77-93-0

Basic information

• Product Name: Triethyl citrate
• Synonyms: 1,2,3-Propanetricarboxylic acid, 2-hydroxy-, triethyl ester;1,2,3-Propanetricarboxylicacid,2-hydroxy-,triethylester;2,3-propanetricarboxylicacid,2-hydroxy-triethylester;2-Hydroxy-1,2,3-propanetricarboxylic acid, triethyl ester;2-hydroxy-propane-1,2,3-tricarboxylicacidtriethylester;Citroflex 2;citroflex2;Crodamol TC
• CAS NO: 77-93-0
• Molecular Formula: C₁₂H₂₀O₇
• Molecular Weight: 276.28
• EINECS: 201-070-7
• Product Categories: Functional Materials;Hydroxycarboxylic Acid Esters (Plasticizer);Plasticizer;Amino ester;catalyst;Pyridines
• Mol File: 77-93-0.mol
• Article Data: 18

Chemical Properties

• Melting Point: -46 °C
• Boiling Point: 294 °C
• Flash Point: >230 °F
• Appearance: Clear/Liquid
• Density: 1.137 g/mL at 25 °C(lit.)
• Vapor Density: 9.7 (vs air)
• Vapor Pressure: 1 mm Hg ( 107 °C)
• Refractive Index: n20/D 1.442(lit.)
• Storage Temp.: -20°C
• Solubility: H2O: soluble
• PKA: 11.57±0.29(Predicted)
• Water Solubility: 5.7 g/100 mL (25 ºC)
• Merck: 14,2326
• BRN: 1801199
• CAS DataBase Reference: Triethyl citrate(CAS DataBase Reference)
• NIST Chemistry Reference: Triethyl citrate(77-93-0)
• EPA Substance Registry System: Triethyl citrate(77-93-0)

Safety Data

• Hazard Codes: Xn
• Statements: 20
• Safety Statements: 24/25-45
• WGK Germany: 1
• RTECS: GE8050000
• TSCA: Yes
• Hazardous Substances Data: 77-93-0(Hazardous Substances Data)

Usage

Description

Triethyl citrate is the triester of citric acid and ethyl alcohol. Triethyl citrate is used as a flavoring agent in foods, as a high boiling solvent and plasticizer for vinyl resins and cellulose acetates, as a plasticizer in the pharmaceutical industry for coating. Triethyl citrate is used as a natural active ingredient and flavor component with excellent deodorizing and skin care properties in cosmetic and personal care products. Triethyl citrate is also used as a plasticizer and humectant for cigarette filters. Furthermore, triethyl citrate is used s a food additive for stabilizing foams, specifically as a whipping enhancer for organic egg whites during processing.

References

[1] RH Dave (2016) Overview of pharmaceutical excipients used in tablets and capsules, Drug Topics (online). Advanstar. [2] http://www.who.int/en/ [3] http://www.in-cosmetics.com [4] http://www.chemicalland21.com [5] https://www.ams.usda.gov/sites/default/files/media/Triethyl%20Citrate%20report%202014.pdf

Chemical Properties

Different sources of media describe the Chemical Properties of 77-93-0 differently. You can refer to the following data:
1. Triethyl citrate is odorless, but has a bitter taste.
2. Colorless, mobile liquid; bitter taste. Solubility in water 6.5 g/100 cc; solubility in oil 0.8 g/100 cc. Combustible.
3. Triethyl citrate is a clear, viscous, odorless, and practically colorless, hygroscopic liquid.

Occurrence

Reported found in Morello cherry, sour cherry and red currant. Also reported found in raw cabbage and white wine.

Uses

Different sources of media describe the Uses of 77-93-0 differently. You can refer to the following data:
1. Triethyl Citrate, is a colorless, odorless liquid used as a food additive to stabilize foams, especially as whipping aid for egg white. It is also used in pharmaceutical coatings and plastics. This compound is a contaminant of emerging concern (CECs).
2. Triethyl Citrate is a sequestrant that is an oily liquid, slightly solu- ble in water. it is found in lemon drinks.

