{{chembox | Verifiedfields = changed | Watchedfields = changed | verifiedrevid = 444239133 | ImageFileL1 = Tropanol - tropine.svg | ImageClassL1 = skin-invert-image | ImageFileR1 = Tropine.png | ImageClassR1 = bg-transparent | PIN = (1''R'',3''r'',5''S'')-8-Methyl-8-azabicyclo[3.2.1]octan-3-ol | OtherNames = α-Tropine; Tropanol; 3-Tropanol | Section1 = {{Chembox Identifiers | CASNo_Ref = {{cascite|correct|??}} | CASNo = 120-29-6 | PubChem = 8424 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = 7YXR19M72Y | MeSHName = Tropine | ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}} | ChemSpiderID = 10180559 | SMILES = CN1[C@@H]2CC[C@H]1C[C@H](C2)O | InChI = 1/C8H15NO/c1-9-6-2-3-7(9)5-8(10)4-6/h6-8,10H,2-5H2,1H3/t6-,7+,8+ | InChIKey = CYHOMWAPJJPNMW-JIGDXULJBD | StdInChI_Ref = {{stdinchicite|changed|chemspider}} | StdInChI = 1S/C8H15NO/c1-9-6-2-3-7(9)5-8(10)4-6/h6-8,10H,2-5H2,1H3/t6-,7+,8+ | StdInChIKey_Ref = {{stdinchicite|changed|chemspider}} | StdInChIKey = CYHOMWAPJJPNMW-JIGDXULJSA-N }} | Section2 = {{Chembox Properties | C=8|H=15|N=1|O=1 | Appearance = White hygroscopic crystalline powder<ref name=pubchem>{{cite web | url=https://pubchem.ncbi.nlm.nih.gov/compound/8424 | title=8-Methyl-8-azabicyclo[3.2.1]octan-3-ol }}</ref><ref name=sigmaaldrich>{{Cite web | url=https://www.sigmaaldrich.com/GB/en/sds/aldrich/93550 | title=Safety Data Sheet - Tropine | website=www.sigmaaldrich.com}}</ref><ref name=merriam-webster>{{cite web | url=https://www.merriam-webster.com/medical/tropine | title=Medical Definition of TROPINE }}</ref> or plates | Odor = Amine-like<ref name=sigmaaldrich></ref> | Density = 1.045 g/cm<sup>3</sup> at 25 °C<ref name=sigmaaldrich></ref><br>1.016 g/cm<sup>3</sup> at 100 °C | MeltingPtC = 64 | BoilingPtC = 233 | SolubleOther = Very soluble in water, diethyl ether, ethanol<ref name="hand">{{Citation | last = Lide | first = David R. | author-link = | year = 1998 | title = Handbook of Chemistry and Physics | edition = 87 | volume = | series = | publication-place = Boca Raton, Florida | publisher = CRC Press | id = | isbn = 0-8493-0594-2 | doi = | oclc = | pages = 3–564 | url = | accessdate =}}</ref> }} | Section7 = {{Chembox Hazards | MainHazards = Toxic | LD50 = {{ubl|>2000 mg/kg (rat, oral)<ref name=sigmaaldrich></ref>|139 mg/kg (mouse, intraperitoneal)|>50 mg/kg (rabbit, intravenous)|280 mg/kg (mouse, intraperitoneal)|>50 mg/kg (rabbit, intravenous)<ref name=pubchem></ref>}} | GHSPictograms = {{GHS06}}{{GHS07}} | GHSSignalWord = Danger | HPhrases = {{H-phrases|H301|H302|H312|H332}} | PPhrases = {{P-phrases|P261|P264|P270|P271|P280|P301+P316|P301+P317|P302+P352|P304+P340|P317|P321|P330|P362+P364|P405|P501}} }} }}
'''Tropine''' is a derivative of tropane containing a hydroxyl group at the third carbon. It is also called 3-tropanol.<ref name="hand"/> It is a poisonous white hygroscopic crystalline powder.<ref name=merriam-webster></ref> It is a heterocyclic alcohol and an amine.<ref name=merriam-webster></ref>
