86404-04-8

Basic information

• Product Name: 3-O-Ethyl-L-ascorbic acid
• Synonyms: 3-O-Ethyl Ascorbyl Ether;3-O-Ethyl-L-ascorbic Acid;ETHYL ASCORBIC ACID;(5r)-5-[(1s)-1,2-dihydroxyethyl]-4-ethoxy-3-hydroxy-5h-furan-2-one;3-o-ethyl-l-ascorbic acid;3-O-ETHYLASCORBICACID;(5R,1'S)-5-(1,2-Dihydroxy-ethyl)-4-ethoxy-3-hydroxy-5H-furan-2-one;(R)-5-((S)-1,2-dihydroxyethyl)-4-ethoxy-3-hydroxyfuran-2(5H)-one
• CAS NO: 86404-04-8
• Molecular Formula: C₈H₁₂O₆
• Molecular Weight: 204.18
• EINECS: 1806241-263-5
• Product Categories: Vitamine C derivative
• Mol File: 86404-04-8.mol
• Article Data: 12

Chemical Properties

• Melting Point: 112.0 to 116.0 °C
• Boiling Point: 551.5 °C at 760 mmHg
• Flash Point: 228.5 °C
• Appearance: /
• Density: 1.46 g/cm³
• Vapor Pressure: 1.84E-14mmHg at 25°C
• Refractive Index: 1.555
• Storage Temp.: 0-10°C
• Solubility: Methanol (Slightly), Water (Slightly)
• PKA: 8.89±0.40(Predicted)
• CAS DataBase Reference: 3-O-Ethyl-L-ascorbic acid(CAS DataBase Reference)
• NIST Chemistry Reference: 3-O-Ethyl-L-ascorbic acid(86404-04-8)
• EPA Substance Registry System: 3-O-Ethyl-L-ascorbic acid(86404-04-8)

Safety Data

• Hazardous Substances Data: 86404-04-8(Hazardous Substances Data)

Usage

Uses

Different sources of media describe the Uses of 86404-04-8 differently. You can refer to the following data:
1. Vitamin C ethyl ether (VC ethyl ether) is a lipophilic and hydrophilic amphoteric vitamin C derivative. It not only retains the redox effect of vitamin C but is also very stable. It is a non-discoloring vitamin C derivative. It is a lipophilic and lookchem amphoteric substance, which not only makes it extremely convenient to use in the formula, but also makes it easy to penetrate the stratum corneum into the dermis. After entering the skin, it is easily decomposed by biological enzymes to play the role of vitamin C, thereby Improve its bioavailability.
2. 3-O-Ethyl-L-ascorbic Acid could be a useful stabilizing agent for a para-hydroxyacetophenone solution. 3-O-Ethyl-L-ascorbic Acid could be a useful stabilizing agent for a para-?hydroxyacetophenone solution.

Mechanism of action

VC ethyl ether penetrates the stratum corneum to reach the melanocytes in the basal layer, inhibits tyrosinase activity, inhibits the formation of melanin, and restores melanin to colorless, thereby effectively whitening the skin. And lookchem and VC ethyl ether can directly participate in the synthesis of collagen and repair skin cell activity after entering the dermis, increasing collagen, so that the skin becomes full and elastic, making the skin delicate and smooth.

Synthesis

The above 3-O-ethyl-5,6-O-isopropylideneascorbic acid 40g dissolved in 200ml of ethanol. 10g of cation-exchange resin was added and was refluxed for 2 hours. The catalyst was removed by an ion exchange resin and concentrated under reduced pressure. After drying, with ethyl acetate: hexane (3: 1) crystallization. After drying, obtained 33.3g 3-O-ethylascorbic acid, yield 94%. It was recrystallized in 100mL ethyl acetate giving 30.6g, yield 87%, mp: 112-114°C.

