Sciencemadness Discussion Board

Amide handling precautions?

FireLion3 - 14-8-2014 at 18:18

I have the opportunity to get some Potassium Amide and I am interested in experimenting with it. Just how hazardous is this to handle? I read that impure/colored samples should be dealt with immediately and can be violently explosive, but what about relatively clean samples? Can I safely remove this from its container and weigh it in open air quickly? Or should it not be exposed to any air at all - if so how do I use it? Do I need a special enclosure that has a heavy inert gas?

Just to be clear I have no intention of ordering it until I understand the risks, but I am interested in learning.

zed - 17-8-2014 at 10:47

Well, I haven't used such reagents, but I understand they aren't too, too, dangerous....if you know what you are doing.

Kinda like wild horses on crack.

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

FireLion3 - 17-8-2014 at 12:46

Well its a strong base, and I know the precautions for handling that, but the whole, shock sensitive explosion if peroxides are formed is kind of sketchy.

AvBaeyer - 17-8-2014 at 19:33

FireLion3,

Typically, agents like potassium or sodium amide need to be handled in a glove box or some sort of inert atmosphere environment. My own experience with "store-bought" amides of this type is that quality is questionable - there is no way to know if the material was handled properly at the vendor end. You could take a chance on buying the stuff as to quality. However, do not try to weigh or otherwise handle the material in the air. It will not be very good amide by the time it gets to your reaction.

What do you plan to do with potassium amide? Would something like sodium hydride in mineral oil dispersion work as an alternative? This material can generally be quickly weighed and handled in a normal working environment. I am assuming that if you can source potassium amide you may well be able to obtain sodium hydride.

AvB

FireLion3 - 17-8-2014 at 21:20

Quote: Originally posted by AvBaeyer  
FireLion3,

Typically, agents like potassium or sodium amide need to be handled in a glove box or some sort of inert atmosphere environment. My own experience with "store-bought" amides of this type is that quality is questionable - there is no way to know if the material was handled properly at the vendor end. You could take a chance on buying the stuff as to quality. However, do not try to weigh or otherwise handle the material in the air. It will not be very good amide by the time it gets to your reaction.

What do you plan to do with potassium amide? Would something like sodium hydride in mineral oil dispersion work as an alternative? This material can generally be quickly weighed and handled in a normal working environment. I am assuming that if you can source potassium amide you may well be able to obtain sodium hydride.

AvB


I know I can get Sodium Metal but I'm not sure about Sodium Hydride. Perhaps if I could make the hydride from the metal - though I am not sure how to do this easily.

I was just planning to make and isolate the Na/K enolates of various compounds and experiment with them.

Couldn't an inert atmosphere be created by having a box filled with a heavy gas, and just weighing it that way? Does the amide really react with the air that quickly? From what I gleaned reading about it, it seemed improper storage lead to the formation of the peroxides, but you are saying they can form within seconds of weighing?

DJF90 - 17-8-2014 at 23:11

You won't be able to isolate the enolates easily/at all. If you want to play with enolate chemistry then make/get some LDA. Enolates are formed in solution as needed (typically in THF at -78 *C).

If you were to use KNH2, what solvent would you use? Typically its prepared and used in liquid ammonia at -33 *C) but it can be used in other solvents as a slurry (e.g. toluene).

You say you have experience with other strong bases; to which do you refer. Bear in mind that alkali amides are hygroscopic and react with water.

Dr.Bob - 18-8-2014 at 05:19

I'll second that, potassium amide is rarely used in normal enolate chemistry, it will have other side reactions, it is not an ideal base for enolate chemistry, better to use either sodium methoxide or nBuLi for simple, thermodynamic reactions, or LDA for kinetic ones.

Sodium hydride is most often used for deprotonating hydrogens on heteroatoms, like NH's on amide or heterocycles. It might work for some other reactions, but not ideal for enolate chemistry as far as I know. And potassium hydride is so reactive that I would never use it outside of a well equipped lab or in a shed far from people and houses. Everything it touches will eventually catch fire unless you are in a dessert environment. Been there, done that, don't want to do it again.

