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SN1 reaction

The S_N1 reaction is a substitution reaction in organic chemistry. "S_N" stands for nucleophilic substitution and the "1" represents the fact that the rate-determining step is unimolecular ^[1] ^[2]. It involves a carbocation intermediate and is commonly seen in reactions of secondary or tertiary alkyl halides or, under strongly acidic conditions, with secondary or tertiary alcohols. With primary alkyl halides, the alternative S_N2 reaction occurs. Among inorganic chemists, S_N1 is referred to perhaps more accessibly as a dissociative mechanism. A reaction mechanism was first proposed by Christopher Ingold et al in 1940 ^[3]

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Mechanism

The S_N1 reaction between a molecule A and a nucleophile B takes place in three steps:

Formation of a carbocation from A by separation of a leaving group from the carbon; this step is slow and reversible ^[4].
Nucleophilic attack: B reacts with A. If the nucleophile is a neutral molecule (i.e. a solvent) a third step is required to complete the reaction. When the solvent is water, the intermediate is an oxonium ion.
Deprotonation: Removal of a proton on the protonated nucleophile by a nearby ion or molecule.

Kinetics

In contrast to S_N2, S_N1 reactions take place in two steps (excluding any protonation or deprotonation). The rate determining step is the first step, so the rate of the overall reaction is essentially equal to that of carbocation formation and does not involve the attacking nucleophile. Thus nucleophilicity is irrelevant and the overall reaction rate depends on the concentration of the reactant only.

rate = k[reactant]

In 1954 it was found that addition of a small amount of lithium perchlorate certain acetolysis reactions (for example that of the tosylate of cholesterol) led to a remarkable reaction rate increase ^[5]. Based on this special salt effect the general mechanism was refined to include a contact ion pair (CIP) with cation and anion together in a solvent cage which then dissociates to a so-called solvent-separated ion pair (SSIP) and then on to free ions (FI). All the interconversions are reversible and the added salt prevents the reformation of CIP from SSIP.

In some cases the S_N1 reaction will occur at an abnormally high rate due to neighbouring group participation (NGP). NGP often lowers the energy barrier required for the formation of the carbocation intermediate.

Scope of the reaction

The S_N1 mechanism tends to dominate when the central carbon atom is surrounded by bulky groups because such groups sterically hinder the S_N2 reaction. Additionally, bulky substituents on the central carbon increase the rate of carbocation formation because of the relief of steric strain that occurs. The resultant carbocation is also stabilized by both inductive stabilization and hyperconjugation from attached alkyl groups. The Hammond-Leffler postulate suggests that this too will increase the rate of carbocation formation. The S_N1 mechanism therefore dominates in reactions at tertiary alkyl centers and is further observed at secondary alkyl centers in the presence of weak nucleophiles.

Stereochemistry

Because the intermediate carbocation is planar, the central carbon is not a stereocenter. Even if it were a stereocenter prior to becoming a carbocation, the original configuration at that atom is lost. Rather, the central carbon can be prochiral. Nucleophilic attack can occur from either side of the plane, so the product might consist of a mixture of two stereoisomers. In fact, if the central carbon is the only stereocenter in the reaction, racemization may occur. This stands in contrast to the S_N2 mechanism, where the chiral configuration of the substrate is inverted. However, an excess of inversion is usually observed, as the leaving group can remain in proximity to the carbocation intermediate for a short time and block nucleophilic attack. For example, in the reaction of 3S-chloro-3-methylhexane with iodide ion, if the carbocation intermediate is free of the leaving group then it is achiral and stands an equal chance of attack on either side. This leads to a mixture of 3R-iodo-3-methylhexane and 3S-iodo-3-methylhexane:

Side reactions

Two common side reactions are elimination reactions and carbocation rearrangement. If the reaction is performed under warm or hot conditions (which favor an increase in entropy), E1 elimination is likely to predominate, leading to formation of an alkene. Even if the reaction is performed cold, some alkene may be formed. If an attempt is made to perform an S_N1 reaction using a strongly basic nucleophile such as hydroxide or methoxide ion, the alkene will again be formed, this time via an E2 elimination. This will be especially true if the reaction is heated. Finally, if the carbocation intermediate can rearrange to a more stable carbocation, it will give a product derived from the more stable carbocation rather than the simple substitution product.

Solvent effects

Since the S_N1 reaction involves formation of an unstable carbocation intermediate in the rate-determining step, anything that can facilitate this will speed up the reaction. The normal solvents of choice are both polar (to stabilise ionic intermediates in general) and protic (to solvate the leaving group in particular). Typical polar protic solvents include water and alcohols, which will also act as nucleophiles.

The Y scale correlates solvolysis reaction rates of any solvent (k) with that of a standard solvent (80% v/v ethanol/water) (k₀) through

$\log { \left ( \frac{k}{k_0} \right ) } = mY \,$

with m a reactant constant (m = 1 for tert-butyl chloride) and Y a solvent parameter ^[6]For example 100% ethanol gives Y = - 2.3, 50% ethanol in water Y = +1.65 and 15% concentration Y = +3.2 ^[7]

References

^ L. G. Wade, Jr., Organic Chemistry, 6th ed., Pearson/Prentice Hall, Upper Saddle River, New Jersey, USA, 2005.
^ J. March, Advanced Organic Chemistry, 4th ed., Wiley, New York, 1992.
^ 188. Mechanism of substitution at a saturated carbon atom. Part XXIII. A kinetic demonstration of the unimolecular solvolysis of alkyl halides. (Section E) a general discussion Leslie C. Bateman, Mervyn G. Church, Edward D. Hughes, Christopher K. Ingold and Nazeer Ahmed Taher J. Chem. Soc., 1940, 979 - 1011, doi:10.1039/JR9400000979
^ Nature of Dynamic Processes Associated with the SN1 Reaction Mechanism Peters, K. S. Chem. Rev.; (Review); 2007; 107(3); 859-873. doi:10.1021/cr068021k 10.1021/cr068021k
^ Salt effects and ion-pairs in solvolysis S. Winstein, E. Clippinger, A. H. Fainberg, and G. C. Robinson J. Am. Chem. Soc.; 1954; 76(9) pp 2597 - 2598; doi:10.1021/ja01638a093
^ The Correlation of Solvolysis Rates Ernest Grunwald and S. Winstein J. Am. Chem. Soc.; 1948; 70(2) pp 846 - 854; doi:10.1021/ja01182a117
^ Correlation of Solvolysis Rates. III.1 t-Butyl Chloride in a Wide Range of Solvent Mixtures Arnold H. Fainberg and S. Winstein J. Am. Chem. Soc.; 1956; 78(12) pp 2770 - 2777; doi:10.1021/ja01593a033

Categories: Substitution reactions | Reaction mechanisms

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