2-Chloroquinoline

Base Information

• Chemical Name: 2-Chloroquinoline
• CAS No.: 612-62-4
• Molecular Formula: C9H6ClN
• Molecular Weight: 163.606
• Hs Code.: 29334900
• European Community (EC) Number: 210-317-8
• NSC Number: 6163
• UNII: UX7RIN8GEW
• DSSTox Substance ID: DTXSID8060612
• Nikkaji Number: J95.371G
• Wikipedia: 2-Chloroquinoline
• Wikidata: Q27291324
• ChEMBL ID: CHEMBL2042580
• Mol file: 612-62-4.mol

Synonyms:2-chloroquinoline

Chemical Property of 2-Chloroquinoline

Chemical Property:

• Appearance/Colour: white to yellowish crystals, powder, chunks
• Vapor Pressure: 0.0136mmHg at 25°C
• Melting Point: 34-37 °C(lit.)
• Refractive Index: 1.652
• Boiling Point: 267.3 °C at 760 mmHg
• PKA: 0.41±0.40(Predicted)
• Flash Point: 141.2 °C
• PSA: 12.89000
• Density: 1.27 g/cm³
• LogP: 2.88820
• Storage Temp.: 0-10°C
• Solubility.: methanol: 0.1 g/mL, clear
• Water Solubility.: Insoluble
• XLogP3: 2.7
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 1
• Rotatable Bond Count: 0
• Exact Mass: 163.0188769
• Heavy Atom Count: 11
• Complexity: 138

Purity/Quality:

98% ^*data from raw suppliers

2-Chloroquinoline ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xi
• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36-37/39

MSDS Files:

SDS file from LookChem

Useful:

• Chemical Classes: Nitrogen Compounds -> Quinolines
• Canonical SMILES: C1=CC=C2C(=C1)C=CC(=N2)Cl
• General Description: 2-Chloroquinoline, also known as NSC 6163, is a heterocyclic compound that serves as a versatile intermediate in organic synthesis, particularly for the preparation of functionalized quinolines. It can be synthesized through a novel method involving 2-vinylanilines, diphosgene, and acetonitrile, which avoids hazardous reagents like phosphorus oxychloride. Additionally, 2-chloroquinoline derivatives, such as 6-bromo-2-chloroquinoline, are valuable precursors in Buchwald-Hartwig amination reactions to produce 2-aminoquinolines with enhanced binding affinity for protein domains like Tec SH3, demonstrating its utility in medicinal chemistry and ligand design.

Technology Process of 2-Chloroquinoline

There total 42 articles about 2-Chloroquinoline which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 99.1%

2-hydroxyquinoline (59-31-4) → 2-Chloroquinoline (612-62-4)

Guidance literature:

With trichlorophosphate; In toluene; for 21h; Reflux; Inert atmosphere;

DOI:10.1021/acs.joc.7b02775

Reference yield: 98.0%

2-bromoquinoline (2005-43-8) → 2-Chloroquinoline (612-62-4)

Guidance literature:

With copper(I) oxide; tetramethlyammonium chloride; L-proline; In ethanol; at 110 ℃; for 10h; Inert atmosphere;

DOI:10.1039/c2cc34944b

Reference yield: 97.0%

2-Chloroquinoline 1-oxide (2423-68-9) → 2-Chloroquinoline (612-62-4)

Guidance literature:

With titanium; In tetrahydrofuran; for 0.25h; Ambient temperature;

DOI:10.1055/s-1987-28152

upstream raw materials:

phosgene

1-methyl-2-quinolin-2(1H)-one

toluene

2-quinolone

Downstream raw materials:

2-(piperidin-1-yl)quinoline

2-(piperazin-1-yl)quinoline

4,4-dimethylmorpholinium chloride

2-benzenesulfonyl-quinoline

Refernces

Novel synthesis of 2-chloroquinolines from 2-vinylanilines in nitrile solvent

10.1021/jo016196i

The study presents a novel method for synthesizing 2-chloroquinolines from 2-vinylanilines using diphosgene in acetonitrile as the solvent. The researchers detail a three-step reaction mechanism involving the generation of phenylisocyanate, quinoline ring formation, and chlorination at the C2 position of the quinoline. The purpose of the chemicals used in the study was to facilitate these steps, with diphosgene reacting with 2-vinylanilines to produce phenyl isocyanate, which then reacts with the acetonitrile to form the quinoline ring. The final step involves the chlorination of the C2 position. This new method eliminates the need for the hazardous use of excess phosphorus oxychloride, which was previously required in the synthesis of 2-chloroquinolines from 2(1H)-quinolinones. The study also discusses the role of acetonitrile as a reactive solvent in the process and provides evidence that the third step, chlorination, is likely the rate-determining step in the reaction.

Sequential and selective Buchwald-Hartwig amination reactions for the controlled functionalization of 6-bromo-2-chloroquinoline: Synthesis of ligands for the Tec Src homology 3 domain

10.1021/jo801808r

The research focuses on the development of new 6-heterocyclic substituted 2-aminoquinolines using Buchwald-Hartwig amination reactions. These compounds are designed to have increased binding affinity for the Tec Src Homology 3 (SH3) domain, a protein-protein interaction domain that is a valuable target for therapeutic agents. The study explores the selective amination of an aryl bromide in the presence of an activated heteroaryl chloride, optimizing reaction conditions to achieve cross-coupling with various cyclic amines. Key chemicals involved in the research include 6-bromo-2-chloroquinoline as the starting material, palladium catalysts such as Pd(OAc)2, various phosphine ligands like CataCXium A (16), and bases like KOtBu and NaOtBu. The reactions also utilize a range of cyclic amines as coupling partners to introduce different heterocyclic substituents at the 6-position of the quinoline ring. The study further investigates the use of lithium bis(trimethylsilyl)amide (LHMDS) as an ammonia equivalent for the amination process to convert 2-chloroquinolines to 2-aminoquinolines, providing an improved method over traditional approaches. The binding affinity of the synthesized compounds with the Tec SH3 domain is assessed through NMR chemical shift perturbation analysis, revealing that the new ligands exhibit enhanced binding affinities compared to the lead compound, 2-aminoquinoline.