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.; ...

, neighbouring group participation (NGP, also known as anchimeric assistance) has been defined by the

International Union of Pure and Applied Chemistry The International Union of Pure and Applied Chemistry (IUPAC ) is an international federation of National Adhering Organizations working for the advancement of the chemical sciences, especially by developing nomenclature and terminology. It is ...

(IUPAC) as the interaction of a reaction centre with a

lone pair In chemistry, a lone pair refers to a pair of valence electrons that are not shared with another atom in a covalent bondIUPAC ''Gold Book'' definition''lone (electron) pair''/ref> and is sometimes called an unshared pair or non-bonding pair. Lone ...

electron The electron ( or ) is a subatomic particle with a negative one elementary electric charge. Electrons belong to the first generation of the lepton particle family, and are generally thought to be elementary particles because they have no kn ...

s in an atom or the electrons present in a

pi bond In chemistry, pi bonds (π bonds) are covalent chemical bonds, in each of which two lobes of an orbital on one atom overlap with two lobes of an orbital on another atom, and in which this overlap occurs laterally. Each of these atomic orbitals ...

contained within the parent molecule but not conjugated with the reaction centre. When NGP is in operation it is normal for the

reaction rate The reaction rate or rate of reaction is the speed at which a chemical reaction takes place, defined as proportional to the increase in the concentration of a product per unit time and to the decrease in the concentration of a reactant per unit ...

to be increased. It is also possible for the

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 ...

of the reaction to be abnormal (or unexpected) when compared with a ''normal'' reaction. While it is possible for neighbouring groups to influence many reactions in organic chemistry (''e.g.'' the reaction of a

diene In organic chemistry a diene ( ) (diolefin ( ) or alkadiene) is a covalent compound that contains two double bonds, usually among carbon atoms. They thus contain two alk''ene'' units, with the standard prefix ''di'' of systematic nomenclature. ...

such as 1,3-cyclohexadiene with

maleic anhydride Maleic anhydride is an organic compound with the formula C2H2(CO)2O. It is the acid anhydride of maleic acid. It is a colorless or white solid with an acrid odor. It is produced industrially on a large scale for applications in coatings and poly ...

normally gives the

endo isomer In organic chemistry, ''endo''–''exo'' isomerism is a special type of stereoisomerism found in organic compounds with a substituent on a bridged ring system. The prefix ''endo'' is reserved for the isomer with the substituent located closest ...

because of a secondary effect ) this page is limited to neighbouring group effects seen with

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 ...

s and S_N2 reactions.

NGP by heteroatom lone pairs

In this type of

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 ...

, one group of the substrate participates initially in the reaction and thereby affects the reaction. Due to NGP, the

gets increased by many folds. A classic example of NGP is the reaction of a

sulfur Sulfur (or sulphur in British English) is a chemical element with the symbol S and atomic number 16. It is abundant, multivalent and nonmetallic. Under normal conditions, sulfur atoms form cyclic octatomic molecules with a chemical formula ...

nitrogen mustard Nitrogen mustards are cytotoxic organic compounds with the chloroethylamine (Cl(CH2)2NR2) functional group. Although originally produced as chemical warfare agents, they were the first chemotherapeutic agents for treatment of cancer. Nitrogen m ...

with a

nucleophile In chemistry, a nucleophile is a chemical species that forms bonds by donating an electron pair. All molecules and ions with a free pair of electrons or at least one pi bond can act as nucleophiles. Because nucleophiles donate electrons, they are ...

, the rate of reaction is much higher for the sulfur mustard and a nucleophile than it would be for a primary or secondary

alkyl In organic chemistry, an alkyl group is an alkane missing one hydrogen. The term ''alkyl'' is intentionally unspecific to include many possible substitutions. An acyclic alkyl has the general formula of . A cycloalkyl is derived from a cycloalk ...

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 ...

without a

heteroatom In chemistry, a heteroatom () is, strictly, any atom that is not carbon or hydrogen. Organic chemistry In practice, the term is usually used more specifically to indicate that non-carbon atoms have replaced carbon in the backbone of the molecula ...

. center, 400px reacts with water 650 times faster than .

NGP by an alkene

The π orbitals of an

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 ...

can stabilize 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 ...

by helping to delocalize the positive charge of the

. For instance the unsaturated

tosylate 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 tolyl group, –, joined to a sulfonyl group, ––, with the open valence on s ...

will react more quickly (10¹¹ times faster for aqueous solvolysis) with a nucleophile than the saturated tosylate. center, 250px The carbocationic intermediate will be stabilized by

resonance Resonance describes the phenomenon of increased amplitude that occurs when the frequency of an applied periodic force (or a Fourier component of it) is equal or close to a natural frequency of the system on which it acts. When an oscillatin ...

where the positive charge is spread over several atoms. In the diagram below this is shown. center, 600px Here is a different view of the same intermediates. Even if the alkene is more remote from the reacting center the alkene can still act in this way. For instance in the following

benzenesulfonate the alkene is able to delocalise the carbocation. center, 650px Also the increase in the rate of the S_N2 reaction of

allyl In organic chemistry, an allyl group is a substituent with the structural formula , where R is the rest of the molecule. It consists of a methylene bridge () attached to a vinyl group (). The name is derived from the scientific name for garlic, ...

