144864-03-9

Upstream product

• 20375-65-9 3-chloro-6-phenylpyradazine 
• 16495-77-5 [(4-chlorophenyl)thio]pentafluorobenzene 

Downstream Products

• 2166-04-3 3-(4-methoxyphenyl)-6-phenylpyridazine 

Relevant academic research and scientific papers

Selective and efficient fluorination of chlorodiazines under solvent-free phase transfer catalysis

3-Chloro-6-phenylpyridazine, 2,3-dichloroquinoxaline and 1,4-dichlorophthalazine were reacted with KF under solvent-free conditions in the presence of a phase transfer agent, with or without microwave irradiation. The chlorine-fluorine exchanges were obta

Nucleophilic Fluorination of Heteroaryl Chlorides and Aryl Triflates Enabled by Cooperative Catalysis

Aryl and heteroaryl fluorides are growing to be dominant motifs in pharmaceuticals and agrochemicals, yet they are rare in both nature and commodity chemicals. As a consequence, there is an increasingly urgent need to develop mild, cost-effective, and scalable methods for fluorination. The most straightforward route to synthesize aryl fluorides is through the halide exchange "halex"reaction, but conditions, cost, and atom economy preclude most available methods from large-scale manufacturing processes. We report a new approach that leverages the cooperative action of 18-crown-6 ether and tetramethylammonium chloride to catalytically access the reactivity of tetramethylammonium fluoride and achieve halex fluorinations under mild conditions with operational ease. The described methodology readily converts both heteroaryl chlorides and aryl triflates to their corresponding (hetero)aryl fluorides in high yields and purities.

Tetramethylammonium Fluoride Alcohol Adducts for SNAr Fluorination

Nucleophilic aromatic fluorination (SNAr) is among the most common methods for the formation of C(sp2)-F bonds. Despite many recent advances, a long-standing limitation of these transformations is the requirement for rigorously dry, aprotic conditions to maintain the nucleophilicity of fluoride and suppress the generation of side products. This report addresses this challenge by leveraging tetramethylammonium fluoride alcohol adducts (Me4NF·ROH) as fluoride sources for SNAr fluorination. Through systematic tuning of the alcohol substituent (R), tetramethylammonium fluoride tert-amyl alcohol (Me4NF·t-AmylOH) was identified as an inexpensive, practical, and bench-stable reagent for SNAr fluorination under mild and convenient conditions (80 °C in DMSO, without the requirement for drying of reagents or solvent). A substrate scope of more than 50 (hetero) aryl halides and nitroarene electrophiles is demonstrated.

Multiple Approaches to the in Situ Generation of Anhydrous Tetraalkylammonium Fluoride Salts for SNAr Fluorination Reactions

This article focuses on the development of practical approaches to the in situ generation of anhydrous fluoride salts for applications in nucleophilic aromatic substitution (SNAr) reactions. We report herein that a variety of combinations of inexpensive nucleophiles (e.g., tetraalkylammonium cyanide and phenoxide salts) and fluorine-containing electrophiles (e.g., acid fluoride, fluoroformate, benzenesulfonyl fluoride, and aryl fluorosulfonate derivatives) are effective for this transformation. Ultimately, we demonstrate that the combination of tetramethylammonium 2,6-dimethylphenoxide and sulfuryl fluoride (SO2F2) serves as a particularly practical route to anhydrous tetramethylammonium fluoride. This procedure is applied to the SNAr fluorination of a range of electron-deficient aryl and heteroaryl chlorides as well as nitroarenes.

Rhodium-catalyzed transformation of heteroaryl aryl ethers into heteroaryl fluorides

A rhodium complex catalyzed the conversion of the C-O bond of heteroaryl aryl ethers to the C-F bond. The reaction of (4-chlorophenylthio)pentafluorobenzene with heteroaryl aryl ethers provided heteroaryl fluorides and heteroaryl (4-chlorophenylthio)tetrafluorophenyl ethers; this involved the cleavage of a single heteroaryl C-O bond under equilibrium conditions. The reaction of heteroaryl aryl ethers with 2-fluorobenzothiazole in which two heteroaryl and aryl C-O bonds were cleaved provided heteroaryl fluorides and aryl fluorides. The reactions were applicable to five-membered and six-membered heteroaryl aryl ethers and also to diaryl ethers possessing one or two electron-withdrawing groups.

Anhydrous Tetramethylammonium Fluoride for Room-Temperature SNAr Fluorination

This paper describes the room-temperature SNAr fluorination of aryl halides and nitroarenes using anhydrous tetramethylammonium fluoride (NMe4F). This reagent effectively converts aryl-X (X = Cl, Br, I, NO2, OTf) to aryl-F under mild conditions (often room temperature). Substrates for this reaction include electron-deficient heteroaromatics (22 examples) and arenes (5 examples). The relative rates of the reactions vary with X as well as with the structure of the substrate. However, in general, substrates bearing X = NO2 or Br react fastest. In all cases examined, the yields of these reactions are comparable to or better than those obtained with CsF at elevated temperatures (i.e., more traditional halex fluorination conditions). The reactions also afford comparable yields on scales ranging from 100 mg to 10 g. A cost analysis is presented, which shows that fluorination with NMe4F is generally more cost-effective than fluorination with CsF.

Selective fluorination by halogen exchange of chlorodiazines and chloropyridines promoted by the 'proton sponge' - Triethylamine tris(hydrogen fluoride) system

The 'proton sponge' - triethylamine tris(hydrogen fluoride) mixtures provide a mild and efficient fluorinating reagent to introduce selectively fluorine atoms by halogen exchange into chlorodiazines and chloronitropyridine series.

NUCLEOPHILIC FLUORINATION OF CHLORINATED N-HETEROCYCLES WITH TETRABUTYLPHOSPHONIUM HYDROGENDIFLUORIDE AND DIHYDROGENTRIFLUORIDE

Fluorination of various chlorinated N-heterocycles with tetrabutylphosphonium hydrogendifluoride (1) or dihydrogentrifluoride (2) readilly proceeded in high yields under mild conditions.