39212-23-2

Basic information

• Product Name: Whiskey lactone
• Synonyms: WHISKEY LACTONE;WHISKY LACTONE;5-butyldihydro-4-methyl-2(3h)-furanon;FEMA 3803;METHYL OCTALACTONE;METHYL OCTALACTONE(TM);(+/-)-5-BUTYL-4-METHYLDIHYDRO-2(3H)-FURANONE;5-BUTYLDIHYDRO-4-METHYL-2(3H)-FURANONE
• CAS NO: 39212-23-2
• Molecular Formula: C₉H₁₆O₂
• Molecular Weight: 156.22
• EINECS: 254-357-4
• Mol File: 39212-23-2.mol
• Article Data: 32

Chemical Properties

• Boiling Point: 93-94 °C5 mm Hg(lit.)
• Flash Point: >230 °F
• Appearance: /
• Density: 0.952 g/mL at 25 °C(lit.)
• Vapor Pressure: 0.027mmHg at 25°C
• Refractive Index: n20/D 1.4454(lit.)
• CAS DataBase Reference: Whiskey lactone(CAS DataBase Reference)
• NIST Chemistry Reference: Whiskey lactone(39212-23-2)
• EPA Substance Registry System: Whiskey lactone(39212-23-2)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36-37/39
• WGK Germany: 2
• Hazardous Substances Data: 39212-23-2(Hazardous Substances Data)

Usage

Uses

Used in Beverage Industry:
Whiskey lactone is used as a flavoring agent for beverages, particularly in the production of whiskey, rum, Irish malt, bourbon whiskey, Scotch, sherry, port, and wine. It imparts a unique woody, coumarinic, coconut, lactonic, creamy, and nutty taste with a toasted nuance, enhancing the overall flavor profile of these drinks.
Used in Aroma Compositions:
Whiskey lactone is also used in the creation of aroma compositions, where its intense, warm, sweet, and coumarin-like odor adds depth and complexity to fragrances. This application takes advantage of the compound's ability to evoke a range of taste characteristics, making it a valuable addition to the world of aromas and perfumes.
Production Methods:
A cis-trans mixture of whiskey lactone can be prepared through a radical addition reaction of pentanal with crotonic acid, followed by reductive cyclization of the resulting ??-oxo acid with sodium boron hydride/sulfuric acid. This process allows for the synthesis of whiskey lactone, which can then be used in various applications across different industries.

Synthesis Reference(s)

Tetrahedron Letters, 26, p. 6225, 1985 DOI: 10.1016/S0040-4039(00)95058-5

Trade name

Methyl octalactoneTM (PFW)

InChI:InChI=1/C9H16O2/c1-3-4-5-8-7(2)6-9(10)11-8/h7-8H,3-6H2,1-2H3

Upstream product

• 141069-42-3 (3R,4R)-3-Methyl-4-(2-methyl-propane-2-sulfinyl)-octanoic acid 
• 141069-52-5 (3R,4R)-3-Methyl-4-(toluene-4-sulfinyl)-octanoic acid 
• 102587-17-7 1-(1,3-Dithianylidene)-2-methyl-3-heptanol 
• 31705-09-6 (2α,3β)-(+/-)-2-Butyltetrahydro-3-methylfuran 
• 4938-52-7 1-hepten-3-ol 
• 87143-54-2 C₁₀H₂₀O₂ 
• 693-03-8 n-butyl magnesium bromide 
• 65038-34-8 3-formyl-butyric acid methyl ester 
• 109-72-8 n-butyllithium 
• 24406-16-4 lithium di-n-butylcuprate 
• 693-04-9 butyl magnesium bromide 
• 142685-47-0 3-methyl-4-oxo-octanoic acid ethyl ester 
• 31705-09-6 (2α,3α)-(+/-)-2-Butyltetrahydro-3-methylfuran 
• 126188-65-6 4-methyl-5-(n-butyl)-2(5H)-furanone 

