Diazonium ions formation

Among the reagents that are classified as weak electrophiles, the best studied are the aromatic diazonium ions, which reagents react only with aromatic substrates having strong electron-donor substituents. The products are azo compounds. The aryl diazonium ions are usually generated by diazotization of aromatic amines. The mechanism of diazonium ion formation is discussed more completely in Section 11.2.1 of Part B. 

Primary amines react readily with nitrosating agents (Scheme 3.1) to provide deamination products. The intermediates, primary nitrosamines (RNHNO), are not stable therefore after a series of rapid reactions, they give rise to the diazonium ion (RN2+), and then decompose to the final products. The reactions of secondary amines can stop at the nitrosamine stage, since no a-hydrogen atoms are available for the necessary proton transfer reactions, which lead to diazonium ion formation. 

REACTION WITH NITROUS ACID, MONO 1. Primary Amines (Diazonium Ion Formation)... 

In the reactions of diazoalkanes considered so far the operation of acid catalysis has not-hgen questioned. One reason has been that the compounds considered are in the main sufficiently stable to require a relatively strong acid for reaction, and little difficulty has arisen in distinguishing the acid-catalysed reaction from competing thermal reactions. For more reactive substrates, the possibility of diazonium-ion formation by proton transfer from an acid as weak as a molecule of a normal hydroxylic solvent has to be taken into account, and separation of acid and thermal reactions is no longer straightforward. In fact many thermal reactions of primary and secondary aliphatic diazoalkanes are known which yield different sets of products in hydroxylic and aprotic solvents and yield mixtures of these products in solvents of intermediate acidity, such as acetamide. It is useful to consider these reactions in the light of experience of other reactions in which the presence of diazonium ions is well authenticated. 

The evidence for diazonium-ion formation in neutral or basic solutions is strong. Nonetheless, a number of serious problems remain. One difficulty is the high reactivity that must be attributed to the diazocompounds. Although aliphatic diazoalkanes can be expected to be particularly reactive towards protonation, the difference between, on the one hand, diazomethane, which requires the presence of a carboxylic acid for the observation of proton exchange at room temperature (van der Merwe et al., 1964) and, on the other hand, diazobutane, which undergoes protonation in methanolic sodium methoxide at —64° (Kirmse and Rinkler, 1962) is somewhat surprising. One would wish to see the acidic character of the solvent catalysis corroborated by a Bronsted relation within which the rate constant for the solvent reaction is compared with that for other molecular acids. 

An indirect electrochemical method developed for nitrite determination may be of general applicability for PAA determination, as shown in equation 13. A nitrite sample is placed into a cell containing a known amount of 3-sulfanilic acid in dilute HC1 at pH 3. After 5 min the diazonium ion formation is complete an excess of catechol (109) is added and the concentration of the remaining 3-sulfanilic acid is determined at +0.12 V with a GCE vs. standard calomel electrode, by measuring the adduct (110) formed between the aromatic amine and the quinone derived from catechol in the diffusion layer of the electrode. The 3-isomer of sulfanilic acid was chosen among the three isomers, aniline and 4-nitroaniline for its highest sensitivity and its lowest LOD, 0.7 pM, with linearity from 20 to 80 pM. A spectrophotometric assay may be carried out for nitrite by measuring at 516 nm the azo dye derived from catechol and the diazonium ion after 3 h ... 

The mechanism is analogous to diazonium ion formation using nitrous acid and aliphatic primary amines. 

They are stable in solution only near room temperature or below, and this limits the range of compounds that can be successfully coupled with diazonium ions. The mechanism of diazonium ion formation is discussed more completely in Part B, Chapter 8, Section 8.2.1. 

The product of this series of steps is an alkyl diazonium ion, and the amine is said to have been diazotized Alkyl diazonium ions are not very stable decomposing rapidly under the conditions of their formation Molecular nitrogen is a leaving group par excel lence and the reaction products arise by solvolysis of the diazonium ion Usually a car bocation intermediate is involved... 

Figure 22 5 shows what happens when a typical primary alkylamine reacts with nitrous acid Because nitrogen free products result from the formation and decomposition of diazonium ions these reactions are often referred to as deamination reactions Alkyl... 

Primary arylamines like primary alkylammes form diazonium ion salts on nitro sation Aryl diazonium 10ns are considerably more stable than their alkyl counterparts Whereas alkyl diazonium 10ns decompose under the conditions of their formation aryl diazonium salts are stable enough to be stored m aqueous solution at 0-5°C for a rea sonable time Loss of nitrogen from an aryl diazonium ion generates an unstable aryl cation and is much slower than loss of nitrogen from an alkyl diazonium ion... 

