Primary aromatic amines, reactions

Primary aromatic amines differ from primary aliphatic amines in their reaction with nitrous acid. Whereas the latter yield the corresponding alcohols (RNHj — ROH) without formation of intermediate products see Section 111,123, test (i), primary aromatic amines 3neld diazonium salts. Thus aniline gives phcnyldiazonium chloride (sometimes termed benzene-diazonium chloride) CjHbNj- +C1 the exact mode of formation is not known, but a possible route is through the phenjdnitrosoammonium ion tlius ... 

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). ... 

Reaction with arenediazonium salts Adding a phe nol to a solution of a diazonium salt formed from a primary aromatic amine leads to formation of an azo compound The reaction is carried out at a pH such that a significant portion of the phenol is pres ent as its phenoxide ion The diazonium ion acts as an electrophile toward the strongly activated ring of the phenoxide ion... 

Acid rhodamines are made by the iatroduction of the sulfonic acid group to the aminoxanthene base. The preferred route is the reaction fluorescein (2) with phosphorous pentachloride to give 3,6-dichlorofluoran (fluorescein dichloride) (23), which is then condensed with a primary aromatic amine in the presence of 2inc chloride and quicklime. This product is then sulfonated. For example, if compound (23) (fluorescein dichloride) is condensed with aniline and the product is sulfonated. Acid Violet 30 Cl45186) (24) is produced. 

V-Phenylsuccinimide [83-25-0] (succanil) is obtained in essentially quantitative yield by heating equivalent amounts of succinic acid and aniline at 140—150°C (25). The reaction of a primary aromatic amine with phosgene leads to formation of an arylcarbamoyl chloride, that when heated loses hydrogen chloride to form an isocyanate. Commercially important isocyanates are obtained from aromatic primary diamines. 

Primary aromatic amines react with aldehydes to form Schiff bases. Schiff bases formed from the reaction of lower aUphatic aldehydes, such as formaldehyde and acetaldehyde, with primary aromatic amines are often unstable and polymerize readily. Aniline reacts with formaldehyde in aqueous acid solutions to yield mixtures of a crystalline trimer of the Schiff base, methylenedianilines, and polymers. Reaction of aniline hydrochloride and formaldehyde also yields polymeric products and under certain conditions, the predominant product is 4,4 -methylenedianiline [101 -77-9] (26), an important intermediate for 4,4 -methylenebis(phenyhsocyanate) [101-68-8], or MDI (see Amines, aromatic amines, l thylenedianiline). 

Reaction with Nitrous Acid. Primary, secondary, and tertiary aromatic amines react with nitrous acid to form a variety of products. Primary aromatic amines form diazonium salts. ... 

Diarylamines are manufactured by the self-condensation of a primary aromatic amine in the presence of an acid, or the reaction of an arylamine with a phenol, at high temperatures. 

Phenyhsonitrile has a powerful characteristic odor it is used as a qualitative test (the carbylamine test) for chloroform or primary aromatic amines. Chloroform reacts with phenols in alkaline solution to give hydroxyaromatic aldehydes in the Reimer-Tiemann reaction eg, phenol gives chiefly Nhydroxyben2aldehyde and some sahcylaldehyde (11) (see Hydroxybenzaldehydes). 

Synthesis. Almost without exception, azo dyes ate made by diazotization of a primary aromatic amine followed by coupling of the resultant diazonium salt with an electron-rich nucleophile. The diazotization reaction is carried out by treating the primary aromatic amine with nitrous acid, normally generated in situ with hydrochloric acid and sodium nitrite. The nitrous acid nitrosates the amine to generate the N-nitroso compound, which tautomerizes to the diazo hydroxide. 

The reaction of an aiyl diazonium salt with potassium iodide is the standar d method for the preparation of aryl iodides. The diazonium salt is prepared from a primary aromatic amine in the usual way, a solution of potassium iodide is then added, and the reaction mixture is brought to room temperature or heated to accelerate the reaction. 

Because diacetylene is unstable, a stable diacetylene derivative, 1-methoxybut-l-en-3-yne (65CB98), is often employed in the synthesis of pyrroles. The reaction with ammonia proceeds under conditions of heterogeneous catalysis (a mixture of reagent vapors is passed through a catalyst-containing reactor heated to 150°C), approaching a yield of 50-70% but with primary aromatic amines, the yield drops to 20%. 

The reactions of 4-alkoxybut-3-en-2-ones with primary aromatic amines and diamines of the aromatic and heteroaromatic series follow analogous schemes. 

The nitrosation of primary aromatic amines 1 with nitrous acid 2 and a subsequent dehydration step lead to the formation of diazonium ions 3. The unstable nitrous acid can for example be prepared by reaction of sodium nitrite with aqueous hydrochloric acid. 

