Menthone

Menthone is a constituent of the essential oils of pennyroyal, peppermint, corn mint, pelargonium geraniums, and other plant species. In most essential oils, it is a minor component.{{Citation |last1=Gaich |first1=T. |title=2.7 Chiral Pool Synthesis: Starting from Terpenes |date=2012-01-01 |work=Comprehensive Chirality |pages=163–206 |editor-last=Carreira |editor-first=Erick M. |url=https://linkinghub.elsevier.com/retrieve/pii/B9780080951676002020 |access-date=2024-12-27 |place=Amsterdam |publisher=Elsevier |doi=10.1016/b978-0-08-095167-6.00202-0 |isbn=978-0-08-095168-3 |last2=Mulzer |first2=J. |editor2-last=Yamamoto |editor2-first=Hisashi}} Menthone was first synthesized by oxidation of menthol in 1881,{{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}}{{update after|2024|12|4}}{{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, Transactions | volume = 39 | pages = 77–83 | doi = 10.1039/CT8813900077 | url = https://zenodo.org/record/1680417 | access-date = 3 December 2024 | via = Zenodo.org}} 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 (2S,5R)-trans-2-isopropyl-5-methylcyclohexanone (see infobox and below)—is the most abundant in nature.{{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}}

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Menthone is a liquid under standard conditions, and has a density of 0.895 g/cm³.{{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.{{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}} 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.{{verification needed|date = December 2024}}

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 spectrometric and spectroscopic evidence (e.g., from 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 framework.{{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}}{{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.{{GoldBookRef|title=absolute configuration|file=A00020}} Hence, four unique stereoisomers are possible for this structure: (2S,5S), (2R,5S), (2S,5R) and (2R,5R).{{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}}{{better source|date = December 2024}}

The (2S,5S) and (2R,5R) stereoisomers project the isopropyl and methyl groups from the same "side" of the cyclohexane ring, are the so-called 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 trans isomers, and are referred to as menthone.{{better source|date = December 2024}} Because the (2S,5R) isomer has an observed negative optical rotation, it is called l-menthone or (−)-menthone. It is the enantiomeric partner of the (2R,5S) isomer: (+)- or d-menthone.{{better source|date = December 2024}}{{verification needed|date = December 2024}}

Menthone and isomenthone interconvert easily, the equilibrium favoring menthone;{{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}}{{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}}{{verification needed|date = December 2024}} Menthone can easily be converted to isomenthone and vice versa via a reversible 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.{{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 | 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].

Menthone is obtained commercially by fractional crystallization of the oils pressed from peppermint and cornmint, sp. Mentha.

In the experimental laboratory, l-menthone may be prepared by oxidation of menthol with acidified dichromate.{{OrgSynth |title = l-Menthone | author = Sandborn, L. T. | volume = 9 | pages = 59 | collvol = 1 | collvolpages = 340 | prep = cv1p0340| year = 1929}}{{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.{{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}}

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Menthone was first described by Moriya in 1881. 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}}

Menthone was one of the original substrates reported in the discovery of the still widely used synthetic organic chemistry transformation, the Baeyer-Villiger (B-V) oxidation,Now used substituting organic peracids—e.g., peracetic acid or m-chloroperbenzoic acid (m-CPBA), and regularly used in laboratory scale syntheses of "pharmaceutical intermediates, steroids, antibiotics and pheromones", see Chen & You, 2024, op. cit. 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.{{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 | doi = 10.1016/B978-0-32-390644-9.00102-5 | isbn = 9780323906456 | url = https://doi.org/10.1016/B978-0-32-390644-9.00102-5 | access-date = 3 December 2024 }}

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.{{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}}{{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 original absolute configuration of that carbon atom changed as its geometry went from terahedral to trigonal planar.{{what|date = December 2024}}{{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}}

• Piperitone
• Pulegone

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Category:Ketones

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Category:Monoterpenes

Category:Isopropyl compounds

Category:Cyclohexanes