Author Topic: Formic acid reduction - comments  (Read 8207 times)

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  • Guest
Formic acid reduction - comments
« on: September 20, 2003, 11:16:00 PM »
Having worked with nitropropene reductions using NaBH4 / formic acid, i would like to share some comments on that reaction type.

First of all: To hell with LAH, these reactions are seriously nice to work with.

The borohydride reduction is well known to many people. It is really fast, and the workup is a breeze.

Reduction of the nitro group can be performed with formic acid, as described in Indian Journal of Chemistry, Section B: Organic Chemistry (2001), 40B(1), 75-77.. Barium has tested the reaction with ammonim formate, so swim decided to test it with formic acid. The reaction is very vigorous and care must be taken when adding the formic acid, as it WILL boil over if added to fast(max. 5% of the formic acid can be added per time).

It is also very important to activate the zink with 5% hydrochloric acid before use. The first run was done without doing this, as swim thought the formic acid would eat through the oxide layer and activate it in-situ. It might have done that in time, but swim was not patient enough. On the second run activated zink was used and the formic acid was added without to much thought. Bad idea, 20% of the reaction mixture got splattered on the hot plate.

Here is the technical writeup, using 2,4,5-trimethoxynitropropene(which was prepared alá Barium):

6 grammes of 2,4,5-trimethoxynitropropene was reduced alá


( to give 5,6 grammes(93% yield) colorless crystals of 2,4,5-trimethoxynitropropane. The only difference was that chloroform was used in stead of toluene for the extraction of the nitroalkane.

5,6 grammes of the isolated crystals where dissolved in 22 mL methanol and mixed with 2,0 grammes of activated Zn. 12 mL 85% formic acid was added in small portions(the first portion caused a major boil over, be seriously carefull; it is even more agressive than LAH reductions). After addition, the mixture was allowed to return to room temperature and filtered to remove the Zn/salt slurry. The remaining liquid was slightly yellowish. The solvent was stripped, and the remains where acidified with HCl and dissolved in water. Afterwards it was washed once with chloroform. The water was basified with sodium hydroxide, which caused a clear oil to fall out(TMA-2). There was not enough time for work up, so yeilds will be posted later.

There is no obvious reason to go through the trouble of making a salt of formic acid, when that can be used straight away.

All in all:

-The reaction is faster than LAH reductions
-It's mega cheap
-It does not want to kill and destroy you like LAH with ethers.
-It's high yielding.
-It's less suspicious chemicals that are used.
-It seems more clean than LAH reductions.

The reaction is so cheap and easy, that swim will refer to it as the Joan Collins reaction from now on!

Swim is definately over his LAH days, that's for sure.



  • Guest
« Reply #1 on: September 20, 2003, 11:57:00 PM »
What a coincidence!!! SWIM was just reading your post while reducing some 2,5-dimethoxynitrostyrene with NaBH4.

Well, he'll give the Joan Collins reaction a try tonight.



  • Guest
Formic acid/Zinc NitroalkAne Reduction
« Reply #2 on: September 21, 2003, 02:12:00 AM »
FYI, the referenced article can be read here:

Indian Journal of Chemistry, Section B: Organic Chemistry (2001), 40B(1), 75-77


Good job, Bandil! I'm looking forward to hearing about your isolated yield of the hydrochloride salt.

Edit: There is one thing in the article which is bogus though, and that is their claim that the product amines are pure directly upon evaporation of the solvent, a microscale test I made on a nitro alcohol had four spots on TLC in addition to the desired product, one was some unreacted starting material, two were unidentified non-polars, and one small spot was even carried through an A/B extraction.

Thus, when using this method an A/B extraction plus recrystallization of the amine salt is mandatory, and distillation desirable (but that's only feasible with larger batches).

But if formates work this good, then how smooth wouldn't it be with two hydrogen sources in one? Naturally, I'm thinking of

Zinc/Hydrazinium Monoformate Reduction of Nitro Compounds to Amines



  • Guest
alkene or alkane ?
« Reply #3 on: September 21, 2003, 05:35:00 AM »
Chief, you describe the subject of your post as "Formic acid/Zinc Nitroalkene Reduction", but on both articles I can only find nitroalkane reductions, no mention of double bonds betting reduced.
In fact in both articles they reduce 4-nitro-cinnamic acid to the 4-amino counterpart in very good (90%) yield, no double bond getting reduced.

I would love to be contradicted on this, of course.  ;)


  • Guest
just curious?
« Reply #4 on: September 21, 2003, 11:57:00 AM »
why do you all prefer to reduce to the nitro alkane and from there to the amine what is the advantage?
if you reduce the nitro propene, or styrene (under strict protocols the end result is the same. is it not.

allow me to provide an example,

the acidic conditions promote the complete reduction of the nitro styrene as it is reduced in a series of stages, fron nitro, to ketoximine, to hydroxamine, to saturated amine, apparantely the lower temps prevevent the complexation of the catalyst with the intermediates which would result in unpredictable results, i.e. incomplete reduction.
you see the protonation of that nitro function helps it form leaving groups and undergo reduction more readily. but there are many caveats.
Since they are dealing with steric factors in this article whic may inhibit the reduction of the propenyl bond because these are nitrostyrenes and not nitropropenes,, however, I belive if this principle is applied to the nitro propenes, give enough time and perhaps an increase in H2 pressure, very positive results may be had in one step instead of two.


