Zn/HCOOH reduction of nitropropane failure

joe_aldehyde · huxleys associate

yesterday i tried GC_MS' method described in the hive files (hydrogenation of C=C bonds, initially proposed by barium) for reducing the nitro group with HCOOH/Zn after reducing the double bond of MDP2NP with NaBH4.
at first, everything went fine - nitropropene was suspended in IPA/H2O, 2molar excess of NaBH4 was added with vigorous stirring in about 20mins until all color of the canary-yellow nitrostyrene had gone. the solution was then saturated with table salt, but no 2 layers formed as described - not very much NaCl would dissolve. so i decanted the IPA "layer" (which in fact made up the whole liquid volume) and dumped it in a beaker with non-activated Zn (as described in the method, this might be one thing responsible for the failure).

upon addition of HCOOH 98% with vigorous stirring, i couldn't see any hydrogen evolution, maybe due to stirring. in the end i was left with an almost colourless to minimally yellow IPA solution which was reduced in volume, acidified with 80ml 10% HCl, extracted twice with 100ml cyclohexane. it was then basified with KOH soln. 50% and extracted 3x with 200ml cyclohexane which was subsequently dried and removed on a rotavap.

another strange thing was that the cyclohexane in the receiving flask turned a bit cloudy upon rotavapping. either there was acid or water in the rotavap, or both.

anyways, in the end, when dissolving the slightly yellow suspected freebase in IPA and adding a bit of HCl conc. and anhydrous ether to crash out the hydrochloride, only a few tiny white bubbles formed. could this have been from overacidification?

Star-light · Blacklight bulb

anime · Thu Jun 09, 2005 2:04 am

It might be best to extract the nitropropane with a non-polar solvent like dcm. The acid addition is necessary for removal of the excess borohydride.

joe_aldehyde · huxleys associate

ah i missed out on that one. of course i acidified to destroy excess borohydride and added two extra drops acetic acid (100%). so anyways, i used all the IPA with the nitronate in it (if it still was a nitronate). doesn't it get reduced when treated with Zn/HCOOH? since HCOOH is added, there is an acidic environment which ought to liberate the nitronate salt, i even added more HCOOH than needed.
adding too much acid after the borohydride reduction is said to cause major trouble, resulting in tar that is.

anime, doesn't DCM mix with IPA? so even if i add a bit more acid, and then use DCM to extract, the IPA and DCM will combine, so i could just as well use the IPA layer itself.

Star-light · Blacklight bulb

There should be no need for DCM. God knows what you did wrong, it's not very easy to mess this up. Did you stir well whilst adding acid slowly? 40% AcOH is best.

anime · Thu Jun 09, 2005 11:22 pm

Star-light · Blacklight bulb

Joe,

if you post a full write up of what you did, then maybe one of us can spot what you did wrong.

joe_aldehyde · huxleys associate

ok, so here we go.

40mmol of mdp2np were suspended in 100ml IPA, with vigorous stirring, 80mmol NaBH4 was added over 15mins, left stirring for 10 more mins. still stirring, glacial acetic acid was used to destroy excess borohydride, adding two extra drops after fizzing ceased. nitrostyrene color was gone, the clear solution had only a minimal yellow tint. added a heap of NaCl, no 2 layers formed so the IPA layer was decanted and used as is. it was added to 400mmol of unactivated Zn powder in a 250ml erectionmeyer with addition funnel and reflux condenser, and 25ml 98% formic acid was added in 20mins, left to stir for another 10 mins. poured in a bit of water, extracted once with cyclohexane (i saved that layer). basified with KOH soln., lots of white clouds in the nonpolar layer. extracted 3x with cyclohexane. combined cyclohexane was removed on the rotavap leaving a yellow-orange oily residue which was taken up in little IPA, to which was added a bit of HCl conc. and moist ether to effect precipitation. all the stuff did was oiling out, and not really much but only like 3 tiny white bubbles.

Star-light · Blacklight bulb

OK, well first off it looks like you got no layer separation because you added no water to the reaction. The separation is between an IPA layer containing the product and a water layer containing dissolved salts.

The procedure that you need to follow can be reviewed here:

https://www.synthetikal.com/hiveboard/picproxie_docs/000501608-BH4.html

At the end of the reaction, the acetic acid that is added to neutralize should be added dropwise, slowly (40% is best).

As for the Zn/HCCOH reduction, I am not familiar with using unactivated Zinc powder (normally this reaction is conducted after activating the zinc powder with dilute HCl and washing with methanol/IPA).

Did you get a lot of heat generation during the reduction? (the reaction normally generates a lot of heat).

It is normal to continue stirring the reaction until it has returned to room temperature.

Your workup is also a bit different from what I would expect. It is normal to filter off the zinc after the reaction, wash the zinc with a little IPA and combine this washing with the filtrate.

The solvent is then removed under vacuum and the resulting product is dissolved in dilute HCl. This amine.HCl solution is then washed with DCM to remove impurities, and separated. The solution is then basified upon which an oil separates which is extracted with toluene, dried and the salt is formed in the normal manner.

Your writeup states that your amine was a yellow-orange oily residue which shows it was very impure (should be water-white) and probably contains unreduced material. Doing an acid base with DCM cleanup as described above will fix this problem and make crystallization much easier when you form a salt.

In addition, using conc. Hcl and moist ether to form a salt is introducing water into the mixture which will make crystallization more difficult if not impossible. You need to try the toluene solution and use HCl gas for best results.

