Chemical Forums
Chemistry Forums for Students => Organic Chemistry Forum => Topic started by: mark-sev on March 05, 2009, 04:43:11 PM
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Sorry for asking this question, but i am just at the start of my organic chem course so i cannot answer myself this question, so i ask you how to synthetise 4-hydroxyacetanilide starting from acetanilide?
Thank you for the answers!
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You first need to show an attempt.
Start with the first thing, what ways have you learned of to put an -OH on a benzene ring?
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I thought there was only the industry method of hydroxylating arenes - conditions too harsh to really use in a lab.
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Nope, there is another way. I'll give mark-sev some time to figure it out before I say it.
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Ok just a hint...
If you were to nitrate acetanilide then seperate the o,p isomers what FGI's could you do to make your title compound?
This is basic in the extreme but will give you a synthetic solution that can easily be undertaken in a lab.
any thoughts?
R.
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Ok just a hint...
what FGI's could you do to make your title compound?
Can you tell us what that means?
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Ok just a hint...
what FGI's could you do to make your title compound?
Can you tell us what that means?
Functional Group Interconversion(s) - see e.g. http://preview.tinyurl.com/anrhmv
S
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Well actually we haven't learnt anything yet about that....before we were learning about Sn1 and Sn2 reactions and eliminations and now we started electrophilic aromatic substitutions, but i guess this could not be the case since -OH is a nucleophile...i would have to look at some books maybe but i don't know if i will find it:D...i guess it's some oxidation or what, but i doubt that would be a very selective way...i'm really at the start of the curriculum...
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Have you learned about the sandmeyer reaction, or maybe the term "diazonium" is familiar? I'm pretty sure russellm and I are thinking about the same thing.
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Nope, i haven't learned about that reaction yet, although i have heard somewhere that from this diazonium salts one can create alcohol group, so i see first one would need an amine group on place 4 on the benzene, so first i would have to make a 4-chloro derivate of acetanilide ( reaction with Cl2 in presence of FeCl3, or is there another way?), and then nucleophilic substitution with NH3, following sandmeyer reaction to diazonium salt and afterwards to alcohol (would this be feasible). Or not, since i found this reaction which involves some to me exotic catalysts: Buchwald-Hartwig reaction (link: http://en.wikipedia.org/wiki/Buchwald-Hartwig_reaction ).
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Yes, that would be feasible (from a quick glance). Easier to do would be to nitrate acetanilide, and then convert the NO2 group into NH2 and create the diazonium. But that is what both russellm and I were getting at I believe.
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Why do you all go from DiAzonium route??? Halo-Benzenes can be easily converted to their -OH counterparts via a base and a Cu catalyst that's all :) !!!
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Don't you get a mixture of products and require harsh conditions by that route?
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Don't you get a mixture of products and require harsh conditions by that route?
No I dont think so. AFAIK An Iodobenzene can be formed by the route of KI3 (prepared instiu by reacting KI + I2) forming p and o but mainly p which thereupon be converted to -OH by reacting with KOH and a Cu salt or Cu alone. Forming primaily p which can be seperated by steam distillation.
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Replacing I- with OH- sounds to me like nucleophilic substitution?? Why is the name of the reaction you are proposing...Shouldn't electrophiles attack the electron-rich aromatic compounds...cause the carbocation made from benzene is highly unstable...correct me if i'm thinking wrong please.
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Replacing I- with OH- sounds to me like nucleophilic substitution?? Why is the name of the reaction you are proposing...Shouldn't electrophiles attack the electron-rich aromatic compounds...cause the carbocation made from benzene is highly unstable...correct me if i'm thinking wrong please.
You're right...aryl halides generally don't undergo nucleophilic substitution by Sn1 or Sn2 mechanisms. The copper is critical. See here if you're interested:
http://www.organic-chemistry.org/namedreactions/ullmann-reaction.shtm
I'd put money on hydrolysis of the diazonium salt. lutesium's way might work, but the reactions aren't usually taught at this level.
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Don't you get a mixture of products and require harsh conditions by that route?
I think so..
Commercial Methods for Preparation of Phenols:
1. From Chlorobenzene (Dow's Process)
"you can obtain 4-chloro derivative of acetanilide using the FeCl3/Cl2 reagent"
Chlorobenzene is heated with 10% aqueous sodium hydroxide solution at about 623 K under 200 atmospheres and in the presence of copper salt acting as catalyst to form sodium phenoxide. The sodium salt when treated with dilute HCl, gives phenol.
2. From Cumene Hydroperoxide method
"The isopropyl group can be added at para position on acetanilide using Friedel-Crafts alkylation (anhyd.AlCl3/ 2-chloro propane)"
Air or oxygen is passed through a suspension of cumene in aqueous sodium carbonate solution in presence of cobalt or manganese naphthenate catalyst. The xidation product is cumene hydroperoxide.
The hydroperoxide is then decomposed by hot dilute sulphuric acid when phenol is formed with liberation of acetone. Acetone is removed from phenol by distillation.
3. From Benzene (Raschig's method)
Vapours of HCl are passed over benzene at 500 K in the presence of copper chloride and excess of air to form chlorobenzene. Steam is then passed through chlorobenzene at 800 K in the presence of silica as catalyst to give phenol.
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Well there's another way...and I think it's quite convenient and well within syllabus. It doesn't require diazotization or copper-catalysts.
The first step is to sulfonate acetanilide via an electrophilic aromatic substitution reaction to place the -SO3H group on the 4th position.
The second step(used as a general way to prepare phenols) is to react the sodium salt of the sulfonate so formed with fused NaOH. It transforms the -SO3Na group into an -ONa group, acidic hydrolysis of which yields -OH.
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I think as far as the original posters question is concerned, he needs to know this will be a two (or more) step process. That is, it won't be a single direct reaction.
I think most textbooks use the diazonium route (which is more than two steps). I think the other method that works well is a Bayer-Villiger type or the cumene route as suggested by uvcyclotron.
While I cannot say what a commercial route might be, I think acylation will give a greater para/ortho ratio and the B.V. reaction will work quite well in this case, but this route is less commonly referenced in textbooks.
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The second step(used as a general way to prepare phenols) is to react the sodium salt of the sulfonate so formed with fused NaOH. It transforms the -SO3Na group into an -ONa group, acidic hydrolysis of which yields -OH.
hey SVXX, this seems like a nice approach to the problem, but I am not sure about the mechanism of the above-mentioned transformation, could you explain it please?
If the reply would be too big and unfit for posting in this thread, then plz PM me. :)