494-90-6

Usage

Uses

Used in Chemical Industry:
MENTHOFURAN is used as a chemical compound for its unique properties, such as its minty odor and hepatotoxic effects, which can be utilized in the development of various chemical products and research applications.
Used in Flavor and Fragrance Industry:
MENTHOFURAN is used as a flavoring agent for its musty, nutty, coffee, raw, and legume taste characteristics, adding a distinct flavor profile to various food and beverage products.
Used in Essential Oils Industry:
MENTHOFURAN is used as a component in essential oils, contributing to their unique aroma and properties. It is found in peppermint oil, corn mint oil, spearmint oil, Scotch spearmint oil, pennyroyal oil, and other Mentha oils, as well as buchu oil.
Used in Research and Development:
MENTHOFURAN is used as a research compound for studying its hepatotoxic effects and potential applications in the development of new drugs or treatments for various health conditions.

Preparation

(+)-Menthofuran [17957-94-7] is isolated fromMentha oils or is prepared synthetically, for example, by treatment of (+)-pulegone with fuming sulfuric acid in acetic anhydride and pyrolysis of the resulting sultone.

Synthesis Reference(s)

The Journal of Organic Chemistry, 48, p. 2442, 1983 DOI: 10.1021/jo00162a037

Synthesis

By thermal decomposition of the sulfone of 3-hydroxy-3,8(9)-methadiene-9-sulfonic acid; the latter is obtained by sulfonapulegone in acetic anhydride.

InChI:InChI=1/C10H14O/c1-7-3-4-9-8(2)6-11-10(9)5-7/h6-7H,3-5H2,1-2H3

Upstream product

• 13341-72-5 menthalactone 
• 89-82-7 pulegone 
• 63549-11-1 4,7-dimethyl-5,6,7,8-tetrahydro-benzo[e][1,2]oxathiine 2,2-dioxide 
• 27579-55-1 2-bromo-4-methylcyclohexanone 
• 24720-64-7 2-(triphenylphosphoranylidene)propionaldehyde 
• 29606-79-9 isopulegone 
• 2565-83-5 (2Z)-1-methoxy-3,7-dimethylocta-2,6-diene 
• 13834-09-8 (3R,3aR,6R,7aR)-3,6-Dimethyl-octahydro-benzofuran 
• 13955-48-1 (3S,3aR,7aS)-3,6-Dimethyl-2,3,3a,4,5,7a-hexahydro-benzofuran 
• 13955-48-1 (3RS,3aRS,7aSR)-3,6-dimethyl-2,3,3a,4,5,7a-hexahydrobenzofuran 
• 88717-91-3 1-O-methyl-10-hydroxynerol 
• 88717-90-2 1-O-methyl-10-hydroxygeraniol 
• 79726-51-5 (3S,3aS,6S,7aS)-3,6-Dimethyl-hexahydro-benzofuran-2-one 
• 79726-51-5 (3R,3aS,6S,7aS)-3,6-Dimethyl-hexahydro-benzofuran-2-one 

Downstream Products

• 1374431-15-8 3,6-dimethyl-2-phenyl-4,5,6,7-tetrahydrobenzofuran 
• 1209986-01-5 4-(3,6-dimethyl-4,5,6,7-tetrahydrobenzofuran-2-yl)benzonitrile 
• 1209986-02-6 2-(4-fluorophenyl)-3,6-dimethyl-4,5,6,7-tetrahydrobenzofuran 
• 490-46-0 (2R,3R)-2-(3,4-dihydroxyphenyl)-3,4-dihydro-1[2H]-benzopyran-3,5,7-triol 
• 88082-60-4 cinnamtannin B-1 

Relevant academic research and scientific papers

In Vivo Studies on the Metabolism of the Monoterpene Pulegone in Humans Using the Metabolism of Ingestion-Correlated Amounts (MICA) Approach: Explanation for the Toxicity Differences between (S)-(-)- and (R)-(+)-Pulegone

