HOME

TheInfoList



OR:

The SN2 reaction is a type of
reaction mechanism In chemistry, a reaction mechanism is the step by step sequence of elementary reactions by which overall chemical change occurs. A chemical mechanism is a theoretical conjecture that tries to describe in detail what takes place at each stage of ...
that is common in
organic chemistry Organic chemistry is a subdiscipline within chemistry involving the scientific study of the structure, properties, and reactions of organic compounds and organic materials, i.e., matter in its various forms that contain carbon atoms.Clayden, J.; ...
. In this mechanism, one bond is broken and one bond is formed in a concerted way, i.e., in one step. The name SN2 refers to the Hughes-Ingold symbol of the mechanism: "SN" indicates that the reaction is a
nucleophilic substitution In chemistry, a nucleophilic substitution is a class of chemical reactions in which an electron-rich chemical species (known as a nucleophile) replaces a functional group within another electron-deficient molecule (known as the electrophile). The ...
, and "2" that it proceeds via a bi-molecular mechanism, which means both the reacting species are involved in the rate-determining step. The other major type of nucleophilic substitution is the SN1, but many other more specialized mechanisms describe substitution reactions. The SN2 reaction can be considered as an analogue of the
associative substitution Associative substitution describes a pathway by which compounds interchange ligands. The terminology is typically applied to organometallic and coordination complexes, but resembles the Sn2 mechanism in organic chemistry. The opposite pathway is ...
in the field of
inorganic chemistry Inorganic chemistry deals with synthesis and behavior of inorganic and organometallic compounds. This field covers chemical compounds that are not carbon-based, which are the subjects of organic chemistry. The distinction between the two disci ...
.


Reaction mechanism

The reaction most often occurs at an
aliphatic In organic chemistry, hydrocarbons ( compounds composed solely of carbon and hydrogen) are divided into two classes: aromatic compounds and aliphatic compounds (; G. ''aleiphar'', fat, oil). Aliphatic compounds can be saturated, like hexane, ...
sp3 carbon center with an
electronegative Electronegativity, symbolized as , is the tendency for an atom of a given chemical element to attract shared electrons (or electron density) when forming a chemical bond. An atom's electronegativity is affected by both its atomic number and the d ...
, stable leaving group attached to it (often denoted X), which is frequently a
halide In chemistry, a halide (rarely halogenide) is a binary chemical compound, of which one part is a halogen atom and the other part is an element or radical that is less electronegative (or more electropositive) than the halogen, to make a fluor ...
atom. The breaking of the C–X bond and the formation of the new bond (often denoted C–Y or C–Nu) occur simultaneously through a
transition state In chemistry, the transition state of a chemical reaction is a particular configuration along the reaction coordinate. It is defined as the state corresponding to the highest potential energy along this reaction coordinate. It is often marked wi ...
in which a carbon under nucleophilic attack is pentacoordinate, and approximately sp2 hybridised. The nucleophile attacks the carbon at 180° to the
leaving group In chemistry, a leaving group is defined by the IUPAC as an atom or group of atoms that detaches from the main or residual part of a substrate during a reaction or elementary step of a reaction. However, in common usage, the term is often limited t ...
, 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 with
inversion Inversion or inversions may refer to: Arts * , a French gay magazine (1924/1925) * ''Inversion'' (artwork), a 2005 temporary sculpture in Houston, Texas * Inversion (music), a term with various meanings in music theory and musical set theory * ...
of the tetrahedral geometry at the central atom. If the substrate under nucleophilic attack is
chiral Chirality is a property of asymmetry important in several branches of science. The word ''chirality'' is derived from the Greek (''kheir''), "hand", a familiar chiral object. An object or a system is ''chiral'' if it is distinguishable from ...
, then this often leads to inversion of configuration (
stereochemistry Stereochemistry, a subdiscipline of chemistry, involves the study of the relative spatial arrangement of atoms that form the structure of molecules and their manipulation. The study of stereochemistry focuses on the relationships between stereois ...
), called a
Walden inversion Walden inversion is the inversion of a stereogenic center in a chiral molecule in a chemical reaction. Since a molecule can form two enantiomers around a stereogenic center, the Walden inversion converts the configuration of the molecule fro ...
. In an example of the SN2 reaction, the attack of Br (the nucleophile) on an
ethyl chloride Chloroethane, commonly known as ethyl chloride, is a chemical compound with chemical formula CH3CH2Cl, once widely used in producing tetraethyllead, a gasoline additive. It is a colorless, flammable gas or refrigerated liquid with a faintly sweet ...
(the electrophile) results in
ethyl bromide Bromoethane, also known as ethyl bromide, is a chemical compound of the haloalkanes group. It is abbreviated by chemists as EtBr (which is also used as an abbreviation for ethidium bromide). This volatile compound has an ether-like odor. Prepara ...
, with
chloride The chloride ion is the anion (negatively charged ion) Cl−. It is formed when the element chlorine (a halogen) gains an electron or when a compound such as hydrogen chloride is dissolved in water or other polar solvents. Chloride salts ...
ejected as the leaving group. : :If the molecule that is undergoing SN2 reaction has a
chiral centre In stereochemistry, a stereocenter of a molecule is an atom (center), axis or plane that is the focus of stereoisomerism; that is, when having at least three different groups bound to the stereocenter, interchanging any two different groups cr ...
, then it is possible that the
optical activity Optical rotation, also known as polarization rotation or circular birefringence, is the rotation of the orientation of the plane of polarization about the optical axis of linearly polarized light as it travels through certain materials. Circul ...
of the product would be different from that of the reactant. In an example, 1-bromo-1-fluoroethane can undergo SN2 reaction to form 1-fluoroethan-1-ol, with the nucleophile being an OH group. In this case, if the reactant is levorotatory, then the product would be dextrorotatory, and vice versa. : SN2 attack occurs if the backside route of attack is not sterically hindered by
substituent A substituent is one or a group of atoms that replaces (one or more) atoms, thereby becoming a moiety in the resultant (new) molecule. (In organic chemistry and biochemistry, the terms ''substituent'' and ''functional group'', as well as ''side ...
s on the substrate (ethyl chloride being the substrate above). Therefore, this
mechanism Mechanism may refer to: * Mechanism (engineering), rigid bodies connected by joints in order to accomplish a desired force and/or motion transmission *Mechanism (biology), explaining how a feature is created *Mechanism (philosophy), a theory that ...
usually occurs at unhindered primary and secondary carbon centres. 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 A carbocation is an ion with a positively charged carbon atom. Among the simplest examples are the methenium , methanium and vinyl cations. Occasionally, carbocations that bear more than one positively charged carbon atom are also encountere ...
intermediary could be formed).


