Nucleophile - Definition, Examples, Types, FAQs

Edited By Team Careers360 | Updated on Jul 02, 2025 05:05 PM IST

In this article we will be discussing about nucleophile, the meaning of nucleophile, definition of nucleophile, examples of nucleophile, what is meant by ambident nucleophile, examples of amident nucleophile. Here we will also discuss about some frequently asked questions related to nucleophile.
Note: In telugu the term ‘ambident’ means ‘Parisara’.

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What is Nucleophilic reagents?

The term reagent means the atomic, molecular, cationic, anionic or radical species that acts upon a substrate in an organic reaction. In mechanistic treatment of organic reactions, three important types of attacking reagents are recognized. They are electrophiles, nucleophiles and free radicals.

A reagent that is electron rich by having at least one lone pair of electrons that it is willing to donate to an electron deficient substrate in a reaction is called a nucleophile or nucleophilic reagent.

Nucleophile definition or define nucleophile or define nucleophile with example: The term nucleophile literally means nucleus loving as phile is the Greek suffix for loving. These are Lewis bases which may be negatively charged ions or neutral molecules which have at least one lone pair of electrons for donation.

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Some of the important nucleophile examples are:

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Reactions in which the attacking reagent is a nucleophile are called nucleophilic reactions.

Some of the terms that are used to explain nucleophiles are:

Nucleophilic nature: This is used to explain the nucleophilic character of a species which shows the affinity of a species towards the positively charged nucleus.
Nucleophilicity: This term denotes the nucleophilic strength of a species. It is generally used to compare the nucleophilic character of various nucleophiles. It is used to indicate the strength of a nucleophile.
Nucleophilic substitution: This type of reaction occurs when a nucleophile attacks positively charged atom present in the molecule and thereby replaces a leaving group by connecting with the positively charged species.

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Types of Nucleophiles

Some of the commonly used nucleophilic species are:

Halogens – The anionic form of halogens generally acts as nucleophiles and its diatomic form does not exhibit the properties of nucleophile. For example I^-acts as a powerful nucleophile in polar protic solvents whereas diatomic iodine (I₂) does not behave as a nucleophile.
Carbon – It is in organometallic reagents and enols carbon acts as nucleophiles. Carbon acts as nucleophiles in the compounds like Grignard reagents, n-butyllithium and organolithium reagents.
Oxygen – The hydroxide ion is an example of a nucleophile containing oxygen atom and here the electron pair is donated by the oxygen atom. Alcohols and hydrogen peroxide are other examples. It is very important to note that intermolecular hydrogen bonding formation occurs in compounds containing oxygen and hydrogen. Hence nucleophilic attack does not takes place during intermolecular hydrogen bonding formation.
Sulphur - H₂S is an example for the nucleophile which contains sulphur. Because of the large size, availability of lone pair of electrons, ease in its polarization, sulphur has good nucleophilic qualities.
Nitrogen – Nitrogen forms various nucleophiles such as ammonia, azides, amines, amides and nitrides.

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What factors determine the strength of a nucleophile?

The important factors which determine strength of a nucleophile are charge, electronegativity, steric hindrance and nature of the solvent.

Charge – When the density of negative charge increases the nucleophilicity also increases. Thus anion is found to be a better nucleophile than a neutral molecule. Hence the conjugate base is always a good nucleophile.

Then,, ,

Electronegativity – A highly electronegative atom acts as a poor nucleophile. Because it does not have a tendency to share its electrons. Thus as electronegativity increases the nucleophilicity decreases.

The order of electronegativity can be given as:

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Then the order of nucleophilicity is:

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Steric hindrance – When the nucleophile is bulky, it is very difficult to attack the substrate and thus the nucleophile becomes weaker.

Then the order of nucleophilicity is:

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Effect of solvent – A polar protic solvent like water or methanol can form hydrogen bond with a nucleophile. This will produce a shell of solvent molecules around the nucleophile and it inhibits the attack of the nucleophile towards the substrate and hence decreases the nucleophilicity.

