Sciencemadness Discussion Board

Benzoic Acid, Carbamid>Benzamid>Anilin?

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dr. nick - 25-7-2005 at 07:45

Swim talked to a real skilled friend who gave him the hint to get anilin from benzoic acid and carbamid via benzamid and bleach (chlor), so he decided to try a test run on this:

1g Carbamid and 2g Benzoic Acid where finely grinded and mixed in a mortar, then filled into a large test tube and fitted with a stopper and a rubber hose leading into a jar of water to avoid any mean smells.

While heating the mix it completely liquefied (clear, slight yellow).

after cooling it re-solidified again.
(Swim's a real pro, so the first thing he did after pulling off the stopper was taking a deep smell - now his nasal cavities will probably stay clear for quite a time ...)

Then some 40ml around 3% Chlorine Bleach where added. After some bubbling, foaming, fuming and changing colours from slight red over redbrown the liquid turned to a nearly black brown. He decided not to smell it this time as he likes his Erythrocytes as they are.

Can anyone give his appraisal on this? is this of any worth? should the black/brown liquid contain some Aniline now? if so, how to get it out there? destillation?
Or can anyone help with some more info on this? temps needed, amounts of bleach needed, is there a better way to benzamid, and so on? maybe to use some hcl with the benzoic acid and the carbamid??

Any hint welcome!

Thanks!

[Edited on 25-7-2005 by dr. nick]

chemoleo - 25-7-2005 at 08:14

Can you come up with a mechanism for this?

Also, I suspect carbamide is urea? Or what is it? Wouldn't you expect to get the condensation product, Phe-CO-NH-CO-NH-CO-Phe ? Did you see moisture appearing after you melted the mix?

Anyway, if this is the product, I don't see how the nitrogen would suddenly move to the Phe. But I don't know enough about this type of chemistry.

As to tests for aniline- that's an easy one. You could diazotise it, turn it into some dye.

For it's potential isolation, add ether/ehtanol, the aniline should precipitate as the hydrochloride salt (check solubilities first)

dr. nick - 25-7-2005 at 10:06

i'm sorry, i'm in the dark myself on this, i wasn't able to get more info on this yet. on the other hand: maybe i simply didn't understand ...

here's what i found in a mail from the mentioned friend:

1. a mentioned possible side reaction:
--------------------------------------------------------------------
One side reaction may cause trouble:

NH2-CO-NH2 + 2 HOOC-Ph --> CO2 + H2NCO-Ph + NH4+ -OOC-Ph--

2. a hint for the benzamid step:
--------------------------------------------------------------------
--you may need to add some acid, like HCl or NaHSO4, which is stronger than benzoic acid, to displace the ammonium ion.--

3. a hint to complete the whole thing
--------------------------------------------------------------------
--cook to make benzamide. Second, add a cool bleach solution to the benzamide and let stir for a couple hours. Finally, add some base and heat the mixture up to complete rearrangement and decarboxylation.
An oily layer of aniline will separate, which canbe extracted with nonpolar solvents.

That's all i can tell at the moment. Possibly i'll be able to talk to him again sometime.
I'll go on with my test runs and will post the results here if somebody is interested ...
unfortunately i'm not much of a chemist yet so all i can do is to describe what i see ...

[Edited on 25-7-2005 by dr. nick]

Ah, I knew it, this rang a bell!

chemoleo - 25-7-2005 at 17:15

It's the Hoffmann Rearrangement what you are talking about!

Check this for instance!!

In the case of acetamide ---> methylamine:
Quote:
The Hoffmann Rearrangement

2 CH3CONH2 + Ca(OCl)2 → 2 CH3CONHCl + Ca(OH)2

2 CH3CONHCl + Ca(OH)2 → (CH3CONCl)2Ca + 2 H2O

(CH3CONCl)2Ca + 2 NaOH → 2 (CH3CONCl)-Na+ + Ca(OH)2

(CH3CONCl)-Na+ --Heat--> CH3CON + NaCl --Rearr.--> CH3N=C=O

CH3N=C=O + H2O + 2 NaOH → CH3NH2 + Na2CO3

CH3NH2 + HCl → CH3NH3+ Cl-

In this experiment, acetamide is first converted into N-chloroacetamide, which, in the presence of alkali, eliminates hydrogen chloride and undergoes rearrangement to form methylisocyanate. Hydrolysis of the latter gives methylamine which is isolated as the hydrochloride. It should be pointed out that the elimination of hydrogen chloride from N-chloroacetamide in the presence of alkali, actually consists of the removal of the hydrogen as a proton to form the alkali salt of N-chloroacetamide; the chloride ion is apparently released from the anion of this salt.


For experimental details, see the above link too. I'd use a modified procedure from the above.

What remains is the making of benzamide in the first place. I don't know the usual synthesis routes, however, in the analogous case, acetamide is made by heating & melting ammonium acetate, so maybe the same could be done with ammonium benzoate.

S.C. Wack - 25-7-2005 at 17:39

Excerpt from Helv. Chim. Acta 29, (1946) pp. 1440-1:

Exemples d'acidolyse de l'urée.

Formamide: 15,8 gr. d'acide formique chauffés avec 18 gr. (une molécule) d'urée à
140—150° jusqu'à cessation du dégagement de gaz (quelques heures) fournissent par
distillation dans le vide 11,3 gr. de formamide passant à 113° sous 20 mm (rendement
84%). — Berend[Ann. 128, 335 (1863)]) a déjà décrit l'action, qualifiée par lui de «déshydrante», de l'urée
sur le formiate d'ammonium et indiqué qu'en chauffant ce sel avec la moitié de son poids
d'urée (environ une demi-molécule) à 140°, on pouvait préparer la formamide avec un
rendement meilleur (mais qu'il n'indique pas) que par simple chauffe du sel: il a formulé
l'équation:

2 HCOONH4 + NH2CONH2 = 2 HCONH2 + C03(NH4)2

Mais c'est bien la réaction qui intervient: en prenant seulement 3/4 de mol. d'urée
(ce qui fournit après acidolyse de 1/2 mol. d'urée un mélange qui contient pour 2 molécules
de formiate d'ammonium une molécule d'urée, à côté de l'amide déjà formée), on obtient
avec la même quantité d'acide seulement 10 gr. d'amide; or l'urée mise en oeuvre fournit
par acidolyse 10,1 gr. de formamide (soit 8,4 gr. si l'on tient compte du rendement de 84%
de l'essai précédent), de sorte que la formation d'amide par déshydratation du sel ammoniacal
est peu importante.

Acétamide: 10 gr. d'urée et 10 gr. d'acide acétique (quantités équimoléculaires)
chauffés dans un ballon à tube ascendant à l'ébullition dégagent du gaz carbonique dès
que la température du mélange atteint 110°. Poursuivant la chauffe deux ou trois heures,
on voit la température de la liqueur s'élever à 220°, avec dégagement non seulement de
CO2, mais aussi d'ammoniaque. La distillation fournit 9,5 gr. d'acétamide (rendement
95%) pratiquement pure, passant à 223°. L'acétate d'ammonium se comporte de même
avec l'urée. Ici encore, la formation d'amide par déshydratation directe du sel ammoniacal
est relativement peu importante: en chauffant l'acide acétique avec la moité de
son poids d'urée dans les mêmes conditions, on n'obtient que 66% (par rapport à l'acide)
d'amide.

Benzamide: La réaction est ici un peu plus lente et ne débute qu'à environ 150°.
Chauffant des quantités équimoléculaires d'acide benzoïque et d'urée 1 heure à 200—230°,
on obtient un produit qui, extrait au benzène bouillant, fournit par refroidissement de
la solution obtenue, de la benzamide identifiée par son p. de f. et le dosage d'azote. Il
reste sur le filtre une certaine quantité de produits de transformation de l'urée (ac. cyanurique,
etc.). Rendement environ 60%.
...

chemoleo - 25-7-2005 at 17:51

Great ref, S.C. wack.
In other words, it can indeed be made with urea.
If it hasn't been obvious:
The reaction is a little slower here (with benzamide) and begins at approximately 150° C. Heating equimolar quantities of benzoic acid and urea for 1 hour at 200-230°, one obtains a recrystallised product that when extracted with hot benzene. On the filter paper, there remains a certain quantity of other products such as urea (cyanuric acid, etc). Yield approximately 60%.

Blind Angel - 25-7-2005 at 18:08

Translation:

-------
Example of urea acidolysis

Formamide: 15,8 g of formic acid heated with 18 g (one mol) of urea at 140-150° until cessation of gas formation (couple of hour) yield by vaccuum distillation 11,3 g of formamide melting at 113° under 20 mm (yield: 84%). - Berend[Ann. 128, 335 (1863)]) has already described the action, qualified by him as deshydrating, of urea on ammonium formate and has noted that heating this salt with half his weight of urea (about half a mol) at 140°, we could separation the formamide with a better yield (but he doesn't indicate it) than by simple heating of the salt: he has formulated the equation:

2 HCOONH4 + NH2CONH2 = 2 HCONH2 + C03(NH4)2

But it's really the reaction that intervenes: by taking only ¾ mol of urea (which yield after acidolysis of ½ mol of urea a mix that already contain for 2 mol of ammonium formiate on mol of urea, beside the already formed amide), we obtain with the same acid quantity only 10 g of amide; but the urea already converted by the acidolysis give 10,1 g of formamide (8,4 g if we count the 84% yield of the precedent try), so the formation of amide by dehydratation of the ammoniacal salt is not very important.

Acetamide: 10 g of urea and 10 g of acietic acid (equimolar quantity) heated in a round bottom flask until boiling give out CO2 as soon as the temperature reach 110°. Continuin the heating during two or three hour we see the temperature of the solution going up to 220°, with release of CO2 and NH3. The distillation yield 9,5 g of acetamide (yield of 95%) praticly pure, melting at 223°. The ammonium acetate is reacting the same way with urea. Here too, the formation of amide by direct deshydratation of the ammoniacal salt is relatively not important: by heating the acetic acid with half his weight of urea in the same conditions, we obtain only 66% (by comparing with the acid) of amide.

Benzamide: The reaction is here a bit slower and start only at about 150°. Heating equimolar quantity of benxoic acid and urea 1 hour at 200-230°, we obtain a product which, once extracted with boiling benzene, yield by cooling of the solution, benzamide identified by it's melting point and the nitrogen proportioning. There is still on the filter a quantity of by-product of the urea transformation (i.e. cyanuric acid, etc.) Yield about 60%
-------

Hope it's good

dr. nick - 26-7-2005 at 04:59

Yow! Thanks all!
That's allmost exhausting :)
I feared i was asking again stupid questions no one even knows what i want to know ... :)

Comes another problem: Getting Benzene from Calciumhydroxide and Sodium Benzoate to clear the benzamide before going on to aniline ...

every task turns out to be a never ending story :)

frogfot - 26-7-2005 at 05:34

Cool, that's an even simpler route to benzamide than "benzoic acid-(92%)->methyl benzoate-(93%)->benzamide" (described on my page).
Defineately gonna try the nearest days :o
Btw, I'm sure the benzene can be substituted. One could probably recryst the product from hot water or aqueous methanol..

