Keras
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Acetanilide synthesis from aniline and acetic acid
Folks,
there is a recipe on the book ‘Experimental Organic Chemistry, Laboratory Manual' describing the synthesis of acetanilide from aniline and glacial
acetic acid only (no acetic anhydride needed), using zinc powder as a catalyst. In essence: mix aniline (10 mL), acetic acid (30 mL) and 0.5 g of Zn
and heat everything at 60 °C for 2 hours under a condenser, here you go.
Problem: I tried that twice, and it doesn’t work. Zero product. Zilch. In the first case, I blamed the zinc I used, which was scavenged from
whatever old experiment I had done, but even fresh zinc powder produced strictly nothing during the workup (though I put the mix in the freeze at -20
°C: the water froze, but no crystals).
I’m really wary of that 'heat at 60 °C' thing. None of the reactants has a boiling point under 120 °C, so I’m wondering what's the use of the
condenser. Apparently, after cursory searching on Internet, that reaction needs refluxing, so 120/130 °C would be more appropriate.
Second point: that tiny quantity of zinc should all dissolve in acetic acid, so what?
Has anyone already done this experiment?
(I unfortunately had exhausted my stash of aniline, so I couldn't plan a third try. I had to remake a batch from PABA, which took some time, and I had
to leave with the aniline not fully purified. I will resume in a fortnight or so.)
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bnull
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The book gives reference 13 for the procedure: V. K. Redasani, V. S. Kumawat, R. P. Kabra, P. Kansagara, S. J. Surana, Applications of green
chemistry in organic synthesis, International Journal of ChemTech Research 2 (2010), no. 3, 1856-1859 (attached). I looked it
up, so here's the procedure in full. Roman numerals indicate each para-substituted acetanilide from a table in the article, I being
ordinary acetanilide.
| Quote: | Synthesis of compounds (I-IV) by green chemistry method:
A mixture of aniline / substituted anilines (3.3g) and zinc dust (0.16g) in acetic acid (10ml) in 100 ml round bottom flask was heated over a gentle
flame using water condenser. Heating was continued for about 45 min., the reaction mixture was then carefully poured in cold water (33ml) in 250ml
beaker with vigorous stirring. The shining crystals of product were separated slowly. After 15 min, crystals were collected by filtration. The solid
crystals were washed over the Buchner funnel with water and product was dried and crystallized in boiling water. |
Rather short, eh? It looks so simple than even an unnamed extra from the old Planet of the Apes (1968) would be able to replicate the procedure, chimp
costume and all. There are 3 possibilities for the failure: (1) you messed it up somehow; (2) the article is bogus; (3) the book is the problem.
(1): we're going to have to wait until you have more aniline to sacrifice. Or someone else can try to repeat it. Let's say for now that it wasn't your
fault.
(2): the article talks of a "gentle flame" and a water condenser, but gives no indication of what should be the temperature. Acetic acid is both
solvent and reagent and boils slightly below 120 ºC, so it seems your supposition is right if the condenser is there for reflux. Let's ignore the
"Mechanism by green chemistry method" since it is a mess (acetylzinc acetate?). The procedure was discussed between H. Meshram and the authors of the
article in a private communication, that we may consider unaccessible since the article is 15 years old and the communication has probably been
deleted or lost since then.
(3): the book has several typos, at least in the first 100 pages. I wouldn't be surprised if the time and temperature indications were wrong or if the
authors of the book simply multiplied the quantities by 3 but had never actually performed the experiment. This is not unheard of (Feynman gives a
fake experiment from a physics book as an example of bad pedagogy in Surely You're Joking, Mr. Feynman!), and the readers who tried to repeat the
procedure from the book would attribute the failure to themselves.
Repeat what is in the article, not in the book, and let the mixture reflux at 120 °C (sounds redundant) for 45 minutes. If nothing happens, do it for
a longer time.
Attachment: Redasani et al. - green synthesis of para-substituted acetanilides.pdf (180kB)
This file has been downloaded 81 times
Best of luck.
[Edited on 9-9-2025 by bnull]
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Keras
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Quote: Originally posted by bnull  |
[…]
| Quote: | Synthesis of compounds (I-IV) by green chemistry method:
A mixture of aniline / substituted anilines (3.3g) and zinc dust (0.16g) in acetic acid (10ml) in 100 ml round bottom flask was heated over a gentle
flame using water condenser. Heating was continued for about 45 min., the reaction mixture was then carefully poured in cold water (33ml) in 250ml
beaker with vigorous stirring. The shining crystals of product were separated slowly. After 15 min, crystals were collected by filtration. The solid
crystals were washed over the Buchner funnel with water and product was dried and crystallized in boiling water. |
Rather short, eh? It looks so simple than even an unnamed extra from the old Planet of the Apes (1968) would be able to replicate the procedure, chimp
costume and all.
|
Thanks a bunch for looking up the source!
