SN1 and SN2 Reaction

SN1 reaction From Wikipedia, the free encyclopedia For other uses, see SN1 (disambiguation). The SN1 reaction is a substitution reaction in organic chemistry. "SN" stands for nucleophilic substitution and the "1" represents the fact that the rate-determining step is unimolecular.[1][2] The reaction involves a carbocation intermediate and is commonly seen in reactions of secondary or tertiary alkyl halides under strongly basic conditions 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 thedissociative mechanism. A reaction mechanism was first proposed by Christopher Ingold et al. in 1940.[3] [edit]Mechanism An example of a reaction taking place with an SN1 reaction mechanism is the hydrolysis of tert-butyl bromide with water forming tert-butyl alcohol:

This SN1 reaction takes place in three steps: 

Formation of a tert-butyl carbocation by separation of a leaving group (a bromide anion) from the carbon atom: this step is slow andreversible.[4]

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Nucleophilic attack: the carbocation reacts with the nucleophile. 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. This reaction step is fast.

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Deprotonation: Removal of a proton on the protonated nucleophile by water acting as a base forming the alcohol and a hydronium ion. This reaction step is fast.

[edit]Scope of the reaction The SN1 mechanism tends to dominate when the central carbon atom is surrounded by bulky groups because such groups sterically hinderthe SN2 reaction. Additionally, bulky substituents on the central carbon increase the rate of carbocation formation because of the relief ofsteric strain that occurs. The resultant carbocation is also stabilized by both inductive stabilization and hyperconjugation from attached alkylgroups. The Hammond-Leffler postulate suggests that this too will increase the rate of carbocation formation. The SN1 mechanism therefore dominates in reactions at tertiary alkyl centers and is further observed at secondary alkyl centers in the presence of weak nucleophiles. An example of a reaction proceeding in a SN1 fashion is the synthesis of 2,5dichloro-2,5-dimethylhexane from the corresponding diol with concentrated hydrochloric acid [5]:

As the alpha and beta substitutions increase with respect to leaving groups the reaction is diverted from SN2 to SN1 [edit]Stereochemistry The carbocation intermediate formed in the reaction's rate limiting step is an sp2 hybridized carbon with trigonal planar molecular geometry. This allows two different avenues for the nucleophilic attack, one on either side of the planar molecule. If neither avenue is preferentially favored, these two avenues occur equally, yielding a racemic mix of enantiomers if the reaction takes place at a stereocenter.[6] This is illustrated below in the SN1 reaction of S-3-chloro-3-methylhexane with an iodide ion, which yields a racemic mixture of 3-iodo-3-methylhexane:

However, an excess of one stereoisomer can be observed, as the leaving group can remain in proximity to the carbocation intermediate for a short time and block nucleophilic attack. This stands in contrast to the SN2 mechanism, where is a stereospecific mechanism where stereochemistry is always inverted. [edit]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. At lower temperatures, SN1 and E1 reactions are competitive reactions and it becomes difficult to

favor one over the other. 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 ashydroxide 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. [edit]Solvent effects 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 stabilize 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

with m a reactant constant (m = 1 for tert-butyl chloride) and Y a solvent parameter.[7] For example 100% ethanol gives Y = −2.3, 50% ethanol in water Y = +1.65 and 15% concentration Y = +3.2.[8]

SN2 reaction From Wikipedia, the free encyclopedia

Ball-and-stick representation of the SN2 reaction of CH3SH with CH3I

Structure of the SN2 transition state The SN2 reaction (also known as bimolecular nucleophilic substitution) is a type ofnucleophilic substitution, where a lone pair from a nucleophile attacks an electron deficientelectrophilic center and bonds to it, expelling another group called a leaving group. Thus the incoming group replaces the leaving group in one step. Since two reacting species are involved in the slow, rate-determining step of the reaction, this leads to the name bimolecular nucleophilicsubstitution, or SN2. Among inorganic chemists, the SN2 reaction is often known as theinterchange mechanism. [edit]Reaction mechanism

The reaction most often occurs at an aliphatic sp3 carbon center with an electronegative, stable leaving group attached to it - 'X' - frequently a halide atom. The breaking of the C-X bond and the formation of the new C-Nu bond occur simultaneously to form a transition state in which the carbon under nucleophilic attack is pentacoordinate, and approximately sp2 hybridised. The nucleophile attacks the carbon at 180° to the leaving group, since this provides the best overlap between the nucleophile's lone pair and the C-X σ* antibonding orbital. The leaving group is then pushed off the opposite side and the product is formed. If the substrate under nucleophilic attack is chiral, this can lead, although not necessarily, to an inversion ofstereochemistry, called the Walden inversion. In an example of the SN2 reaction, the attack of OH− (the nucleophile) on a bromoethane (the electrophile) results in ethanol, with bromide ejected as the leaving group:

