Sciencemadness Discussion Board

Ephedrine from Propiophenone...

evil_lurker - 31-7-2006 at 10:28

I was thinking that if one were to brominate the ketone and subsequently react it with ammonia they could form Cathinone.

From that Cathinone one could add formaldehyde to form the imine and the imine/ketone could be reduced completely to the alcohol, DL-Ephedrine, using sodium borohydride.

Does this sound right?

Sergei_Eisenstein - 31-7-2006 at 10:42

Cathinone may self-condense, yielding a substituted piperazine after reduction.

Organikum - 31-7-2006 at 10:54

I thought this goes like:

- Bromination
- Addition of methylamine to form Methcathione
- Reduction of the methcathione with Al/Hg or NaBH4 to yield (peseudo)ephedrine, or catalytic hydrogenation to yield methamphetamine directly.

Or the Delepine as alternative?

/ORG

Vitus_Verdegast - 31-7-2006 at 11:00

Cathinone is indeed more prone to self-condense than methcathinone, yet when swapping the -Br by -CH3NH2 already quite a lot of pyrazine is formed.
(see Kinetic's old posts for this)

What about propiophenone + R-ONO --> isonitrosopropiophenone --Al/Hg--> norpseudoephedrine
http://www.orgsyn.org/orgsyn/orgsyn/prepContent.asp?prep=cv2...

(Yeah I know it's not ephedrine)

turd - 31-7-2006 at 13:10

This will give a mixture of 2 enantiomeric pairs, quite possibly hard to purify.

Nicodem - 1-8-2006 at 00:19

I believe one enantiomeric pair (one diastereoisomere) should be prevailing as the major product with just about all reducing systems.

In any case, due to symetricity of the reactions, in the total mixture the ratio or R over S conformation at the carbon where the amino is attached would be exactly 50:50 (in case this is what interests the first poster).

[Edited on 1-8-2006 by Nicodem]

Sandmeyer - 3-8-2006 at 07:59

Well a chiral auxiliary can be added to the reduction matrix see following Corey papers: JACS 1987, 109 , 7925; TL 1990, 31, 6111 ; TL 1992, 33 , 4141

BH3-THF is reducing agent (Ar-C=O -> Ar-C-OH) and auxiliary being cat. amnt. of oxazaborolidine, this way one gets > 90% ee. But why would anyone around here care of getting exclusivly one enantiomer?

A more recent example, also detailing preparation of oxazaborolidine

Tetrahedron Volume 59, Issue 42 , 13 October 2003, Pages 8411-8414

Practical enantioselective reduction of ketones using oxazaborolidine catalyst generated in situ from chiral lactam alcohol and borane

Abstract

Reduction intermediate prepared in situ from chiral lactam alcohol 3 and borane at room temperature was found to catalyze the borane reduction of various prochiral ketones with high enantioselectivity up to 98% ee.

Fullpaper: http://rapidshare.de/files/28051042/sdarticle.pdf.html


[Edited on 3-8-2006 by Sandmeyer]

[Edited on 3-8-2006 by Sandmeyer]

LSD25 - 23-1-2008 at 04:34

Organikum,

The question has been dealt with over at WD where the requisite information can now be found.

This material is obviously 'drug-cookery' related, so it is innapropriate for this forum (just ask the person that Polverone says I am not allowed to irritate).

[Edited on 24-2-2008 by LSD25]

Organikum - 23-1-2008 at 08:47

Wow, thanks! I knew about the Rhodium stuff but now I have some reading, very nice.....

Looks I have to whip out the olde setup I used for making benzene and other stuff from benzoic acid, it was so charmingly simple and chemoleos great suggestions for the preparation of metal(II)salts.... :D

/ORG

smuv - 23-1-2008 at 15:52

Quote:
Originally posted by Organikum
Or the Delepine as alternative?


Does the Delepine reaction work for secondary halides? I think hexamine is too bulky to form a proper intermediate with anything but a primary halide.

WizardX - 23-1-2008 at 16:04

Self deleted.

