7085-55-4

Basic information

• Product Name: Troxerutin
• Synonyms: 3μ,4μ,7-Tris[O-(2-hydroxyethyl)]rutin, Troxerutin;Troxerutin，Trihydroxyethylrutin;3',4',7-Tris(hydroxyethyl)rutin;3,5-Dihydroxy-3',4',7-tris(2-hydroxyethoxy)flavone 3-rutinoside;Factor-P-zyma;Tris(hydroxyethyl)rutin;Tris(hydroxyethyl)rutoside;Rufen P-4
• CAS NO: 7085-55-4
• Molecular Formula: C₃₃H₄₂O₁₉
• Molecular Weight: 346.5
• EINECS: 230-389-4
• Product Categories: Aromatics;Heterocycles;Oligosaccharides;Plant extracts;Herb extract;POSORUTIN;Inhibitors;Miscellaneous Natural Products;Natural Plant Extract;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 7085-55-4.mol
• Article Data: 14

Chemical Properties

• Melting Point: 181°C
• Boiling Point: 1058.4 °C at 760 mmHg
• Flash Point: 332 °C
• Appearance: yellow powder
• Density: 1.65 g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.689
• Storage Temp.: Refrigerator
• Solubility: Freely soluble in water, slightly soluble in ethanol (96 per cent) and practically insoluble in methylene chloride.
• PKA: 5.92±0.40(Predicted)
• Merck: 14,9789
• BRN: 4778232
• CAS DataBase Reference: Troxerutin(CAS DataBase Reference)
• NIST Chemistry Reference: Troxerutin(7085-55-4)
• EPA Substance Registry System: Troxerutin(7085-55-4)

Safety Data

• Safety Statements: 22-24/25
• WGK Germany: 3
• RTECS: LK8331500
• Hazardous Substances Data: 7085-55-4(Hazardous Substances Data)

Usage

Chemical Properties

Yellow Powder

Originator

Venoruton,Novartis Co

Uses

Different sources of media describe the Uses of 7085-55-4 differently. You can refer to the following data:
1. Used in the treatment of venous disorders
2. vasoprotectant
3. Troxerutin, a derivative of the naturally occurring bioflavonoid rutin, is thought to inhibit red cell and platelet aggregation, improve erythrocyte deformability, and improve plasma viscosity retinal microcirculation. A double-blind randomized clinical trial compared troxerutin with placebo in 27 patients with CRVO. The limitations of the study included a small number of patients and short follow-up time.

Manufacturing Process

In a nitrogen atmosphere 120 g of caustic soda (3 moles) in solution are added to 610 g of rutin (1 mol) suspended in 2 litres of water, the mixture being vigorously agitated by a mechanical stirrer, 241.5 g of ethylene chlorohydrin being then introduced at 55°C for 10 min. When all the chlorohydrin has been thus added the temperature is progressively raised to 75°C and maintained at this level for 2 hours. After cooling, in a nitrogen atmosphere, the pH value adjusted to 5 by the addition of dilute hydrochloric acid. The solution is kept in an ice box for 24 hours and then filtered to remove any impurities. At reduced pressure the solution is evaporated until dry, the residue taken up in 3 litres of boning methanol which dissolves the tri-(β-hydroxyethyl)rutin formed and leaves the sparingly soluble sodium chloride behind. The tri-(β-hydroxyethyl)rutin is recovered from its methanolic solution either by evaporation and refrigeration, or by evaporation precipitation with absolute ethanol. In either case tri-(β-hydroxyethyl)rutin obtained is in the form of small very hygroscopic crystals which contain alcohol of crystallization.These crystals are quickly shaken washed in a little cold absolute ethanol and then dried in vacuum at 100°C. 680 g of anhydrous tri-(β-hydroxyethyl)rutin are thus obtained in the form of a yellow powder which melts at 156°C.GB Patent No. 833,174; April 21, 1960; Assigned to Zyma S.A., a Swiss Corporation, of Route Etraz, Nyon Canton of Vaud, Switzerland

