Aromatic ketoximes

Preparative scale reduction of oximes at a mercury or lead cathode in acid solution has been used in the conversion of the carbonyl function to amine. Originally, 30-50% sulphuric acid was used as solvent [195] but ethanol with dilute hydrochloric acid is usually satisfactory. Aliphatic and aromatic oximes give amines in 64-86% yields [196]. Aromatic ketoximes are also reducible in alkaline solution and acetophenone oxime has been converted to 1-phenylethylamine in a tri-potassium orthophosphate solution [197], The reduction of oximes in acid solution is tolerant of many other substituents as indicated by a number of examples [198, 199, 200. Phenylglyoxa monoxime in acid solution is however reduced at both the carbonyl and the oxime centres by sodium amalgam to yield 2-amino-1-phenylethanol [201]... 

Falbe and co-workers have studied carbonylation of unsaturated amides to give imides (34), unsaturated amines to give lactams (37), and unsaturated alcohols to give lactones (38). Rosenthal and co-workers studied carbonylation of aromatic ketoximes, (127), phenylhydrazones (131), semicarbazones (129), azines (129), and nitriles (128) to produce phthalimidines. Horiie (65) has described the carbonylation of azobenzenes to give indazolones or 2,4-dioxo-l,2,3,4-tetrahydroquinazolines. Pritchard (121) and Murahashi et al. (103) have described the carbonylation of Schiff s bases to yield substituted phthalimidines. 

The antiapoptopic protein Bcl-xL is responsible for the reduced susceptibility of cancer cells to undergo apoptosis and is therefore a target for the development of new anticancer agents. The structure of a previously identified ligand for Bcl-xL (39) was modified to incorporate a TEMPO spin label (40). By use of spin-labeled (40), an eight-compound library was screened for simultaneous binding to Bcl-xL. From this library an aromatic ketoxime... 

The first step was the bromination of the oxime with bromocuccinimide to yield a bromonitroso compound on which the oxidation of hydrogen peroxide with nitric acid was transformed into bromonitro compound. The latter by acting with sodium borohydride furnished a secondary nitro compound with a yield of 33-80%. The method was particularly suitable for the formation of nitro derivatives of nitro cycloalkanes. The method is unsuitable for aromatic ketoximes and aldoximes. However, Barnes and Patterson [73] extended the method to aldoximes by using ozone as an oxidizing agent on gem-chloro ... 

Orthometallated complexes are intermediates in numerous cyclic carbonylation reactions involving aromatics with nitrogen donor groups in their side chains. For example, aromatic ketoximes and azobenzene are carbonylated at elevated temperatures and pressures with a cobalt carbonyl catalyst to form five-membered ring heterocycles in which a carbonyl group has replaced the metal in the presumed orthometallated intermediate ... 

Phthalimidines from Aromatic Ketoximes, Phenyl-hydra2ones, Semicarba2ones and A2ines... 

Aromatic ketoximes react with a CO/Hg mixture (98.5 1.5) to give phthalimidines [690]. The initial products are probably N-hydroxyphthal-imidines which are then hydrogenated to phthalimidines. 

The ketoxime derivatives, required as starting materials, can be prepared from the appropriate aromatic, aliphatic or heterocyclic ketone. Aldoximes (where R is H) do not undergo the rearrangement reaction, but rather an elimination of toluenesulfonic acid to yield a nitrile. With ketoxime tosylates a Beckmann rearrangement may be observed as a side-reaction. 

The present preparation illustrates the general method for the synthesis of aziridines by reduction of ketoximes 4 having an aromatic ring attached to carbon a or /3 to the oximino function and of aldoximes 4 having the aromatic ring attached to the carbon atom j3 to the oximino group. It has also been applied... 

The Ponzio reaction provides a useful route to gem-dinitro compounds and involves treating oximes with a solution of nitrogen dioxide or its dimer in diethyl ether or a chlorinated solvent. The Ponzio reaction works best for aromatic oximes where the synthesis of many substituted aryldinitromethanes have been reported. Compound (56), an isomer of TNT, is formed from the reaction of dinitrogen tetroxide with the oxime of benzaldehyde (55) followed by mononitration of the aromatic ring with mixed acid. Yields are usually much lower for aliphatic aldoximes and ketoximes. " The parent carbonyl compound of the oxime is usually the major by-product in these reactions. 

