Balz-Schiemann reaction diazonium tetrafluoroborates

In order to use the potentiality of the Balz Schiemann reaction and to increase the specific radioactivity, the tetrafluoroborate anion was substituted for the tetrachloroborate. The fluorination of p-toluidyl diazonium tetrachloroborate. 

Two routes to the electrophilic fluorination of pyrrolo[2,3-3]pyridine A -oxide lead to the 4-fluoro derivative. The Balz-Schiemann reaction route, via a diazonium tetrafluoroborate salt, or a lithium/halogen-exchange reaction followed by quenching with an electrophilic fluorine source, generates the 4-fluoro product in moderate yields <20030L5023>. 

The basic Balz-Schiemann reaction involves the preparation of an insoluble arenediazonium tetrafluoroborate 1, either by direct diazotization of arylamines in aqueous tetra-fluoroboric acid, or by addition of tetrafluoroboric acid or alkaline tetrafluoroborates to an aqueous solution of another arenediazonium salt. After filtration and air-drying, this solid diazonium tetrafluoroborate is decomposed either neat or suspended in an inert solvent. 

The preparation of fliiorobenzo[e]cinnolincs 15 from thecorre.sponding benzo[r]cinnolinamines 14 con.stitutes an e.xample of the thermal Balz-Schiemann reaction in which the diazonium tetrafluoroborate intermediate is obtained from another previously formed diazonium salt. ... 

Fluorobenzo e)cinnoIine (15) Typical Procedure for the Thermal Balz-Schiemann Reaction in Which a Diazonium Tetrafluoroborate Salt is Obtained from Another Previously Formed Diazonium Salt ... 

Besides thermal decomposition of diazonium tetrafluoroborate salts (fluorodediazoniation). the Balz-Schiemann reaction can be carried out under either photochemical or ultrasonic irradiation. 

Several fivc-mcmbered-ring fluoroheteroaromatics, such as 4-fluoroimidazoles/ 4f° 2-fluoroimidazoles (e.g., 21),66 and 3-, 4- and 5-fluoropyrazoles,6 have been synthesized in 10-39 % yield via the Balz Schiemann reaction by photochemical irradiation of the corresponding diazonium salts in tetrafluoroboric acid solution (see Vol. ElOa, p 719ff). 

Photochemical Balz-Schiemann reaction of diazonium fluoroborates continues to be the method of choice to prepare fluoro substituted imidazoles. Thus, 4(5)-fluoroimidazole 1565 is prepared from 4(5)-nitroimidazole 1559 in moderate yield by conversion of the nitro group to the diazonium salt followed by irradiation in aqueous tetrafluoroboric acid. Sugar-fluoroimidazole derivatives 1566 and 1567 were prepared using an iV-silyl derivative of 1565 (Scheme 404). 

The synthesis of 7-azaindoles is a challenging task and there are few efficient routes to substituted derivatives. In the laboratory of C. Thibault, the concise and efficient synthesis of 4-fluoro-1/-/-pyrrolo[2,3-jb]pyridine was achieved. The fluorination was carried out using the Balz-Schiemann reaction. The aromatic amine precursor was prepared via the Buchwald-Hartwig coupling of the aryl chloride with A/-allylamine followed by deallylation. The diazonium tetrafluoroborate intermediate was generated at 0 C and it decomposed spontaneously in 48% HBF4 solution to afford the desired aromatic fluoride. 

One of the earliest means of introducing fluorine selectively into specific positions of aromatic compounds is the Balz-Schiemann reaction [77] which dates back to the 1920s. An isolated arene diazonium tetrafluoroborate is thermolyzed at up to 120 °C to yield the corresponding fluoroaromatic compound. Because of the infamously hazardous nature of isolated diazonium salts the scope of the classical variant of the Balz-Schiemann reaction was limited to the small scale. The high exothermicity of the reaction is most conveniently controlled by diluting the diazonium salt with a solid inert medium such as sea sand. In addition to the danger to the experimenter, the reproducibility of the reaction yield is quite poor. 

Various partly fluorinated pyridines can be synthesized by diazotization of the amino derivatives in aqueous hydrofluoric acid,50 or by using anhydrous hydrogen fluoride followed by thermal decomposition of the diazo-nium fluoride.51,52 There are also many examples of the application of the classical Balz Schiemann reaction to heteroaromatic systems,53,54 and the interesting photolysis of diazonium tetrafluoroborates has given fluoro-imidazole derivatives55,56 and fluorazoles.57... 

More prevalent than diazonium fluorosilicates in so-called modified Baiz-Schiemann reactions have been diazonium hexafluorophosphates.16 In some cases these latter diazonium salts give higher yields of aryl fluorides. Some examples are shown below, with the normal Balz-Schiemann reaction yields using diazonium tetrafluoroborates given in parentheses.163... 

The Balz-Schiemann reaction has been used for the preparation of the 4-iluoro-derivatives of pyridine and 2,5-, 2,6-, and 3,5-lutidine it has also been used to obtain 5-fluoronicotinic acid, required for conversion into the corresponding pyridylmethanol via LiAlH reduction of the ethyl ester. The introduction of F into fluoroaromatic compounds has been achieved via isotopic exchange in diazonium tetrafluoroborates. U.v. irradiation of aqueous solutions of the appropriate diazonium tetrafluoroborates has been used to procure the first ring-fluorinated imidazoks, e.g. photolysis of the diazonium solution obtained by adding sodium nitrite to 2-amino-imidazole in aqueous fluoroboric acid provides 2-fluoroimidazole contaminated with only a small amount of 2-azidoimidazole, the sole product of thermal decomposition of imidazole-2-diazonium tetrafluoroborate. 

Diazotization in the presence of boron trifluoride enables diazonium tetrafluoroborates to be isolated from the reaction mixture and purified. Subsequent controlled decomposition produces the required fluoroaromatic. Although explosion hazards and the toxicity of the isolated salts are significant concerns with this process, known as the Balz-Schiemann process, 4,4 -di-fluorobenzophenone (BDF. 6) has been prepared by this route as a monomer for the production of the engineering plastic poly(ether ether ketone) , or PEEK , by condensation with 1,4-dihydroxybenzene in the presence of potassium carbonate. BDF 6 is superior to its chlorine analog because in aromatic systems the nucleophilic displacement of fluorine is more facile than that of chlorine, leading to a shorter polymerization time and a better quality product containing less degradation impurities. 

Introduction of the fluorine can be done by chloride-fluoride exchange (Reaction scheme 210) or according to the Balz-Schiemann decomposition of diazonium tetrafluoroborate 292 or triazene 293 in liquid hydrogen fluoride (Reaction scheme 210). 

---