For the Hoffmann rearrangement, should one use same conditions as for the alifatic amides? IIRC this was discussed in another thread.. humm

[Edited on 26-7-2005 by frogfot]

dr. nick - 26-7-2005 at 05:51

I hope it will work! would you give me some more info if you made it? i don't get it done practically at the moment, funny thing is:

when the mixture begins to "boil" a lot of it crystallizes at the walls of the vessel (i guess it's the benzoic acid, but not sure), so most of it isn't reacting but hanging around at the glass ...

maybe better using a HB solvent? But how to get the product out of that afterwards? would that work at all?

frogfot - 26-7-2005 at 06:57

Just started a small batch and I get same problem.. the benzoic acid sublimes on walls of the flask.. Maybe this wouldn't decrease the yield on bigger scale.. I dunno..

Couldnt one add a small amount (with regard to the total reaction mix) of solvent with high bp.. like xylene (~140*C).. maby it will continiously wash down the benzoic acid.. A small amount of it hopefully wouldn't affect the temp in the reaction mix. Or am I totally wrong?

Anyway, I'll continiue with this batch and extract it with ether or heptane..

S.C. Wack - 26-7-2005 at 17:39

Not urea, but since I'm posting aniline experimentals here and this is not interesting enough to put anywhere else - an excerpt that I happen to have from JOC 29, 2576 (1964):

"When benzoic acid is heated with nitromethane in
polyphosphoric acid (PPA), aniline is formed in good
yield along with carbon monoxide and carbon dioxide.

...p-Chloroaniline. Reaction of p-Chlorobenzoic Acid with
Nitromethane.-A mixture of 100 g. of PPA, 12.52 g. (0.08 mole)
of p-chlorobenzoic acid and 9.76 g. (0.16 mole) of nitromethane
was heated with stirring at 115' for 90 min. (or until gas evolution
ceased), poured into 200 g. of crushed ice, stirred, and filtered.
p-Chlorobenzoic acid, 3.1 g., was recovered. The filtrate was
then made strongly alkaline with KOH, cooled for 2 hr. at 0,
and filtered. p-Chloroaniline, m.p. 69, 6.1 g. (60% conversion,
80% yield), was isolated; lit. m.p. 70. A mixture melting point
with an authentic sample of p-chloroaniline showed no depression.
The infrared spectrum was superimposable on that of an authentic
sample of p-chloroaniline.

In a similar fashion the following amines were prepared in the
indicated yields from the corresponding carboxylic acids: aniline
(68%), p-toluidine (73%,), and o-toluidine (19%). The low yield
from o-toluic acid may be attributed to steric inhibition of resonance
caused by the o-methyl group and resulting in decreased
protonation of the carboxyl group.

Use of benzoyl chloride instead of benzoic acid gave aniline in
about the same yield (71%,) but in a shorter time. Use of nitroethane
instead of nitromethane gave aniline in 53%, yield from
benzoic acid. Use of 2-nitropropane instead of nitromethane
gave oxides of nitrogen but no aniline..."

I'm sure that everyone will be rushing to make or buy the nitroalkanes to use them to make aniline.

frogfot - 26-7-2005 at 23:01

S.C.Wack, that info is just to good to be true :o
Just gotta search the preparation of polyphosphoric acid..

The urea experiment didn't go well, though I'm sure it never reached 200*C (and lots of benz. a. was on the walls). On prolonged extraction with ether and aqueous Na2CO3 nearly whole mass didn't dissolve. The ether gave a small amount of crystalls (probably benzamide).
Everything smelled like almond.. could it be cyanuric acid? couldn't find its smell on google..

Next time gonna reflux the stuff with half amount of acetamide (bp 222*C)..

[Edited on 27-7-2005 by frogfot]

Nicodem - 27-7-2005 at 01:10

Quote:
Just gotta search the preparation of polyphosphoric acid..


It is made by dissolving P2O5 in 85% phosphoric acid (H3PO4). There is also a preparation in an old Organikum stating it can be made by boiling off water from 85% H3PO4 under vacuum for 6h at 150°C, but I have some doubts that this gives polyphosphoric acid (perhaps it was meant to make a near 100% H3PO4).
Quote:
Everything smelled like almond.. could it be cyanuric acid?


Cyanuric acid is a nonvolatile solid without smell. Probably you meant hydrogen cyanide (HCN). It is unlikely that your experiment produced that. Note that bezaldehyde also smells like almond, but I don't see how urea could reduce benzoic acid.

You don't have to heat up to 200°C for the conversion of an acid to amide with urea. No wander everything sublimates off. Use an oil bath to regulate the temperature at 160-170°C. The reaction works perfectly at this temperature. Anything above will lower the yields due to urea decomposition to biuret, cynuric acid, melamine and other crap. You can tell the reaction is going on well by the evolution of CO2 in tinny bubbles and the ammonia smell. No solvents is needed and if used it would surely lower the yield since urea is not soluble in xylene and similar non polar solvents.

You can wash the product solution in toluene (or what ever you are going to use for extraction) with a solution of NaOH or Na2CO3 to remove any unreacted benzoic acid.

see also: https://sciencemadness.org/talk/viewthread.php?tid=4074

PS: The Hoffman rearrangement is not made like described in the first post of this thread. It is done on the amide and not on a reaction mixture containing urea and all kind of other crap that consumes the hypochlorite. And it is necessary to first let the hypochlorite form the N-chloroamide at a low temperature since at above 50°C the disproportionation of NaOCl to NaCl and NaClO3 occurs rapidly. Only after this induction period at <20°C is the reaction mixture heated to 60-80°C in order for the N-chloroamide to rearrange.

dr. nick - 27-7-2005 at 02:51

hm. i'm trying a little learning by doing here - do i get this right: the benzamide first has to be cleaned (mix with NP and wash with NaOH) before proceeding, right?

Just one more question: is benzamide of any use for any other interesting task?

Thanks!

dr. nick - 15-6-2006 at 10:44

hey!

had a little spare time, so i decided to give it another try -
everything like every time, just did not let the temp rise above 150 C.

then mixed with NP (Cleaning Benzin), heated, filtered and washed the
solid in the filter with 200ml 10% NaOH solution -
and was pretty surprised that it all dissolved ... now he has two layers -
one NP on top of the aquaeous layer and both are somehow dirty now -
Aquaeous is yellowish and there are floating solids in the NP ...

is this good or bad or ... ?
and if it's good - what to do now?

completely confused now!

swid doesn't understand anything now anymore ...

can anyone help, please?

thanks!

ps.: found some info at last, but still not clear what to do now -
it's says amides are polar, so when there was any benzamid present it should be in the NaOH-Solution now?

as far as i understood amides are also rather basic, even if not as much as
amines, but how would one get them out of the solution, now? they will probably not form a top layer like amines, so they can't be salted out with HCL, or can they? Or just evaporating the water?

oh man ...

[Edited on 15-6-2006 by dr. nick]

Dr. Beaker - 15-6-2006 at 15:58

interesting discussion...

I want to make pentafluoro aniline from pentafluoro benzoic acid.
the procedure posted by S.C. Wack looks atractive to me, however I'm afraid the poorly nucleophilic oxygenes of C6F5COOH would hinder any reaction that include protonation of the COOH...
the only way I found 'till now that uses (relatively) simple reagents is this:

C6F5COOH ---> C6F5COCl (using SOCl2)
C6F5COCl ---> C6F5COONH2 (by addition of hydroxyl amine)
C6F5COONH2 ---> C6F5NH2 (-CO2 by heating with K2CO3)


any thoughts anyone?:)

dr. nick - 6-12-2006 at 11:05

Hey!

Can anyone give me (or hint me to) an instruction to the "destructive distillation" of Indigo? You know, Otto Unverdorben and stuff :)
Can not find it, lots and lots of hits on google, but they all only include the same text from wikipedia and that's of no use for me.

Just got some kg of Indigo and don't know what to do with it there
this old project came to mind again :)


Would be great!

Thanks!

garage chemist - 6-12-2006 at 12:04

How is it possible that I never saw this thread?
I have produced and investigated the properties of benzamide (though my target product was benzonitrile).
I produced it by dripping benzoyl chloride into cooled excess conc. ammonia solution under vigorous stirring.
People without access to Benzoyl chloride will of course choose to go the urea route.

Benzamide can be recrystallized from water, but it must not be brought together with alkali because it will hydrolyze and dissolve (product is destroyed then).
I might consider doing a documented synthesis of benzamide and aniline from benzoic acid.

To separate benzamide from unreacted benzoic acid, ammonia solution is added. Only the benzoic acid dissolves, the benzamide remains undissolved (when kept cold).

Aniline was produced from indigo by dry distillation with lime (Ca(OH)2).


Oh, and amond smell during production of benzamide is benzonitrile (dehydration product of benzamide, an oil which is slightly soluble in water). This smells very similar to benzaldehyde.

BTW, are you still reading here Frogfot?

[Edited on 6-12-2006 by garage chemist]

dr. nick - 6-12-2006 at 13:00

that's very interesting - information on simple benzamid is only very sparely available -
be it on the net or in the books available to me!

I have to use the urea/benzoic acid variant so do you have maybe a suggestion how to do it? The sublimation of the benzoic acid every time spoiled any success ...
Quote:
I might consider doing a documented synthesis of benzamide and aniline from benzoic acid.

yes, please, do so - that would be so cool - i already gave it up. My last idea (haven't tried it) was to put the mixed urea/benzoic acid into a aluminum can, than flatten it, closing the ends tight and to heat it in an oil bath, hoping it will not build too much pressure.

Thankful for any hint!

ps.:
Quote:
Aniline was produced from indigo by dry distillation with lime (Ca(OH)2).

could you describe that a bit more in detail? How to do it and so on? Is it maybe like with benzene from sodium benzoat and lime?

garage chemist - 6-12-2006 at 13:38

I have made phthalimide from phthalic anhydride and urea, and sublimation of the phthalic anhydride is also a problem there. The problem is solved by heating fast enough so that the reaction is over in 5 minutes. Only a small amount of sublimation occurs then.
If the heating would have to be done for maybe an hour, sublimation would be a big problem.

I will try to make benzamide from benzoic acid this weekend (I can only experiment on weekends) and report my findings.
I am interested in this because benzoyl chloride is really too expensive and valuable to use it up for making benzamide.

If sublimation turns out to be a problem, I will try to enclose the mixture into a test tube which will be melted shut (e.g. an ampoule) or enclose it into a test tube with ground glass joint and stopper. Though I hope to be able to work in a normal round- bottom flask.

