Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Homogeneous oxidation synthesis method of isosulfan blue and the isosulfan blue synthesized by the method

A synthesis method and homogeneous oxidation technology, applied in the field of isothiocyanate, can solve the problems of low purity of reaction solution, large environmental pollution, difficulty in product purification and the like

Inactive Publication Date: 2019-05-07
JIANGSU JIMING PHARMA TECH
View PDF10 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0013] But it has some relatively big disadvantages: 1. Ammonium dichromate has a relatively large impact on the environment; 2. The patent does not mention the purification and purity of the product; 3. A large amount of deethylated impurities are difficult to purify during the oxidation process
However, potassium permanganate or chromium trioxide are prone to excessive oxidation impurities, and the purity of the reaction solution is lower than 80%, which causes great difficulties in the purification of the product.
[0015] In summary, the existing technology for preparing isosulfur blue has obvious disadvantages
US 7,662,992, US 8,969,616, US 9,353,050, and US 2016 / 0221936 adopt heterogeneous synthesis methods, using silver oxide as the oxidant, but silver oxide is relatively expensive, and silver is a heavy metal that has a relatively large impact on the environment; US patent US20060224003 and Indian patent IN -2012CH03509 uses dichromate or manganese dioxide as an oxidant, which is prone to excessive oxidation impurities and has a relatively large impact on the environment; US Patent US4330476 uses chloranil / NO / NO 2 / The air system is used as an oxidant, and the gas-liquid two-phase reaction uses nitrogen monoxide and nitrogen dioxide, which is relatively harmful to the environment

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Homogeneous oxidation synthesis method of isosulfan blue and the isosulfan blue synthesized by the method
  • Homogeneous oxidation synthesis method of isosulfan blue and the isosulfan blue synthesized by the method
  • Homogeneous oxidation synthesis method of isosulfan blue and the isosulfan blue synthesized by the method

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0039] Add acid blue (10.0g, 18.0mmol), ceric ammonium nitrate (30.0g, 54.0mmol), water (400ml), concentrated nitric acid (2.2g, 22.5mmol), react at -10~10℃ for 3 hours, the central control shows that the raw material is less than 0.5%, and the deethylated impurity is 1.0%; adjust the pH to 7~10 with 20% sodium carbonate solution, filter, and depressurize the filtrate Concentrate; add 100ml of methanol to the residue, filter to remove inorganic salts; concentrate the filtrate under reduced pressure, dissolve the residue in 15ml of water, adjust the pH to acidic with acid, stir for 30min, and filter to obtain isothiocyanic acid; isothiocyanic acid is dissolved in 25ml of water and 20% sodium carbonate solution to adjust the pH to 7-10; add acetone (500ml) to the obtained solution, stir for 1h; filter, wash the filter cake with acetone (150ml) twice, and dry under vacuum at 40°C for 8h to obtain 4.1g of isosulfur blue , purity 99.6%, deethylation impurity 0.12%, unknown single i...

Embodiment 2

[0044] Add acid blue (10.0g, 18.0mmol), ceric ammonium nitrate (30.0g, 54.0mmol), water (400ml), sulfuric acid ( 2.2g, 22.5mmol), react at -10~10°C for 8 hours, the central control shows that the raw material is less than 2.0%, and the deethylated impurity is 0.3%; 20% sodium carbonate solution is adjusted to pH 7~10, filtered, and the filtrate is concentrated under reduced pressure; Add 100ml of methanol to the residue, filter to remove inorganic salts, and concentrate the filtrate under reduced pressure; dissolve the residue in 15ml of water, adjust the pH to acidic with acid, stir for 30min, and filter to obtain isothiocyanic acid; dissolve isothiocyanic acid in 25ml of water , 20% sodium carbonate solution to adjust the pH to 7-10; the resulting solution was added with acetone (500ml), stirred for 1h; filtered, the filter cake was washed twice with acetone (150ml), and vacuum-dried at 40°C for 8h to obtain 3.9g of isosulfur blue, the purity 99.7%, deethylation impurity 0.0...

Embodiment 3

[0046]Add acid blue (10.0g, 18.0mmol), ammonium cerium sulfate (32.0g, 54.0mmol), water (400ml), sulfuric acid ( 2.2g, 22.5mmol), react at -10~10°C for 8 hours, the central control shows that the raw material is less than 0.5%, and the deethylated impurity is 0.3%; 20% sodium carbonate solution is adjusted to pH 7~10, filtered, and the filtrate is concentrated under reduced pressure; Add 100ml of methanol to the residue, filter to remove inorganic salts, and concentrate the filtrate under reduced pressure; dissolve the residue in 15ml of water, adjust the pH to acidic with acid, stir for 30min, and filter to obtain isothiocyanic acid; dissolve isothiocyanic acid in 25ml of water , 20% sodium carbonate solution to adjust the pH to 7-10; the resulting solution was added with acetone (500ml), stirred for 1h; filtered, the filter cake was washed twice with acetone (150ml), and vacuum-dried at 40°C for 8h to obtain 3.9g of isosulfur blue, the purity 99.7%, deethylation impurity 0.0...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention provides a homogeneous oxidation synthesis method of isosulfan blue. The homogeneous oxidation synthesis method comprises the steps that when acid blue is used as a raw material, tetravalent cerium salt is used as an oxidizing agent, water or a mixed solvent of water and other solvents is used as a solvent, the acid blue is oxidized in the presence of acid, thus preparing the isosulfan blue; The method is carried out at the temperature of -10 to10 DEG C, the deethylation impurity rate is less than 0.15%, and the use of expensive oxidant silver oxide and dangerous reagents permanganate and dichromate is avoided, so that the method is greener and more environment-friendly.

Description

technical field [0001] The invention belongs to the technical field of medicine synthesis, and in particular relates to a homogeneous oxidation synthesis method of isosulfur blue and the synthesized isosulfur blue. Background technique [0002] Isosulfur blue is an important cancer diagnostic reagent, its structural formula is: [0003] [0004] The compound is mainly used as a contrast reagent for depicting lymphatic vessels, especially as a diagnostic reagent for cancer. [0005] Isosulfur blue, also known as Purified Patent Blue Violet, is a triarylmethane dye. Isothiranine injection (1%) is commonly used in a mapping procedure called lymph node labeling, an adjunct to lymphography that allows visualization of the lymphatic system by mapping the area of ​​injection, which has been used with high frequency in breast cancer Patient's lymph node marker localization. At the same time, the use of isosulfur blue as a guide for surgical removal of cancer cells is growing b...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
IPC IPC(8): C07C303/32C07C309/46
Inventor 陈剑戈
Owner JIANGSU JIMING PHARMA TECH
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com