Diazotization under anhydrous conditions

The diazotization of the amines is carried out in the usual manner. The volume of water is kept at a minimum since the success of the reaction depends in part on the efficiency with which the unstable intermediate is extracted from the aqueous layer by the organic liquid. Either the previously prepared amine hydrochloride is employed or a paste of the hydrochloride is prepared by dissolving the amine in concentrated hydrochloric acid and then cooling rapidly with stirring. For diazotization a nearly saturated solution of sodium nitrite (1 g. in 2 cc. of water) is used. Little work has been done with very weakly basic amines in the diazo reaction.48 In one instance, the base, l-nitro-2-naphthylamine, was diazotized by means of nitrosylsulfuric acid in sulfuric acid benzene was added and then sodium hydroxide until the mixture was slightly alkaline.49 For the very weak bases, the nitrosoacetyl reaction is recommended, since it is carried out entirely under anhydrous conditions. 

Tetrahydrofuran is widely employed as a solvent for reactions involving benzyne, yet it has been shown to be attacked by benzyne (from anthranilic acid diazotized in situ) to give products derived via the betaine 47.52 In the presence of water 48 and 49 are obtained (23% and 8%, respectively), whereas under anhydrous conditions the main product is 50 (17%) by reaction of 47... 

Alkyl nitrites can also be used in anhydrous media and, for example, 4-hydroxyben-zenediazonium tetrafluoroborate is isolated in 89% yield after diazotization with isopcntyl nitrite, hydrogen fluoride and boron trifluoride in ethanol/diethyl ether.96 Diazotization can also be performed in dichloromethane or ethers (diethyl ether, tetrahydrofuran, 1,2-dimethoxyethane) with terl-butyl nitrite and boron trifluoride-diethyl ether complex which generates nitrosyl fluoride in situ.229 Excess boron trifluoride is used to trap water and tert-butyl alcohol, so that the reaction can be considered as being performed under complete anhydrous conditions. Yields are higher in dichloromethane, but 1,2-dimethoxyethane is preferred for less soluble amines. This procedure has been successfully applied to the synthesis of mono-and difluorobenzo[c]phcnanthrenes.230... 

Not only is thermal fluorodediazoniation possible, but the corresponding pliotochemically induced process is also possible (see Vol. E 10a, p 703). Several aromatic fluorides can be prepared viti diazotization and pliotochemically induced fluorodediazoniation of aromatic amines in anhydrous hydrogen fluoride-organic base solutions. In general, no fluoroaromatic compounds can be isolated if the fluorodediazoniation stage is carried out without photochemical irradiation under similar conditions (rt). 

A new synthetically useful procedure for the preparation of arenediazonium tetrafluoroborates from the corresponding amines involves the in situ generation of nitrosyl fluoride (Scheme 53). The diazotization reactions are performed under mild conditions in an anhydrous solvent, preferably methylene chloride. Excess boron trifluoride etherate traps the alcohol and water produced, and the diazonium salts are precipitated from the reaction medium and isolated by simple filtration. 

---