[Babcock_Hall]

Good Afternoon,

One textbook author (Klein) classifies tert-butoxide as a strong nucleophile.  Daley and Daley (p. 537) say that it is not an effective nucleophile in S_N2 reactions.  However, their own data indicate that it is slightly faster than other alkoxides against methyl iodide.  They explain this by saying that methyl iodide does not itself have any steric crowding.  Solomons (Chapter 6) indicates that if one wants to tilt a reaction of a primary alkyl halide toward E2 elimination and away from S_N2 substitution, that tert-butoxide would be a good choice as a base.  I can rationalize some of these observations by stating that tert-butoxide is a good nucleophile against a methyl carbon, but perhaps not against primary carbons, due to a steric clash between the substrate and tert-butoxide.  However, I don't have data on the rate of substitution or elimination reactions involving primary carbon atoms bearing a leaving group.  Does anyone have any thoughts?

[rolnor]

Good Afternoon,

One textbook author (Klein) classifies tert-butoxide as a strong nucleophile.  Daley and Daley (p. 537) say that it is not an effective nucleophile in S_N2 reactions.  However, their own data indicate that it is slightly faster than other alkoxides against methyl iodide.  They explain this by saying that methyl iodide does not itself have any steric crowding.  Solomons (Chapter 6) indicates that if one wants to tilt a reaction of a primary alkyl halide toward E2 elimination and away from S_N2 substitution, that tert-butoxide would be a good choice as a base.  I can rationalize some of these observations by stating that tert-butoxide is a good nucleophile against a methyl carbon, but perhaps not against primary carbons, due to a steric clash between the substrate and tert-butoxide.  However, I don't have data on the rate of substitution or elimination reactions involving primary carbon atoms bearing a leaving group.  Does anyone have any thoughts?

But methylcarbon is a primary carbon, do you by primary carbon mean a longer chain like ethyl, propyl etc.?

[Babcock_Hall]

When I refer a primary haloalkane, I mean that the carbon having the halogen has exactly one bond to another carbon.  Bromoethane and 1-bromopropane would be examples.

[orgopete]

Ah, a really tough question, why indeed? I too have tried to think about these reactions. I think that t-butoxide is a stronger base due to the electron donation of the methyl groups. I think that in comparing t-butoxide with methoxide or ethoxide one might expect t-butoxide might be faster. Another factor, though one I cannot corroborate, is the effect of the solvent. Reactions of methanol or ethanol probably are all in the alcohol as bulk solvent. That cannot be the case for t-butoxide.

I am familiar with the steric argument, though I have difficulty in understanding it. If I assume the stereoelectronic requirement for a reaction with an alkoxide is linear, then I cannot see how t-butoxide would be more sterically demanding than methoxide. The reaction of an acetylide with a secondary halide gives elimination. Acetylide is generally regarded as having a low steric demand, though a more basic reagent. This begins to make me think the basicity may be a bigger issue than a steric argument. (I am only saying this in trying to understand the chemistry, if asked on a test, the correct answer is 'steric'). In my book, I used the ratio of substitution to elimination for a reaction of t-butoxide with 1-bromooctadecane. The major product is elimination, but substitution also occurs.

I focused on the differences in elimination reactions. I thought that Zaitsev elimination reaction products were E1-like even though E2-kinetics. I argue a neighboring carbocation would allow a shift of electrons from the most electron rich carbon would give the most substituted alkene. A similar analysis of a Hofmann elimination may leave one to think that an ammonium salt would be less electron withdrawing than an equivalent bromide or iodide, less carbocation-like and that would give a Zaitsev product. In that case, the elimination can seem to be more dependent on the CH acidity and give the least substituted alkene.

The best example I could find with t-butoxide v ethoxide is the reaction of 1-chloro-1-methylcyclohexane. Ethoxide will give 1-methylcyclohexene, the Zaitsev product. t-Butoxide will give methylenecyclohexane, a Hofmann product. Bromo and iodide give mainly the Zaitsev product. I reason that chloro is less electron withdrawing and can allow the reaction of t-butoxide to discriminate favoring the acidity of the CH3-group leading to the methylenecyclohexane.

I realize I have not and cannot answer the question directly. The best I can do is to report on some of the differences I have found. Questions of A gives B and C gives D are difficult to correctly analogize. In my manuscript, I have dealt with similar problems and have reached different opinions that one might have found in textbooks. I don't think one can make a direct comparison. How does one gauge the effect of the change in solvent for example? How could a solvent change the effect of the reagent?

[Babcock_Hall]

There is a paper on the reaction of text-butoxide in t-BuOH with methyl iodide:  James O. Shreck, J. Chem. Ed. 43(3) 1966, 149.  The reaction is described as being about 80% complete at 24.5 °C in two hours.

[phth]

I remember reading that the tBuOK with 1-bromopropane will create an E2 reaction as the major product.  Source Ansyln & Dougherty Modern Physical Organic Chemistry: https://www.amazon.com/Modern-Physical-Organic-Chemistry-Anslyn/dp/1891389319

[Babcock_Hall]

One might conclude from Daley and Daley's table that tert-butoxide is a good nucleophile versus methyl iodide.  It would be nice to know its rate constant for a substitution reaction with 1-bromopropane versus other alkoxide ions.  However, I am willing to say that it is a relatively poor nucleophile, based on the relative propensity for E2 over S_N2 reactions involving primary alkyl halides.

[orgopete]

One might conclude from Daley and Daley's table that tert-butoxide is a good nucleophile versus methyl iodide.  It would be nice to know its rate constant for a substitution reaction with 1-bromopropane versus other alkoxide ions.  However, I am willing to say that it is a relatively poor nucleophile, based on the relative propensity for E2 over S_N2 reactions involving primary alkyl halides.

I'm guessing the major product will still be the substitution product, ca 85%. I don't know if the appropriate study has been done or not. Unless a carefully done study were performed, I think it would be difficult to know what the rates are as t-butoxide and methoxide or ethoxide have quite different properties. I think you need a study done in DMSO or another solvent to try to compensate for solvent effects. If I were to guess and this might be what Daley and Daley refer to, the more basic the nucleophile, the faster the reaction, thus RO(-)>ROH. Obviously, that would be a simplistic argument as the halide reaction rate is more like I>Br>Cl>F. As I recall, in an aprotic solvent, fluoride is faster, but does not overtake iodide. That is also probably why this is a difficult question to give a definitive answer to.

[Babcock_Hall]

In the case of Daley and Daley's table, they present the reaction of various nucleophiles with methyl iodide in DMF, and tert-butoxide is modestly faster than ethoxide or methoxide.  Solomons' textbook gives 85/15 as the ration of E2 to S_N2 for test-butoxide in tert-butanol.  I agree that changing the solvent and looking at the same ratio would be an interesting experiment.  Perhaps what I should have said about the nucleophilicity of tert-butoxide is that it depends on the other factors in the reaction.

[orgopete]

I'm guessing the major product will still be the substitution product, ca 85%.

Ya, I really screwed that up. I should have read my own post where I cite the opposite.

Re: Daley and Daley data
That sounds like the kind of data I like to find. It sounds about right (although I don't know what they actually show). I don't think there should be much of a difference between methoxide and ethoxide, so should we expect t-butoxide to be a lot faster (or slower)?