In the last part of this series about lab life I told you about my encounter with two steps of a four-step sequence, now I would like to move on to the next two steps: Preparation of a benzyl chloride and its conversion to a benzyl azide. If you remember I had to convert 7098 kg of the benzyl alcohol ultimately to the azide. According to the plan:

Now benzyl halides are well known for their lachrymatory properties and this one made me cry just thinking about it. You just needed to walk past the building where it was being produced to burst into tears and I had to run 46 batches (1.02 kMol) to make this stuff plus 9 for use tests. In fact we made the chloride then almost immediately converted it to the azide.

As part of the safety procedure in the pre-reaction checks of the equipment the conductance of the enamelled stainless steel reactor was measured to make sure there were no cracks in the enamelling, it was deemed to be ok so we carried on. The alcohol was placed in a 630 L reactor and 312.8 kg of 37% hydrochloric acid was pumped in. The solution was heated slowly to an internal temperature of 90-93°C and held there for 5 hours. During the reaction a two-phase system formed and we all cried. The product was on the bottom and it was separated from the acid after cooling to 40°- 45°C because the compound solidified at 37°C. It was then filtered and the pH adjusted to 9-12 with 30% NaOH solution and stored at 40°C as a two-phase system with water with minimal stirring and constant pH adjustment maintaining the 9-12 range. In the meantime we got things going for the conversion to the benzyl azide, more about that later.

When we examined the filter from the very last reaction we observed bits of blue glass. I hear you say “not again”. I don’t seen to have much luck with enamelled reactors. Well this time we were really lucky, and I mean really. Have a look at these two pictures.

The hole started life as  a hairline crack in the enamel. Now this did not show up in the conductivity tests as it was right up at the top of the reactor where the stirrer joined together with the motor and could not be reached with the equipment we had, a pathetic excuse really. Maybe we should have used Heineken, you know, the beer that reaches places that other beers can’t.  Remember under the enamel is stainless steel and we were using almost boiling 37% hydrochloric acid. So the acid seeped through during the course of the 46 batches and started munching away at the steel. The metal was so thin that if you pinched it between thumb and forefinger you could move the bottom part back and forward. I would say that one more reaction and the stirrer would have broken off at 100 rpm making God only knows what kind of mess. Furthermore it is well known that the presence of iron (rust) benzyl halides decompose exothermically at quite low temperatures. I can’t remember the exact temperatures but it moves the decomposition point (where the exotherm begins in DSC measurements) down about 50 or so degrees and increases the size of the exotherm markedly. So I guess we were lucky on two points, we stopped just in time and we were using steel with a very low iron content. After I saw this and realised the implications I my knees started knocking together and I staggered across the road to a pub and had a few stiff drinks and went home where I continued the treatment.

Back to the chemistry: Working with azides is particularly dangerous because of potential explosion and health hazards. Sodium azide is a very nasty compound. It is a CNS depressant and breathing the dust causes almost immediate breathing problems amongst others, see this page for more information, azides. Furthermore it also contains traces of hydrogen azide, which has similar biological behaviour to sodium azide but has the pleasant habit of being shock sensitive and hence explosive. The stirrer episode was bad enough; and we were using 70 kg of sodium azide per batch, my poor knees (never mind the liver). Even at pH 9 or above one can still detect HN₃ in the gas phase. For the reaction we had an extensive gas washing system with 4 washers filled with 30% sodium hydroxide solution through which the exhaust went. At the end of this chain we periodically monitored for the presence of HN₃ using ferric chloride spot tests, which are very sensitive for this compound. I’m happy to say that at the end of the chain we never detected any HN₃. The reactor was specially made out of high quality tantalum steel, where the heavy metal content was minimised so we hopefully avoided the formation of heavy metal azides, I do not know if tantalum azide exists (perhaps someone who reads this may know) and heated glass tubing was employed for the transfers.

We threw the following into a 630 L reactor; 200 kg water, 2.6 mL of 30%NaOH solution, 700g tetra-n-butylammonium bromide, 70 kg sodium azide and a pH electrode. After heating this mixture to 90-95°C internal temperature and added the alkaline mixture of the benzyl chloride within 60 minutes. As expected the pH drifted during this reaction and it was constantly monitored and kept between 9 and 12. The reaction is exothermic and the temperature control was also monitored closely during the 2 hour stirring at 90-95°C.

We then cooled to room temperature and filtered the lower organic phase (this time no glass was observed!) and removed the aqueous layer. This time everything went ok and from 55 batches we obtained a total of 9284.64 kg with an average purity of 94% and an average yield of 97.9%. All of the batches were released for the next step by QA. At last I was almost finished, I still had to dispose of all the azide containing waste from all the gas washers and all the water layers and reactor cleaning! This was really funny. We disposed of it by treatment of the waste with 37% hydrochloric acid and sodium nitrite, generating nitrogen, laughing gas and various other oxides or nitrogen that were washed out by the exhaust treatment. This was another foaming reaction, but by this time I was immune to foaming, didn’t worry me anymore. The aqueous phases went down to the water treatment plant.

There it was finished at last, with enough material for my colleague to play with. There is still more to tell about this chemistry but that will come later.