Sciencemadness Discussion Board

Phenyl cyanide or Benzonitrile synthesis

DeAdFX - 10-12-2006 at 22:17

http://www.freepatentsonline.com/4605521.html

Is their any way of synthesizing phenyl cyanide(PhCN) in a more benign way. I like a majority of others do not posses Phosphorus chloride, oxalyl chloride, thionyl chloride and so or the "right" solvent to do the reaction in (Dimethyl formamide).

I was thinking of using Acetic Anhydride(dehydration agent) and DMSO(solvent) instead. Would this subsitution work or would I be wasting chemicals.

garage chemist - 11-12-2006 at 02:20

I have done several experiments to the dehydration of benzamide to benzonitrile. Acetic anhydride works, even without solvent.
However, the PhCONH2 must be refluxed with an excess of AA for at least 6 hours (preferably longer). The reaction is slow, and even after 3 hours of reflux unreacted benzamide is present (though the presence of benzonitrile is evident already after 5 minutes of reflux, as the smell shows).
The benzamide can be isolated by fractional distillation of the reaction mix, or by hydrolyzing the reaction mix by pouring into water and extracting the benzonitrile with e.g. chloroform.
The extracted benzonitrile must be distilled to free it from benzamide.

Thionyl chloride (again without solvent) is much faster in its reaction with benzamide, producing a useable yield of benzonitrile after 30 minutes of reflux.
The standard and generally applicable method (for both aliphatic and aromatic amides) is to use phosphorus pentoxide.

Organikum - 11-12-2006 at 03:49

The degradation of phenylalanine with TCCA worked for me, but I cannot say in what yields as I dropped the flask in the workup.

DeAdFX - 11-12-2006 at 10:16

Quote:
Originally posted by garage chemist
I have done several experiments to the dehydration of benzamide to benzonitrile. Acetic anhydride works, even without solvent.
However, the PhCONH2 must be refluxed with an excess of AA for at least 6 hours (preferably longer). The reaction is slow, and even after 3 hours of reflux unreacted benzamide is present (though the presence of benzonitrile is evident already after 5 minutes of reflux, as the smell shows).
The benzamide can be isolated by fractional distillation of the reaction mix, or by hydrolyzing the reaction mix by pouring into water and extracting the benzonitrile with e.g. chloroform.
The extracted benzonitrile must be distilled to free it from benzamide.

Thionyl chloride (again without solvent) is much faster in its reaction with benzamide, producing a useable yield of benzonitrile after 30 minutes of reflux.
The standard and generally applicable method (for both aliphatic and aromatic amides) is to use phosphorus pentoxide.


hmm... 6 hours is a long time. Would it be worth my time to see if a solvent could reduce the time from 6 hours + to something reasonable like an hour? I could try using DMSO, Methylene chloride, xylene, acetone and whatever else i might have laying around.

The patent did mention the usage of Quat ammonium cations as a catalyst to speed up the reaction. However my only source of Quat ammonium cations are from household products(<1% concentration + other shit)[/end rambling...].

edit: crap... Forgot to ask... How long does it take to form Phenyl cyanide from P2O5 and what solvent should be used?

@ Organikum... If I am unable to locate an otc TCCA source could I use Ca(ClO)2 instead? Both chemicals are used as a chlorinating agent in pools.

[Edited on 11-12-2006 by DeAdFX]

[Edited on 11-12-2006 by DeAdFX]

garage chemist - 11-12-2006 at 10:43

In Vogel there's a synthesis of phthalonitrile from phthalamide, which will of course also work for benzonitrile from benzamide. It calls for 6 hours reflux with AA. If you have AA, this is the best method you can use. Adding solvents like DMSO could maybe accelerate the reaction, but it will make workup endlessly more complicated and tedious which means that you will spend more time with the synthesis than if you use AA without solvent.
Why do the 6 hours reaction time even bother you? You can just leave it refluxing unattended. I have to do that too when removing denautrants from ethanol (12 hours reflux with NaOH).

