Meldonium Production via CO2 Saturation and Calcium Hydroxide
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Solution Overview
Problem
Current methods for large-scale production of Meldonium are inefficient due to high production costs, instability of strongly basic ion exchangers, high maintenance costs of electrodialysis equipment, and difficulties in separating double salts, leading to expensive and complex processes.
Innovation Solution
A process involving the use of carbon dioxide or sulphur dioxide to separate double salts of 3-(2,2,2-trimethylhydrazinium)propionate, allowing for the production of high-purity Meldonium using conventional equipment and inexpensive reagents, such as sodium or potassium hydroxide, and solvents like ethanol or propanol-2, facilitating scalable and cost-effective manufacturing.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If strongly basic ion exchange resin is used for hydrolysis and deionisation, then the process can be simplified, but the resin undergoes decomposition and oxidation, requiring large quantities of solvents, acids and bases for regeneration, resulting in high production costs
Solution Approach 1:
The patent replaces expensive and unstable strongly basic ion exchange resins with a cheaper, more stable approach using calcium hydroxide for hydrolysis followed by acidification with gaseous hydrogen chloride. This eliminates the need for resin regeneration with costly acids and bases, reducing both material costs and process complexity while maintaining product purity.
Solution Approach 2:
The patent changes the chemical parameters of the hydrolysis process by using calcium hydroxide instead of strongly basic ion exchange resins, and by adjusting the pH through acidification with gaseous hydrogen chloride. This parameter change achieves complete deionisation and hydrolysis without the decomposition issues of the resin method.
2Reliability
If electrodialysis is used for deionisation, then the process avoids resin decomposition, but highly specialised equipment with corrosion-resistant materials is required, along with constant parameter adjustment due to membrane pollution, resulting in high maintenance costs and complicated scaling-up
Solution Approach 1:
The patent replaces complex and expensive electrodialysis equipment with simple conventional chemical processing equipment. The method uses calcium hydroxide for hydrolysis and gaseous hydrogen chloride for acidification, which can be processed in standard reactors and separation equipment, eliminating the need for specialised corrosion-resistant materials and complex membrane systems.
Solution Approach 2:
The patent substitutes the mechanical/electrical system of electrodialysis with a chemical system using calcium hydroxide and gaseous hydrogen chloride. This chemical approach achieves the same deionisation and hydrolysis functions without requiring electrical fields, specialized membranes, or complex equipment, simplifying the overall process.
3Ease of manufacture
If conventional alkaline hydrolysis is used, then the process is simple, but separation of 3-(2,2,2-trimethylhydrazinium)propionate dihydrate from inorganic salts is difficult due to double salt formation
Solution Approach 1:
The patent changes the chemical parameters by using calcium hydroxide instead of strong bases, and by introducing acidification with gaseous hydrogen chloride at a specific pH range (2-4). This parameter change prevents double salt formation between the product and inorganic salts, enabling complete separation through filtration while maintaining high product purity.
Solution Approach 2:
The patent introduces gaseous hydrogen chloride as an intermediary substance that facilitates separation. The acidification step with HCl forms soluble calcium chloride and prevents double salt formation, allowing the 3-(2,2,2-trimethylhydrazinium)propionate dihydrate to be separated from inorganic salts through filtration, thus achieving high purity without complex separation processes.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
This method enables the production of high-quality Meldonium with purity greater than 99.5% at lower costs, using common chemical technology and equipment, thus addressing the inefficiencies of previous methods and enabling large-scale, affordable production.
Implementation Method 1
double salts of 3-(2,2,2-trimethylhydrazinium)propionate with the inorganic salts formed in the hydrolysis process can thus be separated into their constituents, if the reaction solution in alcohol during precipitation of inorganic salts had been saturated with gaseous acid anhydride, namely carbon dioxide or sulphur dioxide
Implementation Method 2
The mixture was then cooled to 2-4 °C, and saturated with CO2 to pH 8.1-8.5. The precipitate thus formed was filtered off
Implementation Method 3
Crystallization from ethanol or propanol-2 or another appropriate solvent gave 3-(2,2,2-trimethylhydrazinium)propionate dihydrate with m.p. 85-87 °C (purity >99,5%)
Implementation Method 4
starting with 1,1-dimethylhydrazine and esters of acrylic acid 3-(2,2-dimethylhydrazino)propionic acid esters are prepared, which is alkylated by an appropriate alkylating agent
Data Source
AI summary
A method for producing 3-(2,2,2-trimethylhydrazinium)propionate dihydrate by saponification of salts of 3-(2,2,2-trimethylhydrazinium)propionate esters with subsequent purification step using saturation with carbon dioxide or sulphur dioxide in alcoholic solution.