Production Methods

Triethyl citrate is prepared by the esterification of citric acid and ethanol in the presence of a catalyst.

Preparation

By esterification of ethyl alcohol with citric acid.

General Description

Triethyl citrate is a safe direct food additive.

Pharmaceutical Applications

Triethyl citrate and the related esters acetyltriethyl citrate, tributyl citrate, and acetyltributyl citrate are used to plasticize polymers in formulated pharmaceutical coatings. The coating applications include capsules, tablets, beads, and granules for taste masking, immediate release, sustained-release, and enteric formulations. Triethyl citrate is also used as a direct food additive for flavoring, for solvency, and as a surface active agent.

Safety Profile

Moderately toxic by intraperitoneal route. Mildly toxic by ingestion and inhalation. Combustible liquid when exposed to heat or flame. To fight fire, use dry chemical, CO2. When heated to decomposition it emits acrid smoke and irritating fumes. See also ESTERS and CITRIC ACID.

Safety

Triethyl citrate is used in oral pharmaceutical formulations and as a direct food additive. It is generally regarded as a nontoxic and nonirritant material. However, ingestion of large quantities may be harmful. LD50 (mouse, IP): 1.75 g/kg LD50 (rat, IP): 4 g/kg LD50 (rat, oral): 5.9 g/kg LD50 (rat, SC): 6.6 g/kg

storage

Triethyl citrate should be stored in a closed container in a cool, dry location. When stored in accordance with these conditions, triethyl citrate is a stable product.

Incompatibilities

Triethyl citrate is incompatible with strong alkalis and oxidizing materials.

Regulatory Status

GRAS listed. Accepted for use as a food additive in Europe. Included in the FDA Inactive Ingredients Database (oral capsules and tablets). Included in the Canadian List of Acceptable Nonmedicinal Ingredients.

InChI:InChI=1/C12H20O7/c1-4-17-9(13)7-12(16,11(15)19-6-3)8-10(14)18-5-2/h16H,4-8H2,1-3H3

Synthetic route

ethanol (64-17-5) + citric acid (77-92-9) → citric acid triethyl ester (77-93-0)

Conditions	Yield
Stage #1: ethanol With dicyclohexyl-carbodiimide at 20℃; for 36h; Large scale; Stage #2: citric acid at 35℃; for 6h; Temperature; Autoclave; Large scale;	96%
With sulfonated graphene In neat (no solvent) at 90℃; for 4h;	94%
With boric acid; benzenesulfonic acid at 85 - 90℃; for 3h;	93.26%

diethyl 1,3-acetonedicarboxylate (105-50-0) + formic acid ethyl ester (109-94-4) → citric acid triethyl ester (77-93-0)

Conditions	Yield
With potassium hydroxide

ethanol (64-17-5) + ((S)-4-Methoxycarbonylmethyl-5-oxo-[1,3]dioxolan-4-yl)-acetic acid (199341-50-9) → citric acid triethyl ester (77-93-0)

Conditions	Yield
With sodium ethanolate Ambient temperature; Yield given;

ethanol (64-17-5) + ((S)-4-Ethoxycarbonylmethyl-5-oxo-[1,3]dioxolan-4-yl)-acetic acid → citric acid triethyl ester (77-93-0)

Conditions	Yield
With triethylamine Heating; Yield given;

diethyl 1,3-acetonedicarboxylate (105-50-0) + formic acid ethyl ester (109-94-4) + KOH → citric acid triethyl ester (77-93-0)

formic acid ethyl ester (109-94-4) + acetone-dicarboxylic acid-(1.3)-diethyl ester + KOH → citric acid triethyl ester (77-93-0)

phosphorus pentachloride (10026-13-8, 874483-75-7) + citric acid (77-92-9) → citric acid triethyl ester (77-93-0) + aconitic acid chloride