InChI:InChI=1/C33H42O19/c1-14-23(38)26(41)28(43)32(49-14)48-13-21-24(39)27(42)29(44)33(51-21)52-31-25(40)22-17(37)11-16(45-7-4-34)12-20(22)50-30(31)15-2-3-18(46-8-5-35)19(10-15)47-9-6-36/h2-3,10-12,14,21,23-24,26-29,32-39,41-44H,4-9,13H2,1H3/t14-,21+,23-,24+,26+,27-,28+,29+,32+,33?/m0/s1

Synthetic route

oxirane (75-21-8) + rutin (153-18-4) → troxerutin (7085-55-4)

Conditions	Yield
With chitosan In methanol at 75℃; for 3h; Concentration; Temperature; Autoclave;	96%
With natural polymer sodium alginate In methanol at 70℃; for 4h; Temperature; Autoclave;	87.6%
Stage #1: oxirane; rutin With sodium hydroxide In water at 75℃; for 6h; Stage #2: With hydrogenchloride In water pH=4;

rutin (153-18-4) + 2-bromoethanol (540-51-2) → troxerutin (7085-55-4)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 80 - 85℃;	94.9%

rutin (153-18-4) + 2-chloro-ethanol (107-07-3) → troxerutin (7085-55-4)

Conditions	Yield
With potassium hydroxide at 68℃; for 24h; Temperature; Inert atmosphere;	90%
With potassium carbonate In N,N-dimethyl-formamide for 0.133333h; Heating;

oxirane (75-21-8) + 7-mono-O-(β-hydroxyetyl)rutoside (23869-24-1) → troxerutin (7085-55-4)

Conditions	Yield
With pyridine In methanol at 75 - 80℃; Reagent/catalyst; Temperature; Autoclave;	64%
With sodium hydroxide In methanol; water at 60 - 70℃; Reagent/catalyst; Solvent;

oxirane (75-21-8) + rutin (153-18-4) → 7,3',4'-trihydroxyethylisoquercitrine-3-glucoside (266363-39-7) + 7,5',4'-trihydroxyethylisoquercitrine-3-glucoside + 7,4'-dihydroxyethylkaempferol-3-rutinoside (791084-12-3) + 7,4'-di-hydroxyethyl rutoside (13190-91-5) + troxerutin (7085-55-4) + 5,7,3',4'-tetra-hydroxyethyl rutoside (6980-20-7)

Conditions	Yield
With sodium hydroxide In water at 75℃; for 6h; Product distribution / selectivity;

troxerutin (7085-55-4) → 3',4'-bis(2-O-sulfate ethoxy)-7-(2-O-sulfate ethoxy)rutin

Conditions	Yield
Stage #1: troxerutin With triethylamine sulfurtrioxide In N,N-dimethyl acetamide at 20 - 100℃; for 0.5h; Microwave irradiation; Stage #2: With triethylamine In N,N-dimethyl acetamide at 4℃; for 24h; Stage #3: With sodium acetate In water	89%

glutaric acid divinyl ester (10355-47-2) + troxerutin (7085-55-4) → troxerutin vinyl glutarate (1218941-80-0)

Conditions	Yield
With pyridine at 50℃; for 72h; Enzymatic reaction;	65%
With pyridine; alkaline protease from Bacillus subtilis at 50℃; for 120h; Enzymatic reaction; regioselective reaction;

divinyl adipate (4074-90-2) + troxerutin (7085-55-4) → troxerutin vinyl adipate (1218941-81-1)

Conditions	Yield
With pyridine at 55℃; for 96h; Enzymatic reaction;	60%
With pyridine; alkaline protease from Bacillus subtilis at 50℃; for 120h; Enzymatic reaction; regioselective reaction;

azelaic acid divinyl ester (10355-49-4) + troxerutin (7085-55-4) → troxerutin vinyl azelate (1218941-82-2)

Conditions	Yield
With pyridine at 60℃; for 148h; Enzymatic reaction;	57%
With pyridine; alkaline protease from Bacillus subtilis at 50℃; for 120h; Enzymatic reaction; regioselective reaction;

acetic anhydride (108-24-7) + troxerutin (7085-55-4) → 3',4',7-tri-O-(2-acetoxyethoxy)quercetin (1429915-87-6)

Conditions	Yield
With sulfuric acid at 20℃; for 7h;	57%

divinyl sebacate (10355-50-7) + troxerutin (7085-55-4) → troxerutin vinyl sebacate (1218941-83-3)

Conditions	Yield
With pyridine at 60℃; for 120h;	55%
With pyridine; alkaline protease from Bacillus subtilis at 50℃; for 120h; Enzymatic reaction; regioselective reaction;

dodecandioic acid divinyl ester + troxerutin (7085-55-4) → troxerutin vinyl dodecandiate

Conditions	Yield
With pyridine at 50℃; for 96h;	51%

troxerutin (7085-55-4) → 3,5-Dihydroxy-3',4',7-tri-(β-hydroxyethoxy)flavon (23077-88-5)

Conditions	Yield
With hydrogenchloride In methanol Heating; Yield given;

divinyl tridecanedioate (15423-11-7) + troxerutin (7085-55-4) → C48H66O22 (1218941-84-4)

Conditions	Yield
With pyridine; alkaline protease from Bacillus subtilis at 50℃; for 120h; Enzymatic reaction; regioselective reaction;

divinyl butanedioate (13416-90-5) + troxerutin (7085-55-4) → C39H48O22 (1218941-79-7)

Conditions	Yield
With pyridine; alkaline protease from Bacillus subtilis at 50℃; for 120h; Enzymatic reaction; regioselective reaction;

dodecandioic acid divinyl ester + troxerutin (7085-55-4) → C54H71NO21

Conditions	Yield
Multi-step reaction with 2 steps 1: pyridine / 96 h / 50 °C 2: 1-octyl-3-methyl-3H-imidazolium nitrate / 48 h / 60 °C View Scheme

divinyl adipate (4074-90-2) + troxerutin (7085-55-4) → C50H63NO23

Conditions	Yield
Multi-step reaction with 2 steps 1: pyridine / 96 h / 55 °C / Enzymatic reaction 2: N-octylpyridinium tetrafluoroborate / 24 h / 60 °C View Scheme

divinyl sebacate (10355-50-7) + troxerutin (7085-55-4) → C54H71NO23

Conditions	Yield
Multi-step reaction with 2 steps 1: pyridine / 120 h / 60 °C 2: n-butylpyridinium chloride / 36 h / 70 °C View Scheme

troxerutin (7085-55-4) → C46H57NO21

Conditions	Yield
Multi-step reaction with 2 steps 1: pyridine / 72 h / 50 °C / Enzymatic reaction 2: 1-octyl-3-methylimidazolium tetrafluoroborate / 24 h / 50 °C View Scheme

troxerutin (7085-55-4) → C46H56FNO21

Conditions	Yield
Multi-step reaction with 2 steps 1: pyridine / 72 h / 50 °C / Enzymatic reaction 2: 1-octyl-3-methyl-imidazolium bromide / 24 h / 50 °C View Scheme

troxerutin (7085-55-4) → C45H55NO21

Conditions	Yield
Multi-step reaction with 2 steps 1: pyridine / 72 h / 50 °C / Enzymatic reaction 2: 1-hexyl-3-methylimidazolium tetrafluoroborate / 24 h / 50 °C View Scheme

troxerutin (7085-55-4) → C47H57NO21

Conditions	Yield
Multi-step reaction with 2 steps 1: pyridine / 72 h / 50 °C / Enzymatic reaction 2: 1-octyl-3-methyl-imidazolium bromide / 24 h / 60 °C View Scheme

troxerutin (7085-55-4) → C48H59NO23

Conditions	Yield
Multi-step reaction with 2 steps 1: pyridine / 72 h / 50 °C / Enzymatic reaction 2: 1-octylpyridinium bis[(trifluoromethyl)sulfonyl]amide / 30 h / 60 °C View Scheme

troxerutin (7085-55-4) → C52H67NO22

Conditions	Yield
Multi-step reaction with 2 steps 1: pyridine / 148 h / 60 °C / Enzymatic reaction 2: N-n-hexylpyridinium tetrafluoroborate / 36 h / 60 °C View Scheme

