[Leslon]

Hi everyone,

In school we do various multi-step synthesis exercises. For our assignment, we have to do such reactions at home. One of those is terribly hurting my brain  .

Could someone please help me with this one?   

This is how I think it should be:

• 1) Replace the OH with Br through PBr₃ in pyridine
• 2) Use of Mg (Grignard reagent)
• 3) Enlarge the alkyl chain through usage of an epoxide(H₂COCH₂)
• 4) Replace the OH through SOCl₂
• 5) ...I Don't know 

If someone can solve this thing, i would be grateful ad infinitum 

[azmanam]

does the methyl group really turn into a hydrogen atom, or is it a typo - the synthesis changes dramatically depending on the circumstance.

epoxide is no good in the synthesis you've outlined - one too few carbon atoms between ring and oxygen.

[Leslon]

Yes, somehow the methyl turns into a hydrogen, at least I hope it's not a typo..

What "action" would you undertake in enlarging the alkyl chain, instead of the epoxide?

[azmanam]

well, I was a bit dramatic when I said the methyl 'turns into' a hydrogen - no alchemy before lunch.  that's my motto.

Actually, I'm ok with an epoxide in the synthesis, just not where you have it placed.  can you think of another stragegy that will install the hydrogen AND allow you to use an epoxide to append the remaining functionality.

Another exercise that might be useful: do you think you can number the carbon atoms 1-7 on the starting material and map them on to the product.  Which carbons are 1-7 in the product?

[Leslon]

The other strategy I can think of, is the dehydration of the alcohol. Formation of an alkene is the result then. That would install the hydrogen, but how do I apply the epoxide then?

Carbon 1 would the one where the initial OH is bonded. The name of the original molecule is 1-methylcyclohexanol.

[Leslon]

The other strategy I can think of, is the dehydration of the alcohol. Formation of an alkene is the result then. That would install the hydrogen, but how do I apply the epoxide then?

Carbon 1 would the one where the initial OH is bonded. The name of the original molecule is 1-methylcyclohexanol.

Sorry, I forgot to mention that the alkene is then reduced by H₂/Pt

[azmanam]

I like the alkene formation - careful with your net dehydration conditions - watch out for Zaitsev's rule.

H2/Pt is no good after that though, you lose all useful functionality.  You'll need to do something different after alkene formation.

[Leslon]

I would do the dehydration in such way that the least substituted alkene is formed. This results in a double bond between the methyl and C1.

But I have no clue how to extend the alkyl chain through this method..

What do you suggest as the next step?

[azmanam]

So you wanted to eliminate the alcohol so that you could reduce the alkene towards the end goal of installing the hydrogen atom present in the product, yes?

Instead, is there a way to do something different to the alkene such that you can install the hydrogen atom AND give yourself a functional group somewhere else in the molecule that you can use to append the rest of the chain?

(hint: yes, there is)

[Leslon]

Maybe we can apply HBr to the alkene. That would install the H and a useful functional group. Then I would use Mg(Grignard reagent), then an epoxide, then H₃O⁺ to form an alcohol.

The next step would be SOCl₂ to replace the OH with CL.
After that I would use NaCN, to expand the alkyl chain with one extra C.
Then I would use a strong acid with heat to form a COOH group.
Then with the help of LiAlH₄, I reduce the COOH to 1° alcohol.
Now using Na, an alkoxide ion is formed.
The final step would be the application of Br-CH₃ to form the ether.

The elimination of the CH₃ is still a big question mark...

[azmanam]

So elimination to the alkene then hydrohalogenation does the same net effect as the 1-step replacement of the alcohol with halogen.  Your synthesis is what I would do if that hydrogen was a methyl group, but given that you need the hydrogen there, I think you'll be better served with different reaction conditions after forming the alkene

[HW]

Here is my proposal:

First, eliminate the alcohol to form alkene, followed by Hydroboration (anti-Markonikov). After that react the alcohol with PBr3 then formed Grignard's reagent and use it to attack epoxide. Lastly, SN2 reaction with CH3-Br to form the final product.

[weiweishen]

My proposal is first dehydration to form alkene, followed by convert alkene to ketone by OsO4. The ketone then is reduced to OH group that further convert Br. Final step is the replace the Br with grignard reagent

[azmanam]

a) you can't just do acid-cat dehydration of the starting alcohol.  You'll get the Zaitsev elimination product (the endocyclic trisub alkene).  Practically, you'll probably also have a problem treating with SOCl2 to make the chloride - tertiary alcohols are historically difficult to halogenate.

b) OsO4 will make a diol, not a ketone, and while hydroboration/bromination will work.  It would be easier to do anti-markovnikov hydrohalogenation with HBr, peroxides and get there in 1 step.

Here's my route:

1) Mesyl chloride/pyridine (make mesylate) 2) KOtBu (Hoffmann elimination to exocyclic alkene) 3) HBr/ROOH (antimarkov hydrobromination) 4) Mg (Grignard formation) 5) oxetane, then H+/H2O (epoxide opening) 6) NaH, MeI (Williamson Ether Synthesis)

[nj_bartel]

If I had to guess, I think the right answer would be just be thionyl chloride treatment rather than mesylation.  Definitely didn't learn about mesylation during intro organic and didn't learn the mechanism behind thionyl chloride treatment until oxygen chemistry chapter.