Hazardous Chemistry is usually defined as a process involving the use of highly energetic reactions and/or hazardous chemicals. Its use is well established for the commercial synthesis of APIs and intermediates and is offered by specialist CDMOs (Contract Development and Manufacturing Organizations).
Hazardous Chemistry is a key technology in the API process development toolbox, with potential to improve process cycle time, purity and yield, reducing both operational costs and environmental impact.
The use of Hazardous Chemistry can contribute to streamline API synthetic routes. The amount of impurities and by-product generated may also be limited, leading to cost-effective syntheses affording the targeted compound in high yields.
Hazardous Chemistry can also lead to design new chemical structures with interesting bio-active properties, offering the means to improve overall product quality (e.g. Tetrazoles).
No, Hazardous Chemistry is run in similar equipment to classical chemistry and in the case of Novasep sometimes the same. Manufacturing equipment at Novasep Leverkusen is especially designed for running azide chemistry in order that such reactions can be scaled up to 3m³, 6m³ or 12m³ batch size as required. Nevertheless, the safety investigations before transferring and scaling-up Hazardous Chemistry need to be more elaborate than for simple chemistry. But as these tests are performed in-house and within the Process Development department, they are not a great cost contributor.
In case of explosive substances handling, a special permit from the authorities is required. Novasep’s Leverkusen site has such a permit. Azide chemistry is common at Novasep and therefore all production equipment on our site is especially designed for handling sodium azide.
One of the major threats is the formation of highly explosive heavy metal azides. To avoid that, all equipment is set up free of copper and its alloys. This is certainly a significant barrier for starting azide chemistry from scratch. Safety precautions for other Hazardous Chemistry reactions may be implemented on a case-by-case basis.
Our Leverkusen site was originally an explosives manufacturing site, and this continued until 1999.
There are many bunkers on site: most of them are historic legacy but some are still being used for storage, manufacturing (e.g. nitroglycerin), or testing of explosives and high energy compounds (e.g. Koenen test).
Inside the plants, one will find typical reactors, equipped similarly to classical chemistry plants.
The differences are much less obvious and will probably only be noticed if one knows what to look for (e.g. no copper, see Q4).
There are chemical structures that are not easily synthesized without Hazardous Chemistry, such as the group of sartans which typically contain a tetrazole moiety. These are made in one step from a nitrile and an azide, typically sodium azide. For a non-hazardous route, a much longer synthesis would be required and the product itself would still contain the tetrazole which is a critical structure element with high energy content.