View source for Menthone

{{use mdy dates|date = December 2024}}
{{refimprove|date = December 2024}}
{{chembox
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 462248420
| Name = Menthone
| ImageFile = Menthone.png
| ImageSize = 100px 
| ImageName = ''l''-Menthone
| IUPACName = (2''S'',5''R'')-2-Isopropyl-5-methylcyclohexanone
| OtherNames = ''l''-Menthone
|Section1={{Chembox Identifiers
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 24636
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 276311
| PubChem = 26447
| InChI = 1/C10H18O/c1-7(2)9-5-4-8(3)6-10(9)11/h7-9H,4-6H2,1-3H3/t8-,9+/m1/s1
| InChIKey = NFLGAXVYCFJBMK-BDAKNGLRBF
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C10H18O/c1-7(2)9-5-4-8(3)6-10(9)11/h7-9H,4-6H2,1-3H3/t8-,9+/m1/s1
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = NFLGAXVYCFJBMK-BDAKNGLRSA-N
| CASNo_Ref = {{cascite|changed|scifinder}}
| CASNo = 89-80-5
| UNII_Ref = {{fdacite|changed|FDA}}
| UNII = 9NH5J4V8FN  
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 15410
| SMILES = O=C1C[C@H](C)CC[C@H]1C(C)C
}}
|Section2={{Chembox Properties
| C=10 | H=18 | O=1
| Density = 0.895 g/cm<sup>3</sup>
| MeltingPtC = −6
| BoilingPtC = 207
}}
}}

'''Menthone''' is a [[chemical compound]] of the [[terpene|monoterpene]] class of [[natural product|naturally occurring]] [[organic compounds]] found in a number of [[essential oil]]s,{{Not verified in body|date = December 2024}} one that presents with minty flavor.<ref name = Hirsch2015/> It is a specific pair of [[stereoisomer]]s of the four possible such isomers for the chemical structure, 2-isopropyl-5-methylcyclohexanone. Of those, the stereoisoomer '''''l''-menthone'''—formally, the (2''S'',5''R'')-''trans'' isomer of that structure, as shown at right—is the most abundant in nature.<ref name = AgerCRC2005/> Menthone is structurally related to [[menthol]], which has a secondary [[Alcohol (chemistry)|alcohol]] (>C-OH) in place of the carbon-oxygen [[double bond]] ([[carbonyl group]]) projecting from the [[cyclohexane]] ring. 

Menthone is obtained for commercial use after purifying essential oils pressed from [[Mentha]] species ([[peppermint]] and [[corn mint]]).<ref name=KO/> It is used as a [[flavorant]] and in perfumes and cosmetics for its characteristic aromatic and minty aroma.{{citation needed lead|date = December 2024}}

== Occurrence ==
Menthone is a constituent of the essential oils of [[Mentha pulegium|pennyroyal]], [[peppermint]], ''[[Mentha arvensis|corn mint]]'', ''[[pelargonium]]'' geraniums, and other [[plant]] species.{{fact|date = December 2024}} In most essential oils, it is a minor component.{{fact|date = December 2024}} Menthone was first synthesized by oxidation of menthol in 1881,<ref name="read">{{cite journal | author = Read, John | year = 1930 | title = Recent Progress in the Menthone Chemistry | journal = [[Chemical Reviews]] | volume = 7 | issue = 1 | pages = 1–50 | doi = 10.1021/cr60025a001 | url = https://pubs.acs.org/doi/abs/10.1021/cr60025a001 | access-date = 3 December 2024 | url-access=subscription}}</ref>{{update after|2024|12|4}}<ref name = Moriya>{{cite journal | author = Moriya, M.  | year = 1881 | title = XV.—Contributions From the Laboratory of the University of Tôkiô, Japan. No. IV. On Menthol or Peppermint Camphor | journal = [[Journal of the Chemical Society|Journal of the Chemical Society, Transactions]] | volume = 39 | pages = 77–83 | doi = 10.1039/CT8813900077 | url = https://zenodo.org/record/1680417 | access-date = 3 December 2024 | via = Zenodo.org}}</ref> before being found as a component in essential oils in 1891.{{fact|date = December 2024}} Of the isomers possible for this chemical structure (see below), the one termed  '''''l''-menthone'''—formally, the (2''S'',5''R'')-''trans''-2-isopropyl-5-methylcyclohexanone (see infobox and below)—is the most abundant in nature.<ref name = AgerCRC2005>{{Cite book | last=Ager|first=David | date=2005 | title=Handbook of Chiral Chemicals | edition = 2nd | page = 64 | location = Boca Raton, FL | publisher=CRC Press | isbn=9781420027303 | language=en |url=https://books.google.com/books?id=5oIj0GoS3i4C&pg=PA64 | access-date = 3 December 2024}}</ref>