Reaction of aryl diazonium salts with iodide ion (Section 22 17) Adding po tassium iodide to a solution of an aryl diazonium ion leads to the formation of an aryl iodide... 

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... 

In a protic solvent—glycols are often used, with the base being the corresponding sodium glycolate—the reaction proceeds via formation of a carbenium ion 5. The diazo compound 3 can be converted into the diazonium ion 4 through transfer of a proton from the solvent (S-H). Subsequent loss of nitrogen then leads to the carbenium ion 5 ... 

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. 

The reaction of nitrous acid with the amino group of the /3-amino alcohol—e.g. 1-aminomethyl-cyclopentanol 1—leads to formation of the nitrosamine 4, from which, through protonation and subsequent loss of water, a diazonium ion species 5 is formed " —similar to a diazotization reaction ... 

The diazotization of amino derivatives of six-membered heteroaromatic ring systems, particularly that of aminopyridines and aminopyridine oxides, was studied in detail by Kalatzis and coworkers. Diazotization of 3-aminopyridine and its derivatives is similar to that of aromatic amines because of the formation of rather stable diazonium ions. 2- and 4-aminopyridines were considered to resist diazotization or to form mainly the corresponding hydroxy compounds. However, Kalatzis (1967 a) showed that true diazotization of these compounds proceeds in a similar way to that of the aromatic amines in 0,5-4.0 m hydrochloric, sulfuric, or perchloric acid, by mixing the solutions with aqueous sodium nitrite at 0 °C. However, the rapidly formed diazonium ion is hydrolyzed very easily within a few minutes (hydroxy-de-diazonia-tion). The diazonium ion must be used immediately after formation, e. g., for a diazo coupling reaction, or must be stabilized as the diazoate by prompt neutralization (after 45 s) to pH 10-11 with sodium hydroxide-borax buffer. All isomeric aminopyridine-1-oxides can be diazotized in the usual way (Kalatzis and Mastrokalos, 1977). The diazotization of 5-aminopyrimidines results in a complex ring opening and conversion into other heterocyclic systems (see Nemeryuk et al., 1985). 

Salts of diazonium ions with certain arenesulfonate ions also have a relatively high stability in the solid state. They are also used for inhibiting the decomposition of diazonium ions in solution. The most recent experimental data (Roller and Zollinger, 1970 Kampar et al., 1977) point to the formation of molecular complexes of the diazonium ions with the arenesulfonates rather than to diazosulfonates (ArN2 —0S02Ar ) as previously thought. For a diazonium ion in acetic acid/water (4 1) solutions of naphthalene derivatives, the complex equilibrium constants are found to increase in the order naphthalene < 1-methylnaphthalene < naphthalene-1-sulfonic acid < 1-naphthylmethanesulfonic acid. The sequence reflects the combined effects of the electron donor properties of these compounds and the Coulomb attraction between the diazonium cation and the sulfonate anions (where present). Arenediazonium salt solutions are also stabilized by crown ethers (see Sec. 11.2). 

In the context of this section it is important that Ruchardt and Tan (1970 a) found that (solid) benzenediazonium fluoroborate gave benzyne adducts with potassium acetate in the presence of aryne trapping agents such as tetracyclone or anthracene. This is, however, not the case if water is present (Cadogan, 1971). As a consequence of these observations, Cadogan et al. (1971) simplified the formation of arynes from diazonium ions by converting aniline or its substitution products into arynes in a... 

Other Reactions Involving Formation of Aromatic Diazonium Ions... 

The rapid formation of the (Z)-diazoate is followed by the slower (Z/J )-isomeri-zation of the diazoate (see Scheme 5-14, reaction 5). Some representative examples are given in Table 5-2. Both reactions are first-order with regard to the diazonium ion, and the first reaction is also first-order in [OH-], i.e., second-order overall. So as to make the rate constants k and k5 directly comparable, we calculated half-lives for reactions with [ArNj ]0 = 0.01 m carried out at pH = 9.00 and 25 °C. The isomerization rate of the unsubstituted benzenediazonium ion cannot be measured at room temperature due to the predominance of decomposition (homolytic dediazoniations) even at low temperature. Nevertheless, it can be concluded that the half-lives for (Z/ )-isomerizations are at least five powers of ten greater than those for the formation of the (Z)-diazohydroxide (reaction 1) for unsubstituted and most substituted benzenediazonium ions (see bottom row of Table 5-2). Only for diazonium ions with strong -M type substituents (e.g., N02, CN) in the 2- or 4-position is the ratio r1/2 (5)/t1/2 (1) in the range 6 x 104 to 250 x 104 (Table 5-2). 

