Schiemann

The controlled thermal decomposition of dry aromatic diazonium fluoborates to yield an aromatic fluoride, boron trifluoride and nitrogen is known as the Schiemann reaction. Most diazonium fluoborates have definite decomposition temperatures and the rates of decomposition, with few exceptions, are easily controlled. Another procedure for preparing the diazonium fluoborate is to diazotise in the presence of the fluoborate ion. Fluoboric acid may be the only acid present, thus acting as acid and source of fluoborate ion. The insoluble fluoborate separates as it is formed side reactions, such as phenol formation and coupling, are held at a minimum temperature control is not usually critical and the temperature may rise to about 20° without ill effect efficient stirring is, however, necessary since a continuously thickening precipitate is formed as the reaction proceeds. The modified procedure is illustrated by the preparation of -fluoroanisole ... 

The mechanism of the Schiemann reaction is not known with certainty. Two schemes, which have been proposed, are given below. One involves carbonium ion formation ... 

Diazonium salt chemistry provides the principal synthetic method for the prepara tion of aryl fluorides through a process known as the Schiemann reaction In this pro cedure the aryl diazonium ion is isolated as its fluoroborate salt which then yields the desired aryl fluoride on being heated... 

Schiemann reaction (Section 22 17) Preparation of an aryl fluonde by heating the diazonium fluoroborate formed by addition of tetrafluorobonc acid (HBF4) to a diazonium ion Schiffs base (Section 17 10) Another name for an imine a compound of the type R2C=NR ... 

Trifluorobenzene. This compound is formed ia low yield (13—24%) from l,2,3-trichloroben2ene or 2,3-difluorochloroben2ene and KF/CsF ia dimethyl sulfone (204). Likewise, low yields are reali2ed when the Bal2-Schiemann reaction is appHed to 2,3-difluoroaniline or... 

Trifluorobenzene. This isomer, j -trifluoroben2ene, has been prepared ia 63% yield by the Bal2-Schiemann reaction with... 

Tetrafluorobenzene. This isomer has been prepared from 2,3,5-trifluoroaniline [363-80-4] ia 43% yield by the Bal2-Schiemann... 

Tetrafluorobenzene. This compouad has beea prepared from 2,4,5-trifluoroaniline [57491-45-9] by the Bal2-Schiemann reactioa ia 38—46% yield or from peatafluoropheaylhydra2iae [828-39-9] with aqueous sodium hydroxide ia 90—95% yield (221). Its ioni2atioa poteatial is 9.39 V. 

Fluoronaphthalene [323-09-1] is prepared in 54—67% yield from 2-naphthylamine by the Balz-Schiemann reaction or in 51% yield by pyrolysis of indene and chlorofluoromethane at 600°C (77). 

Difluoronaphthalene [315-52-6] is prepared from 4-fluoro-l-naphthylarnine by the Balz-Schiemann reaction. 1,4-Difluoronaphthalene is used in chemical carcinogenesis studies as a synthon for highly condensed difluoro—polycycHc aromatic hydrocarbons (273). 

G. Schiemann and B. Cornils, Chemie und Fechnologie CyclischerFluorverbindungen, E. Enke Vedag, Stuttgart, 1969. 

Fluorinated and iodinated derivatives are usually prepared by halogen exchange reactions, although the Baltz-Schiemann reaction has been applied to the synthesis of 2-fluoroquin-oxaline (66JHC435>. 

This reaction is commonly achieved by diazotization of the amine in fluoro-boric acid, followed by decomposition of the diazonium salt (Schiemann reaction).Thus, l-amino-4-methylestra-l,3,5(10)-trien-17-one (50) is converted to the fluoro derivative (51) in 29% yield. The synthesis of 3-fluoroestra-l,3,5(10)-triene-17-one (55) from estrone proceeds via (52) and (53)... 

New diazotization techniques for the Balz-Schiemann reaction feature alter native mtrosating agents in place of aqueous sodium nitrite or substitution of other salts such as arenediazonium hexafluorophosphates for arenediazoniuin fluoroborates... 

The Bergmann variation of the Balz Schiemann reaction is a two-step process featuring copper- or copper halide-catalyzed decomposition of aqueous or acetone solutions of arenediazonium fluoroborates containing alkyl or halogen substituents [30] A recent modification is a one-step technique featuring simultaneous diazoti-zation and decomposition by addition of aqueous sodium nitrite at 25 °C to a mixture of fluorobonc acid, copper powder, and 2 isopropyl 6 methylaniline to give 2-isopropyl-6 methylfluorobenzene in 73% yield [37]... 

Both photochemical and ultrasound variants of the Balz-Schiemann thermal decomposition step have also been developed A noteworthy feature of either technique is the use of milder fluorodediazoniation conditions... 

This technique has been applied to the synthesis of fluormated dopamine and other compounds of biological significance Fluoroheterocycles such as fluoro-imidazoles [JJ, 36] and fluoropyrazoles [37] can also be prepared by the photo Balz-Schiemann technique (equation 9) Photochemically induced in situ fluoro dediazoniation can also be applied to arenediazonium fluorides in hydrogen fluo nde-pyndine media Thus, o-fluoroanisole is obtained in 73% yield at 20 °C after I8h [dS]... 

The discovery of the Balz-Schiemann reaction in 1927 replaced the earlier Wallach procedure (1886) based on fluorodediazoniation of arenediazonium piper-idides (aryltriazenes) in aqueous hydrogen fluoride [40 41]... 

Applications in agrochemicals [42, 43], pharmaceuticals [44,45], and positron emission tomography (PET) [46, 47, 48 49] have resulted in the resuscitation of the Wallach reaction The Wallach technique provides high-specific-activity F-radiolabeled aromatic fluoride for PET studies, in contrast to the low-specific-ac-tivity product by the Balz-Schiemann route... 

Preparation of aryl fluorides Addition of fluoroboric acid to a solution of a diazonium salt causes the precipitation of an aryl diazonium fluoroborate. When the dry aryl diazonium fluoroborate is heated, an aryl fluoride results. This is the Schiemann reaction it is the most general method for the preparation of aryl fluorides. 

Direct bromination readily yields the 6-bromo derivative (111), just as with uracil. Analogous chlorination and iodination requires the presence of alkalies and even then proceeds in low yield. The 6-chloro derivative (113) was also obtained by partial hydrolysis of the postulated 3,5,6-trichloro-l,2,4-triazine (e.g.. Section II,B,6). The 6-bromo derivative (5-bromo-6-azauracil) served as the starting substance for several other derivatives. It was converted to the amino derivative (114) by ammonium acetate which, by means of sodium nitrite in hydrochloric acid, yielded a mixture of 6-chloro and 6-hydroxy derivatives. A modified Schiemann reaction was not suitable for preparing the 6-fluoro derivative. The 6-hydroxy derivative (115) (an isomer of cyanuric acid and the most acidic substance of this group, pKa — 2.95) was more conveniently prepared by alkaline hydrolysis of the 6-amino derivative. Further the bromo derivative was reacted with ethanolamine to prepare the 6-(2-hydroxyethyl) derivative however, this could not be converted to the corresponding 2-chloroethyl derivative. Similarly, the dimethylamino, morpholino, and hydrazino derivatives were prepared from the 6-bromo com-pound. ... 

---