Downstream Products

• 87433-99-6 C₄H₄O₂(CH₂HgBr)(CH₂CH₂CH₂CH₃) 
• 87434-00-2 CH₃OOCCH₂CH(CH₂HgBr)CH(OOCCF₃)CH₂CH₂CH₂CH₃ 
• 105119-22-0 (4R,5S)-trans-5-n-butyl-4-methyl-4,5-dihydro-2(3H)-furanone 
• 104910-76-1 (3S,4S)-3-Methyl-4-<(1'S,4'R)-4',7',7'-trimethyl-3'-oxo-2'-oxabicyclo<2.2.1>heptan-1'-ylcarbonyloxy>octansaeure-isopropylester 
• 105015-54-1 (3R,4R)-3-Methyl-4-<(1'S,4'R)-4',7',7'-trimethyl-3'-oxo-2'-oxabicyclo<2.2.1>heptan-1'-ylcarbonyloxy>octansaeure-isopropylester 
• 104910-74-9 (3R,4R)-3-Methyl-4-<(R)-2-phenylpropionyloxy>octansaeure-isopropylester 
• 105015-50-7 (3S,4S)-3-Methyl-4-<(R)-2-phenylpropionyloxy>octansaeure-isopropylester 
• 741716-97-2 (3S,4S)-benzyl 3-methyl-4-O-(2',3',4',6'-tetra-O-pivaloyl-β-D-glucopyranosyl)octanoate 
• 741716-98-3 (3R,4R)-benzyl 3-methyl-4-O-(2',3',4',6'-tetra-O-pivaloyl-β-D-glucopyranosyl)octanoate 

Relevant articles and documents

Exploiting the vicinal disubstituent effect on the diastereoselective synthesis of γ and δ lactones

Trifluoroacetic acid catalysed lactonization of vicinal disubstituted γ-hydroxyesters was investigated in different solvents. The reaction kinetics, monitored by NMR spectroscopy, showed that: (i) the vic-disubstituent effect is stereoselective since the anti diastereoisomer ring closes substantially more rapidly than the syn isomer ring; (ii) the anti-vic effect is much stronger than the classical Thorpe-Ingold effect (known also as the gem-disubstituent effect), instead the syn diastereoisomers have rate constants comparable to that of the gem-disubstituted ester; (iii) the vic-effect can be enhanced by increasing the steric hindrance of one of the two substituents or carrying out the reaction in non-polar solvents. DFT computations of energy barriers (ΔG?) were in good agreement with the experimental data. The distortion/interaction-activation strain model together with the Winstein-Holness kinetic scheme gave more insights into the origin of the vic-effect. An application of this effect consists of the diastereomeric resolution of disubstituted γ and δ lactones, among which are the naturally occurring Nicotiana t. lactone, the whisky and cognac oak lactones, and the Aerangis lactone. Both cis and trans diastereoisomers of these lactones were isolated in good yield and with high diastereomeric excess (de >92%). The selectivities of the diastereomeric resolution process, determined by NMR spectroscopy, are reported as well.

Enantioselective, Catalytic One-Pot Synthesis of γ-Butyrolactone-Based Fragrances

Herein the preparative (1 g scale), stereoselective syntheses of various alkyl-substituted γ-butyrolactone fragrances 1 is described. The α,β-unsaturated γ-keto esters 2 as starting materials were synthesized by a Horner-Wadsworth-Emmons reaction and are further reduced by an ene reductase and alcohol dehydrogenase in a one-pot enzyme cascade to nine desired γ-butyrolactones 1, among them whisky (1 c) and cognac lactone (1 d). The products 1 were obtained in moderate to good yields and very good diastereoselectivities. Furthermore, the position of a nBu-substituent was permutated to study the effect on the enzyme cascade.

PROCESS FOR THE ELECTROCHEMICAL PREPARATION OF GAMMA-HYDROXYCARBOXYLIC ESTERS AND GAMMA-LACTONES

γ-Hydroxycarboxylic esters and γ-lactones which are suitable as flavors can be prepared by electrochemical reductive cross-coupling of α,β-unsaturated esters with carbonyl compounds in an undivided electrolysis cell having a cathode composed of lead, lead alloys, cadmium, cadmium alloys, mercury, steel, glassy carbon or boron-doped diamonds and a basic aqueous electrolyte comprising an electrolyte salt which suppresses the cathodic formation of hydrogen.

Lactones 42. Stereoselective enzymatic/microbial synthesis of optically active isomers of whisky lactone

Two different methods, enzyme-mediated reactions and biotrasformations with microorganisms, were applied to obtain optically pure cis- and trans-isomers of whisky lactone 4a and 4b. In the first method, eight alcohol dehydrogenases were investigated as biocatalysts to enantioselective oxidation of racemic erythro- and threo-3-methyloctane-1,4-diols (1a and 1b). Oxidation processes with three of them, alcohol dehydrogenases isolated from horse liver (HLADH) as well as recombinant from Escherichia coli and primary alcohol dehydrogenase (PADH I), were characterized by the highest degree of conversion with moderate enantioselectivity (ee = 27-82%) of the reaction. In all enzymatic reactions enantiomerically enriched not naturally occurring isomers of trans-(-)-(4R,5S)-4b or cis-(+)-(4R,5R)-4a were formed preferentially. In the second strategy, based on microbial lactonization of γ-oxoacids, naturally occurring opposite isomers of whisky lactones were obtained. Trans-(+)-(4S,5R)-isomer (ee = 99%) of whisky lactone 4b was stereoselectively formed as the only product of biotransformations of 3-methyl-4-oxooctanoic acid (5) catalyzed by Didimospheria igniaria KCH6651, Laetiporus sulphurens AM525, Chaetomium sp.1 KCH6670 and Saccharomyces cerevisiae AM464. Biotransformation of c-oxoacid 5, in the culture of Beauveria bassiana AM278 and Pycnidiella resinae KCH50 afforded a mixtures of trans-(+)-(4S,5R)-4b with enantiomeric excess ee = 99% and cis-(-)-(4S,5S)-4a with enantiomeric excesses ee = 77% and ee = 45% respectively.

