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Chemistry Forums for Students => Organic Chemistry Forum => Organic Chemistry Forum for Graduate Students and Professionals => Topic started by: MuscarineChloride on August 10, 2020, 05:52:14 AM

Title: Reactivity of 2,5-Dichlorobenzyl bromide compared to Benzyl bromide
Post by: MuscarineChloride on August 10, 2020, 05:52:14 AM

Hello,

first of all im new to the forum, i hope I am posting correctly, please let me know if i am doing anything wrong.

My question is about the protection of the hydroxyle group of ethyllactate.
In the original paper they used 2,5-dichlorobenzyl bromide and silveroxide as a base in boiling dry dietylether.
I tried to recreate the reaction using benzyl bromide under the same conditions, getting an extremly pore yield.

I was wondering if this is due to the missing +M effects of the Clorides, stabilizing the benzyle cation?
Does benzyl bromide need a higer temperature to react, since the carbocation is less stable, meaning i would have to alter the solvent if I want to do this reaction?

Also I am curious why silveroxide as a base is used in the williamson-ether-synthesis instead of for example stericly hindered substitued Amines.

Greetings and Thanks for the support!

Title: Re: Reactivity of 2,5-Dichlorobenzyl bromide compared to Benzyl bromide
Post by: AWK on August 10, 2020, 08:31:23 AM

Quote

I tried to recreate the reaction using benzyl bromide under the same conditions, getting an extremely pure yield.

After 48 hrs - 63 % yield (purified)
https://pubs.acs.org/doi/suppl/10.1021/ol0359259/suppl_file/ol0359259si20031001_013623.pdf

Title: Re: Reactivity of 2,5-Dichlorobenzyl bromide compared to Benzyl bromide
Post by: MuscarineChloride on August 10, 2020, 09:00:27 AM

Thank you for the reply, unfortunately I cant acces the link for some reason, could you post the DOI?


I should have also mentioned that the reaction time is 6 hours and the reported yield is 90 %.

63 % yield in 48 hours still seems quite low to me, considering its just the introduction of a simple protecting group and the reaction time to me is also surprisingly long compared to the 6 hours and 90 % with 2,5-Dichlorobenzyl bromide.

I have also found a paper using acetonitrile and potassium carbonate at roomtemperature with a reaction time of 36 hours, giving a yield of 96 %. I will probably try that.

Title: Re: Reactivity of 2,5-Dichlorobenzyl bromide compared to Benzyl bromide
Post by: AWK on August 10, 2020, 09:03:46 AM

pubs.acs.org/doi/suppl/10.1021/ol0359259/suppl_file/
check supporting information - it can be downloaded freely.

Title: Re: Reactivity of 2,5-Dichlorobenzyl bromide compared to Benzyl bromide
Post by: OrganicDan96 on August 24, 2020, 10:00:13 AM

do you know of any special properties of silver?

Title: Re: Reactivity of 2,5-Dichlorobenzyl bromide compared to Benzyl bromide
Post by: rolnor on August 24, 2020, 12:49:32 PM

I wonder if it is possible to do it with benzyltrichloroacetimidate with a little TFA? I dont think the ester will interfere.
Here is a lunk; https://kops.uni-konstanz.de/bitstream/handle/123456789/10008/A_Useful_Application_of_Benzyl_Trichloroacetimidate_for_the_Benzylation_of_Alcohols.pdf?sequence=1