  • Guest
SPISSHAK> One of the advantages of this...
« Reply #5 on: September 21, 2003, 12:26:00 PM »
One of the advantages of this method is that you don't NEED any pressurised H2 or other -not so nice- reaction conditions, which i personally like! When the clean up of both products is so easy, why bother pressurising the system etc? It could of course be fun, if it would work, but i think i'd rather stick to the mentioned route.



  • Guest
Bandil it's not as hard as you think
« Reply #6 on: September 21, 2003, 12:59:00 PM »
did you know you can simply befriend an offshore worker who does underwater welding and get all the cylinders of H2 your little heart desires.
just grease the right palms and you'll be amazed how far it can get you. ;)


  • Guest
« Reply #7 on: September 21, 2003, 02:02:00 PM »
You are absolutely right Bandil. There is no point using LAH anymore. The Hive collective have a good array of other reducing agents/methods nowdays.

Spisshak, you are welcome to develop a method to reduce nitroalkenes directly to amines using Zn/formate or formic acid and present it here. The theory seems easy as you correctly described it. But in practice it doesn't give the desired products in yields worth mentioning. A cheap and easy method only using mild reaction conditions to give amphetamines directly from nitropropenes is a classic problem in organic chemistry.


  • Guest
NitroalkAnes & Catalytic Hydrogenations
« Reply #8 on: September 21, 2003, 10:36:00 PM »
Vitus_Verdegast: I'm sorry to say that it was just a spelling error on my part  ::)

SPISSHAK: It hasn't got anything to do with us being unable to procure H2 tanks or anything, in my own case it is because I don't like working with pressurized hydrogen, as it either requires very expensive Parr hydrogenation apparatus (they often cost $2500 when used!), or it involves taking the huge risk of working with amateur-made steel bombs in the hydrogenation reactions. Neither of these options appeal to me, I like to stick with purely chemical methods, at least until my economy allows me to own a real Parr shaker.

Parr - Shaker-Type Hydrogenation Apparatus



  • Guest
formic acid
« Reply #9 on: September 21, 2003, 10:38:00 PM »
I couldn't reply to

Post 351892

(foxy2: "Reduction of nitro groups w. Zinc/Ammonium formate", Chemistry Discourse)
, and than there was Bandil creating a related thread...  ;)

FA Khan, J Dash, C Sudheer, RK Gupta. Chemoselective reduction of aromatic nitro and azo compounds in ionic liquids using zinc and ammonium salts. Tetrahedron Letters 44 (2003) 7783-7787.



Abstract - Nitroarenes were chemoselectively reduced to the corresponding amines using zinc and aqueous ammonium salts in ionic liquids as a safe and recyclable reaction medium. Our results specify the effect of ammonium salts in the process; the combination of Zn/NH4Cl in [bmin][PF6] or Zn/HCO2NH4 in [bmim][BF4] were the suitable conditions for the reduction of nitroarenes. Azobenzenes were also smoothly reduced to hydrazobenzenes with Zn/HCO2NH4 (aq) in recyclable [bmim][BF4] without any over reduction to the corresponding anilines.

Additional notes: preparation of [bmim][PF6] and [bmim][BF4] following (a) S Guernik et al. Chem Commun (2001) 2314-2315, DOI:


(b) PAZ Suarez. Polyhedron 15 (1996) 1217-1219, DOI:


I have to admit that the solvent is a bit more complicated then MeOH, but hey, we are doing chemistry here, no?  ;D  Furthermore, they only tested aromatic nitro compounds, no aliphatic.


  • Guest
« Reply #10 on: September 21, 2003, 10:58:00 PM »
First of all that is a beautiful parr apparatus and a object of envy.
Secondly, on the subject of improvised hydrgenation apparratus, a fire extinguesher is a "turn key"
hydrogenion vessel, it has a valve (for empying oxygen, and introducing hydrogen) and a pressure gauge for measuring pressure and H2 uptake, it can be attached to a rocking arm orbital shaker and a lot of fun can be had from it!
there are other modifications too like coating the interior with xylan 1004 (teflon ala dupont) to make the vessel resistant to corrosive chemicals.


  • Guest
ionic liquids
« Reply #11 on: September 21, 2003, 11:41:00 PM »
Have you checked the price of any ionic liquids lately? I am still baffled that they are not considered laboratory curiosities... Bus as they provide chemists all over the world with a chance to repeat any common reaction in an ionic liquid instead of the usual solvent and publish "hey, this reaction also worked in ionic liquids" in one of the "short communications" journals, and a few months later they publish a full article in another journal where they make a list of a dozen ionic liquids and report the yield differences.