Conditions	Yield
dann mit Alkohol;

ethyl iodide (75-03-6) + citrate silver → citric acid triethyl ester (77-93-0)

Conditions	Yield
at 100℃; in geschlossenem Rohr;

ethanol (64-17-5) + citric acid (77-92-9) → ethyl citrate (4552-00-5) + citric acid α,α'-diethyl ester (101996-63-8) + citric acid triethyl ester (77-93-0)

Conditions	Yield
Amberlyst 15 at 25 - 120℃; for 7 - 16h; Product distribution / selectivity;

5-oxo-1,3-dioxolan-4-ylidenedi(acetic acid) (144-16-1) → citric acid triethyl ester (77-93-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: 86 percent / dimethoxypropane, Dowex 50WX4, MeOH / 24 h / Heating 2: pig liver esterase, aq. phosphate buffer pH=7, aq. NaOH / 2 h / Ambient temperature 3: EtONa / Ambient temperature View Scheme
Multi-step reaction with 3 steps 1: 85 percent / diethoxypropane, Dowex 50WX4, MeOH / 24 h / Heating 2: pig liver esterase, aq. phosphate buffer pH=7, aq. NaOH / 2 h / Ambient temperature 3: Et3N / Heating View Scheme

(5-oxo-[1,3]dioxolane-4,4-diyl)-bis-acetic acid diethyl ester (112535-39-4) → citric acid triethyl ester (77-93-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: pig liver esterase, aq. phosphate buffer pH=7, aq. NaOH / 2 h / Ambient temperature 2: Et3N / Heating View Scheme

(5-oxo-[1,3]dioxolane-4,4-diyl)-bis-acetic acid dimethyl ester (77862-72-7) → citric acid triethyl ester (77-93-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: pig liver esterase, aq. phosphate buffer pH=7, aq. NaOH / 2 h / Ambient temperature 2: EtONa / Ambient temperature View Scheme

methanol (67-56-1) + triethyl O-acetylcitrate (77-89-4) + tert-butylamine (75-64-9) → trimethyl citrate (1587-20-8) + citric acid triethyl ester (77-93-0) + dimethyl 3-(tertbutylcarbamoyl)-3-acetoxy-pentanedioate (1242516-65-9) + 3-(tertbutylcarbamoyl)-3-acetoxy-pentanedioic acid (1242516-64-8)

Conditions	Yield
at 20℃;

ethanol (64-17-5) + citric acid (77-92-9) → Diethyl 2-methylsuccinate (4676-51-1) + citric acid triethyl ester (77-93-0)

Conditions	Yield
With hydrogen In water at 200℃; under 3000.3 Torr; for 6h;	A 19 %Spectr. B n/a

propylamine (107-10-8) + citric acid triethyl ester (77-93-0) → 2-hydroxy-N1,N2,N3-tripropylpropane-1,2,3-tricarboxamide (367493-05-8)

Conditions	Yield
In methanol at 20℃;	96%

citric acid triethyl ester (77-93-0) + N-butylamine (109-73-9) → N1,N2,N3-tributyl-2-hydroxypropane-1,2,3-tricarboxamide (38328-55-1)

Conditions	Yield
In methanol at 20℃;	93%

citric acid triethyl ester (77-93-0) + acetic anhydride (108-24-7) → triethyl O-acetylcitrate (77-89-4)

Conditions	Yield
With 4-(dimethylamino)pyridine hydrochloride at 110℃; for 8h;	90%
sulfuric acid at 80℃; for 3h;	88%
With H-type zeolite catalyst at 60 - 120℃; under 760.051 Torr; for 2.83333h; Reagent/catalyst; Sealed tube; Inert atmosphere;
unter kontinuierlicher Entfernung der entstehenden Essigsaeure;

citric acid triethyl ester (77-93-0) + benzoic acid anhydride (93-97-0) → C19H24O8 (145867-24-9)