InChI:InChI=1/C8H12O6/c1-2-13-7-5(11)8(12)14-6(7)4(10)3-9/h4,6,9-11H,2-3H2,1H3/t4-,6+/m0/s1

Synthetic route

(R)-5-((S)-2,2-dimethyl-1,3-dioxolan-4-yl)-4-ethoxy-3-hydroxyfuran-2(5H)-one (86404-03-7) → 3‐O‐ethyl‐L‐ascorbic acid (86404-04-8)

Conditions	Yield
With hydrogenchloride In methanol at 60℃; for 3h;	98%
With hydrogenchloride In methanol; water at 60℃; for 3h;	98%
With cation-exchange resin In ethanol for 2h; Reflux;	87%

ethyl bromide (74-96-4) + ascorbic acid (50-81-7) → 3‐O‐ethyl‐L‐ascorbic acid (86404-04-8)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20℃; Product distribution / selectivity;	69%

Ethyl methanesulfonate (62-50-0) + ascorbic acid (50-81-7) → 3‐O‐ethyl‐L‐ascorbic acid (86404-04-8)

Conditions	Yield
With triethylamine In ethanol for 1h; Heating;	66%

diethyl sulfate (64-67-5) + ascorbic acid (50-81-7) → 3‐O‐ethyl‐L‐ascorbic acid (86404-04-8)

Conditions	Yield
With triethylamine In ethanol for 1h; Heating;	64%

ethyl bromide (74-96-4) + sodium L-ascorbate (146-75-8, 6381-77-7, 6866-66-6, 7317-67-1, 7378-23-6, 21547-69-3, 58657-35-5, 134-03-2) → 3‐O‐ethyl‐L‐ascorbic acid (86404-04-8)

Conditions	Yield
In dimethyl sulfoxide at 50℃; for 3.5h; Temperature; Sealed tube;	51%

5,6-O-isopropylidene-L-ascorbic acid (15042-01-0) → 3‐O‐ethyl‐L‐ascorbic acid (86404-04-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: 70 percent / sodium bicarbonate / dimethylsulfoxide / 16 h / 50 °C 2: 98 percent / 2M HCl / methanol / 3 h / 60 °C View Scheme
Multi-step reaction with 2 steps 1: triethylamine; toluene-4-sulfonic acid / 6 h / Reflux 2: cation-exchange resin / ethanol / 2 h / Reflux View Scheme
Multi-step reaction with 2 steps 1: sodium hydrogencarbonate / dimethyl sulfoxide / 2 h / 70 °C 2: hydrogenchloride / methanol; water / 3 h / 60 °C View Scheme

ethyl iodide (75-03-6) + sodium L-ascorbate (146-75-8, 6381-77-7, 6866-66-6, 7317-67-1, 7378-23-6, 21547-69-3, 58657-35-5, 134-03-2) → 3‐O‐ethyl‐L‐ascorbic acid (86404-04-8)

Conditions	Yield
In dimethyl sulfoxide at 60℃; for 12h; Temperature; Sealed tube;

diethyl sulfate (64-67-5) + sodium L-ascorbate (146-75-8, 6381-77-7, 6866-66-6, 7317-67-1, 7378-23-6, 21547-69-3, 58657-35-5, 134-03-2) → 3‐O‐ethyl‐L‐ascorbic acid (86404-04-8)

Conditions	Yield
In dimethyl sulfoxide at 40℃; for 12h; Temperature; Sealed tube;

ascorbic acid (50-81-7) → 3‐O‐ethyl‐L‐ascorbic acid (86404-04-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: toluene-4-sulfonic acid / 8 h / 25 °C 2: sodium hydrogencarbonate / dimethyl sulfoxide / 2 h / 70 °C 3: hydrogenchloride / methanol; water / 3 h / 60 °C View Scheme
Multi-step reaction with 3 steps 1: toluene-4-sulfonic acid / 8 h / 25 °C 2: potassium hydroxide / dimethyl sulfoxide / 2 h / 80 °C 3: hydrogenchloride / methanol; water / 3 h / 60 °C View Scheme

3‐O‐ethyl‐L‐ascorbic acid (86404-04-8) + Thioctic acid (1077-28-7, 62-46-4) → L-2-α-lipoyl-3-ethyl-ascorbic acid