Upstream product

• 153-18-4 rutin 
• 540-51-2 2-bromoethanol 
• 75-21-8 oxirane 
• 23869-24-1 7-mono-O-(β-hydroxyetyl)rutoside 
• 107-07-3 2-chloro-ethanol 

Downstream Products

• 1218941-84-4 C₄₈H₆₆O₂₂ 
• 1218941-79-7 C₃₉H₄₈O₂₂ 
• 1218941-80-0 troxerutin vinyl glutarate 
• 1218941-81-1 troxerutin vinyl adipate 
• 1218941-83-3 troxerutin vinyl sebacate 
• 1218941-82-2 troxerutin vinyl azelate 
• 1429915-87-6 3',4',7-tri-O-(2-acetoxyethoxy)quercetin 
• 23077-88-5 3,5-Dihydroxy-3',4',7-tri-(β-hydroxyethoxy)flavon 

Relevant articles and documents

Troxerutin compound

The invention discloses a troxerutin compound prepared by using an advanced on-line process control technology. The troxerutin compound is measured by X-ray powder diffraction, and a X-ray powder diffraction pattern expressed by a 2 diffraction angle shows characteristic diffraction peaks at the 2 of 8.15+/-0.2 degrees, 9.24+/-0.2 degrees, 12.31+/-0.2 degrees, 17.10+/-0.2 degrees, 17.92+/-0.2 degrees, 18.73+/-0.2 degrees and 23.45+/-0.2 degrees. The compound has the characteristics of high purity, low impurity content, good fluidity and good stability.

Preparing method of 3',4',7'-troxerutin

The invention relates to a preparing method of 3',4',7'-troxerutin. The provided preparing method of 3',4',7'-troxerutin comprises the steps of mixing water and rutin at 10-30 DEG C, dropwise adding a catalyst potassium hydroxide solution under the condition of nitrogen protection stirring, slowly adding ethylene chlorohydrin, increasing the temperature to 60-70 DEG C, conducting a thermostatic reaction for 4-5 hours, and then adding potassium hydroxide to continue the reaction for 15-20 hours; the 3',4',7'-troxerutin is obtained after purification and refinement. The 3',4',7'-troxerutin prepared through the method is simple in production technology, and little oxidation hydrolysis by-product is generated, and the 3',4',7'-troxerutin is high in yield. By adopting water as a solution, purification solution formaldehyde can be recycled and utilized at the same time, thus the cost is sharply saved in large-scale production, meanwhile, the generation of waste materials is reduced, and economy and environmental friendliness of production is achieved.

Preparation method of high-content troxerutin

The invention discloses a preparation method of high-content troxerutin and belongs to the technical field of medicinal chemistry. According to the technical scheme, the preparation method of the high-content troxerutin comprises the specific steps that a coarse raw material product rutin is purified and refined to obtain high-content rutin higher than 99.0%; the high-content rutin reacts under the catalytic action of a catalyst natural polymer sodium alginate to prepare troxerutin; the troxerutin is purified to obtain the high-content troxerutin with the content higher than 98.0%. The preparation method refines the raw material rutin, water is adopted as a solvent in the refining process, the method is green and environmentally friendly, and the purity of the obtained rutin can be up to 99.0% or above. In addition, during troxerutin preparation, the natural polymer sodium alginate and appropriate reaction condition are adopted to make reaction reach the best level, and the high-content troxerutin crude drug with content higher than 98.0% can be obtained only by simply purifying the obtained product.