16.7 Benzyne
3 min read•may 7, 2024
is a highly reactive intermediate formed from benzene derivatives. It's characterized by a strained between adjacent carbon atoms, making it unstable and eager to react with various compounds.
In nucleophilic aromatic substitution, benzyne plays a crucial role. Its unique structure allows it to undergo reactions with nucleophiles, forming substituted aromatic compounds that might be tricky to make through other methods.
Benzyne
Formation and structure of benzyne
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- Benzyne is a highly reactive intermediate formed from benzene derivatives
- Commonly formed by elimination of two adjacent substituents from benzene ring (, )
- Possesses a formal triple bond between two adjacent carbon atoms
- Consists of one and two
- Adopts a linear geometry with a bond angle of 180°
- Exhibits significant ring strain and instability due to deviation from typical aromatic structure
- Estimated strain energy of 63 kcal/mol compared to benzene
- Behaves as an due to low-lying
- Readily undergoes addition reactions with nucleophiles (amines, enolates)
Benzyne in nucleophilic aromatic substitution
- Benzyne undergoes nucleophilic aromatic substitution reactions () with various nucleophiles
- Nucleophiles can be neutral (amines, alcohols) or anionic (enolates, alkoxides)
- Mechanism involves initial nucleophilic attack on benzyne
- adds to the highly strained and electrophilic triple bond
- Forms a negatively charged intermediate
- Subsequent protonation of the cyclohexadienyl anion yields the substituted aromatic product
- Proton source can be the solvent or an added acid
- Overall result is substitution of a hydrogen atom with the nucleophile
- Provides access to substituted aromatic compounds that may be difficult to obtain through other methods (direct halogenation, Friedel-Crafts alkylation)
Regioselectivity of benzyne reactions
- Benzyne reactions with substituted arenes can lead to multiple isomeric products
- depends on the nature and position of substituents on the arene
- (EDG) on the arene direct nucleophilic attack to the ortho and para positions
- Examples of EDGs include alkyl, alkoxy, and amino groups
- EDGs increase electron density at ortho and para positions through
- Nucleophile preferentially attacks at these electron-rich positions (, )
- (EWG) on the arene direct nucleophilic attack to the meta position
- Examples of EWGs include nitro, cyano, and carbonyl groups
- EWGs decrease electron density at ortho and para positions through resonance
- Nucleophile preferentially attacks at the less deactivated meta position (, )
- Steric effects can also influence regioselectivity
- Bulky substituents on the arene may hinder nucleophilic attack at nearby positions ()
- Nucleophile may preferentially attack at less hindered positions
Aromaticity and Reactivity
- Benzyne formation disrupts the of the benzene ring
- Loss of aromaticity contributes to the high reactivity of benzyne
- Resonance structures play a crucial role in understanding benzyne's reactivity
- Resonance stabilization is reduced compared to benzene, increasing reactivity
- Benzyne acts as both an electrophile and a nucleophile in reactions
- Its electrophilic nature allows it to react with nucleophiles
- Its nucleophilic character enables reactions with electrophiles
Key Terms to Review (37)
$S_N$Ar: $S_N$Ar, or nucleophilic aromatic substitution, is a type of aromatic substitution reaction where a nucleophile replaces a leaving group on an aromatic ring. This reaction is particularly important in the context of understanding the reactivity and stability of aromatic compounds.
2,6-di-tert-butylaniline: 2,6-di-tert-butylaniline is an organic compound with two tert-butyl substituents on the 2 and 6 positions of an aniline (benzeneamine) ring. This structural feature makes it an important precursor and intermediate in various organic synthesis reactions, particularly in the context of benzyne chemistry.
Anthranilic Acid: Anthranilic acid, also known as 2-aminobenzoic acid, is an organic compound that consists of a benzene ring with a carboxyl group and an amino group attached. It is an important precursor in the synthesis of various pharmaceutical and industrial compounds.
Aromaticity: Aromaticity is a fundamental concept in organic chemistry that describes the unique stability and reactivity of certain cyclic compounds with delocalized pi electron systems. This term is central to understanding the structure, stability, and reactivity of a wide range of organic compounds, including benzene and other aromatic heterocycles.
Aryl Halides: Aryl halides are organic compounds that consist of a halogen atom (fluorine, chlorine, bromine, or iodine) bonded directly to an aromatic ring, such as a benzene ring. These compounds are important in organic synthesis and have various applications in chemistry.
