1,2,3,4-Tetrahydroquinoline
[CAS# 635-46-1]

Identification

• Classification: Pharmaceutical intermediate >> Heterocyclic compound intermediate >> Quinoline compound
• Name: 1,2,3,4-Tetrahydroquinoline
• Synonyms: THQ
• Molecular Formula: C₉H₁₁N
• Molecular Weight: 133.19
• CAS Registry Number: 635-46-1
• EC Number: 211-237-6
• SMILES: C1CC2=CC=CC=C2NC1

Properties

• Density: 1.0±0.1 g/cm³ Calc.^*, 1.061 g/mL (Expl.)
• Melting point: 9 - 14 ºC (Expl.)
• Boiling point: 250.8±10.0 ºC 760 mmHg (Calc.)^*, 249 ºC (Expl.)
• Flash point: 100.6 ºC (Calc.)^*, 101 ºC (Expl.)
• Index of refraction: 1.544 (Calc.)^*, 1.594 (Expl.)

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

Safety Data

• Hazard Symbols: Pictogram(s)
• Risk Codes: R36/37/38
• Safety Description: S26;S36/37

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.	2	H319
Carcinogenicity	Carc.	1B	H350
Serious eye damage	Eye Dam.	1	H318
Acute toxicity	Acute Tox.	4	H302
Acute toxicity	Acute Tox.	4	H332
Skin corrosion	Skin Corr.	1B	H314
Acute toxicity	Acute Tox.	4	H312

Discovory and Applicatios

1,2,3,4-Tetrahydroquinoline is a heterocyclic organic compound belonging to the class of partially saturated quinolines. It consists of a bicyclic structure formed by the fusion of a benzene ring with a partially hydrogenated pyridine ring, resulting in a saturated nitrogen-containing six-membered ring fused to an aromatic ring. This compound is of interest due to its structural similarity to quinoline, but with reduced aromaticity in the nitrogen-containing ring.

The compound was first studied in the mid-20th century as part of research into heterocyclic chemistry, where the synthesis and properties of tetrahydroquinolines and related structures were explored. Its relatively simple structure and accessibility through various synthetic routes have made it a valuable scaffold in organic chemistry.

1,2,3,4-Tetrahydroquinoline can be synthesized by hydrogenation of quinoline or by cyclization methods involving appropriate precursors containing amino and aromatic groups. Its chemistry includes typical reactions of secondary amines and aromatic compounds, such as electrophilic substitution, oxidation, and reduction, making it a versatile intermediate in organic synthesis.

In applied chemistry, 1,2,3,4-tetrahydroquinoline serves as an important building block for the preparation of pharmaceuticals, agrochemicals, and dyes. Its nitrogen-containing heterocyclic core is present in many biologically active molecules, contributing to binding affinity and biological activity. Derivatives of tetrahydroquinoline are found in compounds with activities including antimicrobial, anticancer, anti-inflammatory, and central nervous system effects.

The compound has also been studied as a ligand in coordination chemistry due to the lone pair of electrons on the nitrogen atom, which can coordinate to metal centers. This property is utilized in catalyst design and development of metal complexes for various applications in organic synthesis.

In summary, 1,2,3,4-tetrahydroquinoline is a partially saturated heterocyclic compound related to quinoline. Its discovery and development have supported advances in synthetic organic chemistry and drug discovery. The compound’s structural features and chemical reactivity make it a useful intermediate and scaffold in the synthesis of diverse biologically active molecules and coordination complexes.

References

2002. Antiplasmodial and Cytotoxic Activity of Galipinine and other Tetrahydroquinolines from Galipea officinalis. Planta Medica, 68(1).
DOI: 10.1055/s-2002-19869

2004. Intramolecular Arylation Reactions of Alkenes: A Flexible Approach to Chromans and Tetrahydroquinoline Derivatives. Journal of the American Chemical Society, 126(8).
DOI: 10.1021/ja0397299

2024. Thermodynamics of the Sorption of Quinoline Derivatives, 1,2,3,4-Tetrahydroquinoline and Pyridazino[4,5-c]Quinoline Under Conditions of RP HPLC. Russian Journal of Physical Chemistry A, 98(11).
DOI: 10.1134/s003602442470208x