A Polar aprotic solvent such as acetone or dimethylformamide solvates cations thereby leaves bare nucleophile. This increases its nucleophilicity.

What is meant by Ambident nucleophile?

An anionic nucleophile whose negative charge is delocalized over two unlike atoms can be called ambident nucleophile. The term ambident comes from two latin words ‘ambi’ which means “on both sides” and dens means “tooth”. Hence ambident nucleophile contains teeth on two sides.

Ambident nucleophiles contain two nucleophilic centres or two (-ve) sites and this negative charge is delocalized because of resonance. Hence they can attack a substrate through two sites.

Ambident nucleophile example is nitrite ion. It can attack through ‘O’ atom which results in the formation of alkyl nitrites and also it can attack through ‘N’ which gives nitroalkanes.

Cyanide and thiocyanate are also examples of ambident nucleophiles. Ambident nucleophiles can be shown as:

Nitrite ion:

Lewis structure

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Nitrite ion (NO₂^-) attack through ‘O’atom results in the formation of alkyl nitrites and it attack through ‘N’atom to form nitroalkanes.

Nitroalkane Alkyl nitrite

ethyl nitrite - 109-95-5, C2H5NO2, density, melting point, boiling point, structural formula, synthesis 1642576430970

Cyanide ion:

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Thiocyanate ion: Both the ‘S’ and ‘N’atoms of thiocyanate ion (SCN^-) can act as nucleophiles. Alkyl halide reacts with (SCN^-) through SN₂ reaction to give a mixture of an alkyl thiocyanate and alkyl isothiocyanate.
Enolate ion is an important ambident nucleophile in organic chemistry. Both the ‘C’ and the ‘O’atoms of acetone enolate can act as nucleophiles.

Nucleophilic addition

A nucleophilic addition is a reaction which involves the addition of a nucleophile to a pi-bond of a compound which results in the formation of a new sigma bond. Such type of reactions are more favoured in carbonyl compounds especially in aldehydes and ketones.

An example for nucleophilic addition reaction of acetone with HCN to give acetone cyanohydrin can be shown as:

Methacrylic_acid_synthesis

Nucleophilic substitution

A substitution reaction is one in which an electron rich nucleophile displaces the halogen atom connected to the carbon atom of an alkyl halide. The halide ion that is displaced from the carbon atom can be called leaving group.

General substitution reaction

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Frequently Asked Questions (FAQs)

1. What is meant by solvolysis?

A chemical reaction in which solvents like water or alcohol is involved and is present in great excess can be defined as solvolysis. It is generally a substitution reaction in which an atom or a group of atoms present in a molecule are replaced by another atom or group of atoms. Here the solvents generate electron rich atoms which act as nucleophiles that displace an atom or group of atoms from the substrate molecule.

2. What are the two types of nucleophilic substitution reactions?

Nucleophilic substitution reactions are generally of two types. They are SN1 and SN2 reactions.

SN1 – It is a two step process, occurs in tertiary and secondary alkyl halides, it is a unimolecular reaction and follows first order reaction. The speed of the reaction depends on the amount of alkyl halide.

SN2- It is a one step process, occurs in primary and secondary alkyl halides, the reaction is bimolecular and it is a second order reaction.

3. What are ambident nucleophiles?

It is an anionic nucleophile where delocalisation of nucleophile takes place by resonance over two unlike atoms.

4. Can a neutral molecule act as a nucleophile?

Yes, neutral molecules with lone pairs of electrons, such as water (H2O) or ammonia (NH3), can act as nucleophiles. Their nucleophilicity comes from the ability to donate these lone pairs to form new bonds.

5. What is the difference between a hard and soft nucleophile?

Hard nucleophiles are small, highly charged, and weakly polarizable (e.g., F-, OH-), while soft nucleophiles are larger, less charged, and more polarizable (e.g., I-, RS-). This distinction is important in predicting reactivity patterns.

