Nitrosobenzene, reactions

In direct nitroso aldol reactions of a-branched aldehydes, an L-prolinamide (50) catalyses to give a-hydroxyamino carbonyl compounds which are otherwise dis- favoured ees up to 64% were found.149 Another prolinamide derivative gives similar results in a nitrosobenzene reaction.150 For proline-catalysed cases involving highly substituted cyclohexanones, DFT calculations have highlighted the roles of electro- static and dipole-dipole interactions in the level of de achieved.151 (g)... 

Formation of nitrosobenzene may be explained by disproportionation of the radical anion of nitrobenzene to nitrobenzene and nitrosobenzene, reaction (R13). 

The initial product, nitrosobenzene, is so easily reduced to p-phenylhydroxyl-amine that it has never been isolated in the free state, but its presence has been established by reaction in solution with hydroxylamine to 3deld a phenyldi-azonium salt, which couples readily with a a-naphthylamine to form the dyestuff phenyl-azo-a-naphthylamine (compare Section IV,77) ... 

Add 4 4 g. of recrystaUised -phenylhydroxylamine to a mixture of 20 ml. of concentrated sulphuric acid and 60 g. of ice contained in a 1 litre beaker cooled in a freezing mixture. Dilute the solution with 400 ml. of water, and boil until a sample, tested with dichromate solution, gives the smell of quinone and not of nitrosobenzene or nitrobenzene (ca. 10-15 minutes). Neutralise the cold reaction mixture with sodium bicarbonate, saturate with salt, extract twice with ether, and dry the ethereal extract with anhydrous magnesium or sodium sulphate. Distil off the ether p-aminophenol, m.p. 186°, remains. The yield is 4-3 g. 

The reduction of the nitro group to yield aniline is the most commercially important reaction of nitrobenzene. Usually the reaction is carried out by the catalytic hydrogenation of nitrobenzene, either in the gas phase or in solution, or by using iron borings and dilute hydrochloric acid (the Bechamp process). Depending on the conditions, the reduction of nitrobenzene can lead to a variety of products. The series of reduction products is shown in Figure 1 (see Amines byreduction). Nitrosobenzene, /V-pbenylbydroxylamine, and aniline are primary reduction products. Azoxybenzene is formed by the condensation of nitrosobenzene and /V-pbenylbydroxylamine in alkaline solutions, and azoxybenzene can be reduced to form azobenzene and hydrazobenzene. The reduction products of nitrobenzene under various conditions ate given in Table 2. 

Oxidation. Aromatic amines can undergo a variety of oxidation reactions, depending on the oxidizing agent and the reaction conditions. For example, oxidation of aniline can lead to formation of phenyUiydroxylamine, nitrosobenzene, nitrobenzene, azobenzene, azoxybenzene or -benzoquinone. Oxidation was of great importance in the early stages of the development of aniline and the manufacture of synthetic dyes, such as aniline black and Perkin s mauve. 

Primary synthesis of arylazopyrimidines is used (52JCS3448). It is exemplified in the condensation of phenylazomalondiamidine with diethyl oxalate to give the azopyrimidine (833) (66JCS(C)226). Finally, 5-phenylazopyrimidine may be made by the condensation of pyrimidin-5-amine with nitrosobenzene (5UCS1565) but the reaction seems to have been overlooked for many years. 

Phenazine mono-N-oxides have also been prepared from nitrobenzene derivatives. Condensation of nitrobenzene with aniline using dry NaOH at 120-130 °C results in modest yields of phenazine 5-oxide, although the precise mechanism of this reaction is not well understood (57HC(ll)l) with unsymmetrical substrates it is not possible to predict which of the isomeric fV-oxides will be produced. Nitrosobenzene derivatives also function as a source of phenazine mono-fV-oxides thus, if 4-chloronitrosobenzene is treated with sulfuric acid in acetic acid at 20 °C the fV-oxide is formed (Scheme 21). 

Isoxazolin-5-imines were produced by nitrile oxide addition to cyanoacetates (62HC(17)l,p.7), by the reaction of nitrones with phenylacetonitrile (74CB13), and by base addition of nitrosobenzene to nitriles (Scheme 148) (72LA(762)154). 

IH-Azepine, 1-methoxy carbonyl-cycloaddition reactions, 7, 522 with nitrosobenzene, 7, 520 tricarbonyliron complex acylation, 7, 512-513 conformation, 7, 494 tricarbonylruthenium complex cycloaddition reactions, 7, 520 1 H-Azepine, l-methoxycarbonyl-6,7-dihydro-synthesis, 7, 507... 

The nitroso group, — N = Op is one of the few nonhalogens that is an ortho- and para-directing deactivator. Explain by drawing resonance structures of the carbocation intermediates in ortho, mela, and para electrophilic reaction on nitrosobenzene, C<3Hs N = 0. 

