Nucleophilic addition

Nucleophilic addition

Overview
In organic chemistry
Organic chemistry
Organic chemistry is a subdiscipline within chemistry involving the scientific study of the structure, properties, composition, reactions, and preparation of carbon-based compounds, hydrocarbons, and their derivatives...

, a nucleophilic addition reaction is an addition reaction
Addition reaction
An addition reaction, in organic chemistry, is in its simplest terms an organic reaction where two or more molecules combine to form a larger one....

 where in a chemical compound
Chemical compound
A chemical compound is a pure chemical substance consisting of two or more different chemical elements that can be separated into simpler substances by chemical reactions. Chemical compounds have a unique and defined chemical structure; they consist of a fixed ratio of atoms that are held together...

 a π bond is removed by the creation of two new covalent bond
Covalent bond
A covalent bond is a form of chemical bonding that is characterized by the sharing of pairs of electrons between atoms. The stable balance of attractive and repulsive forces between atoms when they share electrons is known as covalent bonding....

s by the addition of a nucleophile
Nucleophile
A nucleophile is a species that donates an electron-pair to an electrophile to form a chemical bond in a reaction. All molecules or ions with a free pair of electrons can act as nucleophiles. Because nucleophiles donate electrons, they are by definition Lewis bases.Nucleophilic describes the...

.

Addition reactions are limited to chemical compounds that have multiple-bonded atoms:
  • molecules with carbon – hetero multiple bonds like carbonyl
    Carbonyl
    In organic chemistry, a carbonyl group is a functional group composed of a carbon atom double-bonded to an oxygen atom: C=O. It is common to several classes of organic compounds, as part of many larger functional groups....

    s, imine
    Imine
    An imine is a functional group or chemical compound containing a carbon–nitrogen double bond, with the nitrogen attached to a hydrogen atom or an organic group. If this group is not a hydrogen atom, then the compound is known as a Schiff base...

    s or nitrile
    Nitrile
    A nitrile is any organic compound that has a -C≡N functional group. The prefix cyano- is used interchangeably with the term nitrile in industrial literature. Nitriles are found in many useful compounds, one example being super glue .Inorganic compounds containing the -C≡N group are not called...

    s
  • molecules with carbon – carbon double bond
    Double bond
    A double bond in chemistry is a chemical bond between two chemical elements involving four bonding electrons instead of the usual two. The most common double bond, that between two carbon atoms, can be found in alkenes. Many types of double bonds between two different elements exist, for example in...

    s or triple bond
    Triple bond
    A triple bond in chemistry is a chemical bond between two chemical elements involving six bonding electrons instead of the usual two in a covalent single bond. The most common triple bond, that between two carbon atoms, can be found in alkynes. Other functional groups containing a triple bond are...

    s.


Addition reactions of a nucleophile to carbon – hetero double bonds such as C=O or CN triple bond show a wide variety.
Discussion
Ask a question about 'Nucleophilic addition'
Start a new discussion about 'Nucleophilic addition'
Answer questions from other users
Full Discussion Forum
 
Unanswered Questions
Encyclopedia
In organic chemistry
Organic chemistry
Organic chemistry is a subdiscipline within chemistry involving the scientific study of the structure, properties, composition, reactions, and preparation of carbon-based compounds, hydrocarbons, and their derivatives...

, a nucleophilic addition reaction is an addition reaction
Addition reaction
An addition reaction, in organic chemistry, is in its simplest terms an organic reaction where two or more molecules combine to form a larger one....

 where in a chemical compound
Chemical compound
A chemical compound is a pure chemical substance consisting of two or more different chemical elements that can be separated into simpler substances by chemical reactions. Chemical compounds have a unique and defined chemical structure; they consist of a fixed ratio of atoms that are held together...

 a π bond is removed by the creation of two new covalent bond
Covalent bond
A covalent bond is a form of chemical bonding that is characterized by the sharing of pairs of electrons between atoms. The stable balance of attractive and repulsive forces between atoms when they share electrons is known as covalent bonding....

s by the addition of a nucleophile
Nucleophile
A nucleophile is a species that donates an electron-pair to an electrophile to form a chemical bond in a reaction. All molecules or ions with a free pair of electrons can act as nucleophiles. Because nucleophiles donate electrons, they are by definition Lewis bases.Nucleophilic describes the...

.