64bandil · Busy Bee

Sorry about the late reply. Im kinda busy these days...

First of all. Remember water in that BH4 reduction. It's needed in the reaction and most of your borate salts will leave the reaction that way. So, don't proceed untill you get a layer separation in the IPA/water layer. If the nitrostyrene definately is reduced (TLC + white color) and theres too little water for separation, simply add brine.

In the Zn/HCOOH reduction, it's very important to use activated zink. Stirr it with at little acid for a minute or two and then filter. It might work without - but theres a real chance of volcano reaction. Also, 85% instead of 98% formic acid seems to work best - don't know why. It is also a good idea to use potassium formate instead of straight up formic acid. The yields will go up!

Finally: upon workup. Filter the zinc, wash with more IPA, combine and evaporate the solvent. Add water, DCM and basify(!) with sodium hydroxide. This causes the remaining Zinc salts to precipitate as Zn(OH)2. The trick for removing this is washing with 15-20% ammonia. It will complex with the zinc salts and remove the "bucket of paint" appearance (think its called the lemminger reaction). Once it's clear wash with dH2O and extract into acidic water. Wash it with any NP, rebasify and extract the usuall way.

Your formation of the hydrochloride is not totally by the book. Use the azeotropical drying method I always preach - it rocks!

Good luck - Bandil

joe_aldehyde · huxleys associate

i will be using calcium formate since that's what i have on the shelf, are there going to be any problems with that? since the cation of the salt does seem to matter (ammonium vs. sodium vs. potassium formate as tried out by barium in CTHs).

how do i add the formate salt, make a solution out of it and add that instead of the formic acid? i don't understand how the reaction proceeds between the formate salt and Zn to form H2 (nasc.), maybe somebody could clear this up.

bandil, as to your workup, i understand what you mean until "washing with ammonia", the Zn hydroxide or the DCM layer? i also have no idea what the "bucket of paint" stuff is about.
would be nice if you referred me to a source where i can read about your drying method Smile

thanks alot guys, appreciate your comments!

64bandil · Busy Bee

Read "pH control when gassing" in one of the forums. I made the entry about salting there.

When using CTH's, the yields from different cations are usually:

potassium > ammonium > sodium...

So using potassium is obviously best Smile

I can see my description of the lemminger reaction was quite vague, allow me to clarify:

When you basify the remaining product/sludge/Zn salts in an aqueous medium, the Zn++ ions will form the isoluble Zn(OH)2 salt. This wont simply bee a good salt and sediment, but it'll make you'r life miserable by making the water all white and paint like. It'll make emulsions from hell when you try to extract it with a NP.

So, what you do is this: Suspend the product / sludge in a little water / NaOH and make sure everything is really basic. You'll have a gross looking white can of paint. Add decent amounts of DCM to extract the amine. Before you separate the layers, add lots of 25% aq. NH3. This will make the Zinc salts soluble and make the layers separate nicely. Separate the NP and extract the ammonia/water/NaOH/product with more NP.

The NP will contain your product + a little ammonia, which will evaporate once you strip the NP.

I think you havn't noticed the bucket of paint, because your reaction never kicked in. It's the reaction that gives you those nasty Zinc ions...

Regards
bandil

joe_aldehyde · huxleys associate

thanks again bandil, but now i still don't understand HOW to add the formate salt, i can't just drip it in...and as to the reaction of the formate with Zn, i'm still not quite sure how that would work, since the formate ion is in fact a weak base, hence no protons to be reduced to H2 by Zn.
or is HCOO- going to react like that: 2HCOO- -> H2 + 2CO2 + 2e-?

so, if i get that right, the weaker the bond between formate anion and corresponding cation, the better. so calcium is just about overkill here thanks to it's huge electron cloud compared to Na/K/NH4.

why don't i basify with NH3 right away when extracting with DCM or the likes?
considering basicity of NH3 vs. secondary amines in water, secondary amines are stronger bases and thus can't be made freebases using NH3, especially not aq. NH3. but, in fact, upon addition of ammonia to a NaOH solution, the pH ought to be lowered since NH3 can act as a weak acid (pKa=9,25), protonating OH- and subsequently the secondary amines when using an excess of NH3.
good read:
http://www.chemguide.co.uk/inorganic/complexions/aquanh3.html

have you never tried to filter of the Zn(OH)2, which is in fact a [Zn(H2O)4(OH)2] complex?

64bandil · Busy Bee

Yes, it's the formate that does that actual reducing. You simply add the formate salt dry in one portion. It's somewhat less exothermic than with formic acid. I don't know the actual reaction mechanism, but the formate get's broken down to carbon dioxide.

I do not know what makes the cation a good hydrogen donor, so i can't tell you if calcium will work or not.

I suppose you can use ammonia to basify. Im simply oldschool when it comes to working my products up - hence the sodium hydroxide Smile

One advantage of using sodium hydroxide could be that it makes the aqeous phase more polar, thus forcing more goodies into the NP. But its probably a neglible amount...

Yes I have tried filtering the Zn salts. It's damn near impossible, especially with a nice freebase layer floating on top or below. Another solution would be to steam distill the whole mess...

Regards
Bandil

transistor child · gnome

Hypotetically speaking SWIM don't see the Zinc-salts as much of a problem. Extration with toluene works fine, and doesn't give either emulsions or problems with separation of the two phases.