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Topic: Would this proposed synthesis of 2-hexanol from 1 hexanol work?  (Read 6746 times)

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Offline limonade

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First picture:

If I treat my 1 hexanol with an acid strong enough to protonate the primary alcohol, turn it into a good leaving group, have a hydride shift, and then have water perform a nucleophilic attack on the  now secondary carbocation, and then have another water molecule come and deprotonate the newly attached one with  positive charge, to form 2-hexanol.   Why would this not work?

Second picture:

The book chose different reagents and if I try to follow through with their synthesis I get a bit stuck.

From what I follow, they treated the primary alcohol with an PBr3 to convert the alcol into a good leaving group and ultimately underwent Sn2 to form a primary alkyl bromide. Then they took this alkyl bromide, treated it with sodium tertbutoxide , underwent another Sn2 and ended up with a hexyl tert butyl ether.

From their they treated with H2O, H2SO4 cat.

I am not sure where to go from here. Do I just protonate the ether using a proton from the sulfuric acid, and somehow end up cleaving it? I am really not sure what to do here.

I have a midterm coming up really soon so any help is greatly appreciated. Sorry if the pictures are kind of blurry.

Thanks in advance :)

Offline Archer

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Re: Would this proposed synthesis of 2-hexanol from 1 hexanol work?
« Reply #1 on: July 12, 2013, 10:46:58 AM »
Rather than a hydride shift you would be more likely to eliminate H+ and form the alkene as an intermediate (dehydration of alcohol).

Essentially this could re-hydrate under acidic conditions to form the Markovnikov product of the 2° alcohol. I am not familiar with this particualr reaction occuring when dehydrating 1° alcohols though. Just because I am not familiar with it, does not mean that it doesn't happen.

I am not following the rest of your post. Please could you be a little clearer as to what you are asking. You are making an ether from an alkyl halide (Williamson ether synthesis) but what is it that you are confused about?
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Offline limonade

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Re: Would this proposed synthesis of 2-hexanol from 1 hexanol work?
« Reply #2 on: July 12, 2013, 10:55:13 AM »
Where I am stuck is that I don't know how to convert this ether, as the book does, into 2-hexanol using water and sulfuric acid.

Offline limonade

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Re: Would this proposed synthesis of 2-hexanol from 1 hexanol work?
« Reply #3 on: July 12, 2013, 11:10:11 AM »
Rather than a hydride shift you would be more likely to eliminate H+ and form the alkene as an intermediate (dehydration of alcohol).

Essentially this could re-hydrate under acidic conditions to form the Markovnikov product of the 2° alcohol. I am not familiar with this particualr reaction occuring when dehydrating 1° alcohols though. Just because I am not familiar with it, does not mean that it doesn't happen.

I am not following the rest of your post. Please could you be a little clearer as to what you are asking. You are making an ether from an alkyl halide (Williamson ether synthesis) but what is it that you are confused about?


Also, how do you know when to choose elimination over hydride shifts?

Offline Archer

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Re: Would this proposed synthesis of 2-hexanol from 1 hexanol work?
« Reply #4 on: July 12, 2013, 11:37:03 AM »
Quote from: limonade link=topic=69666.msg250714#msg250714

Also, how do you know when to choose elimination over hydride shifts?


In my experience hydride shifts are quite rare and only used in mechanisms when no other explanation can be used. They are quite difficult to prove experimentally as they require replacing the proton in question with deuterium and seeing whether or not it is eliminated or moves to another carbon by analysis with 1H NMR. Without this experimental data it is really just conjecture as to what happens. I would always suggest elimination (if the mechanism fits) before a hydride shift, what does everyone else think?

Could you provide a reference for the book you are working from? This is not the way that I would synthesise 2-hexanol.
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Offline Babcock_Hall

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Re: Would this proposed synthesis of 2-hexanol from 1 hexanol work?
« Reply #5 on: July 12, 2013, 12:51:54 PM »
tert-butyl groups can be relatively unstable in acid, because they form a meta-stable intermediate.

Offline limonade

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Re: Would this proposed synthesis of 2-hexanol from 1 hexanol work?
« Reply #6 on: July 12, 2013, 03:38:38 PM »
Quote from: limonade link=topic=69666.msg250714#msg250714

Also, how do you know when to choose elimination over hydride shifts?