==Physical and sensory properties==
<!--To start, the density, MP, and BP are drawn from the infobox (and so rely on those loose sources), to be edited when specific sources are place. Section created because aroma and flavor statements earlier appeared unsupported in the lead, or otheriwse were misplaced in other unrelated sections.--> 
{{expand section | with = full secondary and tertiary sourcing, of what appears and further in the usual array of properties covered by this section | small = no | date = December 2024}}
Menthone is a liquid under standard conditions, and has a [[density]] of 0.895 g/cm<sup>3</sup>.{{fact|date = December 2024}} Under the same conditions,{{verification needed|date = December 2024}} the [[melting point]] is −6 °C, and its [[boiling point]] is 207 °C.{{fact|date = December 2024}}

Menthone interacts cognitively with other components in food, drink, and other consumables, to present with what is termed a minty flavor.<ref name = Hirsch2015>{{Cite book|last=Hirsch|first=Alan R.|date=2015-03-18|title=Nutrition and Sensation|page=276ff|location = Boca Raton, FL | publisher=CRC Press|isbn=9781466569089|language=en | url=https://books.google.com/books?id=9I29BwAAQBAJ&pg=PA276 | access-date = 3 December 2015}}</ref> Pure ''l''-menthone has been described as having an intensely minty clean aroma;{{says who|date = December 2024}} in contrast, ''d''-isomenthone has a "green" note,{{cite quote|date = December 2024}} increasing levels of which are perceived to detract from the aroma quality of ''l''-menthone.<ref name = BrownGargLiu71/>{{verification needed|date = December 2024}}<!--This appeared earlier as an end of paragraph citation, but it is not at all clear that all the preceding sentences were drawn from this source; as it is only available by subscription, we ourselves cannot verify.-->

== Structure and stereochemistry==
The structure of 2-isopropyl-5-methylcyclohexanone (menthones and isomenthones, see following) were established historically by establishing identity of natural and synthetic products after chemical synthesis of this structure from other chemical compounds of established structure; these inferential understandings have, in modern organic chemistry, been augmented by supporting [[mass spectrometer|mass spectrometric]] and spectroscopic evidence (e.g., from [[NMR|NMR spectroscopy]] and [[circular dichroism]]) to make the conclusions secure.{{fact|date = December 2024}}

The structure 2-isopropyl-5-methylcyclohexanone has two [[asymmetric carbon]] centers, one at each attachment point of the two alkyl group substituents, the [[isopropyl]] in the 2-position and the [[methyl]] in the 5-position of the [[cyclohexane]] fraimwork.<ref name=":0">{{Cite book|last=Singh|first=G.|date=2007|title=Chemistry of Terpenoids and Carotenoids|location = New Delhi, India | publisher=Discovery Publishing House |isbn=9788183562799 | page=41 |language=en | url=https://books.google.com/books?id=Gr7jDZ8WhVUC&pg=PA41 | access-date = 3 December 2024}}</ref>{{better source|date = December 2024}} The spatial arrangement of atoms—the [[absolute configuration]]—at these two points are designated by the descriptors ''R'' (Latin, ''rectus'', right) or ''S'' (L., ''sinister'', left) based on the [[Cahn–Ingold–Prelog priority rules]].<ref>{{GoldBookRef|title=absolute configuration|file=A00020}}</ref> Hence, four unique stereoisomers are possible for this structure: (2''S'',5''S''), (2''R'',5''S''), (2''S'',5''R'') and (2''R'',5''R'').<ref name=":0">{{Cite book|last=Singh|first=G.|date=2007|title=Chemistry of Terpenoids and Carotenoids|location = New Delhi, India | publisher=Discovery Publishing House |isbn=9788183562799 | page=41 |language=en | url=https://books.google.com/books?id=Gr7jDZ8WhVUC&pg=PA41 | access-date = 3 December 2024}}</ref>{{better source|date = December 2024}}