6. Can nucleophiles be categorized based on the atom that acts as the nucleophilic center?

Yes, nucleophiles can be categorized based on their nucleophilic center. Common categories include oxygen nucleophiles (e.g., OH-), nitrogen nucleophiles (e.g., NH3), sulfur nucleophiles (e.g., RS-), and carbon nucleophiles (e.g., CN-).

7. What is nucleophilic substitution?

Nucleophilic substitution is a reaction where a nucleophile replaces another group (called a leaving group) in a molecule. This process is fundamental in organic chemistry and can occur through different mechanisms, such as SN1 or SN2.

8. What is the difference between a nucleophile and a base in organic reactions?

While both nucleophiles and bases donate electrons, a nucleophile forms a new covalent bond in the process, whereas a base typically just removes a proton without forming a new bond to the molecule it's acting upon.

9. What is a nucleophile?

A nucleophile is an electron-rich species that donates electrons to form a new chemical bond. It is attracted to positively charged or electron-deficient areas of molecules, typically seeking out electrophilic centers.

10. How does a nucleophile differ from an electrophile?

A nucleophile donates electrons and is attracted to positive centers, while an electrophile accepts electrons and is attracted to negative centers. Nucleophiles are electron-rich, while electrophiles are electron-poor.

11. What is meant by the term "nucleophilicity"?

Nucleophilicity refers to the relative reactivity of a nucleophile. It is a kinetic concept that describes how quickly a nucleophile will react with an electrophile, as opposed to basicity, which is a thermodynamic concept.

12. How does electronegativity affect nucleophilicity?

Generally, as electronegativity decreases within a group, nucleophilicity increases. This is because less electronegative atoms hold their electrons less tightly, making them more available for bonding.

13. What is the relationship between basicity and nucleophilicity?

While there is often a correlation between basicity and nucleophilicity, they are not always directly related. In protic solvents, stronger bases tend to be stronger nucleophiles, but this relationship can break down in aprotic solvents or with soft nucleophiles.

14. What determines the strength of a nucleophile?

The strength of a nucleophile is determined by factors such as its basicity, polarizability, and the solvent environment. Generally, stronger bases and more polarizable species tend to be stronger nucleophiles.

15. How does solvent polarity affect nucleophilicity?

Polar protic solvents can decrease nucleophilicity by hydrogen bonding with the nucleophile, while polar aprotic solvents can enhance nucleophilicity by not solvating the nucleophile as strongly, leaving it more "naked" and reactive.

16. Can the same species act as both a nucleophile and an electrophile?

Yes, some species can act as both nucleophiles and electrophiles, depending on the reaction conditions and the other reactants present. These are known as ambident species. An example is the cyanide ion (CN-), which can act as a nucleophile through its carbon atom or as an electrophile through its nitrogen atom.

17. How does steric hindrance affect nucleophilicity?

Steric hindrance can significantly decrease nucleophilicity. Bulky groups around the nucleophilic center can physically block its approach to the electrophilic site, slowing down or preventing the reaction.

18. What is the difference between kinetic and thermodynamic control in nucleophilic reactions?

Kinetic control favors the product that forms fastest (determined by activation energy), while thermodynamic control favors the most stable product (determined by Gibbs free energy). The choice between these can affect which nucleophile reacts preferentially in competitive situations.

19. Can nucleophiles be regenerated in catalytic cycles?

Yes, in many catalytic processes, nucleophiles act as catalysts and are regenerated at the end of the reaction cycle. This allows a small amount of nucleophile to facilitate the conversion of a large amount of substrate.

20. How does the periodic table trend affect nucleophilicity?

Generally, nucleophilicity increases down a group in the periodic table due to increasing size and polarizability of the atoms. For example, I- is typically a stronger nucleophile than F-.

21. What is the role of nucleophiles in biological systems?

In biological systems, nucleophiles play crucial roles in many enzymatic reactions, including hydrolysis, phosphorylation, and nucleophilic addition. Many amino acid side chains act as nucleophiles in protein function.

