65253-04-5

Basic information

• Product Name: (-)-8-PHENYLMENTHOL
• Synonyms: (-)-PHENMENTHOL;(-)-8-PHENYLMENTHOL;Cyclohexanol, 5-methyl-2-(1-methyl-1-phenylethyl)-, (1R,2S,5R)-;(-)-8-Phenylmenthol, GC 97%;5-METHYL-2-(1-METHYL-1-PHENYLETHYL)-(1R,2S,5R)-CYCLOHEXANOL;(-)-8-Phenylmenthol,98%;(-)-8-Phenylmenthol,97%;(1R,2S,5R)-5-Methyl-2-(2-phenylpropan-2-yl)cyclohexanol
• CAS NO: 65253-04-5
• Molecular Formula: C₁₆H₂₄O
• Molecular Weight: 232.36
• Mol File: 65253-04-5.mol

Chemical Properties

• Boiling Point: 130 °C (0.7501 mmHg)
• Flash Point: >230 °F
• Appearance: Clear colorless to light yellow/Viscous Liquid
• Density: 0.999 g/mL at 20 °C(lit.)
• Vapor Pressure: 5.55E-05mmHg at 25°C
• Refractive Index: n20/D 1.53(lit.)
• Storage Temp.: 2-8°C
• Solubility: Chloroform (Slightly), Methanol (Very Slightly)
• PKA: 15.21±0.60(Predicted)
• BRN: 3651167
• CAS DataBase Reference: (-)-8-PHENYLMENTHOL(CAS DataBase Reference)
• NIST Chemistry Reference: (-)-8-PHENYLMENTHOL(65253-04-5)
• EPA Substance Registry System: (-)-8-PHENYLMENTHOL(65253-04-5)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36
• WGK Germany: 3
• F: 3-8-10
• Hazardous Substances Data: 65253-04-5(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
(-)-8-Phenylmenthol is used as a key intermediate in the synthesis of piperidine-based analogs of cocaine. These analogs serve as monoamine reuptake inhibitors, which are important in the treatment of various neurological and psychiatric disorders due to their ability to modulate the levels of neurotransmitters in the brain.
Additionally, (-)-8-Phenylmenthol is used as a starting material for the preparation of quinuclidinyl (fluoroalkyl)benzilate. (-)-8-Phenylmenthol acts as a muscarinic receptor antagonist, which has potential applications in the treatment of various conditions, such as Alzheimer's disease and other cognitive impairments, by blocking the action of acetylcholine on muscarinic receptors.

InChI:InChI=1/C16H24O/c1-12-9-10-14(15(17)11-12)16(2,3)13-7-5-4-6-8-13/h4-8,12,14-15,17H,9-11H2,1-3H3/t12-,14-,15-/m1/s1

Upstream product

• 89-82-7 pulegone 
• 88002-15-7 Phenylglyoxylsaeure-<(1R,2S,5R)-5-methyl-2-(1-methyl-1-phenylethyl)-1-cyclohexyl>ester 
• 205057-17-6 (5R)-5-methyl-2-(1-methyl-1-phenylethyl)cyclohexanone 
• 161266-94-0 (1R,2S,5R)-5-methyl-2-(1-methyl-1-phenylethyl)cyclohexyl (1R)-2-(cyclohex-2-ene)acetate 
• 161266-92-8 (R)-Cyclopent-2-enyl-acetic acid (1R,2S,5R)-5-methyl-2-(1-methyl-1-phenyl-ethyl)-cyclohexyl ester 
• 81002-22-4 (R)-3-Phenyl-butyric acid (1R,2S,5R)-5-methyl-2-(1-methyl-1-phenyl-ethyl)-cyclohexyl ester 
• 124842-70-2 (S)-3-Methyl-octanoic acid (1R,2S,5R)-5-methyl-2-(1-methyl-1-phenyl-ethyl)-cyclohexyl ester 
• 104417-88-1 (2S,3R)-2,3-Dihydroxy-2-methyl-butyric acid (1R,2S,5R)-5-methyl-2-(1-methyl-1-phenyl-ethyl)-cyclohexyl ester 
• 77-76-9 2,2-dimethoxy-propane 
• 150178-55-5 (1R,2S,5R)-5-methyl-2-(1-methyl-1-phenylethyl)cyclohexyl (2R,3E)-2-hydroxy-3-octadecenoate 
• 104130-23-6 (2R,6R)-2-(l-phenmenthyloxy)-6-phenyl-4-<(tert-butyldimethylsilyl)-oxy>-2H(5,6)-dihydropyran 
• 128797-13-7 (4aS,8aR)-4-Oxo-decahydro-naphthalene-1-carboxylic acid (1R,2S,5R)-5-methyl-2-(1-methyl-1-phenyl-ethyl)-cyclohexyl ester 
• 81002-23-5 (S)-3-Methyl-heptanoic acid (1R,2S,5R)-5-methyl-2-(1-methyl-1-phenyl-ethyl)-cyclohexyl ester 
• 71804-27-8 (1R,2S,5R)-(+)-5-methyl-2-(1-methyl-1-phenylethyl)cyclohexyl chloroacetate 

