79-81-2

Basic information

• Product Name: Retinol palmitate
• Synonyms: VitaminAPalmitateinOil;VITAMINAPALMITATE,LIQUIDINOIL,1MILLIONIU/G;VITAMINAPALMITATE,USP;[(2E,4E,6E,8E)-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexenyl)nona-2,4,6,8-tetraenyl] hexadecanoate;VITAMIN A PALMITATE(RETINYL PALMITATE)(P);VITAMIN A PALMITATE(RETINYL PALMITATE)(RG);ALL-TRANS-RETINYLPALMITATE;Retinylpalmitat
• CAS NO: 79-81-2
• Molecular Formula: C₃₆H₆₀O₂
• Molecular Weight: 524.86
• EINECS: 201-228-5
• Product Categories: Vitamins and derivatives;BAYPRESS
• Mol File: 79-81-2.mol

Chemical Properties

• Melting Point: 28-29℃
• Boiling Point: 546.51°C (rough estimate)
• Flash Point: 194℃
• Appearance: /oil
• Density: 0.9668 (rough estimate)
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.5250 (estimate)
• Storage Temp.: 2-8°C
• Solubility: Chloroform (Slightly), Ethyl Acetate (Slightly), Methanol (Very Slightly)
• Water Solubility: Soluble in chloroform, ether, and vegetable oils. Insoluble in water.
• Stability: Light Sensitive
• Merck: 13,10073
• BRN: 1917366
• CAS DataBase Reference: Retinol palmitate(CAS DataBase Reference)
• NIST Chemistry Reference: Retinol palmitate(79-81-2)
• EPA Substance Registry System: Retinol palmitate(79-81-2)

Safety Data

• Hazard Codes: T,Xn,F
• Statements: 63-53-61-11
• Safety Statements: 53-23-36/37/39-45-36/37-16-60
• RIDADR: UN1170 - class 3 - PG 2 - Ethanol, solution
• WGK Germany: 3
• RTECS: VH6860000
• F: 8-10-23
• TSCA: Yes
• Hazardous Substances Data: 79-81-2(Hazardous Substances Data)

Usage

Chemical Properties

95.0-100.5% Absorbance @325 nm ≥0.85%

Uses

Different sources of media describe the Uses of 79-81-2 differently. You can refer to the following data:
1. antihypertensive
2. all-trans-Retinyl Palmitate is an ester derivative of Retinol (R252000). all-trans-Retinyl Palmitate is used as a vitamin supplement in the treatment of Vitamin A deficiency. all-trans-Retinyl Palmita te is used as an antioxidant and a source of vitamin A added to low fat milk and other dairy products. all-trans-Retinyl Palmitate is also a constituent of some topically applied skin care products
3. retinyl palmitate is a skin conditioner. This retinoid is considered a milder version of retinoic acid, given its conversion properties. once on the skin, it converts to retinol, which in turn converts to retinoic acid. Physiologically, it is credited with increasing R epidermal thickness, stimulating the production of more epidermal protein, and increasing skin elasticity. Cosmetically, retinyl palmitate is used to reduce the number and depth of fine lines and wrinkles, and prevent skin roughness resulting from uV exposure. Secondary reactions such as erythema, dryness, or irritation are not associated with retinyl palmitate. It is even more effective when used in combination with glycolic acid because it achieves greater penetration. In the united States, its maximum usage level in cosmetic formulations is 2 percent. Retinyl palmitate is the ester of retinol and palmitic acid.
4. vitamin A palmitate is known as a skin “normalizer.” It acts as an antikeratinizing agent, helping the skin stay soft and plump, and improving its water-barrier properties. Because of its impact on the skin’s water-barrier properties, it is useful against dryness, heat, and pollution. It is also an anti-oxidant and is suggested for use in sunscreens. Clinical studies with vitamin A palmitate indicate a significant change in skin composition, with increases in collagen, DnA, skin thickness, and elasticity. Vitamin A palmitate’s stability is superior to retinol.

General Description

Certified pharmaceutical secondary standards for application in quality control provide pharma laboratories and manufacturers with a convenient and cost-effective alternative to pharmacopeia primary standards.Retinyl palmitate belongs to a category of compounds called retinoids, which are chemically similar to vitamin A. It exhibits a beneficial effect on vision, skin and immune function, inhibits cell proliferation and prevents cancer. It is an important dietary as well as a therapeutic compound.

Flammability and Explosibility

Nonflammable

Biochem/physiol Actions

Review: Vitamin A metabolism.

Safety Profile

Mildly toxic by ingestion. An experimental teratogen. Experimental reproductive effects. Human mutation data reported. When heated to decomposition it emits acrid smoke and irritating fumes.

Purification Methods

The palmitate is separated from retinol by column chromatography on water-deactivated alumina with hexane containing a very small percentage of acetone. It is also chromatographed on TLC silica gel G, using pet ether/isopropyl ether/acetic acid/water (180:20:2:5) or pet ether/acetonitrile/acetic acid/water (190:10:1:15) to develop the chromatogram. It is then recrystallised from propylene at low temperature (below -47o). [Beilstein 6 IV 4135.]