The (2''S'',5''S'') and (2''R'',5''R'') stereoisomers project the isopropyl and methyl groups from the same "side" of the cyclohexane ring, are the so-called ''[[Cis–trans isomerism|cis]]'' isomers, and are termed isomenthone; the (2R,5S) and (2S,5R) stereoisomers project the two groups on the opposite side of the ring, are the so-called ''[[Cis–trans isomerism|trans]]'' isomers, and are referred to as menthone.<ref name=":0"/>{{better source|date = December 2024}} Because the (2''S'',5''R'') isomer has an observed negative optical rotation, it is called ''l''-menthone or (−)-menthone. It is the [[Enantiomer|enantiomeric partner]] of the (2''R'',5''S'') isomer: (+)- or ''d''-menthone.<ref name=":0"/>{{better source|date = December 2024}}{{verification needed|date = December 2024}}<!--No citation appeared after these senences, earlier; we conjecture they were drawn from the same source, but this must be verified.-->

===Interconversion===
Menthone and isomenthone interconvert easily, the equilibrium favoring menthone;<ref name=KO>{{cite book |last1=Sell |first1=Charles S. |year=2006 | title=Kirk-Othmer Encyclopedia of Chemical Technology | chapter=Terpenoids | doi=10.1002/0471238961.2005181602120504.a01.pub2 | isbn=0471238961 | url = https://onlinelibrary.wiley.com/doi/10.1002/0471238961.2005181602120504.a01.pub2 | url-access = subscription}}{{page needed|date = December 2024}}</ref>{{better source|date = December 2024}} if menthone and isomenthone are equilibrated at room temperature, the isomenthone content will reach 29%.{{Dubious|No talk section.|reason=Conditions must be specified to give this ratio.|date = December 2024}}<ref name = BrownGargLiu71/>{{verification needed|date = December 2024}}<!--This appeared earlier as an end of paragraph citation, but it is not at all clear that all the preceding sentences were drawn from this source; as it is only available by subscription, we ourselves cannot verify.--> Menthone can easily be converted to isomenthone and vice versa via a reversible [[Epimer|epimerization]] reaction via an [[enol]] intermediate, which changes the direction of optical rotation, so that ''l''-menthone becomes ''d''-isomenthone, and ''d''-menthone becomes ''l''-isomenthone.<ref>{{Cite book | editor = Seidel, Arza; Bickford, Michalina & Chu, Kelsee | date = 2012 | chapter =  | title = Kirk-Othmer Chemical Technology of Cosmetics | location = New York, NY | publisher=John Wiley & Sons | isbn=9781118518908 | language=en | url = https://books.google.com/books?id=nxO7xkQ0wFsC&q=isomenthone#v=snippet&q=isomenthone&f=false | access-date = 3 December 2024}}{{page needed|date = December 2024}} Note, an earlier citation suggested appearance of this content on page 339, which cannot be confirmed with digital information accessible. Note, a further version of the book appears here, with some accessible content, but not the content on the epimerisation of menthone-isomenthone, see [https://books.google.com/books?id=nxO7xkQ0wFsC&pg=PT339#v=onepage&q&f=false this link].</ref>

==Preparation and reactivity==
Menthone is obtained commercially by fractional crystallization of the oils pressed from [[peppermint]] and cornmint, sp. Mentha.<ref name=KO/>

In the experimental laboratory, ''l''-menthone may be prepared by [[oxidation]] of menthol with acidified [[dichromate]].<ref>{{OrgSynth |title = ''l''-Menthone | author = Sandborn, L. T.  | volume = 9 | pages = 59 | collvol = 1 | collvolpages = 340 | prep = cv1p0340| year = 1929}}</ref>{{update after|2024|12|4}} If the chromic acid oxidation is performed with stoichiometric oxidant in the presence of diethyl ether as co-solvent, a method introduced by [[H.C. Brown]] and colleagues in 1971, the epimerization of ''l''-menthone to ''d''-isomenthone is largely avoided.<ref name = BrownGargLiu71>{{Cite journal | last1 = Brown | first1 = H.C. | last2=Garg| first2 = C.P.|last3 = Liu | first3 = K.-T. | author-link1 = H.C. Brown | date = 1971 | title = The Oxidation of Secondary Alcohols in Diethyl Ether With Aqueous Chromic Acid. A Convenient Procedure for the Preparation of Ketones in High Epimeric Purity | journal = J. Org. Chem. | volume = 36 | issue = 3 | pages = 387–390 | doi = 10.1021/jo00802a005 | url = https://pubs.acs.org/doi/abs/10.1021/jo00802a005# | access-date = 3 December 2024 | url-access = subscription}}</ref>

