Nucleophilic addition
In organic chemistry, a nucleophilic addition reaction is an addition reaction where a chemical compound with an electron-deficient or electrophilic double or triple bond, a π bond, reacts with electron-rich reactant, termed a nucleophile, with disappearance of the double bond and creation of two new single, or σ, bonds. The reactions are involved in the biological synthesis of compounds in the metabolism of every living organism, and are used by chemists in academia and industries such as pharma to prepare most new complex organic chemicals, and so are central to organic chemistry. Addition reactions require the presence of groups with multiple bonds in the electrophile: carbon–heteroatom multiple bonds as in carbonyls, imines, and nitriles, or carbon–carbon double or triple bonds.
Contents
Addition to carbon–heteroatom double bonds
Nucleophilic addition reactions of nucleophiles with electrophilic double or triple bond (π bonds) create a new carbon center with two additional single, or σ, bonds.[1] Addition of a nucleophile to carbon–heteroatom double or triple bonds such as >C=O or -C=N show great variety. These types of bonds are polar (have a large difference in electronegativity between the two atoms); consequently, their carbon atoms carries a partial positive charge. This makes the molecule an electrophile, and the carbon atom the electrophilic center; this atom is the primary target for the nucleophile. Chemists have developed a geometric system to describe the approach of the nucleophile to the electrophilic center, using two angles, the Bürgi–Dunitz and the Flippin–Lodge angles after scientists that first studied and described them.[2][3][4]
This type of reaction is also called a 1,2 nucleophilic addition. The stereochemistry 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 with a Lewis acid, 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 or an addition-elimination reaction.
Addition to Carbonyl groups
With a carbonyl compound as an electrophile, the nucleophile can be:[1]
- water in hydration to a geminal diol (hydrate)
- an alcohol in acetalisation to an acetal
- a hydride in reduction to an alcohol
- an amine with formaldehyde and a carbonyl compound in the Mannich reaction
- an enolate ion in an aldol reaction or Baylis–Hillman reaction
- an organometallic nucleophile in the Grignard reaction or the related Barbier reaction or a Reformatskii reaction
- ylides such as a Wittig reagent or the Corey–Chaykovsky reagent or α-silyl carbanions in the Peterson olefination
- a phosphonate carbanion in the Horner–Wadsworth–Emmons reaction
- a pyridine zwitterion in the Hammick reaction
- an acetylide in the Favorskii reaction.
In many nucleophilic reactions, addition to the carbonyl group is very important. In some cases, the C=O double bond is reduced to a C-O single bond and the nucleophile adds on to bond with carbon. An example is the addition of the cyanide ion to formaldehyde. The cyanide ion forms a C-C bond with formaldehyde and one of the C=O bonds breaks.
Addition to Nitriles
With nitrile electrophiles nucleophilic addition take place by:[1]
- hydrolysis of a nitrile to an amide or a carboxylic acid
- organozinc nucleophiles in the Blaise reaction
- alcohols in the Pinner reaction.
- the (same) nitrile α-carbon in the Thorpe reaction. The intramolecular version is called the Thorpe–Ziegler reaction.
Addition to carbon–carbon double bonds
The driving force for the addition to alkenes is the formation of a nucleophile X− that forms a covalent bond with an electron-poor unsaturated system -C=C- (step 1). The negative charge on X is transferred to the carbon – carbon bond.[1]
In step 2 the negatively charged carbanion 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 with sodium to 1,3-diphenylpropane [5] through the intermediate carbanion:
Another exception to the rule is found in the Varrentrapp reaction. Fullerenes have unusual double bond reactivity and additions such has the Bingel reaction are more frequent. When X is a carbonyl group like C=O or COOR or a cyanide 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. In addition when Y-Z is an active hydrogen compound the reaction is known as a Michael reaction. Perfluorinated alkenes (alkenes that have all hydrogens replaced by fluorine) are highly prone to nucleophilic addition, for example by fluoride ion from caesium fluoride or silver(I) fluoride to give a perfluoroalkyl anion.
References
- ↑ 1.0 1.1 1.2 1.3 March Jerry; (1985). Advanced Organic Chemistry reactions, mechanisms and structure (3rd ed.). New York: John Wiley & Sons, inc. ISBN 0-471-85472-7
- ↑ Lua error in package.lua at line 80: module 'strict' not found.
- ↑ Lua error in package.lua at line 80: module 'strict' not found.
- ↑ Lua error in package.lua at line 80: module 'strict' not found.
- ↑ Sodium-catalyzed Side Chain Aralkylation of Alkylbenzenes with Styrene Herman Pines, Dieter Wunderlich J. Am. Chem. Soc.; 1958; 80(22)6001–6004. doi:10.1021/ja01555a029
 |
Wikimedia Commons has media related to Nucleophilic addition reactions. |