Downstream Products

• 129180-91-2 1-(1-methyl-1-phenylethyl)-4-methylcyclohexene 
• 104870-80-6 (1R,2R,5R)-2-(1-methyl-1-phenylethyl)-5-methylcyclohexanol 
• 100101-42-6 (1S,2R,5R)-2-(1-methyl-1-phenylethyl)-5-methylcyclohexanol 
• 84312-20-9 (1R,3R,4S)-8-phenylmenthyl glyoxylate 
• 129214-96-6 (-)-8-phenylneoisomenthyl glyoxylate 
• 100101-43-7 (1S,2R,5R)-5-methyl-2-(1-methyl-1-phenylethyl)cyclohexyl glyoxylate 
• 80595-59-1 bromoacetic acid (-)-8-phenylmenthol ester 
• 129180-92-3 (-)-8-phenylneoisomenthyl bromoacetate 
• 129180-90-1 (+)-8-phenylisomenthyl bromoacetate 
• 104197-95-7 (1R,2S,5R)-2-(1-methyl-1-phenylethyl)-5-methylcyclohexyl nitrooxyacetate 
• 104197-95-7 Nitrooxy-acetic acid (1R,2R,5R)-5-methyl-2-(1-methyl-1-phenyl-ethyl)-cyclohexyl ester 
• 104197-95-7 Nitrooxy-acetic acid (1S,2R,5R)-5-methyl-2-(1-methyl-1-phenyl-ethyl)-cyclohexyl ester 
• 71804-27-8 (1R,2S,5R)-(+)-5-methyl-2-(1-methyl-1-phenylethyl)cyclohexyl chloroacetate 
• 192199-24-9 (1R,3R,4S)-8-phenylmenthyl 2-methylacetoacetate 

Relevant articles and documents

Diastereoselective sulfa-Michael reactions controlled by a biomass-derived chiral auxiliary

A family of chiral auxiliaries derived from the lignocellulosic biomass pyrolysis product levoglucosenone (LGO) has been screened in the sulfa-Michael reaction. When promoted by inorganic bases with potassium counterions, the auxiliary with geminal benzyl substituents showed diastereoselectivity up to 90:10 for a broad range of α,β-unsaturated esters.

Diastereoselective photocycloaddition reactions of 2-naphthalenecarboxylates and 2,3-naphthalenedicarboxylates with furans governed by chiral auxiliaries and hydrogen bonding interactions

By using chiral auxiliaries and hydrogen bonding interactions, we have developed diastereoselective photocycloaddition of 2-naphthalenecarboxylates and 2,3-naphthalenedicarboxylates with furan derivatives. In photoreactions of (?)-menthyl 2-naphthalenecarboxylate with furan and 3-furanmethanol, respective maximum 48% and 40% diastereomeric excesses (d.e.) are observed. In photoreactions of di-8-phenyl-(?)-menthyl 2,3-naphthalenedicarboxylate with 3-furanmethanol, maximum 67% d.e. is obtained. Use of solvents of low polarity, low temperatures and low furan concentration leads to increased diastereoselectivities. Variable-temperature (VT) NMR and fluorescence quenching studies indicate that hydrogen bonding interactions between the carbonyl oxygen of naphthalenecarboxylic acid esters and the OH group in 3-furanmethanol take place in both the ground and excited states. The results of computational studies show that geometries of C2 symmetric naphthalenedicarboxylate reactants are important in governing the high diastereoselectivity in the photoreactions of 2,3-naphthalenedicarboxylates.

Method for Highly Enantioselective Ligation of Two Chiral C(sp3) Stereocenters

A method is described for the joining of two α-lithiated C(sp3) stereocenters efficiently and with retention of configuration. The key step involves the effective removal of two electrons from a chiral organocuprate R2CuLi, by i-propyl 2,4-dinitrobenzoate to form a Cu(III) complex that undergoes at -90 °C accelerated reductive elimination enantioselectively and exclusively without the formation of free radicals.

Diastereoselective anodic hetero- and homo-coupling of menthol-, 8-methylmenthol- and 8-phenylmenthol-2-alkylmalonates

Diastereoselective radical coupling was achieved with chiral auxiliaries. The radicals were generated by anodic decarboxylation of five malonic acid derivatives. These were prepared from benzyl malonates and four menthol auxiliaries. Coelectrolyses with 3,3-dimethylbutanoic acid in methanol at platinum electrodes in an undivided cell afforded hetero-coupling products in 22-69% yield with a diastereoselectivity ranging from 5 to 65% de. Electrolyses without a coacid led to diastereomeric homo-coupling products in 21-50% yield with ratios of diastereomers being 1.17:2.00:0.81 to 7.03:2.00. The stereochemistry of the new stereogenic centers was confirmed by X-ray structure analysis and 13C NMR data.

Synthesis of the Privileged 8-Arylmenthol Class by Radical Arylation of Isopulegol

Hydrogen atom transfer (HAT) circumvents a disfavored Friedel-Crafts reaction in the derivatization of the inexpensive monoterpene isopulegol. A variety of readily prepared aryl and heteroaryl sulfonates undergo a formal hydroarylation to form 8-arylmenthols, privileged scaffolds for asymmetric synthesis, as typified by 8-phenylmenthol. High stereoselectivity is observed in related systems. This use of HAT significantly extends the chiral pool from the inexpensive monoterpene isopulegol.

Diastereoselective Radical Hydroacylation of Alkylidenemalonates with Aliphatic Aldehydes Initiated by Photolysis of Hypervalent Iodine(III) Reagents

Diastereoselective radical hydroacylation of chiral alkylidenemalonates with aliphatic aldehydes is realized by the combination of a hypervalent iodine(III) reagent and UV-light irradiation. The reaction is initiated by the photolysis of hypervalent iodine(III) reagents under mild, metal-free conditions, and is the first example of diastereoselective addition of acyl radicals to olefins to afford chiral ketones in a highly stereoselective fashion. The obtained optically active ketones are useful chiral synthons, as exemplified by the short formal synthesis of (-)-methyleneolactocin.

Asymmetric 1,2-Perfluoroalkyl Migration: Easy Access to Enantioenriched α-Hydroxy-α-perfluoroalkyl Esters

This study has led to the development of a novel, highly efficient, 1,2-perfluoro-alkyl/-aryl migration process in reactions of hydrate of 1-perfluoro-alkyl/-aryl-1,2-diketones with alcohols, which are promoted by a Zn(II)/bisoxazoline and form α-perfluoro-alkyl/-aryl-substituted α-hydroxy esters. With (-)-8-phenylmenthol as the alcohol, the corresponding menthol esters are generated in high yields with excellent levels of diastereoselectivity. The mechanistic studies show that the benzilic ester-type rearrangement reaction takes place via an unusual 1,2-migration of electron-deficient trifluoromethyl group rather than the phenyl group. The overall process serves as a novel, efficient, and simple approach for the synthesis of highly enantioenriched, biologically relevant α-hydroxy-α-perfluoroalkyl carboxylic acid derivatives.

Stereoselective synthesis of trans-THF rings using an oxidative cyclisation-radical deoxygenation sequence: Application to the formal synthesis of trans-(2R,5R)-linalool oxide

An efficient stereoselective synthesis of cis-2,5-disubtituted tetrahydrofuran (THF) diols has been achieved using permanganate-mediated oxidative cyclisation of 1,5-diene precursors. The facial selectivity during the course of cyclisation was induced by incorporating conveniently accessible chiral auxiliaries such as (2R)-10,2-camphorsultam, (S)-4-benzyloxazolidin-2-one and (-)-8-phenylmenthol. The use of (2R)-10,2-camphorsultam furnished the desired THF product as a single isolated diastereoisomer. Conformational analyses are presented to rationalize the origin of facial selectivity and synthetic investigation towards successfully accomplished transformation of cis-2,5-disubstituted THF diols into corresponding trans-THF compounds is also described, leading to a stereoselective formal synthesis of trans-(2R,5R)-linalool oxide.

C-selective and diastereoselective alkyl addition to β,γ-alkynyl-α-imino esters with zinc(II)ate complexes

Since umpolung α-imino esters contain three electrophilic centers, regioselective alkyl addition with traditional organometallic reagents has been a serious problem in the practical synthesis of versatile chiral α-amino acid derivatives. An unusual C-alkyl addition to α-imino esters using a Grignard reagent (RMgX)-derived zinc(II)ate was developed. Zinc(II)ate complexes consist of a Lewis acidic [MgX]+moiety, a nucleophilic [R3Zn]- moiety, and 2[MgX2]. Therefore, the ionically separated [R3Zn]- selectively attacks the imino carbon atom, which is most strongly activated by chelation of [MgX]+. In particular, chiral β,γ-alkynyl-α-imino esters can strongly promote highly regio- and diastereoselective C-alkylation because of structural considerations, and the corresponding optically active α-quaternary amino acid derivatives are obtained within 5 minutes in high to excellent yields.

Highly stereoselective cycloadditions of Danishefsky's diene to (-)-8-phenylmenthyl and (+)-8-phenylneomenthyl glyoxylate N-phenylethylimines

Enantiopure 4-oxo-pipecolic acid derivatives were obtained by double asymmetric induction aza-Diels-Alder reactions between chiral glyoxylate N-phenylethylimines and Danishefsky's diene mediated by zinc iodide. The key to success was the use of iminoacetates possessing two chiral auxiliaries, N-(S)- or N-(R)-1-phenylethyl and (-)-8-phenylmenthyl or (+)-8-phenylneomenthyl. Adducts were formed in good yields (78-81%), with complete regioselectivity and high diastereoselectivity (87-96%). The absolute configuration of the adducts formed was unequivocally assigned through NMR, specific optical rotation and X-ray data of appropriated derivatives. These cycloadducts can serve as precursors for bioactive piperidinic azasugars and pipecolic acid derivatives.