Nitroso amines phenols

The Reaction has the following limitations (i) a compound that can liberate nitrous acid in acid solution is required (e.g., a metallic nitrite or a nitroso-amine, p. 204). (2) Nitrophenols and />-substituted phenols do not give the test. (3) Among the dihydroxyphenols. only resorcinol gives a satisfactory positive test. 

Reductive alkylations have been carried out successfully with compounds that are not carbonyls or amines, but which are transformed during the hydrogenation to suitable functions. Azides, azo, hydrazo, nitro and nitroso compounds, oximes, pyridines, and hydroxylamines serve as amines phenols, acetals, ketals, or hydrazones serve as carbonyls 6,7,8,9,12,17,24,41,42,58). Alkylations using masked functions have been successful at times when use of unmasked functions have failed (2). In a synthesis leading to methoxatin, a key... 

Liebermann s Nitroso Reaction.—When phenol in sulphuric acid, phenyl sulphuric acid, is treated with a nitrite or with nitroso amine a daj k green, red or brown color is obtained which changes to blue or green on addition of an alkali. The test is known as Liebermann s nitroso reaction, and may be used in testing for a phenoly a nitrite or a nitroso amine. 

A large number of other substances are also active inhibitors. These include oxygen, NO (one of the most effective inhibitors, so much so that some highly reactive monomers can be distilled only under an atmosphere of NO), aromatic nitro compounds, numerous nitroso compounds, sulfur compounds, amines, phenols, aldehydes, and carbamates. An interesting inhibitor is molecular oxygen. Being a diradical, oxygen reacts with chain radicals to form the relatively unreac-tive peroxy radical ... 

Dissolve 1 g. of the secondary amine in 3-5 ml. of dilute hydrochloric acid or of alcohol (in the latter case, add 1 ml. of concentrated hydrochloric acid). Cool to about 5° and add 4-5 ml. of 10 per cent, sodium nitrite solution, and allow to stand for 5 minutes. Add 10 ml. of water, transfer to a small separatory funnel and extract the oil with about 20 ml. of ether. Wash the ethereal extract successively with water, dilute sodium hydroxide solution and water. Remove the ether on a previously warmed water bath no flames should be present in the vicinity. Apply Liebermann s nitroso reaction to the residual oil or solid thus. Place 1 drop or 0 01-0 02 g. of the nitroso compovmd in a dry test-tube, add 0 05 g. of phenol and warm together for 20 seconds cool, and add 1 ml. of concentrated sulphuric acid. An intense green (or greenish-blue) colouration will be developed, which changes to pale red upon pouring into 30-50 ml. of cold water the colour becomes deep blue or green upon adding excess of sodium hydroxide solution. 

Some reference to the use of nitrous acid merits mention here. Primary aromatic amines yield diazonium compounds, which may be coupled with phenols to yield highly-coloured azo dyes (see Section IV,100,(iii)). Secondary aromatic amines afford nitroso compounds, which give Liebermann a nitroso reaction Section IV,100,(v). Tertiary aromatic amines, of the type of dimethylaniline, yield p-nitroso derivatives see Section IV,100,(vii). ... 

Ring nitrosation with nitrous acid is normally carried out only with active substrates such as amines and phenols. However, primary aromatic amines give diazonium ions (12-47) when treated with nitrous acid, " and secondary amines tend to give N-nitroso rather than C-nitroso compounds (12-49) hence this reaction is normally limited to phenols and tertiary aromatic amines. Nevertheless secondary aromatic amines can be C-nitrosated in two ways. The N-nitroso compound first obtained can be isomerized to a C-nitroso compound (11-32), or it can be treated with another mole of nitrous acid to give an N,C-dinitroso compound. Also, a successful nitrosation of anisole has been reported, where the solvent was CF3COOH—CH2CI2. " ... 