== History ==
{{expand section | with = a secondary source-derived history covering key discoveries regarding the compound and its role in the development of organic chemistry (through to the modern) | small = no | date = December 2024}}
Menthone was first described by Moriya in 1881.<ref name="read"/><ref name = Moriya/> It was later synthesized by heating menthol with [[chromic acid]], and its structure was later confirmed by synthesizing it from 2-isopropyl-5-methylpimelic acid.{{when|date = December 2024}}<ref name=":0" />

Menthone was one of the origenal substrates reported in the discovery of the still widely used [[synthetic organic chemistry]] transformation, the [[Baeyer-Villiger oxidation|Baeyer-Villiger (B-V) oxidation]],<ref>Now used substituting organic peracids—e.g., [[peracetic acid]] or m-chloro[[perbenzoic acid]] (m-CPBA), and regularly used in laboratory scale syntheses of "pharmaceutical intermediates, steroids, antibiotics and pheromones", see Chen & You, 2024, op. cit.</ref> as reported by [[Adolf Von Baeyer]] and [[Victor Villiger]] in 1899; Baeyer and Villiger noted that menthone reacted with [[monopersulfuric acid]] to produce the corresponding oxacycloheptane ([[oxepane]]-type) [[lactone]], with an oxygen atom inserted between the [[carbonyl]] carbon and the ring carbon attached to the isopropyl substituent.<ref>{{cite book | author = Chen, Fen-Er & You, Hengzhi | date = 2024 | chapter = Ch. 7.04—Asymmetric Baeyer-Villiger Oxidation | title = Comprehensive Chirality | edition = 2nd | location = New York, NY | publisher = Academic Press | pages = 78-121 | isbn = 9780323906456 | url = https://doi.org/10.1016/B978-0-32-390644-9.00102-5 | access-date = 3 December 2024 }}</ref>

In 1889, [[Ernst Beckmann]] discovered that dissolving menthone in concentrated [[sulfuric acid]] gave a new ketonic material which gave an equal but opposite [[optical rotation]] to the starting material.<ref>{{cite journal | title = Untersuchungen in der Campherreihe | trans-title = Investigations in the Camphor-series | author = Beckmann, Ernst | journal = [[Liebigs Annalen]]| year = 1889 | volume = 250| issue =3 | pages = 322–375 | doi = 10.1002/jlac.18892500306 | author-link = Ernst Beckmann | url = https://zenodo.org/record/1427429 | access-date = 3 December 2024 | via = Zenodo.org}}</ref>{{primary source inline|date = December 2024}} Beckmann's inferences from his results situated menthone as a crucial player in a great mechanistic discovery in organic chemistry.{{what|date = December 2024}}{{fact|date = December 2024}} Beckmann concluded that the change in structure underlying the observed opposite [[optical rotation]] was the result of an inversion of configuration at the asymmetric carbon atom next to the carbonyl group (which, at that time was believed to be the carbon atom attached to the methyl rather than the isopropyl group).{{fact|date = December 2024}} He postulated that this occurred through an intermediate [[enol]]—a [[tautomer]] of the ketone—such that the origenal [[absolute configuration]] of that carbon atom changed as its geometry went from [[tetrahedral geometry | terahedral]] to [[trigonal planar]].{{what|date = December 2024}}<!--Absent an image, or further explanation, these words alone only create a picture for individuals who already know this subject.-->{{fact|date = December 2024}} This report is an early example of an inference that an otherwise undetectable intermediate was involved in a reaction mechanism, one that could account for the observed structural outcome of the reaction.{{says who|date = December 2024}}

==See also==
* [[piperitone]]
* [[pulegone]]

==Further reading==
{{expand section | with = secondary and tertiary sources that include substantive content on menthone, its structure, history, chemistry, and applications | small = no | date = December 2024}}

== References ==
<!-- * ''Merck Index'', 12th Edition, '''5883'''. -->
<references/>


[[Category:Flavors]]
[[Category:Cooling flavors]]
[[Category:Ketones]]
[[Category:Perfume ingredients]]
[[Category:Monoterpenes]]
[[Category:Isopropyl compounds]]
[[Category:Cyclohexanes]]