[eru22]

Okay, so I've got these questions for my problem-based-learning session which I got pretty stuck on.. I'm using Bruice's Organic Chemistry 6th ed as textbook and all I have learned from my classes related to the questions is reactions of alkyl halide, alcohol and ether (SN1, SN2, E1, E2, etc)
I don't know whether it's due to my lack of understanding or analytical thinking or maybe confidence but I've always found this kind of questions very difficult to solve. So if there's any advice on mastering this kind of questions it would be very helpful.
And here's the questions

"How to synthesize the following compounds. As starting materials, you may use cyclohexanol and any necessary solvents and inorganic reagents."

a) my idea is first to synthesize methylcyclohexane through grignard reaction using CH3MgBr (I'm not really sure about this since we haven't been taught yet, but the only idea I have is only through this reaction..). next, do monobromination to let the tertiary carbon react with isobutanol in the next step to make the final product.

b) my friend proposes to do Grignard reaction as well (maybe it would be CH3COMgBr).. but based on my understanding I should react it with CHCOO^- in presence of strong acid, since CHCOO^- is a strong base. thus cyclohexanecarboxylic acid is produced and then react it following the procedure in this link http://www.orgsyn.org/orgsyn/prep.asp?prep=cv5p0775

[discodermolide]

Well what reactions of alcohols do you know?
And CH₃COMgBr will not exist as it is a Grignard reagent of a ketone??

[eru22]

substitution (SN1 SN2), dehydration, oxidation and other reactions to convert alcohols into sulfonate esters/alkyl halides
hmm yea I guess so, after reading up some more, Grignard reagent is formed only from alkyl or aryl group? may I know the reason?

[discodermolide]

Think about oxidation of alcohols and see how it fits.
Grignard reagents react with ketones, that is the reason.

[eru22]

I see, oxidizing alcohols produces ketones? thanks, will look it up more
that's for reaction b), how about reaction a)?

[Borek]

I see, oxidizing alcohols produces ketones?

Not exactly. Some alcohols will be oxidized to ketones, some to something else, some will be not oxidized at all (well, technically burning is oxidation too, and in the end all alcohols can be burned, but that's not what we are interested in here).

[discodermolide]

I see, oxidizing alcohols produces ketones? thanks, will look it up more
that's for reaction b), how about reaction a)?

I am talking about reaction a.
One at a time

[orgopete]

I am not familiar with that edition of Paula Bruice, however, from past experience, the problems closely follow with reactions presented in the textbook. If you have not seen Grignard reagents, then I don't think the solution would involve a Grignard reagent. Whether this might use a Gilman reagent, bromination, etc., I don't know.

A Grignard route certainly could work very well for this synthesis, but my recollection is that oxidation reactions occur much later in the book. The synthesis of the ketone seems more likely to be from an acetylene.

[eru22]

Not exactly. Some alcohols will be oxidized to ketones, some to something else, some will be not oxidized at all

umm well, I meant secondary alcohols.. thanks for the addition

I am talking about reaction a.
One at a time

can you please be more specific? after reading some more I'm pretty confident with my answer for a).. can you point out the mistakes?

I am not familiar with that edition of Paula Bruice, however, from past experience, the problems closely follow with reactions presented in the textbook.
A Grignard route certainly could work very well for this synthesis, but my recollection is that oxidation reactions occur much later in the book. The synthesis of the ketone seems more likely to be from an acetylene.

regarding the book, I don't think the questions have such relation to the book, since our lecturer gave us the questions separtely from some other sources..
acetylene? I tried to find a way, but I have yet to find it.. can you give more hint?

[orgopete]

regarding the book, I don't think the questions have such relation to the book, since our lecturer gave us the questions separtely from some other sources..
acetylene? I tried to find a way, but I have yet to find it.. can you give more hint?

