Aldoximes formation

The use of soluble amine bases failed to give products, whereas the heterogeneous conditions KOH/THF proved optimal in promoting aldoxime formation for a broad range of substrates. Optically active nitroalkanes including aromatic (both electron-rich and electron-deficient), heteroaromatic, branched and unbranched aliphatic substrates, as well as substrates that incorporate unprotected alcohol functionalities were successfully reduced. 

Nitriles. Aldehydes are converted in one step into nitriles when heated with hydroxylamine hydrochloride in formic acid. An aldoxime formate is a probable intermediate. The method is a variation of that of van Es. ... 

Conversion of amino acids to aldoximes The understanding of the formation of aldoximes from amino acids was impaired for a long time by controversial conceptions of different research groups, and temporarily it was discussed that three different pathways should be responsible for the aldoxime formation in different plants ... 

Based on inhibitor studies, Wallsgrove and co-workers had been confident that at least in B. napus, flavin-containing mono-oxygenases are involved in the aldoxime formation (Bennett et al, 1993, 1995a,b Dawson et al, 1993). 

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. 

The addition of (E)- and (Z)-crotylboronates 7 to aldoximes 6 has been realized in good yield by performing the reaction under 3-6 x 10° Torr pressure10. The resulting hydroxylamines 8 can easily be reduced to yield the primary amines. The addition of E-l leads preferentially to the anh-diastereomcr 8, while (Z)-crotylboronate 7 shows a modest selectivity towards formation of the vyy -diastereomer 8 (same sense as in the reaction with aldehydes). Some effort has been made to elucidate the mechanism, but this is not yet well understood. 

Nitrile oxides are usually prepared via halogenation and dehydrohalogenation of aldoximes [11] or via dehydration of primary nitro alkanes (Scheme 1) [12]. However, it is important to note that nitrile oxides are relatively unstable and are prone to dimerization or polymerization, especially upon heating. 1,3-Dipolar cycioaddition of a nitrile oxide with a suitable olefin generates an isoxazoline ring which is a versatile synthetic intermediate in that it provides easy access to y-amino alcohols, )5-hydroxy ketones, -hydroxy nitriles, unsaturated oximes, and a host of other multifunctional molecules (Scheme 1) [5a]. Particularly for the formation of )5-hydroxy ketones, nitrile oxide-olefin cycioaddition serve as an alternative to the Aldol reaction. 

The utility of lOOC reactions in the synthesis of fused rings containing a bridgehead N atom such as pyrrolizidines, indolizidines, and quinolizidines which occur widely in a number of alkaloids has been demonstrated [64]. Substrates 242 a-d, that possess properly positioned aldoxime and alkene functions, were prepared from proline or pipecolinic acid 240 (Eq. 27). Esterification of 240 and introduction of unsaturation on N by AT-alkylation produced 241 which was followed by conversion of the carbethoxy function to an aldoxime 242. lOOC reaction of 242 led to stereoselective formation of various tricyclic systems 243. This versatile method thus allows attachment of various unsaturated side chains that can serve for generation of functionalized five- or six-membered (possibly even larger) rings. 

The NHase responsible for aldoxime metabolism from the i -pyridine-3-aldoxime-degrading bacterium, Rhodococcus sp. strain YH3-3, was purified and characterized. Addition of cobalt ion was necessary for the formation of enzyme. The native enzyme had a Mr of 130000 and consisted of two subunits (a-subunit, 27 100 (3-subunit, 34500). The enzyme contained approximately 2 mol cobalt per mol enzyme. The enzyme had a wide substrate specificity it acted on aliphatic saturated and unsaturated as well as aromatic nitriles. The N-terminus of the (3-subunit showed good sequence similarities with those of other NHases. Thus, this NHase is part of the metabolic pathway for aldoximes in microorganisms. 

Aldoximes are normally dehydrated by reaction with dichlorocarbene, produced under soliddiquid two-phase conditions, to yield nitriles in high yield [41, 42], whereas a-hydroxy ketoximes are cleaved with the simultaneous formation of a nitrile and either an aldehyde or ketone (Scheme 7.33). Yields are generally >70% and, in the case of cyclic hydroxy ketoximes, the products are acyclic oxo nitriles [43],... 

Kinetic parameters k, often also and AS, occasionally AV ) for formation and dissociation of several pentacyanoferrate(II) complexes [Fe(CN)5L]" have been established. Ligands L include several S- and A-donor heterocycles,4-methyl- and 4-amino-pyridines, a series of alkylamines, 3- and 4-hydroxy- and 3- and 4-methoxy-pyridines, several amino acids, nicotinamide, " 4-pyridine aldoxime, 3-Me and 3-Ph sydnones, several bis-pyridine ligands,neutral, protonated, and methylated 4,4 -bipyridyl, 1,2-bis(4-pyridyl)ethane and traTO-l,2-bis0-pyridyl)ethene, pyrazine- 4,4 -bipyridyl- and bis(4-pyridyl)ethyne-pentaammine-cobalt(III), edta-ruthenium(III), and pentaammineruthenium-(II)and-(III) complexes of... 

If there were ever a simple comparison of enthalpies of formation to be investigated as part of this chapter it would be the oximes of the aliphatic aldoximes, RCH=NOH, as R proceeds through Me, Et, n-Pr,. Ideally, we would have the values for at least R = Me and Et and then employ the universal methylene increment to derive the remaining values by addition of —20.6 kJmoR for gaseous species and a related ca —26.0 kJ moR for... 

