Diazonium intermediates, formation

A similar reaction occurs when an aqueous solution of a diazonium compound is made strongly alkaline and then warmed with an alkaline solution of stannous chloride. This reaction, however, involves the intermediate formation of the... 

C,H5N,NHC,Hs+HC1 = C,H 5N C1+H,NC,H5- C H5N NC H NH +HC1 gen atom of the aniline molecule, giving aminoazobenzene. Since this reaction is irreversible, whilst the former is freely reversible, the final result is the complete conversion of the diazoaminobenzene into the aminoazobenzene. (The intermediate formation of the benzenediazonium chloride can be demonstrated by adding dimethylaniline, with which the diazonium chloride couples preferentially, giving dimethylaminoazobenzene, C6HsN NC6HiN(CH3)i.)... 

The mechanism of the reaction probably involves the intermediate formation ofthe covalent dlazo-hydroxide from the diazonium salt the former decomposes... 

The EfZ ratio of stilbenes obtained in the Rh2(OAc)4-catalyzed reaction was independent of catalyst concentration in the range given in Table 22 357). This fact differs from the copper-catalyzed decomposition of ethyl diazoacetate, where the ratio diethyl fumarate diethyl maleate was found to depend on the concentration of the catalyst, requiring two competing mechanistic pathways to be taken into account 365), The preference for the Z-stilbene upon C ClO -or rhodium-catalyzed decomposition of aryldiazomethanes may be explained by the mechanism given in Scheme 39. Nucleophilic attack of the diazoalkane at the presumed metal carbene leads to two epimeric diazonium intermediates 385, the sterically less encumbered of which yields the Z-stilbene after C/C rotation 357,358). Thus, steric effects, favoring 385a over 385 b, ultimately cause the preferred formation of the thermodynamically less stable cis-stilbene. 

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. 

The diazonium intermediate releases molecular nitrogen (N2) to form reactive carbonium ions. If the R group is aromatic, the diazonium intermediates can be stabilized as a salt, and are widely used as intermediates in synthetic chemistry. The formation of a diazonium intermediate with sulfanilic acid by acidified nitrite, a source of nitrosonium ion, is the basis for measuring nitrite by the Griess reaction. 

The formation of diazonium salts from aromatic primary amines by reaction with nitrous acid undoubtedly involves the intermediate formation of V-nitroso compounds. The Demjanov and Tiffeneau-Demjanov ring expansions also involve V-nitroso compounds [2]. Some V-nitroso compounds have been used as sources of free radicals and as blowing agents. 

An unusual course of thermolysis occurs in 5-amino- and 5-alkoxytri-azolines, which are formed only as intermediates in the reaction of enamines and enol ethers with azides bearing electron-withdrawing groups it involves cleavage of the N-l/N-2 as well as the C-4/C-5 bonds of the triazoline ring to yield diazoalkanes and imines with one fewer carbon than in the triazolines (amidines and imino ethers) (Scheme 144)233.250 272 431-433 in a cycloelimination reaction, the reverse of diazoalkane-imine cycloaddition. The intermediate formation of a diazonium zwitterion is suggested,233,247 but whether the thermolysis occurs in a one- or two-step reaction is not established. 

Microreactors provide a safe means by which reactions, including multistage schemes, can be undertaken where, otherwise, products involving unstable intermediates may be formed. This is exemplified by Fortt who showed that for a serial diazonium salt formation and chlorination reaction performed in a microreactor under hydrodynamic pumping, significant yield enhancements (15-20%) could be observed and attributed them to enhanced heat and mass transfer [77]. This demonstrates the advantage of microreactor-based synthesis where diazonium salts are sensitive to electromagnetic radiation and static electricity, which in turn can lead to rapid decomposition. Microreactors facilitate the ability to achieve continuous-flow synthesis, which is often not possible with conventional macroscale reactors and batch production. 

Mechanistically the reaction proceeds via a diazonium intermediate that undergoes cyclization by intramolecular nucleophilic attack, nitrogen being the leaving group. However, an alternative mechanism involving thiadiazole 5-oxide formation cannot be excluded80. 

Unlike their aromatic counterparts, however, these diazonium ions are extremely unstable, and lose nitrogen rapidly to give products that strongly suggest intermediate formation of carbonium ions (Problem 23.11, p. 763). 

