Chemical Forums
Chemistry Forums for Students => Organic Chemistry Forum => Organic Chemistry Forum for Graduate Students and Professionals => Topic started by: columbo123 on March 15, 2021, 10:44:06 AM
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Hello everybody,
I am currently planning a synthetic route and the fourth step is planned as shown below.
I am now suspicious of where the lithiation with LDA (or optionally BuLi) is likely to happen. Literature states that HA is favoured over HB in the similar molecule without a OMe group on the phenyl ring. Does anybody have more knowledge on wheter alpha-lithiation at the HA site or ortho-lithiation at HC, promoted by the direct-metallating group OMe, is favoured?
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Ha and Hb is much more acidic then Hc. Its more difficult to know if Ha is more acidic then Hb, I think you have to just try.
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In my group where we synthesise polyaromatic and polyheteroaromatic compounds we have deprotonated at Hc but definitely not with LDA, we use nBuLi.
Though Hb and Ha have similar PKa, I would expect LDA would favour Ha because there is less steric hindrance there.
Sorry I can't be of more help than that.
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If you want to lithiate methoxybenzene you do it at 21°C and with BuLi. Its much easier to lithiate thiophene. I guess Hb is on a carbon that is more conjugated, less "thiophene-like" and therefore less acidic than Ha.
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21°C? how do you maintain that temp? haha
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Thank you for all the suggestions.
I will conduct the experiment somewhen next week and post the result, if any of you are curious too.
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please do!
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Better late than never,
for those of you who were curious: With LDA at -78 °C in THF anh., HA gets deprotonated selectively. A second, very small TLC spot probably indicates partwise attack on HB, but in a neglectable ratio.
Greetings.
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Interesting, thanx!