Tropine is a central building block of many chemicals active in the nervous system, including tropane alkaloids. Some of these compounds, such as long-acting muscarinic antagonists are used as medicines because of these effects.<ref>{{cite journal |last1=Ping |first1=Yu |last2=Li |first2=Xiaodong |last3=You |first3=Wenjing |last4=Li |first4=Guoqiang |last5=Yang |first5=Mengquan |last6=Wei |first6=Wenping |last7=Zhou |first7=Zhihua |last8=Xiao |first8=Youli |title=Production of the Plant-Derived Tropine and Pseudotropine in Yeast |journal=ACS Synthetic Biology |date=10 June 2019 |volume=8 |issue=6 |pages=1257–1262 |doi=10.1021/acssynbio.9b00152|pmid=31181154 |s2cid=184484993 }}</ref>
==Occurrence== Tropine is a natural product found in the plants of deadly nightshade (''Atropa belladonna'') and devil's trumpet (''Datura stramonium'').<ref name=pubchem></ref>
==Chemistry== ===Synthesis=== It can be prepared by hydrolysis of atropine<ref name=Tropacocaine>{{Cite web|url=https://www.seanmichaelragan.com/html/%5B2008-09-10%5D_Cocaine_analog_in_two_steps_from_native_plant_material.shtml|title=[2008-09-10] Cocaine analog in two steps from native plant material|website=www.seanmichaelragan.com}}</ref> or other solanaceous alkaloids.<ref name=merriam-webster></ref><ref>{{cite journal | vauthors=Ladenburg, A | journal=Berichte der deutschen chemischen Gesellschaft | title=Bildung von Tropin aus Tropidin und die Synthese des Atropins | volume=35 | issue=1 | pages=1159–1162 | date= January 1902 | url=https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/cber.190203501191 | doi=10.1002/cber.190203501191}}</ref>
In the laboratory it is made by the reduction of tropinone:<ref>{{cite journal | vauthors=Beckett, AH, Harper, NJ, Balon, ADJ, Watts, THE | journal=Tetrahedron | title=Stereochemistry of the reduction of tropinone | volume=6 | issue=4 | pages=319–330 | date= January 1959 | url=https://linkinghub.elsevier.com/retrieve/pii/0040402059800120 |doi=10.1016/0040-4020(59)80012-0| url-access=subscription }}</ref> Patent:<ref>Rolf Sachse & Albert Schaupp, {{US patent|6005110}} (1999 to Pfleger R Chemische Fabrik GmbH).</ref><ref>Van de Kamp, Sletzinger, {{US patent|2366760}} (1945 to Merck & Co.)</ref>
==Derivatives== List of derivatives that can be made from tropine: #AHN 1-055 HCl: [202646-03-5]<ref>Newman, Amy Hauck; Allen, Andrew C.; Izenwasser, Sari; Katz, Jonathan L. (1994). "Novel 3.alpha.-(Diphenylmethoxy)tropane Analogs: Potent Dopamine Uptake Inhibitors without Cocaine-like Behavioral Profiles". Journal of Medicinal Chemistry. 37 (15): 2258–2261. doi:10.1021/jm00041a002.</ref><ref>Newman, Amy Hauck; Kline, Richard H.; Allen, Andrew C.; Izenwasser, Sari; George, Clifford; Katz, Jonathan L. (1995). "Novel 4'-Substituted and 4',4-Disubstituted 3.alpha.-(Diphenylmethoxy)tropane Analogs as Potent and Selective Dopamine Uptake Inhibitors". Journal of Medicinal Chemistry. 38 (20): 3933–3940. doi:10.1021/jm00020a006. </ref> Patent:<ref>Amy Hauck Newman, {{US patent|5792775}} (1998 to US Department of Health and Human Services).