Editing Substitution reaction

{{short description|Chemical reaction in which one functional group in a compound is replaced by another}}
{{redirect|Aromatic substitution|''ortho/meta/para'' patterns|Arene substitution pattern}}
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.<ref name=":0">{{JerryMarch}}</ref> Substitution reactions are of prime importance in [[organic chemistry]]. Substitution reactions in organic chemistry are classified either as [[electrophile|electrophilic]] or [[nucleophile|nucleophilic]] depending upon the reagent involved, whether a [[reactive intermediate]] involved in the reaction is a [[carbocation]], a [[carbanion]] or a [[radical (chemistry)|free radical]], and whether the [[substrate (chemistry)|substrate]] is [[aliphatic]] or [[aromatic]]. Detailed understanding of a reaction type helps to predict the product outcome in a reaction. It also is helpful for optimizing a reaction with regard to variables such as temperature and choice of [[solvent]].

A good example of a substitution reaction is [[halogenation]]. When [[chlorine]] gas (Cl<sub>2</sub>) is irradiated, some of the molecules are split into two chlorine [[radical (chemistry)|radicals]] (Cl•), whose free electrons are strongly [[nucleophilic]]. One of them breaks a [[carbon–hydrogen bond|C–H covalent bond]] in CH<sub>4</sub> and grabs the hydrogen atom to form the electrically neutral HCl. The other radical reforms a covalent bond with the CH<sub>3</sub>• to form CH<sub>3</sub>Cl ([[methyl chloride]]).

{| class="wikitable" 
|- align="center" 
||
[[Image:SubstitutionReaction.svg|Substitution reaction : chlorination of methane]]
|- align="center"
!chlorination of methane by chlorine
|}

==Nucleophilic substitution==
{{Main|Nucleophilic substitution}}
In organic (and inorganic) chemistry, [[nucleophilic substitution]] is a fundamental class of reactions in which a [[nucleophile]] selectively bonds with or attacks the positive or partially positive charge on an atom or a group of atoms. As it does so, it replaces a weaker nucleophile, which then becomes a [[leaving group]]; the remaining positive or partially positive atom becomes an [[electrophile]]. The whole molecular entity of which the electrophile and the leaving group are part is usually called the [[Substrate (chemistry)|substrate]].<ref name=":0" />

The most general form for the reaction may be given as 
:<chem>Nuc\mathbf{:}- + R-LG -> R-Nuc{} + LG\mathbf{:}-</chem>
where {{chem2|R\sLG}} indicates the substrate. The [[electron pair]] (''':''') from the nucleophile (Nuc:) attacks the substrate ({{chem2|R\sLG}}), forming a new covalent bond {{chem2|Nuc\sR\sLG}}. The prior state of charge is restored when the leaving group (LG) departs with an electron pair. The principal product in this case is {{chem2|R\sNuc}}. In such reactions, the nucleophile is usually electrically neutral or negatively charged, whereas the substrate is typically neutral or positively charged.

An example of nucleophilic substitution is the hydrolysis of an [[alkyl]] bromide, {{chem2|R\sBr}}, under basic conditions, where the ''attacking'' nucleophile is the base {{chem2|OH-}} and the leaving group is {{chem2|Br-}}:
:<chem>R-Br + OH- -> R-OH + Br-</chem>
Nucleophilic substitution reactions are commonplace in organic chemistry, and they can be broadly categorized as taking place at a carbon of a saturated [[aliphatic compound]] carbon or (less often) at an aromatic or other unsaturated carbon center.<ref name=":0" />

=== Mechanisms ===
{{Main|SN1 reaction|SN2 reaction|Nucleophilic acyl substitution}}

