Substitution Reactions
Comparing the SN1 and SN2 Reactions
Last updated: February 3rd, 2023 |
Comparing the SN1 and SN2 Reactions
Since we’ve gone through the different factors that impact the SN1 [see post] and SN2 [see post] reactions, it’s worthwhile to review and summarize the different factors behind each of these two reactions.
Table of Contents
- But First: The Story Of The Cats And The Comfy Chair
- A Chart Comparing The SN1 vs SN2 Reactions
- SN1 vs SN2: The Mechanism For The SN2 Is Concerted. The Mechanism Of The SN1 Is Stepwise
- The Big Barrier For The SN2 Is Steric Hindrance. The Big Barrier For The SN1 Is Carbocation Stability
- For SN2, The Rate Of Reaction Increases Going From Tertiary To Secondary To Primary Alkyl Halides. For SN1 The Trend Is The Opposite
- The SN2 Tends To Proceed With Strong Nucleophiles. The SN1 Tends To Proceed With Weak Nucleophiles
- The SN2 Is Favored By Polar Aprotic Solvents. The SN1 Tends To Proceed In Polar Protic Solvents
- When A Stereocenter Is Involved The SN2 Reaction Provides Inversion Of Stereochemistry. The SN1 Reaction Leads To A Mixture of Retention and Inversion
- Back To The Cats
- Notes
- (Advanced) References and Further Reading
1. The Cats And The Comfy Chair
But first – have you ever heard the story of the cats and the comfy chair?
Cat #1 finds Cat #2 on his comfy chair and wants to sit. He has two options.
- He can wait for Cat #2 to leave, and then sit in the comfy chair.
- He can kick the Cat #2 out of his comfy chair.
Think about that for a second. In the meantime, let’s compare the SN1 and the SN2.
2. A Chart Comparing The SN1 vs SN2 Reactions
3. The Mechanism For The SN2 Is Concerted. The Mechanism Of The SN1 Is Stepwise
- The SN2 reaction is concerted. That is, the SN2 occurs in one step, and both the nucleophile and substrate are involved in the rate determining step. Therefore the rate is dependent on both the concentration of substrate and that of the nucleophile.
- The SN1 reaction proceeds stepwise. The leaving group first leaves, whereupon a carbocation forms that is attacked by the nucleophile.
4. The Big Barrier For The SN2 Is Steric Hindrance. The Big Barrier For The SN1 Is Carbocation Stability
This is the most important thing to understand about each reaction. What’s the one key factor that can prevent this reaction from occurring?
- In the SN2 reaction, the big barrier is steric hindrance. Since the SN2 proceeds through a backside attack, the reaction will only proceed if the empty orbital is accessible. The more groups that are present around the vicinity of the leaving group, the slower the reaction will be. That’s why the rate of reaction proceeds from primary (fastest) > secondary >> tertiary (slowest)
- In the SN1 reaction, the big barrier is carbocation stability. Since the first step of the SN1 reaction is loss of a leaving group to give a carbocation, the rate of the reaction will be proportional to the stability of the carbocation. Carbocation stability increases with increasing substitution of the carbon (tertiary > secondary >> primary) as well as with resonance.
5. For SN2, The Rate Of Reaction Increases Going From Tertiary To Secondary To Primary Alkyl Halides. For SN1 The Trend Is The Opposite
- For the SN2, since steric hindrance increases as we go from primary to secondary to tertiary, the rate of reaction proceeds from primary (fastest) > secondary >> tertiary (slowest).
- For the SN1, since carbocation stability increases as we go from primary to secondary to tertiary, the rate of reaction for the SN1 goes from primary (slowest) << secondary < tertiary (fastest)
Remember that SN1 and SN2 reactions only occur for alkyl halides (and related compounds like tosylates and mesylates). If the leaving group is directly attached to an alkene or alkyne, SN1 or SN2 will not occur!
6. The SN2 Tends To Proceed With Strong Nucleophiles. The SN1 Tends To Proceed With Weak Nucleophiles
- The SN2 tends to proceed with strong nucleophiles; by this, generally means negatively charged nucleophiles such as CH3O(–), CN(–), RS(–), N3(–), HO(–), and others.
