SN1/SN2/E1/E2 Decision
Deciding SN1/SN2/E1/E2 (3) – The Solvent
Last updated: November 29th, 2022 |
The Quick N’ Dirty Guide To SN1/SN2/E1/E2 Reactions, Part 3: The Role of Solvent
Let’s continue with our Quick N Dirty guide to SN1/SN2/E1/E2 – a quick walkthrough of thinking through this reaction decision.
There are four key factors to consider:
- Substrate (first article)
- Nucleophile/Base (previous)
- Solvent (this article)
- Temperature (next)
What’s The Solvent?
Recall that there are two important types of solvents to consider: polar protic solvents and polar aprotic solvents. [See this post: All About Solvents]
Let’s do a little review, looking at polar protic solvents first.
Polar protic solvents are solvents that are capable of hydrogen bonding. Recall that hydrogen bonding occurs where we have a highly electronegative atom such as O or N directly bonded to hydrogen. (See: The Four Intermolecular Forces And How They Affect Boiling Points)
Examples are water (H2O), alcohols (such as CH3OH , CH3CH2OH, t-BuOH) carboxylic acids (such as acetic acid) and even ammonia (NH3).
Quick N’ Dirty Tip: Solvents with OH or NH groups are polar protic solvents
Hydrogen bonding is directly responsible for the high boiling points of solvents such as water and ethanol; the partial positive charges on hydrogen are attracted to the partial negative charges on the electronegative atoms.
This is also why water is such an excellent solvent for charged species such as halide ions; hydrogen bonding solvents surround negatively charged ions like a jacket.
Polar Protic Solvents “Cling” To Nucleophiles via Hydrogen Bonding, And Nucleophilicity Goes Up As We Go Down The Periodic Table
Hydrogen bonds to nucleophiles make the nucleophile less nucleophilic!
- This “jacket” of solvent molecules – much like a protective crowd of security personnel – means that these anionic nucleophiles do not have the freedom of action they would normally have in the absence of clingy hordes of solvent molecules.
- The ability to form hydrogen bonds is highest for small, highly electronegative ions such as fluorine and decreases as ions get larger (and the charge is more diffuse) down a column of the periodic table.
- This means that in polar protic solvents, the nucleophilicity of halide anions increases as we go down the periodic table.
- So the order of nucleophilicity for halides in polar protic solvents is I(-) > Br (-) > Cl (-) > F (-) . Similarly it should be HSe(-) > HS(-) > HO (-) in the oxygen column (chalcogens)
Polar Aprotic Solvents Do Not Hydrogen-Bond With Nucleophiles, And Therefore Nucleophilicity In These Solvents Correlates With Basicity
Now let’s talk about polar aprotic solvents; polar aprotic solvents are polar enough to dissolve charged species (such as halide ions) but do not donate hydrogen bonds.
This means that in solvents such as DMSO, DMF, acetone, or acetonitrile, nucleophilicity correlates much better with basicity (and bond strength, as C-F > C-Cl > C-Br > C-I ) – and therefore nucleophilicity decreases as we go down the periodic table.
So what’s the bottom line when it comes to SN1/SN2/E1/E2?
The bottom line is this:
Quick N’ Dirty Rule #5:
- Polar protic solvents tend to favor elimination (E2) over substitution (SN2)
- Polar aprotic solvents tend to favor substitution (SN2) relative to elimination (E2)
Notes
Struggling with SN1/SN2/E1/E2? Our Org 1 Summary Sheets (PDF) contain a full-page flowchart on deciding SN1/SN2/E1/E2, as well as two more pages summarizing substitution and elimination reactions, in addition to many other Org 1 topics.
Check them out now!
Relating to the last sentence I said… Alcohol Is a polar protic solvent… (but it’s less polar than water… and the textbook kept saying that a less polar solvent favours elimination…)
My last sentence more fittingly refers to the Williamson synthesis.
Sorry for the several comments, I am trawling this site for my chemistry final in 2 weeks.
Oh a couple of other people have asked about the alcoholic and aqueous KOH already-
I’ve found the source with the explanation:
https://flic.kr/p/2ogxqFf
The book says that alkoxide ion prefers to be a base rather than a nucleophile for steric reasons, as opposed to OH- which can go in for an SN2 easier.
The textbook is Pradeep’s New Course Chemistry for Class 12
So yeah, exception to polar protic solvents favouring E2 over SN2.
The second reaction tripped me up because ethoxide ion in ethanol is the usual reagent for the Williamson ether synthesis, which is an SN2 reaction.
(Not on topic, but my textbook also had something confusing about whether it’s better to have a tertiary alkyl halide substrate or a tertiary alkoxide nucleophile for that SN2 reaction…I may ask about it on the comments section of that page)
But as you say it’s not that the SN2 reaction won’t occur at all, it’s that the E2 reaction will occur in greater proportion, I guess. The Williamson page said how we get alkoxide ion from alcohol in situ with Na or NaH, and if the alkoxide ion is given beforehand, we could use a polar aprotic solvent to prevent elimination from competing.
