Pyridine-2 diazonium ions, reactions

Pyridine-2- and -4-diazonium ions are far less stable than benzenediazonium ions. Azolediazonium salts generally show intermediate stability provided diazotization is carried out in concentrated acid, many of the usual diazonium reactions succeed. Indeed, azolediazonium salts are often very reactive in coupling reactions. 

In the context of copper catalysis in important synthetic dediazoniations of arene-diazonium ions, Starkey s group (Bolth et al., 1943, Whaley and Starkey, 1946) isolated blue pyridine complexes with the constitution ArCu(C5H5N)3 by adding copper powder to pyridine solutions of ArNjBF4. However, it is unlikely that arylcopper is a relevant intermediate in these reactions (see Sec. 8.6). 

Kishimoto et al. (1974, 1981) found a general acid catalysis by protonated pyridines in coupling reactions of the 1-naphthoxide ion if weakly electrophilic diazonium ions were used. In this case it is likely that the general acid protonates the carbonyl oxygen of the o-complex, with a concerted or stepwise deprotonation at the 4-position (transition stage 12.150). 

A number of bases, with pyridine heading the list, act as proton acceptors in the electrophilic coupling reaction. Their contribution is particularly useful if voluminous substituents exist in ortho or peri position relative to the coupling location of the intermediate they may also facilitate coupling with diazonium ions of low electrophilicity (e.g., diazophenols). 

The stabilities of pyridine-2- and -4-diazonium ions resemble those of aliphatic rather than benzenoid diazonium cations. Benzenediazonium ions are stabilized by mesomerism which involves electron donation from the ring, but such electron donation is unfavorable in 2- and 4-substituted pyridines. On formation, pyridine diazonium cations normally immediately react with the aqueous solvent to form pyridones. However, by carrying out the diazotization in concentrated HC1 or HBr, useful yields of chloro- and bromopyridines 752 can be obtained. Iodinated pyridines can be obtained in good yield using the Sandmeyer reaction. Aminopyridazines and -pyrazines, 2- and 4-aminopyrimidines, and amino-1,2,4-triazines behave similarly. Nucleophilic fluorination via the BalzSchiemann reaction of diazonium fluoroborates yields fluoropyridines, including 2-fluoropyridines. Fluoroborates can also be converted into fluoro compounds by ultraviolet irradiation. 

Aromatic fluorination A new method of aromatic fluorination involves treatment of aryltriazenes, readily prepared from aryldiazonium ions and dialkyl-amines, with 70% hydrogen fluoride in pyridine. The yields of product from this reaction are usually higher than those obtained by the reaction of HF-pyridine with a diazonium ion (6, 285) o-methoxy, iodo-, bromo- and nitro-substituted aryltriazenes generally give unsatisfactory yields. This method may be useful for the synthesis of " F-labeled compounds. 

Arenediazonium ion reactions often are complex.61 Benzenediazonium fluoro-borate in 2,2,2-trifluoro ethanol (TFE), for example, decomposes by first-order kinetics to give a mixture consisting largely of the ether (62%) formed by solvolysis and fluorobenzene (34%) resulting from reaction with fluoroborate ion. Addition of pyridine changes the kinetic order and gives rise to additional products.62 The same diazonium ion solvolyzes faster in TFE than in water. Because water is a better nucleophile than TFE, it is likely that a nucleophile is not involved in the rate limiting step of the reaction.63 ... 

Some of the typical benzene electrophihc substitution reactions do not occur at all Friedel-Crafts alkylation and acylation fail because pyridines form complexes with the Lewis-acid catalyst required, involving donation of the nitrogen lone pair to the metal centre. Milder electrophilic species, such as Mannich cations, diazonium ions or nitrous acid, which in any case require activated benzenes for success, naturally fail with pyridines. 

If one eliminates specific hydroxonium and hydroxide ion catalysis, which arise from effects on pre-equilibria, in the measured overall rate constants of diazo coupling reactions, one recognizes that there are some reactions which do and some which do not show general base catalysis. A base-catalysed combination, namely the reaction of p-chlorobenzene diazonium ion with 2-naphtholate-6,8-disulphonate anion has been investigated with respect to catalysis (Zollinger, 1955a, c). A non-linear dependence between rate and the concentration of pyridine, 2-, 3-and 4-picoline and 2,6-lutidine was found, corresponding to a ratio = 1 30 for pyridine (B = pyridine). 

Evidence for the intermediacy of the diazonium ion (734) in the reaction of excess diazomethane with 4-bromo-3-phenylcyclobut-3-ene-l,2-dione has been obtained by carrying out the addition in the presence of triethylamine, when the cyclobutenyl-diazomethane (735) was isolated. Surprisingly, when pyridine was used instead of triethylamine, the dihydropyridine (736) was formed. ... 

The kinetics of the diazotization of 4-aminopyridine in 0.0025-5.0 M perchloric acid were studied, and the reaction was believed to proceed by only one mechanism whose kinetic form is first order with respect to the amine as well as to nitrous acid. The rate of the reaction showed an exponential catalytic dependence on the concentration of added perchloric acid and sodium perchlorate. In solutions of constant ionic strength the rate was directly related to the acidity function Hq). The 4-diazonium ion was characterized as 4-(2-hydroxy-l-naphthylazo)pytidine. When 4-aminopyridine is diazotized and treated with Ar,7 A-dimethylaniline, 4-(p-dimethylaminophenylazo)pyridine (DC-95) is obtained. 2-(p-Dimethylaminophenyl)pyridine is isolated when 2-aminopyridine is used instead of 4-aminopyridine. ... 

---