N-Methylhydroxylamine

N-Methylhydroxylamine.—An aqueous solution of nitromethane is mixed with about its own weight of ammonium chloride, the mixture is then cooled (temperature about 10°) and three parts of zinc dust are added in small portions with constant shaking. Zinc dust is now removed by filtration, and it is found that the filtrate reduces ammoniacal silver and Fehling s solutions. The preparation of this easily accessible alkylhydroxylamine as hydrochloride is described by Beckmann, Annalen, 1909, 365, 204. 

Almost without exception the numerous transformations which primary and secondary nitroparaffins undergo involve the aci-iorm, i.e. they take place under conditions in which the salt of the oci-form is produced. Qualitatively the nitroparaffins greatly resemble ketones in their mode of action, although the much greater reaction velocity of the nitro-compounds brings about a quantitative difference. 

Nitrous acid converts -primary nitroparaffins into nitrolic acids and the secondary ones into so-called pseudonitroles, which latter, being nitroso-compounds, are coloured green or blue  

Experiment.—Methylnitrolic acid.1—Nitromethane (3-2 g.) is dissolved in 30 c.c. of ice-cold 2 N-sodium hydroxide solution and a 

---

Thus the structure of the oxazirane must formally involve elimination of water from one molecule each of the carbonyl compound and of an alkyl hydroxylamine. (In the synthesis of oxazirane from N-methylhydroxylamine-O-sulfonic acid and benzaldehyde, this method... 

Formylation of the V-allyl indole derivatives 311 (obtained by allylation of the indole 310) afforded l-allyl-7-formyl-indole 312. Subsequent condensation of 7-formyl indole derivatives 312 with ethyl acetate in presence of sodium ethoxide gave 313 (89S322). Reaction of 312 with N-methylhydroxylamine hydrochloride afforded the cycloadduct, tetracyclic... 

Chiacchio and co-workers <97T13855> reported a stereoselective synthesis of 133 via an intramolecular 1,3-dipolar cycloaddition. Intermediate 132 was generated in situ by the reaction of tra .v-/V-(2-formylphenyl)-i -methyl-2-phcnylcthenc- l -sulfonamide 131 with N-methylhydroxylamine and afforded a tricyclic benzothiazine 133 in 51% yield (Scheme 36). 

When the aldehyde 137 and N-methylhydroxylamine (166) were mixed with silica gel and irradiated with microwaves for 15 min the adduct obtained was 168 (82% yield). A mixture of 137 and N-methylhydroxylamine (166) in alcohol, heated at 120°C in a sealed tube, afforded the products 168 and 169 in an 8 1 ratio (Scheme 9.51) [93], The authors proposed that the selectivity observed in the microwave-induced reaction results from a faster transformation leading to the kinetically controlled product. 

What about the isomers of the hydroxamic acids, the 0-acyl derivatives of hydroxy-lamine Having mentioned early in this study that N-methylhydroxylamine is more stable than its O-isomer, we are thus intrigued by the finding that iV-benzoylhydroxylamine (benzohydroxamic acid), or at least its A -f-butyl derivative, is less stable than its corresponding O-benzoyl isomer as shown by the thermal isomerization of the former to the latter, equation 55. 

Tetramethyl-l,2-oxazepin-5-one and its N- methyl analogue have been prepared by the addition of hydroxylamine and N-methylhydroxylamine to phorone (73TL1615). 

To a cooled and magnetically stirred solution of 23.4 g. (0.28 mole) of N-methylhydroxylamine hydrochloride (Notes 2 and 3) in 40 ml. of methanol is added 15.3 g. (0.282 mole) of sodium methoxide. The cooling bath is removed, and the mixture is stirred at room temperature for 15 minutes. The mixture is filtered rapidly through a 35-mm., coarse, sintered-glass funnel, and the filter cake is washed with 10 ml. of methanol. The filtrates are combined, refiltered, and mixed with 150 ml. of toluene. 