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 Steric effects arise from the spatial arrangement of atoms. When atoms come close together there is a rise in the energy of the molecule. Steric effects are nonbonding interactions that influence the shape ( conformation) and reactivity of ions ...
. Structures that can form highly stable cations by simple loss of the leaving group, for example, as a resonance-stabilized carbocation, are especially likely to react via an SN1 pathway in competition with SN2.


Nucleophile

Like the substrate, steric hindrance affects the nucleophile's strength. The
methoxide In organic chemistry, methoxides are organic salts with a anion. They are the simplest alkoxides. Sodium methoxide and potassium methoxide have widespread use, though other metal-cation variants such as lithium methoxide, rubidium 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 Electronegativity, symbolized as , is the tendency for an atom of a given chemical element to attract shared electrons (or electron density) when forming a chemical bond. An atom's electronegativity is affected by both its atomic number and the d ...
: 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. Verdict - A strong/anionic nucleophile always favours SN2 manner of nucleophillic substitution.


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 Tetrahydrofuran (THF), or oxolane, is an organic compound with the formula (CH2)4O. The compound is classified as heterocyclic compound, specifically a cyclic ether. It is a colorless, water-miscible organic liquid with low viscosity. It is ma ...
, are better solvents for this reaction than polar
protic solvent In chemistry, a protic solvent is a solvent that has a hydrogen atom bound to an oxygen (as in a hydroxyl group ), a nitrogen (as in an amine group or ), or fluoride (as in hydrogen fluoride). In general terms, any solvent that contains a Labile# ...
s because polar protic solvents will
hydrogen bond In chemistry, a hydrogen bond (or H-bond) is a primarily electrostatic force of attraction between a hydrogen (H) atom which is covalently bound to a more electronegative "donor" atom or group (Dn), and another electronegative atom bearing a ...
to the nucleophile, hindering it from attacking the carbon with the leaving group. A polar aprotic solvent with low dielectric constant or a hindered dipole end will favour SN2 manner of nucleophilic substitution reaction. Examples:
dimethylsulfoxide Dimethyl sulfoxide (DMSO) is an organosulfur compound with the formula ( CH3)2. This colorless liquid is the sulfoxide most widely used commercially. It is an important polar aprotic solvent that dissolves both polar and nonpolar compounds and ...
,
dimethylformamide Dimethylformamide is an organic compound with the formula ( CH3)2NC(O)H. Commonly abbreviated as DMF (although this initialism is sometimes used for dimethylfuran, or dimethyl fumarate), this colourless liquid is miscible with water and the majo ...
,
acetone Acetone (2-propanone or dimethyl ketone), is an organic compound with the formula . It is the simplest and smallest ketone (). It is a colorless, highly volatile and flammable liquid with a characteristic pungent odour. Acetone is miscib ...
, etc. In parallel, solvation also has a significant impact on the intrinsic strength of the nucleophile, in which strong interactions between solvent and the nucleophile, found for polar
protic solvent In chemistry, a protic solvent is a solvent that has a hydrogen atom bound to an oxygen (as in a hydroxyl group ), a nitrogen (as in an amine group or ), or fluoride (as in hydrogen fluoride). In general terms, any solvent that contains a Labile# ...
s, furnish a weaker nucleophile. In contrast, polar aprotic solvents can only weakly interact with the nucleophile, and thus, are to a lesser extent able to reduce the strength of the nucleophile.


