Case Study : Safe and Efficient Cyanation with Sravathi Flow Reactors
Background
Cyanation is a crucial process in the synthesis of many high-value chemical products. However, it is a particularly challenging reaction to manage, especially at commercial scale, due to the generation of highly toxic hydrogen cyanide (HCN) gas and the complex reaction conditions required.
The Problem: Overcoming Cyanation Process Challenges
A commercial scale cyanation reaction at a GMP facility presented a series of formidable hurdles that required a sophisticated and safe solution:
- Toxicity: The primary challenge was the generation of highly toxic HCN gas, posing a significant risk to personnel and the environment.
- Complex Reagent Addition: The process required the precise, sequential addition of four different reagents at irregular intervals, with low tolerance for any variability, which is difficult to control in a traditional batch reactor.
- High Exothermicity: The reaction is highly exothermic, necessitating effective heat management to prevent undesirable by-product formation.
- Low Temperature Requirements: The reaction needed to be maintained at a uniform and very low temperature (-30 °C) which is expensive and challenging in large-scale reactors.
- Immiscible Liquids: The reaction involved mixing of immiscible liquids, creating mass transfer limitations that reduce reaction rates.
- Residence Time Control: The process required short residence times for each step but with very low tolerance for variations, which is difficult to achieve consistently in a batch system.
The Solution:
To address these critical issues, a series of Sravathi Flow Reactors were implemented. The Sravathi Flow Reactors system was engineered to operate as a closed loop with inline quenching, eliminating the exposure risk to HCN. Its design, with reactor volumes measured in Liters as opposed to the kilolitres of a traditional batch reactor, drastically reduced the overall risk.
The Sravathi Flow Reactor’s multi-point addition capability was a key feature. Reagents could be added at different locations with precise control, ensuring the correct sequence with tight control of residence times enabling high selectivity. The system's design also allowed for:
- In-line Quenching: An in-line quenching step within the Sravathi Flow Reactor helped to prevent HCN gas from leaving the system.
- Exceptional Heat Removal: The Sravathi Flow Reactor's excellent heat removal capabilities were able to manage the high exothermicity of both the reaction and the quench step, even at the low operating temperature of -30 °C.
- Efficient Mixing: The reactor's design facilitated efficient mixing of immiscible liquids, improving mass transfer and reaction efficiency.
- Precise Residence Time Control: The system allowed for precise control of residence times, which was critical for achieving the desired selectivity.
Results & Achievements
The implementation of the Sravathi Flow Reactor system resulted in a highly successful process that surpassed the performance of previous batch-based methods. The flow reactor achieved >94% selectivity and 85% recovered yield, a significant improvement over the <60% yield obtained from the batch reaction.
This innovative process was successfully scaled up at a GMP facility, producing hundreds of kilograms of a high value cyanation product safely and efficiently. The reduced risk, improved yield, and high selectivity validated the superiority of the continuous flow approach for this challenging chemistry.
Conclusion
The cyanation case study with the Sravathi Flow Reactors is a testament to the power of continuous flow technology in overcoming complex and hazardous chemical synthesis challenges. The system demonstrated its ability to safely handle toxic materials, precisely control multiple process variables, and deliver exceptional performance at a commercial scale.