</ref> Selfsame as JHW-007 (''N''-butyl group). This benzhydrol aromatic entity is the same as for flunamine & vanoxerine. #Atropine<ref>Al-Badr, A. A., Muhtadi, F. J. (1985). "Analytical Profiles of Drug Substances". Atropine. Vol. 14. Elsevier. pp. 325–389. doi:10.1016/S0099-5428(08)60585-7.</ref> #Atromepine<ref>Melone, Gaetano; Vecchi, Alberto; Pagani, Giuseppe; Testa, Emilio (1960). "Notes- Tropine DL-α-Methyltropate (Methylatropine) and Its Optical Antipodes". The Journal of Organic Chemistry. 25 (5): 859–861. doi:10.1021/jo01075a624.</ref><ref>Scarselli, Veniero; Cignarella, Giorgio; Maffii, Giulio (1964). "Structural Changes and Anticholinergic Activity in a Class of Tropic and α-Methyltropic Acid Derivatives". Journal of Medicinal Chemistry. 7 (2): 237–238. doi:10.1021/jm00332a026.</ref> #Benztropine<ref>Richard P. Phillips, {{US patent|2595405}} (1952 to Merck a Co).</ref><ref>Weijlard John, {{US patent|2706198}} (1952 to Merck & Co Inc).</ref> #Bemesetron<ref>{{cite journal | vauthors=((Pento, J. T.)) | journal=Drugs of the Future | title=MDL-72222 | volume=10 | issue=10 | pages=820 | date= 1985 | url=http://journals.prous.com/journals/servlet/xmlxsl/pk_journals.xml_summary_pr?p_JournalId=2&p_RefId=61916&p_IsPs=N | issn=0377-8282 | doi=10.1358/dof.1985.010.10.61916 | access-date=8 December 2025| url-access=subscription }}</ref><ref>John Richard Fozard, Maurice Ward Gittos, EP0067770 (1982 to Merrell Dow France Et Cie).</ref> #Butropium bromide (Coliopan®)<ref>Tanaka, Satoru; Wakabayashi, Tsuneo; Hashimoto, Kazunori; Toyoshima, Shoji (1972). "Studies on Diphenyl Ether Derivatives. III. : Synthesis and Spasmolytic Screening of New Quaternary Salts of Tropine Tropates". YAKUGAKU ZASSHI. 92 (4): 510–513. doi:10.1248/yakushi1947.92.4_510.</ref><ref> DE1950378 idem Satoru Tanaka, Kazunori Hasimoto, US3696110 (1972 to Gisai Kk).</ref> #Ciclotropium (wrong stereochemistry if employing this method)<ref> DE2026661 idem R Bauer, W Schulz, W Sirrenberg, G Walther US3743735 (1973 to Boehringer Sohn Ingelheim).</ref> #Clobenztropine<ref>Fromer Stephen, FR1249205 (1961).</ref><ref>Stephen Fromer, {{US patent|2799680}} (1957).</ref><ref>Dr Stephan Fromer, DE1020634 (1957 to Schenley Lab Inc).</ref><ref>Cyril H. Meld, {{US patent|2782200}} (1957 to Schenley Labora).</ref> #[https://pubchem.ncbi.nlm.nih.gov/#query=D-13264 D-13264]<ref>{{cite journal | vauthors=((Castañer, J.)), ((Thiemer, K.)), ((Klinger, K. H.)), ((Engel, J.)) | journal=Drugs of the Future | title=D-13,264 | volume=7 | issue=12 | pages=869 | date= 1982 | url=http://journals.prous.com/journals/servlet/xmlxsl/pk_journals.xml_summary_pr?p_JournalId=2&p_RefId=1003955&p_IsPs=N | issn=0377-8282 | doi=10.1358/dof.1982.007.12.1003955| url-access=subscription }}</ref> (atropine quat). #Decitropine [1242-69-9]<ref>Dr August Franciscus Harms, DE1152410 (1963 to Koninklijke Pharma Fab Nv).</ref> #Deptropine<ref>{{cite journal | vauthors=((Van Der Stelt, C.)), ((Harms, A. F.)), ((Nauta, W. Th.)) | journal=Journal of Medicinal and Pharmaceutical Chemistry | title=The Effect of Alkyl-Substitution in Drugs--V. Synthesis and Chemical Properties of Some Dibenzo [a,d]1,4-cycloheptadienyl Ethers | volume=4 | issue=2 | pages=335–349 | date= September 1961 | url=https://pubs.acs.org/doi/abs/10.1021/jm50018a008 | doi=10.1021/jm50018a008| url-access=subscription }}</ref><ref> Harms August Franciscus, {{US patent|3119829}} (1964 to Koninklijke Pharmaceutische Fabrieken NV).