And by the way, since you mention it, and on a totally different tangent, I find the 'Planet of the Apes' book (not the movies, mind you, but Pierre
Boulle's original book) absolutely prophetic, provided you replace apes with AI.
| Quote: Originally posted by bnull |
There are 3 possibilities for the failure: (1) you messed it up somehow; (2) the article is bogus; (3) the book is the problem.
(1): we're going to have to wait until you have more aniline to sacrifice. Or someone else can try to repeat it. Let's say for now that it wasn't your
fault.
|
I did it twice, with twice the amounts indicated. The first time, I clearly admit my zinc was not pristine, and was so clogged into small balls that
the magnetic stirrer was unable to move it from the bottom of the flask. But the second time, the zinc was new, very powdery, and did indeed totally
mix with the reactants… until there was none left, which was expected (zinc dissolves in glacial acetic acid, of course).
| Quote: Originally posted by bnull |
(2): the article talks of a "gentle flame" and a water condenser, but gives no indication of what should be the temperature. Acetic acid is both
solvent and reagent and boils slightly below 120 ºC, so it seems your supposition is right if the condenser is there for reflux. Let's ignore the
"Mechanism by green chemistry method" since it is a mess (acetylzinc acetate?). The procedure was discussed between H. Meshram and the authors of the
article in a private communication, that we may consider unaccessible since the article is 15 years old and the communication has probably been
deleted or lost since then.
|
I think that’s the more likely hypothesis. I don’t see the need for a condenser if nothing refluxes, especially when the reaction temperature is
half that of the boiling point of the most volatile component.
| Quote: Originally posted by bnull |
Repeat what is in the article, not in the book, and let the mixture reflux at 120 °C (sounds redundant) for 45 minutes. If nothing happens, do it for
a longer time.
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Okay, I’ll try to extract only a sample of the mixture and see if I can get any crystals from it. If nothing shows up, I’ll just carry on…
[Edited on 9-9-2025 by Keras]
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Diachrynic
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A friend of mine has done and posted this procedure elsewhere successfully: https://illumina-chemie.org/viewtopic.php?p=68138
Here is a translation:
| Quote: |
26 ml of aniline (26.5 g, 0.285 mol), 75 ml of glacial acetic acid (78.8 g, 1.31 mol), and 1.5 g of zinc powder (0.023 mol) are placed in a 250 ml
round-bottom flask and boiled under reflux in an oil bath for 2 hours. The reaction mixture is initially orange in color, but slowly turns gray-yellow
after heating and clears almost completely within half an hour. The zinc powder also dissolves in the process.
After the mixture has cooled down slightly, it is poured into 250 ml of cold water. After stirring briefly, a thick, white, iridescent paste of
acetanilide crystallizes very quickly. The crystallization is allowed to complete in the refrigerator for a few hours and then filtered off. The
precipitate is washed twice with approx. 100 ml of cold water, thoroughly dried and dried in a desiccator over silica gel for one day.
Crude yield: 35.4 g (92% of the theoretical yield)
For recrystallization, the product is suspended in approx. 300 ml of water, heated to almost to the boiling point, and then ethanol is slowly added
until everything has dissolved. The solution is first allowed to cool slowly and then left in the refrigerator overnight. The precipitate is filtered
off again, rinsed with a little cold water, dried first for 1 day in air and then for 1 day in a vacuum desiccator over freshly heated silica gel.
Yield: 23.2 g (60.3% of the theoretical amount) |
we apologize for the inconvenience
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Keras
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| Quote: Originally posted by Diachrynic | A friend of mine has done and posted this procedure elsewhere successfully: https://illumina-chemie.org/viewtopic.php?p=68138
Here is a translation:
| Quote: |
26 ml of aniline (26.5 g, 0.285 mol), 75 ml of glacial acetic acid (78.8 g, 1.31 mol), and 1.5 g of zinc powder (0.023 mol) are placed in a 250 ml
round-bottom flask and boiled under reflux in an oil bath for 2 hours. The reaction mixture is initially orange in color, but slowly turns gray-yellow
after heating and clears almost completely within half an hour. The zinc powder also dissolves in the process.
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Thanks for that. It seems to confirm that refluxing is required, which I was surmising. And I agree on the process, i.e. the colours and the fact that
the solution becomes clear after 30 ~ 45 min.