22. How does resonance affect the nucleophilicity of a species?

Resonance can either enhance or diminish nucleophilicity depending on how it affects electron density at the nucleophilic site. Resonance that increases electron density at this site generally increases nucleophilicity.

23. How does charge affect nucleophilicity?

Generally, negatively charged species are stronger nucleophiles than their neutral counterparts due to their higher electron density. However, this can be modulated by factors like solvation and the nature of the counterion.

24. How do nucleophiles behave in pericyclic reactions?

While pericyclic reactions typically involve the reorganization of π bonds, nucleophiles can play a role in certain types, such as nucleophilic addition to the dienophile in Diels-Alder reactions or in ene reactions.

25. How do nucleophiles behave in radical reactions?

While nucleophiles are typically associated with polar reactions, they can also participate in radical processes. For example, nucleophiles can transfer single electrons to radical species, influencing the course of radical chain reactions.

26. How does nucleophilicity differ in gas phase versus solution?

In the gas phase, nucleophilicity often correlates more closely with basicity as solvation effects are absent. In solution, factors like hydrogen bonding and differential solvation of reactants and products can significantly alter nucleophilic behavior.

27. How do nucleophiles behave in photochemical reactions?

While photochemical reactions often involve radical or excited state processes, nucleophiles can play important roles. For example, they may attack photochemically generated carbocations or participate in electron transfer processes with excited state species.

28. How do nucleophiles interact with transition metal complexes?

Nucleophiles can interact with transition metal complexes in various ways, including ligand substitution, nucleophilic addition to coordinated ligands, and electron transfer processes. These interactions are crucial in many catalytic cycles.

29. How do nucleophiles participate in polymerization reactions?

Nucleophiles can initiate certain types of polymerization reactions, such as anionic polymerization. They can also participate in step-growth polymerizations, like in the formation of polyesters or polyamides.

30. How do nucleophiles behave in electrochemical processes?

In electrochemistry, nucleophiles can participate in various ways. They may undergo oxidation at the anode, generating electrophilic species. Alternatively, they might react with electrochemically generated species, influencing the course of electroorganic syntheses.

31. What is a bidentate nucleophile?

A bidentate nucleophile is a species that can form two bonds with an electrophile. These nucleophiles have two nucleophilic sites and can often form chelate complexes. An example is the ethylenediamine molecule (H2NCH2CH2NH2).

32. How do nucleophiles participate in addition reactions?

In addition reactions, nucleophiles attack electrophilic centers (often carbon-carbon double bonds or carbonyl groups) without displacing any atoms. This results in the formation of a new bond and the conversion of π bonds to σ bonds.

33. What is meant by the term "nucleophilic aromatic substitution"?

Nucleophilic aromatic substitution is a reaction where a nucleophile replaces a leaving group on an aromatic ring. This process typically requires electron-withdrawing groups on the ring to activate it towards nucleophilic attack.

34. How do nucleophiles behave differently in SN1 vs SN2 reactions?

In SN2 reactions, the nucleophile directly displaces the leaving group in a concerted process. In SN1 reactions, the leaving group departs first, forming a carbocation, which is then attacked by the nucleophile in a two-step process.

35. What is a nucleophilic catalyst?

A nucleophilic catalyst is a species that acts as a nucleophile in the rate-determining step of a reaction but is regenerated by the end of the reaction cycle. Examples include DMAP (4-dimethylaminopyridine) in esterification reactions.

36. What is the alpha effect in nucleophiles?

The alpha effect refers to the enhanced nucleophilicity observed when a lone pair-bearing atom is adjacent to the nucleophilic center. Examples include hydroperoxide (HOO-) and hydrazine (H2NNH2).

37. How do nucleophiles interact with carbonyl compounds?

Nucleophiles typically attack the electrophilic carbon of carbonyl compounds, leading to addition reactions. The carbonyl oxygen's electronegativity makes the carbon more susceptible to nucleophilic attack.

38. What is the difference between a leaving group and a nucleophile?

A leaving group is a species that departs during a substitution reaction, carrying away its electrons. A nucleophile, conversely, is the incoming group that brings in electrons to form a new bond.