Conditions	Yield
With 4-(dimethylamino)pyridine hydrochloride at 110℃; for 28h;	88%

citric acid triethyl ester (77-93-0) + dasatanib (302962-49-8) → C22H26ClN7O2S*C12H20O7

Conditions	Yield
In methanol at 20℃; for 3h;	86%

citric acid triethyl ester (77-93-0) → 2-hydroxypropane-1,2,3-tricarbohydrazide (18960-42-4)

Conditions	Yield
With hydrazine hydrate In methanol for 6h; Reflux;	85%
With ethanol; hydrazine hydrate

citric acid triethyl ester (77-93-0) → citric acid α,α'-diethyl ester (101996-63-8)

Conditions	Yield
With sodium hydroxide; chymotripsin; phosphate buffer pH=7 for 96h; Ambient temperature;	85%

citric acid triethyl ester (77-93-0) + Methacryloyl chloride (920-46-7) → C16H24O8 (186351-92-8)

Conditions	Yield
With 1,4-diaza-bicyclo[2.2.2]octane; triethylamine In toluene at 0 - 20℃; for 4h; Inert atmosphere;	82%

added-triethylcitrate + diethyl ether (60-29-7) + citric acid triethyl ester (77-93-0) + isobutylamine (78-81-9) → N,N',N"-tri-iso-butylcitramide (367493-06-9)

Conditions	Yield
In methanol	80.3%

citric acid triethyl ester (77-93-0) + dimethyl aluminum fluoride (753-55-9) → [(C(CH2COOC2H5)2(COOC2H5)O)AlF(CH3)]2 (252270-77-2)

Conditions	Yield
In toluene byproducts: CH4; N2-atmosphere; dropwise addn. of citrate ester to 1 equiv. Al-compd. at room temp., stirring for 24 h; crystn. (-20°C); further crop on concn. of mother liquor; elem. anal.;	63%

diethyl ether (60-29-7) + citric acid triethyl ester (77-93-0) → N1,N2,N3-tributyl-2-hydroxypropane-1,2,3-tricarboxamide (38328-55-1)

Conditions	Yield
With N-butylamine In methanol	58%

diethyl ether (60-29-7) + citric acid triethyl ester (77-93-0) → 2-hydroxy-N1,N2,N3-tripropylpropane-1,2,3-tricarboxamide (367493-05-8)

Conditions	Yield
With propylamine In methanol	55%

citric acid triethyl ester (77-93-0) + 6-(benzyloxy)-1,3-dimethyl-1,3,5-triazine-2,4(1H,3H)-dione → triethyl 2-benzyloxy-1,2,3-propanetricarboxylate (112031-19-3)

Conditions	Yield
With trifluoroacetic acid In 1,4-dioxane at 50℃; for 11h; Molecular sieve; Inert atmosphere;	55%

1-amino-3-methylbutane (107-85-7) + diethyl ether (60-29-7) + citric acid triethyl ester (77-93-0) → N,N',N''-triisopentyl citramide (367493-07-0)

Conditions	Yield
In methanol	52.1%

5%MeOH + citric acid triethyl ester (77-93-0) → 3-Hydroxy-3,4-bis(ethoxycarbonyl)butanoic acid (19958-02-2)

Conditions	Yield
With hydrogenchloride; sodium hydroxide; acetic acid In methanol; ethanol; water	38%

citric acid triethyl ester (77-93-0) + O-benzyl 2,2,2-trichloroacetimidate (81927-55-1) → triethyl 2-benzyloxy-1,2,3-propanetricarboxylate (112031-19-3)

Conditions	Yield
trifluorormethanesulfonic acid In dichloromethane; cyclohexane for 2.5h; Ambient temperature;	5%

citric acid triethyl ester (77-93-0) + sodium cyanoacetic acid ethyl ester (18852-51-2) → 1-cyano-butane-1,2,3,4-tetracarboxylic acid tetraethyl ester (861310-20-5)

