Phosphorous oxychloride was being added slowly in small portions from pressure equalizing dropping funnels to a set of six reaction mixtures containing a substituted isoquinoline-N-oxide in dichloromethane. After about 20% of the addition had been made the operator handed over to a colleague in order to take a break. Shortly after the relief operator restarted the operation one of the reaction mixtures began to froth. Subsequently it climbed out of the condenser and was ejected from the vessel.
It was apparent that the two operators were doing something different. Further investigation deduced that operator two was adding in bigger (& and less often) portions than operator one.
- The reaction is exothermic, and run at gentle reflux
- The process had been modified, with time, from a slow continuous addition to a practice of adding small discrete portions, as it was easier for the operator to control.
- In this case, too big a portion was added, and the resultant boil up rate increase was too big for the apparatus, and the mixture foamed out.
Even minor process changes should always be reviewed by the appropriate team to make sure that the change will not cause any problems. In this case addition as a continuous slow stream was recommended for future production.