InChI:InChI=1/C36H58O3/c1-7-8-9-10-11-12-13-14-15-16-17-18-19-25-34(37)39-35(38)29-31(3)23-20-22-30(2)26-27-33-32(4)24-21-28-36(33,5)6/h20,22-23,26-27,29H,7-19,21,24-25,28H2,1-6H3/b23-20+,27-26+,30-22+,31-29+

Synthetic route

RETINOL (68-26-8) + n-hexadecanoyl chloride (112-67-4) → retinyl palmitate (79-81-2)

Conditions	Yield
In toluene at 35℃; for 1h;	99%
With pyridine In 1,2-dichloro-ethane

palmitic anhydride (623-65-4) + RETINOL (68-26-8) → retinyl palmitate (79-81-2)

Conditions	Yield
With aluminum oxide In Petroleum ether at 40℃; for 2h; Solvent;	97.62%

hexadecanoic acid methyl ester (112-39-0) + Retinol acetate (127-47-9) → retinyl palmitate (79-81-2)

Conditions	Yield
With sodium hydroxide In methanol at 55℃; under 11.2511 - 16.5017 Torr; for 3h; Concentration; Pressure; Large scale;	96%

hexadecanoic acid methyl ester (112-39-0) + RETINOL (68-26-8) → retinyl palmitate (79-81-2)

Conditions	Yield
at 60℃; under 0.750075 Torr; for 3h; Temperature; Large scale;	94%

4-palmitoyloxy-2-methyl-2-buten-1-al + 5-(2,6,6-trimethylcyclohexenyl)-3-methyl-2,4-pentadienyltriphenylphosphonium bromide (62285-98-7) → retinyl palmitate (79-81-2)

Conditions	Yield
With sodium ethanolate In N,N-dimethyl-formamide at -5 - 5℃; for 3h; Wittig Olefination; Inert atmosphere;	91.3%

4-palmitoyloxy-2-methyl-2-buten-1-al + [(2E,4E)-3-methyl-5-(2,6,6-trimethylcyclohex-1-en-1-yl)penta-2,4-dienyl]triphenylphosphonium chloride (53282-28-3) → retinyl palmitate (79-81-2)

Conditions	Yield
With potassium hydroxide In isopropyl alcohol at 5 - 20℃; for 2h; Wittig Olefination; Inert atmosphere;	90.8%

diethyl 3-methyl-5-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2,4-pentadienylphosphonate (186194-14-9) + 2-methyl-4-palmitoyloxy-2-butenal → retinyl palmitate (79-81-2)

Conditions	Yield
Stage #1: diethyl 3-methyl-5-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2,4-pentadienylphosphonate With sodium t-butanolate In toluene at 0℃; for 0.5h; Inert atmosphere; Stage #2: 2-methyl-4-palmitoyloxy-2-butenal In toluene for 3h; Reagent/catalyst; Solvent; Inert atmosphere;	89%

Retinol acetate (127-47-9) + 1-hexadecylcarboxylic acid (57-10-3) → retinyl palmitate (79-81-2) + RETINOL (68-26-8)

Conditions	Yield
With Novozyme 435 (from Candida antarctica immobilized on acrylic resin); Amberlyst A-21 In toluene at 20℃; for 15h; Product distribution / selectivity; Enzymatic reaction;	A 78% B n/a

pyridine (110-86-1) + RETINOL (68-26-8) + n-hexadecanoyl chloride (112-67-4) → retinyl palmitate (79-81-2)

Conditions	Yield
With 1,2-dichloro-ethane

pyridine (110-86-1) + (+/-)-9-palmitoyloxy-3.7-dimethyl-1-(2.2.6-trimethyl-cyclohexen-(6)-yl)-nonatrien-(2ξ.5c.7c)-ol-(4) + toluene (108-88-3) + trichlorophosphate (10025-87-3, 12599-09-6, 63736-95-8) → retinyl palmitate (79-81-2)

Conditions	Yield
at 90 - 95℃;

(+/-)-9-palmitoyloxy-3.7-dimethyl-1-(2.2.6-trimethyl-cyclohexen-(6)-yl)-nonatrien-(2ξ.5c.7c)-ol-(4) + iodine (7553-56-2) + petroleum ether → retinyl palmitate (79-81-2)

4-palmitoyloxy-2-methyl-2-buten-1-al + 3-methyl-5-(2,6,6-trimethyl-1-cyclohexen-1-yl)-1,4-pentadienylphosphonic acid,diethyl ester (128759-92-2) → retinyl palmitate (79-81-2)

Conditions	Yield
With sodium t-butanolate In water; N,N-dimethyl-formamide; toluene

Retinol acetate (127-47-9) + 1-hexadecylcarboxylic acid (57-10-3) → retinyl palmitate (79-81-2)

Conditions	Yield
With Candida sp.99-125 lipase immobilized on SBA-15 In hexane at 30℃; for 6h; Enzymatic reaction;	75.2 %Chromat.
With novozyme 435 In toluene at 20℃; for 20h; Schlenk technique; Inert atmosphere; Enzymatic reaction;

farnesyl alcohol (82010-11-5) → retinyl palmitate (79-81-2)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: TEMPOL; copper(l) chloride / N,N-dimethyl-formamide / 2 h / 30 °C 2.1: 2,3-dicyano-5,6-dichloro-p-benzoquinone / toluene / 0.5 h / 50 °C 3.1: sulfuric acid / 1,2-dichloro-ethane / 0 - 5 °C 4.1: triphenylphosphine / methanol / 1 h / 45 °C 4.2: 1 h / 45 °C 5.1: toluene / 1 h / 35 °C View Scheme

(2E)-farnesal (80442-43-9) → retinyl palmitate (79-81-2)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: 2,3-dicyano-5,6-dichloro-p-benzoquinone / toluene / 0.5 h / 50 °C 2.1: sulfuric acid / 1,2-dichloro-ethane / 0 - 5 °C 3.1: triphenylphosphine / methanol / 1 h / 45 °C 3.2: 1 h / 45 °C 4.1: toluene / 1 h / 35 °C View Scheme

(2E,4E,6Z)-3,7,11-Trimethyl-dodeca-2,4,6,10-tetraenal (13832-89-8, 64197-46-2, 74284-77-8, 83378-81-8, 83378-82-9, 83378-83-0, 83378-84-1) → retinyl palmitate (79-81-2)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: sulfuric acid / 1,2-dichloro-ethane / 0 - 5 °C 2.1: triphenylphosphine / methanol / 1 h / 45 °C 2.2: 1 h / 45 °C 3.1: toluene / 1 h / 35 °C View Scheme

