Piperonal

Piperonal naturally occurs in various plants. Examples include dill, vanilla, violet flowers, and black pepper.

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.{{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}}{{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)₂]|journal=Tetrahedron Letters|date=1982|volume=23|issue=31|pages=3135–3138|doi=10.1016/S0040-4039(00)88578-0}} Synthesis from catechol requires an additional step, Williamson ether synthesis using dichloromethane.{{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}}

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,{{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}} L-DOPA,{{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}} and atrasentan.{{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}}

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. 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).{{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}} Perfumers began to use the fragrance for the first time by the early 1880s.[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}} It is commonly used to add vanilla or almond nuances, generally imparting balsamic, powdery, and floral aspects to a scent's character.The Good Scents Company database entry for [http://www.thegoodscentscompany.com/data/rw1005891.html Heliotropin] {{Webarchive|url=https://web.archive.org/web/20200801012954/http://www.thegoodscentscompany.com/data/rw1005891.html |date=2020-08-01 }}

Piperonyl acetate is a synthetic cherry flavoring.Fenaroli's Handbook of Flavor Ingredients.

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.{{CELEX|32004R0273|text=Regulation (EC) No 273/2004 of the European Parliament and of the Council of 11 February 2004 on drug precursors}}

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• [https://www.tadalafil.org/ Tadalafil vs Sildenafil]

{{EB1911 poster|Piperonal}}

Category:Benzaldehydes

Category:Benzodioxoles