[Edited on 24-1-2008 by WizardX]

JohnWW - 23-1-2008 at 16:14

Quote:
Originally posted by WizardX
Double standards! Why is this thread not locked when the phenylacetonitrile thread was lock for drug related synthesis?

Why should it be stopped? Drugs are good for you! And besides, what about the First Amendment?

[Edited on 24-1-08 by JohnWW]

smuv - 23-1-2008 at 16:23

The other thread was stopped because it was a 'cookery' thread..."I read this in pihkal is it right..." Really though lets try to stay on topic.

Could TCCA be used to chlorinate the ketone, similar to acetone=>chloroacetone? I have seen an abstract showing the synthesis of alpha-chloro-acetophenone with TCCA/BF3 but thats not so convenient.

WizardX - 23-1-2008 at 16:28

Self deleted.

[Edited on 24-1-2008 by WizardX]

WizardX - 23-1-2008 at 16:34

Quote:
Originally posted by Vitus_Verdegast
Cathinone is indeed more prone to self-condense than methcathinone, yet when swapping the -Br by -CH3NH2 already quite a lot of pyrazine is formed.
(see Kinetic's old posts for this)

What about propiophenone + R-ONO ==> isonitrosopropiophenone ==(Al/Hg)==> norpseudoephedrine
http://www.orgsyn.org/orgsyn/orgsyn/prepContent.asp?prep=cv2...

(Yeah I know it's not ephedrine)


The simplest method has already been posted. N methylate the norpseudoephedrine to get ephedrine.

Drunkguy - 24-1-2008 at 06:40

Norpseudoephedrine = Phenylpropanolamine

Phenylpropanolamine is more conveniently prepared by Henry reaction of PhCHO + EtNO2, under mild conditions without the dehydration. The product can be reduced with Zn/HCl and is then distilled under vacuum.

^This reaction was online not that long ago, I think Java uploaded the pdf.

[Edited on 24-1-2008 by Drunkguy]

Attachment: nitrostyrenes.fe-hcl.pdf (428kB)
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chemrox - 24-1-2008 at 22:51

Quote:
[Fullpaper: http://rapidshare.de/files/28051042/sdarticle.pdf.html


Please re-post - I got a file not found on this.. also please consider sharing the TL articles (I can get the JAC)

Thanks,
CRX

Filemon - 27-1-2008 at 13:21

The bromopropiophenone may reduce with Al(iOPr)3 => bromopropanolbenzene => norephedrine

The Al(iOPr)3 don't attack halogens.

http://en.wikipedia.org/wiki/Aluminium_isopropoxide

http://en.wikipedia.org/wiki/Meerwein-Ponndorf-Verley_reduct...


[Edited on 27-1-2008 by Filemon]

[Edited on 27-1-2008 by Filemon]

Nicodem - 27-1-2008 at 14:02

And how do you propose the "bromopropanolbenzene => norephedrine" transformation to happen?
In the reaction of this bromohydrine with NH3 or RNH2 a mixture of Ph-CH(NHR)-CH(OH)-Me and Ph-CH(OH)-CH(NHR)-Me stereoisomers and polyalkylated products are obtained (of course, with NH3 as nucleophile the polyalkylation becomes a serious problem).

Filemon - 27-1-2008 at 14:26

With a great excess of ammonia it is obtained good yields. I gave it for course.

[Edited on 27-1-2008 by Filemon]

S.C. Wack - 27-1-2008 at 14:28

I'm familiar with the reduction of a-bromopropiophenone with Al isopropoxide in a pair of JACS articles, in 1938-40. The results are less than encouraging for the reaction and workup given - there may be good reasons why other reductions are more popular.

The reaction of the alcohol with methylamine is also explored. 10% yield dl-pseudoephedrine from the ketone.

stoichiometric_steve - 1-2-2008 at 15:57

another procedure, using Br2 in DCM, then N-methylpyrrolidone, pretty quick! replace t-butylamine with benzylamine, NaBH4, Pd/C, there goes your PPA.

Drunkguy - 2-2-2008 at 13:07

I have the Henry reaction here. Under vigorous conditions the nitrostyrene is formed because of a dehydration step. Under mild conditions though, this doesnt happen. In the paper I have, Et3N can be used as the choice of mild base. Then for the reduction, zinc can be used. This *does* work although I have not tried it, it will certainly reduce a nitro group, Fe is also possible.

