Sciencemadness Discussion Board

p-hydroxybenzonitrile synthesis

Resonance frequency - 24-10-2011 at 00:34

Hello everybody,

I m trying to synthesize p-hydroxybenzonitrile using following route-->p-hydroxybenzoic acid--> Methyl paraben -->p-hydroxybenzamide-->p-cyanophenol. I have succesfully synthesized o-hydroxybenzonitrile using the same route but the process doesn't works for p- cyanophenol.The reaction proceeds after purging ammonia to methyl paraben but the formed amide gets converted to paraben after some time. Dont suggest me Oxime route & Urea route;coz i have used those succesfully :P
Just wanna know whats exactly wrong when p-hydroxybenzoic acid is used instead of salicylic acid for methyl paraben route :(...Any Idea Guys??

fledarmus - 24-10-2011 at 03:58

I'm not sure exactly what you're saying - does the methyl paraben form the amide but the reaction spontaneously reverses to reform the ester when you remove the ammonia atmosphere? In that case, how are you detecting product formation? If you are actually forming the amide, and you suspect that the methanol which is formed is driving the reaction back to the ester when you purge the ammonia, you might be able to add 4A or 5A molecular sieves to remove the MeOH as it is formed.

Or is the reaction just giving you none of your expected amide product? If that is the case, what are your conditions for going from the ester to the amide? My guess would be that either you are forming an ammonium phenoxide salt which in the ortho case positions the ammonium right next to your ester for the addition reaction, but in the para case keeps it on the opposite side of the ring; or that hydrogen bonding between the ortho hydroxy and the ester stabilize the ammonia addition while the para hydroxy is unable to do that.

In the first case, it is possible that increasing the concentration of your methyl paraben would allow intermolecular reaction, where you don't need such high concentrations in the ortho case because it is an intramolecular reaction. In the second case, you may have to prepare a more active ester to get the ammonia to react.

Resonance frequency - 4-11-2011 at 22:43

Thanks a lot friend!!

I think you are ryt , i was trying to monitor formation of amide by TLC where presence of spot other than methyl paraben was assumed to be amide coz i wasnt having external standard for amide. I was quite prejudice about the reaction mechanism coz i was trying to attack lone pair of Nitrogen from ammonia gas on carbonyl carbon from methyl paraben to form a gem diol which on dehydration supposed to give amide. But formation of ammonium phenoxide seems to be a promising explanation to describe abnormal behaviour of the methayl paraben route. Thanks once again.:)

hemrajpatil - 27-11-2014 at 22:37

I want to make 4 hydroxy benzonitrile by using para hydroxy benzoic acid ,urea and sulphamic acid any idea about this route?

forgottenpassword - 28-11-2014 at 22:07

Quote: Originally posted by hemrajpatil  
I want to make 4 hydroxy benzonitrile by using para hydroxy benzoic acid ,urea and sulphamic acid any idea about this route?
What do you mean? Do you need the experimental procedure? I recall seeing something similar. It seems reasonable enough to try it, at least.

Procedure for manufacturing of para cyano phenol by using Para hydroxy benzoic acid as a raw material

hemrajpatil - 5-12-2014 at 20:46

Hi Everybody,

I want to make 4 hydroxy benzonitrile by using para hydroxy benzoic acid ,urea and sulphamic acid any idea about this route?

Tell us laboratory experimental procedure

forgottenpassword - 5-12-2014 at 23:47

You're the one who keeps mentioning this procedure. You must know SOMETHING about it. What sources do you have already? I wouldn't want to replicate what you already have! It would waste both of our time. If you could list the papers that you have, I shall look to see if there are any others that discuss the same reaction. You posted your first question over a week ago. You could have tried the reaction and TOLD US whether it works, by now.

