Author Topic: trans-4-MAR synth w/o cyanogenbromide writeup!  (Read 11275 times)

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bottleneck

  • Guest
There was also the reference by Rhodium to an...
« Reply #20 on: March 12, 2003, 07:51:00 AM »
There was also the reference by Rhodium to an article on related reactions of ephedrine.

Journal of the Chemical Society;1952;;850-4;Fodor & Koczka;The Stereochemical Course of the Conversion of 2-Ureidoalcohols into Oxazolidines. Part I.pdf

(http://www.geocities.com/botero56/JCS.1952..850-4.Fodor_Koczka.pdf)

Of course it works! I can't believe anyone could fail at this! Trust me, I wouldn't (be able to) write this if it didn't work!!!

Megatherium

  • Guest
This is rather funny.
« Reply #21 on: March 12, 2003, 08:46:00 AM »
This is rather funny.  Today I went to the library to fetch exactly the same article.

I don't know why it isn't on rhodium.ws ...  As far as I am concerned, this is one of the best synthetic routes here on The Hive.  Especially since the PPA precursor can easily be made from scratch.

Rhodium

  • Guest
4-Methylaminorex Review
« Reply #22 on: March 12, 2003, 01:54:00 PM »
I am working on making a 4-Methylaminorex Review article, where this and all other published syntheses are detailed, that's why the addition of this particular preparation has been postponed.

Megatherium

  • Guest
I need a verification for this statement: 'Is...
« Reply #23 on: March 13, 2003, 01:49:00 PM »
I need a verification for this statement:

 'Is (1R*,2S*)-phenylpropanolamine = dl-norephedrine = (+/-)-norephedrine = the precursor needed in the KOCN route for the trans-4-MAR syntheis?'


Rhodium

  • Guest
stereochemistry
« Reply #24 on: March 13, 2003, 02:51:00 PM »
Yes, see

Post 404474

(Rhodium: "Better pictures", Stimulants)
.

You want the chiral centers to be different to each other (1S,2R or 1R,2S), if they are the same (1S,2S or 1R,2R) you've got the pseudo form.

viki

  • Guest
Can phenlyethanolamine and HOCN be used?
« Reply #25 on: March 16, 2003, 08:37:00 PM »
Could phenylethanolamine be used in this reaction. see post 22556 psychokitty.Could HOCN be substituted forKOCN?Cheers


Megatherium

  • Guest
Could phenylethanolamine be used in this ...
« Reply #26 on: March 17, 2003, 08:36:00 AM »
Could phenylethanolamine be used in this reaction

Yes, this would generate straight aminorex.

see post 22556 psychokitty

Post 22556 (missing)

(Orbital: "Re: AMT, Alpha methyl-tryptamine", General Discourse)
, this ref. doesn't check out.  What do you mean?

Could HOCN be substituted for KOCN?

No.  HOCN is generated in situ: phenylethanolamine.HCl + KOCN  --> KCl + HOCN + phenylethanolamine freebase.
Furthermore, one can't prepare and keep (or buy) an HOCN (aq.) solution since HOCN hydrolyses in contact with moisture to NH3 and CO2.  Even in dry organic solvents isocyanic acid readily polymerizes to give a mixture of cyanuric acid and cyamelide.
The stoichiometry of this reaction seems to be VERY important: if an excess of isocyanic acid is used, the biuret reaction kicks in ... effectively destroying the carbamate precursor   R-NH-CO-NH2  -->  R-NH-CO-NH-CO-NH2   :(   What can be more easy than using a balance to accurately weigh the needed amount of NaOCN or KOCN?

SPISSHAK

  • Guest
you have a good explanation there
« Reply #27 on: March 17, 2003, 03:11:00 PM »
What I am wondering is why water is used as a solvent in one of those examples, when it decomposes HOCN to CO2, and NH3?

Megatherium

  • Guest
Well, I don't know, but I think the ...
« Reply #28 on: March 17, 2003, 03:24:00 PM »
Well, I don't know, but I think the Encyclopedia of Reagents for Organic Synthesis is a reliable source.

I read further:

"Preparative methods: by the depolymerization of cyanuric acid or by heating urea.  The gas can be absorbed in ether, THF, CHCl3 or CCl4.  Aqueous solutions of HNCO can be prepared in situ by reacting NaOCN or KOCN with 1 equiv. of dil. HCl or AcOH at temperatures of approx 0 - 15 °C".