^That's certainly a hack-of-alot more straightforward than Friedel-Crafts, alfa-bromination, and aminolysis.

Phenylpropanolamine, though subsequently banned, is good for making U4Euh, which is one heck of an abusable stimulant.

Going back to the thread poster, he seemed to be interested in making ephedrine. A couple of reviews deal exclusively with this topic already. In the attachment the following is noted:

The production of racemic ephedrine from propionic acid is done by the following scheme [65]. By the Friedel-Crafts reaction in benzene, propiophenone is obtained. This is brominated to bromopropiophenone which, without isolation, is converted by the action of methylamine into methylaminopropiophenone. On the catalytic hydrogenation with palladium on carbon or with Raney nickel, a mixture of racemic ephedrine and racemic pseudoephedrine is formed, from which (Xl) is isolated in the form of the hydrochloride.

I also have this one for a more biotic route to follow (though not by me):

Biotransformation of benzaldehyde to
L-phenylacetylcarbinol (L-PAC) by "Torulaspora delbrueckii" and conversion to ephedrine by microwave radiation. (2002)

Why not just get alfa-methyl-styrene, make the epoxide, then react with methylamine. That would give a pair of positional-isomers, but im guessing that the ephedrine products would be preferentially formed, esp. if the conditions are right.

[Edited on 2-2-2008 by Drunkguy]

Attachment: Isolation,_Analysis,_and_Synthesis_of_Ephedrine_and_its_Derivatives.pdf (911kB)
This file has been downloaded 5153 times


Nicodem - 3-2-2008 at 03:13

Quote:
Originally posted by Drunkguy
Why not just get alfa-methyl-styrene, make the epoxide, then react with methylamine. That would give a pair of positional-isomers, but im guessing that the ephedrine products would be preferentially formed, esp. if the conditions are right.

Because you only get a few % yield of the correct regioisomers. See a couple of posts above where the reference about the reaction of the bromohydrine with MeNH2 is described. Since it works by the same mechanism (forming first the epoxide, followed by nucleophilic ring opening), there is no reason to believe a direct use of the epoxide would be any better. Only epoxides of terminal akenes give good regioselectivity in ring opening reactions with basic nucleophiles.

stoichiometric_steve - 3-2-2008 at 04:52

Quote:
Originally posted by Drunkguy
I have the Henry reaction here. Under vigorous conditions the nitrostyrene is formed because of a dehydration step. Under mild conditions though, this doesnt happen. In the paper I have, Et3N can be used as the choice of mild base. Then for the reduction, zinc can be used.


you should try the reaction as described in the patent. there is very, VERY little conversion to the nitroalcohol under the conditions the authors "used" (why does it all work so beautifully when typed up into a patent?). all you get is a thick, viscous mass of triethylamine - ethylnitronate. this is supposed to react with benzaldehyde at -10°C, but surely not in a matter of a few hours - not without solvent and vigorous stirring! also, there is no reasonable workup given.

is it even possible to distill the nitroalcohol without the risk of dehydration?

under these aspects, the propiophenone route looks much, much better, especially the "one-pot" route with DCM/NMP.

Filemon - 3-2-2008 at 07:26

It is also possible to make the condensation nitroalcohol with KOH, increasing the pH at 8 or 10. It is not necessary agitation because it is dissolved.

http://www.orgsyn.org/orgsyn/pdfs/CV5P0833.pdf

smuv - 3-2-2008 at 12:17

A reference for the the rambles of niggaknow from orgsynth . This is a reaction I was not aware of and is pretty interesting.

@niggaknow, if you want people to take you seriously try to express yourself more eloquently.

P.S. Why did you even bother editing that post twice?

niggaknow - 3-2-2008 at 15:18

Di bee da bomb!

2243295

http://www.pat2pdf.org

wa gwan - 4-2-2008 at 13:16

I vaguely remember reading something about reacting alkanophenones with N-bromoalkylamines. So for example N-bromoethylamine would brominate and ethylaminate propiophenone all in one pot without all the joys the two step reaction has to offer.
Anyone familiar with this?