The two-phase mixture containing N-methylhydroxylamine is added dropwise to the refluxing toluene solution of the aldehyde over 3 hours. During this time the distillate is collected and discarded in 2 5-ml. portions until the last such portion collected and discarded is clear (Note 4). Reflux and stirring are continued for an additional 3 hours, and then the clear reaction mixture is allowed to cool. The product is extracted with three 80-ml. portions of 10% aqueous hydrochloric acid. The extracts are combined, and the pH of the solution is adjusted to >12 by the slow addition of 30% aqueous potassium hydroxide. The basic mixture is extracted with two 120-ml. portions of pentane (Note 5), and the combined extracts are washed once with 100 ml. of water and dried over anhydrous potassium carbonate. The pentane is removed on a rotary evaporator and the residue is distilled through a short Vigreux column under reduced pressure to give 19.1-19.6 g. (64-67%) (Note 6) of hexahydro-1,3,3,6-tetramethyl-2,l-benz-isoxazoline, b.p. 90-92° (9 mm.) (Note 7). 

N-Methylhydroxylamine hydrochloride, m.p. 83-84°, purchased from Aldrich Chemical Company, Inc., was used directly. Alternatively, the hydrochloride can be prepared by the reduction of nitromethane with zinc dust and ammonium chloride.2... 

Methyl-k-hydroxyani 1 ine, AK9 N-Methylhydroxylamine, AA32 Methyl 3 hydroxy-L--ni trophenyl ether, AK37... 

Treatment of the ( -lactam 1 with N -methylhydroxylamine gave the expected condensation product, pyrolysis of which in toluene at 110°C led to formation of the isomers 2 in 72% yield. 

The intramolecular nitrone cycloaddition (INC) has been used particularly for the synthesis of amino carbasugars [60, 61]. The following scheme illustrates this strategy (Scheme 16) [60], The cycloaddition of nitrone derived from lactol 49 and an excess of N-methylhydroxylamine occurs from the least hindered face affording the isoxazolidine 51 (85% yield). The amino carbasugar 52 was obtained after the cleavage of the N-0 bond. 

Reaction of MnCl2 with N-methylhydroxylamine in hot alcoholic solution gives MnCl2(MeHNOH)2, for which it is suggested that the ligand co-ordinates with the... 

CYCLOADDITION N-Alkylhydroxy-lamines. f-Butyldimethylsilyl ethylnitron-ate. Cyclopropenone 1,3-propanediyl ke-tal. Hydrogen peroxide-Sodium tungstate. N-Methylhydroxylamine. Phenyl isocyanate. Trimethylamine N-oxide. Trimethylsi-lylmethyl azide. 

NITRONES Hydrogen peroxide-Sodium tungstate. N-Methylhydroxylamine. 

Semicarbazides react in a similar manner. The reaction of carbodiimides with N-methylhydroxylamine affords the expected guanidine derivative resulting from the reaction of the - NH group.555... 

D-Glucose ([52], Fig. 9) has served as an intriguing educt for preparation (31) of the Corey lactone equivalent [59] (32). The iodo compound [53] was readily available from glucose in four steps. Reductive fragmentation, induced by zinc in ethanol, gave the unsaturated aldehyde [54]. Reaction with N-methylhydroxylamine was followed by a spontaneous nitrone cycloaddition to provide the oxazolidine [55]. Catalytic reduction of the N-O bond was accompanied by the unexpected loss of tosylate and aziridine formation. Olefin formation from [56] via the N-oxide and chain extension gave acid [57]. lodolactonization and tri-n-butyltin hydride reduction in the standard fashion led to lactone [58]. After saponification of the benzoates, stereoselective epoxide formation gave epoxy lactone [59]. 

A 1-L, three-necked, round-bottomed flask is fitted with a mechanical stirrer, a reflux condenser attached to a Dean-Stark water separator, and a 250-ml. dropping funnel. The flask is charged with 25.0 g. (0.16 mole) of 3,7-dimethyl-6-octenal (Note 1) and 500 ml. of toluene. The solution is heated to reflux with stirring, and a solution of N-methylhydroxylamine, methanol, and toluene is added (see below). 

---