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kmno4
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It is a banal synthesis, described in countless "manuals", with or without "catalysts" and various proportions amine/acid
Nice modification is addition of K(Na)2S2O7 : it reduces time of reaction (~1 h) and gives practical quantitative yield. Not very cheap modification,
but on small scale, 10 g or so, excellent.
(K(Na)2S2O7 can be easily prepared from thermal decomposition of appropriate persulfate).
For fun - complete procedure with Zn in attachment (in russian, but the orginal version is also available).
Attachment: iya_polaczkowa_rus.pdf (120kB)
This file has been downloaded 85 times
[Edited on 9-9-2025 by kmno4]
Слава Україні !
Героям слава !
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Pumukli
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Roughly 5 years ago I posted an article in Prepublication regarding acetanilide synthesis without acetic anhydride... Last time I checked it was still
there. 
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MaeBorowski
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Vogel calls for heating aniline with a roughly two-fold excess of acetic acid and some powdered zinc, and distilling off the water as it is formed, at
about 105 C on the thermometer. I don't think that the addition of zinc matters too much. I would mix aniline and acetic acid and heat the mixture
while slowly distilling off water through a good Vigreux.
What has been will be again, what has been done will be done again; there is nothing new under the sun. Eccl. 1:9
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Keras
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| Quote: Originally posted by MaeBorowski | | Vogel calls for heating aniline with a roughly two-fold excess of acetic acid and some powdered zinc, and distilling off the water as it is formed, at
about 105 C on the thermometer. I don't think that the addition of zinc matters too much. I would mix aniline and acetic acid and heat the mixture
while slowly distilling off water through a good Vigreux. |
Will do that tomorrow. Apparently, zinc serves as catalyst, so yeah, maybe it’s not required, but it should help the reaction go faster.
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Keras
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Okay, so I can confirm this works. 10 mL aniline + 30 mL acetic acid + 0.6 g Zn → Reflux at 160 °C for 90 min+ → acetanilide. Problem is the
yield: I got only circa 30%. This is however really weird.
First off, this method seems to produce a highly pure product even without recrystallisation. After about 40 minutes+, the zinc dissolves completely
and the resulting liquid is crystal clear (see picture). When this colourless mixture is poured into cold water, pristine white flakes almost
immediately crystallise. I filtered those crystals, and the filtrate showed no sign of unreacted aniline. When I weighted the crystals, still slightly
damp, I found about 15 g, which would, taking into account the extra water, correspond to an almost quantitative yield, consistent with the absence of
leftover aniline.
I recrystallised the product using 100 mL (minimum amount) of water brought to boiling until all the acetanilide dissolved, and, after drying and 2
hours in my vacuum desiccator, got only around 4.75 g of dry flakes. So, either the flakes hold on to a lot of water, and the yield is poor (but in
this case, where did the unreacted aniline go?), or somehow I lost 66% to recrystallisation, which seems unlikely given I cooled the recrystallisation
beaker down to almost 0 °C.
So what???
[EDIT : Picture of flask in the heating mantle while being refluxed and crystallisation thereof when it is poured into cold water.
[Edited on 21-9-2025 by Keras]
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bnull
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What is the melting point of your product? What else is in the filtrate?
Good to see that it (apparently) works. I suppose that who typed the book forgot to put a "1" before "60 °C" and no one bothered to revise the final
version. A suggestion: when reproducing experiments from that book, only follow the instructions given in the references.
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Keras
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Good question. Didn't check yet.
As for the filtrate, what do you mean?
| Quote: Originally posted by bnull |
Good to see that it (apparently) works. I suppose that who typed the book forgot to put a "1" before "60 °C" and no one bothered to revise the final
version. A suggestion: when reproducing experiments from that book, only follow the instructions given in the references. |
Yeah, although typos happen all the time in every book. But you’re right, better double check.
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bnull
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| Quote: | | As for the filtrate, what do you mean? |
This:
| Quote: | | I filtered those crystals, and the filtrate showed no sign of unreacted aniline. |
There may be side products still dissolved.
The book is a translation of the Spanish edition published by Garceta Editorial. It may be worth checking up on that edition. Unless of course if it
was published in the same state of "un-revision".
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Radiums Lab
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By looking at author's name they are Indians. Most of researchers use bunsen burner as flame source.
Water is dangerous if you don't know how to handle it, elemental fluorine (F₂) on the other hand is pretty tame if you know what you are doing.
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Radiums Lab
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I am reffering to first paper's post. Most of the cases he burner is powered by LPG.
Water is dangerous if you don't know how to handle it, elemental fluorine (F₂) on the other hand is pretty tame if you know what you are doing.
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