39. How does hydrogen bonding affect nucleophilicity?

Hydrogen bonding can decrease nucleophilicity by tying up the lone pairs that would otherwise be available for nucleophilic attack. This is why nucleophiles are often less reactive in protic solvents.

40. What is meant by "nucleophilic addition-elimination"?

Nucleophilic addition-elimination is a two-step process where a nucleophile first adds to an electrophilic center (often a carbonyl), followed by the elimination of a leaving group. This mechanism is common in reactions of carboxylic acid derivatives.

41. How do nucleophiles participate in ring-opening reactions?

Nucleophiles can attack electrophilic centers in strained ring systems, causing the ring to open. This is common in reactions with epoxides, where nucleophilic attack leads to ring opening and formation of an alcohol.

42. What is a nucleophilic aromatic addition?

Nucleophilic aromatic addition occurs when a nucleophile adds to an aromatic ring without substitution. This can disrupt aromaticity and is often a step in more complex reaction mechanisms.

43. What is the role of nucleophiles in elimination reactions?

While nucleophiles are more commonly associated with substitution reactions, they can also promote elimination reactions. In E2 reactions, for example, a strong base (which is often also a good nucleophile) can abstract a proton, leading to elimination.

44. What is nucleophilic acyl substitution?

Nucleophilic acyl substitution is a reaction where a nucleophile attacks the carbonyl carbon of an acyl compound (like an acid chloride or ester), displacing a leaving group. This is a common mechanism in the synthesis and interconversion of carboxylic acid derivatives.

45. How does orbital theory explain nucleophilicity?

Orbital theory explains nucleophilicity in terms of the interaction between the highest occupied molecular orbital (HOMO) of the nucleophile and the lowest unoccupied molecular orbital (LUMO) of the electrophile. Stronger nucleophiles typically have higher-energy HOMOs.

46. What is the difference between a nucleophile and a reducing agent?

While there is often overlap, a nucleophile donates electrons to form a new bond, whereas a reducing agent transfers electrons to another species, changing its oxidation state. Some species, like hydride (H-), can act as both.

47. What is the significance of the nucleophile in the Mitsunobu reaction?

In the Mitsunobu reaction, the nucleophile (often a carboxylic acid) is crucial as it ultimately displaces an activated alcohol group. The reaction's utility comes from its ability to invert the stereochemistry at the alcohol carbon.

48. How do nucleophiles participate in organometallic reactions?

In organometallic chemistry, nucleophiles often attack electron-deficient metal centers or ligands. This can lead to ligand substitution, oxidative addition, or other processes fundamental to catalytic cycles.

49. What is a nucleophilic rearrangement?

A nucleophilic rearrangement is a reaction where a nucleophilic part of a molecule attacks another part of the same molecule, leading to a structural reorganization. The pinacol rearrangement is an example of this type of process.

50. What is the role of nucleophiles in phase-transfer catalysis?

In phase-transfer catalysis, nucleophiles (often anions) are transferred from an aqueous phase to an organic phase by a phase-transfer catalyst. This allows reactions between species that would normally be separated by phase boundaries.

51. What is the significance of nucleophiles in green chemistry?

In green chemistry, the use of benign nucleophiles (like water or alcohols) is often preferred to more toxic or environmentally harmful alternatives. Additionally, nucleophilic catalysts can enable more atom-economical and energy-efficient processes.

52. What is the role of nucleophiles in supramolecular chemistry?

In supramolecular chemistry, nucleophilic interactions (like hydrogen bonding or coordination to metal centers) play a crucial role in molecular recognition and self-assembly processes. These interactions help define the structure and function of supramolecular assemblies.

53. What is the importance of nucleophiles in asymmetric synthesis?

In asymmetric synthesis, chiral nucleophiles or nucleophilic catalysts can induce stereoselectivity in reactions. This is crucial for the synthesis of enantiomerically pure compounds, which is particularly important in pharmaceutical chemistry.