Addition reactions are limited to chemical compounds that have multiple-bonded atoms:
  • molecules with carbon – hetero multiple bonds like carbonyl
    Carbonyl
    In organic chemistry, a carbonyl group is a functional group composed of a carbon atom double-bonded to an oxygen atom: C=O. It is common to several classes of organic compounds, as part of many larger functional groups....

    s, imine
    Imine
    An imine is a functional group or chemical compound containing a carbon–nitrogen double bond, with the nitrogen attached to a hydrogen atom or an organic group. If this group is not a hydrogen atom, then the compound is known as a Schiff base...

    s or nitrile
    Nitrile
    A nitrile is any organic compound that has a -C≡N functional group. The prefix cyano- is used interchangeably with the term nitrile in industrial literature. Nitriles are found in many useful compounds, one example being super glue .Inorganic compounds containing the -C≡N group are not called...

    s
  • molecules with carbon – carbon double bond
    Double bond
    A double bond in chemistry is a chemical bond between two chemical elements involving four bonding electrons instead of the usual two. The most common double bond, that between two carbon atoms, can be found in alkenes. Many types of double bonds between two different elements exist, for example in...

    s or triple bond
    Triple bond
    A triple bond in chemistry is a chemical bond between two chemical elements involving six bonding electrons instead of the usual two in a covalent single bond. The most common triple bond, that between two carbon atoms, can be found in alkynes. Other functional groups containing a triple bond are...

    s.

Addition to carbon – hetero double bonds


Addition reactions of a nucleophile to carbon – hetero double bonds such as C=O or CN triple bond show a wide variety. These bonds are polar
Polar bond
In chemistry, a polar bond is a type of covalent bond between two atoms or more in which electrons are shared unequally. Because of this, one end of the molecule has a slight, relative negative charge and the other a slight, relative positive charge...

 (have a large difference in electronegativity
Electronegativity
Electronegativity, symbol χ , is a chemical property that describes the tendency of an atom or a functional group to attract electrons towards itself. An atom's electronegativity is affected by both its atomic number and the distance that its valence electrons reside from the charged nucleus...

 between the two atoms) consequently carbon carries a partial positive charge. This makes this atom the primary target for the nucleophile.

This type of reaction is also called a 1,2 nucleophilic addition. The stereochemistry
Stereochemistry
Stereochemistry, a subdiscipline of chemistry, involves the study of the relative spatial arrangement of atoms within molecules. An important branch of stereochemistry is the study of chiral molecules....

 of this type of nucleophilic attack is not an issue, when both alkyl substituents are dissimilar and there are not any other controlling issues such as chelation
Chelation
Chelation is the formation or presence of two or more separate coordinate bonds between apolydentate ligand and a single central atom....

 with a Lewis acid
Lewis acid
]The term Lewis acid refers to a definition of acid published by Gilbert N. Lewis in 1923, specifically: An acid substance is one which can employ a lone pair from another molecule in completing the stable group of one of its own atoms. Thus, H+ is a Lewis acid, since it can accept a lone pair,...

, the reaction product is a racemate. Addition reactions of this type are numerous. When the addition reaction is accompanied by an elimination the reaction type is nucleophilic acyl substitution
Nucleophilic acyl substitution
Nucleophilic acyl substitution describes the substitution reaction involving nucleophiles and acyl compounds. Acyl compounds are carboxylic acid derivatives including esters, amides and acid halides...

 or an addition-elimination reaction.

Carbonyls


With a carbonyl compound as an electrophile, the nucleophile can be:
  • water
    Water
    Water is a chemical substance with the chemical formula H2O. A water molecule contains one oxygen and two hydrogen atoms connected by covalent bonds. Water is a liquid at ambient conditions, but it often co-exists on Earth with its solid state, ice, and gaseous state . Water also exists in a...

     in hydration
    Hydration reaction
    In organic chemistry, a hydration reaction is a chemical reaction in which a hydroxyl group and a hydrogen cation are added to the two carbon atoms bonded together in the carbon-carbon double bond which makes up an alkene functional group. The reaction usually runs in a strong acidic, aqueous...

     to a geminal
    Geminal
    In chemistry, the term geminal refers to the relationship between two functional groups that are attached to the same atom...

     diol
    Diol
    A diol or glycol is a chemical compound containing two hydroxyl groups A geminal diol has two hydroxyl groups bonded to the same atom...

     (hydrate)
  • an alcohol
    Alcohol
    In chemistry, an alcohol is an organic compound in which the hydroxy functional group is bound to a carbon atom. In particular, this carbon center should be saturated, having single bonds to three other atoms....

     in acetalisation
    Acetalisation
    Acetalisation is an organic reaction that involves the formation of an acetal or ketal. One way of acetal formation is the nucleophilic addition of an alcohol to a ketone or an aldehyde...

     to an acetal
    Acetal
    An acetal is a molecule with two single-bonded oxygen atoms attached to the same carbon atom.Traditional usages distinguish ketals from acetals...

