Pumukli
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Amino acid decarboxylation
I would like to do an amino acid decarboxylation but not sure what to expect. I mean I plan to use high boiling solvent and amino acid and tinker with
keton catalysts but I'm not sure how such a reaction proceeds "process wise". More precisely: why would CO2 leave a fairly strong amine behind and
escape as gas?
What would happen if I tried to distill off the resulting amine at the same time? Would a solid amine-carbonate form somewhere in the colder places of
the equipment?
Would it be possible to monitor the process somewhat "semi-quantitatively" by bubbling the CO2 into dilute acid filled precalibrated gas reservoir?
(Upside down soft-drink flask filled with dilute acid.)
Edit: typos removed
[Edited on 22-6-2018 by Pumukli]
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Metacelsus
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Quote: Originally posted by Pumukli  | | I would like to do an amino acid decarboxylation but not sure what to expect. I mean I plan to use high boiling solvent and amino acid and tinker with
keton catalysts but I'm not sure how such a reaction proceeds "process wise". More precisely: why would CO2 leave a fairly strong amine behind and
escape as gas? |
Entropy. At high temperatures, TΔS makes it favorable to create gases. Also, the CO2 will escape from the reaction vessel, driving the reaction
forward.
I guess you could monitor by bubbling into a gas reservoir (or lime water), but periodically doing TLC would probably be easier.
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Pumukli
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I'm struggling with this reaction.
Measured 9.8 g lysine into a 250ml flask, added 120 ml silicon oil into it and started the heating on a magnetic stirrer/hotplate. No extra catalyst
was used , just "brute force" heating. Up until 190 Celsius nothing remarkable happened. No appreciable bubbling either in the flask or at the end of
the cooler (water wash with plastic tube).
I did not want to stress the heater so turned off heating.
Mixture let to cool down, then added 2 ml cyclohexanone into the flask. Heat applied again, and up until 195 C this time nothing
"decarboxylation-like" happened! No CO2 bubbling was observed, although minor bubbles formed in the flask but I think they were cyclohexanone bubbles
(boiling point is around 150 C if my memory is correct). The smell trap (hose from the upper end of reflux condenser led to a big cup of water) did
not bubbled at all (after it reached the working temperature). Not even the slightest cadaverine stench was present!
The powdered lysine became darker tan/brownish though and a sort of orangish/brownish layer deposited from the vapour phase in the flask. It can be
seen both on the body of the glass thermometer, the lower end of the cooler and the upper sides of the flask. The oil is prety much colorless though.
I tend to suspect that my lysine is not really lysine but maybe lysine-dichloride. I bought several kilograms of this substance exactly for this
decarboxylation. It was OTC and relatively inexpensive. But I did not sourced it from a chem supply company but from a fishing /fish keeping supply
(!) firm. They did not indicated what the exact chemical composition was just sold it as "lysine 98%". :-) So maybe it is the dichloride salt. If it
was it would not decarboxylate would it?
(Previously I tried this decarboxylation in cyclohexanol/cyclohexanone mixture with some NaOH prills added. That time the solution turned vivid orange
brown and started to emit both CO2 and some cadaverine as well. At least I could smell a very unpleasant stench which was not trapped even in a dilute
hcl wash used as odor-trap.)
Probably I should measure the chloride-content of the suspect lysine powder - but how?
Maybe if I tried to convert it to free base before the decarboxylation it would be OK too. But too much NaOH could cause other problems, am I right?
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Metacelsus
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Many bacteria express lysine decarboxylase (which catalyzes the reaction using a pyridoxal phosphate cofactor). Maybe some sort of fermentation would
be effective?
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Pumukli
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It seems I choose a bad subject for my experiments. Lysine seemed soo nice and cheap! :-) Cadaverine seemed so desirable :-) Reaction seemed so
straightforward (and simple) on paper, ouch!
I wanted to experiment with the decarboxylation reaction on my ample lysine stock before I moved on to the more expensive amino acids. :-)
Today I bite the bullet and broke the seal on my precious box of proline powder and tried to run the reaction on it.
Guess what!?
It seems to be working exactly as Scr0t described in his great write-up! I substituted turpentine with silicon oil and spearmint oil with
cyclohexanone and it is still refluxing but yeah, it looks like as it should be. (Orange coloured bubbling mass around 135-140 Celsius.)
There seems to be something weird about lysine and its ketone catalysed decarboxylation. Do anyone has firsthand experiences with this particular
substrate?
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Pumukli
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I reply a follow-up to my previous post.
That silicon oil medium turned out to be far from ideal. At least my particular type of oil was too thick (350 C boiling point range) and it caused
problems when cooled and was poured in a separating funnel. Almost as if you were working with lard! :-)
I got some crude (NaOH dried) pyrrolidine, but it was yellow (cyclohexanone contaminant) and the yield was less than 45%.
I bought a flask of "lighting kerosene" in the hope that it would work as turpentine substitute. There was no real (pine) turpentine in the painter's
shop.
According to the vague product description it was composed of mostly C9 - C13 aliphatic hydrocarbons with low (under 2%) aromatic content and no
olefine content. I tried to distill it first but I could not collect even a drop of low-boiling fraction up until 148 Celsius so I assumed it should
be OK. It worked very well! :-)
I also used a bigger (2 litres) pickle's jar as gasometer. The setup was really something I'd rather not make pictures of and show you (big black
plastic crate as water reservoir, half-bricks as base for the upside down jar, a very heavy brick on top of the jar as safety weight to prevent
falling over due to buoyancy...) but this setup worked really well! From time to time I made marks on the side of the jar at the line of meniscus and
it gave me very good indication of reaction progress and its rate! This way I could determine that the reaction required around 10-12 hours to run to
completion in my setup. (100 mmol l-proline, 1,0 ml cyclohexanone, 130 ml kerosene, 142 C decarboxylation temperature.) The yield of crude proline was
around 75% this time.
I have other things (alternative catalysts ?) to try too, in a few weeks hopefully I'll have the time as well!
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Pumukli
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It is just another update on my decarboxylation trials - which is still an ongoing project :-)
One of our fellow members heard my whinning and sent me a nice ammount of benzophenone for testing. Its test is finsihed. :-) Details will be
published along other catalysts when I finish all the tests I can do or finish the testing of the 10th catalyst - or run out of proline, whichever
comes first. :-)
I have collected reaction kinetics data for 7 different compounds so far, have the 8th candidate synthetized and purified ready to go, and almost
prepared the 9th catalyst today. Almost, because the bleach I have turned out to be only 2.63% active chlorine, which is not enough. (Too much water,
solubility issues.) I can't complain, the bottle only says "active chlorine content <5%" but still. It does matter if it is 4.5% or only 2%! Duh.
Not to mention I had to make thiosulphate solution, iodate standard solution (to standardize the thiosulphate) and do a proper hypochlorite
determination because I suspected something amish with the hypochlorite. It all took time.
In my desperation I even borrowed a jug of different brand of bleach from the neighbour to test. It was even worse (1.48% hypochlorite measured) but
at least it correctly indicated its chlorine content on a small print as 1.5%... :-) It also gave me reassurement regarding my calculations.
I also prepared a catalyst precursor (for the 10th catalyst) a few days ago, but the synth of this catalyst requires more effort than the previous
ones.
The above precursor synth may be worth a dedicated prepub article in itself, because I went macro again and made a substantial ammount of this
compound in two runs. The synth is foolproof when you do it as a lab exercise at school on a 5 grams scale but when you go a bit overboard and reach
for a 30x scale it can be more tricky. Especially when you are an amateur and want to save on reagents and tinker with tried and working Orgsyn
ratios. :-)
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