Hydroxylamines nitrones, hydrolysis

II. HYDROXYLAMINES THROUGH HYDROLYSIS OF HYDROXAMIC ACIDS, OXIMES AND NITRONES... 

Hydrolysis of nitrones, oximes and hydroxamic acids is frequently used as a final step in the preparation of substituted hydroxylamines. Although hydrolysis is the most commonly utilized method for oximes, oxime ethers and nitrones, formation of sensitive hydroxylamines can also be achieved under milder reaction conditions by treatment of... 

Trialkylboron hydrides react with conjugated nitroalkenes to yield nitronate intermediates via a 1,4-addition of the hydride. The corresponding nitroalkanes are easily obtained by using silica gel to proto-nate the nitronate salt. These reactions presumably occur through a common intermediate (36), which is then hydrolyzed to the nitroalkane or reduced by a borane complex to yield hydroxylamine, after hydrolysis. 

Treatment of 2- 5//-dibenz[i>,/]azepin-5-yl acetaldehyde (16), prepared in 68% yield by /V-alkylation of 5/7-dibenz[A,/]azepine with bromoacetaldehyde diethyl acetal followed by acid hydrolysis, with methyl hydroxylamine yields the isolable nitrone 17, which in refluxing toluene undergoes intramolecular 1,3-dipolar cycloaddition at the CIO —Cl 1 alkene bond to give 2,3,3a, 12b-tetrahydro-2-methyl-3,8-methano-8//-dibenz[i>,/]isoxazolo[4,5-r/]azepine (18).235... 

A convenient route to j3-phosphorus nitroxides involves the 1,3-addition of trimethylsilyl phosphites (e.g., diethyl) or trimethylsilyl phosphines (e.g., diphenyl) to aldo nitrones (e.g., a-PBN, DMPO), or keto nitrones (e.g., 2-Et-DMPO or 2-Ph-DMPO), to form a-phosphityl- or a-phosphinyl-O-silylhydroxyl-amines. Acidic hydrolysis provides the corresponding hydroxylamines which are easily oxidized to p-phosphorus-nitroxides (690). 

To avoid overoxidation, primary amines (e.g. 128, equation 89) can be converted into Schiff bases with an aromatic aldehyde. Subsequent oxidation of the resultant imines 129 with an excess of peracids produces oxaziridines 130 and/or nitrones 131. Both of them produce hydroxylamines 132 (equation 89) upon hydrolysis in moderate to good overall yields. Yields of hydroxylamines are considerably better if anisaldehyde instead of benzaldehyde is used for the protection . ... 

Di(octadecyl)hydroxylamine (18) (Seltzer et al., 1989 PospiSil and Nespurek, 1997) was recently introduced commercially for the stabilization of PO, PP in particular. 18 is a hydrolysis-resistant processing stabilizer used in combination with aromatic phosphites, and a long-term heat stabilizer used in combination with suitable HAS. Di-alkylhydroxylamine is considered as scavenger of radicals POO" and P. The latter are trapped by nitroxide or nitrone, arising from the parent hydroxylamine (Eq. 3-7). 

In an interesting sequence of reactions, Grundmann and co-workers have prepared 5-amino-4-nitroisoxazole (67) from the sodium salt of nitromalonaldehyde and hydroxylamine.59 The initially formed sodium malon-dialdoxime nitronate 65 is diacetylated and cyclized to the furazan oxide 66 acid hydrolysis, followed by rearrangement in alkali gives the 5-amino-4-nitroisoxazole (Scheme 13). The same product has also been detected in the decomposition of mercuric fulminate. 

Petrini and co-workers used the bis(methoxymethyl)-protected nitrone 150, also derived frern L-tartrate, as an electrophile rather tfaiui as a 1,3-dipole (Scheme 21, top line) (89). In their key step, reaction with 4-ben loxybutylmagnesium bromide gave the cyclic hydroxylamine 151 in 82% yield (de 90%). Transfer hydrogenation with ammonium formate and a palladium catalyst cleaved both the hydroxylamine and the benzyl ether, affording the aminoalcohol 152. Cyclization via the corresponding primary chloride created the protected indolizidine 153, acidic hydrolysis of t ch completed this short synthesis of ( + )-132 in 16%... 

Addition to the C=N of an imine forms the magnesium amide, which is hydrolyzed to an amine. Isolated C=N double bonds of simple imines are relatively unreactive toward organomagnesium compounds, and may instead be depro-tonated at the a-position. Oximes and other N-substituted imines may react better, although an alternative sequence can produce aziridines. Imminium ions, because of their positive charge, are more reactive, and are useful in making tertiary amines. A-Silylimines yield primary amines after hydrolysis. Grignard reagents also add to one C=N of carbodiimides to produce amidines, and to nitrones to produce hydroxylamines. Some varied examples are shown in Scheme 6. 

The racemic dilithio species 69 was prepared from l-(l,3-dithian-2-yl)pro-pan-l-ol and added to nitrone 62 to provide hydroxylamine 70, which was then subjected to Cope-House pericychc cyclization, installing the methyl substituent at the C-5 position (Scheme 14). The resulting pyrrolizidine AT-oxides 71-72, obtained as a 1 1 mixture in a moderate 55% yield, were submitted to subsequent N—O bond reductive cleavage, providing the desired pyrrolizidines 73-74. A two-step sequence involving hydrolysis of the dithio-ketal and then reduction of the ketone provided the partially protected hya-cinthacine core as a single isomer in 33% yield. Subsequent removal of the... 

The splitting of nitrones may be carried out by hydrolysis with hydrochloric acid (155,178,182), hydrazinolysis (182,186) or most suitably hydroxylaminolysis (183) (Scheme 44). Esters (191-193, 212) are easily converted into N-hydroxyamino acid esters (76, 77,130, 213) by action of hydroxylamine or its crystalline salts such as hydroxylamine hydrochloride (184), oxalate or toluenosulfonate (183) without disturbing the ester function. The salts of the last type are easily crystallized. 

Other 3-aiyl aminopropanoic acid derivatives have been prepared using oxazoli dine derivatives derived from vinyl acetates and hydroxylamines.62 Nitrone 2.126 is more sterically encumbered than the nitrones shown previously, and reaction with vinyl acetate gave a poor yield of 2.727.62 Hydrolysis of 2.337, followed by oxidation and catalytic hydrogenation led to 4-methyl-3-aminopentanoic acid, 2.128. ... 

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