Of isonitramine

The structure of these compounds remained obscure for a long time. Traube originally assigned the structure —N—N—OH to the isonitramino group, but in further researches he found that isonitramines and the derivatives of nitrosohydro-xylamine which he prepared by the action of nitrous acid on -derivatives of hydro-xylamine were identical. He did not, however, draw from this any definite conclusions as to the structure of isonitramines in spite of the fact that by the synthesis of isonitraminoisobutyric acid, Gomberg [63] had confirmed the nitrosohydro-xylamine structure of the isonitramino group. 

Urbanski and Piskorz [60] found that the properties of methylenedi-isonitramine salt differ markedly from those of methylenedinitramine salt. They also established that methylenedi-isonitramine is not a tautomeric modification of methylenedinitramine. In their most recent work [70] they have confirmed the nitrosohydroxylamine structure of isonitramines by examining the infra-red absorption spectra. 

The basis of this old method is the addition of nitric oxide to alcoholic solutions of sodium salts of C-alkyl derivatives of ethyl ace-toacetate (54) 128,129) (Scheme 17). Salts of alkyl derivatives of diethyl malonate (55) were used in Neelakantan s modification (79). In both cases sodium salts of isonitramine (56), stable only in alkaline solution, were formed initially and subsequently transformed into N-hydroxyamino acids (1) by means of concentrated hydrochloric acid. This method using common substrates is quite general and may be used for the synthesis of N-hydroxyamino acids (1) of different types 36, 79). Usually it has been used for the synthesis of N-hydroxyglycine (28) 129) and N-hydroxyphenylalanine (35) (79, 94,129). 

Park et al. also reported an analogous strategy for the synthesis of (+)-isonitramine (107) [61], A phase-transfer catalyzed enantioselective ot-alkylation of lactam 108, followed by subsequent manipulations, was employed for the successful total synthesis of the Nitraria alkaloid (+)-isonitramine (107) (Scheme 21). 

MEDINA in an acronym for MEthylene DINtrA-mine. In earlier literature it was called MEDNA (Ref 2), the latter name later used for the isomeric compd me thylenedi-isonitramine which was obtained by the action of nitric oxide on acet (Beil 1, 592) (See under MEDNA in this... 

It fonns expl heavy metal salts, which according to Urbanski, are weaker initiators than the corresponding metal salts of methylenedi-isonitramine. The decreasing order of brisance of these salts, when primed with MF, in the Pb plate test were Na, Ca, Ba, H and Pb Refs 1) T. Urbanski T, Wesolowski, Wiad-TechnUzbr 18, 28 (1932) 2) T. Urbanski,... 

In this reaction phenylhydroxylamine behaves like a secondary amine. To the class of nitrosohydroxylamines there belong also the so-called isonitramines and the compound of nitric oxide and potassium sulphite. 

The direct nitration of a primary amine to a nitramine with nitric acid or mixtures containing nitric acid is not possible due to the instability of the tautomeric isonitramine in strongly acidic solution (Equation 5.1). Secondary amines are far more stable under strongly acidic conditions and some of these can undergo electrophilic nitration with nitric acid in a dehydrating medium like acetic anhydride. 

Traube [15] prepared methylenedi-isonitramine, the isomer of methylenedinitramine, in the form of a sodium salt, by the action of nitric oxide on acetone, in the pres-... 

T. Urbanski, Zacharewicz and Pietrzyk [61] suggested the use of some methyl-enedi-isonitramine salts (CH2) (N202H)2 as primary explosives. 

The sodium salt of methylenedi-isonitramine was prepared by Traube [62] from acetone and nitric oxide in the presence of sodium alcoholate according to the following chain of reactions ... 

The sodium salt of methylenedi-isonitramine (II) is formed. In an aqueous solution this precipitates with the salts of heavy metals. Some of these salts (e.g. the thallium salt) have the properties of weak initiators. 

Hantzsch [64] described isonitramines as compounds which have either the structure reported by Traube (I) or that of nitrosohydroxylamine (Ila) ... 