CuReUS - 8-12-2014 at 02:48

what about this route

nitrobenzene to Phenyl hydroxyl amine using Zn/aq NH4Cl

http://www.orgsyn.org/demo.aspx?prep=cv1p0445

rearragement of Phenyl hydroxyl amine to para amino phenol by bamberger rearrangement

http://en.wikipedia.org/wiki/Bamberger_rearrangement

treat para amino phenol with NaNO2 +HCl, followed by CuCN to get para hydroxy benzonitrile

Nicodem - 8-12-2014 at 08:13

Quote: Originally posted by CuReUS  
treat para amino phenol with NaNO2 +HCl, followed by CuCN to get para hydroxy benzonitrile

And where do you have the reference to this unusual transformation?

Metacelsus - 8-12-2014 at 08:56

Nicodem, isn't that just a Sandmeyer reaction with cyanide as the nucleophile? Why is it "unusual"?

Anyway, here's a reference: http://www.orgsyn.org/demo.aspx?prep=cv1p0514

Nicodem - 8-12-2014 at 09:17

Quote: Originally posted by Cheddite Cheese  
Nicodem, isn't that just a Sandmeyer reaction with cyanide as the nucleophile? Why is it "unusual"?

Anyway, here's a reference: http://www.orgsyn.org/demo.aspx?prep=cv1p0514

Because the nitrosation of p-hydroxyaniline gives the quinone diazide product. But never mind, meanwhile I actually checked the literature and the quinone diazide formation is reversible so that p- and o-hydroxyanilines can be used in the Sandmeyer reactions.

CuReUS - 9-12-2014 at 02:13

instead of using CuCN ,one can also use copper powder in the presence of excess aqueous KCN

see page 89 https://books.google.co.in/books?id=35xwBwjhe2MC&pg=PA87...

acoording to the orsyn page, nickel cyanide ( NiCN2 ) gives better yield than CuCN

also in the mechanism for sandmeyer reaction ,Cu first acts as reducing and then as oxidizing agent

so instead of CuCN ,can I2 and excess KCN be used

although the active species for the formation of the nitrile is K3Cu(CN)4 :(

since para amino phenol oxidizes rapidly to benzoquinone imine
http://pubs.rsc.org/en/Content/ArticleLanding/1979/P2/P29790...

the diazotization reaction has to be done very quickly,and in the presence of highly acidic conditions,to minimize the oxidation of para amino phenol
also in the wiki sandmeyer page
http://en.wikipedia.org/wiki/Sandmeyer_reaction#Variations

there is a reaction involving an alkyl nitrite with an aromatic amine in the presence of a halogenated solvent ,which reaction is that ?

Nicodem -really clever of you to think about that possibility,i envy your knowledge and your brain ;)

could you please tell more about the quinone dizide reversal ?
how would the quinone structure look for o-hydroxy aniline?

also ,would the diazotization reaction take place faster or give better yields as there is an electron donating OH group para to the NH2 in the ring ?

it would be really helpful if you could post a link to the literature you referred :) (about the quinone diazide)


[Edited on 10-12-2014 by CuReUS]

CuReUS - 7-1-2015 at 01:10

Quote: Originally posted by CuReUS  

nitrobenzene to Phenyl hydroxyl amine using Zn/aq NH4Cl

rearragement of Phenyl hydroxyl amine to para amino phenol by bamberger rearrangement

no need to make the phenyl hydroxylamine from nitrobenzene :)

nitrobenzene can directly be converted to para aminophenol
http://www.sciencemadness.org/talk/viewthread.php?tid=27849#...

[Edited on 7-1-2015 by CuReUS]

Yugen - 8-1-2015 at 11:46

Quote: Originally posted by hemrajpatil  
Hi Everybody,

I want to make 4 hydroxy benzonitrile by using para hydroxy benzoic acid ,urea and sulphamic acid any idea about this route?

Tell us laboratory experimental procedure


Likely the simplest way to do this reaction is through electrosynthesis. First reduce the acid at a lead cathode. Next reflux Benzyl alcohol with HCl and Zinc chloride to get its Benzoyl chloride. Nucleophilic substitution with a large excess of ammonia in a basic ethanol solution will get you the 4-hydroxybenzylamine (if you don't use enough ammonia you will get secondary and tertiary amines, bad for this synth). Finally oxidize the benzylamine at a nickel hydroxide anode to get your product. I haven't tried this, but it seems straight forward enough. Here's the reference for that nickel oxidation.