  • a hydride
    Hydride
    In chemistry, a hydride is the anion of hydrogen, H−, or, more commonly, a compound in which one or more hydrogen centres have nucleophilic, reducing, or basic properties. In compounds that are regarded as hydrides, hydrogen is bonded to a more electropositive element or group...

     in reduction
    Reducing agent
    A reducing agent is the element or compound in a reduction-oxidation reaction that donates an electron to another species; however, since the reducer loses an electron we say it is "oxidized"...

     to an alcohol
    Alcohol
    In chemistry, an alcohol is an organic compound in which the hydroxy functional group is bound to a carbon atom. In particular, this carbon center should be saturated, having single bonds to three other atoms....

  • an amine
    Amine
    Amines are organic compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are derivatives of ammonia, wherein one or more hydrogen atoms have been replaced by a substituent such as an alkyl or aryl group. Important amines include amino acids, biogenic amines,...

     with formaldehyde and a carbonyl compound in the Mannich reaction
    Mannich reaction
    The Mannich reaction is an organic reaction which consists of an amino alkylation of an acidic proton placed next to a carbonyl functional group with formaldehyde and ammonia or any primary or secondary amine. The final product is a β-amino-carbonyl compound also known as a Mannich base...

  • an enolate ion in an aldol reaction
    Aldol reaction
    The aldol reaction is a powerful means of forming carbon–carbon bonds in organic chemistry.Discovered independently by Charles-Adolphe Wurtz and Alexander Porfyrevich Borodin in 1872, the reaction combines two carbonyl compounds to form a new β-hydroxy carbonyl compound...

     or Baylis–Hillman reaction
    Baylis–Hillman reaction
    The Baylis–Hillman reaction is an organic reaction of an aldehyde and an α,β-unsaturated electron-withdrawing group catalyzed by DABCO to give an allylic alcohol. This reaction is also known as the Morita–Baylis–Hillman reaction or MBH reaction. It is named for the Japanese chemist Ken-ichi...

  • an organometallic nucleophile
    Nucleophile
    A nucleophile is a species that donates an electron-pair to an electrophile to form a chemical bond in a reaction. All molecules or ions with a free pair of electrons can act as nucleophiles. Because nucleophiles donate electrons, they are by definition Lewis bases.Nucleophilic describes the...

     in the Grignard reaction
    Grignard reaction
    The Grignard reaction is an organometallic chemical reaction in which alkyl- or aryl-magnesium halides add to a carbonyl group in an aldehyde or ketone. This reaction is an important tool for the formation of carbon–carbon bonds...

     or the related Barbier reaction
    Barbier reaction
    The Barbier reaction is an organic reaction between an alkyl halide and a carbonyl group as an electrophilic substrate in the presence of magnesium, aluminium, zinc, indium, tin or its salts. The reaction product is a primary, secondary or tertiary alcohol...

     or a Reformatskii reaction
    Reformatskii reaction
    The Reformatsky reaction is an organic reaction which condenses aldehydes , 1, with α-halo esters, 2, using a metallic zinc to form β-hydroxy-esters, 3...

  • ylide
    Ylide
    An ylide or ylid is a neutral dipolar molecule containing a formally negatively charged atom directly attached to a hetero atom with a formal positive charge , and in which both atoms have full octets of electrons. Ylides are thus 1,2-dipolar compounds...

    s such as a Wittig reagent or the Corey–Chaykovsky reagent  or α-silyl carbanions in the Peterson olefination
    Peterson olefination
    The Peterson olefination is the chemical reaction of α-silyl carbanions 1 with ketones to form a β-hydroxysilane 2 which eliminates to form alkenes 3.Several reviews have been published....

  • a phosphonate carbanion in the Horner–Wadsworth–Emmons reaction
  • a pyridine zwitterion in the Hammick reaction
    Hammick reaction
    The Hammick reaction, named after Dalziel Hammick, is a chemical reaction described as a thermal decarboxylation of α-picolinic acids in the presence of carbonyl compounds to form 2-pyridyl-carbinols....

  • an acetylide in the Favorskii reaction
    Favorskii reaction
    The Favorskii reaction , named for the Russian chemist Alexei Yevgrafovich Favorskii, is a special case of nucleophilic attack on a carbonyl group involving a terminal alkyne with acidic protons....

