Substitution Reactions

By James Ashenhurst

The SN1 Mechanism

Last updated: December 18th, 2020 |

The SN1 Reaction Mechanism

Previously we saw that there are two important classes of nucleophilic substitution reactions, which differ in their rate laws, dependence on substitution pattern, and the stereochemistry of the products.  Having gone through the SN2 mechanism, today we’ll circle back and look at the second important mechanism for substitution reactions. It’s called the SN1 mechanism.

Let’s look at what the data tells us first.

Table of Contents

  1. Stereochemistry Of The SN1 Reaction: A Mixture of Retention and Inversion is Observed
  2. The Rate Law Of The SN1 Reaction Is First-Order Overall
  3. The Reaction Rate Increases With Substitution At Carbon (Tertiary >> Secondary > Primary)
  4. The Stepwise Reaction Mechanism of the SN1 Reaction
  5. Notes
  6. (Advanced) References and Further Reading

1. Stereochemistry Of The SN1 Reaction: A Mixture of Retention and Inversion is Observed

If we start with an enantiomerically pure product, (that is, one enantiomer), these reactions tend to result in a mixture of products where the stereochemistry is the same as the starting material (retention) or opposite (inversion). In other words, some degree of racemization will take place.

sn1 reaction substitution proceeds with mix of retention and inversion racemization

Compare this to the SN2, which always results in inversion of stereochemistry! Clearly something different must be going on here.

2. The Rate Law Of The SN1 Reaction Is First-Order Overall

We can also measure the rate law of these reactions. When we do so, we notice that the rate is only dependent on the concentration of the substrate, but not on the concentration of nucleophile.

rate law of sn1 reaction is unimolecular only depends on concentration of substrate

Weird. Remember that the SN2 depends on both. Why might this reaction only depend on the concentration of substrate?

3. The Reaction Rate Increases With Substitution At Carbon

When we subtly change the types of substrates (e.g. alkyl halides) we use in these reactions, we find that tertiary substrates (for instance, t-butyl bromide) are considerably faster than secondary alkyl bromides, which are in turn faster than primary*.

sn1 reaction rate is fastest for tertiary and slowest for primary and methyl

Compare that to the case for SN2, where primary was faster than secondary and tertiary hardly reacted at all. Mysterious!

4. The Stepwise Reaction Mechanism of the SN1 Reaction

The best hypothesis we have for this reaction is the stepwise mechanism. In the first step, the leaving group leaves, forming a carbocation. In the second, a nucleophile attacks the carbocation, forming the product.

 

stepwise mechanism of sn1 reaction showing loss of leaving group giving carbocation followed by attack of nucleophile

This explains all of our observations nicely. First of all, the slow step should be formation of the (unstable) carbocation – which only depends on the substrate, not the nucleophile. Furthermore, since the stability of carbocations depends tremendously on substitution pattern (tertiary carbocations are more stable than secondary, which are more stable than primary) this also conveniently explains the dependence of the reaction rate on substitution pattern. Any factor which stabilizes the carbocation, increases the rate at which the leaving group can leave. 

It also helps us understand the stereochemistry. Since the nucleophile is flat,  attack could occur from either face; which means that we obtain a mixture of retention and inversion products.

This is therefore called the SN1 mechanism – Substitution, Nucleophilic, Unimolecular – to contrast with the SN2 (Substitution, Nucleophilic, Bimolecular).

It all seems to work if you’ve got a good leaving group present (like a halogen). But what if you don’t have a good leaving group? In the next post we’ll talk about how to make a poor leaving group into a good one.

Next Post: The Conjugate Acid Is A Better Leaving Group


Notes

*Note – the primary alkyl halide shown here is certainly reacting solely through an SN2 mechanism.

Final note – although it’s often said that the SN1 proceeds with “racemization” of stereocenters, in practice a 50/50 split of stereocenters may not be obtained due to “ion pairing” effects. In other words, the leaving group could leave, but not fully dissociate from the vicinity of the carbocation, which could block a nucleophile from attacking the electrophile from that face. For that reason it’s a little bit more correct to say that it proceeds with a  “mixture of retention and inversion” rather than “racemization”.


(Advanced) References and Further Reading

  1. 56. Mechanism of substitution at a saturated carbon atom. Part V. Hydrolysis of tert.-butyl chloride. 
    Edward D. Hughes.
    J. Chem. Soc. 1935, 235
    DOI: 10.1039/JR9350000255
    Original study where the hydrolysis of t-butyl chloride was found to be first-order in alkyl halide and zero order in base, giving rise to the mechanism we now know as SN1.