Important mechanistic information can be obtained from the reaction rates of the two diazoates with acid. The older literature, e. g., publications by Grachev (1947 a, 1947 b, 1948), by Porai-Koshits (1960), and by Porai-Koshits et al. (1946, 1960), will not be reviewed here because it is outdated and in some cases the results were not reproducible (see Lewis and Suhr 1958 b, footnote 5). On the basis of the above discussion of the formation of the (Z)-diazoate from the diazonium ion by reactions 1 and 2 of Scheme 5-14, one might assume that the reverse process should be easy to follow experimentally. This is not the case, however, as was first shown simultaneously by Lewis and Suhr (1958 b) and by Passet and Porai-Koshits (1958). The investigation of the acidification of (2i)-4-nitrobenzenediazoate is difficult due to irreversible decomposition, particularly at pH >5. Lewis and Suhr (1958b) observed,... 

Fig. 5-3. Dependence of log Ar0bs on pH for the formation of diazonium ions from unsubstituted (E)-diazoate ( ), (F)-2-nitro-4-chlorodiazoate (A), and ( )-2,4-dinitrodiazoate ( ) (Sterba, 1978, p. 71). The full curves are computed from Scheme 5-17.

Evaluation of the kinetics of the formation of diazonium ions from three different (E )-diazoates on the basis of Figure 5-3 indicates that the mechanism followed in a specific case is influenced by the very different dependence of the various steps in Scheme 5-14 on the nature of the substituents. 

In Sections 5.2 and 5.3 it was shown that experimental data are consistent with a direct rearrangement of the (Z)- to the (ii)-diazohydroxide rather than with a recombination after a primary dissociation of the (Z)-isomer into a diazonium ion. Positive evidence for direct formation of the (ii)-diazohydroxide from the diazonium ion and a hydroxide ion (or water) is still lacking (see Scheme 5-15 in Sec. 5.2). For diazo ethers, however, Broxton and Roper (1976) came to the conclusion that there is no direct (Z) >(E) conversion, but rather that in the system ArNj + OCH3/(Z)-diazo ether/(Zi)-diazo ether the (Z)-ether is the kinetically determined product and the (iE )-isomer the thermodynamic product, as shown in Scheme 6-3. 

Semiquantitatively, the reaction of an aromatic diazonium ion with the methoxide ion occurs in three phases. The first is the extremely rapid formation of the (Z)-diazo methyl ether. This is followed by a second, partitioning, phase which in the case of the 4-nitrobenzenediazonium ion at 30 °C is completed in 60 s (Boyle et al., 1971). During this phase, some of the (Z)-diazo ether decomposes to form dediazoniation products (mainly nitrobenzene via the hydro-de-diazoniation reaction) and the rest is converted into the (Zi)-diazo ether. 

The kinetics and mechanism of formation of 2,3-naphthotriazole (6.49) were studied by Oh and Williams (1989). In aqueous solutions of 0.2-1.0 m HC104 the dependence of the reaction on acidity indicated simultaneous involvement of the protonated and unprotonated substrates (6.47 and 6.48 respectively). The unproton-ated form of 2,3-diaminonaphthalen (6.48) reacts with the nitrosyl ion (NO+) on encounter (rate constant k ). The 2-NH3 substituent reduces the reactivity of 6.47 by a factor of about 800 (ki/k2). The rate-limiting formation of the diazonium ion (Scheme 6-33) is followed by a rapid cyclization (Scheme 6-34). 

The significantly lower dediazoniation rate of the l/f-3,5-dimethylpyrazole-4-di-azonium ion (8.22) compared with that of the benzenediazonium ion was the central subject of an MNDO study by Brint et al. (1985). The diazonium ion 8.22 has been recovered unchanged after heating for 3 h at 100 °C in aqueous hydrochloric acid. It is not completely decomposed after a similar treatment for 48 h (Reilly and Madden, 1925). Brint et al. calculated the heats of formation of this diazonium ion and of the corresponding heteroaryl cation 8.23 (Scheme 8-16). They found that the values of A//f for the diazonium ion 8.22 and for the benzenediazonium ion are almost identical, whereas that for the cation 8.23 is much greater. The energy required to dissociate the pyrazolediazonium ion is therefore nearly twice that required for the benzenediazonium ion (A//f = 329 and 194 kJ mol-1, respectively). 

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