- The SN1 tends to proceed with weak nucleophiles – generally neutral compounds such as solvents like CH3OH, H2O, CH3CH2OH, and so on.
7. The SN2 Is Favored By Polar Aprotic Solvents. The SN1 Tends To Proceed In Polar Protic Solvents
- The SN2 reaction is favored by polar aprotic solvents – these are solvents such as acetone, DMSO, acetonitrile, or DMF that are polar enough to dissolve the substrate and nucleophile but do not participate in hydrogen bonding with the nucleophile.
- The SN1 reaction tends to proceed in polar protic solvents such as water, alcohols, and carboxylic acids, which stabilize the resulting (charged) carbocation that results from loss of the leaving group. These also tend to be the nucleophiles for these reactions as well.
8. When A Stereocenter Is Involved The SN2 Reaction Provides Inversion Of Stereochemistry. The SN1 Reaction Leads To A Mixture of Retention and Inversion
- Since the SN2 proceeds through a backside attack, if a stereocenter is present the SN2 reaction will give inversion of stereochemistry.
- By contrast, if the SN1 leads to the formation of a stereocenter, there will be a mixture of retention and inversion since the nucleophile can attack from either face of the flat carbocation.
9. Back To The Cats
So does the story about the cats and the comfy chair make sense now?
- In the SN2, the nucleophile (Cat #1) forms a bond to the substrate (comfy chair) at the same time the leaving group (Cat #2) leaves.
- In the SN1, the leaving group (Cat #2) leaves the substrate (comfy chair), and then the nucleophile (Cat #1) forms a bond.
If this makes sense, you might be ready for the Quick N’ Dirty Guide to SN1/SN2/E1/E2 reactions. Otherwise, join us for our next post when we discuss rearrangement reactions.
Don’t forget – you can download a free 1-page Summary Sheet of SN1 vs SN2 reactions containing all the material on this blog post here: Download SN1 vs SN2 Summary Sheet PDF
Notes
Cat Illustration by my talented cousin, political cartoonist Graeme MacKay
UPDATE . The most perfect cat video ever. Thanks to Alex Roche (Rutgers U.) for sending.
(Advanced) References and Further Reading
- Reaction kinetics and the Walden inversion. Part VI. Relation of steric orientation to mechanism in substitutions involving halogen atoms and simple or substituted hydroxyl groups
W. A. Cowdrey, E. D. Hughes, C. K. Ingold, S. Masterman, and A. D. Scott
J. Chem. Soc. 1937, 1252-1271
DOI: 10.1039/JR9370001252
The points listed in the summary are worth reading for understanding what influences the SN1 and SN2 pathways. - Mechanism of substitution at a saturated carbon atom. Part XXVI. The rôle of steric hindrance. (Section A) introductory remarks, and a kinetic study of the reactions of methyl, ethyl, n-propyl, isobutyl, and neopentyl bromides with sodium ethoxide in dry ethyl alcohol
I. Dostrovsky and E. D. Hughes
J. Chem. Soc. 1946, 157-161
DOI: 10.1039/JR9460000157
Table I in this paper shows the reduction in reaction rate for the SN2 reaction of R-Br with OEt- when R goes from methyl -> ethyl -> n-propyl -> isobutyl -> t-amyl. This can be attributed to sterics, as backside attack of the substituted carbon becomes increasingly challenging. - Mechanism of substitution at a saturated carbon atom. Part III. Kinetics of the degradations of sulphonium compounds
John L. Gleave, Edward D. Hughes and Christopher K. Ingold
J. Chem. Soc. 1935, 234-244
DOI: 10.1039/JR9350000236
This is a useful paper – in the beginning the terms “SN1” and “SN2” are introduced and defined, and Figs. 1 and 2 depict how the two mechanisms can compete depending on the structure of the substrate. - Influence of poles and polar linkings on the course pursued by elimination reactions. Part XVI. Mechanism of the thermal decomposition of quaternary ammonium compounds
E. D. Hughes, C. K. Ingold, and C. S. Patel
J. Chem. Soc. 1933, 526-530
DOI: 10.1039/JR9330000526
