aromatic, pyrrolidine is non-aromatic and adopts a puckered conformation that reduces angle strain. The nitrogen atom carries a lone pair of electrons, making the compound a secondary amine with significant basicity and nucleophilicity. This property allows it to participate readily in a wide range of chemical reactions, including alkylation, acylation, and condensation processes.

Tetrahydropyrrole is commonly prepared by the hydrogenation of pyrrole in the presence of a suitable catalyst, a method that has been well established in the literature. It can also be synthesized from 1,4-diaminobutane through cyclization reactions or by reduction of suitable precursors. These methods provide efficient routes to the compound on both laboratory and industrial scales, yielding a stable liquid that is miscible with water and many organic solvents.

One of the most important applications of tetrahydropyrrole is in organic synthesis, where it serves as a base and nucleophilic catalyst. It is widely used in the formation of enamines when reacted with carbonyl compounds. Enamines are key intermediates in many carbon–carbon bond-forming reactions, such as the Stork enamine reaction, allowing selective functionalization of aldehydes and ketones. This role has made pyrrolidine an essential reagent in synthetic organic chemistry.

In medicinal chemistry, tetrahydropyrrole is a common structural motif found in numerous bioactive compounds and pharmaceuticals. The pyrrolidine ring is present in natural products and synthetic drugs, where it contributes to molecular rigidity, basicity, and the ability to interact with biological targets through hydrogen bonding and ionic interactions. As a result, pyrrolidine derivatives are used in the design of enzyme inhibitors, receptor ligands, and other therapeutic agents.

Tetrahydropyrrole is also used in the production of agrochemicals, rubber chemicals, and corrosion inhibitors. Its reactivity and ability to form stable derivatives make it a versatile intermediate in industrial chemistry. Additionally, it can serve as a ligand in coordination chemistry, binding to metal centers through the nitrogen atom and influencing catalytic activity or stability of metal complexes.

Overall, tetrahydropyrrole is a fundamental nitrogen-containing heterocycle with broad applications in synthesis, industry, and pharmaceutical development. Its combination of basicity, nucleophilicity, and structural flexibility makes it a valuable reagent and building block in modern chemistry.

References

2025. Plant proteins for human and environmental health: knowledge, barriers, and levers for their development, a case study in France. A review. Agronomy for Sustainable Development.
DOI: 10.1007/s13593-025-01034-1

2025. Synthesis of Fully Substituted 1,2,3-Triazoles via Organocatalytic [3+2] Cycloaddition: Incorporation of Pyrazole and Imidazole Scaffolds as Potent EGFR-Targeted Anticancer Agents. Russian Journal of Bioorganic Chemistry.
DOI: 10.1134/s1068162024606633

2025. Synthesis of highly strained para-cyclophanes via ring-expansion [5,5]-sigmatropic rearrangement reaction. Nature Chemistry.
DOI: 10.1038/s41557-025-01878-w