Editing Mescaline (section)

==Chemistry==
Mescaline, also known as 3,4,5-trimethoxyphenethylamine (3,4,5-TMPEA), is a [[substituted phenethylamine]] [[chemical derivative|derivative]].<ref name="PubChem">{{cite web | title=Mescaline | website=PubChem | url=https://pubchem.ncbi.nlm.nih.gov/compound/4076 | access-date=6 November 2024}}</ref><ref name="Doesburg-vanKleffensZimmermann-KlemdGründemann2023" /> It is closely [[structural analog|structurally related]] to the [[dopamine]] (3,4-dihydroxyphenethylamine), [[norepinephrine]] (3,4,β-trihydroxyphenethylamine), and [[epinephrine]] (3,4,β-trihydroxy-''N''-methylphenethylamine).<ref name="PubChem" /> In contrast to the catecholamine neurotransmitters however, mescaline acts on the [[serotonin|serotonergic]] system rather than on the [[dopaminergic]] or [[adrenergic]] systems.

The drug is relatively [[hydrophilic]] with low [[lipophilicity|fat solubility]].<ref name="Doesburg-vanKleffensZimmermann-KlemdGründemann2023" /> Its predicted [[partition coefficient|log P]] ([[XLogP3]]) is 0.7.<ref name="PubChem" />

The physical properties and general chemistry of mescaline have been reviewed.<ref name="Patel1968">{{cite journal | vauthors = Patel AR | title = Mescaline and related compounds | journal = Fortschr Arzneimittelforsch | volume = 11 | issue = | pages = 11–47 | date = 1968 | pmid = 4873202 | doi = 10.1007/978-3-0348-7062-7_1 | isbn = 978-3-0348-7064-1 | url = }}</ref>

===Synthesis===
[[File:Synthetic mescaline powder i2001e0151 ccby3.jpg|right|thumb|Laboratory synthetic mescaline biosynthesized{{clarify|reason=Is it lab synthesized or biosynthesized then lab extracted??|date=March 2025}} from {{nowrap|peyote{{hsp}}{{mdash}}{{hsp}}}}this was the first psychedelic compound to be extracted and isolated<ref>{{cite web|url=https://www.mescaline.com/exp/|title=Mescaline : D M Turner|website=www.mescaline.com}}</ref>]]
[[File:Dried Peyote.jpg|thumb|250px|Dried Peyote (''Lophophora williamsii''), containing around 5-6% mescaline by weight]]

Mescaline was first synthesized in 1919 by [[Ernst Späth]] from 3,4,5-trimethoxy{{shy}}benzoyl chloride.<ref name="Späth_1919" /> Several approaches using different starting materials have been developed since, including the following:

* [[Hofmann rearrangement]] of 3,4,5-trimethoxy{{shy}}phenyl{{shy}}propionamide.<ref>{{cite journal | vauthors = Slotta KH, Heller H |title=Über β-Phenyl-äthylamine, I. Mitteil.: Mezcalin und mezcalin-ähnliche Substanzen |journal= Berichte der Deutschen Chemischen Gesellschaft (A and B Series) |year=1930 |volume=63 |issue=11 |pages=3029–3044 |doi=10.1002/cber.19300631117 }}</ref>
* [[Cyanohydrin reaction]] between [[potassium cyanide]] and [[3,4,5-trimethoxybenzaldehyde|3,4,5-trimethoxy{{shy}}benz{{shy}}aldehyde]] followed by [[acetylation]] and [[Organic redox reaction|reduction]].<ref>{{cite journal| vauthors = Amos D |title= Preparation of Mescaline from Eucalypt Lignin|journal=Australian Journal of Pharmacy |date=1964 |volume=49 |page=529 |url=https://www.erowid.org/archive/rhodium/chemistry/mescalyptus.html}}</ref><ref>{{cite journal| vauthors = Kindler K, Peschke W |title=Über neue und über verbesserte Wege zum Aufbau von pharmakologisch wichtigen Aminen VI. Über Synthesen des Meskalins|journal=Archiv der Pharmazie|year=1932|volume=270|issue=7|pages=410–413|doi=10.1002/ardp.19322700709|s2cid=93188741 }}</ref>
* [[Henry reaction]] of 3,4,5-trimethoxy{{shy}}benz{{shy}}aldehyde with [[nitromethane]] followed by [[Reduction of nitro compounds|nitro compound reduction]] of ω-nitro{{shy}}trimethoxy{{shy}}styrene.<ref>{{cite journal| vauthors = Benington F, Morin R |title=An Improved Synthesis of Mescaline|journal=Journal of the American Chemical Society|year=1951|volume=73|issue=3|pages=1353|doi=10.1021/ja01147a505|bibcode=1951JAChS..73Q1353B }}</ref><ref>{{cite book| vauthors = Shulgin A, Shulgin A |title=PiHKAL: A Chemical Love Story|year=1991|publisher=Transform Press|location=Lafayette, CA|isbn=9780963009609|page=703|url=https://books.google.com/books?id=O8AdHBGybpcC&q=9780963009609}}</ref><ref>{{cite journal| vauthors = Hahn G, Rumpf F |title=Über β-[Oxy-phenyl]-äthylamine und ihre Umwandlungen, V. Mitteil.: Kondensation von Oxyphenyl-äthylaminen mit α-Ketonsäuren|journal=Berichte der Deutschen Chemischen Gesellschaft (A and B Series)|year=1938|volume=71|issue=10|pages=2141–2153|doi=10.1002/cber.19380711022}}</ref><ref>{{cite journal| vauthors = Toshitaka O, Hiroaka A |title=Synthesis of Phenethylamine Derivatives as Hallucinogen|journal=Japanese Journal of Toxicology and Environmental Health|date=1992|volume=38|issue=6|pages=571–580|doi=10.1248/jhs1956.38.571 |url=https://nootropicsfrontline.com/wp-content/uploads/2021/07/wiki_ohshita1992.pdf |archive-url=https://ghostarchive.org/archive/20221009/https://nootropicsfrontline.com/wp-content/uploads/2021/07/wiki_ohshita1992.pdf |archive-date=2022-10-09 |url-status=live|access-date=20 June 2014|doi-access=free}}</ref><ref>{{cite journal| vauthors = Ramirez F, Erne M |title=Über die Reduktion von β-Nitrostyrolen mit Lithiumaluminiumhydrid|journal=Helvetica Chimica Acta|date=1950|volume=33|issue=4|pages=912–916|doi=10.1002/hlca.19500330420}}</ref><ref>{{cite journal| vauthors = Szyszka G, Slotta KH |title=Über β-Phenyl-äthylamine.III. Mitteilung: Neue Darstellung von Mescalin|journal=Journal für Praktische Chemie|date=1933|volume=137|issue=9–12|pages=339–350|doi=10.1002/prac.19331370907}}</ref><ref>{{cite journal| vauthors = Burger A, Ramirez FA |title=The Reduction of Phenolic β-Nitrostyrenes by Lithium Aluminum Hydride|journal=Journal of the American Chemical Society|date=1950|volume=72|issue=6|pages=2781–2782|doi=10.1021/ja01162a521|bibcode=1950JAChS..72.2781R }}</ref>
* [[Ozonolysis]] of [[elemicin]] followed by [[reductive amination]].<ref>{{cite journal| vauthors = Hahn G, Wassmuth H |title=Über β-[Oxyphenyl]-äthylamine und ihre Umwandlungen, I. Mitteil.: Synthese des Mezcalins|journal=Berichte der Deutschen Chemischen Gesellschaft (A and B Series)|year=1934|volume=67|issue=4|pages=696–708|doi=10.1002/cber.19340670430}}</ref>
* [[Carbonyl reduction#Ester reduction|Ester reduction]] of [[Eudesmic acid]]'s [[methyl group|methyl]] [[ester]] followed by [[halogenation]], [[Kolbe nitrile synthesis]], and [[nitrile reduction]].<ref name="Makepeace, Tsao 1951 5495–5496">{{cite journal| vauthors = Makepeace T |title=A New Synthesis of Mescaline|journal=Journal of the American Chemical Society|year=1951|volume=71|issue=11|pages=5495–5496|doi=10.1021/ja01155a562|bibcode=1951JAChS..73.5495T }}</ref><ref>{{cite journal| vauthors = Dornow A, Petsch G |title=Über die Darstellung des Oxymezcalins und Mezcalins 2. Mitteilung|journal=[[Archiv der Pharmazie]]|year=1952|volume=285|issue=7|pages=323–326|doi=10.1002/ardp.19522850704|s2cid=97553172 }}</ref><ref>{{cite book| vauthors = Ikan R |title=Natural Products: A Laboratory Guide 2nd Ed|year=1991|publisher=Academic Press, Inc.|location=San Diego|isbn=978-0123705518|pages=232–235|url=https://books.google.com/books?id=B7P8HQimBAIC&pg=PA243}}</ref>
* [[Amide reduction]] of 3,4,5-trimethoxy{{shy}}phenyl{{shy}}acetamide.<ref>{{cite journal| vauthors = Banholzer K, Campbell TW, Schmid H |title=Notiz über eine neue Synthese von Mezcalin, N-Methyl- und N-Dimethylmezcalin|journal=Helvetica Chimica Acta|date=1952|volume=35|issue=5|pages=1577–1581|doi=10.1002/hlca.19520350519}}</ref>
*Reduction of 3,4,5-trimethoxy{{shy}}(2-nitrovinyl)benzene with lithium aluminum hydride.<ref name="Kovacic_2009" />
* Treatment of tricarbonyl-(η6-1,2,3-trimethoxy{{shy}}benzene) chromium complex with acetonitrile carbanion in [[Tetrahydrofuran|THF]] and iodine, followed by reduction of the nitrile with lithium aluminum hydride.<ref name="Makepeace, Tsao 1951 5495–5496" />

===Analogues===
{{See also|Substituted methoxyphenethylamine|Substituted mescaline analogue}}

A large number of [[structural analogue]]s of mescaline that act as psychedelics have been developed. These drugs often have far greater [[potency (pharmacology)|potency]] than mescaline itself. Examples include [[substituted mescaline analogue|scaline]]s like [[escaline]], [[3C (psychedelics)|3C]]s like [[3,4,5-trimethoxyamphetamine]] (TMA or TMA-1), [[2C (psychedelics)|2Cs]] like [[2C-B]], and [[DOx]] drugs like [[DOM (drug)|DOM]], among others. Other notable analogues of mescaline include [[N-methylmescaline|''N''-methylmescaline]] (found in ''[[Pachycereus pringlei]]'') and [[trichocereine]] (''N'',''N''-dimethylmescaline), among others.