Hydroxylamines, preparation

A - M e t h y 1 -. V- (4 - pen t e n v I) - and, V-methyl-A -(5-hexenyl)hydroxylamine, prepared by reduction or alkylation of nitrones, undergo spontaneous cyclization to pyrrolidine and piperidine N-oxide, respectively. The cyclization is reversible and the equilibrium is affected by the solvent and presumably by the nature and the position of substituents. The optimum solvent for the cyclization is chloroform. The stereochemical outcome, e.g., formation of 14 and 15, is consistent with a concerted mechanism. Cyclic amines can be obtained by catalytic hydrogenation, e.g., 16. 

Hydtoxy ketones, dehydration, 30 preparation, 130, 131, 164, 174 Hydroxy lactones, preparation, 334 Hydroxylamines, preparation, 633 o-Hydroxylamino cyanides, preparation, 6Q7... 

The three hydroxylamine preparation processes produce the following amount of ammonium sulfate ... 

A solution of 2-aminonicotinonitrile (0.6 g, 5 mmol) in ethanolic hydroxylamine (prepared from 2.1 g NIIjOH HC1 and an EtOH solution of NaOEt from 0.7 g of Na and 50 mL of EtOH and filtered from NaCl) was heated under reflux for 7 h. The mixture was concentrated under reduced pressure and the residue was crystallized (EtOH/hexane) to give the carboxamidoxinie yield 0.5 g (65%) mp 128-130 "C. 

Bridge amidines. 8 g. 10-cyano-10-( -dimethylaminopropyl)-10,ll-dihydro-5H-di-benzo[a,d]cyclohepten-5-one refluxed 3 hrs. with hydroxylamine (prepared from the hydrochloride with NaOH in water) in ethanol-water 6 g. bridged y -keto amidoxime dissolved in ethanol, and hydrogenated 2 hrs. at 60°/3 atm. with Raney-Ni -> bridged t/ -keto amidine (Y ca. 100%). F. e. s. G. N. Walker et al., J. Org. Chem. S6, 466 (1971). 

A soln. of hydroxylamine prepared by addition of Na-carbonate to an aq. soln. of hydroxylamine hydrochloride, 5-norbornene-endo-2,3-dicarboxylic anhydride... 

Hydroxylamine is derived from ammonia by replacing one hydrogen atom by a hydroxyl group. It is prepared by the electrolytic reduction of nitric acid, using a lead cathode ... 

Pure hydroxylamine is a crystalline solid of low melting point (306 K) but is rarely prepared because it decomposes above 288 K... 

Metallic Derivatives, (a) Cuprous Acetylide. CujCg. Prepare an ammoniacal solution of cuprous chloride by first adding dilute ammonia to 2-3 ml. of dilute copper sulphate solution until the initial precipitate just redissolves and a clear deep-blue solution is obtained now add an aqueous solution of hydroxylamine hydrochloride drop by drop with shaking until the solution becomes first green and then completely colourless, the cupric salt being thus reduced to the cuprous derivative. 

Prepare a solution of 12 5 g. of hydroxylamine hydrochloride in 20 ml. of water contained in a too ml. conical flask. Dissolve 7 g. of powdered sodium hydroxide in 20 ml. of water, cool the solution in ice-water, and then add it to that of the hydroxylamine hydrochloride. Place a thermometer in the mixed solution, and chill the flask in ice-water until the temperature of the solution is between 5 and 10 . Now add 12 ml. (9 5 gO of dry acetone (preferably from a burette to ensure... 

B) Preparation of the Cuprous Solution, Add 85 ml. of concentrated ammonia solution (d, o-o88) to a solution of 50 g. of crystalline copper sulphate in 200 ml. of water, and cool to 10 . Dissolve 14 5 g. of hydroxylamine hydrochloride (or 17-4 g. of the sulphate) in 50 ml. of water, cool to 10 , and add a solution of 9 g. of sodium hydroxide in 30 ml. of water. Without delay add this hydroxylamine solution with stirring to the copper solution, which will be immediately reduced, but will retain a blue colour. 

The special reducing agent (a solution containing cupro-ammonia ions) is first prepared. Dissolve 63 g. of crystallised copper sulphate in 250 ml. of water in a 1-Utre heaker, add 100 ml. of concentrated ammonium hydroxide solution (sp. gr. 0-88), and cool the solution to 10°. Dissolve 17 8 g. of hydroxylammonium chloride or 21 g. of hydroxylammonium sulphate in 60 ml. of water, cool to 10°, and add 42 -5 ml. of QN sodium hydroxide solution if the resulting solution of tydroxylamine is not clear, filter it at the pump. Without delay add the hydroxylamine solution, with stirring, to the ammoniacal cupric sulphate solution. Reduction occurs at once, a gas is evolved, and the solution assumes a pale blue colour. Protect the reducing agent from the air if it is not used immediately. 

