Tetrahydroisoquinoline

This article is about the simple heterocyclic amine. For the selective MC4 agonist, see THIQ.
Tetrahydroisoquinoline
Names
Other names
1,2,3,4-Tetrahydroisoquinoline
Identifiers
91-21-4 YesY
ChEMBL ChEMBL14346 YesY
ChemSpider 6779 YesY
Jmol interactive 3D Image
PubChem 7046
RTECS number NX4900000
Properties
C9H11N
Molar mass 133.19 g/mol
Appearance Deep yellow liquid
Density 1.05 g/mL
Melting point −30 °C (−22 °F; 243 K)
Boiling point 235 to 239 °C (455 to 462 °F; 508 to 512 K)
Hazards
Irritant (Xi)
R-phrases R36/37/38
S-phrases S26 S36
Flash point 99 °C (210 °F; 372 K) (closed cup)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Infobox references

Tetrahydroisoquinoline is an organic compound with the chemical formula C9H11N. Classified as a secondary amine, it is derived from isoquinoline by hydrogenation. It is a colorless viscous liquid that is miscible with most organic solvents. The tetrahydroisoquinoline skeleton is encountered in a number of bioactive compounds and drugs.[1]

Reactions

As a secondary amine, tetrahydroisoquinoline has weakly basic properties and forms salts with strong acids. It can be dehydrogenated to give isoquinoline and hydrogenated to decahydroisoquinoline. Like other secondary amines, tetrahydroisoquinoline can be oxidized to the corresponding nitrone using hydrogen peroxide, catalyzed by selenium dioxide.[2]

Toxicology

Tetrahydroisoquinoline derivatives may be formed in the body as metabolites of some drugs, and this was once thought to be involved in the development of alcoholism.[3] This theory has now been discredited and is no longer generally accepted by the scientific community,[4] but endogenous production of neurotoxic tetrahydroisoquinoline derivatives such as norsalsolinol continue to be investigated as possible causes for some conditions such as Parkinson's disease.[5][6][7][8][9][10]

Tetrahydroisoquinolines

The tetrahydroisoquinoline skeleton is encountered in a number of drugs,[11] tubocurarine, one of the quaternary ammonium muscle relaxants. Drugs based on 4-substituted tetrahydroisoquinolines include nomifensine[12] and diclofensine. They can be prepared by N-alkylation of benzyl amines with haloacetophenones.[13] Naturally occurring tetrahydroisoquinolines includes cherylline.[14] and latifine.

Esproquin,[15] which shows hypotensive activity by virtue of its α-adrenergic blocking properties, is made from THIQ.