(2E,4E)-3-methyl-5-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2,4-pentadienal (3917-41-7) → retinyl palmitate (79-81-2)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: triphenylphosphine / methanol / 1 h / 45 °C 1.2: 1 h / 45 °C 2.1: toluene / 1 h / 35 °C View Scheme

2-(bromomethyl)-1,3,3-trimethylcyclohex-1-ene (59633-88-4) → retinyl palmitate (79-81-2)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: hexane / 4 h / 50 - 55 °C / Inert atmosphere 2.1: potassium hydroxide / isopropyl alcohol / 1 h / -5 - 5 °C / Inert atmosphere 3.1: potassium hydroxide / water; dichloromethane / 3 h / 10 - 15 °C 3.2: 3 h / 20 - 25 °C 4.1: isopropyl alcohol / 5 h / 55 - 60 °C / Inert atmosphere 5.1: potassium hydroxide / isopropyl alcohol / 2 h / 5 - 20 °C / Inert atmosphere View Scheme
Multi-step reaction with 5 steps 1.1: hexane / 4 h / 50 - 55 °C / Inert atmosphere 2.1: potassium hydroxide / isopropyl alcohol / 1 h / -5 - 5 °C / Inert atmosphere 3.1: sodium hydroxide / water; dichloromethane / 3 h / 15 - 20 °C 3.2: 3 h / 20 - 25 °C 4.1: acetonitrile / 5 h / 50 - 55 °C / Inert atmosphere 5.1: sodium ethanolate / N,N-dimethyl-formamide / 3 h / -5 - 5 °C / Inert atmosphere View Scheme

C28H32P(1+)*Cl(1-) → retinyl palmitate (79-81-2)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: sodium ethanolate / N,N-dimethyl-formamide / 5 h / -5 - 10 °C / Inert atmosphere 2.1: potassium hydroxide / water; dichloromethane / 3 h / 10 - 15 °C 2.2: 3 h / 20 - 25 °C 3.1: isopropyl alcohol / 5 h / 55 - 60 °C / Inert atmosphere 4.1: potassium hydroxide / isopropyl alcohol / 2 h / 5 - 20 °C / Inert atmosphere View Scheme
Multi-step reaction with 4 steps 1.1: sodium ethanolate / N,N-dimethyl-formamide / 5 h / -5 - 10 °C / Inert atmosphere 2.1: sodium hydroxide / water; dichloromethane / 3 h / 15 - 20 °C 2.2: 3 h / 20 - 25 °C 3.1: acetonitrile / 5 h / 50 - 55 °C / Inert atmosphere 4.1: sodium ethanolate / N,N-dimethyl-formamide / 3 h / -5 - 5 °C / Inert atmosphere View Scheme

diethyl [(2,2,6-trimethylcyclohexyl)methyl]phosphonate → retinyl palmitate (79-81-2)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: sodium methylate / N,N-dimethyl-formamide / 1 h / 0 - 15 °C / Inert atmosphere 2.1: potassium hydroxide / water; dichloromethane / 3 h / 10 - 15 °C 2.2: 3 h / 20 - 25 °C 3.1: isopropyl alcohol / 5 h / 55 - 60 °C / Inert atmosphere 4.1: potassium hydroxide / isopropyl alcohol / 2 h / 5 - 20 °C / Inert atmosphere View Scheme
Multi-step reaction with 4 steps 1.1: sodium methylate / N,N-dimethyl-formamide / 1 h / 0 - 15 °C / Inert atmosphere 2.1: sodium hydroxide / water; dichloromethane / 3 h / 15 - 20 °C 2.2: 3 h / 20 - 25 °C 3.1: acetonitrile / 5 h / 50 - 55 °C / Inert atmosphere 4.1: sodium ethanolate / N,N-dimethyl-formamide / 3 h / -5 - 5 °C / Inert atmosphere View Scheme

triphenyl((2,6,6-trimethylcyclohex-1-enyl)methyl)phosphonium bromide (56013-01-5) → retinyl palmitate (79-81-2)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: potassium hydroxide / isopropyl alcohol / 1 h / -5 - 5 °C / Inert atmosphere 2.1: potassium hydroxide / water; dichloromethane / 3 h / 10 - 15 °C 2.2: 3 h / 20 - 25 °C 3.1: isopropyl alcohol / 5 h / 55 - 60 °C / Inert atmosphere 4.1: potassium hydroxide / isopropyl alcohol / 2 h / 5 - 20 °C / Inert atmosphere View Scheme
Multi-step reaction with 4 steps 1.1: potassium hydroxide / isopropyl alcohol / 1 h / -5 - 5 °C / Inert atmosphere 2.1: sodium hydroxide / water; dichloromethane / 3 h / 15 - 20 °C 2.2: 3 h / 20 - 25 °C 3.1: acetonitrile / 5 h / 50 - 55 °C / Inert atmosphere 4.1: sodium ethanolate / N,N-dimethyl-formamide / 3 h / -5 - 5 °C / Inert atmosphere View Scheme

3-methyl-5-acetoxy-1-(2,6,6-trimethyl-1-cyclohexen-1-yl)-1,3-pentadiene (3917-38-2) → retinyl palmitate (79-81-2)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: potassium hydroxide / water; dichloromethane / 3 h / 10 - 15 °C 1.2: 3 h / 20 - 25 °C 2.1: isopropyl alcohol / 5 h / 55 - 60 °C / Inert atmosphere 3.1: potassium hydroxide / isopropyl alcohol / 2 h / 5 - 20 °C / Inert atmosphere View Scheme
Multi-step reaction with 3 steps 1.1: sodium hydroxide / water; dichloromethane / 3 h / 15 - 20 °C 1.2: 3 h / 20 - 25 °C 2.1: acetonitrile / 5 h / 50 - 55 °C / Inert atmosphere 3.1: sodium ethanolate / N,N-dimethyl-formamide / 3 h / -5 - 5 °C / Inert atmosphere View Scheme

