Dullemarc
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Reduction of 4-nitrobenzoic acid
Hey all, new user but old lurker 
Have relly enyoyed this site, found alot of great help and inspiration lurking around for years now 
Now to my "problem" or more like a dilemma.
Final goal is Benzocaine. The 4-NitroBenzoic Acid is made from scratch. Starting out with paint thinner to get toluene.
So now I need to convert my 4-NitroBenzoic Acid to 4-Aminobenzoic acid
There are now 2 ways (I can think of) to get there:
Esterification to ethyl 4-nitrobenzoate and the reduce it to Benzocaine with tin and HCL
Or Reduce the p-nitrobenzoic acid with tin and hydrochloric acid to p-amino benzoic acid, and then esterfied with ethanol and sulfuric acid.
I got 5grams of 4-nitrobenzoic acid, and around 10 grams of Tin(II) chloride crystals (SnCl2·2H2O) I made some time ago in case I needed to test for
gold at some point.
I Got plenty of tin granules and HCL in case I need more .
What produces the better results, and in what order would you do it.
The best word in a laboratory is not eureka, but weird.
[Edited on 22-6-2018 by Dullemarc]
[Edited on 22-6-2018 by Dullemarc]
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CuReUS
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do the esterification first,then reduce -https://pubs.acs.org/doi/10.1021/ja01691a031
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Dullemarc
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Sadly don't have access to https://pubs.acs.org
But what are the paper reason for doing the esterification first?
And thank you for replying
The best word in a laboratory is not eureka, but weird.
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Chemi Pharma
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I'd rather do exactly the opposite. Reduce first, than esterificate.
My reasons are I did this reaction a few times, starting from p-nitrobenzoic acid, that's here in Brazil is cheap and easy to get. The p-amino benzoic
acid produced is very soluble in ethyl alcohol (1g/08 ml alcohol), while p-nitrobenzoic acid don't (1g/110ml alcohol). This way you can effetively
separate the amino species from the nitro species that remains unreduced.
At the end this procedure will afford a much more pure benzocaine than you first esterificate and reduce it later, affording a mixture of ethyl
p-nitrobenzoate and ethyl p-aminobenzoate, which is hard to separate.
And another thing: Nitroarenes with alkyl, halo, phenoxy, carboxilic or carbinol groups attached can be reduced easily not only with tin/SnCl2/HCl,
but with a role of reducing agents like:
a) NiCl2/NaBH4,
b) Fe/HCl,
c) Tin/NH4Br,
d)Fe/acetic acid,
e)(NH4)2SO4/Mg or Al,
f)Fe/CaCl2,
g)Fe/NH4OH,
h)Na2S,
i)Zn/Acetic acid.
Look at the related papers below:
Attachment: nitrocompounds reductions to amines with Na2S.doc (82kB)
This file has been downloaded 482 times
Attachment: nitrocompounds reductions to amines with Zn and acetic acid.doc (109kB)
This file has been downloaded 557 times
Attachment: sodium borohydride-nicl2-reduction of nitro compounds.pdf (399kB)
This file has been downloaded 409 times
Attachment: nitrocompounds reductions to amines with Fe and HCl.doc (78kB)
This file has been downloaded 527 times
Attachment: nitrocompounds reductions to amines with FeSO4 and NH4OH.pdf (361kB)
This file has been downloaded 481 times
Attachment: reduction of nitrocompounds with Fe + CaCl2.pdf (99kB)
This file has been downloaded 1335 times
Attachment: reduction of nitroarenes to anilines with tin and NH4Br.pdf (449kB)
This file has been downloaded 440 times
Attachment: nitrocompounds reductions to amines with Fe and acetic acid.doc (85kB)
This file has been downloaded 458 times
Attachment: reduction of nitrocompounds with Ammonium sulfate and Mg or Al.pdf (115kB)
This file has been downloaded 450 times
EDIT: Chemplayer did exactly the opposite I preach here, in his video on You Tube, and reduced the ethyl p-nitrobenzoate with sodium dithionite which,
I think, it's the worst reducing agent you can use to reduce nitro-arenes, talking in therms of yield. I'm sure his product was highly contaminated
with residual ethyl p-nitrobenzoate unreduced and I don't recommend anyway his method to sinthesize a reazonable pure benzocaine. You can see his
video preparing benzocaine from p-nitrobenzoic acid at his channel at "BitChute Channel", cause now he was banished from you tube.
[Edited on 22-6-2018 by Chemi Pharma]
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Metacelsus
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I've done the reduction with Sn/HCl. It works reasonably well. I would recommend to reduce before esterification, so that you don't have to worry
about ester hydrolysis.
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DraconicAcid
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Not sure if this is helpful, but Merck says that benzocaine is synthesized industrially by the reduction of ethyl nitrobenzoate with water and iron,
and a small amount of acid.
Please remember: "Filtrate" is not a verb.
Write up your lab reports the way your instructor wants them, not the way your ex-instructor wants them.
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Dullemarc
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Quote: Originally posted by Chemi Pharma  |
I'd rather do exactly the opposite. Reduce first, than esterificate.
My reasons are I did this reaction a few times, starting from p-nitrobenzoic acid, that's here in Brazil is cheap and easy to get. The p-amino benzoic
acid produced is very soluble in ethyl alcohol (1g/08 ml alcohol), while p-nitrobenzoic acid don't (1g/110ml alcohol). This way you can effetively
separate the amino species from the nitro species that remains unreduced.
At the end this procedure will afford a much more pure benzocaine than you first esterificate and reduce it later, affording a mixture of ethyl
p-nitrobenzoate and ethyl p-aminobenzoate, which is hard to separate.