However, on investigating the ultra-violet absorption spectra of methylenedi-isonitramine, R. N. Jones and Thorn [67] failed to detect a band characteristic of... 

Under the influence of aqueous solutions of the water soluble salts of heavy metals the sodium salt of methylenedi-isonitramine gives precipitates of the salts of these metals. T. Urbanski, Zacharewicz and Pietrzyk [61] suggested the use of certain heavy metal salts as initiators. Particularly interesting properties were demonstrated by the thallous salt CH2(N202n)2. 

Some of the heavy metal salts of nitromethylisonitramine appear to have initiating properties, which are however considerably weakened by the presence of a nitro group. The salts of type III are therefore weaker initiators than the corresponding metal salts of methylenedi-isonitramine. 

Histrionicotoxins represent a unique structural class of alkaloids found only in dendrobatid frogs (see below). Somewhat similar hydroxy-azaspiro-undecanes, namely, sibirine, nitramine, and isonitramine, occur in certain plants of the genus Nitraria (cf. Ref. 70). 

Nitramine and isonitramine alkaloids of Nitraria spp., previously described as decahydroquinolines, are now considered to be the epimeric spiropiperidines (104 and (105) respectively (A.A. Ibragimov et al, Khim.prirod. Soedin., 1981, 623 Z. Osmanov et al, ibid, 1982, 126),... 

A recent synthesis of (+)-nitramine (275) and (-)-isonitramine (276) has been reported [611]. Resolution of an a-substituted p-ketoester with pig liver esterase was the key improvement to provide the required chiral quaternary carbon. Subsequent cyclization of the piperidine ring gave 275 and 276. In a recent synthesis of sibirine (277), a-deprotonation/alkylation of an imine gave an intermediate having the required quaternary carbon,... 

The addition of 30-40 cc. of water to the gelatinous reaction mixture causes separation of a brown, partly crystalline precipitate. To minimize decomposition, the precipitate is quickly filtered, pressed dry and taken up in ethanol. Upon the addition of a little water and gentle warming, the solution separates into a lower dark brown layer (the sodium salt of methylene di-isonitramine) and the upper pale yellow alcoholic solution of base A and the sodium salt of a-A -methyl pyrrolidylacetic acid. 

The alcoholic solution, freed from the sodium salt of methylene di-isonitramine, is made acid with hydrochloric acid and the alcohol removed under vacuum. The residue is made alkaline, and base A is recovered by digestion of the residue with ether and separation of the ethereal solution which is in turn dried over potassium hydroxide. The residual brown oil, after removal of the solvent, is a mixture of base A and the higher boiling and unchanged cuscohygrine (usually about 4.3 g. (14.3%). Base A may be recovered from this mixture (which is very sensitive to air oxidation) by repeated fractional distillation when it is found to boil at 90-98 (16 mm.) yield, 3.7-4.0 g. 

The failure of cuscohygrine to condense with benzaldehyde, ethyl oxalate and amyl nitrite is hard to accommodate on formula X. Because of the formation of two isomeric hydrazones, and on the erroneous assumptions that base A was di-(a-iV -methylpyrrolidyl)-methane and that methylene di-isonitramine came from a methyl ketone group, Hess and Fink (22) altered Liebermann s formula X so as to represent cuscohygrine as an unsymmetrical di-(JV-methylpyrrolidyl)-propan-2-one (XIII). It has since been found, however, that base A is not identical with di-(a-IV-methyI-pyrrolidyl)-methane prepared by the action of phosgene on pyrrylmagne-sium bromide followed by reduction and methylation (25). Moreover,... 

Esterification. The lipase-mediated esterification is promoted by microwave (90°, 15 min.). Four lipases immobilized in microemulsion-based gels retain their activity in catalyzing esterification. Resolution by selective acetylation of ethyl 6-hydroxy-1-cyclohexenecarboxylate gives access to a chiral intermediate for a synthesis of the spirocyclic alkaloids (+)-nitramine, (+)-isonitramine, and (-)-sibirine. 

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