Hydroxylamines with aromatic

Oximes of some carbonyl compounds can undergo further cyclization reactions (46). jS-Diketones give, for example, heterocyclic compounds. The oxime of propargylaldehyde cannot be isolated because a ring formation takes place and an oxazine is formed. The reaction of hydroxylamine with aromatic a-aminoalkyl ketones is similar to osazone formation (47). Chloral reacts with two molecules of hydroxylamine (48). Carboxylic acids or lactonic oxygen can also react with hydroxylamine (49). 

Neta.1 Ama.lga.ms. Alkali metal amalgams function in a manner similar to a mercury cathode in an electrochemical reaction (63). However, it is more difficult to control the reducing power of an amalgam. In the reduction of nitro compounds with an NH4(Hg) amalgam, a variety of products are possible. Aliphatic nitro compounds are reduced to the hydroxylamines, whereas aromatic nitro compounds can give amino, hydra2o, a2o, or a2oxy compounds. 

The first reported synthesis of hydroxyurea (24) consists of the condensation of hy-droxylamine with potassium cyanate (Scheme 7.14) [87]. Condensation of hydroxy-lamine with ethyl carbamate also gives pure hydroxyurea in good yield after recrystallization (Scheme 7.14) [88]. Nitrogen-15 labeled hydroxyurea provides a useful tool for studying the NO-producing reactions of hydroxyurea and can be prepared by the condensation of N-15 labeled hydroxylamine with either potassium cyanate or trimethylsilyl isocyanate followed by silyl group removal (Scheme 7.14) [89, 90]. Addition of hydroxylamine to alkyl or aryl isocyanates yields alkyl or aryl N-hydroxyureas (Scheme 7.14) [91, 92]. The condensation of amines with aromatic N-hydroxy carbamates also produces N-substituted N-hydroxyureas (Scheme 7.14) [93]. 

Hydroxylamines are usually more accessible than the corresponding nitroso compounds, so only few examples of this reaction have been described in the literature. Aromatic nitroso compounds have been reduced into hydroxylamines with ascorbic acid, gly-oxylic acid and by NADH. It can be safely assumed that any reagent capable of reducing nitro compounds should reduce nitroso compounds as well. 

A convenient synthetic procedure for the preparation of azo compounds, particularly unsymmetrically substituted ones, involves the reaction of aromatic nitroso compounds with aromatic amines [31a, b]. The reaction is of particular interest because the replacement of the amine by the corresponding hydroxylamine leads to the formation of the related azoxy compounds (see Chapter 15, Azoxy Compounds ). 

The oxidation of aromatic hydroxylamines with peracids in the presence of cupric ions produces nitroso compounds. In the rigorous absence of metallic ions, azoxy compounds are formed [32]. On the other hand, the air oxidation is strongly accelerated by metals, the approximate order of activity based on a kinetic study being cupric s ferric > manganous > nickel chromic > cobaltous ions. Silver and stannous ions appear to have no effect [33]. 

The reductive cleavage of hydroxylamine and its derivatives by electro-generated TP and V forming aminyl radicals and the hydroxide ions has been studied intensively. The aminyl radicals are preferably trapped with alkenes and aromatic compounds. Thus, the reaction of hydroxylamine with electro-generated Tp in the presence of maleic acid yields aspartic acid (Eqs. (66)—(69))... 

With some reducing agents, especially with aromatic nitro compounds, the reduction can be stopped at an intermediate stage, and hydroxylamines (9-49), hydrazobenzenes (9-68). 

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). 

With some reducing agents, especially with aromatic nitro compounds, the reduction can be stopped at an intermediate stage, and hydroxylamines (19-46), hydrazobenzenes, azobenzenes (19-80), and azoxybenzenes (19-79) can be obtained in this manner. However, nitroso compounds, which are often postulated as intermediates, are too reactive to be isolated, if indeed they are intermediates. Reduction by metals in mineral acids cannot be stopped, but always produces the amine. 

Nitromethane (NM) is a colorless and transparent liquid explosive with aromatic odor, a relative density of 1.1376, boiling point of 101.2 °C, freezing point of —28.55 °C, flash point of 43 °C (open cup) and refractive index of 1.3818 °. It is soluble in water, ethanol and basic solution, and its aqueous solution is acidic. Nitromethane is miscible with many organic matters to form azeotrope liquid. Itself is a good solvent and can be thickened after a small amount of nitrocellulose is added. Additionally, concentrated acid can decompose into nitromethane into ammonia, hydroxylamine and carbon oxides. 

