Acid chlorides oximes, reaction with

Toray. The photonitrosation of cyclohexane or PNC process results in the direct conversion of cyclohexane to cyclohexanone oxime hydrochloride by reaction with nitrosyl chloride in the presence of uv light (15) (see Photochemical technology). Beckmann rearrangement of the cyclohexanone oxime hydrochloride in oleum results in the evolution of HCl, which is recycled to form NOCl by reaction with nitrosylsulfuric acid. The latter is produced by conventional absorption of NO from ammonia oxidation in oleum. Neutralization of the rearrangement mass with ammonia yields 1.7 kg ammonium sulfate per kilogram of caprolactam. Purification is by vacuum distillation. The novel chemistry is as follows ... 

Electrophilic nitrosation of the carbanion generated from the reaction of an organic base with a strong organic acid, such as a-hydrohexafluoroisobutyronitnle [2], a hydrohexafluoroisobutyric acid or its acid chloride [2], or a hydrotetra fluoroethanesulfonyl fluoride [4], yields the corresponding a-nitroso compound as the major product (equations 2 and 3) The a-hydrohexafluoroisobutyric acid or acid chloride reacts with excess trifluoroacetyl nitrite in dimethylformamide to afford the O substituted oxime [3] (equation 4)... 

Chlorophenyl)-5-(4-methoxyphenyl)isoxazole has also been prepared from the dilithio derivative of 4-ehloroacetophenone oxime by two other methods (a) reaction with anisonitrile (4-methoxybenzoni-trile) followed by acid-catalyzed cyclization8 and (b) condensation of anisolyl chloride (4-methoxybenzoyl chloride) followed by acid-catalyzed cyclization. ... 

Axenrod and co-workers reported a synthesis of TNAZ (18) starting from 3-amino-l,2-propanediol (28). Treatment of (28) with two equivalents of p-toluenesulfonyl chloride in the presence of pyridine yields the ditosylate (29), which on further protection as a TBS derivative, followed by treatment with lithium hydride in THF, induces ring closure to the azetidine (31) in excellent yield. Removal of the TBS protecting group from (31) with acetic acid at elevated temperature is followed by oxidation of the alcohol (32) to the ketone (33). Treatment of the ketone (33) with hydroxylamine hydrochloride in aqueous sodium acetate yields the oxime (34). The synthesis of TNAZ (18) is completed on treatment of the oxime (34) with pure nitric acid in methylene chloride, a reaction leading to oxidation-nitration of the oxime group to em-dinitro functionality and nitrolysis of the A-tosyl bond. This synthesis provides TNAZ in yields of 17-21 % over the seven steps. 

A benzofuran ring replaces one of the benzene rings of the biphenyl moiety present in many of the sartans in the rather more complex drug saprisartan (80-10). It is of note, further, that the acidic proton is provided in this case by a trifluorosulfo-namide instead of the more common tetrazole ring. Construction of the imidazole fragment begins by nitrosation of the (3-ketoester (79-1) by means of sodium nitrite in acid to afford the oxime (79-2). Reaction with acetyl chloride leads to the ester (79-3). Reaction of this last intermediate with the iminoether from propionitrile then affords the imidazole (79-4). 

Yet another piperidine-based antipsychotic agent replaces the butyrophenone or diarylpropyl function found in earlier compounds by a benzopyrimidine group. The synthesis starts by the conversion of the carboxylic acid in piperidine (22-1) to its acid chloride. Reaction with 1,3-difluorobenzene (22-2) in the presence of aluminum chloride affords the acylated product (22-3). Reaction with hydroxylamine leads to the corresponding oxime (22-4). Treatment of that derivative with a base... 

The incorporation of complex side chains at the 7 position based on alkyloximes of 2-amino-thiazole-5-gyloxylamides has provided drugs with very wide antibacterial activity that extend to hitherto resistant species such as pseudomonas. The preparation of one of the simpler side chains involves, first, the formation of the methyl ether from the oxime obtained by the nitrosation of methyl acetoacetate. Chlorination of the product, for example with sulfuryl chloride, gives the intermediate (21-1). The aminothiazole ring is then formed by reaction of that with thiourea to give (21-2). The free acid (21-3) is obtained by saponification of the product. The protected acid chloride (21-5) is obtained by sequential acylation of the amino group with chloroacetyl chloride and then reaction with thionyl chloride. 

The same products were also obtained by treatment of quinuclidin-3-one (2) with hydrazoic acid under Schmidt reaction conditions175 here the process gives mainly the monocyclic amide (147). Reaction of quinuclidin-3-one oxime (103) with arylsulfonyl chlorides in alkali leads to fragmentation and formation of iV-substituted 3-cyano-piperidines.179,177... 

The catalytic oxidation of cyclohexane is performed in the liquid phase with air as reactant and in the presence of a catalyst. The resulting product is a mixture of alcohol and ketone (Table 1, entry 12) [19]. To limit formation of side-products (adipic, glutaric, and succinic acids) conversion is limited to 10-12 %. In a process developed by To ray a gas mixture containing HC1 and nitrosyl chloride is reacted with cyclohexane, with initiation by light, forming the oxime directly (Table 1, entry 12). The corrosiveness of the nitrosyl chloride causes massive problems, however [20]. The nitration of alkanes (Table 1, entry 13) became important in a liquid-phase reaction producing nitrocyclohexane which was further catalytically hydrated forming the oxime. 

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. 

---