Wikipedia:WikiProject Chemicals/Chembox validation/VerifiedDataSandbox and Tetrahydroisoquinoline: Difference between pages

{{About|the simple heterocyclic amine|the selective MC₄ agonist|THIQ}}

| Verifiedimages = changed

| Watchedfields = changed

| verifiedrevid = 470604309

| ImageFile = Tetrahydroisoquinoline.

| PIN = 1,2,3,4-Tetrahydroisoquinoline

| OtherNames =

|Section1={{Chembox Identifiers

| CASNo = 91-21-4

| CASNo_Ref = {{cascite|correct|CAS}}

| Abbreviations = TIQ, THIQ

| ChEMBL_Ref = {{ebicite|correct|EBI}}

| ChEMBL = 14346

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| EC_number = 202-050-0

| PubChem = 7046

| RTECS = NX4900000

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = 56W89FBX3E

| SMILES = c1ccc2c(c1)CCNC2

|Section2={{Chembox Properties

| Formula = C₉H₁₁N

| MolarMass = 133.19 g/mol

| Appearance = Deep yellow liquid

| Density = 1.05 g/mL

| = -30

| 239

| BoilingPt_notes =

| Solubility =

|Section3={{Chembox Hazards

| MainHazards =

| = 99

| FlashPt_notes = (closed cup)

| AutoignitionPt =

| GHS_ref=<ref>{{cite web |title=1,2,3,4-Tetrahydroisoquinoline |url=https://pubchem.ncbi.nlm.nih.gov/compound/7046#section=Safety-and-Hazards |website=pubchem.ncbi.nlm.nih.gov |access-date=12 December 2021 |language=en}}</ref>

| GHSPictograms = {{GHS05}}{{GHS06}}{{GHS08}}

| GHSSignalWord = Danger

| HPhrases = {{H-phrases|301|310|314|332|371|412}}

| PPhrases = {{P-phrases|260|261|262|264|270|271|273|280|301+310|301+330+331|302+350|302+352|303+361+353|304+312|304+340|305+351+338|309+311|310|312|322|330|332+313|337+313|361|362|363|403+233|405|501}}

'''Tetrahydroisoquinoline''' ('''TIQ''' or '''THIQ''') 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.<ref>{{cite journal | doi = 10.1039/A908537H | issue=17 | title=Saturated nitrogen heterocycles | year=2000 | journal=Journal of the Chemical Society, Perkin Transactions 1 | pages=2862–2892 | last1 = Mitchenson | first1 = Andrew}}</ref><ref name=Scott/>

==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]].<ref>{{Cite journal| title = Selenium dioxide catalyzed oxidation of secondary amines with hydrogen peroxide. Simple synthesis of nitrones from secondary amines| journal = Tetrahedron Letters| issue = 21 | first1 = S.| volume = 28| year = 1987| doi = 10.1016/S0040-4039(00)96130-6| last1 = Murahashi| pages = 2383–2386}}</ref>

==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]].<ref>{{Cite journal

| pmid = 350073

| year = 1978

| last1 = Blum | first1 = K.

| last2 = Hamilton

| last3 = Hirst

| last4 = Wallace

| title = Putative role of isoquinoline alkaloids in alcoholism: a link to opiates

| volume = 2

| issue = 2

| pages = 113–120

| journal = Alcoholism: Clinical and Experimental Research

| doi = 10.1111/j.1530-0277.1978.tb04710.x | first2 = M. G. | first3 = M. | first4 = J. E.