SN2 reaction of bromoethane with hydroxide ion. SN2 attack occurs if the backside route of attack is not sterically hindered by substituents on the substrate. Therefore this mechanismusually occurs at an unhindered primary carbon centre. If there is steric crowding on the substrate near the leaving group, such as at a tertiary carbon centre, the substitution will involve an SN1 rather than an SN2 mechanism, (an SN1 would also be more likely in this case because a sufficiently stable carbocation intermediary could be formed.) In coordination chemistry, associative substitution proceeds via a similar mechanism as SN2. [edit]Factors affecting the rate of the reaction Four factors affect the rate of the reaction: 

Substrate. The substrate plays the most important part in determining the rate of the reaction. This is because the nucleophile attacks from the back of the substrate, thus breaking the carbon-leaving group bond and forming the carbon-nucleophile

bond. Therefore, to maximise the rate of the SN2 reaction, the back of the substrate must be as unhindered as possible. Overall, this means that methyl and primary substrates react the fastest, followed by secondary substrates. Tertiary substrates do not participate in SN2 reactions, because of steric hindrance. 

Nucleophile. Like the substrate, steric hindrance affects the nucleophile's strength. The methoxide anion, for example, is both a strong base and nucleophile because it is a methyl nucleophile, and is thus very much unhindered. Tert-butoxide, on the other hand, is a strong base, but a poor nucleophile, because of its three methyl groups hindering its approach to the carbon. Nucleophile strength is also affected by charge and electronegativity: nucleophilicity increases with increasing negative charge and decreasing electronegativity. For example, OH- is a better nucleophile than water, and I- is a better nucleophile than Br- (in polar protic solvents). In a polar aprotic solvent, nucleophilicity increases up a column of the periodic table as there is no hydrogen bonding between the solvent and nucleophile; in this case nucleophilicity mirrors basicity. I- would therefore be a weaker nucleophile than Br- because it is a weaker base.

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Solvent. The solvent affects the rate of reaction because solvents may or may not surround a nucleophile, thus hindering or not hindering its approach to the carbon atom. Polar aprotic solvents, like tetrahydrofuran, are better solvents for this reaction than polar protic solventsbecause polar protic solvents will be solvated by the solvent hydrogen bonding to the nucleophile and thus hindering it from attacking the carbon with the leaving group.

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Leaving group. The leaving group affects the rate of reaction because the more stable it is, the more likely that it will take the two electrons of its carbon-leaving group bond with it when the nucleophile attacks the carbon. Therefore, the weaker the leaving group is as a conjugate base, and thus the stronger its corresponding acid, the better the leaving group. Examples of good leaving groups are therefore the halides (except fluoride) and tosylate, whereas HO- and H2N- are not.

[edit]Reaction kinetics The rate of an SN2 reaction is second order, as the rate-determining step depends on the nucleophile concentration, [Nu−] as well as the concentration of substrate, [RX]. r = k[RX][Nu−]

This is a key difference between the SN1 and SN2 mechanisms. In the SN1 reaction the nucleophile attacks after the rate-limiting step is over, whereas in SN2 the nucleophile forces off the leaving group in the limiting step. In other words, the rate of SN1 reactions depend only on the concentration of the substrate while the SN2 reaction rate depends on the concentration of both the substrate and nucleophile. In cases where both mechanisms are possible (for example at a secondary carbon centre), the mechanism depends on solvent, temperature, concentration of the nucleophile or on the leaving group. SN2 reactions are generally favored in primary alkyl halides or secondary alkyl halides with an aprotic solvent. They occur at a negligible rate in tertiary alkyl halides due to steric hindrance. It is important to understand that SN2 and SN1 are two extremes of a sliding scale of reactions, it is possible to find many reactions which exhibit both SN2 and SN1 character in their mechanisms. For instance, it is possible to get a contact ion pairs formed from an alkyl halide in which the ions are not fully separated. When these undergo substitution the stereochemistry will be inverted (as in SN2) for many of the reacting molecules but a few may show retention of configuration. Sn2 reactions are more common than Sn1 reactions[citation needed]. [edit]E2 competition A common side reaction taking place with SN2 reactions is E2 elimination: the incoming anion can act as a base rather than as a nucleophile, abstracting a proton and leading to formation of the alkene. This effect can be demonstrated in the gasphase reaction between asulfonate and a simple alkyl bromide taking place inside a mass spectrometer:[1][2]

With ethyl bromide, the reaction product is predominantly the substitution product. As steric hindrance around the electrophilic center increases, as with isobutyl bromide, substitution is disfavored and elimination is the predominant reaction. Other factors favoring elimination are the strength of the base. With the less basic benzoate substrate, isopropyl bromide reacts with 55% substitution. In general, gas phase reactions and solution phase reactions of this type follow the same trends, even though in the first, solvent effects are eliminated. [edit]Roundabout mechanism A development attracting attention in 2008 concerns a SN2 roundabout mechanism observed in a gas-phase reaction between chloride ions and methyl iodide with a special technique called crossed molecular beam imaging. When the chloride ions have sufficient velocity, the energy of the resulting iodide ions after the collision is much lower than expected, and it is theorized that energy is lost as a result of a full roundabout of the methyl group around the iodine atom before the actual displacement takes place.

tert-butyl chloride is a typical SN1 reaction: