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

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

Uses

Used in Pharmaceutical Industry:
Benfotiamine is used as a Vitamin B1 analog for its potential therapeutic effects on various health conditions. As a synthetic S-acyl derivative of Thiamine, it offers enhanced bioavailability compared to traditional thiamine, making it a valuable compound in the development of pharmaceutical products.
Used in Research Applications:
In research settings, Benfotiamine is used to study its effects on ischemia and reperfusion in skeletal muscles of rats. This helps in understanding the compound's potential applications in treating conditions related to blood flow and muscle health.
Used in Nutritional Supplements:
Due to its enhanced bioavailability and status as a Vitamin B1 analog, Benfotiamine is also used in the development of nutritional supplements aimed at supporting overall health and well-being.

Originator

Biotamin,Sankyo

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

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

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

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.

Benfotiamine related substance, preparation method, application and detection method

The invention discloses a benfotiamine related substance, a preparation method, application and a detection method. The benfotiamine related substance is a compound C, and the structure of the compound C is shown in the description. The preparation method provided by the invention is simple, and the compound C with the purity meeting the requirement can be prepared. The invention further provides the detection method of the benfotiamine related substance. The high-purity compound C 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.

A method for the production of thiamine benzene phosphorus

The invention relates to a production method of benfotiamine. The production method comprises the following steps: by taking polyphosphoric acid as a phosphoric acid esterification reagent, reacting with vitamin B1, performing hydrolysis at high temperature after the end of reaction, extracting phosphoric acid of a system by using a mixed solution of trioctylamine and an organic solvent after the end of hydrolysis, and then directly adding the organic solvent to precipitate a phosphate monoester crude product of vitamin B1. The obtained crude product is not purified, water is directly used for pulping, the pH value is adjusted by using liquid alkali, the reaction is performed with benzoyl chloride, and solids are filtered. The pH value of filtrate is adjusted to 3.5-4.0, the solids are precipitated, and separation and drying are performed to obtain the white solids, namely benfotiamine. The yield of benfotiamine produced by using the process is high, the product purity is high, the operation is simple, and the production method is environment-friendly and suitable for industrial production.

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.

Glycation Cross-link Breakers to Increase Resistance to Enzymatic Degradation

The present invention relates to a method to treat a grafts, implant, scaffold, and constructs, including allografts, xenografts, autografts, and prosthetics comprising collagen, with an inhibitor of collagen cross-links and/or advanced glycation endproducts (AGE), in order to alleviate the mechanical weakness induced by the cross-links The invention also provides for kits for use in the operating theater during autograft, allograft or xenograft procedures, or for preparing allograft, xenografts or prosthetics that have not been already treated prior to packaging. The kit comprises a first agent or agents that inhibit collagen cross-links and/or advanced glycation endproducts, instructions for use, optionally a wash or rinse agent, and a device for containing the graft and first agent.