1,2,3,4-TETRAHYDROISOQUINOLINE Property

Melting point:

−30 °C(lit.)

Boiling point:

232-233 °C(lit.)

Density 

1.064 g/mL at 25 °C(lit.)

vapor pressure 

3.33-97.9Pa at 20-58.5℃

refractive index 

n20/D 1.568(lit.)

Flash point:

210 °F

storage temp. 

Keep in dark place,Sealed in dry,Room Temperature

solubility 

20g/l

form 

Liquid

pka

9.66±0.20(Predicted)

color 

Clear yellow to brown

Water Solubility 

Soluble in water at 20°C 20g/L.

BRN 

116156

InChIKey

UWYZHKAOTLEWKK-UHFFFAOYSA-N

CAS DataBase Reference

91-21-4(CAS DataBase Reference)

EPA Substance Registry System

Isoquinoline, 1,2,3,4-tetrahydro- (91-21-4)

Safety

Hazard Codes 

Xi

Risk Statements 

36/37/38

Safety Statements 

26-36

WGK Germany 

3

RTECS 

NX4900000

Hazard Note 

Irritant

TSCA 

Yes

HS Code 

29334900

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Danger

Hazard statements

H301Toxic if swalloed

H310Fatal in contact with skin

H314Causes severe skin burns and eye damage

H332Harmful if inhaled

H371May cause damage to organs

H412Harmful to aquatic life with long lasting effects

Precautionary statements

P260Do not breathe dust/fume/gas/mist/vapours/spray.

P273Avoid release to the environment.

P280Wear protective gloves/protective clothing/eye protection/face protection.

P303+P361+P353IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

1,2,3,4-TETRAHYDROISOQUINOLINE Chemical Properties,Usage,Production

Synthesis

To a solution of the isoquinolinone (1.156 g, 9.90 mmol) and tert-butyl alcohol (0.88 mL, 11.9 mmol) in THF (30 mL) at −78 °C was added liquid ammonia (about 280 mL). Lithium was added in small pieces until the blue coloration persisted, after which the solution was stirred at −78 °C for 30 min. The blue coloration was dissipated with piperlyne, 4-methoxybenzyl chloride (4.83 g, 31.00 mmol) in THF (5 mL) was introduced by syringe, and the mixture was stirred for an additional 150 min at −78 °C. Solid ammonium chloride was added and then the ammonia was allowed to evaporate. The pale yellow residue was partitioned between CH2Cl2 (30 mL) and water (40 mL). The layers were separated, and the aqueous layer was extracted with CH2Cl2 (2 × 30 mL). The combined organic layers were washed with 10% sodium thiosulfate solution (20 mL), dried over magnesium sulfate, and concentrated. Flash chromatography (EtOAc:hexane, 2:1) on silica gave 2.21 g (75%) of the tetrahydroisoquinolinone.  
Reference: Schultz, A. G.; Guzi, T. J.; Larsson, E.; Rahm, R.; Thakker, K. Bidlack, J. M. J. Org. Chem. 1998, 63, 7795–7804.

Description

1, 2, 3, 4-TETRAHYDROISOQUINOLINE belongs to tetrahydroisoquinoline compound, which is encountered in a number of drugs, tubocurarine, one of the quaternary ammonium muscle relaxants^1-3. It is used as a reagent in the preparation of4-(1, 2, 4-oxadiazol-5-yl) piperidine-1-carboxamides as antiproliferative tubulin inhibitors¹. It can be used for the synthesis of 1, 2, 3, 4-tetrahydroisoquinoline-3-carboxylic acid (Tic), which has strong applications in peptides and peptidomimetics design and discovery². 1, 2, 3, 4-tetrahydroisoquinoline has been made into some derivatives with potential for prevention of parkinsonism⁴, cancer treatment5 and acting as Anticonvulsant Agents⁶.

Reference

1. https://www.alfa.com/en/catalog/L08143/
2. https://www.ncbi.nlm.nih.gov/pubmed/21235510
3. https://en.wikipedia.org/wiki/Tetrahydroisoquinoline
4. Okuda, K, Y. Kotake, and S. Ohta. "Parkinsonism-preventing activity of 1-methyl-1, 2, 3, 4-tetrahydroisoquinoline derivatives in C57BL mouse in vivo. Biological & Pharmaceutical Bulletin 29.7(2006):1401-1403.
5. Luca, Laura De, et al. "3D Pharmacophore Models for 1, 2, 3, 4‐Tetrahydroisoquinoline Derivatives Acting as Anticonvulsant Agents." Archiv Der Pharmazie 339.7(2006):388-400.
6. Hatano, H, et al. "Tumor-specific cytotoxic activity of 1, 2, 3, 4-tetrahydroisoquinoline derivatives against human oral squamous cell carcinoma cell lines."Anticancer Research 29.8(2009):3079-3086.

Chemical Properties

clear yellow to brown liquid

Uses

1,2,3,4-Tetrahydroisoquinoline is used as a reagent in the preparation of 4-(1,2,4-oxadiazol-5-yl)piperidine-1-carboxamides as antiproliferative tubulin inhibitors.

Definition

ChEBI: 1,2,3,4-tetrahydroisoquinoline is a member of isoquinolines.

Synthesis Reference(s)

The Journal of Organic Chemistry, 40, p. 1191, 1975 DOI: 10.1021/jo00897a001
Tetrahedron Letters, 26, p. 4633, 1985 DOI: 10.1016/S0040-4039(00)98771-9