Hydroxylamines Phenylhydroxylamines

The reaction of a dibromochalcone with hydroxylamine hydrochloride in pyridine gave three products with the expected 2-isoxazoline product as the predominate compound. A ring bromination product and an isoxazole were also isolated (70UC796). The reaction of hydroxylamine with /S-thiosulfates of propiophenone at reflux produced 3-phenyl-2-isoxazo-line (455). At room temperature a bis-Michael product (456) was produced. The reaction with N -phenylhydroxylamine yielded a mono-Michael type product (457) (74CPB1990). 

Phenylhydroxylamine rearranges in sulfuric acid to give mainly p-aminophenol. Industrial routes to this compound have been developed in which phenylhydroxylamine, formed by hydrogenation of nitrobenzene in sulfuric acid over platinum-on-carbon, is rearranged as it is formed. Conditions are adjusted so that the rate of rearran ment is high relative to the rate of hydrogenation of hydroxylamine to aniline (15,17,86). An easy way to obtain a favorable rate ratio is to carry out the reduction with about 1% DMSO present in the sulfuric acid (79,81). 

I. Condensation of N-Monosubstituted Hydroxylamines with Carbonyl Compounds Condensation of N -monosubstituted hydroxylamines with carbonyl compounds is used as a direct synthesis of many acyclic nitrones. The synthesis of hydroxylamines is being carried out in situ via reduction of nitro compounds with zinc powder in the presence of weak acids (NH4CI or AcOH) (14, 18, 132). The reaction kinetics of benzaldehyde with phenylhydroxylamine and the subsequent reaction sequence are shown in Scheme 2.21 (133). 

We now turn to the two aryl hydroxylamines, Af-phenylhydroxylamine and its o-nitro derivative. As liquids, the former compound has an enthalpy of formation that is ca 20 kJmoH more positive than that of the latter. For comparison, we find the enthalpies of the corresponding hquid species without the NHOH group, Le. benzene and nitrobenzene, differ by 36.5 kJmol . Alternatively said, equation 4 is endothermic by 16.1 kJmol . 

The intermediate generated in pyrolysis of IV-acylacetyl-iV-phenylhydroxylamines 48 can form a 3-aza-4-oxa-l,5-diene system (50) (equation 16). A homolytic cleavage of the O—H bond with subsequent rearrangement to the aniline radical, followed by recombination with the hydrogen radical to give the corresponding 0-acyl hydroxylamine 49,... 

Although electrochemical oxidation of Al-cyclohexyl-Al-hydroxylamine in the presence of pyridine afforded the corresponding dimeric nitroso compound with a low yield, A-hydroxy t-alkylamines were transformed into the corresponding nitroso compounds (equation 8) . Similarly, A-phenylhydroxylamine was transformed into nitrosobenzene under similar reaction conditions. ... 

Okamoto and co-workers noted that N-phenylhydroxylamine gave predominately diphenylamine on treatment with benzene in TFA but mostly 4-aminobiphenyl and 2-aminobiphenyl in the stronger acid trifluoromethane-sulfonic acid (TFSA). Similar results were obtained if benzene was replaced by toluene or anisole. The authors suggested that the reaction in TFA proceeded through O-protonated hydroxylamine either via a direct Sn2 displacement on N by the aromatic nucleophile or via attack of the aromatic compound on the N of a nitrenium ion. In TFSA they favored a mechanism in which the diprotonated hydroxylamine lost water to generate an iminium-benzenium dication (11, Scheme 5), a protonated nitrenium ion. " This... 

The similarity of the results obtained with phenyl azide and N-phenyl-hydroxylamine in benzene/TFA indicates that both reactions proceed by similar mechanisms, but N-phenylhydroxylamine in benzene/TFSA produces a higher yield of the C-substitution products 27 and 28 As previously suggested (Scheme 5), N-phenylhydroxylamine can be doubly protonated to yield the dication 11 in strong acids, but the more weakly basic phenyl azide is less likely to be doubly protonated. The differences observed between the behavior of N-phenylhydroxylamine and phenyl azide in TFSA may be due to the inability of phenyl azide to directly generate 11. 

It may be mentioned that an alternative name for hydroxamic acids, treating them as derivatives of hydroxylamine, continues to be used. For example A-phenylbenzohydroxamic acid [PhCON(Ph)OH] has also been named alternatively as A-benzoyl-A-phenylhydroxylamine even in recent literature. 

Nitroso-/ -phenylhydroxylamine, of which cupferron is the ammonium salt, has been made by the action of sodium nitrite and hydrochloric acid on /3-phenylhydroxylamine,1 of hydrogen peroxide on normal phenyldiazotates,2 of sodium alcoholate and hydroxylamine on nitrobenzene,3 of nitric oxide on phenyl magnesium bromide,4 and by the action of permonosulfuric acid on aniline in the presence of amyl nitrite.5... 

