1-oxide amino-, diazonium salts

Oiazonium Salt Formation. The aromatic amino group of aminophenols can be converted to the diazonium salt using sodium nitrite in aqueous acid, although difficidties may be encoimtered when the aminophenol is of low solubiUty or easily oxidized Crystalline diazonium salts have been isolated using the hydrochloride or sidfate of the appropriate aminophenol under anhydrous conditions. Such diazo derivatives find extensive use in the dye industry (27,28). 

Azo-compounds can be obtained by reduction of nitro-compounds, or by oxidation of hydrazo-compounds. They are usually prepared, however, by reacting a phenol or amine with a diazonium salt. The coupling usually takes place in the position para to the hydroxyl or amino group, but if this position is occupied it goes to the ortho position, e.g. 

Oxidative Couplings of Heterocyclic Hydrazones. This method has opened the way to the preparation of azo derivatives of diazo compounds unobtainable by other means, ie, heterocycHc compounds ia which the diazotizable amino group is conjugated with the heterocycHc nitrogen atom as ia 2- and 4-amiQopyridine, compounds which do not normally yield stable diazonium salts (38). The reaction occurs as illustrated by equation 7 for the iateraction of (A/-methylcarbostyryl)hydrazone [28219-37-6] and dimethyl aniline the overall process is oxidation. 

Amino-6-chloro-4-methyl- and 3-amino-6-chloro-5-methyl-pyridazine and 3-amino-6-methylpyridazin-4(l//)-one are transformed with sodium nitrite in the presence of acid into the corresponding oxo compounds. If concentrated hydrochloric acid is used, in some instances the corresponding chloro derivatives are obtained as side products. On the other hand, 3-, 4-, 5- and 6-aminopyridazine 1-oxides and derivatives are transformed into stable diazonium salts, which can easily be converted into the corresponding halo derivatives. In this way 3-, 4-, 5- and 6-bromopyridazine 1-oxides, 5-chloropyridazine 1-oxide, 3,4,5-trichloropyridazine 1-oxide and 6-chloropyridazine 1-oxide can be obtained. 

Diazotization of 4-amino-l,2,5-oxadiazole-3-carbohydroximoyl chloride 132 gives 4-[chloro(hydroxyimino)-methyl]-l,2,5-oxadiazole-3-diazonium salt 133 (Scheme 35). Treatment of the latter with NaN3 afforded 4-azido-l,2,5-oxadiazole-3-carbohydroximoyl chloride 134 and the reaction with NaN02 yielded 2-cyano-2-hydro-xyiminoaceto-hydroximoyl chloride 135. By oxidation of 4-amino-l,2,5-oxadiazole-3-carbohydroximoyl azide 136... 

Three methods for making 4,5,6,7-tetrahydrotriazoIopyridines use two fragments to form the triazole ring. The lithium derivative of A/-nitro-sopiperidine reacts with benzonitrile to give the 3-phenyl derivative 19.28 Diazonium salts react with a-amino acids to give mesoionic triazole oxides if pipecolic acid is used, the product is a tetrahydrotriazolopyridine 3-oxide... 

Two noncatalytic methods have been used to remove amino or hydrazino groups. Diazotization and reduction of the diazonium salt by hypophos-phorous acid removes amino groups from aminotriazolopyridines 173,65 174,66 and 175,65 whereas silver oxide treatment removes hydrazino groups from compounds 176216 and 177.206... 

Aminopyridine /V-oxides can be diazotized, and the diazonium salts undergo coupling, etc. These diazonium salts are stabilized by mesomerism (728), cf (726). Amino groups in pyridazine /V-oxides can also be diazotized and the diazonium group further replaced by other functionality. Nitrosation of 3-amino-1,2,4-triazine 2-oxides and subsequent thermolysis of the diazonium tetrafluoroborate salts afforded 3-fluoro-1,2,4-triazine 2-oxides (85H(23)1969). 

The free bases are much less stable than aniline, particularly 2-amino-pyrroles and -furans which are very easily oxidized or hydrolyzed. 2-Aminofurans substituted with electron-withdrawing groups (e.g. N02) are known and 3-amino-2-methylfuran is a relatively stable amine which can be acylated and diazotized. 2-Aminothiophene can be diazotized and the resulting diazonium salt coupled with (3-naphthol. 2,3-Diaminothiophene has been prepared and isolated as the hydrobromide. The free base is not stable (85JCR(S)296). 

Benzotriazinium betaines (13) and (26) are stable toward acids. They are slightly basic compounds and form salts with acids which are easily hydrolyzed. The corresponding 1-oxides (33) behave similarly, being, for instance, souble in concentrated hydrochloric acid from which they are reprecipitated on dilution with water (27JCS323). 4-Amino-l,2,3-benzotriazines (38) and 4-imino-1,2,3-benzotriazines (39) behave as masked diazonium compounds (40) and the products of acidic treatment of these compounds are best explained as reaction products of the diazonium salts (78HC(33)78>. Treatment of 1,2,3-benzotriazine... 

The aminophenols are chemically reactive, undergoing reactions involving both the aromatic amino group and the phenolic hydroxyl moiety, as well as substitution on the benzene ring. Oxidation leads to the formation of highly colored polymeric quinoid structures. 2-Aminophenol undergoes a variety of cyclization reactions. Important reactions include alkylation, acylation, diazonium salt formation, cyclization reactions, condensation reactions, and reactions of the benzene ring. 

The derivatives (32), (33), and (56) have been prepared by cyclization of the diazonium salts of the appropriate 5-amino-1,2,3-triazoles (55) (Scheme 3). 2,8-Diazaadenine-l-Ar-oxide (32) is formed in 60% yield from the amidoxime (55 X = NOH, R = H), which is made by hydrolysis of 8-azaadenine-1-TV-oxide <60JA3189>. 2,8-Diazahypoxanthine (33) was obtained as a dihydrate in good yield by diazotization of the carboxamide (55 X = O, R = H). The intermediate diazonium salt could be isolated and cyclized rapidly under alkaline conditions <61J0C2396,66JMC733). 2,8-Diazaa-denosine (56) is formed in low yield by diazotization of the carboxamidine (55 X = NH, R = / -d-ribofuranosyl) <72JMC182>. 

Arylanthranils (205) have been obtained from 2-aroylbenzamides by Hofmann degradation and subsequent oxidation, using two moles of sodium hypobromite besides (205), some brominated product was isolated. The anthranil (205) could be reduced (Zn/CaCl2)tothe amino-ketone (206), which with nitrous acid gave some 205, as well as the diazonium salt.345... 

Other leaving groups are effective in the oxidative addition with Pd , and can lead to efficient Heck reactions. An attractive possibihty is an aniline as starting material, with in situ generation of a diazonium salt. While the oxidation of the amino group can occur with Pd° alone at elevated temperatures, dehberate addition of t-butyl nitrite leads to... 

---