Also, in my course we hear that aqueous KOH leads to an SN2 reaction while alcoholic KOH leads to an E2 reaction. I heard the explanation is that OH- is a good nucleophile for an SN2 reaction, and when there’s alcohol and KOH the OH- can deprotonate the alcohol to get alkoxide ion, which is a stronger base than a nucleophile, so takes a proton for an E2 reaction. Does this hold up?
Usually in the Williamson the substrate is a primary alkyl halide. When the substrate is secondary, elimination will compete.
F is a very weak nucleophile because it would rather take a H+ and leave than attack an electrophilic center. This article is incorrect in this regard. This is a special exception.
Fluoride ion (not HF) is perfectly capable of acting as a nucleophile – e.g. TBAF (tetrabutylammonium fluoride)
Can one claim that the polarity of the solvent affects also E1/SN1 ratio?
Both pathways form the same carbocation as the product of the rate-determining step. But in the second step, the solvent can interact with the (usually not charged) base-nucleophile. The higher the solvent’s polarity, the stronger the interaction (that lowers the nucleophilicity more than basicity).
Are these interactions negligible here? Does it have empirical support?
Generally, what effect the solvent has in E1/SN1 reactions?
A little doubt, if solvent consists of Ch3O- ions and Ch3Oh the reaction will be Sn1 or Sn2?
CH3O(-) is a strong nucleophile, and therefore it will be either SN2 or E2.
My question is if polar protic solvents favour E2 over SN2 then why does a alkyl halide when reacted with aq KOH give alcohol as a major product , even though H20 is a more stronger protic solvent than alcoholic media.Even if it isn’t strong , it is still protic so it shouldn’t give SN2 , but it does !!🤔
Primary or secondary alkyl halide? Because if it’s primary, it should have been clear from the start that it’s an SN2. The real question is what happens with secondary alkyl halides. There is vast inconsistency in how instructors handle this, so I strongly suggest SN2 for polar aprotic solvents, and E2 for polar protic.
Thanks a lot !
Glad you found it helpful.
Thanks a lot James for giving us concepts for free what our Professors themselves are confused about. Will you please do us a favour by creating a post on ( though not related to this topic) electrophilic aromatic substitution in disubstituted benzene rings…. I am confused over the exceptional cases.
EAS in disubstituted rings: https://www.masterorganicchemistry.com/2018/03/19/eas-disubstituted-benzenes/
My prof told me that polar protic solvent will favour sn1 reaction because it solvates the carbocation thus increasing the stability. Any comment?
Yes, that is the case, and is consistent with the text of this post.
But what if CN WITH POLAR PROTIC SOLVENT AND NO HEAT
Anytime you see the cyanide anion you’re likely looking at a nucleophilic substitution.
Thank you soo much ! This website has been soo helpful!!
Glad you liked it!
A question on number 2 above – why isn’t E1 with hydride shift possible?
Because of the presence of the strong base KOEt.This will lead to an E2 reaction. If it were just EtOH, then yes, E1 with hydride shift is a possibility.
than why does water, even though being a polar protic solvent favour sn2 mechanism.
Example:
CH3ChHBrCHH3 +OH-(AQ.) = CH3CHOHCH3 (SN2)
CH3CHBrCH3 + OH-(ALCOHOLIC) = CH3CHCH2 (E2 ELIMINATION)
Where are you getting this from?
is it true that polar aprotic solvents are not used in SN1 reactions because some of them can react with the carbocation intermediate and give an unwanted product. Rather, polar protic solvents are preferred ? how eh ?
Polar aprotic solvents cannot react with the carbocation intermediate. Rather, polar protic solvents are used because they are generally more polar than polar aprotic solvents.
I am confused. I thought protic solvents favored sn1/e1 over sn2/e2 vs aprotic solvents favoring e2/sn2 rxns over e1/sn1. Why is that you have compared sn2/e2 here for “protic” solvents than sn1/e1?
I encourage you to go back and read the two previous posts. This is the third in a series of posts on how to deduce SN1/SN2/E1/E2 by asking 4 questions. In the first post we looked at the substrate, and said that tertiary substrates were most likely to undergo sn1/e1 and primary substrates the least likely to undergo sn1/e1. In the second post, we examined the nucleophile, and said that charged nucleophiles/bases would favor sn2/e2 and uncharged nucleophiles would favour sn1/e1. Just by answering those two questions, you can determine whether the reaction will be sn1/e1 or sn2/e2 for most cases. In this third post we show how sn2/e2 can be distinguished in the case of secondary alkyl halides: polar protic solvents tend to favor e2 moreso than sn2.