DeAdFX - 11-12-2006 at 10:51

I am a little paranoid as to what the neighbors think(I can only do chemistry outside unless it is benign). BTW I do not posses this vogel book. Is it in the reference section

[Edited on 11-12-2006 by DeAdFX]

garage chemist - 11-12-2006 at 11:03

Yes its in the library, its the one from Arthur Vogel "Practical Organic Chemistry". It's a very good book.

You can do that reaction inside, as no dangerous fumes are evolved as long as you wait for the reaction to cool down before you take off the reflux condenser.

Nicodem - 11-12-2006 at 14:36

Quote:
Originally posted by Organikum
The degradation of phenylalanine with TCCA worked for me, but I cannot say in what yields as I dropped the flask in the workup.


Actually he is asking about the synthesis of phenyl cyanide (PhCN) and not benzyl cyanide (Ph-CH2-CN) as your reply imply.

garage chemist - 11-12-2006 at 15:06

With P2O5, again no solvent is used. The dry substances are mixed together by shaking in a flask and carefully heated. The benzonitrile can be distilled off in vacuum after the reaction.
This is also outlined in Vogel.

S.C. Wack - 11-12-2006 at 16:07

Excerpt from Ber. 17, 1766 (1884):

Beim Erhitzen von Benzoesäure mit Rhodanblei entwickelt sich ausser dem Benzonitril noch Kohlensäure und Schwefelwasserstoff, während Bleisulfid als Rückstand verbleibt. Hiernach findet diese Reaktion in folgender Weise statt:

2 C6H5COOH + Pb(CNS)2 = 2 C6H5CN + PbS + H2S + 2 CO2.

Benzonitril wurde auf diese Weise zu wiederholten Malon dargestellt and hierbei wegen der leichten Zersetzlichkeit des Rhodanbleies in der Wärme immer etwas mehr als die berechnete Menge desselben in Anwendung gebracht. Die Benzoesäure, wie das Rhodanblei wurden in trockenem Zustande in einer Retorte gemischt und in derselben am Rückflusskühler erwärmt. Mit dem Schmelzen der Benzoesäure beginnt schon die Reaktion; dieselbe wird nach Steigerung der Temperatur auf circa 190° ziemlich lebhaft. Das Erwärmen der Flüssigkeit, welche das Bleisulfid suspendirt enthält, wird hierauf so lange fortgesetzt, bis die Entwickelung von Kohlensäure und Schwefelwasserstoff schwach geworden ist, und dann das gebildete Benzonitril abdestillirt. Das Destillat wird mit verdünnter Natronlauge und Aether geschüttelt, um das Nitrit von mit übergegangener Benzoesäure zu trennen und das Benzonitril fraktionirt. Siedepunkt 191°. Dasselbe wurde in Thiobenzamid übergeführt und für Letzteres der richtige Schmelzpunkt erhalten.

Nach obiger Methode können aus 100 g Benzoesäure im Durchschnitt 50—55 g Benzonitril erhalten werden, so lieferten in einem ungünstigen Fall 30 g Benzoesäure 15 g Benzonitril, in einem günstigeren Fall 70 g der Säure 39 g Nitril.

garage chemist - 11-12-2006 at 16:11

That's the method with lead thiocyanate, which is already available in English in Rhodium's Ketamine synthesis.
I would consider this to be too stinky and maybe expensive with the necessary thiocyanate. But definately interesting nonetheless.

Sandmeyer - 11-12-2006 at 16:39

Speaking about Ketamine and lead, while being bored and browsing orgsyn I found this: http://www.orgsyn.org/orgsyn/prep.asp?prep=cv7p0229

Note that step one gives much better yield on smaller scale...

:P

More interesting perheps would be to do step 1 on p-dimethoxybenzene (or benzodioxole) and use ethyl acetoacetate in place of 2-carbethoxycyclohexanone...

[Edited on 12-12-2006 by Sandmeyer]

Sandmeyer - 11-12-2006 at 20:37

To stay on topic -- aside from what's been allready mentioned there are number of other reliable ways.