By reaction of a primary aromatic amine—e.g. aniline 1—with glycerol 2, and a subsequent oxidation of the intermediate product 4, quinoline 5 or a quinoline derivative can be obtained.As in the case of the related Friedlander quinoline synthesis, there are also some variants known for the Skraup synthesis, where the quinoline skeleton is constructed in similar ways using different starting materials. ... 

Discussion. The formation of coloured compounds by coupling phenols with diazotised primary aromatic amines has long been recognised as a method of determining phenols, and procedures have been evolved whereby the phenol solution is titrated with a diazonium solution which has been calibrated against known concentrations of the phenol. The resultant reaction products are coloured, but many are only sparingly soluble in water and organic solvents and do not therefore lend themselves to colorimetric determination. 

Griess (1864a) had already observed that the diazo compounds obtained from primary aromatic amines in acid solution are converted by alkalis into salts of alkalis. The reaction is reversible. The compounds which Hantzsch (1894) termed sjw-diazotates exhibit apparently the same reactions as the diazonium ions into which they are instantaneously transformed by excess of acid. Clearly the reaction depends on an acid-base equilibrium. 

Diarylamines couple with considerably more difficulty than alkylarylamines. In contrast to primary aromatic amines and alkylarylamines, dialkylarylamines are substituted by diazonium ions only in the 4-, not in the 2-position. This is due to the considerable sensitivity of azo coupling reactions to steric hindrance. 

Primary aromatic amines (e.g., aniline) and secondary aliphatic-aromatic amines (e. g., 7V-methylaniline) usually form triazenes in coupling reactions with benzenedi-azonium salts. If the nucleophilicity of the aryl residue is increased by addition of substituents or fused rings, as in 3-methylaniline and 1- and 2-naphthylamine, aminoazo formation takes place (C-coupling). However, the possibility has also been noted that in aminoazo formation the initial attack of the diazonium ion may still be at the amine N-atom, but the aN-complex might rearrange too rapidly to allow its identification (Beranek and Vecera, 1970). 

In 1882 Griess discovered that in aqueous acidic solution 4-diazobenzenesulfonate and 4-methylaniline react quantitatively to yield 4-toluenediazonium ion and 4-ami-nobenzenesulfonic acid. This phenomenon is called diazo migration or diazo exchange. We now know that it is a consequence of the tautomerism of the initially formed l-(4 -methylphenyl)-3-(4 -sulfophenyl)-triazene, as discussed above. Griess also found another reaction that could not be explained at his time, but which is based on the tautomerism of intermediate triazenes occasionally, the reaction of an arenediazonium salt with a primary aromatic amine in weakly acidic solution yields a mixture of two isomeric aminoazo compounds (Scheme 13-21). 

The reaction of diazo compounds with amines is similar to 10-15. The acidity of amines is not great enough for the reaction to proceed without a catalyst, but BF3, which converts the amine to the F3B-NHR2 complex, enables the reaction to take place. Cuprous cyanide can also be used as a catalyst. The most common substrate is diazomethane, in which case this is a method for the methylation of amines. Ammonia has been used as the amine but, as in the case of 10-44, mixtures of primary, secondary, and tertiary amines are obtained. Primary aliphatic amines give mixtures of secondary and tertiary amines. Secondary amines give successful alkylation. Primary aromatic amines also give the reaction, but diaryl or arylalkyl-amines react very poorly. 

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. " ... 

The reaction has been extended to the formation of primary aromatic amines, but the scope is narrow Citterio, A. Gentile, A. Minisci, F. Navarrini, V. Serravalle, M. Ventura, S. J. Org. Chem., 1984, 49, 4479. 

Secondary amines have been converted to tertiary amines by treatment with lithium dialkylcuprate reagents R2CuLi -t- NHR RNR2 The reaction was also used to convert primary amines to secondary, but yields were lower. However, primary aromatic amines (ArNH2) were converted to diaryl amines (ArNHPh) by treatment with Ph3Bi(OAc)2 and a copper powder catalyst. 

When primary aromatic amines are treated with nitrous acid, diazonium salts are formed. The reaction also occurs with aliphatic primary amines, but aliphatic diazonium ions are extremely unstable, even in solution (see p. 448). Aromatic diazonium ions are more stable, because of the resonance interaction between the nitrogens and the ring ... 

In a related reaction, primary aromatic amines have been oxidized to azo compounds by a variety of oxidizing agents, among them Mn02, lead tetraacetate, O2 and a base, barium permanganate, and sodium perborate in acetic acid, tert Butyl hydroperoxide has been used to oxidize certain primary amines to azoxy compounds. 

Coupling reactions with diazonium salts to yield intensely colored azo derivatives have often been used for the detection of phenols, primary aromatic amines and electron-rich heterocyclics. 

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