Conditions	Yield
With dmap; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide In dichloromethane; chloroform at 25℃;	92%

azelaic acid (123-99-9) + 3‐O‐ethyl‐L‐ascorbic acid (86404-04-8) → 3-O-ethyl-ascorbyl-6-nonanedioate (1210311-35-5)

Conditions	Yield
lipase In tert-Amyl alcohol at 55℃; for 18h;	32.7%

3‐O‐ethyl‐L‐ascorbic acid (86404-04-8) → C29H39NO14

Conditions	Yield
Multi-step reaction with 2 steps 1: acetyl chloride / 3 h / 0 - 20 °C 2: dmap; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide / dichloromethane / 12 h View Scheme

3‐O‐ethyl‐L‐ascorbic acid (86404-04-8) → C26H35NO14

Conditions	Yield
Multi-step reaction with 3 steps 1: acetyl chloride / 3 h / 0 - 20 °C 2: dmap; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide / dichloromethane / 12 h 3: hydrogenchloride / tetrahydrofuran / 1 h View Scheme

3‐O‐ethyl‐L‐ascorbic acid (86404-04-8) + acetone (67-64-1) → (R)-5-((S)-2,2-dimethyl-1,3-dioxolan-4-yl)-4-ethoxy-3-hydroxyfuran-2(5H)-one (86404-03-7)

Conditions	Yield
With acetyl chloride at 0 - 20℃; for 3h;	8.66 g

Upstream product

• 64-17-5 ethanol 
• 50-81-7 ascorbic acid 
• 64-67-5 diethyl sulfate 
• 146-75-8 sodium L-ascorbate 
• 75-03-6 ethyl iodide 
• 74-96-4 ethyl bromide 
• 15042-01-0 5,6-O-isopropylidene-L-ascorbic acid 
• 62-50-0 Ethyl methanesulfonate 
• 86404-03-7 (R)-5-((S)-2,2-dimethyl-1,3-dioxolan-4-yl)-4-ethoxy-3-hydroxyfuran-2(5H)-one 

Relevant articles and documents

A simple efficient synthesis and biological evaluation of 3-O-ethylascorbic acid

A single-step synthesis of 3-O-ethyl-L-ascorbic acid was performed without the induction of protecting groups. Sodium L-ascorbate reacted with ethyl bromide in DMSO to give 3-O-ethylascorbic acid in a yield of 51.0%. 3- O-Ethylascorbic acid enhanced dibutyryl cyclic AMP-induced neurite outgrowth in PC12 cells.

Vitamin C ethyl ether synthesis method

The invention discloses a vitamin C ethyl ether synthesis method, which has the advantages of reasonable process design, mild reaction conditions, high product yield, no need of adopting a resin catalyst and green and environment-friendly production process. The method comprises the following steps of 1) synthesizing a vitamin C protection body by taking stannous chloride and tetrabutylammonium bromide as catalysts, 2) synthesizing a vitamin C protector etherate, 3) adjusting the pH value by using a hydrochloric acid solution to remove a protecting group, and 4) purifying the product by recrystallization with a weak polar solvent. Through the synergistic effect between the stannous chloride and the phase transfer catalyst tetrabutylammonium bromide, reactants are in more sufficient contact, and the reaction speed is increased.

a method for manufacturing 3-O-alkyl-ascorbic acid

3 - O - Alkyl - ascorbic acid. 3 - O -alkyl - ascorbic acid having a low reaction temperature and a high yield. Provided is a process for preparing 3 - O - alkyl - ascorbic acid having a low reaction temperature and simple preparation process and high yield.