Whereas the production of arylnitrenes by the deoxygenation of nitrosobenzenes or nitro-benzenes by trivalent phosphorus reagents and their subsequent intramolecular ring expansion to 3//-azepines are well-known processes, the corresponding intermolecular reactions to form 1//-azepines have been exploited only on rare occasions and appear to be of little preparative value. For example, the highly electrophilic pentafluorophenylnitrene, obtained by deoxygenation of pentafluoronitrosobenzene with triethyl phosphite in benzene solution, produced a low yield (2-10%) of l-(pentafluorophenyl)-l//-azepine, which was isolated as its [4 + 2] cycloadduct with ethenetetracarbonitrile.169 With anisole as the substrate l-(pentafluorophenyl)-l//-azepin-2(3//)-one (16% bp 128 —130 C/0.4 Torr) was obtained. 

An X-ray structural analysis has confirmed that ethyl 1//-azepine-1-carboxylate (1) and nitrosobenzene yield the [6 + 2] adduct 1 1 183-254 255 Subsequently, however, a careful analysis of the reaction mixture by HNMR spectroscopy indicated that a [4 1 2] adduct is also formed, albeit in low yield, to which structure 12 was assigned.256... 

A similar nitrene intermediate can also be postulated in the mechanism of nitrosobenzene hydrogenation. Indeed a standard way of producing Ph-N is from the reaction of Ph-NO with PPhs (17). In the hydrogenation of nitrosobenzene the principal product in the early stages is azoxybenzene [7, 18]. It was suggested that azoxybenzene was formed by the following sequence ... 

Note that the nitrene now allows a common intermediate that can be hydrogenated to anihne from both nitrobenzene and nitrosobenzene. It is also interesting to speculate on another route to form a nitrene on the surface. Phenyl hydroxylamine is a known intermediate whose concentration in solution is highly dependent upon reaction condihons. On adsorption of phenyl hydroxylamine one can write the following ... 

Pyridotriazinone 70 was obtained by the reaction of iV-(2-pyridyl)benzoylacetamide 119 with nitrosobenzene in methanol. The reaction probably involves the attack of two molecules of nitrosobenzene at C-2 of 119 with cleavage of C(l)-C(2) and C(2)-C(3) bonds affording diphenylcarbodiimide and 2-pyridylisocyanate, which undergo a [4+2] heterocycloaddition. Interestingly, the reaction of acetyl analog of 119 did not afford the corresponding bicyclic product, instead, 2-methoxy-2-phenylamino-iV-(2-pyridyl)acetoacetamide was obtained (Equation 14) <2004S2975>. 

A direct synthesis of the thiophene nucleus has been achieved by allowing air-stable cobaltacyclopentadiene complexes (66) to react with sulfur the organometallic complexes are prepared in variable yields in a stepwise fashion from f75-cyclopentadienyIbis(triphenylphosphine)cobalt (65) (Scheme 82) 147,148 Reactions of the complexes 66 with selenium and nitrosobenzene give rise to selenophenes and pyrroles, respectively. 

The way in which aromatic amino compounds lead to the formation of MHb is of some interest in regard to the role played by the first reaction of the pentose phosphate cycle in this reaction system. It has been stated (L5) that nitrosobenzene effects within one hour the conversion of Hb to MHb to the extent of 80% of total pigment according to the following reactions ... 

The reaction in Eq. (15) is under the control of C-6-PDH, that in Eq. (16) is catalyzed by MHbR, while that in reaction (17) is non-enzymatic. It is remarkable that nitrosobenzene is reduced enzymatically to phenylhydroxylamine which oxidizes Hb to MHb and is, by this, reoxidized to nitrosobenzene (L5) the latter substance acts catalyti-cally and not stoichiometrically when forming MHb from Hb by the fact of its regeneration during reaction (17). 

If this concept is right, a decreased MHb formation by nitrosobenzene must be postulated in subjects with lack of G-6-PDH activity. In fact, a deficient MHb formation has been demonstrated in such a case (L5, W3). Thus, reaction (15) has been proved to be rate limiting for reactions (16) and (17). 

The solution is diluted with 200 c.c. of water and boiled until a sample, when mixed with dichromate solution, no longer smells of nitrosobenzene but of quinone (ten to fifteen minutes). To the cooled solution 2 g. of dichromate dissolved in water are added, a downward condenser is attached to the flask containing the mixture, and steam is passed through. The quinone is carried over with the steam. On the mechanism of its formation in this reaction compare p. 310. Test the residue in the flask for ammonia. 

The condensation of nitrosobenzene with phenylhydroxylamine which is described below is an example of this similarity. Hydroxyl-amine and phenylhydrazine also react with nitrosobenzene, but the details of these reactions cannot be given here. 

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