[thekid_frankie]

I am studying for an upcoming exam and we were given a practice test but no answers.  I just want to confirm that I am headed in the right direction with these reactions.
2. Complete each of the following reactions.  Show the stereochemistry of the product when appropriate.
(a)
Now it doesn't specify that it is an S_N2 reaction but reasoning for is the C1 is a secondary carbon.  So this means the nucleophile (CH₃CO₂^-) will approach C1 opposite the leaving group (Br).  The product I have come up with is this:

Now I know that having the nucleophile, especially one of this size, on the axial is not stable but I want to know that I am headed the right way before I start worrying about the stereochemistry.  So am I correct in this being an S_N2 reaction and correct in the product?

This is the first open reaction like this that I have attempted on my own without a book, just like the test, and I really appreciate any help or tips!

[Compaq]

You mentioned yourself that the halide is secondary, which means that S_N2 isn't necessarily favoured over the S_N1 mechanism. For that matter, E1 and E2 are also possible with secondary halides. With that in mind, you need to look at your nucleophile: CH3COO^-

Acetate is a conjugate base to acetic acid, which means it acts as a strong base (acetic acid is a weak acid). Having to look up in my text book, a I see that for secondary halides, elimination is favoured if the nucleophile is a strong base. This is just a generalisation, though, and I'm not too confident in coming with conclusive comments. Maybe someone else will chime in.

[fledarmus]

An S_N2 reaction on a secondary carbon requires a good nucleophile. How is acetate ion as a nucleophile?

[Dan]

Acetate is a good enough nucleophile for S_N2 at a secondary position provided the leaving group is good enough, as 50 years of Mitsunobu reactions will testify. I have even used trifluoroacetate as an S_N2 nucleophile - though this was displacing a triflate at the a-position of a lactone, so a bit of a special case.

Of S_N2, S_N1, E2 and E1 I think the only one that can definitely be ruled out is E2 for stereoelectronic reasons (Br cannot sit with a trans diaxial relationship to any H because the ring is locked by the ^tBu).

This leaves a choice between S_N2, S_N1 and E1.

We have a decent leaving group, but at a secondary position (quite hindered, would form a reasonable carbocation), and a fairly poor nucleophile in a polar protic solvent. I'd expect carbocation pathways to dominate.

[orgopete]

Acetate is a good enough nucleophile for S_N2 at a secondary position provided the leaving group is good enough…

This leaves a choice between S_N2, S_N1 and E1.

We have a decent leaving group, but at a secondary position (quite hindered, would form a reasonable carbocation), and a fairly poor nucleophile in a polar protic solvent. I'd expect carbocation pathways to dominate.

I agree with Dan's analysis. I consider this a poor question to ask on an exam unless you are willing to accept a broad range of answers as correct. Secondary halides can react via either mechanism, the solvent is an SN1 solvent, and the nucleophile is an SN2 nucleophile (depending on concentrations). I don't think you can know a priori what the product should be. None the less, I would argue for the SN2 reaction. The greater the concentrations, the faster the SN2 reaction takes place. By convention, we know there is at least one equivalent of acetate. In practice, this could become an SN1 reaction by diluting the mixture until the nucleophile falls out of the rate analysis. I would consider it mean spirited to say this should be an SN1 reaction because the unspecified conditions were too dilute for an SN2 reaction. If I were grading this, I'd  give credit for all of the choices Dan suggested.

(I noticed in my book that I too have a similar example. I have an axial and equatorial tosylate reacting with one equivalent of cyanide ethanol-water. I was using it to illustrate a higher rate of reaction from an axial displacement than equatorial. However, I do ask for the SN2 product. I don't recall the actual reaction that I used as a model in choosing ethanol-water as the solvent.)

[thekid_frankie]

The majority of the questions on my upcoming exam will be in this fashion.  We will be given a substrate, reagent, and solvent and asked to find the product of the reaction.  The unfortunate part is that they are only taking one answer as the correct answer so we have to consider all aspects of the reaction to give the one with the best yield (chemistry is serious here at GaTech).  The steps I have been taking to complete these are as follows (please correct any inaccuracies):

1.  Look at the substrate, particularly the alpha carbon.  A methyl, primary, or secondary carbon attached to the halide will follow bimolecular mechanisms (when I had tried the reaction above I had not finished the chapter yet so I did not consider the possible E2 reaction).  Tertiary carbons will follow unimolecular mechanisms or E2 reactions.
2.  We then look at the size of the reagent.  A small unhindered base/nucleophile will react primarily by substitution, and larger hindered reagents will follow eliminations.
3.  The next factor is temperature.  High temperatures promote elimination mechanisms (E1 and E2).
4.  Then I will consider basicity and polarizability of the reagent.  Strong, slightly polarized bases will increase the likelihood of elimination, while weakly basic highly polarized bases will support substiution.
5.  Lastly, we look at the solvent.  Now I know that aprotic solvents favor bimolecular reactions.  They don't talk about elimination or substitution but am I safe to assume that aprotic solvents favor both S_N2 and E2?  And protic solvents favor S_N1 and E1?  Or does it not matter with elimination?

Now, those rules will, for our applications, apply mostly to just bimolecular reactions.  We have learned that tertiary halides are the only substrates that follow unimolecular pathways since they have to form a carbocation intermediate that has to be relatively stable.  The general rule given in the textbook is that substitution is favored in most unimolecular reactions.  E1 reactions are only favored at very high temperatures and if elimination is desired it is better to use a strong base to encourage E2 over E1 or S_N1.  No S_N2 reactions occur for tertiary substrates.

After all of these factors, another issue I am having is which take precedence over others?  If I have factors that favor either how do I know if a reaction follows substitution more than elimination?

This is the next reaction I am going to try:

Hopefully this long post doesn't scare people away but I love chemistry and I am really hoping to learn as much as possible.  I don't care too much about grades but when I graduate I want to be able to impress with knowledge more than GPA so I would love to get more insight from the higher intellect here.  Thank you.

[thekid_frankie]

Just worked through the last question I posted.  Here's the mechanism I came up with and the product:

I also included a couple small blurbs about my reasoning, but a little more research than that went into it  seem correct?

Also, is there any way to change the subject of this thread?  It needs to be a little more general than it is now.  And again, thanks to anyone who has stuck with these posts it's a big help.

[Dan]

While I agree that the latest question will be an E2 reaction, I don't agree with your product - the regioselectivity is wrong. You need to consider a very important requirement for E2 - the leaving group and the abstracted proton must be periplanar.

[thekid_frankie]

I didn't seem right, the way I did it, especially with the methyl group attached to that carbon...  How about this:

[Dan]

No. The dihedral angle between the abstracted proton and the leaving group must be 180^o (or 0^o in some special cases) for E2 to occur. The axial-equatorial dihedral angle is 60^oC.

[jj74]

that is not a neopentyl cyclohexane by the way, is it?

[orgopete]

@frankie

I generally agree with your 1-4 steps. My original comment related to the dilemma students face in seeing a reaction with ethanol-water for an SN1 reaction on a tertiary halide. It is natural to begin to expect an SN1 reaction with a secondary halide as well. There have been many kinetic studies on secondary halides, so as a student, this could be anticipated. In addition, reaction rates are dependent on concentrations. Dilution will increase the rate of unimolecular reactions. However, if another nucleophile is included, you should anticipate that it is intended to be present in sufficient concentration to affect the rate of the reaction. In that case, it should be an SN2/E2 reaction.