It could be a patent or journal article but I've got the feeling it was in german if that helps.

[Edited on by wa gwan]

Nicodem - 4-2-2008 at 23:41

You could have tried using the search engine:
https://sciencemadness.org/talk/viewthread.php?tid=3963

PS: You can not use N-bromoethylamine, only the N-bromo secondary amines.

Drunkguy - 5-2-2008 at 06:30

It's not even from a patent, it was a literature entry.

Quote:
Originally posted by stoichiometric_steve

you should try the reaction as described in the patent. there is very, VERY little conversion to the nitroalcohol under the conditions the authors "used" (why does it all work so beautifully when typed up into a patent?). all you get is a thick, viscous mass of triethylamine - ethylnitronate. this is supposed to react with benzaldehyde at -10°C, but surely not in a matter of a few hours - not without solvent and vigorous stirring! also, there is no reasonable workup given.

is it even possible to distill the nitroalcohol without the risk of dehydration?

under these aspects, the propiophenone route looks much, much better, especially the "one-pot" route with DCM/NMP.


Attachment: Henry Reaction.pdf (58kB)
This file has been downloaded 2227 times


stoichiometric_steve - 5-2-2008 at 07:53

Quote:
Originally posted by Drunkguy
It's not even from a patent, it was a literature entry.


that reference looks even more promising. if i ever have the opportunity to try it out, i will report it here. although i have my doubts with H2O as solvent...

wa gwan - 6-2-2008 at 13:04

Quote:
Originally posted by Nicodem
You could have tried using the search engine


I could but I wasn't that interested. If I had been I'd have made of point of remembering it the first time I read it. ;)

unome - 29-10-2009 at 20:15

Propiophenone can be got to via known routes (from benzoic acid and propionic acid by the procedure of Granito & Schultz – attached), there are ref’s from Psychokitty (mainly, although many worked on it, for example, here) on how to brominate propiophenone using Cupric Bromide to a-bromopropiophenone which could then be used in another known route (that of Hyde, Browning & Adams, also attached), ie. by adding the a-bromopropiophenone to an 30% alcoholic solution of methylamine to give Methcathinone in fairly ordinary yields (57% cited), using Adam's Catalyst, appropriately enough, they reduced that to racemic ephedrine/pseudoephedrine...
[img]https://www.sciencemadness.org/whisper/files.php?pid=165102&aid=8931[/img]
Propiophenone.2.Cathinone.JPG - 10kB

Given the difficulty involved in finding bromine in any useable quantity, it became necessary to examine whether any similar routes could be used with chlorine. There is a series of journal articles of interest (one in particular, which is attached - Kosower, et al), which claims good yields of a-chloropropiophenone via the Cupric Chloride chlorination of propiophenone. I am assuming that this could be utilized similarly to the a-bromo derivative to give Methcathinone as well. I have also attached one of the MPV Reduction of Methcathinone papers (the one with the note on the ephedrine series, all that says is that one shouldn’t try and use the bromohydrin (ie. the reduced product with methylamine – ie. use a modified version of that used by Hyde, et al). To top all that off, I have also attached a paper in which Mandelate esters are catalytically reduced to the phenylacetic acid by refluxing with excess Raney Nickel (wonder if precipitated Nickel/Alumina or Urushibara type would work?) in ethanol.

PS The only person I've seen who has claimed any real success with the production of propiophenone from Benzoic & Propionic acid + Iron salts, is Organikum. Perhaps those who are interested might care to look through the Benzene from Benzoic acid threads for his (1) reaction vessel (2) procedure and (3) what he says vis-a-vis black iron oxide pigments. He was (maybe still is) an obnoxious prick at times, but he did KNOW his stuff