References

  1. ↑ Mitchinson, Andrew; Nadin, Alan "Saturated nitrogen heterocycles" Perkin 1 2000, pp. 2862-2892. doi:10.1039/A908537H
  2. ↑ Murahashi, S. (1987). "Selenium dioxide catalyzed oxidation of secondary amines with hydrogen peroxide. Simple synthesis of nitrones from secondary amines". Tetrahedron Letters 28 (21): 2383–2386. doi:10.1016/S0040-4039(00)96130-6.
  3. ↑ Blum, K.; Hamilton, M. G.; Hirst, M.; Wallace, J. E. (1978). "Putative role of isoquinoline alkaloids in alcoholism: a link to opiates". Alcoholism: Clinical and Experimental Research 2 (2): 113–120. doi:10.1111/j.1530-0277.1978.tb04710.x. PMID 350073.,Altshuler, H. L.; Shippenberg (1982). "Tetrahydroisoquinoline and opioid substrates of alcohol actions". Progress in clinical and biological research 90: 329–344. PMID 7202207., Myers, R. D. (1989). "Isoquinolines, beta-carbolines and alcohol drinking: involvement of opioid and dopaminergic mechanisms". Experientia 45 (5): 436–443. doi:10.1007/BF01952025. PMID 2656285.
  4. ↑ Myers, R. D. (1996). "Tetrahydroisoquinolines and alcoholism: where are we today?". Alcoholism: Clinical and Experimental Research 20 (3): 498–500. doi:10.1111/j.1530-0277.1996.tb01081.x. PMID 8727243., Musshoff, F.; Daldrup, T.; Bonte, W.; Leitner, A.; Lesch, O. M. (1996). "Formaldehyde-derived tetrahydroisoquinolines and tetrahydro-beta-carbolines in human urine". Journal of Chromatography B 683 (2): 163–176. doi:10.1016/0378-4347(96)00106-5. PMID 8891913., Sällström Baum, S.; Hill, R.; Kiianmaa, K.; Rommelspacher, H. (1999). "Effect of ethanol on (R)- and (S)-salsolinol, salsoline, and THP in the nucleus accumbens of AA and ANA rats". Alcohol (Fayetteville, N.Y.) 18 (2–3): 165–169. doi:10.1016/S0741-8329(98)00080-9. PMID 10456568., Musshoff, F.; Lachenmeier, D. W.; Schmidt, P.; Dettmeyer, R.; Madea, B. (2005). "Systematic regional study of dopamine, norsalsolinol, and (R/S)-salsolinol levels in human brain areas of alcoholics". Alcoholism: Clinical and Experimental Research 29 (1): 46–52. doi:10.1097/01.ALC.0000150011.81102.C2. PMID 15654290.
  5. ↑ Kotake Y, Tasaki Y, Makino Y, Ohta S, Hirobe M (December 1995). "1-Benzyl-1,2,3,4-tetrahydroisoquinoline as a parkinsonism-inducing agent: a novel endogenous amine in mouse brain and parkinsonian CSF". Journal of Neurochemistry 65 (6): 2633–8. doi:10.1046/j.1471-4159.1995.65062633.x. PMID 7595560.
  6. ↑ McNaught KS, Carrupt PA, Altomare C, Cellamare S, Carotti A, Testa B, Jenner P, Marsden CD (October 1998). "Isoquinoline derivatives as endogenous neurotoxins in the aetiology of Parkinson's disease". Biochemical Pharmacology 56 (8): 921–33. doi:10.1016/S0006-2952(98)00142-7. PMID 9776302.
  7. ↑ Lorenc-Koci E, Smiałowska M, Antkiewicz-Michaluk L, Gołembiowska K, Bajkowska M, Wolfarth S (2000). "Effect of acute and chronic administration of 1,2,3,4-tetrahydroisoquinoline on muscle tone, metabolism of dopamine in the striatum and tyrosine hydroxylase immunocytochemistry in the substantia nigra, in rats". Neuroscience 95 (4): 1049–59. doi:10.1016/S0306-4522(99)00511-4. PMID 10682712.
  8. ↑ Storch A, Ott S, Hwang YI, Ortmann R, Hein A, Frenzel S, Matsubara K, Ohta S, Wolf HU, Schwarz J (March 2002). "Selective dopaminergic neurotoxicity of isoquinoline derivatives related to Parkinson's disease: studies using heterologous expression systems of the dopamine transporter". Biochemical Pharmacology 63 (5): 909–20. doi:10.1016/S0006-2952(01)00922-4. PMID 11911843.
  9. ↑ Lorenc-Koci E, Antkiewicz-Michaluk L, Kamińska A, Lenda T, Zieba B, Wierońska J, Smiałowska M, Schulze G, Rommelspacher H (October 2008). "The influence of acute and chronic administration of 1,2-dimethyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline on the function of the nigrostriatal dopaminergic system in rats". Neuroscience 156 (4): 973–86. doi:10.1016/j.neuroscience.2008.08.050. PMID 18809471.
  10. ↑ Kobayashi H, Fukuhara K, Tada-Oikawa S, Yada Y, Hiraku Y, Murata M, Oikawa S (January 2009). "The mechanisms of oxidative DNA damage and apoptosis induced by norsalsolinol, an endogenous tetrahydroisoquinoline derivative associated with Parkinson's disease". Journal of Neurochemistry 108 (2): 397–407. doi:10.1111/j.1471-4159.2008.05774.x. PMID 19012744.
  11. ↑ Scott, Jack D.; Williams, Robert M. (2002). "Chemistry and Biology of the Tetrahydroisoquinoline Antitumor Antibiotics". Chemical Reviews 102: 1669–1730. doi:10.1021/cr010212u.
  12. ↑ Schneider, C. S.; Weber, K. H.; Daniel, H.; Bechtel, W. D.; Boeke-Kuhn, K. (1984). "Synthesis and antidepressant activity of 4-aryltetrahydrothieno[2,3-c]pyridine derivatives". Journal of Medicinal Chemistry 27 (9): 1150. doi:10.1021/jm00375a011.
  13. ↑ BG 49761
  14. ↑ cherylline
  15. ↑ Gray, Allan P.; Shiley, Richard H. (1973). "Preparation and cardiovascular actions of a group of tetrahydroisoquinoline derivatives". Journal of Medicinal Chemistry 16 (7): 859–861. doi:10.1021/jm00265a028. ISSN 0022-2623.
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