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Chemistry Forums for Students => Organic Chemistry Forum => Topic started by: xshadow on July 24, 2020, 06:37:58 AM

Title: Synthesis exercise - SEAr ?
Post by: xshadow on July 24, 2020, 06:37:58 AM

Hi

I  can 't do this exercise

(https://i.imgur.com/sLDRl54.jpg)

What reagents should   I use?


The textbook  says the is a 2-step synthesis


The only thing I can say is that I need some Electrophilic aromatic substitution and the OR will direct my reagent in para

But  the product has a carbon with  both a -OH group and a -COOH

So strangeee
Any help? Thanks

Title: Re: Synthesis exercise - SEAr ?
Post by: kriggy on July 24, 2020, 07:22:18 AM

The reaction sequence is three steps (or at least the one I figured out). It consists of SeAr, nucleophilic addition and hydrolysis. Try to figure it out :)

Title: Re: Synthesis exercise - SEAr ?
Post by: Borek on July 24, 2020, 07:30:41 AM

Three arrows mean three steps, not two. Two intermediates.

Title: Re: Synthesis exercise - SEAr ?
Post by: xshadow on July 24, 2020, 10:32:55 AM

Quote from: kriggy on July 24, 2020, 07:22:18 AM

The reaction sequence is three steps (or at least the one I figured out). It consists of SeAr, nucleophilic addition and hydrolysis. Try to figure it out :)

I can't figure out

When you speak of nucleophilic addition do you mean a nucleophilic addition to a carbonyl group


I don 't know if that -OH group was a carbonylic group  before and then a nucleophile like ChEMgBr added a CH3 group

But I think is not possible because I have and acid like COOH so I can't have a grignard reagent



The other problem is that the first step should be a SeAr

But which type?
The only  one viable is the  friedel crafts reaction...but of what?

Acylation?
Alkylation?

In acylation the  pi-double bond will attack the C alpha to C=O

Could be that?
Thanks

Title: Re: Synthesis exercise - SEAr ?
Post by: xshadow on July 24, 2020, 10:54:45 AM

https://i.imgur.com/ZnnVfKZ.jpg

(https://i.imgur.com/ZnnVfKZ.jpg)


My doubt here is that the RMgBr could also attack the acyl chloride group

Title: Re: Synthesis exercise - SEAr ?
Post by: hollytara on July 24, 2020, 11:54:18 AM

I think it is:

Friedel Crafts Acylation

Cyanohydrin formation

Hydrolysis of nitrile to amide then acid

Title: Re: Synthesis exercise - SEAr ?
Post by: xshadow on July 25, 2020, 05:25:50 AM

Quote from: hollytara on July 24, 2020, 11:54:18 AM

I think it is:

Friedel Crafts Acylation

Cyanohydrin formation

Hydrolysis of nitrile to amide then acid

Thank you very much
It make sense





Anyway i 've tried another way
Accordung to us can be correct?

(https://i.imgur.com/riRIHV1.jpg)

Ps: in the first step I miss a OR bonded to C=O

Thanks

Title: Re: Synthesis exercise - SEAr ?
Post by: kriggy on July 27, 2020, 04:43:46 AM

Yes this could work as well (at least on paper). While esters are less reactive, sometimes it doesnt matter much because the reaction itself can be fast enough that you might not even have time to quench it. I did addition to methylester and it was complete after I finished addition of my organometalic reagent.

Title: Re: Synthesis exercise - SEAr ?
Post by: rolnor on July 27, 2020, 07:31:29 AM

You can p-brominate, lithiate and add this to ethylpyruvate, then hydrolyse. I wonder if ethyl oxalylchloride is good to use in Friedel-Craft, can it decarbonylate or something? I would think that lithiation and addition to the ethylpyruvate can be considered one step, or?