At the end of this paper, the authors make an important point: “When the various series can be more fully filled in, what has been described as a “ point ” of mechanistic change will probably appear as a region, and thus, just as with reaction (A), we now generalise the original conception of reaction (B) by the contemplation of a range of mechanisms, (Bl)-(B2), both extremes of which have been experimentally exemplified”. Basically, the SN1 and SN2 mechanisms as taught are two extremes of a continuum, and in practice most reactions lie somewhere in between. - Mechanism of substitution at a saturated carbon atom. Part IX. The rôle of the solvent in the first-order hydrolysis of alkyl halides
Leslie C. Bateman and Edward D. Hughes
J. Chem. Soc. 1937, 1187-1192
DOI: 10.1039/JR9370001187 - The Common Basis of Intramolecular Rearrangements. VI.1 Reactions of Neopentyl Iodide
Frank C. Whitmore, E. L. Wittle, and A. H. Popkin
Journal of the American Chemical Society 1939, 61 (6), 1586-1590
DOI: 1021/ja01875a073
An early paper demonstrating that SN1 reactions can be induced by reaction of an alkyl halide with silver salts. In this case, the neopentyl cation quickly rearranges to the significantly more stable t-amyl cation, and those products are obtained. - Reaction kinetics and the Walden inversion. Part I. Homogeneous hydrolysis and alcoholysis of β-n-octyl halides
Edward D. Hughes, Christopher K. Ingold and Standish Masterman
J. Chem. Soc. 1937, 1196-1201
DOI: 10.1039/JR9370001196 - Reaction kinetics and the Walden inversion. Part IV. Action of silver salts in hydroxylic solvents on β-n-octyl bromide and α-phenylethyl chloride
Edward D. Hughes, Christopher K. Ingold and Standish Masterman
J. Chem. Soc., 1937, 1236-1243
DOI: 10.1039/JR9370001236
These two papers examine reactions of 2-octyl halides in an attempt to see if pure SN1 or SN2 pathways on the same substrate can be favored simply by varying the reaction conditions.
Ah, I’m glad it isn’t the “hobo on the bench” analogy anymore, thanks for being considerate enough to change it to cats
I love how they use their tails to balance in the video!
Hi,thanks for the post. But here is question.why protic solvent are favored by SN1 and vice versa?
In SN1 reactions the rate limiting step is loss of leaving group to give a carbocation. Polar protic solvents have a higher dielectric constant and can stabilize the resulting carbocation species that results from ionization. Secondly, polar protic solvents are often the nucleophiles in these reactions and can be neutralized through deprotonation.
In SN2 reactions the rate limiting step is attack of the nucleophile at the alkyl halide. Using a polar aprotic solvent results in a more free nucleophile (free from hydrogen bonding) resulting in a higher reaction rate than if a polar protic solvent were used.
What should i do when both strong and weak nucleophile are present in the reaction??? Should i proceed through SN1 OR SN2???
If the substrate is primary, it will be SN2, since the reaction rate will be faster with a stronger nucleophile.
Nicely Explained really impressed…
**Now, gaining confidence in organic chemistry**
THANK YOU ,
plzz make more blogs on organic chemistry thank you once again…
Cool, thanks for letting me know Sanket. So what could be better about the site?
Why reactivity in SN1 reaction is directly proportional to the on stability of carbonation ? And how ?
Please respond me.
Wonderfully describe. I am a chemistry teacher; I teach that topic to my students as per your article. I like your way of understanding. Thank you so much for sharing your this information about two reactions.
Your blog posts are so helpful, please keep doing what you’re doing! Also love the summary sheet for this subject, super helpful as well.
Glad you found it useful Ky!
Wow.this is very useful site for everyone but please add reactions with mechanisms..
Glad you find the site useful Shailenda!
Is it possible a trans compound react in a SN2 reaction? (eg.trans -1-iodo-4-ethylcyclohexane and methoxide ion)
Or just tehe cis ones react because its possible ” the carbon bonded to the leaving group is attacked by the nucleophile on its back side”? How do we know if its possible to have the mixture of the 2 configurations?
