16320-13-1

Basic information

• Product Name: (S)-5-HEXANOLIDE
• Synonyms: (S)-5-HEXANOLIDE;(S)-6-Methyltetrahydropyran-2-one;(S)-Dihydroparasorbic Acid;(S)-Tetrahydro-6-Methyl-2H-pyran-2-one;(S)-δ-Hexalactone
• CAS NO: 16320-13-1
• Molecular Formula: C₆H₁₀O₂
• Molecular Weight: 114.14
• Product Categories: Chiral Reagents, Heterocycles, Intermediates
• Mol File: 16320-13-1.mol

Chemical Properties

• Melting Point: 31 °C
• Boiling Point: 103-104 C
• Appearance: /
• Density: 1.037 g/cm3(Temp: 21 °C)
• CAS DataBase Reference: (S)-5-HEXANOLIDE(CAS DataBase Reference)
• NIST Chemistry Reference: (S)-5-HEXANOLIDE(16320-13-1)
• EPA Substance Registry System: (S)-5-HEXANOLIDE(16320-13-1)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-27-36/37/39
• Hazardous Substances Data: 16320-13-1(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
(S)-5-HEXANOLIDE is used as a key intermediate for the preparation of biologically active compounds, specifically pheromones. Its unique structure allows for the creation of molecules that can mimic or influence the natural chemical signals used by animals for communication, mating, and other social behaviors.
Used in Chemical Synthesis:
In the field of chemical synthesis, (S)-5-HEXANOLIDE serves as a valuable building block for the development of various pharmaceuticals and agrochemicals. Its enantiomeric purity is crucial for the synthesis of chiral molecules with specific biological activities, ensuring the desired effects and minimizing potential side effects.
Used in Flavor and Fragrance Industry:
Although not explicitly mentioned in the provided materials, (S)-5-HEXANOLIDE, due to its lactone structure, could potentially be used in the flavor and fragrance industry to create unique scents and flavors. The specific application would depend on the compound's olfactory properties and its ability to blend with other components in the formulation of fragrances and flavorings.

Upstream product

• 20266-62-0 Ethyl 5-hydroxyhexanoate 
• 10412-98-3 5-oxohexanenitrile 
• 1120-72-5 (R)-α-methylcyclopentanone 
• 132604-11-6 (S)-5,6-dihydro-4-hydroxy-6-methyl-2H-pyran-2-one 
• 93338-33-1 (S)-3,6-dihydro-6-methyl-2H-pyran-2-one 
• 133710-36-8 5S,6S-5-carboxy-6-methyl-3,4,5,6-tetrahydropyran-2-one 
• 71401-68-8 (R)-(-)-5-hydroxyhexanol 
• 76024-09-4 (2S,6S)-2-methoxy-6-methyltetrahydropyran 
• 10048-32-5 (S)-parasorbic acid 
• 83972-60-5 5s-Hydroxy-capronsaeure 
• 109573-35-5 (+)-4-Ethylthio-6-methyl-5,6-dihydro-2-pyrone 
• 119680-49-8 2-((S)-4-Carboxy-1-methyl-butoxycarbonylmethyl)-4,6-dimethoxy-benzoic acid 
• 96883-06-6 2-[(S)-3-(Tetrahydro-pyran-2-yloxy)-butyl]-malonic acid diethyl ester 
• 103774-09-0 methyl (S)-5-<(tetrahydro-2H-pyran-2-yl)oxy>hexanoate 

Downstream Products

• 139209-88-4 (S)-5-Hydroxy-hexanoic acid ((R)-1-phenyl-ethyl)-amide 
• 139209-88-4 (R)-5-Hydroxy-hexanoic acid ((R)-1-phenyl-ethyl)-amide 
• 126337-14-2 7-tert-Butylsulfanyl-6-phenyl-tetrazolo[1,5-b]pyridazine 
• 483287-68-9 benzoic acid 5-hydroxy-hexyl ester 

Relevant articles and documents

Optical resolution of medium-size lactones by inclusion crystallization with optically active host compounds: remarkable odd-even effects on the chiral recognition

Molecular recognition of medium-size lactones by inclusion complexation with optically active hosts derived from tartaric acid is described. Odd-even effects on the chiral recognition were observed in the enantioselective inclusion with the optically active host compounds in the solid state.

Iridium-Catalyzed Asymmetric Hydrogenation of ?- A nd ?-Ketoacids for Enantioselective Synthesis of ?- A nd ?-Lactones

A highly efficient asymmetric hydrogenation of ?- A nd ?-ketoacids was developed by using a chiral spiro iridium catalyst (S)-1a, affording the optically active ?- A nd ?-hydroxy acids/lactones in high yields with excellent enantioselectivities (up to >99% ee) and turnover numbers (TON up to 100000). This protocol provides an efficient and practical method for enantioselective synthesis of Ezetimibe.

Kinetic resolution of racemic hydroxy ester via asymmetric catalytic hydrogenation and application thereof

The present invention relates to kinetic resolution of racemic δ-hydroxyl ester via asymmetric catalytic hydrogenation and an application thereof. In the presence of chiral spiro pyridyl phosphine ligand Iridium catalyst and base, racemic δ-hydroxyl esters were subjected to asymmetric catalytic hydrogenation to obtain extent optical purity chiral δ-hydroxyl esters and corresponding 1,5-diols. The method is a new, efficient, highly selective, economical, desirably operable and environmentally friendly method suitable for industrial production. An optically active chiral δ-hydroxyl ester and 1,5-diols can be obtained at very high enantioselectivity and yield with relatively low usage of catalyst. The chiral δ-hydroxyl ester and 1,5-diols obtained by using the method can be used as a critical raw material for asymmetric synthesis of chiral drugs (R)-lisofylline and natural drugs (+)-civet, (?)-indolizidine 167B and (?)-coniine.

