2305-25-1

Basic information

• Product Name: ETHYL 3-HYDROXYHEXANOATE
• Synonyms: ETHYL 3 HYDROXY CAPROATE;(+/-)-ETHYL 3-HYDROXYHEXANOATE;ETHYL 3-HYDROXYHEXANOATE;FEMA 3545;3-hydroxy-hexanoicaciethylester;Hexanoic acid, 3-hydroxy-, ethyl ester;Hexanoicacid,3-hydroxy-,ethylester;Ethyl 3-hydroxybhexanoate
• CAS NO: 2305-25-1
• Molecular Formula: C₈H₁₆O₃
• Molecular Weight: 160.21
• EINECS: 218-973-7
• Product Categories: Pharmaceutical Intermediates;Alphabetical Listings;E-F;Flavors and Fragrances
• Mol File: 2305-25-1.mol

Chemical Properties

• Boiling Point: 90-92 °C14 mm Hg(lit.)
• Flash Point: 202 °F
• Appearance: /
• Density: 0.974 g/mL at 25 °C(lit.)
• Vapor Pressure: 0.00608mmHg at 25°C
• Refractive Index: n20/D 1.428(lit.)
• Storage Temp.: Sealed in dry,Room Temperature
• PKA: 14.45±0.20(Predicted)
• CAS DataBase Reference: ETHYL 3-HYDROXYHEXANOATE(CAS DataBase Reference)
• NIST Chemistry Reference: ETHYL 3-HYDROXYHEXANOATE(2305-25-1)
• EPA Substance Registry System: ETHYL 3-HYDROXYHEXANOATE(2305-25-1)

Safety Data

• Safety Statements: 24/25
• WGK Germany: 3
• TSCA: Yes
• Hazardous Substances Data: 2305-25-1(Hazardous Substances Data)

Usage

Uses

Used in Flavor and Fragrance Industry:
ETHYL 3-HYDROXYHEXANOATE is used as a flavoring agent for its sweet, fruity, and grape-like taste with citrus notes, particularly at a concentration of 80 ppm. It is commonly found in the natural aroma of fruits like guava, bananas, and citrus fruits.
Used in Beverage Industry:
ETHYL 3-HYDROXYHEXANOATE is used as a flavor enhancer in the production of beverages such as cognac, Scotch whiskey, red and white wine, and fruit juices like orange, grapefruit, and tangerine juice. It helps to create a more complex and appealing taste profile in these drinks.
Used in Food Industry:
ETHYL 3-HYDROXYHEXANOATE is used as an additive in the food industry to impart a sweet, fruity, and citrusy flavor to various products. It can be found in the natural composition of fruits like pineapple, strawberry, passion fruit, mango, quince, wood apple, mountain papaya, pawpaw, and hog plum (Spondias mombins L.).
Used in Perfumery:
ETHYL 3-HYDROXYHEXANOATE is used as a fragrance ingredient in the perfumery industry due to its fruity odor, which can add depth and complexity to various scent compositions.

Synthesis Reference(s)

The Journal of Organic Chemistry, 39, p. 269, 1974 DOI: 10.1021/jo00916a043

InChI:InChI=1/C8H16O3/c1-3-5-7(9)6-8(10)11-4-2/h7,9H,3-6H2,1-2H3/t7-/m0/s1

Upstream product

• 123-72-8 butyraldehyde 
• 105-36-2 ethyl bromoacetate 
• 927-80-0 1-ethoxyacetylene 
• 117668-85-6 3-Hydroxy-2-phenylselanyl-hexanoic acid ethyl ester 
• 129505-18-6 dimethylsilanyl-acetic acid ethyl ester 
• 64-17-5 ethanol 
• 66997-60-2 (+)-(3S)-3-hydroxyhexanoic acid 
• 1373154-19-8 ethyl (Z)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)hex-2-enoate 
• 16205-90-6 ethyl 2-hexynoate 
• 112083-63-3 ethyl (-)-(2S)-oxirane-2-acetate 
• 112100-39-7 (S)-4-iodo-3-hydroxy-butyric acid ethyl ester 
• 1252813-46-9 (R)-ethyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)hexanoate 
• 3249-68-1 ethyl butyroyl acetate 
• 130158-22-4 ethyl (S)-3-((tert-butyldimethylsilyl)oxy)-4-iodobutanoate 

Downstream Products

• 212610-21-4 Ethyl (2R,3R)-2-Cyclohexylmethyl-3-hydroxyhexanoate 
• 22329-75-5 (2E,4E)-octadienoic acid 