Sandmeyer method via aniline:

http://www.orgsyn.org/orgsyn/prep.asp?prep=cv1p0514

Ullmann method via arylhalide (DMF/NMP/DMA can be used as solvent too):

http://www.orgsyn.org/orgsyn/prep.asp?prep=cv3p0631

From benzaldehyde, via oxime:

http://www.orgsyn.org/orgsyn/prep.asp?prep=cv2p0622

Unrelated stuff of interest:

http://www.orgsyn.org/orgsyn/prep.asp?prep=cv6p0631
http://www.orgsyn.org/orgsyn/prep.asp?prep=cv3p0626

benzylchloride1 - 14-5-2009 at 21:03

A definite presence of benzonitrile can be detected in the synthesis of benzamide from benzoic acid and urea; the melting point of the product is significantly lower due to its presence. Could benzonitrile be produced in modest yields by running this reaction at very high temperatures in a vacuum distillation setup after ammonium carbonate stops subliming out of the reaction mixture? This sounds like an interesting project. Another idea: reflux benzamide with a very high boiling solvent, >Bp 250, distilling a mixture of water, solvent and benzonitrile. After drying, benzonitrile could be isolated via fractional distillation.

Jimmymajesty - 24-3-2015 at 14:47

Hi folks,

How about using ketene directly on benzamide? I might give it a try in the coming weeks. I have a good feeling about this since ketene dehydrates stuff like crazy, it even chars PVC tubes on contact.

Or... how about mixing 4 parts graphite with 1part benzamide put into the microwave for couple of mins then extract the benzonitrile?

Jimmymajesty - 3-4-2015 at 11:42

Hi again,

I gave some thought to it, so how about... dehydrating ethyl benzoate in the presence of NH3 with alumina @ 500°C.

ArCOOEt+NH3=>H2O+Ethylene+ArCN

The yield is stated to be around 40%, I always confused when they say such things, I mean yield per pass or on ethyl benzoate or on NH3?

Anyways I will surely try this out since I never used alumina before.
But sadly my knowledge ends here does anybody happen to know how to isolate the Ar-CN from the mixture?
Many thanks in advance!

Dr.Bob - 3-4-2015 at 20:06

Good luck on keeping the NH3 around for long at 500C. At 500C, the Sm and product would be a gas, which would likely mean that they would have to be passed through a column in an inert carrier gas, and then condensed once out of the column. This sounds more practical for industrial than lab use.

Maybe try ArBr and Cu(CN) with a catalyst.

http://www.chem.ccu.edu.tw/~joyce/referance/ericyang/Coord.%...

I.P. Beletskaya, A.V. Cheprakov / Coordination Chemistry Reviews 248 (2004) 2337–2364
2353
Halide exchange can be performed also with alkenyl bo-
mides, as e.g. in (Eq. (55))
8. C
C bonds
8.1. Cyanation
The exchange of halogen for cyano group by copper(I)
cyanide, the Rosenmund–von Braun reaction, is a classical
method of organic synthesis. The reaction is performed by
prolonged heating with a stoichiometric amount or excess of
CuCN in polar solvents at high temperatures. Though this
is a reliable method with a long and impressive history of
successful application in organic synthesis, similarly to other
Ullmann type processes, a milder protocol is desirable. The
first such method has recently appeared for cyanation of aryl
and heteroaryl bromides. The reaction involves exchange of
bromine by iodine. As other ligand assisted methods, this re-
action shows a high degree of tolerance to functional groups.
However, the reaction is air and moisture sensitive, and re-
quires a huge amount of rather expensive ligand (Eq.
(56)
)
[160]
.
ArBr
NaCN
,
CuI (10 mol%)
,
KI (20 mol%)
,
10DMEDA
−
−−−−−−−−−−−−−−−−−−−−−−−−
→
PhMe
,
110
◦
C
ArCN (56)

[Edited on 4-4-2015 by Dr.Bob]

Jimmymajesty - 3-4-2015 at 23:31

Thanks for the input but these chems are not OTC for me.
Its not the high temp I am worried about I know I can reach it, rather the solid benzamide forming under these circumstances that can make the reaction troublesome
I tried this with ethyl acetate and the whole setup clogged because of solid acetamide.

For the separation, maybe some OTC azeotrope forming material would help, like water. I know that methyl bezoate forms azeotrope, so ethyl benzoate why should not? I do not know anything about Ar-CN though...