5-(2,6,6-trimethyl-cyclohex-1-enyl)-3-methyl-1-chloro-penta-2,4-diene (55732-70-2) → retinyl palmitate (79-81-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: isopropyl alcohol / 5 h / 55 - 60 °C / Inert atmosphere 2: potassium hydroxide / isopropyl alcohol / 2 h / 5 - 20 °C / Inert atmosphere View Scheme

3-methyl-5-bromo-1-(2,6,6-trimethyl-1-cyclohexen-1-yl)-1,3-pentadiene (38987-92-7) → retinyl palmitate (79-81-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: acetonitrile / 5 h / 50 - 55 °C / Inert atmosphere 2: sodium ethanolate / N,N-dimethyl-formamide / 3 h / -5 - 5 °C / Inert atmosphere View Scheme

3,7-dimethylocta-1,6-dien-3-ol (78-70-6) → retinyl palmitate (79-81-2)

Conditions	Yield
Multi-step reaction with 6 steps 1.1: hydrogen bromide; sodium hydroxide / water; dichloromethane / 2 h / 30 - 35 °C / Inert atmosphere 1.2: 2 h / 35 - 40 °C 2.1: hexane / 4 h / 50 - 55 °C / Inert atmosphere 3.1: potassium hydroxide / isopropyl alcohol / 1 h / -5 - 5 °C / Inert atmosphere 4.1: sodium hydroxide / water; dichloromethane / 3 h / 15 - 20 °C 4.2: 3 h / 20 - 25 °C 5.1: acetonitrile / 5 h / 50 - 55 °C / Inert atmosphere 6.1: sodium ethanolate / N,N-dimethyl-formamide / 3 h / -5 - 5 °C / Inert atmosphere View Scheme
Multi-step reaction with 6 steps 1.1: hydrogen bromide; sodium hydroxide / water; dichloromethane / 2 h / 30 - 35 °C / Inert atmosphere 1.2: 2 h / 35 - 40 °C 2.1: hexane / 4 h / 50 - 55 °C / Inert atmosphere 3.1: potassium hydroxide / isopropyl alcohol / 1 h / -5 - 5 °C / Inert atmosphere 4.1: potassium hydroxide / water; dichloromethane / 3 h / 10 - 15 °C 4.2: 3 h / 20 - 25 °C 5.1: isopropyl alcohol / 5 h / 55 - 60 °C / Inert atmosphere 6.1: potassium hydroxide / isopropyl alcohol / 2 h / 5 - 20 °C / Inert atmosphere View Scheme
Multi-step reaction with 6 steps 1.1: sodium hydroxide; thionyl chloride / 1,2-dichloro-ethane; water / 3 h / 40 - 45 °C 1.2: 5 h / 70 - 75 °C 2.1: acetonitrile / 4 h / 60 - 65 °C / Inert atmosphere 3.1: sodium ethanolate / N,N-dimethyl-formamide / 5 h / -5 - 10 °C / Inert atmosphere 4.1: sodium hydroxide / water; dichloromethane / 3 h / 15 - 20 °C 4.2: 3 h / 20 - 25 °C 5.1: acetonitrile / 5 h / 50 - 55 °C / Inert atmosphere 6.1: sodium ethanolate / N,N-dimethyl-formamide / 3 h / -5 - 5 °C / Inert atmosphere View Scheme

1,3,3-trimethyl-2-chloromethylcyclohexene → retinyl palmitate (79-81-2)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: acetonitrile / 4 h / 60 - 65 °C / Inert atmosphere 2.1: sodium ethanolate / N,N-dimethyl-formamide / 5 h / -5 - 10 °C / Inert atmosphere 3.1: sodium hydroxide / water; dichloromethane / 3 h / 15 - 20 °C 3.2: 3 h / 20 - 25 °C 4.1: acetonitrile / 5 h / 50 - 55 °C / Inert atmosphere 5.1: sodium ethanolate / N,N-dimethyl-formamide / 3 h / -5 - 5 °C / Inert atmosphere View Scheme
Multi-step reaction with 5 steps 1.1: acetonitrile / 4 h / 60 - 65 °C / Inert atmosphere 2.1: sodium ethanolate / N,N-dimethyl-formamide / 5 h / -5 - 10 °C / Inert atmosphere 3.1: potassium hydroxide / water; dichloromethane / 3 h / 10 - 15 °C 3.2: 3 h / 20 - 25 °C 4.1: isopropyl alcohol / 5 h / 55 - 60 °C / Inert atmosphere 5.1: potassium hydroxide / isopropyl alcohol / 2 h / 5 - 20 °C / Inert atmosphere View Scheme
Multi-step reaction with 5 steps 1.1: 4 h / 105 - 110 °C / Inert atmosphere 2.1: sodium methylate / N,N-dimethyl-formamide / 1 h / 0 - 15 °C / Inert atmosphere 3.1: potassium hydroxide / water; dichloromethane / 3 h / 10 - 15 °C 3.2: 3 h / 20 - 25 °C 4.1: isopropyl alcohol / 5 h / 55 - 60 °C / Inert atmosphere 5.1: potassium hydroxide / isopropyl alcohol / 2 h / 5 - 20 °C / Inert atmosphere View Scheme
Multi-step reaction with 5 steps 1.1: 4 h / 105 - 110 °C / Inert atmosphere 2.1: sodium methylate / N,N-dimethyl-formamide / 1 h / 0 - 15 °C / Inert atmosphere 3.1: sodium hydroxide / water; dichloromethane / 3 h / 15 - 20 °C 3.2: 3 h / 20 - 25 °C 4.1: acetonitrile / 5 h / 50 - 55 °C / Inert atmosphere 5.1: sodium ethanolate / N,N-dimethyl-formamide / 3 h / -5 - 5 °C / Inert atmosphere View Scheme