Relevant articles and documents

Synthesis method of ethyl 3-hydroxyhexanoate

The invention discloses a synthesis method of ethyl 3-hydroxyhexanoate. The method is characterized by comprising the following steps: reacting bromine with acetic acid to prepare bromoacetic acid; reacting the bromoacetic acid with ethanol in the presence of sulfuric acid to generate ethyl bromoacetate; adding 500kg of dichloromethane and 140kg of n-butyraldehyde into a reaction kettle; adding acatalyst, heating to reflux, dropwise adding 250kg of the ethyl bromoacetate serving as a product obtained in the previous step, controlling the dropwise adding speed, controlling the adding to be completed within 3 hours in a reflux state, preserving heat for 2 hours, cooling to room temperature, washing to neutrality, transferring into a rectifying tower, and rectifying to obtain a qualified product, namely the ethyl 3-hydroxyhexanoate.

Efficient asymmetric synthesis of chiral alcohols using high 2-propanol tolerance alcohol dehydrogenase: Sm ADH2 via an environmentally friendly TBCR system

Alcohol dehydrogenases (ADHs) together with the economical substrate-coupled cofactor regeneration system play a pivotal role in the asymmetric synthesis of chiral alcohols; however, severe challenges concerning the poor tolerance of enzymes to 2-propanol and the adverse effects of the by-product, acetone, limit its applications, causing this strategy to lapse. Herein, a novel ADH gene smadh2 was identified from Stenotrophomonas maltophilia by traditional genome mining technology. The gene was cloned into Escherichia coli cells and then expressed to yield SmADH2. SmADH2 has a broad substrate spectrum and exhibits excellent tolerance and superb activity to 2-propanol even at 10.5 M (80%, v/v) concentration. Moreover, a new thermostatic bubble column reactor (TBCR) system is successfully designed to alleviate the inhibition of the by-product acetone by gas flow and continuously supplement 2-propanol. The organic waste can be simultaneously recovered for the purpose of green synthesis. In the sustainable system, structurally diverse chiral alcohols are synthesised at a high substrate loading (>150 g L-1) without adding external coenzymes. Among these, about 780 g L-1 (6 M) ethyl acetoacetate is completely converted into ethyl (R)-3-hydroxybutyrate in only 2.5 h with 99.9% ee and 7488 g L-1 d-1 space-time yield. Molecular dynamics simulation results shed light on the high catalytic activity toward the substrate. Therefore, the high 2-propanol tolerance SmADH2 with the TBCR system proves to be a potent biocatalytic strategy for the synthesis of chiral alcohols on an industrial scale.

Synthesis of Long-Chain β-Lactones and Their Antibacterial Activities against Pathogenic Mycobacteria

In the quest for new antibacterial agents, a series of novel long- and medium-chain mono- and disubstituted β-lactones was developed. Their activity against three pathogenic mycobacteria—M. abscessus, M. marinum, and M. tuberculosis—was assessed by the resazurin microtiter assay (REMA). Among the 16 β-lactones synthesized, only 3-hexadecyloxetan-2-one (VM005) exhibited promising activity against M. abscessus, whereas most of the β-lactones showed interesting activities against M. marinum, similar to that of the classical antibiotic, isoniazid. Regarding M. tuberculosis, six compounds were found to be active against this mycobacterium, with β-lactone VM008 [trans-(Z)-3-(hexadec-7-en-1-yl)-4-propyloxetan-2-one] being the best growth inhibitor. The promising antibacterial activities of the best compounds in this series suggest that these molecules may serve as leads for the development of much more efficient antimycobacterial agents.

Synthesis of Thelepamide via Catalyst-Controlled 1,4-Addition of Cysteine Derivatives and Structure Revision of Thelepamide

The first enantioselective total synthesis and structural reassignment of (-)-thelepamide, a cytotoxic tetraketide-amino acid from the marine worm Thelepus crispus, is reported. A convergent approach provides access to all thelepamide diastereomers in six steps from four simple building blocks. Key features of the synthesis include the application of Melchiorre's organocatalytic thia-Michael reaction and a sonication-assisted assembly of an unprecedented N,O-acetal-hemiacetal moiety. The corrected structure was confirmed by NMR-DFT analysis.