Probably, the HNCO won't react immediately with the water and it slowly decomposes (hence it is generated in situ).  It 's all a matter of kinetics  :P .

dennis_pro

  • Guest
It's me...
« Reply #29 on: March 18, 2003, 11:47:00 PM »
I'm personally failed this synthesis.
The substituted urea is produced fine, but final HCl condensation always fails for me. I have using pharm. grade PPA. Have tryed two times - the yield is zero.
P.S. I have worked accordingly to method posted here by Rhodium.
P.P.S. Sorry my terrible english :)


Bandil

  • Guest
Are you using the right isomer?
« Reply #30 on: March 19, 2003, 12:53:00 AM »
Are you using the right isomer? Norephedrine that is? It is the only place where one is able to fail, as far as i can see. That would explain why you got the carbamyl, but to amine that falls out!

Regards
Bandil


dennis_pro

  • Guest
Are you using the right isomer? I'm not sure.
« Reply #31 on: March 19, 2003, 07:10:00 PM »
Are you using the right isomer?
I'm not sure. I have used pharmaceutical PPA (GB pharmacopea). It should be racemate or right isomer, according to Rhodium, didn't it?

For me: After refluxing subst.urea with HCl, the solution becomes clear, after adding NaOH it becomes clody and some white precipitate forms. But after extraction with hexane, nothing go to organic phase... Is it amide or amine or what?


Bandil

  • Guest
Instead of basifying with NaOH, try to use...
« Reply #32 on: March 20, 2003, 12:54:00 AM »
Instead of basifying with NaOH, try to use carbonate as described originally. Why are you extracting with an organic phase? Just suction filter the precitiapate. It's pure and ready to use(unless you want the HCl)...

But try to skip the last step and see what happens!

Good luck
Regards bandil!


Rhodium

  • Guest

dennis_pro

  • Guest
So, GB PPA is racemate...
« Reply #34 on: March 20, 2003, 09:36:00 PM »
If it is racemate (50% of right isomer) I have expect 20% yield. But practically obtain less than 1%. And nobody knows why :(

Is SOMEBODY other than Bandil tried this method, or not? Can SOMEBODY confirm ICE yields and identity? Post your methods with comments please.


Vitus_Verdegast

  • Guest
melting point
« Reply #35 on: March 20, 2003, 11:16:00 PM »
Dennis_pro :

what is the melting point of your PPA ?

From the Merck Index:

Phenylpropanolamine (racemic mix of d- and l-norephedrine)
base : 101-101.5°
.HCl : 190-194°
.HCl (+)-form : 171-172°

Norpseudoephedrine
base : 77.5-78°
.HCl : 180-181°


Prometheuz

  • Guest
Confirmation
« Reply #36 on: March 21, 2003, 03:11:00 AM »
SWIM can confirm that SWI Bandil and himself ran the synth 2 times, at different scale, with no deviations from the first write-up. The yield for the second synth has not been established yet, but I am positive it's at least at good as for the first synth.
Hopefully there'll be opportunity to get a NMR done soon.  ;D


SPISSHAK

  • Guest
maybee when you based it
« Reply #37 on: March 21, 2003, 11:46:00 AM »
The ph got too alkaline and hydrolysis ensued.
That could explain not getting any yeilds.

silenziox

  • Guest
(1R,2S)-phenylpropanolamine = l-ppa, not dl-ppa
« Reply #38 on: March 22, 2003, 10:19:00 AM »


Username: Megatherium
Post: I need a verification for this statement:

'Is (1R*,2S*)-phenylpropanolamine = dl-norephedrine = (+/-)-norephedrine = the precursor needed in the KOCN route for the trans-4-MAR syntheis?'



Good grief  :o .. Didn't anyone check this out?
Rhodium also verified that 1r,2s-phenylpropanolamine is dl-ppa ...
The thing is that 1r,2s-ppa equals to l-ppa (cas# 492-41-0).

Rhodium

  • Guest
The * means that the chiral center can point...
« Reply #39 on: March 22, 2003, 11:34:00 AM »
The * means that the chiral center can point either way, as long as the other one is also changed. By not including the * in your nomenclature you have locked the centers into a single position, and the statement is no longer true.