  2. 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
    In the hydrolysis of alkyl bromides by water in formic acid, the relative rates at 100° are MeBr 1.00, EtBr 1.71, iPrBr 44.7, and tBuBr ca. 10^8.
  3. 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
  4. 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.
  5. The Correlation of Solvolysis Rates
    Ernest Grunwald and S. Winstein
    Journal of the American Chemical Society 1948, 70 (2), 846-854
    DOI:
    1021/ja01182a117
    This is a very important paper, discussing the ‘Grunwald-Winstein equation’ for the first time. This equation is an extension of the Hammett equation, taking solvent effects (i.e. ‘ionizing power’) into consideration.
  6. The Reactivity of Bridgehead Compounds of Adamantane
    Paul von R. Schleyer and Robert D. Nicholas
    Journal of the American Chemical Society 1961, 83 (12), 2700-2707
    DOI:
    1021/ja01473a024
    Bridgehead carbocations are generally quite unstable since they cannot achieve the planar geometry necessary for good hyperconjugative stabilization. Somewhat surprisingly, in this paper it is found that the SN1 reaction of 1-bromoadamantane proceeds only about 1000 times slower than that of t-butyl bromide, albeit (of course) only with retention of configuration.
  7. 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.
  8. Mechanism of substitution at a saturated carbon atom. Part XXIX. The rôle of steric hindrance. (Section D) the mechanism of the reaction of neopentyl bromide with aqueous ethyl alcohol
    I. Dostrovsky and E. D. Hughes
    J. Chem. Soc., 1946, 166-169
    DOI:
    10.1039/JR9460000166
    This is an example of an SN1 reaction with rearrangement. Neopentyl bromide in aqueous ethyl alcohol gives t-amyl alcohol (and t-amyl ethyl ether).
  9. Mechanism of substitution at a saturated carbon atom. Part XXXV. Effect of temperature on the competition between unimolecular solvolytic and non-solvolytic substitutions of di-p-tolylmethyl chloride. Activation in the fast step of unimolecular non-solvolytic substitution
    Audrey R. Hawdon, E. D. Hughes and C. K. Ingold
    J. Chem. Soc., 1952, 2499-2503
    DOI:
    10.1039/JR9520002499
    It is possible to run SN1 reactions in the presence of added nucleophile, such as in the hydrolysis of benzyl chlorides in the presence of added sodium azide. The separate rates of formation of the carbocation and production of the azide can thus be measured.
  10. Methanolysis of Optically Active Hydrogen 2,4-Dimethylhexyl-4-phthalate
    von E. Doering and Harold H. Zeiss
    Journal of the American Chemical Society 1953, 75 (19), 4733-4738
    DOI: 10.1021/ja01115a035
    An early example of an SN1 reaction without full racemization. Prof. Doering proposes a mechanism in the paper, interesting read.
  11. Quaternary stereocentres via an enantioconvergent catalytic SN1 reaction
    Wendlandt, A.E., Vangal, P. & Jacobsen, E.N.
    Nature 556, 447–451 (2018)
    DOI:
    1038/s41586-018-0042-1
    This is a rare example of an asymmetric SN1 reaction – normally the SN1 reaction is taught as giving achiral products, but in this particular case it is possible to induce chirality because the carbocation is so highly stabilized (tertiary, benzylic, and propargylic).

Comments

Comment section

25 thoughts on “The SN1 Mechanism

  1. Tremendously useful site, your efforts are highly appreciative, Kindly correct the spelling of Carbocation in the fourth line after mechanism.

  2. You’ve created an awesome website here. I haven’t even used your reaction guide much yet, but I still like being a member simply because I feel like you totally deserve my money for all the help I’m getting from the blog. (It’s taught me more in a few days than my book has all year!)

    Anyway, just wanted to point out that on your starred note at the bottom, I think you meant that the primary alkyl halide is certainly reacting through an SN2 mechanism (not an SN1).

  3. EXTREMELY helpful! The content is very straightforward and understandable! MUCH appreciated! This website will be used for the whole semester!!

  4. In the paragraph under “final note”, I believe “In other words, the leaving group could leave, but not fully dissociate from the vicinity of the carbocation, which could block a nucleophile from attacking the nucleophile from that face” should read “block a nucleophile from attacking the electrophile” instead.Also,In the paragraph under “So what could be going on here?”, I believe “Since the nucleophile is flat, attack could occur from either face; which means that we obtain a mixture of retention and inversion products” should read “Since the electrophile is flat” instead.

  5. I can’t tell you how brilliantly every topic is explained. This is great. Your analogies and phrasing are the only way I understand organic chem. Thanks a ton

    1. The reason is that the resulting carbocation and the leaving group can form what is known as a “tight ion pair”. In a tight ion pair the leaving group has not completely dissociated, and this will block the face of the carbocation that was connected to the leaving group.
      In order for full racemization to occur there needs to be complete dissociation such that either face of the carbocation can be attacked with equal probability.

  6. Thanks for the very helpful site!

    I have a question about the first step in an SN1 reaction – the leaving group leaves. What causes the leaving group to want to leave? Is this action set in motion by heat, light or some other energy source?

    Thanks for the help.

    1. It’s helpful to think of bonds as balls and springs. At any given moment the bond between the carbon and the leaving group is oscillating like two balls connected by a spring, and the bond length is alternating between being shorter than normal and longer than normal. The average is the “bond length”.
      Now imagine the energy as that bond extends to its longest length. The carbon will have a partial positive charge (delta plus) and the leaving group will have a partial negative charge (delta minus). If the carbon is able to stabilize positive charge very well (e.g. a tertiary carbocation) and the leaving group is able to stabilize negative charge very well (e.g. a weak base) then it’s not hard to imagine the bond length getting longer and longer until it goes beyond the length of what we’d consider a normal bond and can be considered a carbocation in the vicinity of a leaving group. If a nucleophilic solvent is around (like CH3OH) it may then “trap” that free carbocation, resulting in a substitution reaction.

      conversely if we have a situation like CH3CH2OH, where we have a bad leaving group (OH) connected to a carbon poorly able to stabilize positive charge (primary) then the energetic barrier for that bond length getting long enough to lead to dissociation is just too high.

    1. I’m not sure what details you mean by “all necessary details”, but even a limited reading of that would neglect issues like stereochemistry, etc. So the answer would be no.

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