    .

Nitriles


With nitrile
Nitrile
A nitrile is any organic compound that has a -C≡N functional group. The prefix cyano- is used interchangeably with the term nitrile in industrial literature. Nitriles are found in many useful compounds, one example being super glue .Inorganic compounds containing the -C≡N group are not called...

 electrophiles nucleophilic addition take place by:
  • hydrolysis of a nitrile
    Nitrile
    A nitrile is any organic compound that has a -C≡N functional group. The prefix cyano- is used interchangeably with the term nitrile in industrial literature. Nitriles are found in many useful compounds, one example being super glue .Inorganic compounds containing the -C≡N group are not called...

     to an amide
    Amide
    In chemistry, an amide is an organic compound that contains the functional group consisting of a carbonyl group linked to a nitrogen atom . The term refers both to a class of compounds and a functional group within those compounds. The term amide also refers to deprotonated form of ammonia or an...

     or a carboxylic acid
    Carboxylic acid
    Carboxylic acids are organic acids characterized by the presence of at least one carboxyl group. The general formula of a carboxylic acid is R-COOH, where R is some monovalent functional group...

  • organozinc nucleophiles in the Blaise reaction
    Blaise reaction
    The Blaise reaction is an organic reaction that forms a β-ketoester from the reaction of zinc metal with a α-bromoester and a nitrile. The final intermediate is a metaloimine, which is hydrolyzed to give the desired β-ketoester....

  • alcohol
    Alcohol
    In chemistry, an alcohol is an organic compound in which the hydroxy functional group is bound to a carbon atom. In particular, this carbon center should be saturated, having single bonds to three other atoms....

    s in the Pinner reaction
    Pinner reaction
    The Pinner reaction is an organic reaction of a nitrile with an alcohol under acid catalysis for instance hydrochloric acid. The product formed is the hydrochloric acid salt of an imino ester or an alkyl imidate, which sometimes is called a Pinner salt...

    .
  • the (same) nitrile α-carbon in the Thorpe reaction
    Thorpe reaction
    The Thorpe reaction is a chemical reaction described as a self-condensation of aliphatic nitriles catalyzed by base to form enamines. The reaction was discovered by Jocelyn Field Thorpe.-Thorpe–Ziegler reaction:...

    . The intramolecular version is called the Thorpe–Ziegler reaction.

Imines and other


With imine
Imine
An imine is a functional group or chemical compound containing a carbon–nitrogen double bond, with the nitrogen attached to a hydrogen atom or an organic group. If this group is not a hydrogen atom, then the compound is known as a Schiff base...

 electrophiles nucleophilic addition take place by:
  • hydrides to amines in the Eschweiler–Clarke reaction
  • water to carbonyls in the Nef reaction
    Nef reaction
    The Nef reaction is an organic reaction describing the acid hydrolysis of a salt of a primary or secondary nitroalkane to an aldehyde or a ketone and nitrous oxide ....

    .


With miscellaneous electrophiles:
  • addition of an alcohol
    Alcohol
    In chemistry, an alcohol is an organic compound in which the hydroxy functional group is bound to a carbon atom. In particular, this carbon center should be saturated, having single bonds to three other atoms....

     to an isocyanate
    Isocyanate
    Isocyanate is the functional group of elements –N=C=O , not to be confused with the cyanate functional group which is arranged as –O–C≡N or with isocyanide, R-N≡C. Any organic compound which contains an isocyanate group may also be referred to in brief as an isocyanate. An isocyanate may have more...

     to form a carbamate
    Carbamate
    Carbamates are organic compounds derived from carbamic acid . A carbamate group, carbamate ester, and carbamic acids are functional groups that are inter-related structurally and often are interconverted chemically. Carbamate esters are also called urethanes.-Synthesis:Carbamic acids are derived...

    .


Nucleophiles attack carbonyl centers from a specific angle called the Bürgi–Dunitz angle.

Addition to carbon – carbon double bonds


The driving force for the addition to alkenes is the formation of a nucleophile
Nucleophile
A nucleophile is a species that donates an electron-pair to an electrophile to form a chemical bond in a reaction. All molecules or ions with a free pair of electrons can act as nucleophiles. Because nucleophiles donate electrons, they are by definition Lewis bases.Nucleophilic describes the...

