Acet-ketoxime

Place 80 g, of hydroxylamine sulphate (or 68-5 g. of the hydrochloride), 25 g. of hydrated sodium acetate, and 100 ml. of water in a 500 ml. flask fitted with a stirrer and a reflux water-condenser, and heat the stirred solution to 55-60°. Run in 35 g (42 nil,) of -hexyl methyl ketone, and continue the heating and vigorous stirring for ij hours. (The mixture can conveniently be set aside overnight after this stage.) Extract the oily oxime from the cold mixture twice with ether. Wash the united ethereal extract once with a small quantity of water, and dry it with sodium sulphate. Then distil off the ether from the filtered extract, preferably using a distillation flask of type shown in Fig. 41 (p. 65) and of ca, 50 ml, capacity, the extract being run in as fast as the ether distils, and then fractionally distil the oxime at water-pump pressure. Collect the liquid ketoxime, b.p. 110-111713 mm. Yield, 30-32 g. 

The strategy for the asymmetric reductive acylation of ketones was extended to ketoximes (Scheme 9). The asymmetric reactions of ketoximes were performed with CALB and Pd/C in the presence of hydrogen, diisopropylethylamine, and ethyl acetate in toluene at 60° C for 5 days (Table 20) In comparison to the direct DKR of amines, the yields of chiral amides increased significantly. Diisopropylethylamine was responsible for the increase in yields. However, the major factor would be the slow generation of amines, which maintains the amine concentration low enough to suppress side reactions including the reductive aminafion. Disappointingly, this process is limited to benzylic amines. Additionally, low turnover frequencies also need to be overcome. 

The conversion of nitroalkanes to ketoximes can be achieved by the reduction with Zn in acetic acid,112 or Fe in acetic acid.113 Nitroalkenes are direcdy reduced into saturated ketoximes by these reagents, which are precursors for ketones (see Section 6.1.4 Nef reaction). Reduction of 3-O-ace-ty lated sugar 1 -nitro-1 -alkenes with Zn in acetic acid gives the corresponding 2,3-unsaturated sugar oximes in high yield, which is a versatile route to 2,3-unsaturated sugar derivatives (Eq. 6.58).114... 

Conceptually interesting is the synthesis of the oxazole system 94 through a Beckmann rearrangement of a-formyl ketoxime dimethyl acetals 93 which demonstrated the possibility of a non-amino acid pathway in the biosynthesis of marine derived oxazoles <06CC1742>. 

Azido derivatives of furazans have proved to be particularly useful for the synthesis of heterocyclic systems. Thus, by 1,3-dipolar addition of l-azido(4-amino-l,2,5-oxadiazol-3-yl)aldoxime 186 to propargyl alcohol and phenylacetyl-ene, bicyclic 4-amino-l,2,5-oxadiazol-3-yl(4-R-l,2,3-triazol-l-yl)ketoximes 187 were obtained (Equation 34) which in reaction with acetic anhydride afforded the corresponding 0-acyl derivatives <2003RJ0574>. 

Peroxyacetic acid generated in situ from sodium perborate and glacial acetic acid has been used for oxime to nitro group conversion. Peroxyimidic acid generated from acetonitrile and hydrogen peroxide has found similar use. An Mo(IV) peroxy complex has been reported for the oxidation of both ketoximes and aldoximes. 

Most of the current preparative methods of oximes from nitroalkenes are not versatile. Reduction of nitroalkenes by CrCl2 or NaH2P02 in the presence of palladium was reported to afford the corresponding oximes, but the yields are not satisfactory. Zn-acetic acid and Na2Sn02 reductions are limited to the preparation of ketoximes only. Electroreduction of alkenes was reported to yield mixmres of ketones and ketoximes, or oximes and acetals (or ketones) depending on the strucmre of nitroalkanes. 

Sera and coworkers, during their investigation on electroreduction of nitroalkenes, found that plates of powder or metalhc lead can reduce nitroalkene 20 to give oxime 21 in acetic acid-DMF solution without electricity (Scheme 18). The reduction of 1-nitro-1-alkenes afforded the corresponding aldoximes or ketoximes in excellent yield. 

The Neber rearrangement was discovered in 1926 during the investigation of the Beckmann rearrangement. It was reported that treatment of ketoxime tosylate 517 with potassium ethoxide followed by acetic and hydrochloric acid produced a-amino ketones 518 (equation 231). 