Obviously, I don't know what is being discussed in the class. If cyclohexyl methyl ketone had to be prepared from cyclohexanol, I might consider making a bromide from the alcohol and coupling it with a vinyl cuprate (I think this chemistry in Bruice?). Bromination-dehydrobromination would give cyclohexylacetylene. Hydration with sulfuric acid plus mercury salts would give the ketone.

I think the book is pretty consistent with the practice problems being related to the chemistry, especially within a chapter. As problems become more lengthy and later chapters, then you will find more reliance upon using reactions from earlier chapters.

I believe it is good pedagogy to use chemistry relevant to the discussion in a chapter. I think Bruice does a good job of that. If your instructor is extending the chemistry in some other manner, I wouldn't know about it. I tried to give an answer consistent with the chemistry of the early chapters.

[discodermolide]

About reaction a.
You have the methyl-cyclohanol, why brominate it?
Why just do a Williamson ether synthesis using the alkoxide from the alcohol and react with the primary bromide, isobutylbromide?

[eru22]

About reaction a.
You have the methyl-cyclohanol, why brominate it?
Why just do a Williamson ether synthesis using the alkoxide from the alcohol and react with the primary bromide, isobutylbromide?

I see! I get it, let me summarize the whole reactions then,
1. Oxidation - cyclohexanol is oxidized to form a ketone, cyclohexanone
2. Grignard reaction - using CH₃MgBr as Grignard reagent, methyl-cyclohexanol is produced
3. Preparing the alkoxide ion - react methyl-cyclohexanol with NaH to produce methyl-cyclohexide ion, Na⁺ and H₂
4. Williamson ether synthesis - the alkoxide ion and isobutyl-bromide are reacted via alkyl halide's SN2 reaction to produce the product wanted.

Is that right?

I believe it is good pedagogy to use chemistry relevant to the discussion in a chapter. I think Bruice does a good job of that. If your instructor is extending the chemistry in some other manner, I wouldn't know about it. I tried to give an answer consistent with the chemistry of the early chapters.

Wow so true, that method actually helps a lot. Thanks so much. After seeing the explanation and referring to the book, I found everything in it. However, I did need to turn back and forth each pages, and when I realized, I had actually learned those chapters but I had not read deeper the subchapters (like hydration and Williamson ether synthesis). Guess I need to save some time to read the whole book myself

Obviously, I don't know what is being discussed in the class. If cyclohexyl methyl ketone had to be prepared from cyclohexanol, I might consider making a bromide from the alcohol and coupling it with a vinyl cuprate (I think this chemistry in Bruice?). Bromination-dehydrobromination would give cyclohexylacetylene. Hydration with sulfuric acid plus mercury salts would give the ketone.

I just read about coupling reactions, by coupling it with "vinyl cuprate", did you mean "vinyl lithium cuprate" (H₂CCH)₂CuLi? Can a Gilman reagent be acetylenyl lithium cuprate? So that it would give cyclohexylacetylene directly. And yet, I couldn't find explanation of bromination-dehydrobromination mechanism..

[discodermolide]

"2. Grignard reaction - using CH3MgBr as Grignard reagent, methyl-cyclohexanone is produced
3. Preparing the alkoxide ion - react methyl-cyclohexanone with NaH to produce methyl-cyclohexide ion, Na+ and H2
4. Williamson ether synthesis - the alkoxide ion and isobutyl-bromide are reacted via alkyl halide's SN2 reaction to produce the product wanted."

This is wrong.
Reacting cyclohexanone with methyl Grignard gives the methylcyclohexanol after work-up.
However you may be able to take the intermediate "methylcyclohexan-OMgBr" and react it directly in the ether synthesis.
If not then work-up, make the alkoxide with a suitable base then do the ether synthesis.

[eru22]

This is wrong.
Reacting cyclohexanone with methyl Grignard gives the methylcyclohexanol after work-up.

oops, I mistyped it. fatal mistake. I really meant that "methyl-cyclohexanone" for "methyl-cyclohexanol". now I've edited it

[discodermolide]

I thought it may have been a typo. It looks better now