{{chembox | Verifiedfields = changed | Watchedfields = changed | verifiedrevid = 394986228 | Name = Piperonal | ImageFile = Piperonal structure.png | ImageClass = skin-invert | ImageName = | PIN = 2''H''-1,3-Benzodioxole-5-carbaldehyde | OtherNames= Heliotropin; Heliotropine; Piperonyl aldehyde; Protocatechuic aldehyde methylene ether; 3,4-methylenedioxybenzaldehyde; |Section1={{Chembox Identifiers | UNII_Ref = {{fdacite|correct|FDA}} | UNII = KE109YAK00 | ChEBI_Ref = {{ebicite|correct|EBI}} | ChEBI = 8240 | ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL = 271663 | StdInChI_Ref = {{stdinchicite|changed|chemspider}} | StdInChI = 1S/C8H6O3/c9-4-6-1-2-7-8(3-6)11-5-10-7/h1-4H,5H2 | StdInChIKey_Ref = {{stdinchicite|changed|chemspider}} | StdInChIKey = SATCULPHIDQDRE-UHFFFAOYSA-N | SMILES1 = c1cc2c(cc1C=O)OCO2 | CASNo_Ref = {{cascite|correct|CAS}} | CASNo = 120-57-0 | Beilstein = 131691 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 13859497 | EC_number = 204-409-7 | Gmelin = 4186 | KEGG = C10812 | PubChem = 8438 | SMILES = O=Cc1ccc2OCOc2c1 }} |Section2={{Chembox Properties | C=8 | H=6 | O=3 | Appearance = Colorless crystals<ref name=Merck>{{Merck12th}}</ref> | Density = 1.337 g/cm<sup>3</sup> | MeltingPtC = 37 | MeltingPt_ref = <ref name=Merck/> | BoilingPtC = 263 | BoilingPt_ref = <ref name=Merck/> | Solubility = Soluble in 500 parts<ref name=Merck/> }} |Section3={{Chembox Hazards | GHSPictograms = {{GHS07}} | GHSSignalWord = Warning | HPhrases = {{H-phrases|317}} | PPhrases = {{P-phrases|261|272|280|302+352|321|333+313|363|501}} | MainHazards = | FlashPt = | AutoignitionPt = | LD50 = 2700 mg/kg (orally in rats)<ref name=Merck/> }} |Section4={{Chembox Legal status | legal_AU = | legal_BR = D1 | legal_BR_comment = <ref>{{Cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=2023-03-31 |title=RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial |trans-title=Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control|url=https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |url-status=live |archive-url=https://web.archive.org/web/20230803143925/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |archive-date=2023-08-03 |access-date=2023-08-15 |publisher=Diário Oficial da União |language=pt-BR |publication-date=2023-04-04}}</ref> | legal_EU = category 1 precursor | legal_EU_comment = <ref name=EULegality>{{CELEX|32004R0273|text=Regulation (EC) No 273/2004 of the European Parliament and of the Council of 11 February 2004 on drug precursors}}</ref> | legal_US = List I | legal_US_comment = <ref name=DEADiversion>{{cite web |title=List I and II Regulated Chemicals - Alphabetical Order |url=https://www.deadiversion.usdoj.gov/schedules/orangebook/f_chemlist_alpha.pdf?page=2 |website=www.deadiversion.usdoj.gov |publisher=DEA Diversion - US DOJ |access-date=21 September 2025 |page=2 |date=19 September 2025}}</ref> | legal_UK = | legal_UN = }} }}
'''Piperonal''', also known as '''heliotropin''', is an organic compound which is commonly found in fragrances and flavors. The molecule is structurally related to other aromatic aldehydes such as benzaldehyde and vanillin. The methylenedioxyphenyl group is found in other fragrances.<ref name=Ullmann>{{cite book|last1=Panten |first1=Johannes |last2=Surburg |first2=Horst |title=Ullmann's Encyclopedia of Industrial Chemistry |chapter=Flavors and Fragrances, 3. Aromatic and Heterocyclic Compounds |date=2016 |pages=1–45 |doi=10.1002/14356007.t11_t02 |isbn=978-3-527-30673-2 }}</ref>
== Natural occurrence == Piperonal naturally occurs in various plants. Examples include dill, violet flowers, and black pepper.
==Preparation== Piperonal can be prepared by the oxidative cleavage of isosafrole or by using a multistep sequence from catechol or 1,2-methylenedioxybenzene. Synthesis from the latter chemical is accomplished through a condensation reaction with glyoxylic acid followed by cleaving the resulting α-hydroxy acid with an oxidizing agent.<ref name=Ullmann /><ref name = syn>{{cite journal|author1=Fatiadi, Alexander |author2=Schaffer, Robert |name-list-style=amp |title=An Improved Procedure for Synthesis of DL-4-Hydroxy-3-methoxymandelic Acid (DL-"Vanillyl"-mandelic Acid, VMA)|journal=Journal of Research of the National Bureau of Standards Section A|year=1974|volume=78A|issue=3|pages=411–412|doi=10.6028/jres.078A.024|pmid=32189791 |pmc=6742820 |doi-access=free}}</ref><ref>{{cite journal|last1=Nwaukwa|first1=Stephen|last2=Keehn|first2=Philip|title=Oxidative cleavage of α-diols, α-diones, α-hydroxy-ketones and α-hydroxy- and α-keto acids with calcium hypochlorite [Ca(OCl)<sub>2</sub>]|journal=Tetrahedron Letters|date=1982|volume=23|issue=31|pages=3135–3138|doi=10.1016/S0040-4039(00)88578-0}}</ref> Synthesis from catechol requires an additional step, Williamson ether synthesis using dichloromethane.<ref>{{cite journal|author1=Bonthrone, W. |author2=Cornforth, J. |name-list-style=amp |title=The methylenation of catechols|journal=Journal of the Chemical Society|issue=9 |year=1969|pages=1202–1204|doi=10.1039/J39690001202}}</ref>
==Reactions== Piperonal, like all aldehydes, can be reduced to its alcohol (piperonyl alcohol) or oxidized to give its acid (piperonylic acid).