I do not have any references on the production of aniline from indigo, but I know that it was made by dry distillation with lime.
For me this information would already be enough to start experimentation (if I needed aniline, which isn't the case).

BTW, I have a detailed synthesis of aniline from benzamide. It's in Organikum. I can put a short summary here if there is interest. However, sodium hypobromite is used. If sodium hypochlorite would have to be used instead, its concentration would have to be exactly known.
In the lab, NaOBr is very much favored over NaOCl because it can be made fresh and of exactly known concentration from bromine, NaOH solution and ice.

dr. nick - 7-12-2006 at 00:54

Hey, thank you -

that's very encouraging, going to give it another try then, too - i had no idea how long the reaction would need to finish. Maybe the "juice can idea" isn't that stupid in the end, too.

Hm, Bromine is a problem, maybe on could get it from Bromine pool tabs?
I wonder how to do that.

Looking forward to your report, aniline so-to-say OTC is a long harbored dream of mine!

ps: the dry distillation: all i can think of would be like using the same procedure like for Benzene from sodium benzoat and lime ... think i'll give it a try. thanks!

[Edited on 7-12-2006 by dr. nick]

Pabpa - 7-12-2006 at 11:47

Hi,

I've done this reaction several times. It's very easy: 1kg benzoic acid, 2kg urea and 10ml phosphoric acid are heated for 2h at 170°C (should be carried out in an efficient hood or outside). Benzamide is purified by recrystallization from H2O and then from 9% ammonia solution.

Pabpa - 7-12-2006 at 23:26

Quote:
The sublimation of the benzoic acid every time spoiled any success ...


Are you sure about the sublimation of benzoic acid? The white stuff might be ammonium cabonate. ;)

dr. nick - 8-12-2006 at 00:33

Quote:
Are you sure about the sublimation of benzoic acid? The white stuff might be ammonium cabonate.

Are you sure? That would be great - got to check that out - gonna heat some of my benzoic acid alone to see what happens and will report again!

Thanks!

Btw.: the Phosphoric acid might maybe help to prevent the sublimation (or what ever) by washing the stuff down again - maybe my error is the too small scale? i always do it in a test tube.

Pabpa - 8-12-2006 at 01:22

Quote:
Btw.: the Phosphoric acid might maybe help to prevent the sublimation (or what ever) by washing the stuff down again - maybe my error is the too small scale? i always do it in a test tube.


The phosphoric acid (or phosphorous acid) is used as a catalyst. You can do it in a test tube, too. But you need only one drop of phosphoric acid in this case. Have you noticed the smell of ammonia and bubbles coming out of the hot liquid?

dr. nick - 8-12-2006 at 01:25

Quote:
Have you noticed the smell of ammonia and bubbles coming out of the hot liquid?

Sure, both - bubbles like beer and smells like, well, ammonia :)
But the walls where almost full of crystals after some minutes

Pabpa - 8-12-2006 at 02:46

Quote:

But the walls where almost full of crystals after some minutes


Are these crystals soluble in cold water? Is there carbon dioxide released when treated with an acid (acetic acid, HCl...)?

dr. nick - 8-12-2006 at 03:18

oh - got to test that, will report later!

dr. nick - 8-12-2006 at 12:07

ok then -
once again i put 2g Carbamide and 4g Benzoic Acid into a large test tube and heated it just as much as it needed to liquefy both substances. After around 5 min. the whole test tube walls where full of fluffy, snowy white cristals that almost closed the tube.
The rest of the mixture on the bottom of the tube has (after cooling) a slighly yellow-dirty white color with maybe a 1mm thick darker, more gray top layer that seems to be a bit more clear as the rest and evolved tiny bubbles after the rest of the mix was already compact again. Very hard to see in such small amounts, maybe only an optical delusion.

When some of the white-fluffy-snow crystals from the vessel walls where mixed with a little cold tap water they dissolved almost completely very fast, but when i mixed some more of that stuff with around 25% HCL the powder didn't dissolve. Not sure there was CO2 emission, but the walls of the vessel became a bit milky. When it spoiled the fluffy-snow-HCL-mix to the drain it began to fizz after it came into contact with the waterdrops in there.

Hm. Now what does this mean?

btw: the described fluffy stuff has a smell like, i don't know, sweet, nice, almost tasty :)

garage chemist - 8-12-2006 at 13:17

I'm gonna do some experiments today.
Are the proportons of 1 part benzoic acid and 2 parts urea correct? If yes, then it's a large excess of urea. But maybe that is needed to keep sublimation down and make the reaction proceed rapidly. I'll use those proportions, and add a drop of phosphoric acid.

Pabpa - 8-12-2006 at 14:14

Quote:
Are the proportons of 1 part benzoic acid and 2 parts urea correct? If yes, then it's a large excess of urea.


0.25mol benzoic acid and 1mol urea. You might read this b4:

http://v3.espacenet.com/textdoc?DB=EPODOC&IDX=DE869639&a...

dr. nick - 9-12-2006 at 01:29

oh ...
i thought it was 2 part Benzoic Acid to 1 Part Urea ... ?
Hm, maybe only the excess of Benzoic Acid sublimates?

Btw: that doc is interesting - so you say in the case of Benzamid
Ammomia solution can be used to wash the Product and then it can
be recrystallised from hot water?
cool! Since i scraped the sublimed what-ever from the test tube walls
there didn't happen much more sublimation when heating again -
interesting (to me) i found that there builded a solid white core in the yellow,
hot bubbling liquid.

garage chemist - 9-12-2006 at 01:33

The patent you posted is very good: short but contains everything that is needed. BTW, are you from germany Pabpa?

Anyway, last evening I did some experiments, without having read the patent before. It was a success: I can verify that benzamide is formed in an urea/benzoic acid melt, even without addition of phosphoric acid.

2g benzoic acid and 4g urea were ground together in a mortar to yield an intimate mix of the constituents.
This was transferred into a 50ml beaker which was covered loosely with a teflon sheet. The beaker was placed on a wire gauze (without ceramic or asbestos) and heated directly with the bunsen burner. The mix rapidly melted, and when heated further, gas evolution and boiling was observed (vigorous bubbling). Lots of crystals sublimed to the walls of the beaker and to the teflon, which prevented loss of product/educt via sublimation. Ammonia was smelled in the escaping gases.
The mix was heated and kept bubbling vigorously for 2-3 minutes, the teflon sheet was tapped from time to time to make the crystals fall down into the melt again.
It was then left to cool.

To the still warm, solidified mix there was added 30ml water and it was heated again, under stirring. As the water reached the boiling point, all solids dissolved after some stirring to yield a clear solution.
The heat source was removed and 20% ammonia solution added with stirring until the solution aqcuired a strong smell of it (about 5ml). This keeps benzoic acid and cyanuric acid from precipitating, because they get bound up as their soluble ammonium salts.
The solution was left to cool. After it was at room temperature, it was cooled further to 5°C. It was only after some stirring that the benzamide started to crystallize, apparently its crystallization is slow. Lots of white flocculent crystals filled the liqid after half an hour.
The benzamide was filtered with suction and washed with ice- cold water until free from ammonia odor. It formed a white fluffy powder which was placed in the vacuum desiccator to dry (it should be dry by now). The yield does not seem to be good, but this can be improved by longer heating time.

Today I will determine its melting point to clear all doubts on the identity of the product.

The next step will be upscaling (20g benzoic acid) and usage of phosphoric acid.

If I have a few tens of grams of benzamide, the Hofmann degradation will be performed to yield some aniline.
I have looked in Organikum and they give a procedure which uses NaOCl, made directly before the reaction by bubbling a measured amount of chlorine through icecold NaOH solution. I will use this method.

[Edited on 9-12-2006 by garage chemist]

dr. nick - 9-12-2006 at 01:50

wow - cool!
i'm sorry-haven't found that in Organikum yet -
please, which edition of Organikum do you use?

[Edited on 9-12-2006 by dr. nick]

garage chemist - 9-12-2006 at 02:20

I have the 15th edition of Organikum. The preparation is for 3,4- Dimethoxyaniline from the corresponding benzamide, not for unsubstituted aniline, but that doesn't matter of course.

dr. nick - 9-12-2006 at 02:27

Thank you!

If been so long after this without success that i already had given it up!
Would you mind to report if you're done with it (Hoffmann Degradation, I mean)?

Anyway, thanks again :)

[Edited on 9-12-2006 by dr. nick]

garage chemist - 9-12-2006 at 03:13

Yes, I will report my experimental findings here, and if the production of aniline turns out to work well, I will make detailed synthesis instructions.

But why exactly did you give up? You didn't even try to synthesize anilin, you made no effort to isolate any product and you didn't even try to see if the intermediate was being formed. What you have done can not be called synthesis, not even experiment.

dr. nick - 9-12-2006 at 04:58

i do not have sufficient knowledge, even not much basic knowledge, almost no talent of and for chemistry - just a lately developed interest (last 3 years maybe). Now i try to get into it the only way i can think of being of value to me - some "learning by doing" - that means i do not know what to expect as results so i never know if i did it right.

That's why i gave up.

to me it looked like my experiments always went wrong and i wasn't able to ask the right questions and also couldn't find out myself. You can damn me for being around here on that base, but as there's no "kindergarden forum" for my interests i'm still here :)

[Edited on 9-12-2006 by dr. nick]

Pabpa - 9-12-2006 at 05:00

Quote:
I have looked in Organikum and they give a procedure which uses NaOCl, made directly before the reaction by bubbling a measured amount of chlorine through icecold NaOH solution. I will use this method.


It might be easier to avoid the preparation of chlorine and use household bleach instead:

http://designer-drugs.com/pte/12.162.180.114/dcd/pdf/hofmann...

DeAdFX - 10-12-2006 at 21:48

I kinda feel stupid asking this but... I wish to do this experiment but my only source of ammonia contains sodium silicates + other filler material. Is this source of Ammonia acceptable for the purifying stage of Benzamide or should I try and capture the ammonia gas released from the benzamide syntheis and use that?

garage chemist - 16-12-2006 at 08:51

OK, the stuff from my described experiment IS NOT BENZAMIDE.
It doesn't melt even at 180°C, while a sample of pure benzamide from benzoyl chloride and ammonia had the correct melting point of 124°C. I am really glad that I did the melting point determination.

I did a new experiment, this time with 5g benzoic acid and 5g urea and a few drops of 85% phosphoric acid (less than 0,1ml).
This looked much better.
I heated it in a 100ml rbf with the small flame of a bunsen burner so that it fizzed gently. Sublimated material was periodically melted back into the reaction mix by heating the upper walls with a bunsen burner. After a few minutes, ammonia smell was present and got intense shortly afterwards. It was left fizzing with continued heating until the melt started to partially solidify despite the heating and smell of benzonitrile started to become noticeable (about 30- 45min, I didn't look at my watch).
After addition of 50ml water and 4ml 20% ammonia, heating dissolved nearly all solids. It was decanted from a little undissolved material and left to cool in a beaker, and many small needles slowly appeeared which look nice and uniform. The melting point test will show if they are the desired product.

