Oximes reductive hydrolysis

Nitriles and oximes are considered together because of common features. Both functions are reduced to primary amines, both undergo coupling reactions to secondary amines, and both are subject to reductive hydrolysis. These similarities arise from a common intermediate, an imine. The imine is... 

On treatment with dimethyl sulfoxide-acetic anhydride followed by sequential oximation, reduction, detritylation, and acid hydrolysis, a tetra-(6-0-trityl)-cyclohexaamylose was reported to afford 2-amino-2-deoxy-D-glucose, in addition to D-glucose, indicating459 that... 

A related sequence was used by Kozikowski and Park (74) to prepare the ring skeleton of streptazolin (200), a compound that exhibits antibacterial and antifungal effects. In this approach, the tricyclic isoxazoline intermediate 198 was formed in the key cycloaddition step (Scheme 6.86). Thus, the reaction of oxime 197 (obtained from 4-piperidone) with sodium hypochlorite-triethylamine afforded tricyclic isoxazoline 198 in very good yield. This cycloadduct was converted to p-hydroxyketone 199 by reduction/hydrolysis using Raney Ni in the presence of acetic acid. Racemic streptazolin (200) was obtained from 199 in several additional steps (74). 

In a similar approach, Shishido et al. (241) used oxime 215 [derived from the monoterpene (+)-citronellal (214)] for the synthesis of (—)-mintlactone (218) and (+)-isomintlactone (219), sweet compounds isolated from some Mentha species (Scheme 6.89). Bicyclic isoxazoline 216 was obtained in good yield from the cycloaddition. As expected, the product possessing tra i-l,4-substimtion prevailed. Reductive hydrolysis of the major isomer of 216 using hydrogen-Raney Ni-trimethyl borate provided p-hydroxyketone 217. This compound was dehydrated to give an enone and this was followed by carbonyl reduction-lactonization to complete the synthesis of both lactones 218 and 219 (241). 

The sesquiterpene skeleton has also been assembled by the intramolecular nitrile oxide cycloaddition sequence. Oxime 238 (obtained from epoxy silyl ether 237), on treatment with sodium hypochlorite gave isoxazoline 239, which was sequentially hydrolyzed and then subjected to the reductive hydrolysis conditions-cyclization sequence to give the furan derivative 240 (330) (Scheme 6.93). In three additional steps, compound 240 was converted to 241. This structure contains the C11-C21 segment of the furanoterpene ent-242, that could be obtained after several more steps (330). 

This was demonstrated by Fukumoto and co-workers in a synthesis of (+)-albicanol (251), a sesquiterpene with potent hsh antifeedant properties (272,273). Oxime 248 [prepared from the (+)-Wieland-Miescher ketone 247] was subjected to cycloaddition using sodium hypochlorite and gave isoxazoline 249 in very good yield (Scheme 6.95). Conversion of 249 into (3-hydroxyketone 250 was again accomplished by the reductive hydrolysis sequence using Raney Ni and trimethyl... 

Kozikowski and Li (268) also made use of this protocol for the construction of the hexahydronaphthalene portion of the hypocholesteremic agent compactin (256) (see Section 6.4.2.2). The oxime derived by from alcohol 253 (via y-lactone 252) was heated with aqueous sodium hypochlorite in the presence of triethylamine to give the tricyclic isoxazoline adduct 254 (Scheme 6.96). Reductive hydrolysis and dehydration afforded enone 255, which in several further steps led to compactin (256) (268). 

The phenanthrenequinone oxime 54 was built in four steps from the two benzenoid precursors 52 and 53. Beckmann rearrangement of 54 furnished the cyano-acid 55. The latter, after reduction to the corresponding cyano-aldehyde, was homologated by Knoevenagel condensation with malonic acid to give, after reduction, hydrolysis and esterification, the diester 56. This compound underwent Dieckmann condensation, installing the seven-membered C-7 ketone 57 in 69% yield after hydrolysis and decarboxylation of the intermediate (3-ketoester. 

Dihalogenation of oxindole followed by alkaline hydrolysis of the 3,3-dihalooxindole has been applied to the synthesis of some isa-tins. A number of oxindoles have been treated with nitrous acid to give isatin-3-oximes. ° Reduction of the oximes to 3-aminooxindoles followed by ferric chloride oxidation gave isatins. 