Piperonal can be used in the synthesis of some pharmaceutical drugs including tadalafil,<ref>{{cite journal|author1=Gilla, G.|author2=Anumula, R.R.|author3=Aalla, S.|author4=Vurimidi, H.|author5=Ghanta, M.R.|name-list-style=amp|title=Synthesis and characterization of related substances and metabolite of tadalafil, a PDE-5 inhibitor|journal=Organic Communications|year=2013|volume=6|issue=1|pages=12–22|url=http://www.acgpubs.org/OC/2013/Volume%206/Issue%201/2-OC-1204-256.pdf|access-date=2015-01-21|archive-date=2018-10-24|archive-url=https://web.archive.org/web/20181024112519/http://www.acgpubs.org/OC/2013/Volume%206/Issue%201/2-OC-1204-256.pdf|url-status=live}}</ref> L-DOPA,<ref>{{cite journal | doi = 10.1248/cpb.10.680| title = Studies on Optically Active Amino Acids. I. Preparation of 3-(3, 4-Methylenedioxyphenyl)-D-, and -L-alanine| journal = Chemical & Pharmaceutical Bulletin| volume = 10| issue = 8| pages = 680–688| year = 1962| last1 = Yamada| first1 = Shun-Ichi| last2 = Fujii| first2 = Tozo| last3 = Shioiri| first3 = Takayuki| pmid = 14002245| doi-access = free}}</ref> and atrasentan.<ref name="Winnvon Geldern1996">{{cite journal|last1=Winn|first1=Martin|last2=von Geldern|first2=Thomas W.|last3=Opgenorth|first3=Terry J.|last4=Jae|first4=Hwan-Soo|last5=Tasker|first5=Andrew S.|last6=Boyd|first6=Steven A.|last7=Kester|first7=Jeffrey A.|last8=Mantei|first8=Robert A.|last9=Bal|first9=Radhika|last10=Sorensen|first10=Bryan K.|last11=Wu-Wong|first11=Jinshyun R.|last12=Chiou|first12=William J.|last13=Dixon|first13=Douglas B.|last14=Novosad|first14=Eugene I.|last15=Hernandez|first15=Lisa|last16=Marsh|first16=Kennan C.|title=2,4-Diarylpyrrolidine-3-carboxylic AcidsPotent ETASelective Endothelin Receptor Antagonists. 1. Discovery of A-127722|journal=Journal of Medicinal Chemistry|volume=39|issue=5|year=1996|pages=1039–1048|issn=0022-2623|doi=10.1021/jm9505369|pmid=8676339}}</ref>
== Fragrance == Piperonal has a floral odor which is commonly described as being similar to that of vanillin or cherry. For this reason it is commonly used in fragrances and artificial flavors.<ref name=Ullmann /> The compound was named heliotropin after the 'cherry pie' notes found in the heliotrope flower's fragrance (even though the chemical is not present in the flower's true aroma).<ref>{{Cite web|url=http://www.bojensen.net/EssentialOilsEng/EssentialOils13A/EssentialOils13A.htm|title=Essential oils|access-date=2012-09-02|archive-date=2019-12-23|archive-url=https://web.archive.org/web/20191223140607/http://www.bojensen.net/EssentialOilsEng/EssentialOils13A/EssentialOils13A.htm|url-status=live}}</ref> Perfumers began to use the fragrance for the first time by the early 1880s.<ref name=fashion>[https://books.google.com/books?id=_wGaNRoHWI0C&dq=1869+fittig+and+mielk&pg=PA107 The Force of Fashion in Politics and Society]: Global Perspectives from Early Modern to Contemporary Times By Beverly Lemire {{ISBN|9781409404927}}</ref> It is commonly used to add vanilla or almond nuances, generally imparting balsamic, powdery, and floral aspects to a scent's character.<ref>{{cite web |title=heliotropin|url=https://scentsandflavors.com/database/9dbb4f8d-d5e7-4f34-aa9c-1681004947d7|website=Scents and Flavors |publisher=Scents and Flavors |access-date=3 April 2026}}</ref>
Piperonyl acetate is a synthetic cherry flavoring.<ref>Fenaroli's Handbook of Flavor Ingredients.</ref>
== Use in MDMA manufacture == Due to their role in the manufacture of MDMA, safrole, isosafrole, and piperonal are Category I precursors under regulation no. 273/2004 of the European Community.<ref name=EULegality/>
== References == {{reflist}}
== External links == {{EB1911 poster|Piperonal}}
Category:Benzaldehydes Category:Benzodioxoles