Nucleophilic substitutions can proceed by two different mechanisms, unimolecular nucleophilic substitution ([[SN1 reaction|S<sub>N</sub>1]]) and bimolecular nucleophilic substitution ([[SN2 reaction|S<sub>N</sub>2]]). The two reactions are named according tho their [[Rate equation|rate law]], with S<sub>N</sub>1 having a first-order rate law, and S<sub>N</sub>2 having a second-order.<ref name=":03">{{Cite book |last=Bruice |first=Paula Yurkanis |title=Organic Chemistry |publisher=Pearson Education Inc. |year=2011 |isbn=978-0-321-66313-9 |edition=6th |location=1900 E. Lake Ave., Glenview, IL 60025 |pages=332-365 |language=English}}</ref>
[[File:SN1 Reaction Mechanism.jpg|thumb|S<sub>N</sub>1 reaction mechanism occurring through two steps]]
The S<sub>N</sub>1 mechanism has two steps. In the first step, the leaving group departs, forming a [[carbocation]] (C<sup>+</sup>). In the second step, the nucleophilic reagent (Nuc:) attaches to the carbocation and forms a covalent sigma bond. If the substrate has a [[Chirality|chiral]] carbon, this mechanism can result in either inversion of the [[stereochemistry]] or retention of configuration.  Usually, both occur without preference. The result is [[racemization]].

The stability of a carbocation (C<sup>+</sup>) depends on how many other carbon atoms are bonded to it. This results in S<sub>N</sub>1 reactions usually occurring on atoms with at least two carbons bonded to them.<ref name=":03" /> A more detailed explanation of this can be found in the main [[SN1 reaction]] page.
[[File:SN2 reaction mechanism.png|thumb|S<sub>N</sub>2 reaction mechanism]]
The S<sub>N</sub>2 mechanism has just one step. The attack of the reagent and the expulsion of the leaving group happen simultaneously. This mechanism always results in inversion of configuration. If the substrate that is under nucleophilic attack is chiral, the reaction will therefore lead to an inversion of its [[stereochemistry]], called a [[Walden inversion]].

S<sub>N</sub>2 attack may occur if the backside route of attack is not [[sterically hindered]] by substituents on the substrate. Therefore, this mechanism usually occurs at an unhindered [[primary carbon]] center. If there is steric crowding on the substrate near the leaving group, such as at a [[tertiary carbon]] center, the substitution will involve an S<sub>N</sub>1 rather than an S<sub>N</sub>2.<ref name=":03" />
[[File:General Scheme for Base Catalyzed Nucleophilc Acyl Substitution.png|thumb|Nucleophilic acyl substitution mechanism]]
Other types of nucleophilic substitution include, [[nucleophilic acyl substitution]], and [[nucleophilic aromatic substitution]]. Acyl substitution occurs when a nucleophile attacks a carbon that is doubly bonded to one oxygen and singly bonded to another oxygen (can be N or S or a [[halogen]]), called an [[Acyl group|acyl]] group. The nucleophile attacks the carbon causing the double bond to break into a single bond. The double can then reform, kicking off the leaving group in the process.

Aromatic substitution occurs on compounds with systems of double bonds connected in rings. See [[Aromatic compound|aromatic compounds]] for more.

== Electrophilic substitution ==
{{Main|Electrophilic substitution}}
[[Electrophile]]s are involved in [[electrophilic substitution]] reactions, particularly in [[electrophilic aromatic substitution]]s.

In this example, the benzene ring's electron resonance structure is attacked by an electrophile E<sup>+</sup>. The resonating bond is broken and a carbocation resonating structure results. Finally a proton is kicked out and a new aromatic compound is formed.
{| class="wikitable"
|+Electrophilic aromatic substitution
|[[File:Electrophilic_aromatic_substitution.svg|Electrophilic aromatic substitution]]
|- align="center"
!<small>'''1:''' Free benzene + electrophile; '''2a:''' Benzene attacks electrophile;</small>
<small>'''2b:''' Resonance of benzene-electrophile intermediate; '''3:''' Substituted reaction product</small>
|}


Electrophilic reactions to other unsaturated compounds than [[Arene|arenes]] generally lead to [[electrophilic addition]] rather than substitution.

== Radical substitution ==
A [[radical substitution]] reaction involves [[radical (chemistry)|radicals]]. An example is the [[Hunsdiecker reaction]].