Method for synthesizing 3-O-alkyl-5,6-O-isopropylidene ascorbic acid by using circulation method

The invention provides a method for synthesizing 3-O-alkyl-5,6-O-isopropylidene ascorbic acid by using a circulation method. The method comprises the following steps: enabling excessive 5,6-O-isopropylidene-ascorbic acid to react with an alkali and an alkyl reagent in a high-boiling-point polar aprotic solvent; after the reaction is completed, performing extraction with a low-polarity aprotic solvent; performing water washing treatment on the low-polarity aprotic solvent extraction liquid; performing concentration so as to obtain 3-O-alkyl-5,6-O-isopropylidene ascorbic acid; supplementing thealkali and the alkyl solvent into the high-boiling-point polar aprotic solvent extraction residue liquid; continuing a next batch of reactions for synthesizing the 3-O-alkyl-5,6-O-isopropylidene ascorbic acid; and performing deprotection on the 3-O-alkyl-5,6-O-isopropylidene ascorbic acid, so as to obtain 3-O-alkyl ascorbic acid. The method is good in selectivity, complete in raw material reaction, high in total yield and free of organic waste emission and has great industrial application values, and the synthesis cost can be greatly reduced.

Crystal form A of 3-O-ethyl-L-ascorbic acid, its preparation method and whitening composition

The present invention relates to the field of crystals and in particular, to a crystal form A of 3-O-ethyl-L-ascorbic acid, its preparation method and a whitening composition. The characteristic peaksof the crystal form A of 3-O-ethyl-L-ascorbic acid are characterized by X-ray diffraction pattern and prove that the crystal form A is formed. The crystal form A has good stability, especially excellent thermal stability and long-term storage stability.

Preparation method of 3-O-alkyl ascorbic acid

The invention discloses a preparation method of 3-O-alkyl ascorbic acid. The method is characterized in that ascorbic acid with protecting groups reacts with one of organic phosphate, sulfonic ester and organosulfate on the condition that tertiary amine exists, solvent does not need to be used for extraction after the reaction, treating is performed by directly using water, therefore, the reaction and aftertreatment time is short, the purity is high, and a large amount of dimethylsulfoxide and extraction solvent are prevented from being used. According to the preparation method of the 3-O-alkyl ascorbic acid, ethyl alcohol, methyl alcohol, isopropanol, acetonitrile and the like can be adopted as the solvent used in the reaction, the organic phosphate or the sulfonic ester or the organosulfate and the like is adopted as an alkylating reagent, water is taken as the solvent for purification and separation after etherification, therefore, the cost is significantly lowered, environmental protection is achieved, and the time is shortened.

Ascorbic Acid Derivatives

The present invention discloses the ascorbic acid derivatives. The inventive molecules that combine with one or two hydrophilic headgroups connected by a hydrophobic spacer can increase skin penetration.

Method for Preparing Crystalline 3-0-Alkyl-Ascorbic Acid

The present invention relates to a method for preparing 3-O-substituted ascorbic acid derivatives represented by formula 1, in which 5,6-O-isopropylidene ascorbic acid is reacted with a halide in an organic solvent in the presence of the anion exchange resin absorbed with multi-iodine anions and then deprotected. The method of the present invention has an advantage of providing a target compound with high purity and high yield by finishing the reaction within a short period of time at room temperature.

ASCORBIC ACID DERIVATIVES HAVING ALPHA-LIPOYL GROUPS AND PROCESS FOR PREPARING THE SAME

The present invention provides an ascorbic acid derivative having an α-lipoyl group and a process for preparing the same. The ascorbic acid derivative of the present invention has excellent stability in an aqueous medium, and thus can minimize denaturation caused by environmental factors such as temperature, light, oxygen, and water, even when being stored in an aqueous composition for a long eriod of time.

METHOD FOR PREPARING CRYSTALLINE 3-0-ALKYL-ASCORBIC ACID

The present invention relates to a method for preparing 3- O- substituted ascorbic acid derivatives represented by formula 1, in which 5, 6-O-isopropylidene ascorbic acid is reacted with a halide in an organic solvent in the presence of the anion exchange resin absorbed with multi-iodine anions and then deprotected. The method of the present invention has an advantage of providing a target compound with high purity and high yield by finishing the reaction within a short period of time at room temperature.