1-hexadecylcarboxylic acid (57-10-3) → retinyl palmitate (79-81-2)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: magnesium chloride; di-tert-butyl dicarbonate / ethyl acetate / 5 h / 25 - 35 °C 2.1: selenium(IV) oxide; tert.-butylhydroperoxide / 18 h / 25 - 30 °C / Inert atmosphere 3.1: sodium t-butanolate / toluene / 0.5 h / 0 °C / Inert atmosphere 3.2: 3 h / Inert atmosphere View Scheme

3-methyl-2-buten-1-ol (556-82-1) → retinyl palmitate (79-81-2)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: magnesium chloride; di-tert-butyl dicarbonate / ethyl acetate / 5 h / 25 - 35 °C 2.1: selenium(IV) oxide; tert.-butylhydroperoxide / 18 h / 25 - 30 °C / Inert atmosphere 3.1: sodium t-butanolate / toluene / 0.5 h / 0 °C / Inert atmosphere 3.2: 3 h / Inert atmosphere View Scheme

retinyl palmitate (79-81-2) → retinol (68-26-8, 2052-63-3, 6018-74-2, 17706-49-9, 22737-96-8, 22737-97-9, 29444-25-5, 34218-73-0, 39815-04-8, 69686-68-6, 69686-69-7, 74743-94-5, 84415-27-0, 84415-28-1, 85354-09-2, 85354-10-5, 93380-02-0, 98462-62-5, 137121-52-9)

Conditions	Yield
With potassium hydroxide In ethanol; isopropyl alcohol at 90℃; for 1.25h;	90%

retinyl palmitate (79-81-2) → Hexadecanoic acid 2-hexadecanoyloxymethyl-3,6-dimethyl-5-[(1Z,3E)-2-methyl-4-(2,6,6-trimethyl-cyclohex-1-enyl)-buta-1,3-dienyl]-6-[(1E,3E,5E)-4-methyl-6-(2,6,6-trimethyl-cyclohex-1-enyl)-hexa-1,3,5-trienyl]-cyclohex-3-enylmethyl ester

Conditions	Yield
at 80℃; for 120h; Kinetics; Further Variations:; Solvents; Temperatures; Dimerization;

retinyl palmitate (79-81-2) → 13-cis-retinoic acid (4759-48-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: 90 percent / aq. 10percent KOH / propan-2-ol; ethanol / 1.25 h / 90 °C 2: 58 percent / MnO2, NaCN / acetonitrile; acetic acid / 62 h / 20 °C 3: aq. 5percent KOH / ethanol / 0.5 h / Heating View Scheme

retinyl palmitate (79-81-2) → all-trans-retinoic-acid (302-79-4)

Conditions	Yield
Multi-step reaction with 3 steps 1: 90 percent / aq. 10percent KOH / propan-2-ol; ethanol / 1.25 h / 90 °C 2: 58 percent / MnO2, NaCN / acetonitrile; acetic acid / 62 h / 20 °C 3: 77 percent / aq. 5percent KOH / ethanol / 0.5 h / Heating View Scheme

retinyl palmitate (79-81-2) → ethyl retinoate (3899-20-5, 51249-34-4, 59699-82-0, 85354-08-1, 86708-67-0, 86708-68-1, 86708-69-2, 86708-70-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: 90 percent / aq. 10percent KOH / propan-2-ol; ethanol / 1.25 h / 90 °C 2: 58 percent / MnO2, NaCN / acetonitrile; acetic acid / 62 h / 20 °C View Scheme

retinyl palmitate (79-81-2) → 20,14-retro-Retinoic acid (138093-35-3)

Conditions	Yield
Multi-step reaction with 4 steps 1: 90 percent / aq. 10percent KOH / propan-2-ol; ethanol / 1.25 h / 90 °C 2: 58 percent / MnO2, NaCN / acetonitrile; acetic acid / 62 h / 20 °C 3: 77 percent / aq. 5percent KOH / ethanol / 0.5 h / Heating 4: 1.) lithium diisopropylamide, HMPA / 1.) THF, hexane, -60 deg C, 5 min, 2.) THF, hexane, -70 deg C, 45 min View Scheme
Multi-step reaction with 4 steps 1: 90 percent / aq. 10percent KOH / propan-2-ol; ethanol / 1.25 h / 90 °C 2: 58 percent / MnO2, NaCN / acetonitrile; acetic acid / 62 h / 20 °C 3: 77 percent / aq. 5percent KOH / ethanol / 0.5 h / Heating 4: 1.) n-BuLi, diisopropylamine / 1.) THF, hexane, 0 deg C, 10 min, 2.) THF, hexane, -60 deg C, 5 min View Scheme

retinyl palmitate (79-81-2) → 14-ethyl-20,14-retro-retinoic acid (138093-38-6)

Conditions	Yield
Multi-step reaction with 4 steps 1: 90 percent / aq. 10percent KOH / propan-2-ol; ethanol / 1.25 h / 90 °C 2: 58 percent / MnO2, NaCN / acetonitrile; acetic acid / 62 h / 20 °C 3: 77 percent / aq. 5percent KOH / ethanol / 0.5 h / Heating 4: 1.) lithium diisopropylamide, HMPA / 1.) THF, hexane, -60 deg C, 5 min, 2.) THF, hexane, -70 deg C, 45 min View Scheme

retinyl palmitate (79-81-2) → 14-isopropyl-20,14-retro-retinoic acid (138093-39-7)