The metabolism of nitrobenzenes to quinone-imines arises from a six-electron reduction of the nitro group to the corresponding aniline metabolite via the intermediate nitroso and hydroxylamine analogs. Aromatic ring hydroxylation by CYP ortho or para to the aniline nitrogen then generates the aminophenol derivative. The conversion of a nitrobenzene derivative to a quinone-imine is illustrated with the catechol-O-methyltransferase inhibitor tolcapone, an... 

The fact that substitution of bromine in compounds of type (127) with hydroxylamine is accompanied by Walden inversion led Noce et al. (158) to the first synthesis of optically active N-hydroxyamino acids L- and D-N-hydroxyleucine (66). The same method was later used to synthesize the aromatic D-amino acids N-hydroxytyrosine (35) and N-hydroxyphenylalanine (34) (159). Reaction of hydroxylamine with a,a -dibromopimelic acid gave l-hydroxy-2,6-piperidine dicarbox-ylic acid (134) (158). Shin (160) studied the reaction of esters (128) and (129) with hydroxylamine in the presence of triethylamine and obtained the ethyl (77) and tert miy (130) esters of N-hydroxyamino acids as oils. 

The main drawback of the previous approach is the use of TBHP or other radical initiator that is consumed or decomposed in the initiation steps of the chain mechanism. It would be even more convenient if no organic sacrificial initiator is added. In this regard, the pioneer work of Ishii et al. using aromatic A-hydroxylamines in combination with first-row transition metal ions such as Co ", Fe ", or Mn + has shown that by coordination of the A-hydroxylamine with these transition metals oxyl radicals are formed and these oxyl radicals can act as suitable radical initiators [40,41] (Scheme 2.12). Due to the stability of the molecule and the corresponding oxyl radical, A-hydroxylphthalimide (NHPI) has been one of the preferred organic initiators in combination with Co " or Fe " ions. 

Diamino-l/f-pyrunidine-2-thione was coupled with aromatic aldehydes (At = Ph, d-Cl-CeHt) to give the corresponding SchiffhasQS 20. Treatment of 20 with chloroacetic acid gave thiazolo[3,2-a]pyrimidine 21, which was condensed with j>-chlorobenzaldehyde to give compound 22. Compound 22 was condensed with hydroxylamine to give isoxazolo[4,5-J]thiazolo[2,3-a]pyrimidine 23 as shown in Scheme 9 [27]. 

Nitro- and Xitroso-derivatives and Hydroxylamines.— The reduction of /S-nitro-styrenes (106) to the nitrophenylethanes (107) and subsequent base-catalysed condensation with aromatic aldehydes Ar CHO gives rise to the substituted nitro-styrene (108), which on further reduction leads to the dibenzyl ketone (109). Nitrobenzene reacts with organo-lithium or -magnesium derivatives, as shown in Scheme 15, yielding p-alkylated products (110). ... 

Oximes, hydrazines and semicarbazones. The hydrolysis products of these compounds, t.e., aldehydes and ketones, may be sensitive to alkali (this is particularly so for aldehydes) it is best, therefore, to conduct the hydrolysis with strong mineral acid. After hydrolysis the aldehyde or ketone may be isolated by distillation with steam, extraction with ether or, if a solid, by filtration, and then identified. The acid solution may be examined for hydroxylamine or hydrazine or semicarbazide substituted hydrazines of the aromatic series are precipitated as oils or solids upon the addition of alkali. 

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. 

Two substituents on two N atoms increase the number of diaziridine structures as compared with oxaziridines, while some limitations as to the nature of substituents on N and C decrease it. Favored starting materials are formaldehyde, aliphatic aldehydes and ketones, together with ammonia and simple aliphatic amines. Aromatic amines do not react. Suitable aminating agents are chloramine, N-chloroalkylamines, hydroxylamine-O-sulfonic acid and their simple alkyl derivatives, but also oxaziridines unsubstituted at nitrogen. Combination of a carbonyl compound, an amine and an aminating agent leads to the standard procedures of diaziridine synthesis. 

Here a typical property of three-membered rings wdth two hetero atoms is shown and this property is also found in the diaziridines. Only with the oxaziranes which are substituted by aryl groups in the 3-position does the hydrolysis by acids occur according to Eq. (14) with formation of an aromatic aldehyde and alkyl hydroxylamine. 

---