By Brad Moyle


Introduction

Nucleophilic substitution reactions are a class of reactions that are most commonly studied in the context of organic chemistry. These reactions involve an electron-rich molecule, called a nucleophile (or nucleus-loving), bonds with an electron-poor atom or molecule, called an electrophile (or electron-loving). The formation of this new bond also causes the electrophile to break a bond, releasing an atom or group of atoms called the leaving group.

In general, the equation for a nucleophilic substitution reaction is shown below. The leaving group here is a halogen atom, represented by X, and the nucleophile is represented by Y. The nucleophile shown below has a net charge of -1 but nucleophiles can also have a charge of 0. This equation incorporates both SN1 and SN2 mechanisms into one; the difference between these two mechanisms will be described in more detail below.

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General equation for nucleophilic substitution reaction.


SN1 Mechanism


The SN1 mechanism is a two-step nucleophilic substitution mechanism which occurs in two separate steps. It can be best remembered as a Substitution Nucleophilic 1 molecule (i.e. unimolecular). Because this reaction occurs in two separate stages, the rate of the reaction depends only on the slow step and the reaction is considered unimolecular. SN1 substitutions most commonly occur on tertiary and sometimes secondary halogenoalkanes. The two steps of the SN1 mechanism are shown in the image below.

image103.gif
Mechanism showing the two steps of the SN1 reaction. Note that the first step is the rate-determining step and the second step is the fast step.


The first step in the SN1 mechanism is the departure of the leaving group. This leaves behind a carbocation that is stabilized by the inductive effects of neighbouring carbon atoms. The second step of the SN1 mechanism is the addition of an electron-rich nucleophile which is attracted to the positively charged carbocation. This causes a reversal of the geometry of the molecule about the reaction centre, which can be most easily seen in the video below.

The following video shows a good example of an SN1 substitution on a saturated hydrocarbon. The pink sphere in this video represents a halogen atom, which are excellent leaving groups in nucleophilic substitution. Note the clear distinction between the first step and the second step, and the transition state complex characterized by the carbon atom with a less favourable 120° bond angle. Credit for this video goes to YouTube account m770596.



SN2 Mechanism


The SN2 mechanism ultimately accomplishes the same process but generally only occurs in primary and sometimes secondary halogenoalkanes. SN2 substitutions occur in a single step and can be best remembered as a Substitution Nucleophilic 2 molecules (i.e. bimolecular). Because the rate of this reaction depends on the concentration of both molecules involved in the single step, it is considered bimolecular. The one-step mechanism for SN2 substitution is shown below.

image101.gif
Mechanism for SN2 substitution. Note how the reaction occurs in a single step.


The single-step SN2 mechanism involves the donation of electrons by the nucleophile to the carbon atom, and the release of the leaving group (generally a halogen atom, as mentioned above). The resultant molecule is essentially identical to the product of the SN1 mechanism, ignoring the fact that the reaction centre shown here is a primary carbon.

The following video shows a good example of a SN2 substitution on a saturated hydrocarbon. Note how the reaction occurs in a single step, with the substituting group approaching the reaction centre before the leaving group has departed. Credit for this video goes to YouTube account m770596.


History & Development


The idea of nucleophilic substitution was first characterized by Edward Hughes and Christopher K. Ingold in 1935 at Leeds University and University College London. Their original proposition was that the SN1 and SN2 mechanisms worked in competition with one another, which is essentially still the main idea of nucleophilic substitution today. Their original paper relating to the development of the theories surrounding nucleophilic substitution can be found here.
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Sir Christopher K. Ingold
Edward Hughes
Edward Hughes



Sources

Lewis, E., & Berry, M.. (2000). As and a level chemistry. Harlow, Essex, United Kingdom: Pearson Education Limited 2009.

"nucleophilic substitution." Encyclopædia Britannica. Encyclopædia Britannica Online. Encyclopædia Britannica, 2011. Web. 29 Apr. 2011. <http://www.britannica.com/EBchecked/topic/421958/nucleophilic-substitution>

Greeves, Nick, & Berry, Neil. (2010). Nucleophilic substitution at saturated carbon. Retrieved from http://www.chemtube3d.com/Nucleophilic%20substitution%20at%20saturated%20carbon%20-%20Nucleophilic%20substitution%20via%20SN1%20and%20SN2.html

dave. (2008, August 24). Nucleophilic substitution reactions – sn1 & sn2 stereochemistry. Retrieved from http://biochem.co/2008/08/nucleophilic-substitution-reactions-sn1-sn2-stereochemistry/

m770596, . (Producer). (2008). Sn1 nucleophilic substitution reaction. [Web]. Retrieved from http://www.youtube.com/watch?v=yJlSTWED8Iw&feature=related

m770596, . (Producer). (2008). Sn2 nucleophilic substitution reaction. [Web]. Retrieved from http://www.youtube.com/watch?v=pTp0R6WuSks&feature=related

Carey, F.A. (2007). Organic chemistry, 7th ed.. Virginia, USA: McGraw Hill.

Carey, F.A. (2002). Nucleophilic substitution reactions. Retrieved from http://www.mhhe.com/physsci/chemistry/carey/student/olc/graphics/carey04oc/ref/ch04nucle.html

Masson, M. (2008, August 1). Curly arrows - nucleophilic substitution reactions. Retrieved from http://www.abdn.ac.uk/curly-arrows/org/n1.shtml

Hartshorn, S.R. (1973). Aliphatic nucleophilic substitution. London: Cambridge University Press.


The ucl periodic table of the lecturers - edward david hughes. (2010, September 20). Retrieved from http://www.chem.ucl.ac.uk/resources/history/people/hughes.html

1937 sir christopher ingold. (2011). Retrieved from http://www.ucl.ac.uk/chemistry/history/chemical_history/slides/1937
Hughes, E.D., Ingold, C.K., & Scott, A.D. (1937). Reaction kinetics and the walden inversion. part ii. homogeneous hydrolysis, alcoholysis, and ammonolysis of α-phenylethyl halides. J. Chem. Soc., 10, 1201.1208.

Further Reading


Further information on this topic can be found in AS and A Level Chemistry by Lewis & Berry (2008) on pages 448 - 453. The McGraw Hill Online Learning Centre website also has a comprehensive section, with many excellent visual aids, that can be found at http://www.mhhe.com/physsci/chemistry/carey/student/olc/ch04nucle.html. (This website is intended as a complement to Organic Chemistry texbook by Francis A. Carey (2002).) Finally, An excellent discussion of the use of curly arrows in reaction mechanisms can be found on the University of Aberdeen's website relating to this topic at http://www.abdn.ac.uk/curly-arrows/org/n1.shtml.