As a preliminary conclusion, the addition of phosphoric acid seems to be essential for the reaction to occur.

[Edited on 16-12-2006 by garage chemist]

Pabpa - 17-12-2006 at 04:04

I just tried the Organikum synthesis of aniline with success. Took bleach (2.8% NaOCl solution -> DanKlorix) instead of chlorine + KOH. I'm distilling it now.

garage chemist - 17-12-2006 at 04:56

Would you give us a report of the synthesis, e.g. the used amounts of reactants, what you have done exactly etc...? Just like I did with my report of the benzamide synthesis above. That would be nice.

The product from my last experiment with phosphoric acid (described above) has the correct melting point and is indeed benzamide. I did an additional test by boiling a sample with acetic anhydride- upon hydrolyzing the mixture with hot water, the almond odor of benzonitrile was evident and the identity test thus positive.
I will do a larger batch (25g benzoic acid), either today or next week. I will also have to get some more benzoic acid, and I'll have to go to the pharmacy for that (which is stupid because chemicals are at least twice as expensive there than from internet suppliers, but its the only way to get it before christmas holidays).

dr. nick - 17-12-2006 at 08:07

Quote:
the melt started to partially solidify despite the heating

can confirm that so far.

DeAdFX - 17-12-2006 at 10:08

Quote:
Originally posted by garage chemist
Would you give us a report of the synthesis, e.g. the used amounts of reactants, what you have done exactly etc...? Just like I did with my report of the benzamide synthesis above. That would be nice.

The product from my last experiment with phosphoric acid (described above) has the correct melting point and is indeed benzamide. I did an additional test by boiling a sample with acetic anhydride- upon hydrolyzing the mixture with hot water, the almond odor of benzonitrile was evident and the identity test thus positive.
I will do a larger batch (25g benzoic acid), either today or next week. I will also have to get some more benzoic acid, and I'll have to go to the pharmacy for that (which is stupid because chemicals are at least twice as expensive there than from internet suppliers, but its the only way to get it before christmas holidays).


I would but I cannot purify the benzamide yet(no ammonia water). I am waiting on some rubber tubing so I can synthesis some from urea. But here is what I have done so far.

Anywho I heated up Urea and Benzoic acid in a filter flask with a saran wrap cap and a tygon tube in some water. The reactants where in a 4mol:1mol ratio scaled down to ~13.5(urea)grams 7(benzoic)grams(to lazy to convert to mols). The mixture was heat for 1 hour with the temperature maintained between 160-180C. About 45 minutes into the reaction the temperature dropped 20c to 150C and continued to drop some more (10C) until I turned the heat up so more. I am wondering if this 45 min mark indicates completition or if I wasn't paying attention.

The flask began to fog up as benzoic acid crystals formed on the sides. The reaction smelt strongly of Ammonia and benzoic acid. The crystals were difficult to knock back into the reaction mixture because of the shape of the filter flask. I think a beaker with some saran wrap would work better. I don't expect a very high yeild(10-35%) unless those crystals on the side happen to be benzamide.

The reason for using the filter flask was because I was hoping to capture the ammonia from the reaction so I could recycle it. I only got a couple bubbles before the nipple side got clogged.

[Edited on 17-12-2006 by DeAdFX]

Nicodem - 17-12-2006 at 10:41

Quote:
Originally posted by garage chemist
2g benzoic acid and 4g urea were ground together in a mortar to yield an intimate mix of the constituents.
This was transferred into a 50ml beaker which was covered loosely with a teflon sheet. The beaker was placed on a wire gauze (without ceramic or asbestos) and heated directly with the bunsen burner.

I'm afraid you will only get a bunch of a biuret, cynuric acid and other similar crap if you do things with such negligence. You should use an oil bath and maintain it for 3h at 170-180°C instead of using brute force aka Bunsen burner. Use 4 equivalents of urea and 15mol% of boric or metaboric acid rather than phosphoric acid. At least that is how I used to prepare amides out of carboxylic acids with excellent yields (though I never tested the method on any benzoic acid).

garage chemist - 17-12-2006 at 11:22

I certainly will not heat up an oil bath for such small test runs. The small pilot flame of my burner has very often done a good job at keeping things hot throughout a reaction. The conditions are not "brute force", as the flame is really small.
For actual synthesis of useable amounts of product it will be a different story. I will use an oil bath then.

Where did you get the procedure with boric acid as catalyst? Is that also from a patent? I'd like to read that procedure.

BTW, I got 3g Benzamide from 5g benzoic acid with the synthesis above, using equal weights of urea and benz and with H3PO4 as catalyst and with 45min heating with bunsen burner.
Biuret, cyanuric acid and the like don't bother me as they will stay in solution due to the added ammonia.

EDIT: Check out this patent: US5550286
They use stochiometric amounts of urea and phosphorous acid (which is H3PO3, NOT H3PO4) in an inert high- boiling hydrocarbon solvent and get yields of 70- 90% with benzamides (substituted and unsubstituted).
With H3PO4 instead of H3PO3 they get 60% yield for benzamide, which isnt that great, but the unreacted benzoic acid can be recycled by acidifying the filtrate from the amide precipitation.


[Edited on 17-12-2006 by garage chemist]

Nicodem - 17-12-2006 at 15:21

Quote:
Originally posted by garage chemist
I certainly will not heat up an oil bath for such small test runs.

Well, the temperature control is of huge importance in organic synthesis, hence the oil bath. But if you manage to control the heat with a flame, never mind.
Quote:
Where did you get the procedure with boric acid as catalyst? Is that also from a patent? I'd like to read that procedure.

I know from this work that the carboxylic acids get activated by complexing with the boric acid which itself gets activated by its equilibrium with metaboric acid at elevated temperatures. It is similar like the phosphoric acid<>pyrophosphoric acid thing, but more effective at the given temperature. But anyway, I never compared the yields with the uncatalyzed reaction so the addition of the boric acid might just as well be obsolete.

garage chemist - 17-12-2006 at 15:35

Hmm, the orgsyn prep looks interesting- but the use of an organic solvent makes the procedure more time- consuming and more expensive. I think I'll stay with the urea melt method. I might try adding boric acid instead of phosphoric acid though, and I will first ensure temperature control (oil bath).

markgollum - 17-12-2006 at 15:38

I have made enough fairly pure benzamide by the benzoic acid > methylbenzoate > benzamide route for several experiments.
But I am uncertain how to proceed with the hoffman rearraingment even several hours at the university library came up empty as to how exactly it is done.

This what I did.
First I made 295g of benzoic acid from sodium benzoate and HCl.

Next I made the methyl benzoate as per the procedure on frogfot's page.

67.66 g of benzoic acid was added to 227.25mL MeOH and ~8ml 90% H2SO4 in a glass pressure vessel. (Not necessary just seemed convenient)
The mixture was kept at 50-62C for 6 hours, left overnight at room temp.
The next day I filtered the contents (a fair bit of a fine white pecipitate formed right at the beginning when the chemicals were first mixed) added a bit more H2SO4 > more whit ppt, refiltered, then transfered to an erlenmeyer and refuxed for an hour.
Next the MeOH was distilled off and the residue was poured into water with lots of NaHCO3 to neutralize the acid and washed with more water.
Yield was poor ~42mL of methyl benzoate. ( The white ppt was NaHSO4 from some sodium benzoate in the benzoic acid)

Next the 42mL of methyl benzoate was added to a 150mL glass pressure vessel containing 40mL of selfmade ammonia water (not saturated but NH3 gas would not dissolve rapidly enough to prevent the bubbles from reaching the surface) 55mL of MeOH was added and more ammonia gas was bubbled in for about 30min, (at one point I became impatient and increased the gas flow to much resulting in the eruption spilling ~20mL of solution) the pressure vessel was closed and kept at room temp for 2 weeks.
(two layers, top one water and methanol, bottom the majority of the methyl benzoate)

At the end of the 2 weeks during which I would often shake the vessel to form an emulsion, only about 1/3 of the methyl benzoate had reacted so I decided to warm the flask to speed things along.
I made a "warm box" by suspending some nichrome wire and pushing a thermometer through the lid of a styrofoam box I had received some glassware from Ebay in.
After 2.5 days at 50-65C the methyl benzoate layer had completely dissapeared and the solution had become clear.
On cooling to RT a mass of white crystals precipated.
The methanol and ammonia were boiled off and the I recrystalized the benzamide from water.
The resulting crystals smelled strongly of methyl benzoate and would turn into an oil at about 80C, so I decided to boil the crude benzamide in 6% HCl IIRC (might have been 4%) to preferentially hydrolyse the ester.
The solution was boiled gently for about an hour, left overnight, neutralized with the exact amount of NaOH necessary, heated and cooled to redissolve and reprecipitate the crystals, filtered, then the crystals were rinsed with cold water, dryed, and weighed.
A sample was taken to the Uni and its melting point was taken.

Final results 11.2g of benzamide melting point 126C literature 132C (not bad considering the principal impurity is a liquid)

[Edited on 17-12-2006 by markgollum]

[Edited on 17-12-2006 by markgollum]

[Edited on 17-12-2006 by markgollum]

[Edited on 17-12-2006 by markgollum]

Benzamide2.JPG - 63kB

garage chemist - 17-12-2006 at 15:52

Quote:
Originally posted by markgollum

The resulting crystals smelled strongly of methyl benzoate and would turn into an oil at about 80C, so I decided to boil the crude benzamide in 6% HCl to preferentially hydrolyse the ester.
The solution was boiled gently for about an hour, left overnight, neutralized with the exact amount of NaOH necessary, heated and cooled to redissolve and reprecipitate the crystals, filtered, then the crystals were rinsed with cold water, dryed, and weighed.
A sample was taken to the Uni and its melting point was taken.

Final results 11.2g of benzamide melting point 126C literature 132C (not bad considering the principal impurity is a liquid)

[Edited on 17-12-2006 by markgollum]

[Edited on 17-12-2006 by markgollum]



NO! Why did you boil the amide in HCl? Thats a sure way to hydrolyze it! This explains the bad yield.
You could have steamdistilled the methyl benzoate from the aqueous solution (benzamide is very soluble at 100°C) of the amide, that would have been a correct procedure. After cooling, you would have obtained recrystallized benzamide which can then be freed from benzoic acid residues by treatment with ammonia solution.

[Edited on 17-12-2006 by garage chemist]

markgollum - 17-12-2006 at 16:02

I know that acids and bases hydrolyse amides ,
however all the textbooks I read claim that a prolonged reflux with acid is necessary and that the preferred method to hydrolyse an amide is to boil with 30% NaOH.

Besides if I had hydrolysed a large amount of the amide, I think I would have noticed the low solubility benzoic acid precipitating.

