Amines ketoximes

Many organosilanes have been employed over the years as crosslinkers speed of reaction, the nature of the byproducts, and cost have been major factors in the selection of systems for commercialization. Crosslinker silanes that have been employed are those that afford as byproducts alcohols,carboxylic acids, amines, ketoximes, aldoximes, and amides.Examples of some of these organosilanes are shown below ... 

Cycloahphatic amine synthesis routes may be described as distinct synthetic methods, though practice often combines, or hybridi2es, the steps that occur amination of cycloalkanols, reductive amination of cycHc ketones, ring reduction of cycloalkenylarnines, nitrile addition to ahcycHc carbocations, reduction of cyanocycloalkanes to aminomethylcycloalkanes, and reduction of nitrocycloalkanes or cycHc ketoximes. 

The treatment of ketoximes with lithium aluminum hydride is usually a facile method for the conversion of ketones into primary amines, although in certain cases secondary amine side products are also obtained. Application of this reaction to steroidal ketoximes, by using lithium aluminum deuteride and anhydrous ether as solvent, leads to epimeric mixtures of monodeuterated primary amines the ratio of the epimers depends on the position of the oxime function. An illustrative example is the preparation of the 3(x-dj- and 3j5-di-aminoandrostane epimers (113 and 114, R = H) in isotopic purities equal to that of the reagent. 

Die Hydrolyse wird bei aliphatischen Oximen im alkalischen, bei Aryl-aldoximen und -ketoximen wegcn der alkalisch auftretenden Disproportionierung zum Amin und Oxim (s. a. S. 372) im sauren durchgefiihrt. Einigc, z. B. Diaryl-ketoxime, werden nur bei hoherer Temperatur reduziert. 

Certain ketoximes can be converted to nitriles by the action of proton or Lewis acids. Among these are oximes of a-diketones (illustrated above), a-keto acids, a-dialkylamino ketones, a-hydroxy ketones, p-keto ethers, and similar compounds. These are fragmentation reactions, analogous to 17-25 and 17-26. For example, ot-dialkylamino ketoximes also give amines and aldehydes or ketones besides nitriles. 

Both aldoximes and ketoximes can be reduced to primary amines with LiAlH4. The reaction is slower than with ketones, so that, for example, PhCOCH=NOH gave 34% PhCHOHCH=NOH. Among other reducing agents that give this reduc-... 

It was possible to effect lOOC reaction leading to six-membered rings, e.g., 220 in low yield (ca. 20%) by heating the reaction mixture at 110 °C (Eq. 22) [59]. In fact, Oppolzer and Keller [60] had previously reported the lOOC reaction of 219 to 220 in 20% yield by heating at 110 °C. Furthermore, the scope of these oxime-olefin cycloadditions has been extended to ketoximes, e.g., 221. The latter was prepared by amination of a-bromoacetophenone with allylamine 214a. Heating of 221 at 110 °C for 8 h led to cycloaddition with formation of the fused pyrrolidine 222 in 88% yield. As in Scheme 25, only one... 

The DKR processes for secondary alcohols and primary amines can be slightly modified for applications in the asymmetric transformations of ketones, enol esters, and ketoximes. The key point here is that racemization catalysts used in the DKR can also catalyze the hydrogenation of ketones, enol esters, and ketoximes. Thus, the DKR procedures need a reducing agent as additional additive to enable asymmetric transformations. 

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. 

In 1994, the scope of this p-hydroxy sulfoximine ligand was extended to the borane reduction of ketimine derivatives by these workers. The corresponding chiral amines were formed with enantioselectivities of up to 72% ee, as shown in Scheme 10.57. It was found that the A -substituent of the ketimine had a major influence on the asymmetric induction, with a ketoxime thioether (SPh) being the most successful substrate. 

Ketoximes and oximes of 2-oxo-acids are hydrogenated to amines by [CoH(CN)5]3-. The latter reaction allows the preparation of a-amino-acids by reductive amination of 2-oxo-acids in aqueous ammonia. At 40-50 °C and 70 bar H2 the yields are ca. 90% [146]. 

Similarly the reduction of both aldoxime and ketoxime gives again primary amines. 

An early approach to the formation of chiral amines by nonenzymatic asymmetric synthesis was the reduction of prochiral ketoximes and their O-tetrahydropyranyl and O-methyl derivatives with lithium aluminum hydride-3-0-benzyl-1,2-0,0-cyclohexylidene-a-D-glucofuranose complex (16)33 in ether and prochiral ketoximes... 

Reduction of ketoximes is one of the most useful ways to primary amines. 

Reduction of cyclohexanone oxime with lithium aluminum hydride in tetra-hydrofuran gave cyclohexylamine in 71% yield [809], and reduction of ketoximes with sodium in methanol and liquid ammonia [945] or in boiling ethanol [946] afforded alkyl amines, usually in good to high yields. Stannous chloride in hydrochloric acid at 60° reduced the dioxime of 9,10-phenanthra-... 

Oximes of a,/i-unsatiirated ketones, on reduction with lithium aluminum hydride, depending on the structure of the ketoxime and on the reaction conditions, yield unsaturated amines, saturated amines, and sometimes aziridines in fair yields [947],... 

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]... 

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 . 

Recently, Scialdone and colleagues have employed phosgenated />-nitrophenyl(poly-styrene) ketoxime (Phoxime, 76) resin in the synthesis (via 77 and 78) of acyclic and heterocyclic amino-acid-derived ureas 79 too (Scheme 42). Resin 75 was first reacted with an amino acid and TMSCl in pyridine, and the resulting carbamate acid resin 77 was then coupled with an amine under standard carbodiimide protocol (HOBt/DIC in DMF) to obtain the carbamate amide resin 79. 

The Neber rearrangement is usually performed with ketoxime tosylates but ketone trimethylhydrazonium halides (519), iV,iV-dichloro-5ec-alkyl amines (520), N-chloroimines (521) and A-chloroimidates (522) may also be precursors for the reaction. Only the Neber rearrangement of oxime derivatives will be analysed in this chapter. 

By analogy with the biogenesis of oximes via oxidation of amino acids or biogenic amines, the biosynthetic pathway for insertion of the ketoxime function into the antibiotic, nocardicin A (18), was shown to be dependent on the oxidation of the corresponding primary amine precursor of 18 by cytochrome PTSO ". Similarly, the formation of the ketoxime bond of verongamine (17) is attributed to the oxidation of a primary amine precursor . 

The effect of ligands on the character and degree of the inner-sphere reorganization during electroreduction of aqua-, aquahydroxy-, hydroxy-, and ethylene-diamine tetraacetic acid (EDTA) complexes of Zn(II) [95] and electrochemical process of Zn(II) complexed by different ligands - glycinate [96], ethanol amine [97], azinyl methyl ketoximes [98], aspartame [99], glutathione [100, 101] and several cephalosporin antibiotics [102] -were studied at mercury electrodes in aqueous solutions. 

The isocyanate-ketoxime is usually made in situ during the manufacture of the isocyanate, thereby minimizing environmental and worker exposure to the isocyanate. In ketoxime form, the isocyanate is no longer electrophilic and, therefore, not reactive. When ready to be used in coatings, the ketoxime moiety is removed thermally during application, thereby regenerating the isocyanate and enabling it to react with the intended nucleophile (usually an amine) without the risk of human exposure. 

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