Aldoximes, hydrogenation

It is usually an oxime, either isolated or prepared in situ. The a-groups of the oxime may be alkyl, aryl, heteroaryl (ketoxime) and one may be hydrogen (aldoxime). 

It uill be easily understood from these formula why the /3-compound should yield bcn/onitrile vith acetic anhydride whilst thea-compoiind does not. Thepio imity of hydrogen and hydioxyl m the former case facilitates the formation and elimination of water. In this way the configuration of most of the aldoximes may be ascertained. 

With aldoximes (R = H) a migration of hydrogen is seldom found. The Beckmann rearrangement therefore does not give access to iV-unsubstituted amides. 

OH elimination from ortho substituted aldoximes 179 (X = CH2, NH, O) may be at least partially the result of a hydrogen migration/cyclization/elimination process, whereby the heterocycles 182 are formed72 (46). A metastable peak shape analysis, the investigation of 2H-labelled derivatives and the study of positional isomers indicate that in addition to 182 the protonated isocyanide 183 is formed via a mechanism which is not fully understood. However, it is known that the generation of 183 occurs without any detectable interaction with the XH ortho substituent. 

Anhydrous peroxytrifluoroacetic acid is not easy to handle, but the procedure has recently been revised.121 Namely, reaction of urea-hydrogen peroxide complex (UHP) with tri-fluoroacetic anhydride in acetonitrile at 0 °C gives solutions of peroxytrifluoroacetic acid, which oxidize aldoximes to nitroalkanes in good yields (Eqs. 2.58 and 2.59). Ketoximes fail to react under these conditions, the parent ketone being recovered. 

Aldehyde 26 was treated with hydroxylamine hydrochloride in refluxing methanol to give a mixture of (E)- and (Z)-pyrrolotriazine 40 in 59% and 21% yield, respectively. Dehydration of aldoxime 40 with trifluoromethanesulfonic anhydride and triethylamine in dichloromethane afforded triazine 41. Conversion of the nitrile 41 to the deprotected amide 42 was accomplished in 96% yield on treatment of 41 with basic hydrogen peroxide in ethanol <2001CAR77>. 

Yields are frequently moderate for Scholl reactions. Aldoximes are not usually compatible with these harsh reaction conditions and are very sensitive to factors such as temperature and reaction time. Consequently, oxidation to the corresponding carboxylic acid is a major side-reaction. However, both the ketoxime (51) and the aldoxime (53) are reported to give good yields of the corresponding m-dinitro compounds, (52) and (54) respectively, on treatment with absolute nitric acid in methylene chloride followed by hydrogen peroxide. 

Some recent advances have been reported in oxime oxidation, including the in situ generation of peroxytrifluoroacetic acid from the reaction of urea hydrogen peroxide complex with TFAA in acetonitrile at 0 °C This method gives good yields of nitroalkanes from aldoximes but fails with ketoximes. 

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. 

Aldoximes yielded primary amines by catalytic hydrogenation benzaldehyde gave benzylamine in 77% yield over nickel at 100° and 100 atm [803, with lithium aluminum hydride (yields 47-79%) [809, with sodium in refluxing ethanol (yields 60-73%) [810] and with other reagents. Hydrazones of aldehydes are intermediates in the Wolff-Kizhner reduction of the aldehyde group to a methyl group (p. 97) but are hardly ever reduced to amines. 

In Table 2 are listed the hydroxylamines, oximes and hydroxamic acids for which we have determined the gas phase structures. We tried to select a representative group in each category. There are two types of oximes, as indicated, aldoximes and ketoximes. Due to restricted rotation around the C=N double bond, these can exist in two isomeric forms (except when R = H for an aldoxime and R = R" for a ketoxime). We have investigated both isomers in nearly every instance. For aldoximes, they are generally labeled syn when the H and OH are on the same side of the double bond and anti when on opposite sides. Note that the ketoximes in Table 2 contain one pair of isomers in which the >C=NOH group is not bonded to two carbons instead one bond is to a chlorine. One of these isomers wiU be of interest in Section B.D in the context of hydrogen bonding vi lone pair—lone pair repulsion. 

FIGURE 2. Structures of the four 2-pyridyl aldoxime isomers in Table 2, shown from top to bottom in order of increasing stability. The black atom in each ring is the nitrogen the small white atoms are hydrogens. (Figure 2 is continued on the next page.)... 

Oximes are a class of chemical compounds with general formula R R C=N0H, where R is an organic side chain and R may be either hydrogen, forming an aldoxime, or another organic residue, forming a ketoxime (Chart 1). 