The reductive cleavage of the N—O bond of oximes is a reaction which has been widely used by synthetic chemists. When accompanied by reduction of the C=N bond the reaction leads to the formation of primary amines. Reactions of this type are described in Chapters 1.2-1.8, this volume. The reductive cleavage of cyclic oximes, particularly isoxazoles and 4,5-dihydroisoxazoles, has been used as a key step in several target syntheses of natural products. These cleavage reactions are covered in Chapter 3.8, this volume however, some of the methods which clearly bring about cleavage of the N—O bond before reduction of the C=N bond are also described in this section. The products of these reactions are A-unsub-stituted imines. Unless the imines are sterically protected or unless special precautions are employed in the work-up, the isolated products are usually carbonyl compounds formed by hydrolysis (Scheme 19). Reductive hydrolysis reactions of this type are also included here. 

Ketoximes are deprotonated by EGB to the oxime anion, which requires a more negative potential for its reduction. Fluorenone oxime gave for n = 1 unchanged oxime, fluorenone (hydrolysis of fluorenone imine), fluorenone imine, and some 0-butylfluorenone oxime, presumably formed by attach of the oxime anion on TBABF4 [62]. 

Fig. (6). A simple and enantioselective synthesis of (+)-albicanol (66) is desccribed. The hydroxy-ketone (60), prepared from the (-) Wieland-Miescher ketone, undergoes ring cleavage with lead tetra-acetate in methanol. The resulting product on ketalization leads the formation of the product (61) which is converted to oxime (63) by the standard reactions. Intramolecular cyclization followed by reductive hydrolysis and methylenation afforded (+)- albicanol (66).

Dissolving metal reduction of the oxime and hydrolysis gave lR,3R-3-aminocyclo-pentane-1-carboxylic acid, 7.41. An identical approach was used to prepare cyclohexane derivatives. Reaction of 7.129 " with hydroxylamine76b.77 nd subsequent... 

An intramolecular photocyclization of eucarvone (54), which contains all of the required carbon atoms, was used by Ayer and Browne (96) to give cyclopentanone (55) (Scheme 11). Transposition of the keto group, Beckman fragmentation of the resultant oxime (58), hydrolysis and reduction completed the synthesis. 

The imides, primaiy and secondary nitro compounds, oximes and sulphon amides of Solubility Group III are weakly acidic nitrogen compounds they cannot be titrated satisfactorily with a standard alkaU nor do they exhibit the reactions characteristic of phenols. The neutral nitrogen compounds of Solubility Group VII include tertiary nitro compounds amides (simple and substituted) derivatives of aldehydes and ketones (hydrazones, semlcarb-azones, ete.) nitriles nitroso, azo, hydrazo and other Intermediate reduction products of aromatic nitro compounds. All the above nitrogen compounds, and also the sulphonamides of Solubility Group VII, respond, with few exceptions, to the same classification reactions (reduction and hydrolysis) and hence will be considered together. 

Alloxan forms an oxime (1007) which is the same compound, violuric acid, as that formed by nitrosation of barbituric acid likewise, a hydrazone and semicarbazone. Reduction of alloxan gives first alloxantin, usually formulated as (1008), and then dialuric acid (1004 R = OH) the steps are reversible on oxidation. Vigorous oxidation with nitric acid and alkaline hydrolysis both give imidazole derivatives (parabanic acid and alloxanic acid, respectively) and thence aliphatic products. Alloxan and o-phenylenediamine give the benzopteridine, alloxazine (1009) (61MI21300). 

Oximes are cleaved by oxidation, reduction, or hydrolysis in the presence of another carbonyl compound. Some synthetically useful methods are shown below. 

This method is an adaptation of that of Dengel. -Methoxy-phenylacetonitrile can also be prepared by the metathetical reaction of anisyl chloride with alkali cyanides in a variety of aqueous solvent mixtures by the nitration of phenylaceto-nitrile, followed by reduction, diazotization, hydrolysis, and methylation 1 by the reduction of ct-benzoxy- -methoxy-phenylacetonitrile (prepared from anisaldehyde, sodium cyanide, and benzoyl chloride) and by the reaction of acetic anhydride with the oxime of -methoxyphenylpyruvic acid. ... 

In vitro studies on rat liver preparations confirmed the postulated metabolic pathway of nonenzymatic hydrolysis of the oxime 11.69 to the ketone 11.70, followed by enzymatic reduction to 11.71, hydroxylation to diols, and glucuronidation. Clearly, the first step in this metabolic scheme is the nearly quantitative hydrolysis of the oxime to the ketone. 

---