Production Method 1

153034-86-7

81290-20-2

81565-18-6

Reaction Conditions

1.1 Reagents: Cuprous iodide ,  Potassium fluoride Solvents: Dimethylformamide ,  N-Methyl-2-pyrrolidone
1.2 Reagents: Ammonium hydroxide Solvents: Water

Reference

Trifluoromethyl-substituted pyridines through displacement of iodine by in situ generated (trifluoromethyl)copper

Cottet, Fabrice; et al, European Journal of Organic Chemistry, 2002, (2), 327-330

Production Method 2

58310-28-4

153034-86-7

81565-18-6

Reaction Conditions

1.1 Reagents: 1,8-Diazabicyclo[5.4.0]undec-7-ene ,  Tetrakis(acetonitrile)copper(1+) hexafluorophosphate Solvents: Dimethylformamide ;  5 h, 100 °C

Reference

DBU-Promoted Trifluoromethylation of Aryl Iodides with Difluoromethyltriphenylphosphonium Bromide

Wei, Yun; et al, Chinese Journal of Chemistry, 2016, 34(5), 481-484

Production Method 3

73583-37-6

1300746-79-5

81565-18-6

Reaction Conditions

1.1 Solvents: Dimethylformamide ;  8 h, 80 °C

Reference

Copper-Mediated Perfluoroalkylation of Heteroaryl Bromides with (phen)CuRF

Mormino, Michael G.; et al, Organic Letters, 2014, 16(6), 1744-1747

Production Method 4

153034-86-7

17378-82-4

44498-05-7

81565-18-6

Reaction Conditions

1.1 Reagents: Sodium hydroxide ,  Cesium fluoride Solvents: Dimethylformamide ;  3 h, 75 °C

Reference

Trifluoromethylation of (hetero)aryl iodides and bromides with copper(I) chlorodifluoroacetate complexes

Lin, Xiaoxi; et al, RSC Advances, 2016, 6(79), 75465-75469

Production Method 5

153034-86-7

81565-18-6

Reaction Conditions

1.1 Reagents: 1,8-Diazabicyclo[5.4.0]undec-7-ene ,  Tetrakis(acetonitrile)copper(1+) tetrafluoroborate Solvents: Dimethylformamide ;  5 h, 120 °C

Reference

1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU)-Promoted Decomposition of Difluorocarbene and the Subsequent Trifluoromethylation

Zheng, Jian; et al, Organic Letters, 2015, 17(3), 532-535

Production Method 6

22253-59-4

81565-18-6

Reaction Conditions

1.1 Reagents: Thionyl chloride

Reference

Convenient Approaches to 4-Trifluoromethylpyridine

Jiang, Biao; et al, Organic Process Research & Development, 2001, 5(5), 531-534

Production Method 7

22253-59-4

81565-18-6

Reaction Conditions

1.1 Reagents: Thionyl chloride

Reference

Synthesis and antitumor evaluation of novel monoindolyl-4-trifluoromethylpyridines and bisindolyl-4-trifluoromethylpyridines

Jiang, B.; et al, Bioorganic & Medicinal Chemistry Letters, 2001, 11(4), 475-477

Production Method 8

17129-06-5

81565-18-6

Reaction Conditions

1.1 Reagents: Chlorotrimethylsilane ,  Zinc Solvents: Tetrahydrofuran
1.2 Reagents: Hydrochloric acid
1.3 Solvents: Water
1.4 Solvents: Ethyl acetate
2.1 Reagents: Phosphorus oxychloride
2.2 Solvents: Dichloromethane

Reference

Convenient Approaches to 4-Trifluoromethylpyridine

Jiang, Biao; et al, Organic Process Research & Development, 2001, 5(5), 531-534

Production Method 9

3796-24-5

81565-18-6

Reaction Conditions

1.1 Reagents: m-Chloroperbenzoic acid Solvents: Dichloromethane
2.1 Reagents: Thionyl chloride

Reference

Convenient Approaches to 4-Trifluoromethylpyridine

Jiang, Biao; et al, Organic Process Research & Development, 2001, 5(5), 531-534

2-Chloro-4-(trifluoromethyl)pyridine Raw materials

• 4-(Trifluoromethyl)pyridine
• Phosphonium, (difluoromethyl)triphenyl-, bromide
• 4-Bromo-2-chloropyridine
• 2-Chloro-4-iodopyridine
• Copper(1+),bis(1,10-phenanthroline-kN1,kN10)-, (T-4)-
• Acetic acid, 2-chloro-2,2-difluoro-, ion(1-)
• trimethyl(trifluoromethyl)silane
• 4-Ethoxy-1,1,1-trifluoro-3-buten-2-one
• 4-(Trifluoromethyl)pyridine 1-oxide
• (1,10-Phenanthroline)(trifluoromethyl)copper

2-Chloro-4-(trifluoromethyl)pyridine Preparation Products

• 2-Chloro-4-(trifluoromethyl)pyridine (81565-18-6)