Attachment: Bromination.Cupric.Bromide.pdf (391kB)
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Attachment: Chlorination.Cupric.Chloride.pdf (556kB)
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Attachment: CTH.RaNi.EtOH.EthylMandelate.pdf (413kB)
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Attachment: MPV.Bromoketones.NB.Ephedrine.Series.pdf (571kB)
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Attachment: Synthetic.Homologs.of.Ephedrine.Hyde.etal..pdf (400kB)
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Attachment: Decarboxylation.StudiesII.Prep.Alkyl.Phenyl.Ketones.Granito.Schultz.pdf (422kB)
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[Edited on 30-10-2009 by unome]

unome - 4-11-2009 at 16:30

Here is a procedure in which the authors (Patrick, McBee & Hass) prepare the relevant benzedrine derivative by displacement of 1-phenyl-2-chloropropane with either ammonia/methylamine, which is the pretty much the final link in the chain;)

Attachment: amination.phenyl-2-chloropropane.pdf (359kB)
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VestriDeus - 17-11-2009 at 16:15

Isn't ephedrine like a schedule II controlled substance??

entropy51 - 17-11-2009 at 18:11

Quote: Originally posted by VestriDeus  
Isn't ephedrine like a schedule II controlled substance??
No, but sales are tightly regulated and monitored closely.

unome - 24-12-2009 at 05:08

I've been thinking about something, we've all seen the papers where students are shown how to make Bupropion? Well, they use Br2 in CH2Cl2 to brominate propiophenone in no time flat (and virtually 100% yield), remove the CH2Cl2 (distillation @40'C), thus isolating the nasty ketone without having to come into contact with it.

They then alkylate t-butylamine in NMP which is a good solvent, water miscible, which simplifies workup as they only take the organic layer once they base out the alkaloid.

What about a modification of that for Methcathinone? Methcathinone has been made before now by dropping a-bromopropiophenone into an ice cold alcoholic (read absolute ethanol or thereabouts) solution of methylamine...

Quote:
Taken from:

SYNTHETIC HOMOLOGS OF d,l-EPHEDRINE

J. F. Hyde, E. Browning and Roger Adams

J. Am. Chem. Soc., 1928, 50 (8), pp 2287–2292
DOI: 10.1021/ja01395a032

Page 4/6 (2290):

Reaction of the Bromo Ketones with Methylamine.

One-tenth of a mole of the bromo ketone was added drop-wise with vigorous stirring to 0.25 mole of methylamine (in the form of a 30% solution in absolute alcohol) over the required period of time (one hour for bromopropiophenone, seventeen to eighteen hours for a-bromobutyrophenone, twenty-four hours for a-bromovalerophenone). The reaction flask was immersed in ice water during the reaction and stirring was continued for one-half to three-quarters of an hour after the addition of the bromo compound. Cold, concd. hydrochloric acid was then added very slowly along with some finely cracked ice until the mixture was acidic. If it became warm the product turned very dark in color and a larger proportion of tar was produced. At this point the reaction mixture was orange or red due to the presence of some bromo ketone that had not reacted and to the formation of certain tarry by-products. These were extracted with ether from the water layer and the bromo ketone recovered. The water layer was evaporated to dryness in vacuo, treated with a little chloroform and evaporated to dryness again to assist in removing the moisture from the rather hard mass. After standing in a vacuum desiccator for a day, the residue was extracted several times with fresh portions of chloroform and each time the insoluble crystals of methylamine hydrochloride were filtered. The chloroform solution was then evaporated until it was very concentrated, and acetone was added to cause the crystallization of the amino ketone hydrochloride. Recrystallization was carried out by dissolving in a small amount of alcohol, filtering, and adding about twice the volume of acetone in small portions.


Personally, albeit hypothetically, I'd have to suggest utilizing the isolation procedure outlined in the Bupropion synthesis... The solubility of Methylamine base in water is 108g/100mL, whereas the solubility of Methcathinone base in water is virtually nil.

I'd suggest adding a non-polar solvent, toluene/xylene/etc. then removing the volatile(s), ie. any remaining methylamine base and the ethanol.

No nasty, hard to get chemicals (saving methylamine, propiophenone & bromine of course).

