Imepitoin Synthesis Process Yield and Purity
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Solution Overview
Problem
Existing methods for synthesizing imepitoin are inefficient, with low yields and high costs due to the use of Soxhlet equipment, extraction with hot acetone, and crystallization in large solvent volumes, making them unsuitable for industrial-scale production.
Innovation Solution
A cost-effective and scalable process for preparing imepitoin and its intermediates in high yield and purity without chromatographic purification or crystallization, utilizing alkylation, Urech-type hydantoin synthesis, and acid-catalyzed reversible reactions under controlled conditions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If conventional methods using Soxhlet equipment and extraction with hot acetone are used, then purification can be achieved, but the process becomes complex and unsuitable for industrial scale
Solution Approach 1:
The patent extracts and eliminates the need for complex purification steps (Soxhlet extraction, hot acetone treatment, crystallization) by using a simplified filtration method. The improved process achieves purification through selective filtration of the reaction mixture, removing impurities without requiring complex equipment or multiple treatment steps, thus resolving the contradiction between purification quality and process complexity
Solution Approach 2:
The patent replaces expensive and complex purification equipment (Soxhlet extractor, distillation apparatus, crystallization equipment) with simple, inexpensive filtration equipment. This allows industrial-scale production while maintaining product purity, eliminating the need for specialized equipment and reducing operational costs
2Manufacturing precision
If extraction with hot acetone and crystallization in large solvent volumes are used, then impurities can be removed, but operational costs increase and productivity decreases
Solution Approach 1:
The patent changes the purification parameters from using large volumes of hot acetone and crystallization conditions to a filtration process at moderate temperatures. This parameter change reduces solvent consumption, lowers operational costs, and maintains high productivity by eliminating time-consuming extraction and crystallization steps while achieving the required product purity
Solution Approach 2:
The patent extracts and eliminates the need for costly and time-consuming purification operations (hot acetone extraction, crystallization) by implementing a direct filtration method. This removes unnecessary process steps that reduce productivity and increase operational costs, while still achieving effective impurity removal
3Productivity
If morpholine hydrochloride is used as catalyst, then the reaction can proceed, but the cost increases due to the chemical being expensive
Solution Approach 1:
The patent replaces expensive morpholine hydrochloride catalyst with cheaper alternative catalysts or catalytic conditions. This substitution maintains reaction efficiency and productivity while significantly reducing the cost of reagents, making the process economically viable for industrial production
Solution Approach 2:
The patent changes the catalytic system from morpholine hydrochloride to alternative catalysts or reaction conditions. This parameter change in the catalytic system maintains reaction efficiency while using more cost-effective materials, resolving the contradiction between productivity and reagent cost
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 process achieves an overall yield of 68% with imepitoin purity exceeding 99.5%, eliminating the need for crystallization and reducing operational costs, making it suitable for industrial application.
Implementation Method 1
reaction of 4-chloroaniline with a base selected from potassium carbonate, sodium carbonate, potassium acetate or sodium acetate and an additive selected from potassium or sodium iodide, in a solvent selected from acetonitrile, tetrahydrofuran, dimethylformamide, acetone, or an alcohol, at room temperature, for 15-60 min., addition of a compound of formula (II) wherein X is a halogen or a leaving group, and heating at a reaction temperature between 50-80 °C, for 3-24 h
Implementation Method 2
obtention of a compound of formula (III) by an Urech-type hydantoin synthesis which comprises the following steps: b1) reaction of compound of formula (I) with potassium or sodium cyanate, in a solvent selected from acetic acid or hydrochloric acid, at a reaction temperature between 100-120 °C, for 4-24 h., b2) cooling at room temperature, to precipitate compound (III), b3) isolation of compound (III) by filtration, washing with a solvent, and drying
Implementation Method 3
obtention of imepitoin by an acid-catalyzed reversible reaction which comprises the following steps: c1) reaction of morpholine as reactant and solvent, with ammonium chloride, at a reaction temperature between 110-140 °C, for 0.5-1.5 h, c2) addition of the compound (III) to the mixture of morpholine and ammonium chloride at a temperature between 110-140 °C, c3) heating the mixture to a temperature between 110-140 °C
Implementation Method 4
c4) distillation of morpholine, drying with a desiccant agent, and return of the dried morpholine to the reaction mixture that it is maintained at a temperature between 110-140 °C, for 6-12 h
Implementation Method 5
c7) cooling the reaction mixture to a temperature between 100-120 °C, c8) slow addition of toluene and morpholine to the reaction mixture at a temperature between 100-120 °C, c9) filtration of the solid, washing with a solvent, preferably water, and drying under vacuum at a temperature between 40-60 °C, preferably 50 °C
Data Source
AI summary
The present invention describes an improved process for the preparation of imepitoin by means of an efficient preparation of its intermediate 1-(4-chlorophenyl)imidazolidine-2,4-dione followed by condensation with morpholine in the presence of ammonium chloride. Particularly, the invention relates to a process which provides imepitoin in high yield by removing the water generated in the reaction using a continuous process to distil, dry and recirculate the dried morpholine back to the reactor. More particularly, the invention relates to a process that provides imepitoin with very high purity by a simple washing with toluene and water. Still more particularly, the invention relates to a cost-effective process that is scalable for industrial application.