Hydroxylamines and Oximes. For RNH—OH compounds, prefix the name of the radical R to hydroxylamine. If another substituent has priority as principal group, attach the prefix hydroxyamino- to the parent name. For example, C6II5NIIOII would be named A-phenylhydroxylamine, but HOC6H4NHOH would be (hydroxyamino)phenol, with the point of attachment indicated by a locant preceding the parentheses. 

The catalytic effect of copper is shown in the reduction of nitrobenzene, which at a copper cathode is reduced to aniline, but while copper sponge under ordinary chemical conditions will reduce phenyl-hydroxylamine to aniline it has no effect upon nitrobenzene, and the inference is that in electrolytic reduction phenylhydroxylamine may be first formed by electrolysis, and this substance is then converted to aniline largely by the catalytic effect of the copper cathode. 

The reaction of picryl chloride with hydroxylamine hydrochloride is worth mentioning. As Borsche [24] observed, instead of the expected phenylhydroxylamine derivative, picramide was formed ... 

Nitrosobenzene is readily synthesized by the chromic acid oxidation of /3-phenylhydroxylamine, which in turn is prepared by the reduction of nitrobenzene by the action of zinc dust and ammonium chloride (53%) The hydroxylamines need not be isolated. In other preparations, ferric chloride is employed as oxidant. ... 

Blechert has developed an interesting synthesis of 2-substituted indoles which involves the conjugate addition of V-phenylhydroxylamine salts (or V-phenylnitrones) to electron-deficient allenes, followed by carbanion-accelerated hetero-Cc rearrangement of the Michael adduct. For exanple, addition of the hydroxylamine salt (46) to the allenyl sulfone (47) produces the anion (48), which undergoes rapid 3.3-sigmatropic rearrangement to afford the -keto sulfone (49). Cyclization to the indole proceeds smoothly upon exposure to formic acid (Scheme 3). 

The preparation of N-phenylhydroxylamine in high yields from nitrobenzene under catalytic transfer hydrogenation conditions is also possible utilizing wet 5% rhodium on carbon and hydrazine hydrate. Unfortunately, the transition metal catalysts tend to be expensive and the high temperatures required can be detrimental, particularly when the resulting hydroxylamines are explosive in nature. ... 

The reduction of nitrobenzene can give, in suitable conditions, phenyl-hydroxylamine and azoxybenzene. Since nitrobenzene gives its radical-anion readily (see e.g., Kolker and Waters, 1964) and nitrosobenzene forms its radical-anion when reduced in basic solution and forms the corresponding neutral radical, PKNHO, when reduced in acidic solution (Gutch and Waters, 1964), a likely reaction path to phenylhydroxylamine is the following ... 

N-2-Thenoyl-N-p-tolylhydroxylamin(I) und N-2-Thenoyl-N-phenyl-hydroxylamin(ll) (347) sowie N-Cinnamoyl-N-phenylhydroxylamin(III) (277) sind rccht selektive Rcagcntien fur die Bestimmung von Vanadium. Aus 3 bis 5 n salzsaurer Losung laBt sich das violette Vanadium-... 

The enthalpies of formation of /V-hydroxyaniline (A-phenylhydroxylamine) and its o-nitro derivative, as liquids, 7 and —13 kJmol-1, are from Reference 5. That these are almost the only hydroxylamines for which there are reported enthalpy of formation values80 makes them hard to compare. Nonetheless, we find these data suspect. The o-nitro group in phenylhydroxylamine decreases the enthalpy of formation by ca 20 kJ mol-1 while it decreases the enthalpy of formation of aniline by 45 kJmol-1. 

A wide variety of hydroxylamines, e.g. 7V-phenylhydroxylamine, 0-benzoyl-A-ter/-butylhy-droxylamine, and A-(a-cyanoalkyl)hydroxylamines, added smoothly to cyclopropanone or 1-acetoxycyclopropanol to form the adducts 13, 15 and 17, which were conveniently converted into -lactams 14, 16 and 19 a procedure which resembles the cyclopropylcarbinyl cyclobutyl rearrangement. The former two reagents gave hydroxyamine-type adducts 13 and 15, which rearranged spontaneously into )5-lactams, while with the latter reagent subsequent reaction of the adduct 17 with p-toluenesulfonyl chloride was required to form a species 18 which easily underwent ring enlargement. ... 

Hydroxylamine derivatives are used in determination of certain metals [112,113]. For example, the substitution of a benzoyl group (CeHsCO) for one of hydrogen atoms in hydroxylamine gives benzohydroxamic acid. Other important reagents in this group are N-benzoyl-N-phenylhydroxylamine (BPHA), also called N-phenylbenzohydroxamic acid [114,115] and N-furoylphenylhydroxylamine. All these reagents form extractable chelates and are used for determination of metals, e.g., V(V), Mn, Ti, Fe(III), and Nb. 

Besides BPHA, many other hydroxylamine derivatives have been proposed for determining vanadium, including A-cinnamoyl-A-phenylhydroxylamine (CHCI3, e = 6.3-10 ) [34], A-benzoyl-A-(o-tolyl)hydroxylamine [35], and A-(/n-tolyl)-A-phenylhydroxylamine [36]. 

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