PS There are MANY, MANY articles that state categorically that hydrogenation of ephedrone with 10% Pd/C @ 55psig (~4Atm IIRC) gives desoxyephedrine directly.:cool:

[Edited on 24-12-2009 by unome]

Attachment: Hyde.Browning.Adams.Synthetic.Homologs.of.Ephedrine.Hyde.etal..pdf (400kB)
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[Edited on 24-12-2009 by unome]

[Edited on 24-12-2009 by unome]

Waffles SS - 14-3-2010 at 10:45

May NaBH4 or LiAlH4 use for make ephedrine from ehedrone?(replace for hydrogenation step by Raney Nickel)
NaBH4 and LiAlH4 is reducing agent and convert Ketones to Alcohols

[Edited on 14-3-2010 by Waffles SS]

Melgar - 17-3-2017 at 18:37

If I'm not mistaken, NaBH4's specialty is converting carbonyl oxygens to alcohols. LiAlH4, not so much.

NitratedKittens - 30-3-2017 at 23:21

Just how is this not in detritus right now?

clearly_not_atara - 30-3-2017 at 23:57

Better question: why did Melgar, who usually knows what he's doing, bump a thread that was last replied to in 2010?

Melgar - 31-3-2017 at 04:30

Quote: Originally posted by clearly_not_atara  
Better question: why did Melgar, who usually knows what he's doing, bump a thread that was last replied to in 2010?

Too many tabs open and I forgot which one was which. Noticed someone say something that didn't seem accurate, and did a quick reply. Sorry, my bad.

On the other hand, this is like the first time anyone here has said anything nice about me in years! Everyone is normally such pricks here, including me, come to think of it.

Waffles SS - 31-3-2017 at 08:48

I am sorry for my stupid 7 years ago question.

[Edited on 31-3-2017 by Waffles SS]

Melgar - 31-3-2017 at 12:28

It's okay Waffles, you've come a long way since then!

Incidentally, I managed to get my hands on some propiophenone, and am looking for interesting reactions that use it. The one referenced earlier in this thread sounds really interesting, which is why I had it open in the first place:

http://www.orgsyn.org/demo.aspx?prep=cv2p0363

However, it would be nice to know if there's any possible alternative to HCl gas. If I'm going to screw around with HCl gas that's not incorporated into the end product, I may as well make HBr gas, so I can collect the vapors in water and save them for later. My thought is that the yields would improve slightly with HBr, but I could very easily be wrong.

Also, I seem to be able to store alkyl nitrites indefinitely, by adding some sodium carbonate to the containers, so how important is it really, that the nitrites be freshly prepared? Is it just so the stoichometry comes out right?

[Edited on 3/31/17 by Melgar]

karlos³ - 31-3-2017 at 13:34

A nice alternative to HCl gas?

I´ve got one for you, tested and tried!

Look here, that was my reference to use this reaction on propiophenone, which worked very good on it.
http://chemistry.mdma.ch/hiveboard/novel/000492480.html'
Try it! Yield is at least as good as using acidic catalyst!

Edit: Of course the nitro ester should be distilled freshly in any case.

[Edited on 31-3-2017 by karlos³]

Melgar - 31-3-2017 at 14:00

Quote: Originally posted by karlos³  
A nice alternative to HCl gas?

I´ve got one for you, tested and tried!

Look here, that was my reference to use this reaction on propiophenone, which worked very good on it.
http://chemistry.mdma.ch/hiveboard/novel/000492480.html'
Try it! Yield is at least as good as using acidic catalyst!


Wait... this is an isonitroso compound, not a nitro anything. At the end, the one guy says it's reducing a nitroalkene to an amine, which isn't actually true, since it's just a ketoxime, which is what "isonitroso" is an old term for. Oximes, being imines of hydroxylamine, which are apparently far more stable than ordinary imines.

It uses sodium ethoxide though, which basically necessitates that you have metallic sodium. (Which I do, but when coming up with novel synthetic routes, the more OTC the better, IMO) I wonder if aluminum ethoxide would suffice?

Quote:
Edit: Of course the nitro ester should be distilled freshly in any case.

Nitro esters... you mean like nitroglycerin? Or ethyl nitrate? ;)

[Edited on 3/31/17 by Melgar]

clearly_not_atara - 31-3-2017 at 21:43

Quote:
It uses sodium ethoxide though, which basically necessitates that you have metallic sodium.