Thus, a new and convenient procedure has been developed by Defrancq and coworkers for the synthesis of 3 -ohgonucleotide conjugates 83 through the formation of glyoxyhc oxime bonds (Scheme 44). This has been achieved by using a novel sohd support 82 for ODN synthesis. Support 82 was conveniently prepared from a commercially available serine derivative in a few steps. The glyoxylic oxime bonds showed higher stability than aldoxime bonds at acidic to neutral pH but lower stabihty at alkaline pH. 

Rare-earth exchanged [Ce ", La ", Sm"" and RE (RE = La/Ce/Pr/Nd)] Na-Y zeolites, K-10 montmorillonite clay and amorphous silica-alumina have also been employed as solid acid catalysts for the vapour-phase Beckmann rearrangement of salicylaldoxime 245 to benzoxazole 248 (equation 74) and of cinnamaldoxime to isoquinoline . Under appropriate reaction conditions on zeolites, salicyl aldoxime 245 undergoes E-Z isomerization followed by Beckmann rearrangement and leads to the formation of benzoxazole 248 as the major product. Fragmentation product 247 and primary amide 246 are formed as minor compounds. When catalysts with both Br0nsted and Lewis acidity were used, a correlation between the amount of Br0nsted acid sites and benzoxazole 248 yields was observed. 

The formation of a very electrophilic intermediate 258 from 256 and 257 is proposed (equation 78). The hydroxyl group of the oxime adds to 259, giving a reactive cationic species 260 that rearranges and affords the nitrile 261 (in the case of aldoxime, equation 79), or the amide 262 upon hydrolytic workup (equation 80). The conversion of 260 to the nitrilium ion should occur through a concerted [1,2]-intramolecular shift. This procedure can be applied in the conversion of aldoximes to nitriles. It was observed that the stereochemistry of the ketoximes has little effect on the reaction, this fact being explained by the E-Z isomerization of the oxime isomers under the reaction conditions. 

Mahadevan, in his 1973 review, proposed a scheme for the formation of diverse oximes from amino acids that involves A-hydroxylation of the amino group, to form the corresponding HA derivative, which is then further converted to the corresponding more stable oxime function . According to this scheme, the A-hydroxylation of amino acids leads to the unstable intermediate, 22, that is converted to the aldoxime, 23, or to the less stable... 

Sorghum P450 , (CYP71E1) Conversion of aldoxime 26 to p-hydroxymandelonitrile en route to formation of dhurrin 120... 

The formation of nitriles from aldoximes was at that time a well-known reaction, at least in its general lines. Gabriel and Meyer found that o-nitrobenzonitrile was obtained by heating o-nitrobenzaldoxime, prepared in an indirect way, with sodium acetate and acetic anhydride Lach prepared benzonitrile in a similar way, and Dollfuss transformed aldoximes of the aliphatic series into nitriles by simple treatment with acetic anhydride. The complicated character of this reaction was demonstrated by the classical work of Beckmann and Hantzsch, who... 

L-Aldono-1,4-lactones can be prepared from o-aldose perpivaloates and perace-tates (compounds of type 17) [28]. The method implies formation of aldoximes (18), followed by mesylation (Scheme 7). The resulting 5-0-mesyl glyconitrile derivatives (19) are then submitted to acid-catalyzed hydrolysis giving the corresponding 1,4-lactones 20a-c. 

The oxidation of aldoximes and amidoximes (methods Q and R) is not a practical process but rather a way of formation. The reactions have been described because oxadiazoles have been isolated among a lot of other oxidation products. 

Inasmuch as myositis was reported in the second paper as well as in the first,52 this response must be induced by the oximes and not by bacteria. The second paper showed that oral doses of 1 and TMB-4 CI2 induced the same sort of scar formation as II in the gastric mucosa, so that this response may be induced by either the oxlmlno group or the quaternary nitrogen atom. It would be informative in this regard to have the results of an experiment in which capsules of pyridine-2-aldoxime and of N-methylpyridinium chloride were administered in a similar fashion. 

Nitriles from aldoximesThe Vilsmeier reagent reacts with ketoximes to form the O-formate, but converts aldoximes into nitriles in excellent yields. 

The formation constants of the Cu11, Znn, Nin and Pd11 chelates of selenophene-2-aldoxime (50) were determined by Bark and Griffen194 as part of a study on O, S and Se analogous ligands. The unusual order Se > S > O which was found was attributed to the aromatic nature of the chelates. 

When the reaction is carried out in boiling DMSO, no significant gain in the yield of benzamide (30%) is observed. Since under these conditions the primary dehydration of aldoximes is evident, the formation of benzamide is most likely to result from hydration of the intermediate benzonitrile rather than by the Beckmann rearrangement scheme. 

Under the same conditions, aldoximes (E- and Z-isomers), along with the formation of diadduct 144, are sometimes dehydrated to nitriles, ethyl acetate being the second reaction product. This is explained (60RTC888) by decomposition of the intermediate O-vinyloxime 145 (Scheme 71) which, however, has never been isolated. 

Nitriles were also obtained in the reaction of aldoximes with - N,N-diethylamino)propyne via the supposed formation of Ovinyloxime 146 (Scheme 72) (77S338). In both cases, the intermediate O-vinyloximes (145,146), instead of pyrrolization, prefer decomposition into nitrile and carbonyl compounds. 

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