Nitrile oxides 1,4,2,5-dioxadiazines

These routes are dimerization to furoxans 2 proceeding at ambient and lower temperatures for all nitrile oxides excluding those, in which the fulmido group is sterically shielded, isomerization to isocyanates 3, which proceeds at elevated temperature, is practically the only reaction of sterically stabilized nitrile oxides. Dimerizations to 1,2,4-oxadiazole 4-oxides 4 in the presence of trimethylamine (4) or BF3 (1 BF3 = 2 1) (24) and to 1,4,2,5-dioxadiazines 5 in excess BF3 (1, 24) or in the presence of pyridine (4) are of lesser importance. Strong reactivity of nitrile oxides is based mainly on their ability to add nucleophiles and particularly enter 1,3-dipolar cycloaddition reactions with various dipolarophiles (see Sections 1.3 and 1.4). 

Symmetrical 1,2,4,5-dioxadiazines are formed by [3 + 3] dimerization of arene nitrile oxides in the presence of pyridine (74JCS(Pl)l95l). The sulfonylsulfur diimide (579) cyclizes to the 1,3,2,4,6-dithia-triazine (580) on heating in DMF (71AG(E)264). 

In a few cases, carbohydroximidoyl chlorides may be converted into 1,4,2,5-dioxadiazines without isolation of a nitrile oxide, e.g. treatment of trinuoroacelohydroximidoyl chloride with cesium fluoride in bis(2-methoxyethyl) ether (diglyme) at room temperature gives 3,6-bis(triflu-oromethyl)-l,4,2,5-dioxadiazine (1) in 34% yield.14... 

Other modes of dimerization of nitrile oxides have been observed. With Lewis acid catalysis 1,4,2,5-dioxadiazines (25) can be produced,161 and l,2,4-oxadiazole-4-oxides (26) may arise in the presence of a high alkali concentration.85 Fulminic acid (HCNO) forms a variety of oligomers, but no furoxan (24 R = H) is isolated,5 and phenylglyoxylonitrile oxide (PhCO CNO) forms a second product, reportedly a tetramer (see Section IV,A,2). But these are exceptional cases usually it is only dimerization to the furoxan that is observed. 

Dimerization of nitrile oxides is one of the most important methods of synthesis of 1,2,5-oxadiazole iV-oxides (furoxans). However, this process can also lead to formation of symmetrical 1,4,2,5-dioxadiazines. The dipyridyl dioxadiazine 20 was obtained in 59% yield by treatment of 2-pyridyl hydroximinoyl chloride hydrochloride with triethylamine and pyridine in ethanol <2003EJI405>. The coumarin nitrile oxide 196 was dimerized with pyridine in ethanol to give the dioxadiazine 197 in 66% yield (Scheme 34). When a chloroform solution of the nitrile oxide 196 was heated at reflux in the absence of base, the furoxan 198 was produced in 70% yield (Scheme 34). Attempted purification of 196 by recrystallization caused dimerization into furoxan 198 <1998JHC619>. 

Dioxadia%ines. Dimerization of aryl nitrile oxides (Scheme 34) - currently unclear how conditions (e.g., inclusion/exclusion of added base) influence which product (1,4,2,5-dioxadiazine or 1,2,5-oxadiazole A-oxide (fur-oxan)) is favored. 

Coupling Reactions. Dimerization of aromatic nitrile oxides can be catalyzed by pyridine, affording 3,6-diaryl-1,4,2,5-dioxadiazines in good yields (eq 20). Other nucleophiles such as 4-phenylpyridine, 4-methylpyridine, 4-dimethylaminopyridine, and N-methylimidazole are also suitable catalysts for the reaction. 

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