Comparing the SN1 and SN2 Reactions
Last updated: February 6th, 2021 |
Hey! You can now download a free 1-page Summary Sheet of SN1 vs SN2 reactions containing all the material on this series of blog posts here: Summary Sheet – SN1 vs SN2
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
- (Advanced) References and Further Reading
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.
- 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)
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.
- 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.
- 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.
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
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.
- 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
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
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
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
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
- 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
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
- 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
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.