Attachment: Oxidation of primary amines to nitriles at the nickel hydroxide electrode.pdf (108kB)
This file has been downloaded 549 times

Loptr - 9-1-2015 at 14:07

Quote: Originally posted by Yugen  
Quote: Originally posted by hemrajpatil  
Hi Everybody,

I want to make 4 hydroxy benzonitrile by using para hydroxy benzoic acid ,urea and sulphamic acid any idea about this route?

Tell us laboratory experimental procedure


Likely the simplest way to do this reaction is through electrosynthesis. First reduce the acid at a lead cathode. Next reflux Benzyl alcohol with HCl and Zinc chloride to get its Benzoyl chloride. Nucleophilic substitution with a large excess of ammonia in a basic ethanol solution will get you the 4-hydroxybenzylamine (if you don't use enough ammonia you will get secondary and tertiary amines, bad for this synth). Finally oxidize the benzylamine at a nickel hydroxide anode to get your product. I haven't tried this, but it seems straight forward enough. Here's the reference for that nickel oxidation.



Where do you get nickel hydroxide electrodes?

Nickel hydroxide electrodes

Yugen - 9-1-2015 at 16:52

You get nickel hydroxide electrodes from a nickel nitrate solution, a plain nickel electrode anode, and an inert cathode of some other material type. Probably a graphite cathode would work. Running a current through the solution will reduce the nickel nitrate to nickel hydroxide and nitric acid. As this happens the nickel hydroxide will cover the graphite cathode in a thin film of NiOH, forming the desired electrode for the nitrile synthesis.

Also the reaction likely benefits from the nitric acid entering the solution because the acid will react with the nickel anode to generate more nickel nitrate. Since electrosynthesis works on the surface of the electrode you don't need a thick layer on the graphite. You will have to experiment to see how much NiOH you will need to deposit, but it is safe to say that you won't need a thick NiOH cake for the reaction to work.

Source:

From the Handbook of Inorganic Chemicals by Pradyot Patnaik (page 618)
Quote:

Nickel hydroxide in high purity is prepared by an electrolytic process using metallic nickel as the anode and nickel nitrate solution as the electrolyte. Nickel hydroxide is electrodeposited at an inert cathode.

Nickel nitrate may be prepared by several methods based on the reaction of dilute nitric acid on nickel powder, nickel oxide or nickel carbonate. The reaction is exothermic and requires controlled cooling during production.


Enjoy :)

CuReUS - 9-1-2015 at 23:11

Quote: Originally posted by Yugen  

Next reflux Benzyl alcohol with HCl and Zinc chloride to get its Benzoyl chloride

don't you mean benzyl chloride ? are you sure ZnCl2 will be necessary? since the benzylic carbocation is stabilized by resonance,the substitution should take place easily.
Quote:
Nucleophilic substitution with a large excess of ammonia in a basic ethanol solution will get you the 4-hydroxybenzylamine(if you don't use enough ammonia you will get secondary and tertiary amines, bad for this synth)

you could also do the delepine reaction to get only primary amine :)
http://en.wikipedia.org/wiki/Del%C3%A9pine_reaction

for making p-hydroxybenzonitrile from p-hydroxybenzoic acid
you could either convert the COOH to COCl ,treat it with NH3 and then dehydrate the amide using P2O5 to get nitrile

or you could esterify the COOH,treat it with DIBAL to get CHO and then react it with HN3 to get the p-hydroxybenzonitrile
http://en.wikipedia.org/wiki/Diisobutylaluminium_hydride#Use...

http://en.wikipedia.org/wiki/Schmidt_reaction

[Edited on 10-1-2015 by CuReUS]