Leaving group

The stability of the leaving group as an anion and the strength of its bond to the carbon atom both affect the rate of reaction. The more stable the conjugate base of the leaving group is, the more likely that it will take the two electrons of its bond to carbon during the reaction. 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, due to its strong bond to the carbon atom) and
tosyl In organic chemistry, a toluenesulfonyl group (tosyl group, abbreviated Ts or Tos) is a univalent functional group with the chemical formula –. It consists of a Toluene, tolyl group, –, joined to a sulfonyl group, ––, with the open vale ...
ate, whereas HO and H2N are not.


Reaction kinetics

The rate of an SN2 reaction is second order, as the
rate-determining step In chemical kinetics, the overall rate of a reaction is often approximately determined by the slowest step, known as the rate-determining step (RDS or RD-step or r/d step) or rate-limiting step. For a given reaction mechanism, the prediction of the ...
depends on the nucleophile concentration, /nowiki>Nu/nowiki> as well as the concentration of substrate, X/nowiki>. : r = k X/nowiki>Nu/nowiki> 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. It has been shown that except in uncommon (but predictable cases) primary and secondary substrates go exclusively by the SN2 mechanism while tertiary substrates go via the SN1 reaction. There are two factors which complicate determining the mechanism of nucleophilic substitution reactions at secondary carbons: # Many reactions studied are solvolysis reactions where a solvent molecule (often an alcohol) is the nucleophile. While still a second order reaction mechanistically, the reaction is kinetically first order as the concentration of the nucleophile–the solvent molecule, is effectively constant during the reaction. This type of reaction is often called a pseudo first order reaction. # In reactions where the leaving group is also a good nucleophile (bromide for instance) the leaving group can perform an SN2 reaction on a substrate molecule. If the substrate is chiral, this inverts the configuration of the substrate before solvolysis, leading to a racemized product–the product that would be expected from an SN1 mechanism. In the case of a bromide leaving group in alcoholic solvent Cowdrey et al. have shown that bromide can have an SN2 rate constant 100-250 times higher than the rate constant for ethanol. Thus, after only a few percent solvolysis of an enantiospecific substrate, it becomes racemic. The examples in textbooks of secondary substrates going by the SN1 mechanism invariably involve the use of bromide (or other good nucleophile) as the leaving group have confused the understanding of alkyl nucleophilic substitution reactions at secondary carbons for 80 years /sup>. Work with the 2-adamantyl system (SN2 not possible) by Schleyer and co-workers, the use of azide (an excellent nucleophile but very poor leaving group) by Weiner and Sneen, the development of sulfonate leaving groups (non-nucleophilic good leaving groups), and the demonstration of significant experimental problems in the initial claim of an SN1 mechanism in the solvolysis of optically active 2-bromooctane by Hughes et al. /sup> have demonstrated conclusively that secondary substrates go exclusively (except in unusual but predictable cases) by the SN2 mechanism.