It’s completely possible. With cyclohexanes, the important thing to note is that the leaving group must be axial in order for the SN2 to occur.
Your website is a Godsend. Thank you!
Thanks Blake!
This is very impressive. I’m having a Msc. In applied organic chemistry. And it helped me to explain this to my students. The cat example is nice. Thank you.
Ha! Thanks Shiral!
Just wanna say that I already bought all your cheat sheets and it is a big help!! Thank you for clear explanations :)
Thank you so much for supporting the site Cacia!
Good explanation. Specially the story of the cats and the relation with the reactions is very good. Thank you
Thank you very much for your views regarding the Sn1 and Sn2 reaction……..This will help me alot…..
Thank you so much for great revision of Sn1 and Sn2 reactions .!
Really helpful, especially with the cartoon illustrations. Thank you
Thank my cousin Graeme for that, ha!
I know primary substrates favor SN2 and E2 reactions – but my book talks about how a primary carbocation can form in an SN1 reaction if it is accompanied by a simultaneous rearrangment. The book specifically says it can happen as a result of a methyl shift. My question is: can it also happen via a simultaneous hydride shift? Or only through a methyl shift? My teacher has given us some problems to work through that would require a primary carbocation to form through a hydride shift, and I just want to make sure that is feasible.
Yes, it can certainly happen through a simultaneous hydride shift.
SN1 mechanism — the rate of reaction depends on substract. It is independent of nucleophile. So it can show ist order mechanism (unimolecular). It is more than 1 step mech.
Most stable carbo cation will favour sn1 mech.
Polar protic solvent will favour
Best solvolysis can favour
More steric hindered can show sn1 mech.
What about the effect of the polar aprotic solvent on the rate of rxn? That’s a valid question, and it’s unfortunately not addressed.
I’d love to see direct data on that. At the moment I haven’t been able to find anything that would provide a direct comparison. If I do, I’ll put it in.
The link for the exercises is broken :(
I’ve taken it down. ASU has changed their website.
Studying for my DAT and this gave so much of everything I needed and nothing I didn’t! Thank you!
Glad to hear it, Tye!
thank you so much this was the best help i could find on the subject – turned me around on understanding substitution rxns!!
why tertiary alkyl halides prefer nucleophilic reactions more easily via sn1 mechanism ?
Carbocation stability is the brief answer.
Personally, I think steric effects should also be considered.
Even with the help given, I am having trouble with how kinetics can be used to tell the difference between SN1 and SN2.
Double the concentration of substrate and double the concentration of nucleophile. If the reaction is first order overall, the reaction rate will only double. If the reaction rate is second order overall, the reaction rate will quadruple.
Great explanation.. simple, precise and easy to understand. thanks a bunch :)
what is the reason for the recemized product in SN1 reaction? to be precise with the question.. the no. of front side and back side attack is same. why it doesn’t differ?
Great analogy and summary! Thank you so much! I shall definitely be reading more of your work!
But I am little bit confused in trend of nucleophilisity of halogens in polar aprotic solvents.
Thank you
Thanks Peaches!
Thanks for this great explanation! If you didnt know whether the reaction was Sn1 or Sn2, what physical property could you use to distinguish them?
If it’s a chiral secondary alkyl halide, then you could use optical rotation to distinguish them.
you are great!! Thank u very much
Which one allows for a better control over the configurations of products SN1 or SN2?
SN2, of course, because it is stereospecific.
Here what do you mean by inversion of configuration.Is it relative or absolute
Relative.
It is very un-PC to be using homeless people in this analogy, imagine if you changed the analogy to a black person on the bench and a white person wanting to sit down (quite offensive). You have a cartoon of two cats wanting to sit in a basket, why not just use that analogy; how about just two people, one sitting on the bench and the other wanting to sit on the bench, no socio economic issues implied. Apart form that very useful information.
This analogy is fab…Its so clever and easy to remember! Thank you so much…I made use of it in my oxford interview!