Result: The chemist got two more publications under his belt, he didn't have to work hard doing it, he'll get a grant renewal as he has done publishable work, and zero usable chemistry is added to the world's chemistry libraries.


  • Guest
I don't see why BMIM.HCl, prized at only ~$50...
« Reply #12 on: September 22, 2003, 06:50:00 AM »
I don't see why BMIM.HCl, prized at only ~$50 per 50g, can't be competitive to MeOH  :P .

But than again, I added the article as a curiosity. I wansn't expecting anyone to try it, as [bmim][PF6] and [bmim][BF4] both need a special (and complicated?) preparation. Personally, I will just fetch a new jerry can of MeOH...


  • Guest
Parr hydrogenation
« Reply #13 on: September 23, 2003, 10:02:00 AM »
Spisshak, I have a Parr hydrogenation opp. and it not capel of reducing the nitropropen to the amine, trust mee.
Usual you end up with some polymeres and some oxime.


  • Guest
The final TMA-2 yield was only 2.0 grammes.
« Reply #14 on: September 26, 2003, 10:23:00 PM »
The final TMA-2 yield was only 2.0 grammes. This is due to a number of factors:

The first reaction was run without activated zink. This failed reaction was separated a couple of times, back and forth, which caused a lot of loss.

Second there was a volcano reaction when the activated zink was used, which caused some loss.

So next time, swim will be armed with more patience and sense. The yields can only go up from here :)

Another note:
The reaction was tried with plain phenyl-2-nitropropene. The nitropropene was contaminated with benzaldehyde, dur to a brain glitch. The final yield ended up being next to nothing. I'm pretty sure the benzaldehyde ruined the borohydride reduction(by being reduced to benzylalcohol). But the experminet will be retried with pure phenyl-2-nitropropene, to get a better overview of the yields!



  • Guest
« Reply #15 on: September 27, 2003, 07:55:00 AM »
Can you use Formic acid instead of LAH in this reaction.
Indole glyoxyl amide ------formic acid---->dmt

To a stirred mixture of 15 g LiAlH4 in 100 ml anhydrous
ether (or THF [used]) slowly add the sticks (or solution
[used]) of IGA until 20 g have been added. Keep the rate of
reaction at a reasonable rate or boil-over may occur [do
say!]. Stir and reflux for 90 minutes after the addition is
complete. Cool in an ice bath and begin to cautiously [do
say!] hydrolyse with chips of ice or a cold solution of
methanol, added through the condenser. When there is no
further reaction, add a few ml extra water and allow to settle
finally and decant the clear liquid into an evaporating
vessel. Filter the residue and wash several times with
ether-methanol or THF-methanol [used]. Evaporate the combined
extracts and if necessary, seed the heavy syrup with crystals
of DMT.

synth of DMT and DET



  • Guest
According to this document: Re: Aliphatic and...
« Reply #16 on: September 27, 2003, 10:23:00 AM »
According to


( document:

Aliphatic and aromatic nitro compounds are selectively and rapidly reduced to their corresponding amino derivatives in good yields using Ammonium Formate and commercial Zinc dust. This system is found to be compatible with several sensitive functionalities including halogens, -OH, -OCH3, -CHO, -COCH3, COC6H5, -COOH, -CO2C6H5, -CONH2, -CN, -CH=CHCOOH, -NHCOCH3. The reduction can be carried out not only with HCOONH4 but also with HCOOH.

As there are no aliphatic or aromatic nitro groups, that needs reduction, it will most likely not work.


  • Guest
Explanation for huge excess of acid?
« Reply #17 on: October 01, 2003, 01:02:00 PM »
Can anyone explain why they choose to use 10X molar excess of formic acid in relation to the nitro compound? With ammonium formate they only use 8:5 molar ration.



  • Guest
hydrogen donor
« Reply #18 on: October 01, 2003, 01:33:00 PM »
I guess it is because ammonium formate is a better/faster hydrogen donor than formic acid


  • Guest
« Reply #19 on: October 03, 2003, 03:54:00 PM »
Here is a report of my failure, so that others will not repeat it:

No 2,5-dimethoxyphenyl-2-nitroethane (edited typo) could be isolated due to dimerisation, so another substrate was tried, the same as Bandil used in his first report: 2,4,5-trimethoxyphenyl-2-nitropropene.

7.5g 2,4,5-TMP2NP was smoothly reduced to the corresponding nitropropane using NaBH4 in EtOAc/EtOH a la Barium, yield 7.2g colorless crystals of 2,4,5-trimethoxyphenyl-2-nitropropane.

Next, everything was done as Bandil stated, using 5gr nitropropane, except that a small excess of Zn and HCOOH were used (2.5g and 15 mL), and, I think this is the reason of my failure, I used a cold waterbath constantly through the reaction to control the temperature.
After final workup 300 mg TMA-2.HCl was obtained  :( .

Next time I'll let the exothermic rxn go with good refluxing, and maybe even apply heat at the end until the last bits of Zn are consumed.