The major in vivo metabolites of (S)-(-)-pulegone in humans using a metabolism of ingestion-correlated amounts (MICA) experiment were newly identified as 2-(2-hydroxy-1-methylethyl)-5-methylcyclohexanone (8-hydroxymenthone, M1), 3-hydroxy-3-methyl-6-(1-methylethyl)cyclohexanone (1-hydroxymenthone, M2), 3-methyl-6-(1-methylethyl)cyclohexanol (menthol), and E-2-(2-hydroxy-1-methylethylidene)-5-methylcyclohexanone (10-hydroxypulegone, M4) on the basis of mass spectrometric analysis in combination with syntheses and NMR experiments. Minor metabolites were be identified as 3-methyl-6-(1-methylethyl)-2-cyclohexenone (piperitone, M5) and α,α,4-trimethyl-1-cyclohexene-1-methanol (3-p-menthen-8-ol, M6). Menthofuran was not a major metabolite of pulegone and is most probably an artifact formed during workup from known (M4) and/or unknown precursors. The differences in toxicity between (S)-(-)- and (R)-(+)-pulegone can be explained by the strongly diminished ability for enzymatic reduction of the double bond in (R)-(+)-pulegone. This might lead to further oxidative metabolism of 10-hydroxypulegone (M4) and the formation of further currently undetected metabolites that might account for the observed hepatotoxic and pneumotoxic activity in humans.

A Novel Synthesis of Methylenecyclopropane Spiro-Linked with Cycloalkanes via a Cyclization of Allylic Epoxides and Its Application to a Synthesis of Fused 3-Methylfurans

Ring closure of allylic epoxides derived from 1-chloroalkyl phenyl sulfoxides and cyclic ketones with lithium diisopropylamide (LDA) in 3-Exo-Tet mode gave spiro-linked methylenecyclopropanes having a hydroxyl group in good yields.Oxidation of these compounds gave ketones, which were then treated with p-toluenesulfonic acid in 1,4-dioxane or DMSO at 100 deg C to give fused 3-methylfurans in good overall yields.This procedure was applied to a synthesis of menthofuran from 4-methylcyclohexanone.

FURANNULATION STRATEGY. AN EFFICIENT SYNTHESIS OF FUSED 3-METHYLFURANS

A two-step synthesis of fused 3-methylfurans (furannulation) by the addition of enolate anion of cyclic 1,3-dicarbonyl compounds to allenic sulfonium salt is described.

TOTAL SYNTHESIS OF VARIOUS ELEMANOLIDES

Starting with a suitable substituted divinyl cyclohexanone, eleven naturally occurring 12.8-elemanolides bearing exo-methylene or methyl groups at C-11 and differing in substitution as well as in relative configuration, have been synthesized in racemic form.An approach to elemanolides with additional oxygen functionalities is principally possible by modification of the basic concept.Methods for the oxidative generation of terpenoid exo-methylene lactone and furan units are exemplified by synthesis of menthofuran and the p-menthenolides from isopulegols.

Regiospecific Functionalization of the Monoterpene Ether 1,3,3-Trimethyl-2-oxabicyclooctane (1,8-Cineole). Synthesis of the Useful Bridged γ-Lactone 1,3-Dimethyl-2-oxabicyclooctan-3-->5-olide

