chemrox
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return to PPA>aminorex discussion
I have an interest in Bandits PPA>aminorex syn. I want to apply it to a ring substituted phenylpropanolamine of possible value. Anyway, I was
abroad and had the opportunity of trying the Bandit workup. I failed twice and had to pack up and fly home. The intermediate did not form an oily
layer but rather a white precipitate. The second reaction never got faintly pink and the yield of white powdery material was under a tenth of
theoretical. I return this summer and will by then have the starting materials for the other, legal compound but want to perfect the technique and
debug the issues. Lots of advice and speculation appreciated. The original cyanate reference and article would be most helpful. I suspect pH is one
of the issues.
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roamingnome
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you speak of future distant analogs
but in my preliminary reading this article is intriging
http://www.teknoscienze.com/images/documenti/supplements/d%C...
acetaldehyde + benzaldehyde with BAL protien. This creates R-2-HPP derivative
the "reverse" of L-PAC I then wonder of ketone reduction and oxazoline formation leading to possible medications and therapeutic advances....
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chemrox
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Have you worked with biological derivatives like BAL? I haven't. Don't know shit about them. However would like to learn if they can be had or made
without the national debt of Lichtenstein
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roamingnome
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i have not worked with BAL protien, but stayed tuned people are working on biosynths.
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had or made without the national debt of Lichtenstein
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protiens are everywhere for pennies, in bacteria, yeast, fungus, even potatos
purifying them in concentration can get a bit more envolved
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roamingnome
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oh no not another free patent &%^$
http://www.freepatentsonline.com/4418047.html
United States Patent 4418047
Stable isocyanic acid compositions containing isocyanic acid in an organic solvent
yes even I am getting quite tired, but i have too much free time on my hands. Sue me...
a molar equivalent of HCNO somehow reacted with free amine to yield carbamylation
for research puposes only
use only for educational facilities and certifed people
keep out of the reach of children
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chemrox
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Thank you very much!
I figured out the issues pH and not enough heat .. really requires boiling water solution at max reflux
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jon
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right at ph 5-6.5 the cyanic acid produced gets hydrolysed according to this paper to CO2 and NH4OH.
www.rsc.org/delivery/_ArticleLinking/DisplayArticleForFree.c...
the hydrolysis rate drops preciptiously from ph 6-8 ph 8 is optimal.
if you refer to the graph (fig 1) all the other side reactions of isocyanic acid is incedental to side reaction A (hydrolysis) this gives the
carbonate ion which catalyzes further hydrolysis.
a look at graph 2 or figure 2 shows molar yeild as function of PH from PH 8-12 the yeild of carbamoyl gylcine is close to quantitative at the Ph you
indicated you attempted this (PH5) yeilds are more like 10%.
[Edited on 27-1-2007 by jon]
[Edited on 27-1-2007 by jon]
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chemrox
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A couple of years ago I prepared a small quantity of 2,4,5 trimethoxyphenylpropanolamine from the aldehyde. I want to conver this to the MAR by way
of the cyanate method. I had more of the unsubstituted material but was reluctant to do anyhting because of the legal ramifications. Not wanting to
waste my precious trimethoxy amino alcohol, I plunged and tried the synth as I understood it. The posted synths by Bandil suggest much lower pH's and
this may be the problem. I got the product (which I promptly destroyed) in about 40% yield. The reaction mixture pH rose to about 8 or 9 during the
reaction of cyanate with the alcoholamine. When acid wad added a white precipitate had formed. Acid was added in 3:1 excess of the intermediate.
This made a clear solution of pH 2 which was boiled hard for about 3-4 hours. No pinkish color developed but on adding base (Na2CO3 followed by
NH4OH) white crystals precipitated. 2.7 g of these were collected and dried. A mass of them, that were kind of stuck together was separated. This
mass had a pinkish hue. It was dissolved in HCl (10M follwed by 2X H20 making ~ 3M). That solution was definitely pink. White crystals precipitated
on basification as before. Another 2g were obtained this way and that made the yield around 40% realtive to the starting aminoalcohol. All were
immediately flushed.
I would like to try on more run before using up my substituted material and before making another aminoalcohol from piperonal which I have a lot of.
I wanted to do something fun with the piperonal that wouldn't bring me under one of the many restrictive regs and might have some interesting
characteristics. I don't think the 2,4,5 will be anything but you never know...
Anyway, I will read what you sent me with great care and adjust accordingly. I had heard this was a pH sensative process and kept track as things
moved along. What do you make of the fact that although the reaction misture was started at almost neutral pH, the reaction progressed to make a high
pH?
[Edited on 28-1-2007 by chemrox]
[Edited on 28-1-2007 by chemrox]
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chemrox
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From reading the article(on screen) it looks as though ammonia,CO2 and bicarbonate are generated in the first reactions with cyanate and water.. when
I did it, evolution of CO2 was not observed but high pH was observed. Any thoughts there?
From the glycine curves, as you indicated, the reax wouldn't go well without the high pH. I didn't get time v. pH data but I started neutral and
ended high. Wondering if introduction of NH4+ at the start would help or hinder. I need to print this at the office and read it thoroughly!
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jon
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if you start at a PH of 6.5 and up the cyanic acid will not hydrolyse to any great extent but will some so you won't observe vigorous CO2 evolution.
As the PH increases above a certain point the carbamoylation slows down quite a bit that's why in the synthetic part of the article the examples
indicate they titurate with HCl to keep the PH around 7.5 at this PH the best rate is observed but still an excess is employed due to this hydrolysis
we're talking about.
I think the PH goes up as the cyanic acid gets incorporated so there's less acid floating around hence a higher PH.
It's a real good read isn't it?
I dunno if this is appropriate but in the process of destroying that substituted goodie were you able to elucidate any of it's subjective
component
As to 40% yeild that's about right when you consider that only one enatiomer (50%) gives the goods the other the oxazolidinone (a cyclic amide)
[Edited on 27-1-2007 by jon]
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chemrox
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uhhh .. a U2U will follow,
does this mean that the reaction should be maintined at 7.5 by adding acid as the pH goes up..as, as you say, the cyanic acid is consumed?
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chemrox
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Guess not-the titrations were for the experimental data and different techniques and different pH ranges were maintained. Check the syn for glycine:
N-Carbamoylglycine C-Gly. To a warm (50 C), stirred solution
of 3.75 g (50 mmol) glycine in 50 mL water was added 5.27
g (65 mmol) potassium cyanate. The reaction was followed by
HPLC analysis (eluent: aqueous KH2PO4 (10 mM) sodium
hexanesulfonate (5 mM), adjusted to pH 2.5 with H3PO4, UV
detection at 195 nm). After 10 h stirring at 50 C (the pH
meanwhile rose from 7.12 at the beginning to 10.0 at the end of
the reaction), the mixture was chilled, and filtered through a
column containing AG-50-X2 cation-exchange resin (H form;
further elution with water). After water evaporation in vacuo,
then drying in a heating desiccator, the major fraction afforded
4.88 g (41.3 mmol, 83%) pure C-Gly (hydantoic acid: mp
165 C. δH 3.66 (2H, d, J = 5.6 Hz, Hα , 5.64 (2H, s, NH2), 6.14
(1H, t, J = 5.6 Hz, NH), identical physical data to an authentic
sample from Sigma). A further fraction (824 mg) contained ca.
90 mol% C-Gly (6.6 mmol) and 10 mol% urea (NMR). Overall
yield C-Gly 95%.
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