Biocatalytic Characterization of Human FMO5: Unearthing Baeyer-Villiger Reactions in Humans

Flavin-containing mono-oxygenases are known as potent drug-metabolizing enzymes, providing complementary functions to the well-investigated cytochrome P450 mono-oxygenases. While human FMO isoforms are typically involved in the oxidation of soft nucleophiles, the biocatalytic activity of human FMO5 (along its physiological role) has long remained unexplored. In this study, we demonstrate the atypical in vitro activity of human FMO5 as a Baeyer-Villiger mono-oxygenase on a broad range of substrates, revealing the first example to date of a human protein catalyzing such reactions. The isolated and purified protein was active on diverse carbonyl compounds, whereas soft nucleophiles were mostly non- or poorly reactive. The absence of the typical characteristic sequence motifs sets human FMO5 apart from all characterized Baeyer-Villiger mono-oxygenases so far. These findings open new perspectives in human oxidative metabolism.

Stereodivergent preparation of valuable γ- Or δ-hydroxy esters and lactones through one-pot cascade or tandem chemoenzymatic protocols

A series of enantiopure hydroxy esters and lactones has been synthesized in a chemodivergent manner via alcohol dehydrogenase (ADH) reduction of the corresponding keto esters by means of cascade or tandem protocols. Thus, ADH from Rhodococcus ruber (ADH-A) or Lactobacillus brevis (LBADH) afforded both antipodes in a very selective way when dealing with small derivatives. With bulkier substrates, ADH from Ralstonia sp. (RasADH) was successfully employed to achieve the synthesis of enantioenriched γ- or δ-hydroxy esters. To isolate the corresponding lactones, two different approaches were followed: a cascade reaction by spontaneous cyclization of the hydroxy ester intermediate, or a one-pot two-step tandem protocol. Moreover, a chemoenzymatic route was designed to obtain a chiral brominated lactone, which enabled further modifications in a sequential fashion by Pd-catalyzed reactions, affording relevant functionalized lactones.

Remote ester group leads to efficient kinetic resolution of racemic aliphatic alcohols via asymmetric hydrogenation

A highly efficient method for kinetic resolution of racemic aliphatic alcohols without conversion of the hydroxyl group has been realized; the method involves hydrogenation mediated by a remote ester group and is catalyzed by a chiral iridium complex. This powerful, environmentally friendly method provides chiral δ-alkyl-δ-hydroxy esters and δ-alkyl-1,5-diols in good yields with high enantioselectivities even at extremely low catalyst loading (0.001 mol %).

Enantioselective route to ketones and lactones from exocyclic allylic alcohols via metal and enzyme catalysis

A general and efficient route for the synthesis of enantiomerically pure α-substituted ketones and the corresponding lactones has been developed. Ruthenium- and enzyme-catalyzed dynamic kinetic resolution (DKR) with a subsequent Cu-catalyzed α-allylic substitution are the key steps of the route. The α-substituted ketones were obtained in high yields and with excellent enantiomeric excess. The methodology was applied to the synthesis of a naturally occurring caprolactone, (R)-10-methyl-6-undecanolide, via a subsequent Baeyer-Villiger oxidation.

Chemoenzymatic synthesis of (2R)-2-hydroxyundecan-6-one

Optimisation of kinetic resolution of racemic 5-hydroxyhexanenitrile (2) was performed; acetylation with vinyl acetate, catalyzed by Pseudomonas cepacia lipase immobilized on ceramics (PS-C) in n-hexane, afforded (5R)-acetoxy-hexanenitrile [(R)-3] with 94% ee and 94% yield; E = 83. Deacetylation of (R)-3, protection of (R)-2 by tert-butyldimethylsilyl group, Grignard reaction of (R)-4 with n-pentyl magnesium bromide, and final deprotection of (R)-5 afforded the title compound (R)-6 in 32% overall yield from 1 and 94% enantiomeric purity. Absolute configuration of (R)-6 was assigned by chemical correlations to (5R)-methyl-5-pentanolide [(R)-7].

Potential and Limitations of Palladium-Cinchona Catalyst for the Enantioselective Hydrogenation of a Hydroxymethylpyrone

The palladium-catalyzed enantioselective hydrogenation of 4-hydroxy-6-methyl-2-pyrone afforded up to 85% excess to the (S)-enantiomer of the corresponding 5,6-dihydropyrone, under very mild conditions (1 bar, room temperature). This is the highest enantioselectivity achieved so far with chirally modified Pd, demonstrating the potential of this catalyst in the enantioselective hydrogenation of unsaturated compounds. A complicating feature of the reaction is the limited stability of cinchonidine under reaction conditions, which results in a decline of the initial enantiomeric excess (ee) with reaction time. Continuous feeding of a minute amount of cinchonidine during reaction allows maintenance of the high initial ee with an overall substrate/modifier molar ratio of ca. 20.

Applications of highly enantioenriched alcohols bearing a phenylthio group in the preparation of ring compounds. The two-pot synthesis of an enantiopure spiroacetal pheromone bearing three chiral centers

The new chiron (S)-6-phenylthio-2-hexanol (3) was prepared in high enantiomeric excess by baker's yeast reduction of the corresponding ketone. Enantioenriched alcohols 1, 2 and 3, prepared previously by a similar procedure, or their racemic counterparts, were transformed into ring closed compounds 5-methyl-2-(phenylthio)tetrahydrofuran (9), 6-methyl-2- (phenylthio)tetrahydropyran (10), 2-methyl-1-phenylsulfonyl cyclopropane (14), cyclobutane (15), cyclopentane (16), and a bee pheromone, (2S,6R,8S)- 2,8-dimethyl-1,7-dioxaspiro[5.5]undecane (20).