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 formation of S A -tetrachloroazobenzene, l,3-bis(3,4-dichlorophenyl)triazine, and 3,3, 4,4 -tetrachlorobiphenyl from 3,4-dichloroaniline and nitrate by E. coli presumably involves intermediate formation of the diazonium compound by reaction of the amine with nitrite (Corke et al. 1979) (Figure 4.29g). 

The second reaction goes best with a cuprous oxide catalyst. This method, which probably involves diazonium intermediates, can be used to prepare substituted aromatic arsenicals such as (4-ClC6H4)2AsCl. It has also been found that air oxidation of a mixture of arsenic trichloride and an aryl-hydrazine in the presence of cupric chloride results in the formation of aryl arsenicals 156). 

In addition to the classical techniques for diazotization in aqueous solution, diazonium ions can be generated by reaction with alkyl nitrites. This method is frequently used for in situ formation of diazonium intermediates in organic solvents. 

Primary aromatic amines differ from primary aliphatic amines in their reaction with nitrous acid. Whereas the latter yield the corresponding alcohols (RNHj — ROH) without formation of intermediate products see Section 111,123, test (i), primary aromatic amines 3neld diazonium salts. Thus aniline gives phcnyldiazonium chloride (sometimes termed benzene-diazonium chloride) CjHbNj- +C1 the exact mode of formation is not known, but a possible route is through the phenjdnitrosoammonium ion tlius ... 

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... 

In contrast to the acid, sodium nitrite should not in general be added in excess. Firstly, as far as the ratio of amine to nitrite is concerned, diazotization is practically a quantitative reaction. In consequence, it provides the most important method for determining aromatic amines by titration. Secondly, an excess of nitrous acid exerts a very unfavorable influence on the stability of diazo solutions, as was shown by Gies and Pfeil (1952). Mechanistically the reactions between aromatic diazonium and nitrite ions were investigated more recently by Opgenorth and Rtichardt (1974). They showed that the primary and major reaction is the formation of aryl radicals from the intermediate arenediazonitrite (Ar —N2 —NO2). Details will be discussed in the context of homolytic dediazoniations (Secs. 8.6 and 10.6). 

P-coupling occurs in the formation of azophosphonic esters [ArN2PO(OCH3)2] from diazonium salts and dimethyl phosphite [HPO(OCH3)2] (Suckfull and Hau-brich, 1958). P-coupled intermediates are formed in the reaction between diazonium salts and tertiary phosphines, studied by Horner and Stohr (1953), and by Horner and Hoffmann (1956). The P-azo compound is hydrolyzed to triphenylphosphine oxide, but if a second equivalent of the tertiary phosphine is available, phenyl-hydrazine is finally obtained along with the phosphine oxide (Scheme 6-26 Horner and Hoffmann, 1958). It is likely that an aryldiazene (ArN = NH) is an intermediate in the hydrolysis step of the P-azo compounds. 

A number of approaches have been tried for modified halo-de-diazoniations using l-aryl-3,3-dialkyltriazenes, which form diazonium ions in an acid-catalyzed hydrolysis (see Sec. 13.4). Treatment of such triazenes with trimethylsilyl halides in acetonitrile at 60 °C resulted in the rapid evolution of nitrogen and in the formation of aryl halides (Ku and Barrio, 1981) without an electron transfer reagent or another catalyst. Yields with silyl bromide and with silyl iodide were 60-95%. The authors explain the reaction as shown in (Scheme 10-30). The formation of the intermediate is indicated by higher yields if electron-withdrawing substituents (X = CN, COCH3) are present. In the opinion of the present author, it is likely that the dissociation of this intermediate is not a concerted reaction, but that the dissociation of the A-aryl bond to form an aryl cation is followed by the addition of the halide. The reaction is therefore mechanistically not related to the homolytic halo-de-diazoniations. 

The only really different case is the azo coupling reaction of nitroethane investigated by Sterba and coworkers (Machacek et al., 1968a, 1968b). With the 4-nitrobenzenediazonium ion the reaction is zero-order with respect to diazonium ion and first-order in both nitroethane and base. Obviously the rate-limiting step is the dissociation of nitroethane the formation of the anion is slower than its subsequent reaction with this diazonium ion. For reactions with diazonium ions of lower reactivity it was found necessary to use the reaction system of Scheme 12-64 with the nitroethane anion as steady state intermediate (Machacek et al., 1968b). 

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