Recently nitrosamines have attracted attention because of their marked carcinogenic activity in a wide variety of animal species Q, ). Nitrosamines are likely to be carcinogens in man as well human exposure to these compounds is by ingestion, inhalation, dermal contact and vivo formation from nitrite and amines Nitrite and amines react most rapidly at an acidic pH A variety of factors, however, make nitrosation a potentially important reaction above pH 7 these include the presence of microorganisms, and the possibilities of catalysis by thiocyanate, metals and phenols, and of transnitrosation by other nitroso compounds. 

X. ., -(4-nitroso-phenyl)-amin % Umwandlung, bez. auf 4-Nitroso-phenol... 

The nitrosation of phenols proceeds in a manner similar to that of tertiary amines. For example, l-nitroso-2-naphthol has been prepared from the sodium salt of /9-naphthol by treatment with sodium nitrite and sulfuric acid near 0°C [29], This general procedure, suitably modified, has been used to prepare other nitrosophenols such as p-nitrosophenol (m.p. 135°-136°C) [30]. 

Diazonium salts can be prepared directly by replacement of an aromatic hydrogen without the necessity of going through the amino group.136 The reaction is essentially limited to active substrates (amines and phenols), since otherwise poor yields are obtained. Since the reagents and the substrate are the same as in reaction 1-3, the first species formed is the nitroso compound. In the presence of excess nitrous acid, this is converted to the diazonium... 

The lower members of the homologous series of 1. Alcohols 2. Aldehydes 3. Ketones 4. Acids 5. Esters 6. Phenols 7. Anhydrides 8. Amines 9. Nitriles 10. Polyhydroxy phenols 1. Polybasic acids and hydro-oxy acids. 2. Glycols, poly-hydric alcohols, polyhydroxy aldehydes and ketones (sugars) 3. Some amides, ammo acids, di-and polyamino compounds, amino alcohols 4. Sulphonic acids 5. Sulphinic acids 6. Salts 1. Acids 2. Phenols 3. Imides 4. Some primary and secondary nitro compounds oximes 5. Mercaptans and thiophenols 6. Sulphonic acids, sulphinic acids, sulphuric acids, and sul-phonamides 7. Some diketones and (3-keto esters 1. Primary amines 2. Secondary aliphatic and aryl-alkyl amines 3. Aliphatic and some aryl-alkyl tertiary amines 4. Hydrazines 1. Unsaturated hydrocarbons 2. Some poly-alkylated aromatic hydrocarbons 3. Alcohols 4. Aldehydes 5. Ketones 6. Esters 7. Anhydrides 8. Ethers and acetals 9. Lactones 10. Acyl halides 1. Saturated aliphatic hydrocarbons Cyclic paraffin hydrocarbons 3. Aromatic hydrocarbons 4. Halogen derivatives of 1, 2 and 3 5. Diaryl ethers 1. Nitro compounds (tertiary) 2. Amides and derivatives of aldehydes and ketones 3. Nitriles 4. Negatively substituted amines 5. Nitroso, azo, hy-drazo, and other intermediate reduction products of nitro com-pounds 6. Sulphones, sul-phonamides of secondary amines, sulphides, sulphates and other Sulphur compounds... 

In support of this view the p-amino-phenols themselves readily yield quinones. Also most p-substituted primary amines, e.g., p-diamines, p-alkylamines, such as p-toluidine, sulphanilic acid and its derivatives, behave similarly. In fact, the reaction can be used as a test for p-substi-tuted primary amines. p-Benzoquinone is usually made from aniline for the other p-quinones the p-amino-phenols, which are easily obtained by reduction of the p-nitroso-phenols and of azo-phenols, are employed. These reactions also apply, but not so widely, in the naphthalene series. 