Nicodem - 17-12-2006 at 16:06

Quote:
Originally posted by garage chemist
Hmm, the orgsyn prep looks interesting- but the use of an organic solvent makes the procedure more time- consuming and more expensive. I think I'll stay with the urea melt method.

The method at Orgsyn is for the amines coupling with carboxylic acids and is useless for the direct preparation of N-unsubstituted amides or amides of lower boiling amines. Only its theoretical principle was taken for the amide formation with urea - that is the boric acid catalysis. Otherwise, with urea the active reagent in the carboxylic acid activation and amidation is presumed to be the ammonium cyanate (NH4OCN) that forms in equilibrium at elevated temperatures (I don't remember where I read this anymore). But anyway the H3PO4 or H3BO3 both activate the acid themselves as well as increase the concentration of free cyanic acid that is also able to activate the carboxylic acid for the reaction with ammonia/urea.

According to Synthetic Organic Chemistry (Wagner&Zook, 1953) the following paper should contain the preparation of benzamide with urea (if I understood it well): Cherbuliez and Landolt, Helvetica Chimica Acta 29 (1946) 1438.
Quote:
NO! Why did you boil the amide in HCl? Thats a sure way to hydrolyze it! This explains the bad yield.

No way would 1h of boiling in 6% harm much the benzamide. Amides are nearly as easy to hydrolyze when compared to esters.

Pabpa - 21-12-2006 at 00:41

Quote:
Originally posted by garage chemist
Would you give us a report of the synthesis, e.g. the used amounts of reactants, what you have done exactly etc...? Just like I did with my report of the benzamide synthesis above. That would be nice.


I'll scale it up and give a description next year. I'd like to use calcium hypochlorite because it's less expensive.

dr. nick - 24-12-2006 at 14:05

after mixing the ammonia- and water washed product of the given procedure (urea+benzoic acid) with some chlor bleach solution i got a brown liquid which smell somehow reminds me of "garlic breath" with a somehow alcoholic by-taste ... how would you describe the smell of aniline?

darn, i really could use a small amount of it to be able to compare.

[Edited on 24-12-2006 by dr. nick]

[Edited on 24-12-2006 by dr. nick]

[Edited on 24-12-2006 by dr. nick]

garage chemist - 25-12-2006 at 04:41

Aniline smells unpleasant, though not fishy as one might expect.
The smell is weak and yes, "bad breath" is somewhat fitting as a description.
But the smell is in no way useful as an indicator of its presence! You need to isolate it and charaterize its properties (e.g. derivatization as the acetanilide and recording the melting point of this)!

How have you isolated the benzamide product? Dissolved in hot water, adding ammonia and letting cool to crystallize like I have done?

And did you add some extra NaOH to your bleach like it is necessary for a hofmann degradation?

BTW, I recently made a benzamide batch using 15g each of benzoic acid and urea, and 5 drops H3PO4. I have crystallized it by now, what remains to be done is filtering, washing and drying. I will report the yield.

[Edited on 25-12-2006 by garage chemist]

dr. nick - 25-12-2006 at 04:57

Quote:
And did you add some extra NaOH to your bleach like it is necessary for a hofmann degradation?
Ah, i knew i missed something - been thinking about it, but not under the same point of view - and as it was already pretty basic i didn't add extra NaOH.
How much/to what ph should the NaOH be added?

At the moment i'm just adding a little HCL to get the solution to neutral/slightly sour ph to try and see if i'd get some anilin.hcl maybe ... I don't see any other way to get the anilin out of the watery solution ...

It was a very small amount this time, will start another run with more next time.
You used Benzoic Acid:Urea 1:1? To compensate the loss of sublimating Benzoic Acid?
Good idea, i guess - will do it that way, too!

[Edited on 25-12-2006 by dr. nick]

Sauron - 25-12-2006 at 06:46

Is aniline suddenly hard to buy? If so it's a good thing I have a lot of it on hand. If you work with it much keep an eye on your fingernails and peek in the mirror once in a while. Dark blue lips and/or a blue band on your nails is a Bad Sign that you have over exposed yourself.

garage chemist - 25-12-2006 at 07:04

Calculate the stochiometry of the hoffmann and add enough NaOH for the solution to still be strongly basic after reaction.

Quote:
At the moment i'm just adding a little HCL to get the solution to neutral/slightly sour ph to try and see if i'd get some anilin.hcl maybe ... I don't see any other way to get the anilin out of the watery solution ...

Oh man! :mad: Are you sure you should make any aniline if you are that ignorant of its properties?
Aniline-HCl is SOLUBLE in water, just as ANY amine hydrochloride/other mineral acid salt!
Anline is isolated by making the reaction mix BASIC and steamdistilling the aniline out of the solution.
The distillate is extracted with ether or DCM, the organic phase dried with Na2SO4 and the solvent distilled away to leave the aniline.
You could even directly extract the basified reaction mix with solvent, although the product will be less pure.

dr. nick - 25-12-2006 at 10:37

i am aware of that.

when the water is evaporated the salt (if there is any) should be left, right?
so come down again, please, 'k? :P

btw.: thanks for the steamdistilling hint, also good to know a simple a/b would work also.

[Edited on 25-12-2006 by dr. nick]

garage chemist - 25-12-2006 at 16:58

But with evaporation you have all the sodium salts in there as well. It simply is not a valid procedure.
Normal distillation of the basified reaction mix should do the same as steamdistillation, I think you might even see aniline oil drops in the first distillate.
I have isolated toluidine from a nitrotoluene reduction by normal distillation of the aqueous mix, so it should work just as well with aniline.

BTW, I got 12,8g benzamide from the 15g benzoic acid.
I also did another batch with 20g benzoic acid (1h 30min at 180-185°C), which yielded 17g benzamide!
This works very good. Lets hope that the benzonitrile production works as well. I have yet to synthesize the benzyltriethylammonium chloride as a catalyst for the reaction of benzamide with thionyl chloride.

However, the melting point of the benzamide is consistently too low (around 118°C, while it should be from 124-128°C). Recrystallization is obviously required for obtaining a pure product.
I'll see what yields of benzonitrile I will get from the crude product.

dr. nick - 26-12-2006 at 00:58

i see.
thanks, you're very helpful!

In case one has (not in this case) pure aniline.hcl - what are the visual (sensual) properties of it? i don't have a merck index (mac here), is there something equivalent to it?

Just out of interest: Benzonitrile - Phenylcyanide, what could it be used for?

please be indulgent with me, i'm no complete idiot (i guess), i simply do not have much chemical literacy, so i'm tinkering around with the equivalent of an adult chem experimentation kit, trying to learn something the interesting way. i think i know enough (i hope) on safety, but that's it.



thanks!

[Edited on 26-12-2006 by dr. nick]

garage chemist - 26-12-2006 at 08:24

Aniline is not stored as the HCl salt. Contrary to aliphatic amines, which do not store well as the freebase (CO2 uptake from the air) aniline is a weak base which does not take up CO2 at all and stores fine as the freebase. Also, the aniline has a much smaller storage volume than its hydrochloride.
I also think that the hydrochloride is strongly hygroscopic, although I am not sure of that. But there must be a reason why aniline is never handled as its salt and always as the oil.

It is clear what you have to do: basify your reaction mix and distill off about half of its volume. Extract the distillate with ether or DCM, dry the extract with Na2SO4 and evaporate the solvent.

Benzonitrile can be reacted with grignard reagents to form an imine complex which is hydrolyzed to the phenylketone on heating with aqueous acid. For example, the reaction of ethylmagnesium bromide with benzonitrile would afford propiophenone after workup and hydrolysis.
And as you might know the reagent ethyl bromide is very easily made from ethanol and HBr. Only the grignard formation might be difficult without the proper drying agents for making absolute ether.

dr. nick - 26-12-2006 at 10:32

Thank you,
this should help a lot!

btw: wether there is some aminobenzen in my product or not, after evaporating the water there is a dark brown sludge left on the bottom of the vessel with plaques of whiteish crystalline matter within - to me that looks promising, even if don't want the hcl either. Next runs will take place after method described above!

Hm, not bad - propiophenon ... there was something i can't remember yet, got to look it up, didn't it have to do something with phenylmagnesium bromide ... ? well, probably another story.

garage chemist - 2-1-2007 at 10:14

Full benzamide synthesis documentation with pictures and writeup is now available here:
http://www.versuchschemie.de/htopic,8165,.html

[Edited on 2-1-2007 by garage chemist]

Benzoate --> Benzoic acid --> Benzamide --> Aniline

smuv - 14-10-2008 at 21:22

So I made some aniline this weekend. Everything was a little rushed forcing me to make some stupid mistakes, but all in all it went pretty well. Sorry for some crappy pictures.

Benzoic acid

160.2g Potassium benzoate
~300mL Water
170mL 20.2% Hydrochloric acid

Potassium benzoate was added to the beaker followed by ~300mL water. The mixture was stirred and heated until homogeneous. Next, the hydrochloric acid was added in two portions and the precipitate was recovered via vacuum filtration; some distilled water was used to complete the transfer.

A portion of this crude product was recrystallized (probably was unnecessary as benzoate was a high grade and HCl was previously distilled). I accomplished this by dissolving as much crude benzoic acid as I could into 900mL of 90c distilled water, then increasing the temp to 100c and quickly vac filtering. The filtrate was allowed to slowly cool to room temp and then was placed in the freezer. Crystals were recovered via vac filtration and the filter cake was dried in the filter funnel.

Benzamide
40g Benzoic acid
59g Urea (3 eq)
3g boric acid (15 mol %)

The benzoic acid, urea and boric acid were added to a 250mL filter flask and everything was mixed until quasi-homogonous. A thermometer adapter was jerry rigged out of a piece of damp paper towel and into this a thermometer was placed with its bulb submersed in the powdered mixture. To the sidearm of the flask a piece of surgical tubing was affixed, the other end of the tubing was placed just above a beaker of water which was covered with a damp paper towel. The filter flask was placed in an oil bath and heated for ~3h at 170-180c; I want to note that heat up took about 30-40 minutes because my hotplate is pretty weak (anyone else think their Nuova is a little sissy when it comes to heat?). Evolution of gas began around 110c and became progressively more vigorous with increasing temperature. Every 10min or so, the thermometer was used to tap any sublimate off the side of the flask (most of it seemed to be ammonium carbonate). The hose on the sidearm was functional, but not as expected; ammonium carbonate would just fill the tubing and hang out there. Every hour I removed the tube and washed it out with water. This setup worked pretty well to contain the smell of ammonia, which could only be detected when cleaning the sidearm tube or removing the thermo adapter to kick off the sublimate. Towards the end of the 3h the bubbling waned and some suspended solids were noted in the melt. After 3 hours at 170-180c the melt was poured slowly into a beaker filled with 400mL sodium bicarbonate solution, some more water was used to complete the transfer. Next, more bicarbonate was added followed by enough NaOH to make solution strongly basic to pH test paper. The solution was stirred for a while; it had a spicy cinnamon like smell (benzonitrile, I presume). The whole mess was vacuum filtered, dried in the funnel and allowed to stand overnight. Mass of ultra-crude product, 35.6g.