==Organometallic substitution==
[[Coupling reaction]]s are a class of metal-catalyzed reactions involving an [[Organometallics|organometallic]] compound RM and an organic halide R′X that together react to form a compound of the type R-R′ with formation of a new [[carbon–carbon bond]].  Examples include the [[Heck reaction]], [[Ullmann reaction]], and [[Wurtz–Fittig reaction]]. Many variations exist.<ref>{{cite book |last=Elschenbroich |first=C. |last2=Salzer |first2=A. |title=Organometallics: A Concise Introduction |edition=2nd |year=1992 |publisher=Wiley-VCH |location=Weinheim |isbn=3-527-28165-7 }}</ref>

== Substituted compounds ==
'''Substituted compounds''' are compounds where one or more hydrogen atoms have been replaced with something else such as an [[alkyl]], [[Hydroxyl|hydroxy]], or [[halogen]]. More can be found on the [[Substituted compound|substituted compounds]] page.

==Inorganic and organometallic chemistry==
While it is common to discuss substitution reactions in the context of organic chemistry, the reaction is generic and applies to a wide range of compounds.  Ligands in coordination complexes are susceptible to substitution.  Both associative and dissociative mechanisms have been observed.<ref>Basolo, F.; Pearson, R. G. "Mechanisms of Inorganic Reactions." John Wiley and Son: New York: 1967. {{ISBN|0-471-05545-X}}</ref><ref>{{cite book |first=R. G. |last=Wilkins |title=Kinetics and Mechanism of Reactions of Transition Metal Complexes |url=https://archive.org/details/kineticsmechanis00wilk_0 |url-access=registration |edition=2nd |publisher=VCH |location=Weinheim |year=1991 |isbn=1-56081-125-0 }}</ref>

[[Associative substitution]], for example, is typically applied to [[Organometallic chemistry|organometallic]] and [[coordination complex]]es, but resembles the [[SN2 reaction|Sn2 mechanism]] in [[organic chemistry]].  The opposite pathway is [[dissociative substitution]], being analogous to the [[SN1 reaction|Sn1 pathway]]. 

Examples of associative mechanisms are commonly found in the chemistry of 16e [[Square planar molecular geometry|square planar]] metal complexes, e.g. [[Vaska's complex]] and [[Potassium tetrachloroplatinate|tetrachloroplatinate]]. The [[rate law]] is governed by the [[Associative substitution#Eigen-Wilkins mechanism|Eigen–Wilkins Mechanism]].
[[File:AssveRxn.png|520px|center]]

[[Dissociative substitution]] resembles the [[SN1 reaction|S<sub>N</sub>1 mechanism]] in organic chemistry.  This pathway can be well described by the [[cis effect|''cis'' effect]], or the labilization of CO ligands in the ''cis'' position. Complexes that undergo dissociative substitution are often [[coordinative unsaturation|coordinatively saturated]] and often have [[octahedral molecular geometry]]. The [[entropy of activation]] is characteristically positive for these reactions, which indicates that the disorder of the reacting system increases in the rate-determining step. Dissociative pathways are characterized by a [[rate determining step]] that involves release of a ligand from the coordination sphere of the metal undergoing substitution.  The concentration of the substituting [[nucleophile]] has no influence on this rate, and an intermediate of reduced coordination number can be detected. The reaction can be described with k<sub>1</sub>, k<sub>−1</sub> and k<sub>2</sub>, which are the [[rate constant]]s of their corresponding intermediate reaction steps:

:<chem>L_\mathit{n}M-L <=>[-\mathrm L, k_1][+\mathrm L, k_{-1}] L_\mathit{n}M-\Box ->[+\mathrm L', k_2] L_\mathit{n}M-L'</chem>
Normally the rate determining step is the dissociation of L from the complex, and [L'] does not affect the rate of reaction, leading to the simple rate equation:

:<chem> Rate = {\mathit k_1 [L_\mathit{n}M-L]}</chem>

== Further reading ==

* Imyanitov, Naum S. (1993). "Is This Reaction a Substitution, Oxidation-Reduction, or Transfer?". ''J. Chem. Educ''. '''70''' (1): 14–16. [[Bibcode (identifier)|Bibcode]]:1993JChEd..70...14I. [[Doi (identifier)|doi]]:10.1021/ed070p14.

==References==
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{{Reaction mechanisms}}
{{Organic reactions}}

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[[Category:Substitution reactions| ]]