Aryne: An aryne, also known as a benzyne, is a highly reactive intermediate species in organic chemistry that consists of a benzene ring with a triple-bonded carbon-carbon unit. Arynes are important in many organic reactions and are often used as reactive intermediates in the synthesis of various compounds.
Arynic Substitution: Arynic substitution is a type of electrophilic aromatic substitution reaction in organic chemistry where an electrophile replaces a hydrogen atom on an aromatic ring, such as a benzene ring. This process is particularly relevant in the context of understanding benzyne, a highly reactive intermediate in certain aromatic substitution reactions.
Benzenediazonium Salts: Benzenediazonium salts are a class of organic compounds containing the diazonium functional group, where a nitrogen-nitrogen double bond is attached to a benzene ring. These salts are important intermediates in organic synthesis, particularly in the Sandmeyer reaction and other electrophilic aromatic substitution reactions.
Benzenediazonium-2-carboxylate: Benzenediazonium-2-carboxylate is an organic compound consisting of a benzene ring with a diazonium group (-N≡N+) attached at the 2-position and a carboxylate group (-COO-) at the same position. This compound is a key intermediate in various organic reactions, particularly in the context of benzyne formation.
Benzyne: Benzyne is a highly reactive intermediate species in organic chemistry, characterized by the presence of a triple-bonded carbon-carbon unit within a benzene ring. This reactive intermediate plays a crucial role in various organic reactions, particularly in the context of nucleophilic aromatic substitution and the formation of benzyne-derived compounds.
Cycloaddition: Cycloaddition is a fundamental organic chemistry reaction in which two or more unsaturated molecules, or parts of the same molecule, combine to form a cyclic adduct. This process is a powerful tool for the synthesis of a wide range of carbocyclic and heterocyclic compounds, and it is particularly important in the context of alkene oxidation, carbene addition, the Diels-Alder reaction, and various thermal electrocyclic and cycloaddition reactions.
Cyclohexadienyl Anion: The cyclohexadienyl anion is a resonance-stabilized aromatic species that is an important intermediate in many organic reactions, particularly those involving benzyne intermediates.
Diels-Alder Reaction: The Diels-Alder reaction is a type of cycloaddition reaction in organic chemistry where a conjugated diene reacts with a dienophile to form a cyclic product. It is a powerful tool for the synthesis of complex cyclic compounds and is widely used in organic synthesis.
Diels–Alder cycloaddition reaction: The Diels–Alder cycloaddition reaction is a chemical process in organic chemistry where a conjugated diene reacts with a substituted alkene (dienophile) to form a six-membered ring. This reaction occurs through a single, concerted step without the formation of intermediates.
Electron-Donating Groups: Electron-donating groups are functional groups or substituents that have the ability to donate or contribute electrons to a molecule, typically a benzene ring or other aromatic system. These groups can have a significant impact on the reactivity, stability, and properties of the molecule.
Electron-Withdrawing Groups: Electron-withdrawing groups are functional groups or substituents in a molecule that have a strong affinity for electrons, making them attractive to electrons. This property can significantly influence the reactivity, stability, and spectroscopic properties of the molecule.
Electrophile: An electrophile is a species that is attracted to electron-rich regions and seeks to form new bonds by accepting electron density. Electrophiles play a crucial role in many organic reactions, including polar reactions, electrophilic aromatic substitution, and nucleophilic acyl substitution, among others.
Elimination-Addition: Elimination-addition is a reaction mechanism in organic chemistry where a molecule first undergoes an elimination reaction, followed by the addition of a new functional group or atom. This process is particularly relevant in the context of the E1 and E1cB reactions, as well as the formation of benzyne intermediates.
Fluoride Ion: The fluoride ion (F-) is a negatively charged ion of the element fluorine, a highly reactive halogen. It is an important species in organic chemistry, particularly in the context of benzyne reactions.
Isotope Labeling: Isotope labeling is a technique used in organic chemistry to track the movement and fate of specific atoms within a molecule by substituting a naturally occurring isotope with a radioactive or stable isotope. This method provides valuable insights into reaction mechanisms, metabolic pathways, and the structure of organic compounds.
John D. Roberts: John D. Roberts was an American organic chemist who made significant contributions to the understanding of organic reaction mechanisms, particularly in the area of benzyne intermediates. He is known for his pioneering work in the field of physical organic chemistry, which helped elucidate the fundamental principles underlying chemical reactions.
Lowest unoccupied molecular orbital (LUMO): The LUMO is the lowest energy molecular orbital that does not contain electrons but can accept them during chemical reactions or excitations. It plays a crucial role in determining the reactivity and properties of molecules, especially in conjugated systems analyzed by ultraviolet spectroscopy.
