22457-89-2

Basic information

• Product Name: Benfotiamine
• Synonyms: benzoylthiamineo-monophosphate;berdi;betivina;bietamine;biotamin;btmp;neurostop;nitanevril
• CAS NO: 22457-89-2
• Molecular Formula: C₁₉H₂₃N₄O₆PS
• Molecular Weight: 466.45
• EINECS: 245-013-4
• Product Categories: Aromatics;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals;Phosphorylating and Phosphitylating Agents;Sulfur & Selenium Compounds;Pharmaceutical intermediate;BIOTAMIN;API
• Mol File: 22457-89-2.mol
• Article Data: 6

Chemical Properties

• Melting Point: 165 C
• Boiling Point: 745.1 °C at 760 mmHg
• Flash Point: 404.4 °C
• Appearance: White crystalline powder
• Density: 1.444 g/cm³
• Vapor Pressure: 2.55E-23mmHg at 25°C
• Refractive Index: 1.645
• Storage Temp.: 2-8°C
• Solubility: Aqueous Acid (Slightly), DMSO (Heated, Sonicated)
• PKA: 1.84±0.10(Predicted)
• Merck: 14,1041
• CAS DataBase Reference: Benfotiamine(CAS DataBase Reference)
• NIST Chemistry Reference: Benfotiamine(22457-89-2)
• EPA Substance Registry System: Benfotiamine(22457-89-2)

Safety Data

• Hazard Codes: Xn
• Statements: 20/21/22-36/37/38
• Safety Statements: 26-36
• WGK Germany: 2
• RTECS: DH6910000
• Hazardous Substances Data: 22457-89-2(Hazardous Substances Data)

Usage

Chemical Properties

crystals

Originator

Biotamin,Sankyo

Uses

Different sources of media describe the Uses of 22457-89-2 differently. You can refer to the following data:
1. S-Benzoylthiamine O-monophosphate has been used to determine its effect on ischemia and reperfusion in skeletal muscles of rat.
2. Vitamin B1 analog. Synthetic S-acyl derivative of Thiamine (T344185).

Definition

ChEBI: A thioester that is a synthetic analogue of thiamine obtained by acylative cleavage of the thiazole ring and O-phospohorylation.

Manufacturing Process

28.6 g 84% phosphoric acid was heated to temperature about 270°C. After cooling to 100°C 4 g thiamine hydrochloride (vitamin B1 hydrochloride) was added and left at temperature 100°C before an isolation of HCl was ended. After adding of an ice water and acetone, phosphate ester of vitamin B1 was fallen. The precipitate was dissolved in 17 ml 1 N HCl and stood at ambient temperature 7 days for a hydrolysis. Then a solution was with acetone diluted and the mixture was cooled, whereupon vitamin B1 monophosphate hydrochloride was isolated. The solution of 4.3 parts vitamin B1 monophosphate hydrochloride in 16 parts of water was diluted with 11 parts 15% NaOH, 2.1 parts benzoyl chloride was dropwise added with stirring and cooling. The obtained mixture was neutralized, evaporated in vacuum, acidified with concentrated HCl to pH 3.5- 4, whereupon a crude S-derivative of vitamin B1 monophosphate ester was precipitated. The product was suspended in water, was bringing with NaOH to pH 7 and was acidified to pH 4. 3.4 g refined S-benzoylthiamine Omonophosphate was prepared; MP: 165°C (with decomposition).

Therapeutic Function

Analgesic

General Description

S-Benzoylthiamine O-monophosphate (Benfotiamine) is an amphiphilic S-acyl thiamine derivative. It is a lipid-soluble vitamin. Benfotiamine?contains a thiazole ring. Benfotiamine has a greater bioavailability than thiamine.

Biochem/physiol Actions

S-Benzoylthiamine O-monophosphate (Benfotiamine) is a therapeutic agent. It helps in the prevention of diabetic complications such as, retinopathy, neuropathy and nephropathy. Benfotiamine inhibits the synthesis of glycation end products (AGEs) in diabetes. Benfotiamine is considered as a nutraceutical product for the prevention of diabetic neuropathy.

InChI:InChI=1/C19H23N4O6PS/c1-13(23(12-24)11-16-10-21-14(2)22-18(16)20)17(8-9-29-30(26,27)28)31-19(25)15-6-4-3-5-7-15/h3-7,10,12H,8-9,11H2,1-2H3,(H2,20,21,22)(H2,26,27,28)/b17-13+

Upstream product

• 532-40-1 thiamine monophosphate chloride 
• 98-88-4 benzoyl chloride 
• 59-43-8 vitamin B₁ 
• 10023-48-0 2-[3-[(4-amino-2-methylpyrimidin-5-yl)methyl]-4-methyl-1,3-thiazol-3-ium-5-yl]ethyl dihydrogen phosphate 
• 495-23-8 2-[3-[(4-amino-2-methylpyrimidin-5-yl)methyl]-4-methyl-1,3-thiazol-3-ium-5-yl]ethyl hydrogen phosphate 
• 67-03-8 Thiamine hydrochloride 

Relevant articles and documents

Benfotiamine related substance as well as preparation method, application and detection method thereof

The invention discloses a benfotiamine related substance as well as a preparation method, application and a detection method thereof. The benfotiamine related substance is a compound H, and the structure of the compound H is shown in the description. The preparation method provided by the invention is simple, and the compound H with the purity meeting the requirement can be prepared. The invention also provides a detection method of the benfotiamine related substance. The high-purity compound H can be used as a benfotiamine reference substance or standard substance, and has a good application prospect.

A Thiamin benzene phosphorus compound and its preparation and its pharmaceutical compositions containing the compounds

The invention relates to a benfotiamine compound, a preparation method and a pharmaceutical composition containing the benfotiamine compound, and belongs to the technical field of medicines. The compound has a chemical structural formula shown as (img file='DDA0000454523390000011.TIF' wi='1320' he='570' /); and a X-ray diffraction pattern of the benfotiamine compound is as shown in figure 1. The preparation method comprises the following steps of: adding crude benfotiamine and purified water to a reaction flask; dropping proper amount of alkaline solution; heating to 60 to 90 DEG C, wherein the temperature of 70 to 80 DEG C is better; dropping dilute acid to regulate pH (Power of Hydrogen) to be 3.5 to 4.0; adding a mixed solvent of ethanol, dimethylformamide and chloroform; controlling the temperature to be 60 to 90 DEG C, wherein the temperature of 70 to 80 DEG C is better; growing the grain; performing suction filtration; cleaning the gain with purified water and acetone in sequence; performing vacuum drying to obtain the finished product of benfotiamine. The benfotiamine is a novel crystal compound which shows an obviously improved solubility; in addition, a benfotiamine tablet prepared from the benfotiamine compound is high in dissolubility.

BENFOTIAMINE POLYMORPHS, PREPARATION METHOD AND USE THEREOF

The present invention is directed to polymorphs of benfotiamine, their methods of preparation and the use thereof. The crystalline forms of benfotiamine are crystalline forms A, B, C, D and E, and can be distinguished by their respective patterns of X-ray powder diffraction, DSC, infrared spectroscopy, Raman spectroscopy, and preparation methods. The invention is also directed to the use of the above-mentioned polymorphs of benfotiamine for treating Vitamin B1 deficiency, metabolism-related disorders, psychiatric diseases and disorders, diabetes complications, or neurodegenerative diseases. The different crystalline forms of benfotiamine are obtained using different synthetic routes and solvent ratios. The crystalline polymorphs are substantially pure. The invention not only provides new crystalline forms of benfotiamine, but also solvates thereof, especially hydrates.