Reaction of aldoximes with dimedone derivatives under microwave irradiation leads to partially hydrated acridine derivatives . Eused heterocyclic compounds containing partially hydrogenated pyridine and quinoUne rings were prepared by intramolecular cycloaddition reaction of 5-alkynyl oxime derivatives . (Z)-l,10a-Dihydropyrrolo[l,2-i>]... 

Both cyclic and acyclic ketoximes may be used in this transformation and the reaction is usually performed in an alcohol solution containing equimolar quantities of alkoxide. For a successful reaction, the starting material usually contains at least an a-methylene group but the presence of only one a-hydrogen may suffice. When treated with base the 0-acylated aldoximes do not react via the Neber rearrangement and instead they undergo an E2 elimination to cyanides or isocyanides. 

Chloramine-T has also been employed, both as a halogenating reagent and base the reaction proceeds in good yield with aromatic as well as with aliphatic aldoximes (81). The role of chloramine-T probably involves an initial chlorination of the aldoxime to give the hydroximoyl chloride, followed by base-catalyzed hydrogen chloride elimination to afford the nitrile oxide (81). 

The presence of the double bond (carbonyl group C 0) markedly determines the. chemical behavior of the aldehydes. The hydrogen atom connected directly to the carbonyl group is not easily displaced. The chemical properties of the aldehy des may be summarized by (1) they react with alcohols, with elimination of H2O, to form ace t i (2) they combine readily with HCN to form cyanohydrins, (3) they react with hydroxylamine to yield aldoximes (4) they react with hydrazine to form hydrazones (5) they can be oxidized lulu fatty acids, which contain die same [lumber of carbons as in the initial aldehyde 5) they can be reduced readily to form primary alcohols. When bcnzaldchydc is reduced with sodium amalgam and HjO, benzyl alcohol C,f l - -C f I Of I is obtained. The latter compound also may be obtained by treating benzaldehyde with a solution of cold KOH in which benzyl alcohol and potassium benzoate are produced. The latter reaction is known as Cannizzaro s reaction. 

Aldoximes are reduced to amines by hydrogen at 180—220° in the presence of reduced nickel or copper with benzaldoxime, however, the chief product is benzaldehyde when copper is used, and toluene when nickel is used.13... 

Sanui and co-workers [67] carried out hydroformylation of polypentenamer (PPA). They converted hydroformyl group of the modified PPA to the aldoxime and subsequently to nitrile derivatives (Scheme 4.5). Then they carried out hydrogenation to convert the amorphous, unsaturated nitrile derivative to the crystalline saturated polymer. 

Chlorination of aldoximes. NCS converts aryl aldoximes to hydroxamic acid chlorides without significant chlorination of the aryl group. This reaction has been used for a novel synthesis of nitrile oxides. Thus reaction of salicylaldoxime (1) with NCS followed by dehydrochlorination with pyridine generates a nitrile oxide, which is trapped by styrene to give the isoxazoline 2. The N-O bond can be cleaved by catalytic hydrogenation to 3, which is converted into the chalcone 4 on elimination of water. This product can be converted by classical methods to the flavanone 5 and the flavone 6. An analogous route can be used to synthesize 2-... 

Oxazole IV-oxides cannot be made by oxygenation of oxazoles. The only method of synthesis remains the condensation of monooximes of 1,2-dicarbonyl compounds with aldehydes in the presence of hydrogen chloride (equation 132) (15CB897). The aldehyde may be aromatic or aliphatic (including formaldehyde) and the oxime may be derived from an aromatic diketone or it may be an a-keto aldoxime, leading to a 2,5-disubstituted oxazole IV-oxide. It may also contain an additional carbonyl group as in equation (133). 

Disubstituted thiazoles are readily obtained by the action of a-mercapto ketones (278) on nitriles (279). The reaction is carried out in benzene solution at 0°C by passing a current of dry hydrogen chloride through the mixture (Scheme 199). In a variation of this reaction, by refluxing a-mercapto ketones (278) with aldoximes (280) for 2 hours at 100 °C, 2,4-di- or 2,4,5-tri-substituted thiazoles are obtained in good yields (Scheme 200). 

Fukunishi K, Kitada K, Naito I (1991) A facile preparation of iminoxy dimers by hydrogen peroxide/peroxidase oxidation of aldoximes. Synthesis 237-238... 

In the catalytic hydrogenation of aldoximes with Raney nickel Paul (101) observed a small amount of rearrangement of the aldoxime to the acid amide. Raney nickel induces the rearrangement which takes place... 

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