Amines via diazonium salts

Dsaminalion ot aromatic amines via diazonium salts, by means of alcohols (Giiess), oi P02H3,Sn(0H)2.etc. 

Table 1. Formation of Arylmercurials from Aromatic Amines via Diazonium Salts...

The nitro group is converted to versatile functionalities. A carbon-carbon double bond can be produced from nitroalkane by elimination of a nitro group with vicinal hydrogen as nitrous acid. The Nef reaction is also often used for transformation from nitroalkanes to ketones. The most useful chemical modification of a nitro group is the reduction furnishing oximes and amines, and further chemical conversion to various functionalities can be performed via diazonium salts. 

Other general reactions of amines would be nucleophilic displacement, electrophilic aromatic substitution in anilines and substitution via diazonium salts. 

Functionalize SWNH via diazonium salt to incorporate amine and carboxylic groups which may interact better with proteins and biological molecules. 

Aromatic Hydrazines. A general synthesis for aryUiydraziaes is via diazotization of aromatic amines, followed by reduction of the resulting diazonium salt (18) ... 

This reaction is commonly achieved by diazotization of the amine in fluoro-boric acid, followed by decomposition of the diazonium salt (Schiemann reaction).Thus, l-amino-4-methylestra-l,3,5(10)-trien-17-one (50) is converted to the fluoro derivative (51) in 29% yield. The synthesis of 3-fluoroestra-l,3,5(10)-triene-17-one (55) from estrone proceeds via (52) and (53)... 

Inclusion of a para acetyl group requires a somewhat different approach to the preparation of these compounds. Reaction of the diazonium salt from p-aminoacetophenone with sulfur dioxide affords the sulfonyl chloride, 203 this is then converted to the sulfonamide, 204, Elaboration via the carbamate with cyclohexyl-amine affords acetohexamide (205). ... 

The chlorine can be disconnected with the alternative polarity via the diazonium salt to amine (19) (guideline 4), The amino group is more powerfully electron-donating than OMe so we can disconnect the NO group. The amino group is itself derived from another nitro group. 

An alternative strategy, avoiding the danger of over-reaction with diax.omethane, is to make the diazonium salt, by diazotisation of a hydroxy amine (14), available from the original ketone (12) via epoxide (13),... 

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. 

The triazene linker can be used for the immobilization of aromatic diazonium salts, and therefore for aromatic amines, but not for aliphatic amines due to the instability of their diazonium salts. Cleavage of the linker can be achieved under mild acidic conditions to yield the benzylamine resin and the corresponding diazonium salt [136,145,146]. The main difference between the preparation of triazenes in solution and triazenes on solid support is the respective amine, namely bisben-zylamine and polymer-supported benzylamine 114. In solution, it was used in excess to quench unstable diazonium salts and force the reaction to completion. In the solid-phase approach it was immobilized and cannot be used in excess with respect to low loadings. A simple three-step procedure (Scheme 36) starting from benzylamine resin 114 via carboxylate 115 led to the successful preparation of ester resins 116 in essentially higher loadings. Treatment of resin 114 with 4-carboxy-benzene diazonium tetrafluoroborate yielded benzoic acid resin 115. 

Until recently no satisfactory procedure for the direct conversion of a primary aliphatic amine into an alkyl halide was available. This contrasts sharply with the ready conversion of primary aromatic amines into aryl halides via the diazonium salt (Section 6.7, p.922). However a useful method has not been discovered which is not only applicable to the synthesis of simple alkyl and aralkyl chlorides, bromides, iodides and fluorides, but could clearly be of value when it is required to replace an amino group in a naturally occurring amine by a halogen.92... 

Whereas the Ti linker involves an immobilization of a diazonium salt on an amine resin, the T2 linker represents the reversal of this concept. As outlined in Scheme 10, m-aminophenol (54) was attached to Merrifield resin 53 by displacing the chloride group via the phenolic group with the aid of sodium hydride in dimethylformamide (DMF) (see Experimental... 

This route is particularly valuable for substituents that cannot easily be added by electrophilic substitution such as OH or CN. Table 2.2 gives you a selection of reagents. For the addition of CN, Cl or Br, copper (I) derivatives usually give the best results. So the aryl nitrile 46 might come from amine 47 via a diazonium salt and routine disconnections lead us back to toluene. 

Aromatic amines may be converted to their diazonium salts with nitrous acid. The hapten may then be bound via azo linkages to the tyrosine (shown), histidine, lysine, and possibly arginine and tryptophane residues of the carrier protein by mixing the... 

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... 

Reaction with Primary Amines Formation of Diazonium Salts Primary amines react with nitrous acid, via the nitrosonium ion, to give diazonium cations of the form... 

In the Pschorr synthesis (Scheme 12.12), a Perkin reaction (see Chapter 6) between 2-nitrobenzaldehyde and sodium phenylacetate in the presence of acetic anhydride yields 3-(2-nitrophenyl)-2-phenyl-propenoic acid. Reduction of the nitro group and deamination of the resulting amine via its diazonium salt (see Chapter 8) is accompanied by cyclization. Thermal decarboxylation completes the sequence. 

SANDMEYER GATTERMANN Aromatic substitution Substitution of an amine group via the diazonium sait by nucleophiles such as cr, Br, c. CN-R-S", HO, some via cuprous salt catalysis. 

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