Piperonal: Difference between revisions

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{{chembox

| Verifiedfields = changed

| Watchedfields = changed

| verifiedrevid = ~~306855349~~

| verifiedrevid = 394986228

| Name = Piperonal

| ImageFile = Piperonal structure.png

| ~~ImageSize~~ = ~~200px~~

| ImageName =

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| PIN = 2''H''-1,3-Benzodioxole-5-carbaldehyde

| ImageName =

| OtherNames= Heliotropin; Heliotropine; Piperonyl aldehyde; Protocatechuic aldehyde methylene ether; 3,4-methylenedioxybenzaldehyde;

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| ~~IUPACName~~ = 1,3-~~benzodioxole~~-5-carbaldehyde

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|Section1={{Chembox Identifiers

| OtherNames= heliotropine, protocatechuic aldehyde methylene ether

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

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| Section1 = {{Chembox Identifiers

| 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

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| ChemSpiderID = ~~8130~~

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

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| SMILES = O=Cc1ccc2OCOc2c1

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| ChemSpiderID = 13859497

| EC_number = 204-409-7

| Gmelin = 4186

| KEGG = C10812

| PubChem = 8438

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| SMILES = O=Cc1ccc2OCOc2c1

}}

| Section2 = {{Chembox Properties

|Section2={{Chembox Properties

| C=8 | H=6 | O=3

| Formula = C8H6O3

| Appearance = Colorless crystals<ref name=Merck>{{Merck12th}}</ref>

| MolarMass = 150.13 g/mol

| Density =

| Density = 1.337 g/cm3

| ~~MeltingPt~~ = ~~35-~~37 °C

| MeltingPtC = 37

| MeltingPt_ref = <ref name=Merck/>

| BoilingPtC = ~~264~~

| BoilingPtC = 263

| SolubleOther = THF 7.44 M, ethanol 4.99 M, methanol 7.29 M <ref>[http://oru.edu/cccda/sl/solubility/allsolvents.php?solute=piperonal Solubility of piperonal in non-aqueous solvents]{{Verify credibility|date=December 2009}}</ref>

| BoilingPt_ref = <ref name=Merck/>

| Solvent = [[THF]], [[ethanol]], [[methanol]]

| 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_US =

| legal_UK =

| legal_UN =

}}

'''Piperonal''', also known as '''heliotropin''', is an [[organic compound]] which is commonly found in fragrances and flavors.<ref name=Ullmann>Karl-Georg Fahlbusch, Franz-Josef Hammerschmidt, Johannes Panten, Wilhelm Pickenhagen, Dietmar Schatkowski, Kurt Bauer, Dorothea Garbe and Horst Surburg "Flavors and Fragrances" in Ullmann's Encyclopedia of Industrial Chemistry, Wiley-VCH, Weinheim, 2003. {{doi|10.1002/14356007.a11_141}}</ref> The molecule is structurally related to other [[aromatic]] [[aldehyde]]s such as [[benzaldehyde]] and [[vanillin]].

'''Piperonal''', also known as '''heliotropin''', is an aromatic [[aldehyde]] that comes as transparent crystals, C8H6O3, and has a floral odor commonly described as being similar to that of [[vanillin]] and [[cherry]]. It is used as flavoring and in [[perfume]]. It can be obtained by oxidation of [[piperonyl alcohol]] or the reduction of [[piperic acid]]. It is also a minor natural component of the extract of [[vanilla]]. It is a common additive in inexpensive synthetic vanilla flavor and candies.

== Natural occurrence ==

Piperonal has powerful aromatherapeutic qualities which appear to elevate mood and general well-being. Tests performed by the Memorial Sloan-Kettering Cancer Center in New York demonstrated a reduction in the anxiety of patients receiving an [[Magnetic resonance imaging|MRI]] by as much as 63 percent.<ref>[http://micro.magnet.fsu.edu/primer/techniques/polarized/gallery/pages/heliotropinsmall.html Heliotropin], Polarized Light Microscopy Digital Image Gallery</ref>

Piperonal naturally occurs in various plants. Examples include [[dill]], [[vanilla]], [[Viola odorata|violet flowers]], and [[black pepper]].

==~~Chemistry~~==

==Preparation==

Piperonal can be prepared by the oxidative cleavage of [[isosafrole]] or by using a multistep sequence from [[catechol]] or [[1,3-Benzodioxole|1,2-methylenedioxybenzene]]. Synthesis from the latter chemical is accomplished through a [[condensation reaction]] with [[glyoxylic acid]] followed by [[Bond cleavage|cleaving]] the resulting [[Alpha hydroxy acid|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)2]|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 may be used in the synthesis of [[3,4-Methylenedioxyamphetamine|3,4-methylenedioxyamphetamine]] (MDA). In one synthetic path, [[nitroethane]] in a [[glacial acetic acid]] solution with an [[ammonium acetate]] catalyst yields a substituted [[nitrostyrene]] via a [[condensation reaction]]. This intermediate can then be reduced by a strong reducing agent such as [[lithium aluminium hydride]] (LiAlH4) to yield MDA.

Piperonal, like all [[aldehyde]]s, can be [[Carbonyl reduction#Aldehyde and ketone reduction|reduced]] to its [[Alcohol (chemistry)|alcohol]] (piperonyl alcohol) or oxidized to give its [[carboxylic acid|acid]] ([[piperonylic acid]]).

<ref> [http://www.erowid.org/library/books_online/pihkal/pihkal.shtml PiHKAL] </ref>

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>

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==References==

== 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 [[Flavoring#Flavor creation|artificial flavors]].<ref name=Ullmann /> The compound was named heliotropin after the 'cherry pie' notes found in the [[Heliotropium|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>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 }}</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>{{CELEX|32004R0273|text=Regulation (EC) No 273/2004 of the European Parliament and of the Council of 11 February 2004 on drug precursors}}</ref>

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== References ==

==External links==

== External links ==

[[Category:~~Aldehydes~~]]

[[Category:Benzaldehydes]]

[[Category:DEA List I chemicals]]

[[Category:Benzodioxoles]]

[[de:Piperonal]]

[[fr:Héliotropine]]

[[it:Piperonale]]

[[nl:Heliotropine]]

[[pl:Piperonal]]

[[ru:Гелиотропин]]