LUMO: LUMO, or Lowest Unoccupied Molecular Orbital, is a fundamental concept in molecular orbital theory that describes the energy level of the highest-energy orbital that is not occupied by electrons in the ground state of a molecule. The LUMO is crucial in understanding the stability and reactivity of conjugated systems, as well as the behavior of molecules in various photochemical and pericyclic reactions.
Meta-cyanoaniline: meta-Cyanoaniline is a chemical compound with the formula C6H4(NH2)(CN), where the amino (NH2) and cyano (CN) functional groups are positioned in the meta configuration on a benzene ring. This compound is an important precursor in organic synthesis, particularly in the production of various pharmaceuticals and other specialty chemicals.
Meta-nitroaniline: meta-Nitroaniline is an organic compound with the chemical formula C₆H₆N₂O₂. It is a derivative of aniline with a nitro group (-NO₂) substituted at the meta position on the benzene ring. This structural feature makes meta-nitroaniline an important intermediate in the synthesis of various dyes, pharmaceuticals, and other organic compounds.
Nucleophile: A nucleophile is a species that donates a pair of electrons to form a covalent bond with another atom or molecule. Nucleophiles are central to understanding many organic reactions, including polar reactions, electrophilic addition reactions, and nucleophilic substitution reactions.
O-Dichlorobenzene: o-Dichlorobenzene, also known as 1,2-dichlorobenzene, is an aromatic organic compound with the chemical formula C6H4Cl2. It is a colorless liquid with a characteristic sweet, pleasant odor and is an important precursor in the synthesis of various chemicals and pharmaceuticals.
Ortho Effect: The ortho effect is a concept in organic chemistry that describes the tendency of substituents to direct the position of subsequent electrophilic aromatic substitution reactions on a benzene ring. It refers to the preference for new substituents to attach to the position adjacent (ortho) to an existing substituent on the benzene ring.
Ortho-anisidine: Ortho-anisidine is an aromatic organic compound with the chemical formula C₆H₇NO. It is a derivative of aniline with a methoxy group attached in the ortho position on the benzene ring. Ortho-anisidine is an important intermediate in the synthesis of various dyes, pharmaceuticals, and other chemicals.
Para-Toluidine: para-Toluidine is an organic compound with the chemical formula CH3C6H4NH2. It is a colorless solid that is used in the production of dyes, pesticides, and other chemicals. In the context of organic chemistry, para-toluidine is particularly relevant to the topic of benzyne reactions.
Regioselectivity: Regioselectivity refers to the preference of a chemical reaction to occur at a specific site or region of a molecule, leading to the formation of one regioisomeric product over another. This concept is particularly important in the context of electrophilic addition reactions of alkenes, electrophilic aromatic substitution, and other organic transformations.
Resonance: Resonance is a fundamental concept in organic chemistry that describes the ability of certain molecules to exist in multiple equivalent structures or resonance forms. This phenomenon arises from the delocalization of electrons within the molecule, leading to the stabilization of the overall structure and the distribution of electron density across multiple atoms.
Strained Cycloalkyne: A strained cycloalkyne is a cyclic organic compound containing a carbon-carbon triple bond, where the ring structure imposes significant strain on the molecule. This strain arises from the deviation of the bond angles and bond lengths from their ideal values, leading to increased reactivity and unique chemical properties.
Triple Bond: A triple bond is a covalent bond in which three pairs of electrons are shared between two atoms, resulting in a very strong and stable chemical connection. This type of bond is particularly important in the context of organic chemistry, as it is a key structural feature in certain classes of compounds known as alkynes.
Triple bonds: A triple bond is a chemical bond where three pairs of electrons are shared between two atoms. It is the strongest and shortest type of covalent bond found in molecules.
π Bonds: π Bonds, also known as pi bonds, are a type of covalent bond that forms between atoms through the overlap of their p-orbitals. These bonds are characterized by the sharing of electron density above and below the plane of the bonded atoms, creating a cloud-like distribution of electrons. π Bonds are essential in the understanding of chemical bonding theory, the structure of benzyne, and the molecular orbitals of conjugated pi systems.
σ Bond: A σ bond is a type of covalent chemical bond formed by the head-on overlap of atomic orbitals, resulting in an increased electron density along the internuclear axis. This type of bond is essential in the understanding of organic chemistry concepts such as benzyne and sigmatropic rearrangements.