Next, I took two grab samples and tried to get a mp, both were super high; it looks like my initial workup kind of sucked. I ground the product in a mortar and pestle and divided it into two portions to search for a suitable workup. I took one portion and added it to ~100ml denatured alcohol and heated the mixture to boiling with some vigorous swirling. I allowed the solution to cool to room temp (to hopefully precip everything but the benzamide). After cooling, the mix was vac filtered and filter cake was washed with some alcohol. The filtrate was placed in a casserole dish and most of the ethanol was evaporated, some nice plates precipitated out on cooling. The mp of this product was 119-120c, the low melting point is presumably due to a benzonitrile impurity (although crystals were odorless). This product was deemed pure enough, so the same workup was performed on the other half of crude product. Both crystal crops were combined giving 16.5g of benzamide or a 41.6% yield.


(The reagents)


(The reaction, about halfway through. No thats not motor oil!)


(Basic solution used to remove reaction junk from melt, my problem child)


(product precipitated from ethanol)


(ghetto melting point apparatus)

Aniline
33g NaOH
330mL Water
10.5g TCCA (containing few percent CuSO4)
16.5g Benzamide

A 10% sodium hydroxide solution was prepared, it was chilled slightly (~15c) and added to a 500mL Erlenmeyer flask. A stir bar was added followed by the TCCA (it contained a few percent CuSO4). Immediately after addition the solution took a peculiar red black tinge which could not be explained by cupric hydroxide floc. All the TCCA dissolved with a very minimal amount of gas evolution and warming. Next the benzamide was added and the solution was stirred until most of it dissolved (~10 min). The solution darkened over the ten minutes to a turbid white-yellow and finally an opaque maroon. Everything was setup for reflux and the solution was slowly heated (over the course of ~20 min) to 60c and maintained at 60-65c for 20 minutes. The temp was pretty easy to maintain by lifting the flask off of the hotplate to moderate temp. After this heating, the apparatus was setup for simple distillation, an Erlenmeyer flask was a bad choice for this, and half way through I switched to a 1000mL fb flask. At first the distillate was a milky white but with time a faint yellow orange distillate began coming over. After about 250mL was distilled, I halted the operation to go sleep. The distillation was not complete though as the distillate coming over was still strongly basic to universal test paper. The steam distillate was saturated with NaCl and extracted 3x with ~30mL DCM. The extracts were dried over calcium chloride, vac filtered and filter cake washed with DCM. The solvent was evaporated off on a water bath. The last traces of DCM and moisture were removed by briefly heating the aniline just to boiling over a free flame. The final mass of crude aniline was 10.9g or an 86.6% yield. I wish I had time to distill this product, but I simply did not and will not for a long time.


(Solution after stirring for 20 minutes)


(steam distillation setup, before replacing Erlenmeyer with FB flask)


(receiver before ugly yellow stuff started coming over)


(aniline's density is so close to that of water, it sinks in distilled water, but floats in brine)


(pooled extracts)


(aniline ready to be re-distilled)

Improvements, questions, discussion

Benzamide
What the hell did I do wrong?

I would have followed garage_chemist’s workup but I didn’t have any surfactant free ammonia on hand. I thought a strongly basic solution would remove most of urea’s decomposition products, no? I had planned to take the crude crystals and extract them with boiling heptane but I didn’t have the time to distill some heptane. Although GC’s workup was much easier I think mine worked ok, can anyone see any problems with it that would have killed my yields?

This reaction is driven forward by the loss of ammonium carbonate, could my somewhat closed apparatus have something to do with my crappy yields?

Aniline
I was surprised that the steam distillate came over colored, is this normal?

I had never done a steam distillation before, was testing the distillate as it came over with pH paper a good metric to judge the progress of the distillation or would I have read strongly basic forever due to traces of aniline coming over?

I think I could get by using less sodium hydroxide; I just took the Organicum procedure and replaced Chlorine with TCCA. In the future I think I will strongly chill the sodium hydroxide solution before adding TCCA.

Sorry to be so long winded, I just want to catalog everything as accurately as possible so others can repeat and provide comments about my procedures.

Nicodem - 14-10-2008 at 23:07

Excellent work! Thanks for sharing.

Comments:

About benzamide preparation... The unreacted benzoic acid is not the main problem, so you primary focusing on its removal may have not been the optimal choice. Among the side products of the reaction there are plenty of urea decomposition products (biuret, cianuric acid and its amides...). I would suggest to rather attempt recrystallizing the whole mess in toluene (or xylene) to remove these insoluble and high melting side products. This will also remove the unreacted benzoic as long as there is not much left. If the melting point is still not optimal, you can then recrystallize again, but this time from water. A double recrystallization using solvents of opposite polarity (when possible) gives the best purity (ethanol dissolves too much benzamide at RT and is perhaps not the best choice). Also, it is possible that the reaction is over already in one hour and using longer times just creates more biuret and other crap increasing losses in the work up.

About the Hoffman rearrangement... Nice. The critique is about using CaCl2 for drying the extract. You should know that CaCl2 is incompatible with amines and alcohols, complexing with them. Rather use Na2SO4 or MgSO4 next time. Also, it would be nice if you could make a TLC of the aniline to see if it is clean from chloroanilines which can also come over with steam. Or at least measure its bp. I would not worry too much about your aniline not being colourless, but still the information about its actual purity would be good.

smuv - 15-10-2008 at 07:35

Thanks for the critique

benzamide: I agree, ethanol was a sub optimal solvent, it is just what I pure on hand. I will probably follow up on this in the future (when I have time in my lab). I want to clarify, I didn't really recrystallize from ethanol, I drove off like 90% of the solvent and let it cool; while some pretty chunks formed it wasn't a true recrystallization. I did this as you can expect to minimize the loss of benzamide with this sub optimal solvent.

Aniline: About the desiccant, wow! I know this and just totally overlooked it; thanks for pointing it out! About purity, I would very much have liked to further characterize the product but I just didnt have time over my short Columbus day vacation.


I would like to repeat this process in the future and hopefully optimize it, as I think it could be modified to painlessly make large quantities of aniline, very useful for the amateur chemist. Unfortunately I attend a university far from my home lab which means during the semester I have little time to focus on this hobby. This is why everything was rushed and my aniline was not further characterized.

Jor - 15-10-2008 at 07:47

Why did you talk about yourself as 'swim' and 'he' in the first post?
Ive read it before, and all the guys on drugsforums use it, they call theirselves SWIM. Why?

smuv - 15-10-2008 at 08:00

Someone who isn't me.

It is a stupid way to avoid self incrimination.

In the future, ask stuff like this in the proper forum or do a google search so threads don't get side-tracked.

That being said, I have no idea why someone would want to remain anonymous while making aniline. What are you going to do with it, go make psychedelic dyes?

Klute - 15-10-2008 at 10:14

Beautifull work! Thank you very much for sharing!

I've not much to add, maybe that KOH or K2CO3 are evry well suite dfor drying amines.

The fact that your amine came out colored during the steam distn doesn't necessarily means that it is heavily contaminated. Commercial aniline turns yellow after a while exposed to light in any case, and the impurities are very colored, so that very little casues quite some discoloration. I'm sure a quick fractionnation will remove them. I would suggest keeping your distille dproduct in a amber bottle, away from light and heat.

It's a real pleasure to read such reports. Thank you again for your time in posting this!

smuv - 15-10-2008 at 20:36

Thank you for the kind words.

Speaking of purity, if I require very pure aniline, can I achieve this by directly distilling my product or should I employ other means of purification as well? I assume fractional distillation is the way to go, can I do this with minimal product decomposition without hassling with a vacuum distillation?

jarynth - 16-10-2008 at 00:29

Quote:
Originally posted by smuv
I was surprised that the steam distillate came over colored, is this normal?


Don't confuse distillation with discoloration. It does purify your product, but even tiny impurities can give it a strong coloration. Many freshly made, colorless aromatic compounds turn darker when exposed to light, air, etc. Some volatiles already have a color of their own, e.g. the essential oil of cinnamon bark.

Ullmann - 17-10-2008 at 11:20

Good Work!

Best way to purify aniline is distillation in vacuo IMHO....

Benzamide...

smuv - 30-11-2008 at 20:38

Unhappy with the yields from the previous benzamide synth, I investigated different catalysts for the amidation of benzamide in a urea melt. In practice I did a shitty job controlling some variables; therefore, I don’t really know how reliably my results can be compared to one another.

Benzoic acid synthesis
224g Potassium Benzoate
422mL water
142mL 31.45% HCl solution

The Potassium Benzoate was dissolved in warm water and HCl was added. Benzoic acid immediately precipitated out, and the solution was allowed to cool to room temp. The crude benzoic acid was collected via vacuum filtration, using the filtrate to complete the transfer and the filter cake was sucked fairly dry. The crude benzoic acid was dissolved in 3.5L of boiling water (a very little bit steam distilled creating very beautiful crystalline benzoic acid snow!), the vessel was insulated and allowed to slowly cool overnight. The solution was vacuum filtered, using the filtrate to complete the transfer, washed with ca. 250-300mL water and sucked dry. The benzoic acid was dried at 150-200F in an oven for about an hour.

The entire procedure was done 2x in parallel yielding ~300g of benzoic acid.


(300g of recrystallized benzoic acid)

Benzamide synthesis
I tried three different catalysts for the synthesis of benzamide from urea and benzoic acid. I used a phosphoric acid catalyst, a boric acid catalyst, a zinc oxide catalyst and an uncatalyzed control. The uncatalyzed, phosphoric acid catalyzed and boric acid catalyzed processes for formation of amides are known to literature, however I wanted to give the zinc oxide catalyst a try because I thought it might work well for this reaction.

Boric acid catalyzed reaction
90g Benzoic acid
133g Urea
6.9g Boric acid

Phosphoric acid catalyzed reaction
90g Benzoic acid
133g Urea
1.75mL Phosphoric acid

Zinc oxide catalyzed reaction
90g Benzoic acid
133g Urea
11.8g ZnO

Uncatalyzed reaction
30g Benzoic acid
43.7g urea

All reactions were performed in parallel; the 3 catalyzed reactions were run in 500mL Erlenmeyer flasks while the uncatalyzed reaction was run in a 250mL filter flask. The flasks were covered with aluminum foil and heated for 2.5 hours on a sand bath. The sublimate was tapped down from time to time. I tried to maintain the temperature of the melts at 180c, but because I left the reactions more unattended than I should have, I did a poor job at this. Additionally, the temperatures varied a good deal melt to melt, which made things tricky. About 33% through the reaction, the phosphoric acid and zinc oxide catalyzed melts were running at 210c, the uncat. was 205c and the boric acid was 185c. Later I undershot the temperatures, and they hovered around 150c. For the last hour I got the temps a little closer around 190-200c.


