Oximes with ketones

Fragments Reaction of Trifluoroalkane-2,3-Dione-3-Oximes with Ketones... 

The oximes of ketones undergo the Beckmann rearrangement on treatment with phosphorus pentachloride (118). 

Not only do oximes undergo the Beckmann rearrangement, but so also do esters of oximes with many acids, organic and inorganic. A side reaction with many substrates is the formation of nitriles (the abnormal Beckmann rearrangement, 17-31). Cyclic ketones can be converted directly to lactams in one laboratory step by... 

The rather restricted range of available aliphatic nitro compounds has been extended by the discovery that oximes of ketones, e.g, (15) can be oxidised to secondary nitro compounds (16) with the per-acid CF COgH,... 

Reductive cross-dimerization has been established with ketones and 0-meth-oximes upon reduction in isopropanol with a Sn cathode as a convenient route to yS-amino alcohols, diastereoselectivities of up to 85 15 were obtained. A chiral ligand was obtained this way from the coupling of (-) - menthone with O-methyl acetaldoxime. Similarly, ketones could be coupled to hydrazones and nitrones. Also, intramolecular couplings were achieved with good yields and diastereoselectivity (Fig. 56) [308]. 

Various types of aromatic aldehydes with electron donating and withdrawing groups were cleanly and rapidly condensed with hydroxylamine hydrochloride at 90 °C, giving the corresponding -isomer of oximes (with OH anti to aryl) in excellent yields in the presence of CUSO4. However, aromatic ketones such as benzophenone did not afford the corresponding oximes under these conditions. 

One exception is the reaction of acetone oxime with divinyl ketone in the presence of an equimolar amount of zinc(II) bromide (162). Acetone oxime reacts with divinyl ketone on heating in THE at reflux, leading to both conjugate addition and nitrone cycloaddition, producing a 5 1 mixture of regioisomers with 8-oxa-l-azabicyclo[3.2.1]octan-4-one as the major isomer (Scheme 11.42). On the other hand, in the presence of an equimolar amount of zinc(II) bromide, 7-oxa-l-azabicyclo[3.2.1]octan-4-one is the major isomer (97 3) in a total yield of 97%, indicating that the Lewis acid has controlled the regioselectivity of the second step, namely, the cycloaddition. 

Intermolecular reactions between 0-benzyl oximes and ketones (or aldehydes) are limited to those with formaldehyde O-benzyl oxime. However, intramolecular coupling proceeds with carbonyl-tethered oxime ethers (Equation (69)). 

The lactam (2) is obtained in 87% yield by treating cycloheptanone with sodium azide and concentrated hydrochloric acid (54JA2317). Beckmann rearrangement of cycloheptanone oxime with concentrated sulfuric acid gives (2) in 88% yield (58JA1510). Alternatively, the ketone gives (2) directly by reaction with hydroxylamine sulfonate in 95% formic acid (79S537). 

Reaction with alcohols is general for diazo compounds, but it is most often performed with diazomethane to produce methyl ethers or with diazo ketones to produce a-keto ethers, since these kinds of diazo compounds are most readily available. With diazomethane593 the method is expensive and requires great caution. It is used chiefly to methylate alcohols and phenols that are expensive or available in small amounts, since the conditions are mild and high yields are obtained. Hydroxy compounds react better as their acidity increases ordinary alcohols do not react at all unless a catalyst such as HBF4594 or silica gel595 is present. The more acidic phenols react very well in the absence of a catalyst. Oximes, and ketones that... 

Many of the methods discussed in this section can also be treated as combinations of more than two fragments. For instance, in the cyclization of a-hydrazono oximes with orthocarboxylates described in the next section, the a-hydrazono oximes (635) are treated as a five-atom fragment, but since these compounds are usually prepared from ketones by nitrosation and reaction of the oximino ketones with hydrazine, the entire reaction sequence may be described asa[2 + l+ 2+ l] combination. 

When the hydroxyliminoenamines (797) were treated with hydrazine, 2,3-dihydro-l,2,4-triazine 4-oxides (799) were obtained. The intermediates are the a-hydrazono oximes (798) which as indicated above (c/. 635 ->637, Section 2.19.4.2.1) can also be cyclized with ketones to afford the 2,3-dihydro derivatives (800 Scheme 31) (75S794,76GEP2527490). 

Beckmann Rearrangement results when oximes of ketones are treated with certain reagents such as phosphorus pentachloride. 

Aldehydes (e.g., citral, cinnamic aldehyde, etc.) and certain ketones e.g., acetone) react with hydroxylamine hydrochloride forming oximes with the liberation of hydrochloric acid (Z. a., 1895, 623) which can be titrated in presence of methyl orange. 

During condensation of 4-fluoroacetophene oxime with acetylene, along with possible substitution of fluorine, the regeneration of 4-fluoroace-tophenone (yield 24%) becomes a prominent process, as compared with other oximes, especially when calcined potassium hydroxide and dry DMSO are used (Scheme 9). Ketone is likely to form owing to nucleophilic addition of the hydroxide anion to the C=N bond of oxime [90ZOR(ip)J. 

The condensation of methyl perfluorophenyl ketone oxime with acetylene (KOH/DMSO, 100°C, 2 hr, 12 atm) failed to afford the expected pyrrole [90ZOR(ip)]. 

Not surprisingly, the anion derived from 3//-pyrrolizine is a stronger nucleophile than compound 1 itself. Thus the anion reacts with deuterium oxide to give 31//,32//-pyrrolizine, but attempts at further enrichment give mixed deuteriopyrrolizines.83,115 The anion reacts with ketones to give azafulvenes such as 248 and 268.43,115 It seems possible that the reported formation of the oxime of 3//-pyrrolizin-3-one (269) from 3//-pyrrolizine and... 

The addition of ZnBi 2 to die tandem 1,3-azaprotio cyclotransfer-cycloaddition of a ketoxime with divinyl ketone results in rate enhancement and the exclusive formation of l-aza-7-oxabicyclo[3.2.1]octan-3-ones.79 The 1,3-dipolar cycloaddition of 1-aza-l-cyclooctene 1-oxide with alkenes produces the corresponding isoxazolidines in high yields with a minimum of polymeric material.80 The cycloaddition of thiophene-2 -carbaldehyde oxime with acetonitrile and methyl acrylate produces the 1,3-dipolar adduct, substituted isoxazolidines, and not the previously reported 4 + 2-adducts.81 Density functional theory and semi-empirical methods have been used to investigate the 3 + 2-cycloaddition of azoxides with alkenes to produce 1,2,3-oxadiazolidines.82 The 3 + 2-cycloaddition of a-nitrosostyrenes (62) with 1,3-diazabuta-l,3-dienes (63) and imines produces functionalized cyclic nitrones (64) regioselectively (Scheme 22).83... 

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