Org Prep Daily

November 12, 2007

Only under Communism

Filed under: Uncategorized — milkshake @ 10:05 pm

chaos.jpg Credit: Jiri Sliva

When I was doing my thesis work in Prague I was stubborn about working on my own project and for that I needed a lab. A great man, docent Karel Capek took me in. He was a carbohydrate chemist, and he also had a fine reputation as a pharma process chemist. He once said that all his research papers would perhaps amount to a footnote in some monograph but he was proud of the projects he did for the industry – like developing a new Tamoxifen manufacturing route which made it available to the patients in Czechoslovakia. (The drug would be too expensive to import. For his patent-busting synthetic process he got dragged into a litigation by ICI – but he prevailed). Docent Capek had his hand in a number of useful chemical processes, mostly manufacturing drugs and food additives. And probably his weirdest industry experience was the project of recycling chloramphenicol base. I think the story is quite illustrative of the chemistry done under the ‘real socialism’.

Chloramphenicol used to be an important antibiotic and the Spofa plant was the main producer in the Eastern Bloc. One enantiomer of the drug is active, the other one is only toxic and the amine precursor (sans dichloroacetyl) can be resolved by fractional crystallization. This separation was done in Spofa on a ton scale and they had a problem with the unwanted enantiomer – for years they have been putting this sideproduct into barrels. When they eventually run out of the storage space they took the barrels to a landfill… Capek was told that a great reward awaited the man who finds a way of recycling the unwanted enantiomer. (“You build yourself a villa with the money you get for solving this thing.”)

And Capek promptly solved the problem – an oxidation of the benzylic OH produced an easy-to-racemize aminoketone intermediate that was one step back on the synthetic scheme. The chemistry was nice and simple, just one step (the oxidation was done on the unprotected amino-diol with 2 chiral centers – and the used oxidant was aqueous KBrO3) . But under the ‘real socialism’ even the simplest things could never be quite as simple – everything was very political and red-tape ridden and management did not care about the profitability because every silly detail was planed out centrally. Then there was a resistance on the plant floor – against any changes in the established manufacturing route. A headache-producing innovation was best to be avoided. And this oxidation procedure was a radical chain reaction that was initiated by visible light – it needed a dedicated glass-top reactor equipped with floodlights and there were no funds allocated for such pilot project in the production plan, etc.

One day a reactor with 2,4,5-trichlorophenol in Seveso plant in Italy overheated and bursted. The accident released a kilo quantity of the TCDD dioxin and contaminated wide area in a spectacular fashion; there were hundreds of cases of serious poisoning. The Seveso plant was shut down and like in Chernobyl, the center zone remained off limits for years until extensive decontamination could be completed. The Seveso plant was also the world’s main producer of p-nitroacetophenone – the starting material in the Spofa synthesis of chloramphenicol.

Since no other supplier could suddenly provide Spofa with the starting material in the sufficient quantity, the Spofa management was getting desperate. So they built the illuminated reactor. They sent bulldozers on an excavation mission. And in the end there was so much of the “undesired” enantiomer dug out from the landfill that for a year all chloramphenicol in Czechoslovakia was manufactured from those recovered barrels.

Docent Capek never got the money to build a mansion – but the brightly-lit oxidation reactor became a showpiece impressing the visitors in the Spofa plant…

7 Comments »

  1. Your stories are always so sweet and heart warming. I’m beginning to think Kafka’s only unique quality was the fact that he was published.

    Comment by Kyle Finchsigmate — November 13, 2007 @ 10:26 am

  2. As with chloramphenicol, pasta is mined,

    http://www.mazepath.com/uncleal/pasta.htm

    “8^>)

    Comment by Uncle Al — November 13, 2007 @ 2:37 pm

  3. Milkshake
    Awesome story, where do you get this stuff?

    Uncle Al,
    Awesome story, where do you get this stuff?

    Comment by Rhenium — November 14, 2007 @ 6:04 pm

  4. Please share more of these stories with us (if you have them).

    Comment by Jordan — November 19, 2007 @ 4:15 pm

  5. Very interesting,

    I dont know why, but I have the feeling that I’ve heard of other stories like Capek’s before.

    Comment by HOMO-LUMO — December 4, 2007 @ 11:57 am

  6. Why was the plant feeded by the undesired enantiomer only for year, if it produced the drug for many years (as I understood)?

    Comment by kolpak — September 14, 2008 @ 4:53 pm

  7. I suppose they could have been going at it for a longer time if they could find the material, I don’t know what their situation was with the “landfill storage” – this is the story how I heard it from the guy who developed the recycling process.

    By the way, a nice literature aggregator you have – now I have no longer an excuse to skip on reading all the main journals…

    Comment by milkshake — September 14, 2008 @ 5:13 pm


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