The regiospecific functionalization at C-5 and difuctionalization at C-5/C-8 and C-5/C-10 of the monoterpene 1,3,3-trimethyl-2-oxabicyclooctane (1) is described.Chromyl acetate oxidation of 1 afforded 1,3,3-trimethyl-2-oxabicyclooctan-5-one (6) in 60percent yield along with 28percent of unreacted 1 and minor amounts of exo-1,3,3-trimethyl-2-oxabicyclooctan-5-ol acetate (9), 1,3,3-trimethyl-2-oxabicyclooctane-5,8-dione (13), exo-8-acetoxy-1,3,3-trimethyl-2-oxabicyclooctan-5-one (16), 1,3,3-trimethyl-2-oxabicyclooctane-5,7-dione (14), and orcinol (15).On digestion with oxalic or phthalic acid, ketone 6 was converted into a mixture of piperitenone (20), 3-methyl-2-cyclohexenone (22), acetone, and traces of isopiperitenone (21), while 60percent sulfuric acid at room temperature yielded 20 as the sole reaction product.Oxidation of 6 with chromyl acetate yielded diketone 13, which decomposed into orcinol (15) on digestion with either boiling water or a 2.5percent sodium bicarbonate solution.Sodium borohydride or lithium aluminum hydride reduction of 6 gave stereospecifically exo-1,3,3-trimethyl-2-oxabicyclooctan-5-ol (7) while reduction with sodium-ethanol or aluminum isopropoxide in isopropyl alcohol (equilibrium conditions) yielded a 3:2 mixture of the alcohols 7 and 8, respectively.Treatment of 7 with phosphoryl chloride produced 1,3,3-trimethyl-2-oxatricyclo5,8>octane (25) together with minor amounts of the chlorocineoles 10 and 11.Pyrolysis of the methyl xanthate of 7 yielded 1,3,3-trimethyl-2-oxabicyclooct-5-ene (2).Photolysis of 7 in the presence of mercuric oxide and iodine or iodosylbenzene diacetate and iodine gave the tricyclic diether 29, which was quantitatively converted into the bridged γ-lactone 30 by oxidation with ruthenium tetraoxide.Oxidation of 29 with chromyl acetate yielded a 1:1 mixture of 30 and the formate lactone 31.Lithium aluminum hydride reduction of 30 produced diol 37, which was converted into menthofuran (44) in five steps.

Chemical Tranformation of Terpenoids. V. Acidic Conversions of 10-Hydroxygeraniol and 10-Hydroxynerol Derivatives Leading to Cyclic Monoterpenoids

Acid treatment of 1-O-acetyl-10-hydroxygeraniol (5a), 1-O-methyl-10-hydroxygeraniol (5b), 1-O-acetyl-10-hydroxynerol (6a), and 1-O-methyl-10-hydroxynerol (6b) was investigated under various conditions.It was found that treatment of 5a and 6a with HCOOH gave menth-1-ene-8,9-diol (7), while treatment of 5a, 5b, 6a, or 6b with BF3-etherate in CH2Cl2 furnished two menthofuran-type compounds (9, 10) and two bicyclooct-2-ene derivatives (17, 24).Both 9 and 10 were successfully converted to menthofuran (16) and 17 was converted to a bicyclooctenone derivative (23) which was a key intermediate for a synthesis of juvabione (27).Keywords - geraniol; nerol; 10-hydroxygeraniol; 10-hydroxynerol; 10-hydroxygeraniol derivative; 10-hydroxynerol derivative; uroterpenol; menthofuran; bicyclooct-2-ene derivative

Reactions of Carboxonium Ions of Cyclic Acetals, VII. - Synthesis of rac-4,5,6,7-Tetrahydro-3,5-dimethyl-1-benzofuran and of a Mixture of its 3,4- and 3,6-Dimethyl Isomers

Thermolysis of the 4-methylene-1,3-dioxolanes 4 or of the β-oxa-γ,δ-enones 6 leads in the presence of protons to rac-4,5,6,7-tetrahydro-3,5-dimethyl-1-benzofuran (5a) and to a mixture of its 3,4- and 3,6-dimethyl isomers 5b/5c.The mechanism of the furan formation has been investigated.

PHOTOCHEMICAL TRANSFORMATION OF UNSATURATED SULTONES INTO FURANS

Photolysis of unsaturated sultones I and IV afforded 2,4-dimethylfuran (III) and menthofuran (V), respectively.