Identification of a Robust Carbonyl Reductase for Diastereoselectively Building syn-3,5-Dihydroxy Hexanoate: A Bulky Side Chain of Atorvastatin

t-Butyl-6-cyano-(3R,5R)-dihydroxyhexanoate is an advanced chiral precursor for the synthesis of the side chain pharmacophore of cholesterol-lowering drug atorvastatin. Herein, a robust carbonyl reductase (LbCR) was newly identified from Lactobacillus brevis, which displays high activity and excellent diastereoselectivity toward bulky t-butyl 6-cyano-(5R)-hydroxy-3-oxo-hexanoate (7). The engineered Escherichia coli cells harboring LbCR and glucose dehydrogenase (for cofactor regeneration) were employed as biocatalysts for the asymmetric reduction of substrate 7. As a result, as much as 300 g L-1 of water-insoluble substrate was completely converted to the corresponding chiral diol with >99.5% de in a space-time yield of 351 g L-1 d-1, indicating a great potential of LbCR for practical synthesis of the very bulky and bi-chiral 3,5-dihydroxy carboxylate side chain of best-selling statin drugs.

Study of Class i and Class III Polyhydroxyalkanoate (PHA) Synthases with Substrates Containing a Modified Side Chain

Polyhydroxyalkanoates (PHAs) are carbon and energy storage polymers produced by a variety of microbial organisms under nutrient-limited conditions. They have been considered as an environmentally friendly alternative to oil-based plastics due to their renewability, versatility, and biodegradability. PHA synthase (PhaC) plays a central role in PHA biosynthesis, in which its activity and substrate specificity are major factors in determining the productivity and properties of the produced polymers. However, the effects of modifying the substrate side chain are not well understood because of the difficulty to accessing the desired analogues. In this report, a series of 3-(R)-hydroxyacyl coenzyme A (HACoA) analogues were synthesized and tested with class I synthases from Chromobacterium sp. USM2 (PhaCCs and A479S-PhaCCs) and Caulobacter crescentus (PhaCCc) as well as class III synthase from Allochromatium vinosum (PhaECAv). It was found that, while different PHA synthases displayed distinct preference with regard to the length of the alkyl side chains, they could withstand moderate side chain modifications such as terminal unsaturated bonds and the azide group. Specifically, the specific activity of PhaCCs toward propynyl analogue (HHxyCoA) was only 5-fold less than that toward the classical substrate HBCoA. The catalytic efficiency (kcat/Km) of PhaECAv toward azide analogue (HABCoA) was determined to be 2.86 × 105 M-1 s-1, which was 6.2% of the value of HBCoA (4.62 × 106 M-1 s-1) measured in the presence of bovine serum albumin (BSA). These side chain modifications may be employed to introduce new material functions to PHAs as well as to study PHA biogenesis via click-chemistry, in which the latter remains unknown and is important for metabolic engineering to produce PHAs economically.

The synthesis of medium-chain-length β-hydroxy esters via the reformatsky reaction

The synthesis of medium-chain-length β-hydroxy esters in good yield via the Reformatsky reaction is described. This work will be used as the basis for further investigation of hydroxyalkanoate polymers as potential feedstock for biofuel production.

Identification of an ε-keto ester reductase for the efficient synthesis of an (R)-α-lipoic acid precursor

Abstract A novel reductase (CpAR2) with unusually high activity toward an ε-keto ester, ethyl 8-chloro-6-oxooctanoate, was isolated from Candida parapsilosis. The asymmetric reduction of ethyl 8-chloro-6-oxooctanoate using Escherichia coli cells coexpressing CpAR2 and glucose dehydrogenase genes gave ethyl (R)-8-chloro-6-hydroxyoctanoate, a key precursor for the synthesis of (R)-α-lipoic acid, in high space-time yield (530 gL-1d-1) and with excellent enantiomeric excess (>99%). This bioprocess was shown to be viable on a 10-L scale. This method provides a greener and more cost-effective method for the industrial production of (R)-α-lipoic acid.

Improving the toolbox of bioreductions by the use of continuous flow systems

Packed bed reactors can be used as an interesting alternative on the bioreduction of β-ketoesteres mediated by immobilized microorganisms. Here in, we report our results on the bioreduction of ethyl 3-oxohexanoate by immobilized Kluyveromyces marxianus cells and tert-butyl 3-oxobutanoate by immobilized Rhodotorula rubra cells under continuous flow conditions leading the desired β-hydroxy esters corresponding in high yields and enantiomeric excess.

Total synthesis of micromide: A marine natural product

This paper describes an efficient procedure for the synthesis of micromide, a natural product that shows anti-solid-tumor activity. Our strategy involved the synthesis of N-nosyl-protected amino acids and their N-methylation with iodo-methane. The hindered oligopeptides containing N-methyl amino acids were synthesized in excellent yields and high purities.[ampi]]