Conditions	Yield
With ethanol

citric acid triethyl ester (77-93-0) + sodium cyanoacetic acid ethyl ester (18852-51-2) → rac-4-oxocyclopentane-1,2-dicarboxylic acid (1703-61-3)

Conditions	Yield
With ethanol Verseifung des neben 1-Cyan-butan-tetracarbonsaeure-(1.2.3.4)-tetraaethylester entstehenden Produkts mit Schwefelsaeure;

citric acid triethyl ester (77-93-0) → citric acid β-ethyl ester (4552-01-6)

Conditions	Yield
Verseifung;
With sodium hydroxide; Petroleum ether

citric acid triethyl ester (77-93-0) → 3-Hydroxy-3,4-bis(ethoxycarbonyl)butanoic acid (19958-02-2)

Conditions	Yield
With sodium hydroxide durch fraktionierte Verseifung;
With sodium hydroxide; Petroleum ether at 0℃;

citric acid triethyl ester (77-93-0) → Diethyl-3-(ethoxycarbonyl)pent-2-endioat (5349-99-5)

Conditions	Yield
With phosphorus trichloride Destillation des Reaktionsproduktes;
With phosphorus pentachloride Destillation des Reaktionsproduktes;
Multi-step reaction with 2 steps 1: 88 percent / H2SO4 / 3 h / 80 °C 2: 89 percent / 1.5 h / 275 °C View Scheme

citric acid triethyl ester (77-93-0) → sulfurous acid bis-(1,2-bis-ethoxycarbonyl-1-ethoxycarbonylmethyl-ethyl ester)

Conditions	Yield
With pyridine; thionyl chloride; diethyl ether at 10℃;

citric acid triethyl ester (77-93-0) → (4-hydroxy-3,6-dioxo-hexahydro-pyridazin-4-yl)-acetic acid hydrazide

Conditions	Yield
With hydrazine hydrate

citric acid triethyl ester (77-93-0) + phenyl isocyanate (103-71-9) → 2-phenylcarbamoyloxy-propane-1,2,3-tricarboxylic acid triethyl ester

Conditions	Yield
at 130℃;

citric acid triethyl ester (77-93-0) + acetyl chloride (75-36-5) → triethyl O-acetylcitrate (77-89-4)

citric acid triethyl ester (77-93-0) + chlorophosphoric acid diphenyl ester (2524-64-3) → 2-diphenoxyphosphoryloxy-propane-1,2,3-tricarboxylic acid triethyl ester (102089-54-3)

Conditions	Yield
With pyridine

methanol (67-56-1) + citric acid triethyl ester (77-93-0) + lithium sodium dianion of methyl acetoacetate (64670-05-9) → methyl 1,8-dihydroxy-6-(ethoxycarbonyl)-2-(methoxycarbonyl)-3-naphthylacetate (107182-07-0)

Conditions	Yield
With calcium acetate 1.) THF, 0 deg C, 2 h; 2.) reflux, 2 h; Yield given. Multistep reaction;

citric acid triethyl ester (77-93-0) + acetoacetic acid methyl ester (105-45-3) → methyl 1,8-dihydroxy-6-(ethoxycarbonyl)-2-(methoxycarbonyl)-3-naphthylacetate (107182-07-0)

Conditions	Yield
With n-butyllithium; calcium acetate; sodium hydride 1.) THF, hexane, 1 h, room temperature, 2.) MeOH, 2 h, reflux; Yield given. Multistep reaction;

Upstream product

• 105-50-0 diethyl 1,3-acetonedicarboxylate 
• 109-94-4 formic acid ethyl ester 
• 64-17-5 ethanol 
• 77-92-9 citric acid 
• 199341-50-9 ((S)-4-Methoxycarbonylmethyl-5-oxo-[1,3]dioxolan-4-yl)-acetic acid 
• 10026-13-8 phosphorus pentachloride 
• 75-03-6 ethyl iodide 
• 144-16-1 5-oxo-1,3-dioxolan-4-ylidenedi(acetic acid) 
• 112535-39-4 (5-oxo-[1,3]dioxolane-4,4-diyl)-bis-acetic acid diethyl ester 
• 77862-72-7 (5-oxo-[1,3]dioxolane-4,4-diyl)-bis-acetic acid dimethyl ester 
• 67-56-1 methanol 
• 77-89-4 triethyl O-acetylcitrate 
• 75-64-9 tert-butylamine 