FireLion3 - 18-8-2014 at 10:53

I am strongly aware how reactive with water these are and the need for inert solvents. Solvent won't be an issue, there are plenty of inert solvents, as you suggested DJF90, Toluene, Xylene, to name a few. Why can't the enolates from Amides be isolated easily?

If you have an active methylene compound like a ketone and react Sodium or Potassium Amide, will you not get the Na or K salt while ammonia gas is given off? Remove the solvent with vacuum and you should be left with the enolate, the stability of which in a moist atmosphere would depend on how acidic the starting compound was. I don't see any reason why such an enolate could not be isolated.

Dr.Bob, I considered the various alkoxides but the one disadvantage they have is giving off the alcohol once the acidic compound is deprotonated. Alcohols are known to be reactive and interfere with quite a bit of enolate dependent reactions.

Potassium Hydride.... fires...sounds fun! Not. I think I'll stay far away from that, for some time. I can't imagine Sodium Hydride being much safer.

Dr.Bob - 18-8-2014 at 12:19

[If you have an active methylene compound like a ketone and react Sodium or Potassium Amide, will you not get the Na or K salt while ammonia gas is given off? ]
Ammonia is a very nucleophilic amine. I would expect it to react MUCH quicker than an alcohol in the same situation, once the enolate is formed. That's why people use nBuLi, once it abstracts a proton, it forms butane, which is quite unreactive and eventually evaporated (but not at -78C). LDA is too sterically hindered to react as a nucleophile in most cases, once protonated, thus it is the base of choice for many reactions. I may not have phrased the reality perfectly, but that is the way that I think of them.

Sodium hydride is not trivial to work with, but I would say an order of magnitude less prone to fires and safer to work with. I would not have thought it to be so much either, but learned quickly that KH is a nightmare without a drybox. We used a dry bag, but when you try to get a spatula or glassware out, it would almost always catch fire from traces of KH (we are very humid in NC).

FireLion3 - 18-8-2014 at 12:26

Sodium Hydroxide could be a good base if only the water could be removed, to which there are a number of ways. Perhaps if the water is removed by drying agents or through fractional freezing, this could drive the equilibrium forward to form the enolate which would usually be very far to the left. This resulting enolate could then be dissolved in whatever solvent.


DJF90 - 18-8-2014 at 21:37

Alkali hydroxides are very strong bases in the absence of water. There are literature reports of NaOD being able to exchange protons with a thiophene in the 2-position (pKa =38 approx). I've done a little work in this area myself. Typically I had used KOH/TBAB/toluene to do some reactions in the presence of a suitable electrophile. I've even used aq. KOH-Methanol to deprotonate and iodinate phenylacetylene (pKa =22).

You'd be better off using LDA to form your enolates, otherwise you're going to be dealing with equilibrium quantities which means you'll see the aldol reaction to a fairly large extent

[Edited on 19-8-2014 by DJF90]

FireLion3 - 26-8-2014 at 08:17

I've been reading that mixing Sodium or Potassium metal with an active methylene like a ketonewould cause formation of the corresponding enolate, giving off hydrogen gas, with very little alcohol being formed, and minimal coupling product - largely due to the heavily unfavored sterics of ketones.

To cite a specific example:
http://books.google.com/books?id=UZgwAAAAYAAJ&pg=PA956&a...
Quote:

If acetone is treated with metallic sodium, a reaction takes place resembling that of sodium on methyl and ethyl alcohols, free hydrogen is evolved and a white, flaky solid, sodium acetonate, is produced.
....
the whole operation being conducted under a stream of pure and dry hydrogen. By this means, the reaction is rendered less violent, only slight reduction of acetone to isopropyl alcohol takes place, and the sodium acetonate separates in white flakes and may be freed from ether by placing it over solid paraffin, in a vacuum.


It's interesting that when they add hydrogen it doesn't increase the reaction rate. Using another inert gas may further reduce reduction of the ketone. They also do not mention cooling it at all, which I imagine may help to a large degree.

Acetone is one of the lesser hindered ketones. Since it is not exactly what I plan to be working with, I imagine other active methylene compounds that are more sterically hindered may form even less amounts of alcohol. Sodium can be gotten, but I am not how easily it could be powdered.