Yugen - 10-1-2015 at 00:46

Quote: Originally posted by CuReUS  
Quote: Originally posted by Yugen  

Next reflux Benzyl alcohol with HCl and Zinc chloride to get its Benzoyl chloride

don't you mean benzyl chloride ? are you sure ZnCl2 will be necessary? since the benzylic carbocation is stabilized by resonance,the substitution should take place easily.
Quote:
Nucleophilic substitution with a large excess of ammonia in a basic ethanol solution will get you the 4-hydroxybenzylamine(if you don't use enough ammonia you will get secondary and tertiary amines, bad for this synth)

you could also do the delepine reaction to get only primary amine :)
http://en.wikipedia.org/wiki/Del%C3%A9pine_reaction

for making p-hydroxybenzonitrile from p-hydroxybenzoic acid
you could either convert the COOH to COCl ,treat it with NH3 and then dehydrate the amide using P2O5 to get nitrile

or you could esterify the COOH,treat it with DIBAL to get CHO and then react it with HN3 to get the p-hydroxybenzonitrile
http://en.wikipedia.org/wiki/Diisobutylaluminium_hydride#Use...

http://en.wikipedia.org/wiki/Schmidt_reaction


Ah you are right, Benzoyl chloride should be corrected to be Benzyl chloride... damned old school names, I always add a vowel that shouldn't be in there :) IPAC names are better but nobody uses them for some reason...

Anyways, benzyl chloride probably can be made easily from benzyl alcohol without Zinc chloride, but why not strive for higher yields? Even textbooks recommend more vigorous conditions in their protocols for benzyl chloride prep. For instance Vogel's 5th edition calls for the powerful chlorination agent SO2Cl2... even when they go to that extreme they only get a 79% yield. If adding a little zinc dust to the reflux boosts one's yield even a couple percentage points it still seems like a win to me. It's not exactly like zinc is rare or anything, scratch a U.S. penny and you'll see what I mean.

And yes, you could get your desired product through a number of ways (which is why O-chem interests me). For instance the Wikipedia page for toluene describes an easier way to benzyl chloride than using electrosynthesis from benzoic acid. I just find electrosynthesis to be interesting so it jumps to mind first.

As for the amine reaction, I agree, amine alkylation is a terrible idea. I admit that totally. It just doesn't take a whole lot of forethought to do things that way. That is you can walk into most home labs and do an experiment without calling on Sigma Aldrich and the like. Buying hexamethylenetetramine for a Delépine reaction or buying phthalimide for a Gabriel synthesis is just too much work in a totally different way (the problem of stocking a lab). Plus buying reagents which have no other use than to form amines is bound to attract unwanted attention from NSA and DEA authority types. Even if you aren't doing anything bad, nobody enjoys that kind of harassment and invasion of privacy.

Loptr - 12-1-2015 at 12:18

Quote: Originally posted by Yugen  
You get nickel hydroxide electrodes from a nickel nitrate solution, a plain nickel electrode anode, and an inert cathode of some other material type. Probably a graphite cathode would work. Running a current through the solution will reduce the nickel nitrate to nickel hydroxide and nitric acid. As this happens the nickel hydroxide will cover the graphite cathode in a thin film of NiOH, forming the desired electrode for the nitrile synthesis.

Also the reaction likely benefits from the nitric acid entering the solution because the acid will react with the nickel anode to generate more nickel nitrate. Since electrosynthesis works on the surface of the electrode you don't need a thick layer on the graphite. You will have to experiment to see how much NiOH you will need to deposit, but it is safe to say that you won't need a thick NiOH cake for the reaction to work.

Source:

From the Handbook of Inorganic Chemicals by Pradyot Patnaik (page 618)

Quote:

Nickel hydroxide in high purity is prepared by an electrolytic process using metallic nickel as the anode and nickel nitrate solution as the electrolyte. Nickel hydroxide is electrodeposited at an inert cathode.

Nickel nitrate may be prepared by several methods based on the reaction of dilute nitric acid on nickel powder, nickel oxide or nickel carbonate. The reaction is exothermic and requires controlled cooling during production.


Enjoy :)


Interesting. I never really got into electrochemistry in college, and didn't use my head before asking that question!

Electroplating, of course!