(The sand bath...)

After 2.5 hours, the melts were poured into empty Griffin beakers and allowed to cool to just above 100c. To the 3 catalyzed reactions 500mL of water was added and to the uncatalyzed, 150mL of water was added. The solutions were boiled with stirring and a 28% solution of ammonia was added (35mL for the cat, 10.5mL for uncat). Next the solutions were cooled to just below room temp and vac filtered. The filter cakes were crushed up and dried in an oven at about 150F.

To purify the benzamide, the idea was to extract the crude products with boiling xylol, filter out the undissolved junk and allow the benzamide to crystallize out upon cooling. I tried this for the phosphoric acid cat. reaction two times. Both times the benzamide immediately crystallized clogging the filter funnel. I believe to efficiently do this a heated filter funnel would be required and/or a very large amount of xylol would need to be used. I was able to recover most of the product (I think) by allowing the very little xylol that passed through the funnel to cool, and collecting the precipitate by vac filtration. The whole filtration apparatus was washed with warm denat. ethanol to recover most of the benzamide which had clogged it. I took what had precipitated on the filter paper and dissolved this in hot ethanol as well; both alcohol solutions were combined, boiled, allowed to cool to ca. 35c and vac filtered. The ethanol was then slowly evaporated in a gently heated casserole dish. The precipitated benzamide was collected and dried in an oven at 150F. The other reaction products were extracted with ethanol (250mL for the ZnO, 325mL for Boric acid, 150 for uncat), filtered, cooled to ca. 35c and the solvent was evaporated.


(Melt from boric acid catalyzed reaction dissolved in boiling water)


(Water recrystallized, boric acid catalyzed, reaction product)


(After filtering and cooling the warm ethanol extracts benzamide slowly precipitated)


(Product recovered from phosphoric acid cat reaction: precipitate after evaporating ethanol on left, extract from boiling xylol on right.)


Yields
Phosphoric acid cat. 36.8g (precip. from xylol + precip. from EtOH) --> 41% yield
Boric Acid cat. 73.3g --> 82% yield
ZnO cat. 32.8g --> 37% yield
Uncatalyzed 18.1g --> 61% yield


(final pure(ish) products)

I didn’t perform any melting point assays, but visually the products from the ZnO and uncatalyzed reaction looked a fair bit darker than the phosphoric and boric acid catalyzed reactions. The portion of phosphoric acid catalyzed reaction product that precipitated from xylol was not crystalline but was a very clean white powder.

Discussion

Benzoic acid synthesis
I made a mistake with this synthesis, I found out only after the fact that the HCl I was using was 31.45% instead of 34% as I had assumed; therefore instead of using a 10% excess of HCl I only used the stoichiometric amount. I hope this is the reason for the lowish yields for this simple preparation. Of course a percentage was also lost in the recrystallization.

Benzamide synth
The results are all over the place. Throughout the reaction the boric acid catalyzed reaction stayed closest to the 180c target which could explain the higher yields. It is possible that a lot of benzamide was lost in the phosphoric acid catalyzed reaction with the xylol mishaps. I think it is fair to bet that ZnO doesn’t do a good job catalyzing this reaction at the temps used, it is possible that at lower temps it may be more effective. The only concrete conclusion that I can come to, is that boric acid does a pretty good job as a catalyst.

I think I got higher yields with the boric acid catalyzed reaction than in my previous experiment, because I recrystallized the product from boiling water. While this did not really remove all the impurities because I never filtered the solution hot, I think it allowed the benzamide to precipitate out of the solution as distinct crystals rather than stay trapped in the solidified melt. I believe the ethanol extracted product could be made very pure by recrystallization from xylol. Also simply recrystallizing from hot water (in my hands) did not provide a sufficiently pure product, as even the water recrystallized product from the boric acid catalyzed reaction, which dissolved completely in boiling water did not fully dissolve in boiling ethanol.

Conclusion
As a comparison of different catalysts for the synthesis of amides from carboxylic acids, I view this experiment as a failure. On the other hand, for the production of a fair bit of benzamide (albiet less than I had wanted) this series of experiments was successful.

Notes:
I have been using the term catalyst loosely, for the phosphoric acid and boric acid catalyzed reactions, precatalyst would probably be a better term.

The idea for the ZnO catalyst came from research into the synthesis of ethylene carbonate from urea and ethylene glycol; in this reaction ZnO catalyzes the formation of ammonium cyanate. Additionally, I thought ZnO’s weak acid and weak base sites might help stabilize the various transition states required to form the amide.

That’s all…

[Edited on 12-1-2008 by smuv]

Nicodem - 1-12-2008 at 00:55

Regardless of the lossy variable control in your parallel experiments, I think your work does give quite some useful data on this reaction. There is not much about amide formation with urea on this forum and yours are great contributions to this simple method of COOH->CONH2 transformation. Thanks!
If you have time enough it would be nice if you would do a review of your experiments and literature data that you gathered during your work, and post it in the Prepublication section.

Klute - 1-12-2008 at 10:03

Nice work Smuv, thank you for taking time to share this with us!

smuv - 1-12-2008 at 22:07

Thank you both for your appreciation.

@ Nicodem I may one day post something in prebulication about this process, but for now my research of this reaction is not complete. I would be interested to hear of your experience with the boric acid catalyzed reaction (substrates and yields if you still have the data).

Mechanism
The role ammonium cyanate plays in this reaction was not immediately clear to me, here is the mechanism; it is interesting IMO.


Source: Molecules 2006, 11, 318-324

[Edited on 12-2-2008 by smuv]

Taoiseach - 1-12-2008 at 23:22

Awesome work smuv, thanks for sharing!

:cool:

Urea Acidolysis

Alchemist - 22-3-2009 at 10:05

Hello all,

Beside the 3 examples that where given in "Examples of Urea acidolysis" , Formic Acid, Acetic Acid, Benzoic Acid with Urea to make Formamide, Acetamide, and Benzamide, does anyone know of others that work with Urea? If so do you have information you can add to the list?

For example would Oxalic Acid and Urea make Oxamide?

Thanks the Alchemist.....

[Edited on 23-3-2009 by Alchemist]

benzylchloride1 - 22-3-2009 at 19:09

The Hoffman Elimination reaction is the most difficult part of this type of synthesis. Nice work with this synthesis. I have used this reaction to make anthranilic acid from phthalimide. The only problem is that anthranilic acid is difficult to precipitate in high yields du to the fact that it is an amino acid which has a narrow isoelectric point over which it will precipitate. This method should be applicable to phthalic acid diamide for the synthesis of o-phenylenediamine. The use of TCCA is extremely interesting, it keeps the reaction volume low for easy work up. This may be applicable to making 3-aminopyridine from nicotinamide.

smuv - 22-3-2009 at 21:19

@alchemist: if by urea acidolysis you mean the formation of amides by cooking them up in a urea melt, then yes there are many substrates which this application is applicable to. The only thing that would inhibit a carboxylic acid from reacting that I can think of is if the acid had other functional groups that also reacted in the urea melt. I had wanted to try comparative examples between dichloro, trichloro and acetic acid a few months ago, but my synthesis of trichloro and dichloroacetic acid failed...

@benzylchloride1 the reaction volume can likely be kept even lower if the the formation of the formation of the N-chloramide were done in methanol. In methanol this chlorination goes like a shot because the cyanuric acid is insoluble in MeOH. The hoffmann rearrangement in methanol unfortunately gives rise to urethanes. I bet though, addition of the solution of the N-chloramide in MeOH to a NaOH solution would yield the amine. An attempt was made w/ urea --> hydrazine a while ago, but it didn't work out (not really a model substrate). An attempt was planned to try this on a dihydrocinnamide but the formation of the dihydrocinnamic acid did not go as planned. More work on this rxn is planned eventually, although for now, time is scarce.

benzylchloride1 - 23-3-2009 at 20:24

I am currently running the benzamide synthesis. I heated 90g of benzoic acid, 133g urea and 6.9g boric acid in a 500 mL flask. The mixture was heated at 165 c for 2.5 hours. The product was poured into a glass dish and broken up. The product was well mixed with water and filtered. The filtrate was acidified to recover unreacted benzoic acid. Around 25g precipitated out estimated. The crude benzamide is currently covered with methanol and will be heated to boiling, filtered from urea condensation by products and then concentrated with a rotary evaporator. I should have a melting point, and a percentage yeild within 2 days.

smuv - 24-3-2009 at 07:26

Did you dissolve the melt and recrystallize from a dilute boiling ammonia solution? This IS necessary to get the best yields as much product stays trapped inside the melt; methanol cannot dissolve benzamide that is surrounded by biuret.

That being said, I am glad to see someone repeating one of my experiments!

[Edited on 3-24-2009 by smuv]

Ebao-lu - 24-3-2009 at 10:05

Nice, smuv! Boric acid seems to be a versitile catalyst for -CO(X) activation. And how did you get rid of biuret? What is the purpose of using dilute NH3 solution(to remove biuret)? Biuret is also poor soluble in cold water, and moderately soluble in ethanol, so it is possible some biuret is still there(not sure). Try to dissolve the rest products (ZnO, B(OH)3, uncatalysed) in boiling xylene to see if there is some crap

benzylchloride1 - 29-3-2009 at 21:20

I got a very low percentage yield around 27% after recrystallization from methanol. Only a small amount of urea condensation product was obtained after filtering. Upon heating the product with aqueous NaOH, a strong odor of ammonia was apparent, due to the hydrolysis of the amide.I ground the crude fusion product in a morter and pestle before recrystalization. The product melted at 120 degrees Celsius. The product must be contaminated with benzoic acid due to the low melting point. Upon acidifying the aqueous filtrate, a large quantity of unreacted benzoic acid was recovered. The mixture did not get hot enough during the fusion, 165 degrees Celsius. I am currently producing aniline from the benzamide I obtained. I steam distilled the aniline out of the reaction mixture, salted out and extracted the aniline with toluene. The toluene extract is now drying over NaOH. Alot of oily tar was produced in the reaction, lowering the yeild. How could the tar formation be minimized?

smuv - 30-3-2009 at 04:10

I think you should read my experiments and feedback I received from other members as it seems like you are repeating some of my mistakes.

Methanol is a really bad solvent for recrystallization or purification of benzamide as benzamide is very soluble in it as well as some of the condensation products formed from urea. This could explain your poor yields.

If you heat the crude melt in boiling dilute ammonia water, all benzoic acid as well as many other impurities are removed.

The low mp is not due to benzoic acid, it is due to benzonitrile.

This being said, In my hands I got variable results w/ this amidation.

