Halogenation of Aldoximes

The chlorination of aldoximes I is the classical method of synthesis of hydroxamoyl chlorides II. Werner and his co-workers in 1894 ( 5-69 this method to synthesize a variety of aromatic hydroxamoyl chlorides. 

This reaction can be conducted using chlorine as the chlorinating agent in a variety of solvents, such as chloroform diethylether ( ), or, preferably, in concentrated hydrochloric acid ( 0,41,66,75 recent patent 

4 Phenylbenzhydroxamoyl Chloride ( ). To 10 g 4-phenylbenzaldoxime suspended in 50 ml of SN hydrochloric acid at 0°C an equivalent amount of chlorine is added. The resulting crude hydroxamoyl chloride (11 g, 94 %) is removed by filtration, and recrystallization from cyclohexane yields pure 4-phenylbenzhydroxamoyl chloride, m.p. 129-130°C. 

Trimethylacethydroxamoyl Chloride To a suspension of 50.5 g (0.5 mole) of trimethylacetaldoxime in 150 ml of cone, hydrochloric acid and 350 g ice, 35.5 g (0.5 mole) of chlorine is added. After stirring for two hours the reaction mixture is extracted several times with diethyl ether (300 ml total). The dried ether extract is evaporated and the residue is dissolved in 100 ml of petroleum ether. Upon chilling with dry ice 63.0 g (93 %) of trimethylacethydroxamoyl chloride, m.p. 33 C, is obtained. 

The volatile compound should be handled under a hood because it strongly irritates the mucous membranes. 

---

Owing to their tendency to dimerize to furoxans (1,2,5-oxadiazole 2-oxides), nitrile oxides 5 are usually generated in situ, i.e., in the presence of suitable dipolarophiles such as alkenes, alkynes, etc., from stable precursors such as aldoximes 12 (X = H) or from primary nitroalkanes 13 (Scheme 2) [5,57-67]. Generation of nitrile oxides 5 from aldoximes 12 (X = H) involves either direct oxidation or halogenation of aldoximes 12 (X = H) to hydroximoyl halides 12 (X = Cl or Br) followed by dehydrohalogenation [5,57-67,79,80]. Alternatively, nitrile oxides 5 are conveniently generated via dehydration of primary nitroalkanes 13 [ 17,38,39,65,66,81-95]. This review covers the literature in the last 10-15 years pertaining to the chemistry of isoxazoHnes synthesized from primary nitroalkanes 13. 

---