I like the article very much, but I would draw your attention to the paragraph
”The dependence of rate on the substrate”
Given that for the Sn1 reaction the big barrier is carbocation stability,that is to say that
the carbocation stability increases with increasing substituents on the carbon
( tertiary>secondary>> primary……instead of saying that resonance is a factor,
I would like to make this clearer by saying that tertiary groups are EWG groups
and because they are electron withdrawing they make the carbocation a better
electrophile.This in turn renders the cation strong enough to react with a weak
nucleophile.
Note….the above is not a correction ..just for clarity
Hey in SN1 why tertiary is more reactive though it is relatively stable
The stability of the tertiary carbon allows it to be a stronger carbocation compared to primary carbon which is very unstable as it the carbocation formed would be unstable. If the carbocation is unstable then it can just react in reverse with the leaving group and the reaction wouldn’t proceeed. So reactivity of SN1 reaction increases as the groups around carbon increase
Hello, I have a question about steric hindrance for an Sn2 reaction. Specifically with cycloalkanes. I thought that the higher the number of carbons a cycloalkane has (the more corners it has) the more likely it was for a nucleofile to attack it from the inside. In my chemistry book on the other hand there’s a table with relative reactivity. And it puts Cyclopentane (more reactive) before Cyclohexane. Why doesn’t this one follow the rule? Many thanks in advance! Love your website!
Hi – not sure exactly what you mean by the “inside” . In the case of cyclopentane and cyclohexane, the ring isn’t big enough for the nucleophile to fit in the “inside” of the ring.
Hard to say re: cyclopentane vs. cyclohexane. I can’t imagine there’s a huge difference. cyclohexane has the barrier of requiring the leaving group to be axial.
Could it have something to do with angle strain? increased angle strain in the cyclopentane could lead to a higher energy of the starting materials, and thus, a lower barrier to cross to undergo an SN2 reaction?
Thank you so much. I love organic chemistry but it’s very hard at times. My professor talks waaay too fast so I’m missing out on important details. Love this piece of text…
This is absolutely wonderful resource! I understand it now, and it’s nowhere as complex that my lecturer made it look!
Thanks so much!
Glad you found it useful Michal!
Awesome explaination with some simple but effective intellectual ideas!!!!!!……
What’s with the hobo story huh?
Am a student taking organic chemistry at Kenyatta University-Kenya, this is so helpful to me
Thank You so much.
i need the example and difference btween SN1 and SN2
i need example for both SN1 and SN2 to differentiate between them
Thanks for the great explanation. I have a question about the rate of Sn1 reaction, how would a primary carbocation that can undergo an alkyl shift to become tertiary fit in, I know that a primary carbocation is slower than secondary, but the shift would stabilize it. Or does the shift take enough time that it wouldn’t end up being faster than a secondary?
If talking about the rate of formation of a free carbocation, formation of primary carbocations is slower than that of secondary. However, it is very rare that primary carbocations form – when alkyl shifts occur to a primary carbon, it is usually a concerted rearrangement mechanism that doesn’t strictly go through a free carbocation. That makes it difficult to strictly compare the rates since they occur through different mechanisms.
Thank you so much for the nice explanations. Your explanations helped me get several difficult points cleared.
Thanks for the write up. Truly helpful.
all of these come out in our quiz. this is very accurate and well explained (;
Glad you were well prepared!
I’m studying Organic Chemistry from Clayden, but I really like this website to have some extra background, mnemonics and nice summaries.
I wanted to check the exercises pointed out at the end of this lecture, but the link gives an error (404 – File or directory not found.).
Oh, thank you!
This was so helpful!! I love how simple you break it down. THANK YOU SO MUCH!!!
in General chemistry, there is chapter about kinetics. If you guys are confused about rate determining steps, I would encourage reading that chapter or review it thoroughly. I will try to explain it here a little.
1) SN1 ,
Since the rate determining steps depend on the carbocations, so we look at 1st order kinectic , which can be found by.
k= [Electrophile] , where k is rate of reaction , as the the concetration of electrophile goes down, the reactions is reaching towards end, or stopping or decreasing, whatever you think is appropriate at given electrophile concentration.
2) SN2, you will need good Nuceophile and electrophile, thus intermediate stage is 5 ligands, and conculsion is four , sp3 to sp3, but remember it does have 5 ligands, intermediate, which is VSPER Theory, 5 ligands, is Trigonal bipyramidal.
K = [electrophile] [nucelphile]
k is rate of the reaction, depends on both electrophile and nucelophile, so it is second order, 1 step, fast reaction.
So as the both increases the reaction rate will go up, if one goes down, it is kind of like limited reagents , which one exhaust first etc, if one is exhausted, does not matter, how much you have the other, the reaction WILL NOT Proceed.
So I would say, conclusion to this summary, Relate Both, general chemistry and organic chemistry, it will make MUCH MORE SENSE, and you will never forget :)
Sir Thank you, I was looking for this article. You’d explained it very nice. Even my teacher couldn’t.
Sir will you please explain me why alpha-halocarbonyl compounds are not much reactive with Sn1 mechanism?
The carbocation that forms is destabilized by the adjacent electron withdrawing C=O group, making this a very unstable carbocation.
Thank you sir, it was very helpful.
Wow – such a good website and so well explained thank you sooooo much. Way better then my lectures :)
This was so outrageously helpful. I will definitely be using this site for much of my orgo work this year.
Thank you, very glad to hear it.
in problem 10 you mention that allylic halide is more reactive and rxn is SN2. Allylic system are more reactive becoz of resonance for which there must be formal charge intermediate as in SN1 not SN2. So why is it that without any charged intermediate the left bromine is favored.
Thanks very much, this was a great review of the topic!
Hey, just a question here. I know that the branching of the base/nucleophile will direct the reaction towards E2 or Sn2, where steric hinderance of the base/nu: will most likely lead to an E2 rxn, b/c the H+ protons are more accessible.
Does branching of the base/nucleophile have any affect on E1 or Sn1?
I do know that branching of the substrate helps stabilize the carbocation…
Since the rate-determining step of SN1 and E1 reactions is formation of the carbocation, an event independent of the nucleophile, branching of the base/nucleophile does not have a significant effect on these reactions.
Well actually the branching of a base/nucleophile can have an effect. Lets think about the carbocation during its transition state. It positively charged and thus in an ideal world it would want to be stabilised, thus reducing its energy. If you have large bases this can almost protect the transition state, providing mixed effects with the stabilisation of the cation being good, the steric hindrance for the nucelophile being bad.
For the SN2, since steric hindrance decreases as we go from primary to secondary to tertiary, the rate of reaction proceeds from primary (fastest) > secondary >> tertiary (slowest).
*Shouldn’t this be “steric hindrance increases as we go from *
Fixed. thanks for pointing that out!
actually steric hinderence increases as we move from primary to secondary. hope this will help….
Some of my students challenged me to do the upcoming class in haiku. Since a fractonal distillation lab is pretty dull to supervise after everyone is up and running, I put the introduction to SN1 in haiku format. (Each done on a powerpoint slide with a pretty background…)
Leaving group breaks off
Forming carbocation
SN1, first step
very reactive
intermediate species
they need electrons
tertiary good
hyperconjugation helps
resonance does too
add more Nu? No help.
the rate is independent
that’s kinetic proof
climbing two mountains
reaction coordinate
C+ is high pass
how do you decide?
SN1 or SN2
there are many factors.
Nicely done!
Crystal clear. Beautiful analogy. Here comes James, frighten the poor hobo away so he can seat himself on the bench. James must be big and intimidating.
I can’t claim credit for the analogy – I heard it secondhand. But it’s effective isn’t it?
It is and thanks for making it comprehensible. I v already covered this with my students but I ll use this to refresh them again.
im a little confused with the analogy though. according to the purpose of the lucas test (which determines if the substrate is primary, secondary or tertiary) tertiary rxns undergoing sn1 mechanisms are faster than secondary rxns undergoing sn1 rxns and yet faster than primary substrates undergoing sn2 mechanisms. it seems to me like kicking the hobo off the bench (sn2) would be a lot faster than waiting for him to leave (sn1). flip flopped from the actual speeds of the mechanisms. can u elaborate on the analogy. b/c i would rlly love to use something like that to go by on the MCAT. thanks