For the purposes of the hofmann rearangement, most impurities but the condensation products of urea will not interfere w/ the reaction; for this reason rigorous purification of the benzamide is IMO unnecessary. For the Hofmann rearrangement, very good cooling, stirring and slow addition of the amide are absolutely paramount! I had previously stated that the addition of the amide does not appear to be exothermic; on large scales it is, and allowing the temp to rise even to 15c markedly reduces yields. This being said, I did get some tar formation every time during this synthesis.

There is 1 modification you may wish to try if you repeat (I had planned to try it). Make a sol of .33-.45 eq of TCCA and add the amide to this slowly w/ stirring and rigorous cooling. If the amide does not go into sol, add 1 eq of NaOH. Once the amide goes into sol, then add the rest of the NaOH (6 eq in total IIRC) slowly with very good cooling. Allow the sol to slowly come to RT after addition, then heat slowly to ~75c.

By this method you are first generating the N-chloroamide w/ less risk of degradation of the chloramide to benzoic acid and ammonia (which I believe is a competing reaction).

p.s. I am glad to see someone try this reaction, and hope that w/ further experimentation you work out some of the problems you have encountered. I also know all to well, it is very easy for someone to find flaws in something you have done after the fact. I hope you are not discouraged and the second time around can improve the yields.

p.p.s. In my hands tar formation did not seem to significantly impact yields. Although I vaguely recall more tar formation in a large scale reaction where I added my amide too quickly and consequently allowed the temp of the solution to rise.


[Edited on 3-30-2009 by smuv]

Amides from Esters

smuv - 9-5-2009 at 20:59

Preface
To further research amidations in molten urea, the synthesis of benzamide from methyl benzoate performed.

Methyl Benzoate
This is straight from vogel...

30g Benzoic acid
100 mL Methanol
~3 mL Sulfuric acid

Refluxed 4.5 hours. Allowed to stand overnight. Separated ester, extracted aqueous phase w/ CH2Cl2. Combined Organics, washed with bicarbonate and water. Dried over CaCl2. Removed solvent via distillation.

Obtained 10.9g of a clear just slightly yellow oil.

Benzamide
10.9g Methyl benzoate
11g Urea
.75g Boric Acid

Mixed everything, heated in oil bath for 2 hours. Oil bath temp was increased from 140c to 170c over course of rxn. At first yellow plates precipitated but with further heating heating a lot of brownish colored trash precipitated. By end 2h only ca. 4mL of molten stuff remained, the rest was solid. The melt was allowed to cool and 125mL of 10% NH3 solution was added. Solution was boiled with stirring for ~10min and allowed to cool in a water bath. About 3mL of oily methyl benzoate remained unreacted. The solution was vac filtered and obtained off-white powder was dried in oven. Yield 2.95g (30%) of a fairly clean product.

Discussion
The yields of the esterification are probably low because the sulfuric acid used was drain cleaner, and likely contained a fair bit of water.

For the amidation, in the future more urea should be used, because a lot of methyl benzoate was left unreacted, and would have had no chance to react if the rxn was extended longer because most of the urea was decomposed after 2h. Also less ammonia solution should be used in work-up as the solubility of benzamide in water is 1g /~75mL. Additionally unreacted methyl benzoate could have dissolved some of the benzamide as well.

Despite these shortcomings, the purpose was to determine if esters react well in this reaction, it appears with some subtle modifications, this process can be applied to esters if so desired. Of course there are other ways of making amides from esters, some are more convenient. However, this is just one more choice for the amateur chemist.

[Edited on 5-10-2009 by smuv]

benzylchloride1 - 11-5-2009 at 18:39

Allowing the ester to stand overnight in the presence of the acid could have contributed to hydrolysis of the ester, lowering the yields. I have conducted the methyl benzoate synthesis several times and always got above a 70% yield after distilling the ester. I used 96% ACS grade H2SO4, I only use this acid for esterifications and other synthesis where water content is an issue. The 92% drain cleaner can be concentrated by distillation if suitable apparatus and a hood is available. The ammonolysis with the formation of the benzamide is best conducted at room temperature. At high temperatures, basic hydrolysis is a competing reaction. Ammonium benzoate will be the predominate product. I have prepared acetamide from ethyl acetate in this manner; the amide is isolated by distillation.

smuv - 11-5-2009 at 19:01

Quote:
Allowing the ester to stand overnight in the presence of the acid could have contributed to hydrolysis of the ester, lowering the yields.


Edit: Actually you are right, for the synthesis of ethyl acetate, the equilibrium constant is 3 at room temp and 4 at 100c so this could have reduced yields.
Quote:
The ammonolysis with the formation of the benzamide is best conducted at room temperature.


Eh you missed the whole point of my post.

The product after the urea melt was not heated with ammonia solution to form benzamide, this was done to remove impurities (namely benzoic acid and biuret) from the crude product. It is really something you should have done in your synthesis, it would have increased the yields of your alcohol extraction by allowing the benzamide to re-crystallize free from biuret and other condensation products and thus accessible to solvation by the alcohol.

[Edited on 5-12-2009 by smuv]

[Edited on 5-12-2009 by smuv]

benzylchloride1 - 11-5-2009 at 19:15

I am sorry that I misread your post. Using urea to form an amide form an ester is a new reaction for me. I have always used ammonia for forming amides from esters. I plan on running this synthesis again using your modifications that produce the highest yields of product. My aniline from my first synthesis would not totally dissolve in concentrated hydrochloric acid. All of my ammonialysis reactions with aqueous ammonia proceded in high yields. I really want to synthesize around 100ml of aniline by this method; I have benzene, but the nitration and reduction require chemicals that are some what costly for me. In a dilute aqueous acidic solution, ester hydrolysis would be the predominate reaction.

smuv - 11-5-2009 at 19:24

Quote:
Using urea to form an amide form an ester is a new reaction for me.


Now you understand why i tried it. :P

Via the urea melt method, you could easily make that quantity of aniline (provided you have a 3L flask for the hoffmann rearrangement). Read my posts above, I gave tips regarding steps to take for larger scale hoffmann rearrangements, namely, COOLING!

Also, I am starting to get the impression, that the size of the flask is important. I ran the above reaction in a 250mL flask (too lazy to clean a 100mL flask) and I think in larger flasks the urea might decompose more quickly without reacting with the ester/carboxylic acid.

benzylchloride1 - 14-5-2009 at 20:53

I conducted a benzamide synthesis several days ago. 90g of benzoic acid, 133g of urea and 6.9g of boric acid were mixed together in a 500mL flask. The flask was heated with a mantle and kept at 180C for 2.5 hours. The product was poured into a glass bowl and transferred to 500mL of water in a 1L beaker. 100mL of 10% ammonia was added and the mixture was heated to boiling. The solution was then filtered from amorphous byproducts and upon cooling, benzamide crystals filled the flask. The product was filtered after allowing the solution to cool over night. The product was washed with water and dried in a 70C oven. 52g of product was obtained, with a melting point of 120C. The product was obtained with a percentage yield of 59%. Another synthesis was carried out today, and is currently cooling and crystalizing. The mixture was kept between 190C and 210C to see the effect on yields. More urea condensation products were noted and the mixture had a definite benzonitrile odor. The fume hood works extremely well, the odor was only apparent when the odor of the mixture was carefully tested. Does anyone know if benzamide could be heated to a high temperature under vacuum to produce benzonitrile and water as the side product? This could be turned into a working procedure for the synthesis of this compound without using hard to obtain reagents such as SOCl2, AC20, P4O10, etc.

Random - 15-1-2011 at 10:19

Quote: Originally posted by Dr. Beaker  
interesting discussion...

I want to make pentafluoro aniline from pentafluoro benzoic acid.
the procedure posted by S.C. Wack looks atractive to me, however I'm afraid the poorly nucleophilic oxygenes of C6F5COOH would hinder any reaction that include protonation of the COOH...
the only way I found 'till now that uses (relatively) simple reagents is this:

C6F5COOH ---> C6F5COCl (using SOCl2)
C6F5COCl ---> C6F5COONH2 (by addition of hydroxyl amine)
C6F5COONH2 ---> C6F5NH2 (-CO2 by heating with K2CO3)


any thoughts anyone?:)


Does that mean that we can make aniline from benzoic acid and hydroxylamine?

smuv - 15-1-2011 at 10:38

Its not as simple as that, see: lossen rearrangement.

UnintentionalChaos - 15-1-2011 at 11:20

Perhaps this has been pointed out before, but consider the following:

Instead of using the urea as a source of ammonia, why not use it as a means to irreversibly consume water sideproduct (forming ammonium carbamate and ammonium carbonate).

Perhaps we could try heating ammonium benzoate in a urea melt. Keeping the temperature as low as possible while still having it molten minimizes formation of biuret, but may still be enough to dehydrate the ammonium benzoate.

Or for that matter, what about molten ammonium sulfamate as dehydrating agent? It's non-acidic and the sideproduct is not organic soluble. Presumably the hydration to diammonium sulfate is rather energetically favorable. An issue with this would be the higher melting point of the sulfate product, however, and an excess to keep the melt liquid might go to the nitrile (which would itself be great, but not what's wanted here)

[Edited on 1-15-11 by UnintentionalChaos]

smuv - 15-1-2011 at 12:31

For a normal transesterification, the use of a dehydrating agent indeed does push reactions to completion. But if you look at the mechanism for the reaction given further up the page, you will notice that water is not produced. In this reaction urea does not simply provide a source of ammonia, instead it serves as a source of isocyante.

Random - 15-1-2011 at 16:33

I figured lossen rearrangement includes messing with isocyanates. Aren't those extremly toxic?

Random - 26-3-2011 at 01:53

I tried today synthesis of benzamide in a test tube. I mixed urea and benzoic acid which filled half of the test tube then I started heating it using a candle. After some time urea melted and I continued to heat it. I started to notice weak fruity/cat shitty smell, but after some time smelling it my heart rate became faster and I did get some strange feeling of not feeling right. This was one outside, I stopped heating it and left it outside now. By the way, I was leading the vapors into vinegar hopefully to neutralize ammonia, but a big amount of vapors escaped from that too, maybe if some isocyanate was made the vapors were also burned with candle forming HCN?

Edit:

I left it outside and it stopped smelling bad, now I have some crystalline mass with reduced volume, I am not even sure if it's benzamide or ammonium benzoate or maybe even urea? The mass hardened from liquid phase as I see because it had floating some more benzoic acid on it. Benzoic acid volume greatly decreased and I think almost nothing sublimated (there is just some little sublimated dust on the test tube walls).

Now, I want to see if I had success with that so I will attempt hoffman degradation using bleach. Do I need to use sodium hydroxide currently? I don't have it, but maybe Na2CO3 could work too?

I also have some calcium hydroxide too, but the synthesis of NaOH from Na2CO3 and NaOH wasn't success this time.
[Edited on 26-3-2011 by Random]

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