Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Reactions at the Benzylic Position: Oxidation and Reduction00:59

Reactions at the Benzylic Position: Oxidation and Reduction

4.8K
The benzylic position describes the position of a carbon atom attached directly to a benzene ring. Benzene by itself does not undergo oxidation. In contrast, the benzylic carbon is quite reactive in the presence of strong oxidizing agents such as KMnO4 or H2CrO4. Therefore, alkylbenzenes are readily oxidized to benzoic acid, irrespective of the type of alkyl groups.
4.8K
Electrophilic Aromatic Substitution: Fluorination and Iodination of Benzene01:13

Electrophilic Aromatic Substitution: Fluorination and Iodination of Benzene

7.3K
Bromination and chlorination of aromatic rings by electrophilic aromatic substitution reactions are easily achieved, but fluorination and iodination are difficult to achieve. Fluorine is so reactive that its reaction with benzene is difficult to control, resulting in poor yields of monofluoroaromatic products. To address this, Selectfluor reagent is used as a fluorine source in which a fluorine atom is bonded to a positively charged nitrogen.
7.3K
Benzene to 1,4-Cyclohexadiene: Birch Reduction Mechanism01:18

Benzene to 1,4-Cyclohexadiene: Birch Reduction Mechanism

2.6K
Birch reduction uses solvated electrons as reducing agents. The reaction converts benzene to 1,4-cyclohexadiene. The reaction proceeds by the transfer of a single electron to the ring to form a benzene radical anion. This anion is highly basic—it abstracts a proton from the alcohol to form a cyclohexadienyl radical. Another single electron transfer gives the cyclohexadienyl anion. A proton transfer from the alcohol forms 1,4-cyclohexadiene. Since this reduction occurs via radical anion...
2.6K
Electrophilic Aromatic Substitution: Chlorination and Bromination of Benzene01:15

Electrophilic Aromatic Substitution: Chlorination and Bromination of Benzene

10.4K
Chlorination and bromination are important classes of electrophilic aromatic substitutions, where benzene reacts with chlorine or bromine in the presence of a Lewis acid catalyst to give halogenated substitution products. A Lewis acid such as aluminium chloride or ferric chloride catalyzes the chlorination, and ferric bromide catalyzes the bromination reactions. During the bromination of alkenes, bromine polarizes and becomes electrophilic. However, in the bromination of benzene, the bromine...
10.4K
Nucleophilic Aromatic Substitution: Elimination–Addition01:11

Nucleophilic Aromatic Substitution: Elimination–Addition

5.0K
Simple aryl halides do not react with nucleophiles. However, nucleophilic aromatic substitutions can be forced under certain conditions, such as high temperatures or strong bases. The mechanism of substitution under such conditions involves the highly unstable and reactive benzyne intermediate. Benzyne contains equivalent carbon centers at both ends of the triple bond, each of which is equally susceptible to nucleophilic attack. This 50–50 distribution of products is...
5.0K
Reduction of Benzene to Cyclohexane: Catalytic Hydrogenation01:28

Reduction of Benzene to Cyclohexane: Catalytic Hydrogenation

5.6K
Unlike the easy catalytic hydrogenation of an alkene double bond, hydrogenation of a benzene double bond under similar reaction conditions does not take place easily. For example, in the reduction of stilbene, the benzene ring remains unaffected while the alkene bond gets reduced. Hydrogenation of an alkene double bond is exothermic and a favorable process. In contrast, to hydrogenate the first unsaturated bond of benzene, an energy input is needed; that is, the process is endothermic. This is...
5.6K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Discovery of PF-07054894, a Potent Squaramide-Based CCR6 Antagonist Displaying High CXCR2 Selectivity.

Journal of medicinal chemistry·2025
Same author

Conformational Role of Methyl in the Potency of Cyclohexane-Substituted Squaramide CCR6 Antagonists.

Journal of medicinal chemistry·2025
Same author

Synthesis of Highly Substituted Aminotetrahydropyrans Enabled by Stereospecific Multivector C-H Functionalization.

Organic letters·2023
Same author

Identification of parallel medicinal chemistry protocols to expand branched amine design space.

Organic & biomolecular chemistry·2022
Same author

Discovery of Tyrosine Kinase 2 (TYK2) Inhibitor (PF-06826647) for the Treatment of Autoimmune Diseases.

Journal of medicinal chemistry·2020
Same author

A Radical Approach to Anionic Chemistry: Synthesis of Ketones, Alcohols, and Amines.

