What Might be the Best Cleaning Solvent for Cleaning the Reactor Walls of a Plant Reactor

acetamide model

The walls of a large-scale reactor can sometimes be difficult to clean.  The problem is compounded because they are not easily accessible and cannot be inspected closely. Methods that can be applied in the laboratory for many reasons are off-limits. Scrubbing is impractical, dangerous, and potentially damaging to the equipment. What is needed is a powerful but innocuous solvent that can work by vapor condensation not just below the surface of the refluxing liquid cleaner but above the surface and on the reactor walls where the reaction mixture may have splashed, caked, and baked.

In the very old literature, a common, inexpensive, and innocuous compound was claimed to be the best solvent known and one that would dissolve both organic and inorganic materials; salts as well as uncharged covalent molecules: molten boiling acetamide.  Acetamide can be synthesized in situ in the reactor by heating ammonium carbonate and acetic acid and distilling out water. This in fact is the first preparation in the First Collective Volume of Organic Synthesis. 
Acetamide has bp (760 mm) 222.0 C ; bp (100 mm) 158 C; bp (40 mm) 136 C;  bp (20 mm) 120 C; bp (10 mm) 105 C; or bp (5 mm) 92 C. 
As a white solid, it has mp 82.3 C. 
The solubility is 2 grams per ml of water. 
Acetamide has been advocated as a “green” solvent [http://acs.confex.com/acs/green07/techprogram/S3384.HTM]
The ninth edition of the Merck Index describes it as:
 “Solvent; molten acetamide is an excellent solvent for many organic and inorganic compounds. Solubilizer; renders sparingly soluble substances more soluble in water by mere addition or by fusion.”  Way back in 1933, Professor O.F. Stafford of the University of Oregon wrote that acetamide dissolved more different chemicals than any other known solvent. [J. Am. Chem. Soc., 1933, 55 (10), pp 3987–3988].

Process chemists sometimes forget that their responsibility is for the minimized overall cost of the process and this is much more than the chemicals only cost. The throughput per unit of time is a major factor in the overall cost. That time includes the equipment cleaning time required between batch runs and between the end of one campaign and a new one for another product that is to be run with the same equipment. It makes little sense to invest extensive research efforts in reducing processing time when the same throughput efficiencies can be more easily achieved by reducing cleaning time between runs.

Many plants use a standard cleaning protocol implemented as an SOP.  Special cleaning procedures are resorted to only when it fails to remove all the contamination. In some cases, the standard cleaning or rinsing will even exaggerate a problem. For example, in the synthesis of adamantane described in Organic  Synthesis Coll. Vol. III pg. 16-19, specific instructions are provided to avoid treating the vessel with water until acetone is used first to completely remove the tar.

Development chemists are the first to get an indication that special cleaning problems could arise after certain processing. Giving the plant scale-up people a heads-up and some suggestions will improve both teamwork and overall efficiency.

Since acetamide is Ames negative it is a moot point as to whether it should be considered as a “genotoxic impurity”; it is, however, a modest-potency carcinogen with a TD50 value of 180 mg/kg/day.