Conditions	Yield
Multi-step reaction with 4 steps 1: 90 percent / aq. 10percent KOH / propan-2-ol; ethanol / 1.25 h / 90 °C 2: 58 percent / MnO2, NaCN / acetonitrile; acetic acid / 62 h / 20 °C 3: 77 percent / aq. 5percent KOH / ethanol / 0.5 h / Heating 4: 1.) lithium diisopropylamide, HMPA / 1.) THF, hexane, -60 deg C, 5 min, 2.) THF, hexane, -70 deg C, 45 min View Scheme

retinyl palmitate (79-81-2) → methyl 14-ethyl-20,14-retro-retinoate (138093-44-4)

Conditions

Yield

Multi-step reaction with 5 steps 1: 90 percent / aq. 10percent KOH / propan-2-ol; ethanol / 1.25 h / 90 °C 2: 58 percent / MnO2, NaCN / acetonitrile; acetic acid / 62 h / 20 °C 3: 77 percent / aq. 5percent KOH / ethanol / 0.5 h / Heating 4: 1.) lithium diisopropylamide, HMPA / 1.) THF, hexane, -60 deg C, 5 min, 2.) THF, hexane, -70 deg C, 45 min 5: 77 percent / diethyl ether / 20 h / 0 °C View Scheme

retinyl palmitate (79-81-2) → methyl 14-isopropyl-20,14-retro-retinoate (138093-45-5)

Conditions

Yield

Multi-step reaction with 5 steps 1: 90 percent / aq. 10percent KOH / propan-2-ol; ethanol / 1.25 h / 90 °C 2: 58 percent / MnO2, NaCN / acetonitrile; acetic acid / 62 h / 20 °C 3: 77 percent / aq. 5percent KOH / ethanol / 0.5 h / Heating 4: 1.) lithium diisopropylamide, HMPA / 1.) THF, hexane, -60 deg C, 5 min, 2.) THF, hexane, -70 deg C, 45 min 5: 89 percent / diethyl ether / 0.5 h / 0 °C View Scheme

retinyl palmitate (79-81-2) → 13-cis-14-Ethylretinoic acid (138231-98-8)

Conditions

Yield

Multi-step reaction with 6 steps 1: 90 percent / aq. 10percent KOH / propan-2-ol; ethanol / 1.25 h / 90 °C 2: 58 percent / MnO2, NaCN / acetonitrile; acetic acid / 62 h / 20 °C 3: 77 percent / aq. 5percent KOH / ethanol / 0.5 h / Heating 4: 1.) lithium diisopropylamide, HMPA / 1.) THF, hexane, -60 deg C, 5 min, 2.) THF, hexane, -70 deg C, 45 min 5: 77 percent / diethyl ether / 20 h / 0 °C 6: 1.) MeONa, 2.) 10percent aq. KOH / 1.) MeOH, reflux, 7 h, 2.) EtOH, reflux View Scheme

retinyl palmitate (79-81-2) → 14-Ethylretinoic acid (138093-41-1)

Conditions

Yield

Multi-step reaction with 6 steps 1: 90 percent / aq. 10percent KOH / propan-2-ol; ethanol / 1.25 h / 90 °C 2: 58 percent / MnO2, NaCN / acetonitrile; acetic acid / 62 h / 20 °C 3: 77 percent / aq. 5percent KOH / ethanol / 0.5 h / Heating 4: 1.) lithium diisopropylamide, HMPA / 1.) THF, hexane, -60 deg C, 5 min, 2.) THF, hexane, -70 deg C, 45 min 5: 77 percent / diethyl ether / 20 h / 0 °C 6: 1.) MeONa, 2.) 10percent aq. KOH / 1.) MeOH, reflux, 7 h, 2.) EtOH, reflux View Scheme

retinyl palmitate (79-81-2) → 13-cis-14-Isopropylretinoic acid (138231-99-9)

Conditions

Yield

Multi-step reaction with 6 steps 1: 90 percent / aq. 10percent KOH / propan-2-ol; ethanol / 1.25 h / 90 °C 2: 58 percent / MnO2, NaCN / acetonitrile; acetic acid / 62 h / 20 °C 3: 77 percent / aq. 5percent KOH / ethanol / 0.5 h / Heating 4: 1.) lithium diisopropylamide, HMPA / 1.) THF, hexane, -60 deg C, 5 min, 2.) THF, hexane, -70 deg C, 45 min 5: 89 percent / diethyl ether / 0.5 h / 0 °C 6: 1.) NaH, 2.) 20percent aq. KOH, 18-crown-6 / 1.) DMF, 50 deg C, 90 min, 2.) EtOH, reflux View Scheme

retinyl palmitate (79-81-2) → 14-Isopropylretinoic acid (138093-42-2)

Conditions

Yield

Multi-step reaction with 6 steps 1: 90 percent / aq. 10percent KOH / propan-2-ol; ethanol / 1.25 h / 90 °C 2: 58 percent / MnO2, NaCN / acetonitrile; acetic acid / 62 h / 20 °C 3: 77 percent / aq. 5percent KOH / ethanol / 0.5 h / Heating 4: 1.) lithium diisopropylamide, HMPA / 1.) THF, hexane, -60 deg C, 5 min, 2.) THF, hexane, -70 deg C, 45 min 5: 89 percent / diethyl ether / 0.5 h / 0 °C 6: 1.) NaH, 2.) 20percent aq. KOH, 18-crown-6 / 1.) DMF, 50 deg C, 90 min, 2.) EtOH, reflux View Scheme

retinyl palmitate (79-81-2) → (2Z,4E,6E,8E)-2-Ethyl-3,7-dimethyl-9-(2,6,6-trimethyl-cyclohex-1-enyl)-nona-2,4,6,8-tetraenoic acid methyl ester (138232-01-6)