Journal of the American Chemical Society·2019

Related Experiment Video

Updated: Jan 1, 2026

Efficient Construction of Drug-like Bispirocyclic Scaffolds Via Organocatalytic Cycloadditions of α-Imino γ-Lactones and Alkylidene Pyrazolones
10:17

Efficient Construction of Drug-like Bispirocyclic Scaffolds Via Organocatalytic Cycloadditions of α-Imino γ-Lactones and Alkylidene Pyrazolones

Published on: February 7, 2019

7.2K

Oxidative Cyclization Approach to Benzimidazole Libraries.

Eric P Arnold1, Prolay K Mondal1, Daniel C Schmitt1

  • 1Pfizer Worldwide Research and Development , Eastern Point Road , Groton , Connecticut 06340 , United States.

ACS Combinatorial Science
|December 21, 2019
PubMed
Summary

A new parallel synthesis method allows for diverse benzimidazole analogs by using anilines for C4-C7 variation. This approach expands chemical space and aids medicinal chemistry projects.

Keywords:
C−H aminationPIDAamidinesbenzimidazolesoxidative cyclizationparallel synthesis

More Related Videos

A Direct, Regioselective and Atom-Economical Synthesis of 3-Aroyl-N-hydroxy-5-nitroindoles by Cycloaddition of 4-Nitronitrosobenzene with Alkynones
07:30

A Direct, Regioselective and Atom-Economical Synthesis of 3-Aroyl-N-hydroxy-5-nitroindoles by Cycloaddition of 4-Nitronitrosobenzene with Alkynones

Published on: January 21, 2020

8.6K
Palladium N-Heterocyclic Carbene Complexes: Synthesis from Benzimidazolium Salts and Catalytic Activity in Carbon-carbon Bond-forming Reactions
19:58

Palladium N-Heterocyclic Carbene Complexes: Synthesis from Benzimidazolium Salts and Catalytic Activity in Carbon-carbon Bond-forming Reactions

Published on: July 30, 2017

10.1K

Related Experiment Videos

Last Updated: Jan 1, 2026

Efficient Construction of Drug-like Bispirocyclic Scaffolds Via Organocatalytic Cycloadditions of α-Imino γ-Lactones and Alkylidene Pyrazolones
10:17

Efficient Construction of Drug-like Bispirocyclic Scaffolds Via Organocatalytic Cycloadditions of α-Imino γ-Lactones and Alkylidene Pyrazolones

Published on: February 7, 2019

7.2K
A Direct, Regioselective and Atom-Economical Synthesis of 3-Aroyl-N-hydroxy-5-nitroindoles by Cycloaddition of 4-Nitronitrosobenzene with Alkynones
07:30

A Direct, Regioselective and Atom-Economical Synthesis of 3-Aroyl-N-hydroxy-5-nitroindoles by Cycloaddition of 4-Nitronitrosobenzene with Alkynones

Published on: January 21, 2020

8.6K
Palladium N-Heterocyclic Carbene Complexes: Synthesis from Benzimidazolium Salts and Catalytic Activity in Carbon-carbon Bond-forming Reactions
19:58

Palladium N-Heterocyclic Carbene Complexes: Synthesis from Benzimidazolium Salts and Catalytic Activity in Carbon-carbon Bond-forming Reactions

Published on: July 30, 2017

10.1K

Area of Science:

  • Organic Chemistry
  • Medicinal Chemistry
  • Synthetic Chemistry

Background:

  • Library approaches for benzimidazole synthesis typically focus on N1 and C2 variations.
  • Limited chemical space coverage is a challenge when varying the C4-C7 positions, often requiring specific 1,2-dianiline building blocks.

Purpose of the Study:

  • To develop an efficient parallel synthesis of benzimidazoles with diverse C4-C7 substitution.
  • To enable the use of anilines as a readily available diversity set for generating benzimidazole C4-C7 structure-activity relationship (SAR) data.

Main Methods:

  • An amidine formation followed by an oxidative cyclization sequence was developed.
  • Phenyliodine(III) diacetate (PIDA) or copper-mediated oxidation was employed for amidine annulation.
  • The protocol was adapted for the synthesis of aza-benzimidazoles from aminopyridines.

Main Results:

  • The developed sequence efficiently generates benzimidazoles with variations at the C4-C7 positions using anilines.
  • Both N-H and N-alkyl benzimidazoles were successfully synthesized.
  • The protocol has been applied to four medicinal chemistry projects for analog production.
  • An analogous sequence was effective for synthesizing aza-benzimidazoles.

Conclusions:

  • This novel method provides a powerful tool for parallel synthesis of diverse benzimidazoles, significantly expanding accessible chemical space.
  • The approach facilitates rapid SAR exploration at the C4-C7 positions, crucial for drug discovery.
  • The methodology is versatile, applicable to both benzimidazoles and related aza-benzimidazoles.