In my experience hydride shifts are quite rare and only used in mechanisms when no other explanation can be used. They are quite difficult to prove experimentally as they require replacing the proton in question with deuterium and seeing whether or not it is eliminated or moves to another carbon by analysis with 1H NMR. Without this experimental data it is really just conjecture as to what happens. I would always suggest elimination (if the mechanism fits) before a hydride shift, what does everyone else think?

Could you provide a reference for the book you are working from? This is not the way that I would synthesise 2-hexanol.

Thank you for your help and explanation. I really do appreciate it. The book that I am working from is Organic Chemistry by T.W. Grham Solomons and Fryhle
http://www.amazon.com/Organic-Chemistry-T-Graham-Solomons/dp/0470556595


The picture here is the problem statement and solution:

Offline Babcock_Hall

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Re: Would this proposed synthesis of 2-hexanol from 1 hexanol work?
« Reply #7 on: July 12, 2013, 05:10:24 PM »
It may help to bear in mind that the tert-butoxide anion is a strong base but a poor nucleophile.

Offline orgopete

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Re: Would this proposed synthesis of 2-hexanol from 1 hexanol work?
« Reply #8 on: July 12, 2013, 07:12:30 PM »
Re: original question

Dehydration of 1-butanol gives a mixture of 1-butene and cis and trans-2-butene. Presumably, a hydride shift occurs to give a secondary carbocation. Loss of a proton can give the three products. Direct loss of a proton can also give 1-butene, the minor product. Therefore, if acid catalyzed hydrolysis were used, a mixture of hexanols would result.

The suggested route also encounters a problem in which conditions to dehydrate a primary alcohol must exist along with conditions in which a secondary alcohol is hoped to prevail. I anticipate the equilibrium would not be favorable. A successful addition to an alkene must also overcome an unfavorable acid-base equilibrium. Alkenes are much less basic than an alcohol. An acid would preferentially protonate an alcohol, potentially leading to dehydration if too acidic. The success depends upon a relatively unfavorable alkene protonation leading to alcohol. In this way, treatment with HBr can succeed as a basic alcohol leads to a much less basic bromide.

None the less, a common alternate is to use a mercury catalyzed addition to an alkene and a reductive demercuration step. You may find an OrgSyn prep for an oxymercuration, which I believe attests to a broader generality.
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Offline Archer

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Re: Would this proposed synthesis of 2-hexanol from 1 hexanol work?
« Reply #9 on: July 13, 2013, 03:06:38 AM »
It may help to bear in mind that the tert-butoxide anion is a strong base but a poor nucleophile.

I agree, you have dehydrohalogenation to the alkene (beta elimination of a proton by the butoxtide).

The ether is not the intermediate, I thought perhaps the reaction scheme you were working from suggested it was.

Halide -> alkene -> 2° alcohol.
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Offline magician4

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Re: Would this proposed synthesis of 2-hexanol from 1 hexanol work?
« Reply #10 on: July 13, 2013, 05:21:33 AM »
in addition:

ref. method 1, there's a lot of side-reactions besides the movement of the alkene function to an undesired position: the whole range of primary carbocation actions you might think of
besides that, under the conditions described the (desired) sec. alcohol i.m.h.o. would dehydrate even faster than the original educt, and you could have a shift of the double bond without any hydride involved

with respect to the real product most likely formed as main product instead, I would put my bets on hexan-2-yl-hexyl ether


regards

Ingo
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Offline wang yangwu

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Re: Would this proposed synthesis of 2-hexanol from 1 hexanol work?
« Reply #11 on: July 13, 2013, 09:17:04 AM »
I just came across this and was curious if elimination with a non nucleophilic base followed by hydroboration oxidation could work?

Offline Dan

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Re: Would this proposed synthesis of 2-hexanol from 1 hexanol work?
« Reply #12 on: July 13, 2013, 10:42:34 AM »
I just came across this and was curious if elimination with a non nucleophilic base followed by hydroboration oxidation could work?

Check the regioselectivity of hydroboration.
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Offline limonade

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Re: Would this proposed synthesis of 2-hexanol from 1 hexanol work?
« Reply #13 on: July 13, 2013, 04:42:52 PM »
"It may help to bear in mind that the tert-butoxide anion is a strong base but a poor nucleophile."

Sorry x/ Looks like I need to review my elimination reactions.
Thanks to all answers. I have the following mechanism now, which is correct

Offline Archer

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Re: Would this proposed synthesis of 2-hexanol from 1 hexanol work?
« Reply #14 on: July 14, 2013, 02:48:02 AM »
That's more like it!
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