Conditions

Yield

Multi-step reaction with 6 steps 1: 90 percent / aq. 10percent KOH / propan-2-ol; ethanol / 1.25 h / 90 °C 2: 58 percent / MnO2, NaCN / acetonitrile; acetic acid / 62 h / 20 °C 3: 77 percent / aq. 5percent KOH / ethanol / 0.5 h / Heating 4: 1.) lithium diisopropylamide, HMPA / 1.) THF, hexane, -60 deg C, 5 min, 2.) THF, hexane, -70 deg C, 45 min 5: 77 percent / diethyl ether / 20 h / 0 °C 6: MeONa / methanol / 7 h / Heating View Scheme

Upstream product

• 110-86-1 pyridine 
• 68-26-8 RETINOL 
• 112-67-4 n-hexadecanoyl chloride 
• 108-88-3 toluene 
• 10025-87-3 trichlorophosphate 
• 7553-56-2 iodine 
• 128759-92-2 3-methyl-5-(2,6,6-trimethyl-1-cyclohexen-1-yl)-1,4-pentadienylphosphonic acid,diethyl ester 
• 127-47-9 Retinol acetate 
• 57-10-3 1-hexadecylcarboxylic acid 
• 623-65-4 palmitic anhydride 
• 112-39-0 hexadecanoic acid methyl ester 
• 82010-11-5 farnesyl alcohol 
• 80442-43-9 (2E)-farnesal 
• 13832-89-8 (2E,4E,6Z)-3,7,11-Trimethyl-dodeca-2,4,6,10-tetraenal 

Downstream Products

• 68-26-8 retinol 
• 4759-48-2 13-cis-retinoic acid 
• 302-79-4 all-trans-retinoic-acid 
• 3899-20-5 ethyl retinoate 
• 138093-35-3 20,14-retro-Retinoic acid 
• 138093-38-6 14-ethyl-20,14-retro-retinoic acid 
• 138093-39-7 14-isopropyl-20,14-retro-retinoic acid 
• 138093-44-4 methyl 14-ethyl-20,14-retro-retinoate 
• 138093-45-5 methyl 14-isopropyl-20,14-retro-retinoate 
• 138231-98-8 13-cis-14-Ethylretinoic acid 
• 138093-41-1 14-Ethylretinoic acid 
• 138231-99-9 13-cis-14-Isopropylretinoic acid 
• 138093-42-2 14-Isopropylretinoic acid 
• 138232-01-6 (2Z,4E,6E,8E)-2-Ethyl-3,7-dimethyl-9-(2,6,6-trimethyl-cyclohex-1-enyl)-nona-2,4,6,8-tetraenoic acid methyl ester 

Relevant articles and documents

Synthesis of retinyl palmitate catalyzed by Candida sp.99-125 lipase immobilized on fiber-like SBA-15 mesoporous material

Candida sp.99-125 lipase was suitable for transesterification of fats and oils to produce fatty acid methyl ester. The adsorption of Candida sp.99-125 lipase onto the fiber-like SBA-15 mesoporous material has been studied. The unaltered structural order of the fiber-like SBA-15 before and after the adsorption has been confirmed by FT-IR, SEM and N2 adsorption. The amount of adsorbed Candida sp.99-125 lipase depends both on the solution pH and reaction time. Good adsorption capacity of Candida sp.99-125 lipase on fiber-like SBA-15 may be due to solution pH from 5.0 to 9.0 especially at 7.0 (93.99 mg enzyme per gram silica is obtained and the activity recovery is 281.05%). A high lipase loading (135.9 mg enzyme per gram silica) was obtained, but it did not produce a proportionate level of catalytic activity. The immobilized Candida sp.99-125 lipase showed increased adaptability in the hydrolysis of p-nitrophenyl acetate compared to free Candida sp.99-125 lipase at pH 5.0-9.0. Meanwhile, the immobilized Candida sp.99-125 lipase showed higher thermal stability than that of free Candida sp.99-125 lipase. And the synthesis of retinyl palmitate in organic solvent with the immobilized Candida sp.99-125 lipase was investigated. The influence factors, such as: the solvent used, the molar ratio and concentrations of substrates, the reaction time and the amount of lipase were studied and optimized. In the conditions of transesterificating 0.164 g retinyl acetate and 0.32 g palmitic acid, 10 mL of solvent hexane, 1:4 of mass ratio of lipase to retinyl acetate, and 6 hours of reaction time, 74.6% of retinyl acetate was converted into retinyl plamitate. Copyright

Synthesis method of 4-palmitoyloxy-2-methyl-2-butenal and synthesis method of vitamin A palmitate

The invention discloses a synthesis method of a vitamin A palmitate intermediate 4-palmitoyloxy-2-methyl-2-butenal, application of the vitamin A palmitate intermediate 4-palmitoyloxy-2-methyl-2-butenal in vitamin A palmitate synthesis, and a method for synthesizing vitamin A palmitate by using the intermediate. According to the method, in the process of introducing aldehyde group, solvent-free reaction conditions are adopted, so that the use of organic solvents is avoided while the reaction yield is increased, the production cost is reduced, the operation is simple and convenient, and the method is suitable for industrial large-scale production.

Method for preparing vitamin A and vitamin A ester

The invention provides a novel method for preparing vitamin A and vitamin A ester by taking farnesol as a raw material. The method comprises the following steps: carrying out oxidation reaction on farnesol and oxygen under the action of a catalyst and a cocatalyst to generate farnesal; carrying out dehydrogenation reaction on farnesal to generate dehydrofarnesal; carrying out cyclization reactionon the dehydrofarnesal under the catalysis of acid to generate a cyclized intermediate; carrying out a reaction on the cyclized intermediate with chloroisopentenol to generate vitamin A; carrying outan esterification reaction on vitamin A to generate vitamin A ester. The method avoids the defects of an existing process, and the process line is economical and effective.