• 1. Fast synthesis of copper nanoclusters through the use of hydrogen peroxide additive and their application for the fluorescence detection of Hg2+ in water samples?
  Liao Xiaoqing,Li Ruiyi,Li Zaijun,Sun Xiulan,Wang Zhouping,Liu Junkang New J. Chem., 2015,39, 5240-5248
• 2. Excellent kinetics of single-phase Gd-doped ceria fuel electrodes in solid oxide cells?
  Andreas Nenning,Manuel Holzmann,Jürgen Fleig,Alexander K. Opitz Mater. Adv., 2021,2, 5422-5431
• 3. Evidence that the availability of an allylic hydrogen governs the regioselectivity of the Wacker oxidation
  Matthew J. Gaunt,Jinquan Yu,Jonathan B. Spencer Chem. Commun., 2001, 1844-1845
• 4. Exceptional activity of sub-nm Pt clusters on CdS for photocatalytic hydrogen production: a combined experimental and first-principles study?
  Qiyuan Wu,Shangmin Xiong,Peichuan Shen,Shen Zhao,Alexander Orlov Catal. Sci. Technol., 2015,5, 2059-2064
• 5. Establishing the accuracy of position-specific carbon isotope analysis of propane by GC-pyrolysis-GC-IRMS
  ChangjieLiu,PengLiu,XiaofengWang,XiaoqiangLi,JuskeHorita

• Solvents and Organic Chemicals Organic Compounds Organoheterocyclic compounds Pyridines and derivatives 2-halopyridines
• Solvents and Organic Chemicals Organic Compounds Organoheterocyclic compounds Pyridines and derivatives Halopyridines 2-halopyridines

Introduction to 2-Chloro-4-(trifluoromethyl)pyridine (CAS No: 81565-18-6)

2-Chloro-4-(trifluoromethyl)pyridine, with the chemical formula C?H?ClF?N, is a significant intermediate in the field of pharmaceutical and agrochemical synthesis. This compound, identified by its CAS number 81565-18-6, has garnered considerable attention due to its versatile applications in the development of novel active pharmaceutical ingredients (APIs) and specialty chemicals. The presence of both chloro and trifluoromethyl substituents on the pyridine ring imparts unique reactivity, making it a valuable building block for synthetic chemists.

The< strong>2-chloro-4-(trifluoromethyl)pyridine molecule exhibits a distinct electronic distribution due to the electron-withdrawing nature of the trifluoromethyl group and the electron-donating effect of the chlorine atom. This balance of electronic properties facilitates various chemical transformations, including nucleophilic substitution, metal-catalyzed cross-coupling reactions, and heterocyclic ring formations. These reactions are pivotal in constructing complex molecular architectures essential for drug discovery.

In recent years, 2-chloro-4-(trifluoromethyl)pyridine has been extensively studied for its role in the synthesis of biologically active compounds. One notable area of research involves its application in developing kinase inhibitors, which are critical in treating cancers and inflammatory diseases. The trifluoromethyl group, in particular, is known to enhance metabolic stability and binding affinity to biological targets, making it a preferred moiety in medicinal chemistry.

A groundbreaking study published in the Journal of Medicinal Chemistry highlighted the utility of 2-chloro-4-(trifluoromethyl)pyridine in generating potent JAK2 inhibitors. The researchers demonstrated that incorporating this pyridine derivative into the drug scaffold led to compounds with improved selectivity and efficacy against inflammatory cytokine pathways. This finding underscores the importance of< strong> 2-chloro-4-(trifluoromethyl)pyridine as a key intermediate in addressing chronic inflammatory disorders.

Beyond pharmaceuticals, 2-chloro-4-(trifluoromethyl)pyridine finds applications in agrochemicals, where it serves as a precursor for herbicides and pesticides. The trifluoromethyl group's stability under environmental conditions enhances the durability of these agrochemicals, ensuring prolonged activity against pests and weeds. Recent advancements in green chemistry have also explored sustainable synthetic routes for producing< strong> 2-chloro-4-(trifluoromethyl)pyridine, aligning with global efforts to minimize environmental impact.

The synthesis of< strong> 2-chloro-4-(trifluoromethyl)pyridine typically involves fluorination and chlorination reactions on a pyridine backbone. Modern methodologies often employ catalytic systems that improve yield and reduce byproduct formation. For instance, transition metal catalysts such as palladium and copper have been optimized for facilitating selective fluorination at the 4-position of the pyridine ring. These innovations not only enhance efficiency but also contribute to cost-effective production scales suitable for industrial applications.

In conclusion, 2-chloro-4-(trifluoromethyl)pyridine (CAS No: 81565-18-6) is a multifaceted compound with far-reaching implications in pharmaceuticals and agrochemicals. Its unique structural features enable diverse synthetic transformations, making it indispensable in drug discovery and crop protection strategies. As research continues to uncover new applications, this compound will undoubtedly remain at the forefront of chemical innovation.

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