The secondary allylic methylamine 324 can be prepared by the allylation of A -methylhydroxylamine (323), followed by hydrogenolysis[201], Monoallylation of hydroxylamine, which leads to primary allylamines, is achieved using the jV,0-bis-Boc-protected hydroxylatnine 326. N -... 

Hydroxylysine (328) was synthesized by chemoselective reaction of (Z)-4-acet-oxy-2-butenyl methyl carbonate (325) with two different nucleophiles first with At,(9-Boc-protected hydroxylamine (326) under neutral conditions and then with methyl (diphenylmethyleneamino)acetate (327) in the presence of BSA[202]. The primary allylic amine 331 is prepared by the highly selective monoallylation of 4,4 -dimethoxybenzhydrylamine (329). Deprotection of the allylated secondary amine 330 with 80% formic acid affords the primary ally-lamine 331. The reaction was applied to the total synthesis of gabaculine 332(203]. 

Thiazolyloxy)propanediol-1.2-acetonide (198) has been prepared from 4-Br-thiazole (197) (Scheme 101) (440). Thiazolopyridazines (199) or thiazolooxazines (200) can be obtained from the 4-alkoxyderivalives (201) by treatment with hydrazine or hydroxylamine, respectively (Scheme 102) (441). 

The purity of a synthetic preparation of methylethyl ketone (C4H8O) can be determined by reacting the ketone with hydroxylamine hydrochloride, liberating HCl (see Table 9.10). In a typical analysis, a 3.00-mL sample was diluted to 50.00 ml and treated with an excess of hydroxylamine hydrochloride. The liberated HCl was titrated with 0.9989 M NaOH, requiring 32.68 ml to reach the end point. Report the percent purity of the sample, given that the density of methylethyl ketone is 0.805 g/mL. 

Reactions with Amines and Amides. Hydroxybenzaldehydes undergo the normal reactions with aUphatic and aromatic primary amines to form imines and Schiff bases reaction with hydroxylamine gives an oxime, reaction with hydrazines gives hydrazones, and reactions with semicarbazide give semicarbazones. The reaction of 4-hydroxybenzaldehyde with hydroxylamine hydrochloride is a convenient method for the preparation of 4-cyanophenol (52,53). 

Electrolytic reductions generally caimot compete economically with chemical reductions of nitro compounds to amines, but they have been appHed in some specific reactions, such as the preparation of aminophenols (qv) from aromatic nitro compounds. For example, in the presence of sulfuric acid, cathodic reduction of aromatic nitro compounds with a free para-position leads to -aminophenol [123-30-8] hy rearrangement of the intermediate N-phenyl-hydroxylamine [100-65-2] (61). 

Other Applications. Hydroxylamine-O-sulfonic acid [2950-43-8] h.2is many applications in the area of organic synthesis. The use of this material for organic transformations has been thoroughly reviewed (125,126). The preparation of the acid involves the reaction of hydroxjlamine [5470-11-1] with oleum in the presence of ammonium sulfate [7783-20-2] (127). The acid has found appHcation in the preparation of hydra2ines from amines, aUphatic amines from activated methylene compounds, aromatic amines from activated aromatic compounds, amides from esters, and oximes. It is also an important reagent in reductive deamination and specialty nitrile production. 

Cyanopyridazines add ammonia, primary and secondary amines and hydroxylamine to give amidines or amidoximes. Substituted amides, thioamides and carboximidates can be also prepared. With hydrazine, 3-pyridazinylcarbohydrazide imide is formed and addition of methylmagnesium iodide with subsequent hydrolysis of the imine affords the corresponding pyridazinyl methyl ketone. 

Af-Oxides, e.g. (125), were similarly prepared using hydroxylamine to give intermediates such as (124) (79JOC1695, 78H(9)1327), and an alternative synthesis of Af-oxides involves cyclization of 3-acylamino-2-aroylpyridine oximes (126) —> (127) (69MIP21500). 

The powerful aminating agents hydroxylamine O-sulfonic acid and O-mesitylenesulfonyl-hydroxylamine have been used to prepare compounds (270)-(274) (80JCR(M)0514,76CPB2267). 

In theory, three isoxazolines are capable of existence 2-isoxazoline (2), 3-isoxazoline and 4-isoxazoline. The position of the double bond may also be designated by the use of the prefix A with an appropriate numerical superscript. Of these only the 2-isoxazolines have been investigated in any detail. The preparation of the first isoxazoline, 3,5-diphenyl-2-isoxazoline, from the reaction of )3-chloro-)3-phenylpropiophenone with hydroxylamine was reported in 1895 (1895CB957). Two major syntheses of 2-isoxazolines are the cycloaddition of nitrile A-oxides to alkenes and the reaction of a,/3-unsaturated ketones with hydroxylamine. Since 2-isoxazolines are readily oxidized to isoxazoles and possess some of the unique properties of isoxazoles, they also serve as key intermediates for the synthesis of other heterocycles and natural products. 

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