Preparation method of vitamin A ester intermediate C15 and vitamin A ester

The invention provides a preparation method of a vitamin A ester intermediate C15 and vitamin A ester. The method comprises the following steps: carrying out a halogenation reaction and a cyclizationreaction on 3, 7-dimethyl-3-hydroxy-1, 6-octadiene as an initial raw material, carrying out a substitution reaction on the obtained product and triphenylphosphine or triester phosphite to prepare a corresponding Wittig reagent, carrying out a Wittig reaction on the Wittig reagent and 2-methyl-4-acetoxy-2-butenal, performing acidifying, hydrolyzing and acidifying the obtained product, and carryingout a substitution reaction on the hydrolyzed and acidified product and triphenylphosphine or triester phosphite to prepare C15. The vitamin A ester can be prepared by carrying out a Wittig reaction on the obtained C15 and 2-methyl-4-R3 substituent carbonyloxy-2-butenal. The method has the advantages of single reaction type, easy operation and realization of reaction conditions, safe and environment-friendly operation, simple post-treatment and low cost; and the reaction activity is strong, the reaction selectivity is high, the atom economy is high, and the target product yield and purity arehigh.

Preparation method of vitamin A palmitate

The invention belongs to the technical field of medicines, in particular to preparation of vitamin A palmitate and a composition thereof. Aiming at solving the technical problem, the invention provides a preparation method of vitamin A palmitate. The preparation method comprises the steps of carrying out alcoholysis on vitamin A acetate with an alcohol solvent to obtain retinol, and then adding methyl palmitate for alcoholysis again to obtain vitamin A palmitate. The preparation method is simple in process, is environmentally friendly, and has high purity and high yield.

Synthesis method of vitamin A higher fatty acid ester

The invention discloses a synthesis method of vitamin A higher fatty acid ester, which includes the following steps: a) performing an esterification reaction to vitamin A alcohol and higher fatty acid anhydride in an organic solvent under catalysis of an alkaline metal oxide; and b) performing after treatment after the reaction is finished to obtain the vitamin A higher fatty acid ester. The method is less in reaction by-products, is high in product purity and is good in product quality. The product is more than 97.5% in content and is more than 96.5% in yield through high performance liquid chromatography detection. The vitamin A higher fatty acid ester enables storage, transportation and application of vitamin A to be more convenient. An analytic method in pharmacopeia proves that vitamin A palmitate is 1750000-1780000 IU/g in biological titer and is more than 97.5% in content through the high performance liquid chromatography detection, so that the vitamin A palmitate can be marketed as commodity directly, and is widely applied in the fields of medicines, feed additives and food additives.

TRANSESTERIFICATION PROCESS OF RETINOL ESTERS

The present invention relates to a transesterification process of specific compounds comprising isoprenoid units.

An LC/MS/MS method for stable isotope dilution studies of β-carotene bioavailability, bioconversion, and vitamin A status in humans

Isotope dilution is currently the most accurate technique in humans to determine vitamin A status and bioavailability/ bioconversion of provitamin A carotenoids such as α -carotene. However, limits of MS detection, coupled with extensive isolation procedures, have hindered investigations of physiologically-relevant doses of stable isotopes in large intervention trials. Here, a sensitive liquid chromatography- tandem mass spectrometry (LC/MS/MS) analytical method was developed to study the plasma response from coadministered oral doses of 2 mg [ 13 C 10 ] α -carotene and 1 mg [ 13 C 10 ]retinyl acetate in human subjects over a 2 week period. A reverse phase C 18 column and binary mobile phase solvent system separated α -carotene, retinol, retinyl acetate, retinyl linoleate, retinyl palmitate/retinyl oleate, and retinyl stearate within a 7 min run time. Selected reaction monitoring of analytes was performed under atmospheric pressure chemical ionization in positive mode at m/z 537 ? 321 and m/z 269 ? 93 for respective [ 12 C] α -carotene and [ 12 C] retinoids; m/z 547 ? 330 and m/z 274 ? 98 for [ 13 C 10 ] α -carotene and [ 13 C 5 ] cleavage products; and m/z 279 ? 100 for metabolites of [ 13 C 10 ]retinyl acetate. A single one-phase solvent extraction, with no saponification or purification steps, left retinyl esters intact for determination of intestinally-derived retinol in chylomicrons versus retinol from the liver bound to retinol binding protein. Coadministration of [ 13 C 10 ] retinyl acetate with [ 13 C 10 ] α -carotene not only acts as a reference dose for inter-individual variations in absorption and chylomicron clearance rates, but also allows for simultaneous determination of an individual's vitamin A status. - Oxley, A., P. Berry, G. A. Taylor, J. Cowell, M. J. Hall, J. Hesketh, G. Lietz, and A. V. Boddy. An LC/MS/MS method for stable isotope dilution studies of α -carotene bioavailability, bioconversion, and vitamin A status in humans. Copyright

Preparation of retinyl esters

Long-chain esters of retinol are prepared via a chemoenzymatic process from short-chain retinyl esters and an appropriate long-chain acid or ester in the presence of an enzyme. Use of various additives enhance the yield of the desired ester and facilitated its purification.

USE OF NANODISPERSIONS IN PHARMACEUTICAL END FORMULATIONS

A description is given of the use of a nanodispersion, which comprises (a) a membrane-forming molecule, (b) a coemulsifier and (c) a lipophilic component, in pharmaceutical end formulations, the nanodispersion being obtainable by (α) mixing the components (a), (b) and (c) until a homogeneous clear liquid is obtained, and (β) adding the liquid obtained in step (α) to the water phase of the pharmaceutical end formulations, steps (α) and (β) being carried out without any additional supply of energy. The nanodispersions used according to this invention are suitable as transport vehicles for pharmaceutical active agents.