The formation of Af-nitrosamines which usually separate as orange-yellow oils or low melting solids indicates the presence of a secondary amine. Confirm the formation of the nitrosamine by the Liebermann nitroso reaction. This consists in warming the nitrosamine with phenol and concentrated sulphuric acid. The sulphuric acid liberates nitrous acid from the nitrosamine, and the nitrous acid reacts with the phenol to form p-nitrosophenol, which then combines with another molecule of phenol to give red indophenol. In alkaline solution the red indophenol yields a blue indophenol anion. 

Reduction of aromatic nitro groups occurs in three steps, via nitroso and hydroxylamine intermediates, to the amine. The amine can go on to form polymeric residues by a mechanism analogous to that for oxidative coupling of phenols, as in Equation 2. Abiotic nitro reduction is well documented for pesticides that contain aromatic nitro groups, such as the phosphorothioate esters methyl and ethyl parathion (22, 30-33). 

In addition to the need to monitor known problematic compounds, newer compounds are being identified as potential threats to humans and as such need to be monitored in the atmosphere. For example, researchers reported (10) that several chemical and instrumental analyses of HPLC fractions provided evidence for the presence of /V-nitroso compounds in extracts of airborne particles in New York City. The levels of these compounds were found to be approximately equivalent to the total concentrations of polycyclic aromatic hydrocarbons in the air. Since 90% of the N-nitroso compounds that have been tested are carcinogens (10), the newly discovered but untested materials may represent a significant environmental hazard. The procedure involved collecting samples of breathable, particulate matter from the air in New York City. -These samples were extracted with dichloro-methane. Potential interferences were-removed by sequential extractions with 0.2 N NaOH (removal of acids, phenols, nitrates, and nitrites) and 0.2 N H2S04 (removal of amines and bases). The samples were then subjected to a fractional distillation and other treatments. Readers interested in the total details should consult the original article (10). Both thin-layer chromatography (TLC) and HPLC were used to separate the compounds present in the methanolic extract. 

While the mtrosation of phenols occurs at least as readily as that of tertiary aromatic amines -such as dimethylaniline, the conditions must be very carefully controlled owing to the ease with which most phenols oxidize. For this reason a higher proportion of tarry by-products is formed and the yields are smaller than in the case of the dialkylanilines. Taking o-cresol as a typical example of a phenol with an unsubstituted para- position, the main product of the reaction is />-nitroso-o-cresoL... 

Peroxide complexes of molybdenum(VI) are intermediates in industrially important epoxidation reactions. The so-called Mimoun-type complexes [Mo 0(02)2LaxLeq]° " (12) generally exhibit pentagonal-bipyramidal structures, with an axial 0x0 group trans to Lax and Leq, and two peroxo groups in the equatorial plane. These complexes are effective reagents for the selective oxidation of alcohols to aldehydes, amines to nitroso compounds, sulfldes to sulfoxides and then to sulfones, phenols to o-quinones, and in the sulfoxidation of thianthrene-5-oxide. 

Disposal methods for some of the more common classes of organic compounds may be found in Chemical Safety Matters (hydrocarbons halogenated hydrocarbons alcohols and phenols ethers, thiols, and organosnlfnr componnds carboxylic acids and derivatives aldehydes ketones amines nitro and nitroso componnds and peroxides). 

Nitroso compounds are of relatively limited importance in aromatic chemistry. However, since the nitroso group is easily reduced to an amino group, they do offer an indirect route to aromatic amines. The nitrosa-tion of phenols and dialkylanilines and the subsequent reduction are pertinent examples. The nitroso group is also readily oxidized to a nitro group. 

Aromatic tertiary amines and phenolic compounds undergo nuclear nitro sation, as illustrated by the synthesis of p>nitrosodimethyl aniline (89%)i nitrosophenol (80%), and l-nitroso-2-naphthol (99%) In the reaction of a-naphthol, an isomeric mixture of the nitrosonaphthols is obtained. The nitrosation of phenols with nitrous acid usually produces p nitroso compounds however, o-nitiosophenols can be prepared by nitrosating phenols in the presence of cupric sulfate. ... 

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