- SN1 reaction
The SN1 reaction is a
substitution reactionin organic chemistry. "SN" stands for nucleophilic substitutionand the "1" represents the fact that the rate-determining stepis unimolecular [ 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.] . It involves a carbocationintermediate 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 SN2 reaction occurs. Among inorganic chemists, the SN1 reaction is often known as the dissociative mechanism. A reaction mechanismwas first proposed by Christopher Ingoldet al in 1940 ["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]
The SN1 reaction between a molecule A and a nucleophile B takes place in three steps:
#Formation of a
carbocationfrom A by separation of a leaving groupfrom the carbon; this step is slow and reversible ["Nature of Dynamic Processes Associated with the SN1 Reaction Mechanism" Peters, K. S. Chem. Rev.; (Review); 2007; 107(3); 859-873. DOI|10.1002/chin.200722274 ] .
#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
Deprotonation: Removal of a proton on the protonated nucleophile by a nearby ion or molecule.
In contrast to SN2, SN1 reactions take place in two steps (excluding any protonation or deprotonation). The
rate determining stepis the first step, so the rate of the overall reaction is essentially equal to that of carbocationformation and does not involve the attacking nucleophile. Thus nucleophilicityis irrelevant and the overall reaction ratedepends on the concentration of the reactant only.
:rate = k
In 1954 it was found that addition of a small amount of
lithium perchlorateto certain acetolysisreactions (for example that of the tosylateof cholesterol) led to a remarkable reaction rate increase ["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] . 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 cagewhich 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 SN1 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 SN1 mechanism tends to dominate when the central carbon atom is surrounded by bulky groups because such groups sterically hinder the SN2 reaction. Additionally, bulky substituents on the central carbon increase the rate of carbocation formation because of the relief of
steric strainthat occurs. The resultant carbocation is also stabilized by both inductive stabilization and hyperconjugationfrom attached alkylgroups. The Hammond-Leffler postulatesuggests that this too will increase the rate of carbocation formation. The SN1 mechanism therefore dominates in reactions at tertiary alkylcenters and is further observed at secondary alkylcenters in the presence of weak nucleophiles.
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, racemizationmay occur. This stands in contrast to the SN2 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 iodideion, 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:
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 SN1 reaction using a strongly basic nucleophile such as hydroxideor methoxideion, 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.
Since the SN1 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
solvolysisreaction rates of any solvent (k) with that of a standard solvent (80% v/v ethanol/ water) (k0) through
with m a reactant constant (m = 1 for
tert-butyl chloride) and Y a solvent parameter ["The Correlation of Solvolysis Rates" Ernest Grunwald and S. Winstein J. Am. Chem. Soc.; 1948; 70(2) pp 846 - 854; DOI|10.1021/ja01182a117] For example 100% ethanol gives Y = - 2.3, 50% ethanol in water Y = +1.65 and 15% concentration Y = +3.2 ["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]
Nucleophilic acyl substitution
Neighbouring group participation
*Electrophilic Bimolecular Substitution as an Alternative to Nucleophilic Monomolecular Substitution in Inorganic and Organic Chemistry / N.S.Imyanitov. J. Gen. Chem. USSR (Engl. Transl.) 1990; 60 (3); 417-419.
* [http://www.chemhelper.com/sn1.html Diagrams] : Frostburg State University
* [http://www.usm.maine.edu/~newton/Chy251_253/Lectures/Sn1/Sn1FS.html Exercise] : the University of Maine
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