strong or weak nucleophile of halides and acetate

[justdominate]

I have read some other threads regarding this and I understand that the relative strength of halide nucleophiles depend on the solvent used.

This was the answer posted by Dr. Romano in this thread Halides weak or strong nucleophiles?

Halogens such as I- are EXCELLENT reactions when used in a polar protic solvent. The order of reactivity will be I- >Br->Cl> F-. As you can see Iodine is best. Fluorine is the worst because the polar solvent solvates the ion and renders this nucleophile useless since it is captured in a hydrogen bonded molecular solvent cage. Now....let's change the solvent to polar aprotic such as HMPT, DMSO, THF, or acetone. We now see the order is reversed ! F- > Cl- >Br->I-. Hopefully you see that F- will be a very good nucleophile.

So my question is can halide nucleophiles (Cl-,Br-,I-, not counting F-) undergo Sn2 reaction regardless of solvent? From my Chad's notes, I have it written down as I-,Br-,Cl- as being strong nucleophile but weak bases. Also, can the DAT ever give a question on this without giving us the solvent? One of the quiz questions on BC from Dr. Mike Christiansen was using LiI as the nucleophile (solvent was not given) and he's answer was Sn1 reaction.

Lastly I'm still unsure if acetate ion is a strong or weak nucleophile. From the notes and quizzes on BC (Dr. Mike Christiansen), he has it listed as a weak nucleophile which will under go Sn1 reaction. But from the answer given by Dr. Romano from the thread above, he states that "For your other question, your notes are correct. Acetate ion is a fairly good nucleophile and prefers to do the SN2 reaction mechanism."

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[NextStepTutor_2]

Hi justdominate,

In DAT questions, halides reactants are often in the form of HCl, HBr, etc with no other solvent information. You can expect these halides to participate in substitution reactions. Sn1 versus Sn2 predictions will often depend on substitution (tertiary, secondary, primary). They may test you on solvent effect concepts within a reaction or directly - i.e. what are the effects on nucleophilicity or the effects on the stability of carbocation intermediates - but this isn't that common.

As far as the acetate ion, you can expect it to react as a nucleophile but not as a base. It is not a particularly strong nucleophile d/t resonance stabilization of its charge [order of nucleophilicity: CH3CO2(–) < HO(–) < CN(–) < CH3S(–)]. But, it is nucleophilic and will react with a good electrophile. I would again say that Sn1 v Sn2 depends more on the substrate - primary will always be Sn2, tertiary Sn1 (if permitted by solvent).

Hope this helps. Let me know if you have any other questions.

Alicia
(26 AA, 30 Organic Chemistry score)

 

[DAT Destroyer]

I have read some other threads regarding this and I understand that the relative strength of halide nucleophiles depend on the solvent used.

This was the answer posted by Dr. Romano in this thread Halides weak or strong nucleophiles?

Halogens such as I- are EXCELLENT reactions when used in a polar protic solvent. The order of reactivity will be I- >Br->Cl> F-. As you can see Iodine is best. Fluorine is the worst because the polar solvent solvates the ion and renders this nucleophile useless since it is captured in a hydrogen bonded molecular solvent cage. Now....let's change the solvent to polar aprotic such as HMPT, DMSO, THF, or acetone. We now see the order is reversed ! F- > Cl- >Br->I-. Hopefully you see that F- will be a very good nucleophile.

So my question is can halide nucleophiles (Cl-,Br-,I-, not counting F-) undergo Sn2 reaction regardless of solvent? From my Chad's notes, I have it written down as I-,Br-,Cl- as being strong nucleophile but weak bases. Also, can the DAT ever give a question on this without giving us the solvent? One of the quiz questions on BC from Dr. Mike Christiansen was using LiI as the nucleophile (solvent was not given) and he's answer was Sn1 reaction.

Lastly I'm still unsure if acetate ion is a strong or weak nucleophile. From the notes and quizzes on BC (Dr. Mike Christiansen), he has it listed as a weak nucleophile which will under go Sn1 reaction. But from the answer given by Dr. Romano from the thread above, he states that "For your other question, your notes are correct. Acetate ion is a fairly good nucleophile and prefers to do the SN2 reaction mechanism."

The solvent can accelerate a reaction by as much as ten million fold. The solvent is usually the dominating factor . In the SN2 and Sn1 reaction, the solvent usually plays a major role. If you see a primary halide, we want to use a solvent that is polar aprotic since we want to do SN2. DMF, THF , HMPT, or acetone are fine examples. We bend these rules a bit when nucleophiles such as ethoxide, sulfur nucleophiles, phosphorus nucleophiles, or cyanides are used. For example, 1-bromopentane can be made into 1- ethoxypentane if we reacted it with sodium ethoxide in ethanol. The explanation is not clear cut, but normally we stay with the polar aprotic solvents. I have used nucleophiles like CH3SNa with DMF AND with ethanol to do the SN2. Guess what ? Both worked since sulfur is such a great nucleophile, but it was SLOWER with the polar protic solvent like ethanol. Acetate is only a fair nucleophile, since it has resonance. The electron density is not localized on a single oxygen atom . It does BOTH SN1 and SN2,,,,,,but in my 30 years doing the reactions, I find acetate has a strong bias towards SN2 reactions. Dr. Joseph Hornback at the University of Denver used acetate with DMF on 2-bromo butane and it went SN2 at 96% yield !!!!! 96% do you hear !! If you used acetic acid solvent , the yield and rate would have been much less . Acetate is not a very strong base, thus gives clean SN2 reactions . If you used acetate in an acetic acid solution , yes,,,,it is POSSIBLE to have some competing SN1, For your purposes, I would keep life simple. The DAT surely will. For primary halides, do SN2, if you see a Sulfur, Cyanide, or acetate nucleophile ...do SN2 regardless of the solvent. However, like I said, with acetate, it is a bit tricky. The halides are MORE SOLVENT SENSITIVE than these nucleophiles under discussion . . As I pointed out,,,,,in a polar aprotic solvent, F is the best, In a polar protic solvent, I is the best, These are great rules of thumb. Yes..anyone that makes up an organic chemistry question needs to put in the solvent or reaction conditions because this may confuse a reader, so I indeed feel your frustration. If the halide is tertiary, we normally want to do an SN1 reaction. Now, your acetate nucleophile can do SN1 BUT E1 also competes. In the SN1, the solvent is SUPER CRITICAL.....since the carbocation needs a polar protic environment to be stabilized. Do yourself a HUGE favor,,,,,instead of trying to learn from a video clip, get the text by David Klein. The reading style is easy. Dr. Klein reviews what I have just stated in a nice easy to understand fashion. I hope this helps. Feel free to join my Facebook DAT study group and you and I can debate this even more !!!

Dr. Jim Romano