}},{{Cite journal

| pmid = 7202207

| year = 1982

| last1 = Altshuler | first1 = H. L.

| last2 = Shippenberg

| title = Tetrahydroisoquinoline and opioid substrates of alcohol actions

| volume = 90

| pages = 329–344

| journal = Progress in Clinical and Biological Research

}}, {{Cite journal

| pmid = 2656285

| year = 1989

| last1 = Myers | first1 = R. D.

| title = Isoquinolines, beta-carbolines and alcohol drinking: involvement of opioid and dopaminergic mechanisms

| volume = 45

| issue = 5

| pages = 436–443

| journal = Experientia

| doi = 10.1007/BF01952025

| s2cid = 1513683

}}</ref> This theory has now been discredited and is no longer generally accepted by the scientific community,<ref>{{Cite journal

| pmid = 8727243

| year = 1996

| last1 = Myers | first1 = R. D.

| title = Tetrahydroisoquinolines and alcoholism: where are we today?

| volume = 20

| issue = 3

| pages = 498–500

| journal = Alcoholism: Clinical and Experimental Research

| doi = 10.1111/j.1530-0277.1996.tb01081.x

}}, {{Cite journal

| pmid = 8891913

| year = 1996

| last1 = Musshoff | first1 = F.

| last2 = Daldrup

| last3 = Bonte

| last4 = Leitner

| last5 = Lesch

| title = Formaldehyde-derived tetrahydroisoquinolines and tetrahydro-beta-carbolines in human urine

| volume = 683

| issue = 2

| pages = 163–176

| journal = Journal of Chromatography B

| doi = 10.1016/0378-4347(96)00106-5 | first2 = T. | first3 = W. | first4 = A. | first5 = O. M.

}}, {{Cite journal

| doi = 10.1016/S0741-8329(98)00080-9

| pmid = 10456568

| year = 1999

| last1 = Sällström Baum | first1 = S.

| last2 = Hill

| last3 = Kiianmaa

| last4 = Rommelspacher

| title = Effect of ethanol on (R)- and (S)-salsolinol, salsoline, and THP in the nucleus accumbens of AA and ANA rats

| volume = 18

| issue = 2–3

| pages = 165–169

| journal = Alcohol (Fayetteville, N.Y.) | first2 = R. | first3 = K. | first4 = H.

}}, {{Cite journal

| pmid = 15654290

| year = 2005

| last1 = Musshoff | first1 = F.

| last2 = Lachenmeier

| last3 = Schmidt

| last4 = Dettmeyer

| last5 = Madea

| title = Systematic regional study of dopamine, norsalsolinol, and (R/S)-salsolinol levels in human brain areas of alcoholics

| volume = 29

| issue = 1

| pages = 46–52

| journal = Alcoholism: Clinical and Experimental Research

| doi = 10.1097/01.ALC.0000150011.81102.C2 | first2 = D. W. | first3 = P. | first4 = R. | first5 = B.