AvBaeyer - 12-1-2015 at 20:02

I wish to comment on Yugen's statements about the preparation of benzyl chloride from benzyl alcohol. There is no need for zinc chloride or any exotic chlorinating agents or reaction conditions. Benzyl alcohol reacts cleanly with concentrated hydrochloric acid (12M) to give the chloride in very good yields after distillation [Ref: JF Norris, American Chemical Journal 1907, v38, 647-642]. I have run this reaction several times on several different scales. An example preparation I have done follows (do with with gloves and good ventilation!):

60 ml of 12M hydrochloric acid is added to 20.0 g benzyl alcohol whereupon one obtains a clear solution. The reaction mixture is slowly heated to 60C (oil bath) during which it becomes cloudy and an oil begins to separate. After about 20 minutes at 60C the reaction, which is now biphasic, is removed from the heating bath and cooled to ambient. The mixture is transferred to a separatory funnel (use caution) and the upper layer (benzyl chloride) isolated. The aqueous layer is extracted 1x25 ml hexanes and the extract is conbined with the crude benzyl chloride. The combined organic layers are washed 2x25ml water, 1x25ml 5% sodium bicarbonate and 2x25 ml brine then dried over calcium chloride. Removal of the hexanes by distillation affords 21.7 g (92%) of a colorless product. Distillation affords 19.4 g (83%, bp 51-52 C @ 5 mm) pure benzyl chloride. A small pot residue remains.

Note: This reaction also works with hardware store muriatic acid (ca 10M) but is not so clean as the benzyl alcohol is not completely soluble. However, addition of 1 ml 12M HCL for each 10ml of 10M HCl gives a reasonable result similar to the above procedure. It just takes a bit longer.

Although I have not yet tried, I assume that the used 12M HCl could be recycled after "fortifcation" with a small amount of fresh 12M HCl.

Hope this is of interest,

AvB

CuReUS - 13-1-2015 at 03:39

Quote: Originally posted by Yugen  
Buying hexamethylenetetramine for a Delépine reaction or buying phthalimide for a Gabriel synthesis is just too much work in a totally different way

I am sure our energetic forum friends will agree that making Hexamine is easier than making instant coffee ;)

https://www.youtube.com/watch?v=d2N0zAoVYew

IIRC,chemosynthesis was talking about an OTC source for phthalimide,

http://www.sciencemadness.org/talk/viewthread.php?tid=45844#...

but personally I don't prefer the gabriel synthesis because hydrolysing the intermediate can be quite difficult :(
Quote:
Even textbooks recommend more vigorous conditions in their protocols for benzyl chloride prep. For instance Vogel's 5th edition calls for the powerful chlorination agent SO2Cl2... even when they go to that extreme they only get a 79% yield.

is it SO2Cl2 or SOCl2 ?
Quote:
For instance the Wikipedia page for toluene describes an easier way to benzyl chloride than using electrosynthesis from benzoic acid.

if you are talking about using HCl/H2O2 for making benzyl chloride,I dont think that will work.
http://chemwiki.ucdavis.edu/Organic_Chemistry/Hydrocarbons/A...

using TCCA or passing Cl2 in boiling toluene is the answer
Quote:
Anyways, benzyl chloride probably can be made easily from benzyl alcohol without Zinc chloride, but why not strive for higher yields? .... If adding a little zinc dust to the reflux boosts one's yield even a couple percentage points it still seems like a win to me...

in chemistry,less is more :D

[Edited on 14-1-2015 by CuReUS]

CuReUS - 19-1-2015 at 02:05

Quote: Originally posted by hemrajpatil  
I want to make 4 hydroxy benzonitrile by using para hydroxy benzoic acid ,urea and sulphamic acid any idea about this route?

This thread might help you
http://www.sciencemadness.org/talk/viewthread.php?tid=38017

riyaaz98 - 31-5-2016 at 11:41

i need some more information on
treat para amino phenol with NaNO2 +HCl, followed by CuCN to get para hydroxy benzonitrile


any articles of patents??

thanks for the help !!

DraconicAcid - 31-5-2016 at 12:05

Hmmm....This seems like an accessible way to convert an acid into an aldehyde without expensive borohydrides or LiH4.