A-Oximino ketones

Both 2-nitro steroids 235 and 239 exist as the enols in ethanol, and are photolysed to give the corresponding a-diketones 237 and 238 (23% in 1 1 ratio)133 (equation 108) and 240 (equation 109), but different monoxime 236 and 241, respectively. On the contrary, 4-nitroketone 242 exists in the keto form, and is photolysed to give the a-oximino ketone 243 and its tautomer 244 without the diketones (equation 110). 

In addition to 1,2-dicarbonyl compounds, 1,2-diaminobenzenes condense with a-oximino ketones <2000JHC355>, epoxides <1999SC3459>, ethyl pyruvate <2000H(52)911>, and ethyl carboethoxyformimidate <19978301, 1999J(P1)1789> to produce quinoxaline derivatives. 

A particular class of quinoxaline A-oxides can be synthesized by a reaction sequence starting from condensation of anilines with a-oximino ketones (Scheme 50) <1998S1769>. The key step is oxidation of the oxime to an a-acetoxy nitroso group, which behaves as an electrophile leading to the formation of the quinoxaline ring. 

Pyrazine A -oxides have been conveniently synthesized by oxidation of pyrazines (Section 8.03.5.2), and by condensation of a-amino nitriles with a-oximino ketones (Section 8.03.9.3). 

After development has taken place in a layer containing silver halide, two images are present a negative one in metallic silver and a positive one in silver halide. The silver halide can be converted to a silver salt of a thiobarbituric acid, which is less soluble than the silver halide. Nitrosation of this insoluble silver salt produces an a-oximino ketone, which when treated with iron(II) ion yields a positive image in blue-green iron chelate.136... 

Similarly, the a-methylene group of acetoacetic ester is oximinated by the action of sodium nitrite in glacial acetic acid (63%). Nitrosation of alkylated malonic, acetoacetic, and benzoyl acetic esters with subsequent cleavage affords an excellent synthesis for a-oximino esters, RC(=-NOH)COjC2Hj. A survey of several possible procedures for this conversion has been made." If a /3-keto acid is nitrosated, then the Carboxyl group is lost and an a-oximino ketone is formed, viz.,... 

A closely related reaction involves the conversion of a-oximino ketones to nitriles by pyrolysis or by the action of thionyl chloride (75%). This reaction constitutes a step in a series for the synthesis of aliphatic acids from valeric to lauric acids. 

Whereas a-amino ketones readily form imidazoles with formamide, they are often not easy to prepare. Accordingly, they can be replaced by precursors, a-oximino ketones, which can be reduced either by dithionite or using catalytic mehods in formamide at 70-100 °C. Ring closure can then be achieved by raising the temperature (Scheme 80). When a-ketol esters are used it appears that the imidazole formation may in this instance proceed by way of the oxazole. A further special case is the formation of 4,5-disubstituted imidazoles from 1-chloro-l,2-epoxides and formamide. One recent example of an application of Bredereck s method is the synthesis of the imidazolepropanol (144) from 3-bromo-2-methoxytetra-hydropyran (Scheme 81) (80AHC(27)241). 

Oximes.—Oximes of some saturated ketones are reduced by aqueous alkaline sodium borohydride under reflux to give the corresponding alcohols. Selective reduction of a 3,17-dioxime is possible, at C(3). a -Oximino-ketones afford diols. Diborane, in contrast, reduces oximes to give alkyl hydroxylamines a recent variant using sodium borohydride on silica gel in benzene gave the... 

A modified method for the removal of the C-4 methyl groups of lanosterol has been published. The methods for degrading the side-chain of lanosterol continue to be improved.A series of degraded lanost-8-en-7,ll-diones (23) has been prepared. No attack at C-12 was observed under conditions which afforded the disophenols (24) and the a-oximino-ketones (25). ... 

A detailed study of the irradiation of O-acyl-a-oximino ketones has been carried out. Both N-0 bond fission and Norrish Type I... 

From 1,2-Diamino Compounds and their Synthetic Equivalents ( [4 + 2] Components") From a-Amino Ketones and a-Oximino Ketones ("[3 + 3] Components")... 

A classical synthesis of alkyl- and arylpyrazines involves dimerization of a-amino carbonyl compounds, which may be produced by many methods such as reduction of a-oximino ketones, aminolysis of a-halogeno ketones (Section 6.0T11.2), oxidation of a-amino alcohols and reduction of a-amino acids . The condensation of 1,2-diamines with a-dicarbonyl compounds is available for the synthesis of particularly quinoxaline derivatives (Section 6.03.11.1). The synthetic methods which rely on self-condensation, however, provide only symmetrically substituted pyra-... 

A new primary synthesis of 2-amino-3-arylpyrazines is accomplished by reaction of aroyl cyanides with 1,2-diaminoethane (Scheme 33). An important synthesis is that of 2-amino-3-cyano-5-sub-stituted pyrazines, which are conveniently synthesized by condensation of aminomalononitrile with a-oximino ketones and then deoxygenation of the resulting pyrazine jV-oxides (Scheme 37). 

The intriguing structure of these steroids coupled with their potent biological activity and limited availability makes them an attractive challenge for the synthetic organic chemist. One of the key features of any attempted synthesis is the central heterocyclic ring. The classical method of pyrazine synthesis involves the dimerization of a-amino ketones. A steroidal example relevant to the cephalostatin problem was reported15 as early as 1968 (Scheme 4) androstanolone (1) was converted to a-oximino ketone 2, which was hydrogenated to afford the hydrochloride salt of a-amino ketone 3. The salt was neutralized to the free base, and condensed in situ to yield symmetrical dimer 4 in modest overall yields. 

Ortho esters are also effective for Beckmann fragmentation of a-oximino ketones. 

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