</ref> #Fentonium<ref>Teotino, U.M . et al, Eur. J. Med. Chem .-Chim. Ther ., 1968, 3, 453 (synth, pharmacol)</ref><ref>, GB1026640 idem Davide Della Bella, Uberto Teotino, US3436458 (1969 to Whitefin Holding Sa).</ref> #Flutropium bromide (wrong stereoisomer using this method of synthesis).<ref> DE2540633 idem Rolf Banholzer, Rudolf Bauer, Alex Heusner, Werner Schulz, {{US patent|4042700}} (1977 to Boehringer Ingelheim Gmbh).</ref> #Homatropine<ref> Chemnitius, F. (1927). "Zur Darstellung des Homatropins". Journal für Praktische Chemie. 17 (1): 142–146. ISSN 0021-8383. doi:10.1002/prac.19271170105.</ref> #PG-9 [156143-26-9] Maleate salt: [155649-00-6] Synthesis:<ref name=PG-9>{{cite journal | vauthors=((Gualtieri, F.)), ((Conti, G.)), ((Dei, S.)), ((Giovannoni, M. P.)), ((Nannucci, F.)), ((Romanelli, M. N.)), ((Scapecchi, S.)), ((Teodori, E.)), ((Fanfani, L.)), ((Ghelardini, C.)), ((Giotti, A.)), ((Bartolini, A.)) | journal=Journal of Medicinal Chemistry | title=Presynaptic Cholinergic Modulators as Potent Cognition Enhancers and Analgesic Drugs. 1. Tropic and 2-Phenylpropionic Acid Esters | volume=37 | issue=11 | pages=1704–1711 | date= May 1994 | url=https://pubs.acs.org/doi/abs/10.1021/jm00037a022 | doi=10.1021/jm00037a022}}</ref><ref name=chiral/> Pharmacol:<ref>Ghelardini, Carla; Galeotti, Nicoletta; Bartolini, Alessandro; Furukawa, Shoei; Nitta, Atsumi; Manetti, Dina; Gualtieri, Fulvio (1998). "Memory Facilitation and Stimulation of Endogenous Nerve Growth Factor Synthesis by the Acetylcholine Releaser PG-9". The Japanese Journal of Pharmacology. 78 (3): 245–251. doi:10.1254/jjp.78.245. ISSN 0021-5198.</ref><ref>Ghelardini C, Galeotti N, Gualtieri F, Marchese V, Bellucci C, Bartolini A. Antinociceptive and antiamnesic properties of the presynaptic cholinergic amplifier PG-9. J Pharmacol Exp Ther. 1998;284(3):806-16. PMID: 9495837.</ref><ref>Ghelardini, C., Galeotti, N., Romanelli, M. N., Gualtieri, F., Bartolini, A. (March 2000). "Pharmacological Characterization of the Novel ACh Releaser α‐tropanyl 2‐(4‐bromophenyl)propionate (PG‐9)". CNS Drug Reviews. 6 (1): 63–78. doi:10.1111/j.1527-3458.2000.tb00138.x.</ref> #Methoxytropacin HCl: [74051-44-8] #Prampine [7009-65-6]{{Citation needed|date=December 2025}} #Pudafensine<ref>Dan Peters, et al. WO2011092061 (to NTG Nordic Transport Group AS).</ref> (by Mitsunobu inversion chemistry) #SM-21 (other codenames covered too)<ref name=chiral>{{cite journal | vauthors=((Romanelli, M. N.)), ((Bartolini, A.)), ((Bertucci, C.)), ((Dei, S.)), ((Ghelardini, C.)), ((Giovannini, M. G.)), ((Gualtieri, F.)), ((Pepeu, G.)), ((Scapecchi, S.)), ((Teodori, E.)) | journal=Chirality | title=Synthesis and enantioselectivity of the enantiomers of PG9 and SM21, new potent analgesic and cognition-enhancing drugs | volume=8 | issue=3 | pages=225–233 | date= 1996 | url=https://onlinelibrary.wiley.com/doi/10.1002/(SICI)1520-636X(1996)8:3<225::AID-CHIR1>3.0.CO;2-G | doi=10.1002/(SICI)1520-636X(1996)8:3<225::AID-CHIR1>3.0.CO;2-G| url-access=subscription }}</ref><ref name=Bartolini>Alessandro Bartolini, et al. WO1994001435 (Abiogen Pharma SRL).