Oxidation of arylmethyl ketoximes by phenyliodoso diacetate in glacial acetic acid was second order overall, first order each in substrate and oxidant.145 Iodine allowed the oxidative dimerization of glycine ester enolates with low to moderate diastereoselec-tivity that is consistent with kinetic control.146 Although malonic acid is not oxidized by iodate under acidic conditions, oxidation proceeds in the presence of catalytic ruthenium(III). A mechanism is put forward to account for the observed orders of reaction.147 The rate of periodate oxidation of m-toluidine in acetone-water increases with ionic strength.148... 

The same concept is applicable to allylic alcohols, ketones, or ketoximes. Enol acetates or ketones were successfully converted in multi-step reactions to chiral acetates in high yields and optical yields through catalysis by Candida antarctica lipase B (CALB, Novozyme 435) and a ruthenium complex. 2,6-Dimethylheptan-4-ol served as a hydrogen donor and 4-chlorophenyl acetate as an acyl donor for the conversion of the ketones (Jung, 2000a). 

Figure 18.15 Resolution of ketoximes to amine acetates via EMCR (Kim, 2002).

The EMCR has been extended from obtaining enantiomerically pure alcohols to obtaining such amines. Prochiral ketoximes were transformed to optically active amine acetates in a coupled CALB/palladium catalysis in the presence of an acyl donor at 1 atm hydrogen (Figure 18.15) (Choi, 2001). 

Oximes, Tosylhydrazones, and Related Derivatives.—Ketoximes afford enimides in refluxing acetic anhydride-pyridine.181 Theproduct (207) from 5a-cholestan-3-one oxime (206), for example, gave 3-acetylamino-5a-cholest-2-ene (208) in 93% yield after chromatography on alumina. Use of succinic instead of acetic anhydride, with pyridine, gave the enimide (209) which was stable to chromatography. A radical mechanism is proposed. Reduction of ketoximes by Cr11, V11, or Tiin salts in acetic anhydride affords the same enamides, by acetylation of the intermediate imines. The... 

The conversion of steroidal ketoximes and the derived oxime acetates, benzoates and methyl and benzyl ethers into enamides was described by Barton and coworkers621,622. For example, the oxime of 5-a-cholestan-3-one (147) forms with acetic anhydride in pyridine the enamide 148 which, under the reaction conditions, is acetylated on nitrogen to form the enimide 149. Chromatography on alumina cleaves the enimide to the enamide. 

Alternatively, Kim and coworkers showed [26] that prochiral ketoximes could be converted into optically active amines by hydrogenation over Pd-on-C in the presence of CaLB and ethyl acetate as both acyl donor and solvent, presumably via DKR of the amine formed in situ (see Fig. 9.16). 

Silyl-directed Beckmann fragmentation. A trimethylsilyl group in the p- or p -position of cyclic ketoxime acetates controls the regio- and stereochemistry of the double bond formed on Beckmann fragmentation catalyzed by trimethylsilyl triflate. 

Acetylenes allenes. Nitrimines, prepared from ketoximes and nitrous acid, on acylation with acetic anhydride and pyridine with catalysis by 4-dimethylamino-pyridine fragment to alkynes and/or allenes. ... 

Various trisubstituted imidazoles (xix) have been synthesized in good yields by Shaabani et al. [19] via the condensation of 1,2-diketone or a-hydroxyketone or a-ketoxime with various aromatic aldehydes and ammonium acetate using a solid acid catalysis. 

The nitroparaffins are condensed with aldehydes to yield nitro alcohols (70-80%), which on acetylation and treatment with an aqueous methanolic solution of sodium bicarbonate are converted to nitroolefins (80-84%). These compounds are reduced to the corresponding ketoximes by zinc and acetic acid (50-60%). Reduction with iron and dilute hydrochloric acid gives good yields of either ketones or ketoximes, depending upon the amount of hydrochloric acid used. The ketoximes can be hydrolyzed to ketones by refluxing with dilute sulfuric acid in the presence of formalin, which acts as a hydroxylamine acceptor (80%). The over-all yields from the nitroolefins are 40-60%. In this manner, certain otherwise difficultly obtainable ketones are prepared. Semicarbazones have been converted to ketones by treatment with sodium nitrite in glacial acetic acid, with aqueous oxalic acid, or with phthalic anhydride. ... 

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