Enantioselective reduction of ketoxime ethers with chiral boron hydrides produces chiral 0-alkylhydroxylamines with variable ee. Reduction of oxime ethers of type 94 (equation 65) with norephedrine-derived oxazoborolidine 95 proceeds with very high ee. However, an analogous reduction of acyclic aromatic oximes with chiral oxab-orazolidines produced a mixture of amine and hydroxylamine . 

The term oxime dates to the 19th century, a combination of the words oxygen and imide. Oximes exist as two stereoisomers syn (Z) and anti (E). Aldoximes, except for aromatic aldoximes, exist for the most part as the syn isomer, while ketoximes are obtained as both syn and anti isomers, which can be separated almost completely. Recently, Kolandaivel and Senthilkumar have studied the molecular structure and conformational stability of anti and syn conformers of some aliphatic aldoximes by employing the ab initio and density funetional theory (DFT) methods. 

Boron trifluoride etherate was used in conjunction with the reducing agent borane to rearrange aromatic O-triisopropylsilyl ketoximes to cyclic and acyclic aniline derivatives. The steric hindrance of the substituents on the silicon atom, the size of the aliphatic ring and the presence of alkoxy substituents on the aryl group played important roles in the aniline formation. 

Sheradsky has found that the hydroxyl function of a ketoxime such as acetophenone oxime can be made to react with DMAD when the reaction is carried out in methanol with a basic catalyst, to give mixture of the fumarate and maleate isomers (164) in the ratio 2 1. This mixture on heating undergoes a hetero-Cope rearrangement followed by cyclization and dehydration to give dimethyl 5-phenylpyrrole-2,3-dicarboxylate (168) (Scheme 25). Similarly, Heindel and Chun have reported that vinyl ether adducts (171), obtained by the condensation of arylamide oximes with DMAD, get thermally converted into oxa-diazolines (172) or imidazolinones (174), depending on the reaction conditions. A similar reaction occurs with aromatic amidoxime-methyl propiolate adducts to give imidazoles (170) (Scheme 26). 1,2,4-Dioxazoles have been reported to be formed in the reaction of hydrox-amic acids with DMAD. - ... 

Similarly, (S4N4.SbCl5) reacted with alkyl methyl ketoximes 84 in aromatic solvents (e.g benzene and toluene) to give 3-alkyl-4-methyl-l,2,5-thiadiazoles 85, albeit in low yields (3-37%). A mechanism for the formation of 85 was proposed and the regioselective formation of 85 ascribed to the stability of an enamine intermediate. Suprisingly, this appears to be only the second example of a synthesis of a 3,4-dialkyl-l,2,5-thiadiazole that has been reported in the literature <99H147>. 

It turned out that the acetylene-assisted pyrrolization of ketoximes could be successfully extended to oximes of condensed aromatic ketones, such as 1- and 2-acetylnaphthalenes (Scheme 10) (82KGS1351). 

In the course of evaluating the area of application and limitation of pyrrole formation from ketoximes and acetylene, it has been found (82ZOR2620) that this may involve aromatic dioximes. From diacetylben-zene dioxime (18), for example, a one-stage transition to l,4-bis(l-vinyl-2-pyrrolyl)benzene (19) was accomplished (Scheme 11). 

The ketoximes containing only tertiary or aromatic radicals in any combination do not form pyrroles when reacting with acetylene in the presence of superbases (79MI2 80KGS1299). In the case of ketoximes with secondary alkyl radicals, 4//-2-hydroxy-2,3-dihydropyrroles or 3//-pyrroles are formed (see Sections IV.B,C). 

In attempts (76IZV690 80KGS1299 81MI4) to extend the pyrrole synthesis from ketoximes and acetylenes to aldoximes, the oximes of both aliphatic and aromatic aldehydes have been found to readily convert to the corresponding nitriles upon moderate heating (60-140°C) in KOH/DMSO. 

Thus, the reaction of ketoximes with acetylene catalyzed by the superbase pair KOH/DMSO offers the simplest approach to 3//-pyrroles, highly reactive, inaccessible, and so far poorly studied pyrrole isomers with no aromatic conjugation. 

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