E2 competition

A common
side reaction A side reaction is a chemical reaction that occurs at the same time as the actual main reaction, but to a lesser extent. It leads to the formation of by-product, so that the yield of main product is reduced: : + B ->[] P1 : + C ->[] P2 P1 is th ...
taking place with SN2 reactions is elimination reaction, 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 In organic chemistry, an alkene is a hydrocarbon containing a carbon–carbon double bond. Alkene is often used as synonym of olefin, that is, any hydrocarbon containing one or more double bonds.H. Stephen Stoker (2015): General, Organic, an ...
. This pathway is favored with sterically hindered nucleophiles. Elimination reactions are usually favoured at elevated temperatures because of increased
entropy Entropy is a scientific concept, as well as a measurable physical property, that is most commonly associated with a state of disorder, randomness, or uncertainty. The term and the concept are used in diverse fields, from classical thermodynam ...
. This effect can be demonstrated in the gas-phase reaction between a
sulfonate In organosulfur chemistry, a sulfonate is a salt or ester of a sulfonic acid. It contains the functional group , where R is an organic group. Sulfonates are the conjugate bases of sulfonic acids. Sulfonates are generally stable in water, non-o ...
and a simple
alkyl bromide Organobromine compounds, also called organobromides, are organic compounds that contain carbon Chemical bond, bonded to bromine. The most pervasive is the naturally produced bromomethane. One prominent application of synthetic organobromine comp ...
taking place inside a
mass spectrometer Mass spectrometry (MS) is an analytical technique that is used to measure the mass-to-charge ratio of ions. The results are presented as a '' mass spectrum'', a plot of intensity as a function of the mass-to-charge ratio. Mass spectrometry is us ...
: : With
ethyl bromide Bromoethane, also known as ethyl bromide, is a chemical compound of the haloalkanes group. It is abbreviated by chemists as EtBr (which is also used as an abbreviation for ethidium bromide). This volatile compound has an ether-like odor. Prepara ...
, the reaction product is predominantly the substitution product. As
steric hindrance Steric effects arise from the spatial arrangement of atoms. When atoms come close together there is a rise in the energy of the molecule. Steric effects are nonbonding interactions that influence the shape ( conformation) and reactivity of ions ...
around the electrophilic center increases, as with
isobutyl In organic chemistry, butyl is a four-carbon alkyl radical or substituent group with general chemical formula , derived from either of the two isomers (''n''-butane and isobutane) of butane. The isomer ''n''-butane can connect in two ways, givi ...
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 Benzoic acid is a white (or colorless) solid organic compound with the formula , whose structure consists of a benzene ring () with a carboxyl () substituent. It is the simplest aromatic carboxylic acid. The name is derived from gum benzoin, wh ...
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 In chemistry, solvent effects are the influence of a solvent on chemical reactivity or molecular associations. Solvents can have an effect on solubility, stability and reaction rates and choosing the appropriate solvent allows for thermodynamic a ...
are eliminated.


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 Iodomethane, also called methyl iodide, and commonly abbreviated "MeI", is the chemical compound with the formula CH3I. It is a dense, colorless, volatile liquid. In terms of chemical structure, it is related to methane by replacement of one h ...
with a special technique called ''crossed molecular beam imaging''. When the chloride ions have sufficient velocity, the initial collision of it with the methyl iodide molecule causes the methyl iodide to spin around once before the actual SN2 displacement mechanism takes place.''Surprise From SN2 Snapshots Ion velocity measurements unveil additional unforeseen mechanism'' Carmen Drahl
Chemical & Engineering News ''Chemical & Engineering News'' (''C&EN'') is a weekly news magazine published by the American Chemical Society, providing professional and technical news and analysis in the fields of chemistry and chemical engineering.Arrow pushing Arrow pushing or electron pushing is a technique used to describe the progression of organic chemistry reaction mechanisms. It was first developed by Sir Robert Robinson. In using arrow pushing, "curved arrows" or "curly arrows" are drawn on the ...
*
Christopher Kelk Ingold Sir Christopher Kelk Ingold (28 October 1893 – 8 December 1970) was a British chemist based in Leeds and London. His groundbreaking work in the 1920s and 1930s on reaction mechanisms and the electronic structure of organic compounds was resp ...
*
Finkelstein reaction The Finkelstein reaction named after the German chemist Hans Finkelstein, is an SN2 reaction (Substitution Nucleophilic Bimolecular reaction) that involves the exchange of one halogen atom for another. It is an equilibrium reaction, but the react ...
*
Neighbouring group participation In organic chemistry, neighbouring group participation (NGP, also known as anchimeric assistance) has been defined by the International Union of Pure and Applied Chemistry (IUPAC) as the interaction of a reaction centre with a lone pair of electro ...
*
Nucleophilic acyl substitution Nucleophilic acyl substitution describe a class of substitution reactions involving nucleophiles and acyl compounds. In this type of reaction, a nucleophile – such as an alcohol, amine, or enolate – displaces the leaving group of an acyl deriv ...
*
Nucleophilic aromatic substitution A nucleophilic aromatic substitution is a substitution reaction in organic chemistry in which the nucleophile displaces a good leaving group, such as a halide, on an aromatic ring. Aromatic rings are usually nucleophilic, but some aromatic compou ...
* SN1 reaction * SNi *
Substitution reaction A substitution reaction (also known as single displacement reaction or single substitution reaction) is a chemical reaction during which one functional group in a chemical compound is replaced by another functional group. Substitution reactions ar ...


References

{{DEFAULTSORT:Sn2 Reaction Nucleophilic substitution reactions Reaction mechanisms