An expedient synthesis of olfactory lactones by intramolecular hydroacylalkoxylation reactions

A series of 4,5-disubstituted γ-lactones, including whisky and cognac lactones, was synthesised in four steps from a readily available chiral precursor. By using an intramolecular hydroacylalkoxylation reaction in the final step, a correlation between the (E)/(Z) configuration of the precursor and the product distribution has been established, for the first time, in this type of cyclisation reactions. Copyright

Applications of 1-alkenyl-1,1-heterobimetallics in the stereoselective synthesis of cyclopropylboronate esters, trisubstituted cyclopropanols and 2,3-disubstituted cyclobutanones

1-Alkenyl-1,1-heterobimetallics are potentially very useful in stereoselective organic synthesis but are relatively unexplored. Introduced herein is a practical application of 1-alkenyl-1,1-heterobimetallic intermediates in the synthesis of versatile cyclopropyl alcohol boronate esters, which are valuable building blocks. Thus, hydroboration of 1-alkynyl-1-boronate esters with dicyclohexylborane generates 1-alkenyl- 1,1-diboro species. In situ transmetalation with dialkylzinc reagents furnishes 1-alkenyl-1,1-borozinc heterobimetallic intermediates. Addition of the more reactive Zn-C bond to aldehydes generates the key B(pin) substituted allylic alkoxide intermediates. An in situ alkoxide directed cyclopropanation proceedswith the formation of two more C-C bonds, affording cyclopropyl alcohol boronate esters with three new stereocenters in 58-89percent isolated yields and excellent diastereoselectivities (>15:1 dr). Oxidation of the B-C bond provides trisubstituted α-hydroxycyclopropyl carbinols as single diastereomers in good to excellent yields (75-93percent). Facile pinacol-type rearrangement of the α-hydroxycyclopropyl carbinols provides access to both cis- and trans-2,3-disubstituted cyclobutanones with high stereoselectivity (>17:1 dr in most cases) from a common starting material. This methodology has been applied in the synthesis of quercus lactones A and B.

SN2′ boron-mediated Mitsunobu reactions - A new one-pot three-component synthesis of substituted enamides and enol benzoates

The conversion of (3-hydroxy-1-propen-1-yl)boronates to substituted enamides and enol benzoates is readily achieved in a one-pot procedure consisting of a regiocontrolled Mitsunobu reaction with convenient nucleophiles, followed by allylboration of aldehydes. Wiley-VCH Verlag GmbH & Co. KGaA, 2009.

Oxidative rearrangement of 2-alkoxy-3,4-dihydro-2H-pyrans: stereocontrolled synthesis of 4,5-cis-disubstituted tetrahydrofuranones including whisky and cognac lactones and crobarbatic acid

Oxidation of 2-alkoxy-3,4-dihydro-2H-pyrans 3 with dimethyldioxirane or MTO/urea-H2O2 followed by Jones oxidation leads to rearrangement and stereocontrolled formation of 4,5-cis-disubstituted tetrahydrofuranones. The method is applied to the synthesis of the whisky lactone 9, cognac lactone 10 and crobarbatic acid 17.

An asymmetric, SmI2-mediated approach to γ-butyrolactones using a new, fluorous-tagged auxiliary

A new, fluorous-tagged chiral auxiliary has been developed for the asymmetric, SmI2-mediated coupling of aldehydes and α,β-unsaturated esters. γ-Butyrolactones are obtained in moderate to good isolated yield and in high enantiomeric excess. The fluorous tag allows the auxiliary to be conveniently recovered by fluorous solid-phase extraction (FSPE) and reused.

Oxidative rearrangement of 2-alkoxy-3,4-dihydro-2H-pyrans: Stereocontrolled synthesis of 4,5-cis-disubstituted tetrahydrofuranones

Oxidation of 2-alkoxy-3,4-dihydro-2H-pyrans with dimethyldioxirane followed by Jones oxidation leads to rearrangement and stereocontrolled formation of 4,5-cis-disubstituted tetrahydrofuranones; the method is applied to the synthesis of the whisky lactone 13 and cognac lactone 14.