}}</ref> 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]].<ref name="pmid7595560">{{cite journal |vauthors=Kotake Y, Tasaki Y, Makino Y, Ohta S, Hirobe M |title=1-Benzyl-1,2,3,4-tetrahydroisoquinoline as a parkinsonism-inducing agent: a novel endogenous amine in mouse brain and parkinsonian CSF |journal=Journal of Neurochemistry |volume=65 |issue=6 |pages=2633–8 |date=December 1995 |pmid=7595560 |doi= 10.1046/j.1471-4159.1995.65062633.x|s2cid=39449026 }}</ref><ref name="pmid9776302">{{cite journal |vauthors=McNaught KS, Carrupt PA, Altomare C, Cellamare S, Carotti A, Testa B, Jenner P, Marsden CD |title=Isoquinoline derivatives as endogenous neurotoxins in the aetiology of Parkinson's disease |journal=[[Biochemical Pharmacology (journal)|Biochemical Pharmacology]] |volume=56 |issue=8 |pages=921–33 |date=October 1998 |pmid=9776302 |doi= 10.1016/S0006-2952(98)00142-7}}</ref><ref name="pmid10682712">{{cite journal |vauthors=Lorenc-Koci E, Smiałowska M, Antkiewicz-Michaluk L, Gołembiowska K, Bajkowska M, Wolfarth S |title=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 |journal=Neuroscience |volume=95 |issue=4 |pages=1049–59 |year=2000 |pmid=10682712 |doi= 10.1016/S0306-4522(99)00511-4|s2cid=13549697 }}</ref><ref name="pmid11911843">{{cite journal |vauthors=Storch A, Ott S, Hwang YI, Ortmann R, Hein A, Frenzel S, Matsubara K, Ohta S, Wolf HU, Schwarz J |title=Selective dopaminergic neurotoxicity of isoquinoline derivatives related to Parkinson's disease: studies using heterologous expression systems of the dopamine transporter |journal=Biochemical Pharmacology |volume=63 |issue=5 |pages=909–20 |date=March 2002 |pmid=11911843 |doi= 10.1016/S0006-2952(01)00922-4}}</ref><ref name="pmid18809471">{{cite journal |vauthors=Lorenc-Koci E, Antkiewicz-Michaluk L, Kamińska A, Lenda T, Zieba B, Wierońska J, Smiałowska M, Schulze G, Rommelspacher H |title=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 |journal=Neuroscience |volume=156 |issue=4 |pages=973–86 |date=October 2008 |pmid=18809471 |doi=10.1016/j.neuroscience.2008.08.050 |s2cid=44658852 }}</ref><ref name="pmid19012744">{{cite journal |vauthors=Kobayashi H, Fukuhara K, Tada-Oikawa S, Yada Y, Hiraku Y, Murata M, Oikawa S |title=The mechanisms of oxidative DNA damage and apoptosis induced by norsalsolinol, an endogenous tetrahydroisoquinoline derivative associated with Parkinson's disease |journal=Journal of Neurochemistry |volume=108 |issue=2 |pages=397–407 |date=January 2009 |pmid=19012744 |doi=10.1111/j.1471-4159.2008.05774.x |doi-access=free }}</ref>

==Tetrahydroisoquinolines==

The tetrahydroisoquinoline skeleton is present in a number of drugs,<ref name=Scott>{{cite journal | last1 = Scott | first1 = Jack D. | last2 = Williams | first2 = Robert M. | year = 2002 | title = Chemistry and Biology of the Tetrahydroisoquinoline Antitumor Antibiotics | journal = Chemical Reviews | volume = 102 | issue = 5| pages = 1669–1730 | doi = 10.1021/cr010212u | pmid = 11996547 }}</ref> such as [[tubocurarine]], one of the [[quaternary ammonium muscle relaxants]]. Drugs based on 4-substituted tetrahydroisoquinolines include [[nomifensine]]<ref>{{Cite journal| last1 = Schneider | first1 = C. S.| last2 = Weber| last3 = Daniel| last4 = Bechtel| last5 = Boeke-Kuhn| title = Synthesis and antidepressant activity of 4-aryltetrahydrothieno[2,3-c]pyridine derivatives| journal = [[Journal of Medicinal Chemistry]]| volume = 27| issue = 9| pages = 1150–1155| year = 1984 | doi = 10.1021/jm00375a011 | first2 = K. H. | first3 = H. | first4 = W. D. | first5 = K.| pmid = 6471069}}</ref> and [[diclofensine]]. They can be prepared by ''N''-alkylation of benzyl amines with halo[[acetophenone]]s.<ref>{{Patent|BG|49761}}</ref> Naturally occurring tetrahydroisoquinolines include [[cherylline]]<ref>[http://www.chemspider.com/Chemical-Structure.81315.html cherylline]</ref> and [[latifine]].

[[Esproquin]],<ref name="GrayShiley1973">{{cite journal|last1=Gray|first1=Allan P.|last2=Shiley|first2=Richard H.|title=Preparation and cardiovascular actions of a group of tetrahydroisoquinoline derivatives|journal=Journal of Medicinal Chemistry|volume=16|issue=7|year=1973|pages=859–861|issn=0022-2623|doi=10.1021/jm00265a028|pmid=4146907}}</ref> which shows hypotensive activity by virtue of its α-adrenergic blocking properties, is made from THIQ.

==References==

{{Reflist}}

[[Category:Tetrahydroisoquinolines| ]]