</ref> #SM-25 is the ester between tropine and clofibric acid.<ref name=Bartolini/> #Tropabazate{{Citation needed|date=December 2025}} #Tropacine<ref>Basel Gesellschaft Fuer Chemis [ch], CH202181 (1939 to Ciba), C.A. 33, 89228(1939).</ref><ref>Friess, S.L.; Reber, L.J.; Thommesen, W.C.; Greenbaum, L.J.; Standaert, F.G.; Hudak, W.V. (1960). "Toxicologic properties and stereochemical configuration in derivatives of the tropanol series". Toxicology and Applied Pharmacology. 2 (5): 574–588. ISSN 0041-008X. doi:10.1016/0041-008X(60)90024-7.</ref><ref>XU, Rong; SIM, Meng-Kwoon; GO, Mei-Lin (1998). "Synthesis, Antimuscarinic Activity and Quantitative Structure-Activity Relationship (QSAR) of Tropinyl and Piperidinyl Esters". CHEMICAL & PHARMACEUTICAL BULLETIN. 46 (2): 231–241. doi:10.1248/cpb.46.231.</ref> #Tropacocaine (by Mitsunobu inversion chemistry)<ref name=Tropacocaine/> #Tropanserin<ref> J. R. Fozard and M. W. Gittos, US4563465 (1986 to Merrell Dow Pharmaceuticals Inc.)</ref><ref>Fozard John Richard; Gittos Maurice Ward +, GB2131420 (1984 to Merrell Toraude & Co +); CA, 101,230355</ref> #Tropatepine<ref> DE1952206 idem J Boissier, R Ratouis, US3725415 (1973 to Ind Pour La Fab Antibiotiques).</ref> #Tropine benzilate ("BAT") #Tropirine<ref> Harms, A. F., Chim. Ther., 1968, 3, 277.</ref><ref> van der Stelt C, Hofman PS, Funcke AB, Nauta WT. Synthesis and pharmacological properties of some 5H-benzo(4,5)cyclohepta(1,2-b)pyridine derivatives. Arzneimittelforschung. 1968 Jun;18(6):756-8. PMID: 4387811.</ref> #Tropodifene<ref> Fedosowa; Magidson Zhurnal Obshchei Khimii, 1956 , vol. 26, p. 3475, 3477; engl. Ausg. S. 3867, 3868.</ref> #Xenytropium<ref>Laszlo Gyermek, {{US patent|2833773}} (1958).</ref> #Zepastine<ref> Abraham Weber, Jacques Jean Frossard, {{US patent|3700663}} (1972 to Mead Johnson & Co).</ref> #3-Perfluorophenoxytropane ([https://pubchem.ncbi.nlm.nih.gov/compound/14575207 PC14575207])<ref>Grover C. Helsley, Larry Davis, Gordon E. Olsen, {{US patent|4861889}} (1989 to Hoechst-Roussel Pharmaceuticals, Inc.).</ref> #[https://pubchem.ncbi.nlm.nih.gov/compound/46905316 PC46905316] (Ibuprofen)<ref name=PG-9/> &[https://pubchem.ncbi.nlm.nih.gov/compound/16115711 PC16115711] (Naproxen).{{Citation needed|date=December 2025}} #Tropine p-chlorophenoxyacetate [6658-61-3]<ref name="pmid1227878">{{cite journal | vauthors = Zakharevskiĭ AS, Shadurskiĭ KS | title = [Pharmacological properties of some p-chlorophenoxyacetic acid derivatives] | language = Russian | journal = Farmakologiia I Toksikologiia | volume = 38 | issue = 2 | pages = 154–9 | date = 1975 | pmid = 1227878 | doi = | url = }}</ref> (c.f. Meclofenoxate).
== See also == * Atropine * Pseudotropine * Scopine * Tropane alkaloid * Tropinone
== References == {{reflist}}
Category:Tropanes Category:Secondary alcohols