Hydroxamic acid chlorides

The first synthesis of a 3,5-diarylisoxazole from aryl hydroxamic acid chlorides and sodium phenyl acetylides was that effected by Weygand and Bauer in 1927. Beginning in 1946, when Quilico and Speroni showed that acid chlorides of hydroxamic acids on treatment with alkalies readily yielded nitrile oxides,numerous isoxazole and especially A -isoxazoline derivatives have been prepared. 

The reaction with hydroxamic acid chlorides has been extensively used recently by Italian chemists to synthesize di- and poly-isoxa-zolyls, as exemplified by 5-substituted 3,3 -diisoxazolyIs (29). °... 

NITRILE OXIDES. Nitrile oxides are a well known class of compds represented by R.C N- 0, and are usually prepd by treating hydroxamic acid chlorides with a mild alkali, thus eliminating HQ (Ref 2). Wieland (Refs 1 3) was responsible for the first isolation of free nitrile oxides. These compds are somewhat unstable, showing a marked tendency to dimerize to (he corresponding furoxanes (1,3-dipolar addition) (Refs 2 3). The nitrile oxides add to a considerable number of carbenes, as benzonitrUe oxide (for example) to a large number of olefins in ether at 20° (Ref 3)... 

Chloroximes (hydroxamic acid chlorides) react with dicyandiamide to yield 5-guanido-oxadiazoles Mb)... 

Benzonitrile oxide (C in Figure 15.44) is an isolable 1,3-dipole. It can be generated from benzaldoxime and anNaOH/Cl2 solution. Under these reaction conditions the oxime/nitroso anion (A B) is initially formed and chlorine disproportionates into Cl—O and chloride. An SN reaction of the negatively charged C atom of the anion A B at the Cl atom of Cl— O or of Cl—O—H affords the oc-chlorinated nitroso compound E, which tautomerizes to the hydroxamic acid chloride D. From that species, the nitrile oxide C is generated via a base mediated 1,3-elimination. Isoxazoles are formed in the reactions of C with alkynes (Figure 15.44), while isoxazolines would be formed in its reactions with alkenes. 

Chlorination of aldoximes. NCS converts aryl aldoximes to hydroxamic acid chlorides without significant chlorination of the aryl group. This reaction has been used for a novel synthesis of nitrile oxides. Thus reaction of salicylaldoxime (1) with NCS followed by dehydrochlorination with pyridine generates a nitrile oxide, which is trapped by styrene to give the isoxazoline 2. The N-O bond can be cleaved by catalytic hydrogenation to 3, which is converted into the chalcone 4 on elimination of water. This product can be converted by classical methods to the flavanone 5 and the flavone 6. An analogous route can be used to synthesize 2-... 

Nitrile oxides from hydroxamic acid chlorides... 

Nitrile oxides 7 react as 1,3-dipoles with alkynes in a [3+2] cycloaddition to give isoxazoles (Quilico synthesis). The nitrile oxides are generated in situ. They are obtained, for instance, by dehy-drohalogenation of hydroxamic acid chlorides (cr-chloraldoximes) with triethylamine ... 

The nomenclature of this class of compounds is not at all clear. For example, the following names can be found in the literature hydroxamic acid chlorides, hydroxamic chlorides, hydroximic chlorides (Beilstein lists them as Hydroximsaure chloride ), and acyl and aroylchloride oximes. The latter names are used by Chemical Abstracts, Although the name benzoyl chloride oxime for benzhydroxamoyl chloride is formally correct, it does not reflect the close relationship between hydroxamoyl chlorides and hydroxamic acids, their hydrolysis products. In order to be consistent with the nomenclature used in the earlier chapters, I prefer the term hydroxamoyl to hydroxamic chloride. The interrelationship of the halides with the corresponding acids is shown below, and R is representative of the alkyl, aryl, acyl, aroyl, and carbalkoxy group. 

A number of D,L-aminodeoxysugars were synthesised by reduction of 2-isoxazolines. The overall process required three steps involving addition of hydroxamic acid chlorides (generated from aldoximes, NCS and triethylamine using basic alumina or florisil as a solid-phase base) to dienes, followed by stereospecific hydroxy-... 

Trifluoroacetonitrile AT-oxide, generated in situ by dehydrochlorination of the corresponding hydroxamic acid chloride with triethylamine, has been trapped with several dipolarophiles (see Scheme 22) it failed to attack perfluorobutyronitrile, in contrast to benzonitrile JV-oxide (see Scheme 23), and apparently gave unidentified high-boiling material rather than a furoxan in the absence of a suitable dipolarophile. Trifluoromethyltetrazolato-complexes prepared via 1,3-dipolar cycloadditions between trifluoroacetonitrile and azido-complexes of Group IB metals (e.g. see Scheme 24) have received attention (seep. 349). ... 

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