Boffis
International Hazard
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Hydrolysis of l-Theanine and the synthesis of Ethylurea
I required some N-substituted alkyl ureas to prepare N-substitute alloxan-5-oximes derivatives (I have discussed my interest in these compounds
previously) and while looking arounds for syntheses of these compounds I came across and interesting synthesis of alkylureas through the condensation
of nitrourea with an aliphatic (or aromatic) primary amine 1). Some secondary amines give rise to N,N-di-substituted ureas too. I have sources a
methylamine and several other primary amines but I was looking at quick routes to ethylamine when I noticed that the amino-acid theanine is the
ethylamide of glutamic acid. My idea was alkali hydrolysis of the theanine with gentle distillation to drive off the volatile amine and collect the
vapours in cold water followed by direct reaction with nitrourea without isolation of the ethylamine. I am pleased to report that the experiment was
completely successful. I am sure that the preparation of nitrourea has been previously discussed to death in the “Energetics” section of SM so I
will not describe its preparation here though I did develop a method of preparing urea nitrate from sodium nitrate.
The chemistry is as follow:
The hydrolysis of theanine
C7H14N2O3 + 2NaOH -> C5H7NO4Na2 +
C2H5NH2 + H2O
The two main products of this reaction are di-sodium glutamate which is very soluble and ethylamine which is volatile and distils off as it is formed.
Ethylurea from the amine and nitrourea:
C2H5NH2 + CH3N3O3 -> C2H5NHCONH2 +
N2O + H2O
Nitrourea breaks down in boiling in water but in the presence of an amine forms a substituted urea and nitrous oxide. While this may seem an obscure
method of making ureas it has the advantage over the amine salt + potassium cyanate method that no other solid is formed in theory. A small excess of
nitrourea is required to make up for that that simply decomposes.
Experimental
Hydrolysis of l-Theanine
10.00g of l-theanine were suspended in 20ml of warm water in a 100ml flask and stirred while 9.5ml of 50% sodium hydroxide solution diluted with 20ml
of water were added. The solid dissolved to give a clear solution which on warming quickly began to smell “fishy”. A simple bent distillation head
was added to the flask with a condenser and delivery tail into a flask containing a little cold water (12-15ml). The mixture was then slowly distilled
until about 20ml had distilled over. Very little amine escaped as ethylamine is very soluble in cold water.
The formation of ethylurea
The distillate from the previous experiment was assumed to contain 2.59g (theoretical yield) of ethylamine. To this were added 6.10g of recrystallized
nitrourea and the mixture warmed gently until the nitrourea dissolved in a small beaker. The mixture was heated in the open beaker until the steady
effervescence ceased and then transferred to a shallow ceramic bowl on a steam bath and evaporated until a thick oily colourless liquid was achieved.
When no further loss of liquid appears to be occurring the liquid was allowed to cool and crystallise, this took almost 12 hours before
crystallisation began but once initiated it solidified quickly to a moist solid.
The crude material is virtually impossible to dry further and the small amount of moisture seemed difficult to remove from the benzene solution when I
tried to recrystallize it as described in the original paper. In the end two method of purification were found.
1) The crude ethylurea (about 5.1g but moist) was placed in a nominal 100ml conical flask and 45ml of dry benzene added. The mixture was distilled
slowly so that only one drop passed over every 3 or 4 seconds until about 23-25ml had passed over and the distillate ran clear. The clear liquid
contents of the flask were cooled a little and poured into a small glass bowl and covered with a watch glass to stop benzene fume escaping. The bowl
was chilled in the fridge when it virtually solidified into a mass of translucent colourless flakes. These were filter from the included fluid and the
crystals dried as much as possible by drawing air through them. They were finally dried in the fume hood on a clock glass. The product weighed 4.53g
and melt between 88-90°C; (89% of theory based on the theanine used.
2) Alternatively add just enough water to completely dissolve the solid on gentle warming to 40°C, a few ml, then 3.7ml of 68% nitric acid and cool
quickly in an ice-water bath. When the pure white, crystalline mass is cold, about 5-8°C stir up the solid and drain on a Buchner funnel and suck as
dry as possible. Finally dry in a desiccator over calcium oxide, the yield was 7.27g of ethylurea nitrate. This method has the advantage of not
requiring benzene, however, I will have to liberate the free urea and dry it thoroughly for the barbituric acid stage of the synthesis.
Recovery of the glutamic acid
The residue from the original distillation was evaporated down to about 17-18ml and acidified with 30% HCl, about 12ml (avoid adding to much!)
were required. No solid precipitated from the warm solution but on cooling small white spherical aggregates of glutamic acid started to form.
Eventually, almost the entire solution solidifies until stirred when it turns into a thick, granular slurry but which is very difficult to filter and
the solid recovered rather sticky. It dried to a hard white granular mass weighing 6.95g (82.5% of theory)
1) Dearrangement of nitrourea and its application in synthesis JACS Davis & Blanchard 1929, p1790-1801
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Pumukli
National Hazard
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Nicely written report!
Very interesting that the synthesys sequence gave such a high yield, including work-up!
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