Prothioconazole Intermediate One-Pot Synthesis Without Isolation
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Solution Overview
Problem
The existing methods for preparing prothioconazole intermediates, such as 2-(1-chlorocycloprop-1-yl)-3-(2-chlorophenyl)-2-hydroxypropyl-1-hydrazine and 2-[2-(1-chlorocyclopropyl)-3-(2-chlorophenyl)-2-hydroxypropyl]-1,2,4-triazolidine-3-thione, face challenges related to the instability of the hydrazine derivative and the need for solvent evaporation, which poses safety concerns and limits industrial application.
Innovation Solution
A one-pot process using water-insoluble solvents like toluene for the reaction of oxirane with hydrazine, followed by reaction with formaldehyde and thiocyanate, avoids the isolation of the hydrazine intermediate and simplifies the process by allowing direct use of the crude product, thereby enhancing stability and yield.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If the hydrazine derivative is isolated and purified through solvent evaporation, then the purity of the intermediate is improved, but safety risks increase and process complexity increases
Solution Approach 1:
The patent combines the hydrazine derivative synthesis step with the subsequent triazolidine formation step into a one-pot process. The crude hydrazine derivative generated in situ reacts directly with isothiocyanate without isolation, eliminating the need for solvent evaporation and intermediate handling, thus resolving the safety concerns while maintaining product purity
Solution Approach 2:
The patent extracts the problematic isolation and purification steps from the overall synthesis process. By removing the intermediate isolation step that requires solvent evaporation, the process eliminates safety risks associated with handling and concentrating hydrazine derivatives while still achieving the desired purity in the final product
2Manufacturing precision
If multiple isolation and purification steps are performed, then the purity of intermediates is improved, but the process complexity and time consumption increase
Solution Approach 1:
The patent merges two separate synthetic steps (hydrazine derivative formation and triazolidine formation) into a single one-pot operation. The reaction sequence proceeds without isolating the intermediate, reducing the number of unit operations, equipment requirements, and process complexity while maintaining acceptable purity levels through direct transformation
3Quantity of substance
If solvent evaporation is performed to concentrate the hydrazine derivative, then the concentration of the intermediate is improved, but energy consumption increases and safety concerns arise
Solution Approach 1:
The patent removes the solvent evaporation step from the process by designing a one-pot synthesis where the crude hydrazine derivative reacts directly in the reaction medium. This eliminates the energy-intensive concentration step while still achieving the desired product formation and purity
Solution Approach 2:
The reaction system uses the solvent present during hydrazine derivative formation as the reaction medium for the subsequent triazolidine formation. The solvent serves dual purposes: as the medium for generating the intermediate and as the medium for its direct transformation, eliminating the need for separate concentration and re-dissolution steps
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 approach achieves high yield and purity of the thiono derivative without the need for intermediate isolation, reducing safety risks and simplifying industrial processes.
Implementation Method 1
a two-phase reaction between an oxirane of Formula (II) and hydrazine in the presence of water and the first solvent or mixture of solvents
Implementation Method 2
reacting the mixture comprising the neutral form of a hydrazine derivative of Formula (I) and the first solvent or mixture of solvents resulting from step (i) with formaldehyde and a thiocyanate
Data Source
AI summary
The present invention is directed to a process for the preparation of a hydrazine derivative by reaction of the corresponding oxirane with hydrazine, that uses as only solvent toluene. The process provides excellent yields and purities and allows to proceed without purification in a one-pot scheme. Toluene additionally reduces the excess of hydrazine needed to complete the reaction, significantly reducing the waste treatment costs and even allows the hydrazine to be recycled into the reaction.