5-Fluorouracil Refining via Solvent Crystallization
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current methods for synthesizing 5-fluorouracil often result in products with high impurity levels, making it difficult to meet stringent quality standards, and existing refining methods are not effective in completely removing impurities like 5-methoxyuracil and dihydropyrimidine-2,4,5(3H)-trione, which can lead to unpredictable effects and toxicity in pharmaceutical applications.
Innovation Solution
A refining method involving heating and dissolving 5-fluorouracil in an organic solvent, followed by cooling and crystallization, and subsequent filtration and drying, which effectively reduces impurity levels to below 0.05%, achieving a purity of over 99.9% and meeting or exceeding international pharmacopoeia standards.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If conventional synthesis methods (condensation cyclization method) are used to prepare 5-fluorouracil, then the production cost is low and raw materials are easily available, but the product contains high levels of impurities (individual impurity >0.5%, total impurities >0.75%) that are difficult to remove
Solution Approach 1:
The patent applies parameter changes by adjusting the solvent system (using dimethyl sulfoxide as solvent), temperature parameters (heating to 80-100°C for dissolution, then cooling to 5-25°C for crystallization), and pH parameters (adjusting to pH 2-4 with hydrochloric acid) to optimize the crystallization process and achieve high purity product
Solution Approach 2:
The patent utilizes phase transitions through the dissolution-crystallization process: the crude 5-fluorouracil is dissolved in hot dimethyl sulfoxide to form a saturated solution, then cooled to induce crystallization of pure 5-fluorouracil while impurities remain in the mother liquor or form separate crystals, achieving separation and purification
2Manufacturing precision
If multiple purification steps are applied to remove impurities, then the product purity increases, but the production cost increases and the process becomes more complex
Solution Approach 1:
The patent segments the purification process into distinct sequential steps: dissolution in dimethyl sulfoxide, filtration to remove insoluble impurities, pH adjustment, and controlled crystallization. This segmentation allows each step to target specific impurity types, achieving high purity through simple, modular operations rather than complex continuous processing
Solution Approach 2:
The patent uses dimethyl sulfoxide as an intermediary solvent that selectively dissolves 5-fluorouracil while leaving many impurities undissolved or differently soluble. This intermediary solvent enables efficient separation through simple filtration and crystallization, avoiding the need for complex chromatographic or multiple extraction procedures
3Manufacturing precision
If exhaustive purification is performed to meet strict pharmacopoeia standards, then the product quality improves, but the yield decreases and production time increases
Solution Approach 1:
The patent applies partial action by performing a single crystallization cycle that achieves sufficient purification (purity >99.5%) without repeating the process multiple times. The controlled crystallization conditions (temperature, solvent ratio, pH) are optimized to maximize purity achievement in one step, maintaining high yield while meeting pharmacopoeia standards
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
The method achieves high-purity 5-fluorouracil with a yield of over 70%, completely removing impurities to levels below 0.01%, surpassing existing standards and ensuring product safety and efficacy.
Implementation Method 1
heating and dissolving 5-fluorouracil in an organic solvent
Implementation Method 2
dissolving 5-fluorouracil in an organic solvent
Implementation Method 3
cooling and crystallization
Implementation Method 4
cooling and crystallization
Implementation Method 5
subsequent filtration and drying
Implementation Method 6
subsequent filtration and drying
Data Source
AI summary
Disclosed is a method for refining 5-fluorouracil, comprising the following steps: dissolving 5-fluorouracil in an organic solvent, preferably DMSO, heating and stirring until dissolved; naturally cooling the filtrate until a crystal is precipitated; filtering, washing a filter cake using a polar solvent, and draining and drying under reduced pressure. By using the new refining method, the content of impurities in 5-fluorouracil may be reduced to less than 0.01%, the product purity is more than 99.98%, and the refining yield is higher than 70%. In addition, the refining method of the present invention has a simple process, convenient operation, low production costs, high product purity, a stable process, and is suitable for industrial production.