Amines coupling with diazonium

The primary aromatic amines which will be preferentially nitrosated rather than diazotized are those which do not bear strongly electron-withdrawing substituents and are capable of coupling with diazonium salts to give azo dyes. 

Coupling Components With Condensed Cyclic Ammo nium Residues. Heterocyclic compounds in which the condensed benzene ring is substituted by a hydroxyl or an amino group can be coupled with diazonium compounds and may also be quatemized, either prior or subsequent to the coupling reaction, to yield cationic azo dyes. l,2-Dialkyl-6-nitroindazolium salts are reduced to the 6-amino compounds and then coupled with diazonium salts of aromatic amines. These dyes (e g., 21) color polyacrylonitrile in bright yellow to orange shades [64],... 

Aryldiazonium salts are weak electrophiles. Consequently, they undergo Ar-SE reactions via sigma complexes (azo couplings) only with the most strongly activated aromatic compounds. Only phenolates and secondary and tertiary aromatic amines react with them. Primary aromatic amines react with diazonium salts, too, but via their N atom. Thus, triazenes, that is, compounds with the structure Ar—N=N—NH—Ar are produced. Phenol ethers or nonde-protonated phenols can react with aryldiazonium salts only when the latter are especially good... 

Nitrogen s extra pair of electrons, which is responsible for the usual basicity of nitrogen compounds, is involved in the tt cloud, and is not available for sharing with acids. In contrast to most amines, therefore, pyrrole is an extremely weak base (ATj, -- 2.5 X 10 14). By the same token, there is a high electron density in the ring, which causes pyrrole to be extremely reactive toward electrophilic substitution it undergoes reactions like nitrosation and coupling with diazonium salts which are characteristic of only the most reactive benzene derivatives, phenols and amines. 

Like other aromatic compounds, these five-membered heterocycles undergJ nitration, halogenation, sulfonation, and Friedel-Crafts acylation. They are mucji more reactive than benzene, and resemble the most reactive benzene derivatives (amines and phenols) in undergoing such reactions as the Reimer-Tiemann reaction, nitrosation, and coupling with diazonium salts. 

It is a white solid (r.d. 1.28 m.p. 123-124°C b.p. 295°C) used in rubber as an antioxidant. Naphthalen-2-ol will couple with diazonium salts at the 1 -position to form red azo compounds, a reaction used in testing for the presence of primary amines (by making the diazonium salt and adding naphthalen-2-ol). 

Primary aromatic amines and their N-mono- and N,N-dialkyl derivatives can be coupled with diazonium salts in a slightly acid medium. The reaction can be carried out using stabilized diazonium salts (which do not contain free nitrous acid), for example, with p-nitrobenzenediazonium fluoroborate (17) or with a salt with 1-naphthalenesulfonate. The reaction takes place in dilute acetic acid in the presence of sodium acetate. Recently, 4-azo-benzenediazonium fluoroborate was proposed as the reagent, and dimethyl sulfoxide or dimethylformamide (18, 19) as the reaction medium in which intensely colored di-cations of bis-azo dyes can be formed. 

The most important reaction of the diazonium salts is the condensation with phenols or aromatic amines to form the intensely coloured azo compounds. The phenol or amine is called the secondary component, and the process of coupling with a diazonium salt is the basis of manufacture of all the azo dyestuffs. The entering azo group goes into the p-position of the benzene ring if this is free, otherwise it takes up the o-position, e.g. diazotized aniline coupled with phenol gives benzeneazophenol. When only half a molecular proportion of nitrous acid is used in the diazotization of an aromatic amine a diazo-amino compound is formed. 

Diazonium salts couple readily with aromatic primary amines, giving diazoamino compounds. If for instance an aqueous solution of aniline sulphate is diazotised with a deficiency of nitrous acid, only part of it is converted into benzenediazonium sulphate and the latter then couples with the unchanged aniline to give diazoaminobenzene. The reaction is carried out at the opti-CeHsNHj.HjSO + HONO = CbHsNjHSO, + zHaO... 

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). ... 

In the presence of proton-donative organic solvents (alcohols), aliphatic amines do not react with diazonium, whereas aromatic amines form mainly triazenes and also para-aminoazo compounds, which subsequently interact slowly with an excess of diazo reagent via N-coupling and form disazo derivatives. 

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. 

Diazoamino compounds, (LXIII) produced by coupling a diazonium ion with a primary aromatic amine, viz. 

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. 

In the presence of acids, sulfanilic acid — like other primary aromatic amines — reactt with nitrite to yield a diazonium compound that can couple with a suitable aromatic amine to yield an azo dye. 

The production of azo pigments relies almost exclusively on the azo coupling reaction [1,2] to afford the azo group. Diazotization of an aromatic amine yields a diazonium compound, which subsequently reacts with a coupling component ( coupling ). 

Two of these systems were studied as models—the acetylation of choline in brain to give acetyl choline (Hebb, Nachmansohn), and of sulfanilamide (the active component in prontosil, Chapter 3) in liver (Lipmann). Sulfanilamide is rapidly inactivated by acetylation on the p-amino group and then excreted. Sulfanilamide is easily diazotized the diazonium salt formed can be coupled with N-( 1 -naphthyl)ethylenedi-amine dihydrochloride to give a pink derivative (Bratton and Marshall, 1939). This formed the basis for an elegant colorimetric assay. Only the free p-amino group reacts, so that as acetylation proceeded color formation diminished. 

The spacer arm length between the hapten and the carrier is in the range of 6 to 8 A, which should eliminate any steric interference with carrier side chains. According to the protocol described by Schultz the haptens were coupled to BSA and KLH via A-(3-dimethylaminopropyl)-A -ethylcarbodiimide or the N-hydroxysuccinimide ester at pH 5.5 in water. Other coupling strategies include substitution with diazonium salts and reductive amination. The ratio of hapten-carrier range between 8 and 15 haptens per carrier. 

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