Downstream Products

• 77-89-4 triethyl O-acetylcitrate 
• 1703-61-3 rac-4-oxocyclopentane-1,2-dicarboxylic acid 
• 14774-37-9 (tetrahydro-2H-pyran-4-yl)methanol 
• 1587-20-8 trimethyl citrate 
• 1242516-57-9 1,6-dimethyl 5-ethyl citrate 
• 1242516-58-0 1,2-diethyl-3-methyl-2-hydroxypropane-1,2,3-tricarboxylate 
• 112031-19-3 triethyl 2-benzyloxy-1,2,3-propanetricarboxylate 
• 145867-24-9 C₁₉H₂₄O₈ 
• 70289-34-8 tri(n-pentyl) citrate 
• 19958-02-2 3-Hydroxy-3,4-bis(ethoxycarbonyl)butanoic acid 
• 2565-87-9 2-phosphonooxy-1,2,3-propane tricarboxylic acid 
• 4552-00-5 ethyl citrate 
• 101996-63-8 citric acid α,α'-diethyl ester 

Relevant articles and documents

Citrate plasticizer

The invention discloses a citrate plasticizer and a preparation method thereof, and the preparation method of citrate comprises the following steps: firstly, citric acid and alcohol react to prepare citric acid triester, and then dianhydride acylation is carried out to prepare carboxyl-containing citric acid triester. After chlorination, the carboxyl-containing citric acid triester and the tris(2-ethoxyl) isocyanurate are subjected to esterification reaction to prepare triester citrate containing the isocyanurate. According to the present invention, the preparation method has characteristics of simple operation, wide raw material source and mild reaction condition, and meets the industrial production, the prepared triester citrate containing isocyanurate has a good plasticizing effect and excellent thermal stability, low-temperature flexibility, solvent extraction resistance, migration resistance and flame retardance, and can be widely applied to plastic rubber plasticizers.

METHOD FOR THE PRODUCTION OF METHYLSUCCINIC ACID AND THE ANHYDRIDE THEREOF FROM CITRIC ACID

A process for the preparation of methylsuccinic acid in any form, including its salts, its mono- and diester derivatives and the anhydride thereof, which comprises reacting citric acid or a derivative thereof in decarboxylation conditions, said process comprising (i) reacting citric acid or mono- and diester derivatives thereof in a non- aqueous solvent, specifically excluding alcohols, on a metallic catalyst at a temperature between 50 to 400°C and under a partial hydrogen pressure from 0.1 to 50 bar or (ii) reacting citric acid or any salt thereof or mono-, di- and triester derivatives thereof on a metallic catalyst in solvents comprising at least 5% water, at a temperature of from 50 to 400°C under a hydrogen partial pressure from 0.1 to 400 bar

Method for preparing triethyl citrate through mesoporous silica-supported N,N-dicyclohexyl carbodiimide

The invention discloses a method for preparing triethyl citrate through mesoporous silica-supported N,N-dicyclohexyl carbodiimide. The method comprises the specific step that citric acid and absolute ethyl alcohol are subjected to an esterification reaction to synthesize triethyl citrate through the mesoporous silica-supported N,N-dicyclohexyl carbodiimide. Mesoporous silica is adopted for supporting an esterification reaction condensing agent, no obvious corrosivity exists, the esterification reaction efficiency and yield are improved, the purity is good, the reaction period is greatly shortened, the aftertreatment technology is simplified, the esterification reaction condition is mild, the technology is simple, and the method is suitable for industrial production.