 X that forms a covalent bond
Covalent bond
A covalent bond is a form of chemical bonding that is characterized by the sharing of pairs of electrons between atoms. The stable balance of attractive and repulsive forces between atoms when they share electrons is known as covalent bonding....

 with an electron-poor unsaturated
Saturation (chemistry)
In chemistry, saturation has six different meanings, all based on reaching a maximum capacity...

 system -C=C- (step 1). The negative charge on X is transferred to the carbon – carbon bond.


In step 2 the negatively charged carbanion
Carbanion
A carbanion is an anion in which carbon has an unshared pair of electrons and bears a negative charge usually with three substituents for a total of eight valence electrons. The carbanion exists in a trigonal pyramidal geometry. Formally a carbanion is the conjugate base of a carbon acid.where B...

 combines with (Y) that is electron-poor to form the second covalent bond.

Ordinary alkenes are not susceptible to a nucleophilic attack (apolar bond). Styrene reacts in toluene
Toluene
Toluene, formerly known as toluol, is a clear, water-insoluble liquid with the typical smell of paint thinners. It is a mono-substituted benzene derivative, i.e., one in which a single hydrogen atom from the benzene molecule has been replaced by a univalent group, in this case CH3.It is an aromatic...

 with sodium
Sodium
Sodium is a chemical element with the symbol Na and atomic number 11. It is a soft, silvery-white, highly reactive metal and is a member of the alkali metals; its only stable isotope is 23Na. It is an abundant element that exists in numerous minerals, most commonly as sodium chloride...

 to 1,3-diphenylpropane through the intermediate carbanion:

Another exception to the rule is found in the Varrentrapp reaction
Varrentrapp reaction
The Varrentrapp reaction is an organic reaction involving the chemical decomposition of an α,β-unsaturated acid into two other acid fragments by action of molten alkali. This reaction pioneered by F...

. Fullerene
Fullerene
A fullerene is any molecule composed entirely of carbon, in the form of a hollow sphere, ellipsoid, or tube. Spherical fullerenes are also called buckyballs, and they resemble the balls used in association football. Cylindrical ones are called carbon nanotubes or buckytubes...

s have unusual double bond
Double bond
A double bond in chemistry is a chemical bond between two chemical elements involving four bonding electrons instead of the usual two. The most common double bond, that between two carbon atoms, can be found in alkenes. Many types of double bonds between two different elements exist, for example in...

 reactivity and additions such has the Bingel reaction
Bingel reaction
The Bingel reaction in fullerene chemistry is a fullerene cyclopropanation reaction to a methanofullerene first discovered by C. Bingel in 1993 with the bromo derivative of diethyl malonate in the presence of a base such as sodium hydride or DBU...

 are more frequent.

When X is a carbonyl group like C=O or COOR or a cyanide
Cyanide
A cyanide is a chemical compound that contains the cyano group, -C≡N, which consists of a carbon atom triple-bonded to a nitrogen atom. Cyanides most commonly refer to salts of the anion CN−. Most cyanides are highly toxic....

 group (CN), the reaction type is a conjugate addition reaction. The substituent X helps to stabilize the negative charge on the carbon atom by its inductive effect
Inductive effect
In chemistry and physics, the inductive effect is an experimentally observable effect of the transmission of charge through a chain of atoms in a molecule by electrostatic induction...

.

In addition when Y-Z is an active hydrogen compound the reaction is known as a Michael reaction
Michael reaction
The Michael reaction or Michael addition is the nucleophilic addition of a carbanion or another nucleophile to an alpha, beta unsaturated carbonyl compound. It belongs to the larger class of conjugate additions. This is one of the most useful methods for the mild formation of C-C bonds...

.

Perfluorinated alkenes (alkenes that have all hydrogens replaced by fluorine
Fluorine
Fluorine is the chemical element with atomic number 9, represented by the symbol F. It is the lightest element of the halogen column of the periodic table and has a single stable isotope, fluorine-19. At standard pressure and temperature, fluorine is a pale yellow gas composed of diatomic...

) are highly prone to nucleophilic addition, for example by fluoride ion from caesium fluoride
Caesium fluoride
Caesium fluoride , is an inorganic compound usually encountered as a hygroscopic white solid. It is more soluble and more readily dissociated than sodium fluoride or potassium fluoride. It is available in anhydrous form, and if water has been absorbed it is easy to dry by heating at 100 °C for...

 or silver(I) fluoride
Silver(I) fluoride
Silver fluoride , also known as argentous fluoride and silver monofluoride, is a compound of silver and fluorine. It is a ginger-coloured solid, melting point 435 °C, which blackens on exposure to moist air. Unlike other silver halides such as silver chloride it is soluble in water to the extent...

to give a perfluoroalkyl anion.