Choosing the right refrigeration system is critical to a safe and economical process. A range of chemical reactions and processes can benefit from the use of low temperature technologies, particularly in the chemical and pharmaceutical industries. For example, in organic and organometallic synthesis, low temperature operation is important to achieve the balance between reactivity, selectivity and yield of the reaction. In the case of highly exothermic reactions, proper cooling is critical to control heat release and avoid reaction runway.

Two common cooling methods can be used to keep temperatures sufficiently low and control an exothermic reaction: low-temperature mechanical refrigeration and cryogenic refrigeration via sublimation of carbon dioxide or evaporation of liquid nitrogen (LIN). Thorough selection of the refrigeration method is critical to providing a safe and economical operation process.

For reaction cooling, mechanical refrigeration must work at the limit of its lower temperature range, which is not only challenging but also expensive. In addition, if the equipment's maximum potential is only occasionally utilized, then a lot of costly capital equipment may be left sitting around doing nothing. Mechanical refrigeration is provided by a chiller that includes a compressor - sometimes single-, but often two-stage - as the heart of the system. When the temperature requirements drop lower than -58°F (-50°C), the chiller system becomes more complex with a multi-stage cascade design and multiple refrigerants.1 It also is known that mechanical refrigeration provides a limited ability to cope with widely or rapidly varying heat loads.2

  • Cryogenic refrigeration provides much more flexibility in terms of temperature ranges and cooling regime variability when compared to mechanical refrigeration.

  • Cryogenic refrigeration by means of sublimation of carbon dioxide can be a viable option for controlling some cold chemistry reactions and can reach temperatures as low as -108°F (-78°C) at atmospheric pressure.

  • Alternately, LIN can achieve much lower temperatures of -320°F (-195°C) and a higher refrigeration capacity per mass unit than CO2 (figures 1 and 2).

  • Liquid nitrogen may provide a design engineer more confidence in the cooling system's control as well as allow a chemist the full flexibility needed when choosing which synthesis route to follow.

There are three primary options for cooling reaction vessels with LIN:

  • Direct

  • Semi-indirect

  • Indirect.

Each method has advantages and disadvantages.

Direct injection of LIN achieves maximum efficiency and is inexpensive to install, but solvent entrainment, foaming and localized freezing can occur. This option often is used in emergency situations because vaporizing LIN can quickly provide rapid cooling to the reaction process should an unsafe or runaway situation occur.

In a semi-indirect method, heat transfer takes place by flowing liquid nitrogen either through a coil inside a reactor or through a reactor cooling jacket. The main benefits of this method include accurate temperature control, the ability to reuse the nitrogen, and simplicity. Drawbacks include reduced efficiency, demand on reactor volume, and the expense of the cryogenic construction and corrosion-resistant materials.

Indirect heat transfer occurs in systems where LIN is exchanged with a suitable heat transfer fluid in an external heat exchanger. This approach has the most system flexibility, provides accurate temperature control and accommodates large heat loads. Many reaction processes already utilize a heat transfer fluid/medium that is either cooled or heated accordingly to provide flexibility in multi-step reaction processes.

Regardless of the method used, one of the important considerations when using LIN for cooling purposes is a properly designed supply system that minimizes nitrogen loss at all the stages and ensures good quality liquid nitrogen for a specific application.

While reaction cooling requirements may vary significantly - from maintaining a steady low temperature to fast heat removal during reaction content additions - LIN refrigeration is capable of providing a flexible, reliable, environmentally-friendly and economic cooling option. In many applications, cryogenics can be seen as specialized; however, cryogenics provide distinct advantages in many instances.

The most common use of nitrogen in a chemical plant is as an inert blanketing gas.3 If the evaporated LIN from the cooling process can be recovered and used elsewhere in the plant, the running costs of the system can be reduced dramatically.Liquid nitrogen often is portrayed as an expensive option, but when improved reaction yields and selectivity, reduced unwanted byproducts and the relatively low capital costs involved are taken into consideration, LIN becomes an economically attractive choice. 


1. ASHRAE Refrigeration Handbook, “Ultra-low Temperature Refrigeration,” Chapter 39 (2002).
2. “Capacitance: Key Design Consideration for Refrigerated Central Cooling Systems for Batch Process Plants,” Pharmaceutical Engineering, Vol. 21, No. 4 (2002).
3. “Nitrogen: A Security Blanket for the Chemical Industry,” Chemical Engineering Progress, 107 (11), pp. 50-55 (Nov. 2011).