bromide with a nucleophile compared with the reaction of n-propyl bromide is because the orbitals of the π bond overlap with those of the

. In the allyl system the alkene orbitals overlap with the orbitals of a S_N2 transition state. center, 100px

NGP by a cyclopropane, cyclobutane or a homoallyl group

If Cyclopropylmethyl chloride is reacted with

ethanol Ethanol (abbr. EtOH; also called ethyl alcohol, grain alcohol, drinking alcohol, or simply alcohol) is an organic compound. It is an Alcohol (chemistry), alcohol with the chemical formula . Its formula can be also written as or (an ethyl ...

and

water Water (chemical formula ) is an inorganic, transparent, tasteless, odorless, and nearly colorless chemical substance, which is the main constituent of Earth's hydrosphere and the fluids of all known living organisms (in which it acts as a ...

then a mixture of 48% cyclopropylmethyl alcohol, 47%

cyclobutanol Cyclobutanol is an organic compound with the chemical formula C4H8O. It contains a cyclobutyl group with a hydroxyl In chemistry, a hydroxy or hydroxyl group is a functional group with the chemical formula and composed of one oxygen atom cov ...

and 5% homoallyl alcohol (but-3-enol) is obtained. This is because the carbocationic intermediate is delocalised onto many different carbons through a reversible ring opening. NGP in CPMs

NGP by an aromatic ring

In the case of a

benzyl In organic chemistry, benzyl is the substituent or molecular fragment possessing the structure . Benzyl features a benzene ring () attached to a methylene group () group. Nomenclature In IUPAC nomenclature, the prefix benzyl refers to a substi ...

halide the reactivity is higher because the S_N2 transition state enjoys a similar overlap effect to that in the allyl system according to the molecular orbital theory. center, 100px An

aromatic In chemistry, aromaticity is a chemical property of cyclic ( ring-shaped), ''typically'' planar (flat) molecular structures with pi bonds in resonance (those containing delocalized electrons) that gives increased stability compared to satur ...

ring can assist in the formation of a

ic intermediate called a phenonium ion by delocalising the positive charge. center, 650px When the following

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 tolyl group, –, joined to a sulfonyl group, ––, with the open valence on s ...

ate reacts with

acetic acid Acetic acid , systematically named ethanoic acid , is an acidic, colourless liquid and organic compound with the chemical formula (also written as , , or ). Vinegar is at least 4% acetic acid by volume, making acetic acid the main component ...

solvolysis In chemistry, solvolysis is a type of nucleophilic substitution (S1/S2) or elimination reaction, elimination where the nucleophile is a solvent molecule. Characteristic of S1 reactions, solvolysis of a chirality (chemistry), chiral reactant affor ...

then rather than a simple S_N2 reaction forming B, a 48:48:4 mixture of A, B (which are enantiomers) and C+D was obtained . center, 600px The mechanism which forms A and B is shown below. center, 600px

NGP by aliphatic C-C or C-H bonds

Aliphatic C-C or C-H bonds can lead to charge delocalization if these bonds are close and antiperiplanar to the leaving group. Corresponding intermediates are referred to a

nonclassical ions Nonclassical carbocations are stabilized by charge delocalization from contributions of neighbouring or bonds, which can form bridged intermediates or transition states. Nonclassical ions have been extensively studied with the 2-norbornyl sy ...

, with the 2-norbornyl system as the most well known case.

External links

IUPAC definition

References

# ''Advanced organic chemistry'', page 314, Jerry March (4th Ed), Wiley-Interscience. # ''Studies in

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 ...

. I. The

Stereospecific In chemistry, stereospecificity is the property of a reaction mechanism that leads to different stereoisomeric reaction products from different stereoisomeric reactants, or which operates on only one (or a subset) of the stereoisomers."Overlap Con ...

Wagner-Meerwein rearrangement of the

Isomer In chemistry, isomers are molecules or polyatomic ions with identical molecular formulae – that is, same number of atoms of each element – but distinct arrangements of atoms in space. Isomerism is existence or possibility of isomers. Iso ...

s of 3-Phenyl-2-butanol''

Donald J. Cram Donald James Cram (April 22, 1919 – June 17, 2001) was an American chemist who shared the 1987 Nobel Prize in Chemistry with Jean-Marie Lehn and Charles J. Pedersen "for their development and use of molecules with structure-specific inter ...

J. Am. Chem. Soc. The ''Journal of the American Chemical Society'' is a weekly peer-reviewed scientific journal that was established in 1879 by the American Chemical Society. The journal has absorbed two other publications in its history, the ''Journal of Analytic ...

; 1949; 71(12); 3863-3870
Abstract
# {{Note, Cram2 ''Studies in Stereochemistry. V. Phenonium Sulfonate Ion-pairs as Intermediates in the Intramolecular Rearrangements and Solvolysis Reactions that Occur in the 3-Phenyl-2-butanol System''

; 1952; 74(9); 2129-213
Abstract
Physical organic chemistry Chemical kinetics