This post was very helpful, but an answer from my lecturer about this confused me. The reaction was a primary haloalkane with NaOH, with water as the solvent. I thought that since water is obviously a polar protic solvent, an E2 reaction would be favoured, but my lecturer told me that the reaction is Sn2. Now I’m really confused. Any explanation?
If it’s a primary alkyl halide, it’s almost certainly SN2. the only exception would be if you have an extremely bulky base/nucleophile like t-BuO- , and then, possibly, you might get elimination (e2)
Hi! I’m a sophomore chem major who is currently in organic chemistry, and I just wanted to say thanks for this resource! I studied this stuff for ages but couldn’t get it to all line up correctly in my head. This gave me a great frame of reference and an excellent systematic approach with which to approach these problems, which was just what I needed. ^^ Thanks again! You may have earned me ten points on my final!
Thanks Kayleigh! So glad you’ve found this website useful! James
Dear James,
I’ve been getting conflicting information from different sources, or maybe I’m just not interpreting it correctly. From what you say here, when the situation is set up for a bimolecular reaction, a polar aprotic solvent will favor SN2 and protic will favor E2. However I have also seen sources that list polar aprotic as a “good” solvent for E2, and this makes sense to me, because with a protic solvent wouldn’t you run the risk of protonating the base before it can abstract the beta-H?
I think the same question! But I guess the effect of polar protic solvents on the nucleophiles will be much more severe than that on the bases. Is that right?
Yes! The nucleophile is attacking carbon here (specifically orbitals on carbon) which are much more difficult to access (and thus sensitive to steric hindrance) than the 1s orbital on a hydrogen [ie when something acts as a Bronsted acid]
Thank you very much for this. Honestly, I chose this over Khan Academy (mainly because I’m in quite a rush to learn this before an exam and you gave a wonderful yet concise explanation). I honestly preferred this over Khan Academy and even the 2nd language book for organic chemistry. I definitely plan on recommending this to classmates and even to my professor so that he may recommend it to future students. Cheers!
Yes!!!!! I completely agree!!! Love this site and I have already told my classmates about it! Thanks so much!!! So helpful and I love how you use funny pictures and explanations, stuff sticks better that way! Orgo final tomorrow!
great blog, I have learned a lot, thanks for all of your hard work, if I may ask a question though, I am sure I am just missing this but WHY are polar protic solvents preferred for E2? I would think that there are a bunch of H+ floating around and for E2 we need a strong base, that this would bind to the protons before ever reaching the nucleophile?
My thoughts exactly!
It’s not so much that polar protic solvents are preferred for E2, it’s that polar protic solvents are less favoured for SN2. Polar protic solvents lead to hydrogen bonding of the nucleophile, which you can think of as making the nucleophile more “sterically hindered”. Since nucleophilic substitution is more sensitive to steric hindrance than acid-base reactions (i.e. attacking the H of the C-H bond) a polar protic solvent will tend to decrease the rate of substitution (relative to elimination) .
In a situation where both reactions compete (e.g. secondary alkyl halide with a strong base like NaOH) this can be the difference between favouring substitution (SN2) vs favouring elimination (E2).
My Organic Chem Prof said this is wrong. Polar protic solvents slow down second order reactions because Protic solvents weaken bases and Nucleophiles.
E2 and Sn2 are favoured by polar aprotic i think that’s a mistake question 2 can’t be E2 it is E 1
Please post the next installment soon!!
2 comments :)
-I think it may be important to say that in the truly ‘toss up’ cases (like #2 above), if we ran the reaction and analyzed the results by, say, GC/MS (something we do in our ugrad OChem labs… tho not for this reaction), we’d probably see BOTH E2 and SN2 products… but with protic solvents the E2 is the major organic product, and with aprotic solvents the SN2 is the major organic product. It’s not as if one solvent gives 100% of elimination, and another solvent gives 100% of substitution.
-I also have my students analyze the reactions in this way. What does the nucleophile tell us? What does the electrophile tell us? What does the solvent tell us? I use these to generate ‘evidence for’ a mechanism, or ‘evidence against’ a mechanism.
That’s my comment. I would hesitate to use a phrase like ‘rule out’ since psychologically that’s exclusionary thinking. I could conjure up an example where the evidence from the nucleophile ‘rules out’ an SN2 mechanism… but based on the other evidence SN2 is exactly the pathway (off the top of my head, KOtBu + MeBr). But if I tell myself a Big Bulky Base ‘rules out’ SN2, I exclude that possibility mentally. ‘Evidence against’ mentally tells me this is not my first choice… but it’s not impossible.
(Also, I tell my students solvent can sometimes lean us in one direction or another, but solvent should never be used as ‘evidence against’ a particular mechanism… especially because our SN2 lab uses ethanol as the solvent!)