Balz-Schiemann conditions

The initial experiments were performed on crystalline films of arenediazonium tetrafluoroborates which decomposed into fluoroarenes at room temperature (or below 30 C) under UV irradiation (350 nm).247 In some cases, the result is even better than under Balz-Schiemann conditions, e.g. formation of 1 the diazonium tetrafluoroborates, particularly those bearing substituents known to favor competitive hydrodediazoniation, such as dialkylamino, do not deliver reduced products under photochemical conditions. 

Only 2-azidoiinidazole under Balz-Schiemann conditions. b Hct-NH2 not stable. 

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... 

The Wallach reaction, the thermal decomposition of an aryl triazene (Scheme 46), has also been attempted as an alternative to the Balz-Schiemann reaction [54,220,221]. Although a wide variety of experimental conditions have been tried, the radiochemical yields remain low. 

Dediazoniation itself is not dramatically dependent on the hydrogen fluoride/pyridine ratio, as shown from the dediazoniation of benzenediazonium tetrafluoroborate (previously isolated) in hydrogen fluoride/pyridine mixtures provided that the hydrogen fluoride/pyridine ratio is larger than 6, fluorobenzene is always obtained in quantitative yield (for hydrogen fluoride/ pyridine ratios below 6, byproducts result from the phenyl cation and free pyridine).10 These observations have resulted in new, very efficient syntheses of 4-fluorophenols 2 involving dediazoniation, in hydrogen fluoride/pyridine mixtures, of crystalline 4-hydroxy benzenediazonium chloride and tetrafluoroborate 3 (formed under anhydrous conditions)89,96 as well as quinone-diazide (formed from aminophenol in tetrafluoroboric acid).93,97 Such methods are more efficient than the Balz-Schiemann reaction under standard conditions. 

The Balz-Schiemann synthesis can be applied not only to substituted anilines but also to aminobiphcnyls1,131 or amino-substituted fused polyaromatic compounds, such as naphthalene,1114,119,129 anthracene,136 phenanthrene,1135 acenaphthene,133 fluorene,1,131,134 benzanthracene,130 136 pyrene,136 chrysene,136 fluoranthene,131 fluorenone,1,131 anthra-quinone,1,137,139,140 benzanthrone,1,117,118 phenanthraquinone,138 or xanthone.132 Fluorinated pyridines,1,141"146 methylpyridincs,126,147 149 pyridinecarboxylic acids,150 quinolines,1,151 isoquinolines,152 quinazolone,1 thiazoles,153,154 isothiazoles,156 benzothiazoles,157 thiadiazoles,155 and thiophenes154 can also be obtained from the corresponding aminated heterocycles. Modified Balz-Schiemann methods are recommended for amino nitrogen-containing heterocycles, the diazonium salts of which are rather water-soluble and unstable (a violent explosion was reported for pyridine-3-diazonium tetrafluoroborate).159 These new techniques have also been specially adapted for pyrazol-, imidazol-, or triazolamines which fail to react under classical conditions.158... 

Diazotization procedures. Widely used for the production of aromatic fluorine is the Balz-Schiemann reaction. The approach involves diazotization of the aniline and isolation of the insoluble tetrafluoroborate salt, followed by decomposition under heating conditions (Fig. 32). Initially introduced in 1927 [137,138], it did not achieve commercial utility until the mid-1980s. A modification of the Balz-Schie-mann reaction involves replacing the tetrafluoroborate with other counterions such as a fluorine anion [139],... 

Since dialkyltriazenes were first used in aromatic fluorination by Wallach, ° many fluoroaro-matic compounds have been obtained in high yield by the decomposition of 3,3-dialkyl-l-aryl-triazenes with various fluorides in acidic media (see Vol. ElOa, p 725fT). Aryltriazenes are a potential source of aryldiazonium salts under controlled, mild, acid conditions. Therefore, this replacement (Route A) can be considered as a type of Balz-Schiemann reaction (see Section... 

Since volatile, anhydrous hydrogen fluoride is extremely corrosive and toxic, the fluorodediazo-niatron of aromatic amines with this agent require.s special apparatus and. safety conditions, which are not available in most laboratories. Thus, the decomposition of diazonium tclra-fliioro bo rates, which can be readily prepared from aromatic amines and casier-to-handle tetra-fluoroboric acid, is the commonest fluorodediazoniation process, usually referred to as the Balz-Schiemann reaction (see Vol. E 10a, p 705IT). 

Extensive research has been focused on introducing fluorine into molecules, which can modify their physicochemical properties. Nowadays, around 30% of pharmaceutical compounds contain fluorine. Several methodologies are available and are mainly based on the use of readily commercially available fluorinating reagents. Usually, for aromatic systems, the Balz-Schiemann or the Halex reactions are the processes of choice, whereas for aliphatic systems, electrophilic or nucleophilic fluorinations are required. Despite the fact that cheap starting materials are used in these processes, the harsh conditions remained an obstacle due to poor functional group tolerance. 

Historically, aryl fluorides were prepared by either Balz-Schiemann-type reactions or though the Halex process [70-75], Although a number of these procedures were quite successful, many of them required the use of toxic reagents or harsh conditions. To address these issues and provide practical routes to aryl fluorides, a host of alternative protocols have been developed [6, 76-78]. In addition to this work, a number of methods for the synthesis of aryl halides have been developed. The following sections will highlight several practical versions. 

The use of forcing conditions in the modified Balz-Schiemann reaction has permitted the preparation of a number of 6-fluoro- and 2,6-difluoro-purines, including the 6-fluoro-2-trifluoromethyl compound (109) (Scheme 42).s8 ... 

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