And another thing: Nitroarenes with alkyl, halo, phenoxy, carboxilic or carbinol groups attached can be reduced easily not only with tin/SnCl2/HCl,
but with a role of reducing agents like:
a) NiCl2/NaBH4,
b) Fe/HCl,
c) Tin/NH4Br,
d)Fe/acetic acid,
e)(NH4)2SO4/Mg or Al,
f)Fe/CaCl2,
g)Fe/NH4OH,
h)Na2S,
i)Zn/Acetic acid.
EDIT: Chemplayer did exactly the opposite I preach here, in his video on You Tube, and reduced the ethyl p-nitrobenzoate with sodium dithionite which,
I think, it's the worst reducing agent you can use to reduce nitro-arenes, talking in therms of yield. I'm sure his product was highly contaminated
with residual ethyl p-nitrobenzoate unreduced and I don't recommend anyway his method to sinthesize a reazonable pure benzocaine. You can see his
video preparing benzocaine from p-nitrobenzoic acid at his channel at "BitChute Channel", cause now he was banished from you tube.
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First of all thank you, been reading and will do so tormorrow aswell.
Really interesting reading so far.
Have decided I will go with the reduce first, then esterificate.
And I did not know chemplayer have had to move sites. Thought the channel just died, but happy to see them still going strong. But ye their method
seems a bit messy.
How should I reduce it, should I just add plenty of tin and HCL and reflux it for a long time since its granules and not powder.
Or will 10grams of Tin(II) chloride crystals (SnCl2·2H2O) in water do the trick?
[Edited on 22-6-2018 by Dullemarc]
The best word in a laboratory is not eureka, but weird.
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Chemi Pharma
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| Quote: Originally posted by Dullemarc | | How should I reduce it, should I just add plenty of tin and HCL and reflux it for a long time since its granules and not powder. Or will 10grams of
Tin(II) chloride crystals (SnCl2·2H2O) in water do the trick? |
@Dullemarc, you'd better follow the directions given by "Nile Red" in his You tube channel in the video where he reduces nitrobenzene to aniline with
tin/HCl.
"Nile Red" ever have a nice work up and theoretical support for the reactions he gives away. I'm sure that after saw the video you'll be able to
adaptate the procedure to p-nitrobenzoic acid. He covered in another video the esterification of PABA to it's ethyl ester as well.
Take a look on these videos and reply later:
https://www.youtube.com/watch?v=nKWOZajmAQo
https://www.youtube.com/watch?v=RiTN1EYB-rs
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zed
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Me, I'm lazy.
I like my chemistry, but Para Amino Benzoic Acid, is available as an OTC supplement.
https://purebulk.com/paba-powder-para-aminobenzoic-acid/
Inexpensive too.
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UC235
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I'd just buy the PABA if it were me. Consider Thiourea dioxide as a reducing agent. It's most active in alkaline solutions and your acid will be
soluble as the sodium salt, making for an easy homogenous reduction.
Ammonia is also a suitable base and was used successfully when I prepared luminol.
Attachment: thiox reduction nitroaromatics.pdf (140kB)
This file has been downloaded 441 times
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CuReUS
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the nitro group being electron withdrawing would activate the COOH to undergo esterification faster,whereas the amino would do the exact opposite and
might also end up getting alkylated | Quote: Originally posted by Chemi Pharma | | first esterificate and reduce it later, affording a mixture of ethyl p-nitrobenzoate and ethyl p-aminobenzoate, which is hard to separate.
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the paper I linked gives an yield of 98%.Also,the esterification and reduction happen in one pot
that's why the jacs paper uses alcoholic HCl
[Edited on 23-6-2018 by CuReUS]
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wildfyr
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The Bechamp reduction (iron filings and HCl) is a very mild and less toxic nitro reduction technique than the tin based one. You also can't conceive
of anything with easier to obtain starting materials. You can also get a lot of the metallic garbage out using a magnet.
Make sure you push it all the way or else there will be diazo compound impurities (highly colored). This is true for most nitro reductions.
I also agree, reduce then esterify. All but the most mild nitro reductions will probably hydrolyze the ester. I've played this game before trying to
get selectivity for reducing nitro (over an aldehyde), and found myself using some pretty obscure mild nitro reduction procedures (to poor effect).
Its dead easy to esterify this with absolute alcohol and a drop of sulfuric acid stirring over night.
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Tsjerk
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How do you workup the ester? Distill of the ethanol and dilute the ester in any non-polar and wash with carbonate?
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CuReUS
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the bechamp reaction is not as easy as it seems-http://www.sciencemadness.org/talk/viewthread.php?tid=63564#...
http://www.sciencemadness.org/talk/viewthread.php?tid=462&am...
| Quote: | | All but the most mild nitro reductions will probably hydrolyze the ester. |
how does it matter if the reducing
agent is strong or weak ?what matters is whether there is water or not.
NO water=NO "hydro"lysis
| Quote: | | I've played this game before trying to get selectivity for reducing nitro (over an aldehyde), and found myself using some pretty obscure mild nitro
reduction procedures (to poor effect). |
which reducing agent did you use? and on what substrate? because good ol dithionite can do the job-https://www.sciencedirect.com/science/article/pii/S004040390...
another way using a little obscure reagent-http://pubs.rsc.org/-/content/articlelanding/2014/gc/c3gc420...
using bechamp-pubs.acs.org/doi/abs/10.1021/jm020235g | Quote: Originally posted by Tsjerk | | How do you workup the ester? Distill of the ethanol and dilute the ester in any non-polar and wash with carbonate? |
you don't need to,according to the paper I linked above,because the esterification followed by reduction happens in one pot
[Edited on 24-6-2018 by CuReUS]
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