To post this on the forum that made famous the OTC synthesis of sodium ethoxide?
http://www.sciencemadness.org/talk/viewthread.php?tid=2656

Melgar - 31-3-2017 at 22:51

Quote: Originally posted by clearly_not_atara  
Quote:
It uses sodium ethoxide though, which basically necessitates that you have metallic sodium.


To post this on the forum that made famous the OTC synthesis of sodium ethoxide?
http://www.sciencemadness.org/talk/viewthread.php?tid=2656

Hence, the reason I qualify all my statements with words like "basically", "probably", "likely", and "virtually". There's no such thing as 100% certainty in science!

It seems to work based on the fact that a saturated NaOH solution is heavier than a sodium alkoxide solution, and sodium ethoxide is much more soluble in ethanol than sodium hydroxide is. This makes me wonder if you could do it as a batch, by putting quicklime (calcium oxide) at the bottom. Or stirring anhydrous ethanol and sodium hydroxide with a quicklime suspension. Or if it'd be possible to have an electrolysis cell going with sodium hydroxide in alcohol? I never really thought much about routes to alkali alkoxides, just because I've rarely had much use for one.

edit: Ok, so I set up an experiment with potassium hydroxide in methanol. That was the only alcohol I had that was more than 95% pure, other than n-butanol. I don't quite know why I opted for potassium. There are definitely bubbles at the cathode, and they're very fine. Over time, if this is generating an alkoxide, current should increase, as the concentration of the alkoxide makes it more conductive, right? And if it's not, the current should decrease, since then it'd just be using residual water to generate the hydrogen, which would gradually get used up.

edit2: I'd still be curious if aluminum ethoxide would work for a reaction like this.

[Edited on 4/1/17 by Melgar]

clearly_not_atara - 31-3-2017 at 23:27

Quote:
Ok, so I set up an experiment with potassium hydroxide in methanol. That was the only alcohol I had that was more than 95% pure, other than n-butanol. I don't quite know why I opted for potassium. There are definitely bubbles at the cathode, and they're very fine. Over time, if this is generating an alkoxide, current should increase, as the concentration of the alkoxide makes it more conductive, right? And if it's not, the current should decrease, since then it'd just be using residual water to generate the hydrogen, which would gradually get used up.


Methanol is unique among aliphatic alcohols in that it's more acidic than water (pKa 15.5 vs 15.7) so methoxide is the predominating species in any mixture of KOH and methanol. However IIRC it is not practical to dehydrate methanol with KOH because the solubility is so high, owing to methanol's acidity.

I believe such solutions can also be dehydrated over K2CO3.

karlos³ - 6-4-2017 at 14:35

Quote: Originally posted by Melgar  

Wait... this is an isonitroso compound, not a nitro anything. At the end, the one guy says it's reducing a nitroalkene to an amine, which isn't actually true, since it's just a ketoxime, which is what "isonitroso" is an old term for. Oximes, being imines of hydroxylamine, which are apparently far more stable than ordinary imines.

It uses sodium ethoxide though, which basically necessitates that you have metallic sodium. (Which I do, but when coming up with novel synthetic routes, the more OTC the better, IMO) I wonder if aluminum ethoxide would suffice?

Quote:
Edit: Of course the nitro ester should be distilled freshly in any case.

Nitro esters... you mean like nitroglycerin? Or ethyl nitrate? ;)

[Edited on 3/31/17 by Melgar]


Well, the reduction itself there, I don´t know if this works as advertised. Probably it does on isonitrosoacetophenone as used in this example, but not so likely with our substrate. Anyway!

I would think that an alcoholic solution of KOH/NaOH in dry alcohol, which then does contain some alkoxide, would be worth a try.
So the metallic sodium may not be needed.
However, I used it as I wanted to follow the procedure as close as possible, and it has worked fine, with very satisfying results already on the first attempt.

As for the "nitro ester", please excuse this! :o
It was late and, of course I meant nitrite esters, e.g. isopropyl nitrite, amylnitrite and similar, and not nitrate...
The former was what I´ve used by the way.