Diazonium side reactions

The controlled thermal decomposition of dry aromatic diazonium fluoborates to yield an aromatic fluoride, boron trifluoride and nitrogen is known as the Schiemann reaction. Most diazonium fluoborates have definite decomposition temperatures and the rates of decomposition, with few exceptions, are easily controlled. Another procedure for preparing the diazonium fluoborate is to diazotise in the presence of the fluoborate ion. Fluoboric acid may be the only acid present, thus acting as acid and source of fluoborate ion. The insoluble fluoborate separates as it is formed side reactions, such as phenol formation and coupling, are held at a minimum temperature control is not usually critical and the temperature may rise to about 20° without ill effect efficient stirring is, however, necessary since a continuously thickening precipitate is formed as the reaction proceeds. The modified procedure is illustrated by the preparation of -fluoroanisole ... 

The most important side reaction during diazotization may lead to the formation of the diazoamino compound (Sec. 2.2.1). The diazonium compound may combine with unreacted amine to form the side product (Sec. 2.2.1). This effect is particularly prominent if it arises from a change of concentration. Insufficient nitrite pre-... 

The kinetics of the coupling mechanism include a number of sometimes very fast and competitive side reactions. The following steps, for instance, proceed simultaneously as a separately prepared diazonium salt solution is combined with an initially dissolved coupling component ... 

Arenediazonium salts reacted with tetramethyltin under very mild conditions in acetonitrile yielding the corresponding toluenes [63] and this reaction could be carried out in aqueous media, as well [64] (Scheme 6.29). Similar to the Heck reactions discussed in 6.1.1, a one-pot procedure could be devised starting from anilines, with no need for the isolation of the intermediate diazonium salts. The pH of the solutions should always be kept below 7 in order to avoid side reactions of the diazonium salts, however, unlike with the Heck reactions, HCl or H2SO4 can also be used. Since organotin compounds are easily hydrolysed in acidic solutions, a careful choice of the actual pH is required to ensure fast and clean reactions. Diaryliodonium salts are hydrolytically stable and also react smoothly with various organotin compounds (Scheme 6.29) [65]. 

This preparative scheme leads to only 30% yield due to the side reactions between the meto-astatoaniline diazonium salt and astato-phenol, which cannot be eliminated even by continuous extraction of the product with n-heptane (167). All the astatophenols synthesized to date have been identified by either HPLC (99,104) or TLC (160,166,167). Their dissociation constants (KJ have been established from extraction experiments by measuring the relative distribution of compounds between aqueous borax buffer solutions and n-heptane as a function of acidity. On the basis of these derived values, the Hammett a-constants and hence the field (F) and resonance (R) effects have been estimated for these compounds (167) (see Table VI). The field effect for astatine was found to be considerably weaker than that for other halogens the resonance effect was similar to that for iodine (162). 

Firstly, various side reactions result from impurities left in the diazonium tetrafluoroborate (water, sodium nitrite, washing solvents). As already discussed, residual water or alcohols (often used to wash the solid diazonium tetrafluoroborate after filtration) substitute the diazo group in an ionic process to produce phenols or alkoxyarenes as byproducts. Residual alcohol can also lead to arenes through a radical hydrodediazoniation process, especially when electron-withdrawing groups are present, as in 3-fluoro-2-methoxy-5-(methoxyearbonyl)benzenediazo-nium tetrafluoroborate (ArF/ArH 4 1)227 or in 2-methyl-5-nitrobenzenediazonium tetrafluoroborate.240 Such radical phenomena increase when sodium nitrite is present as impurity... 

As mentioned in the preceding section, several side reactions occur during the thermal decomposition of diazonium tetrafluoroborates, especially with derivatives reluctant to react which require high temperature levels. Thus, it can be imagined that the required energy could be supplied in a form other than heat. Indeed, photochemical decomposition as well as sonication of arenediazonium tetrafluoroborates has been proposed. 

The main advantage of photochemical fluorodediazoniation lies in the fact that, under very mild conditions, UV irradiation promotes it more efficiently than most of the side reactions. Thus, this technique has been successfully applied to diazonium tetrafluoroborates which fail to deliver aryl fluorides thermally, such as 4,5-dimethoxy-2-[2-(trifluoroacetamido)ethyl]ben-zenediazonium tetrafluoroborate which is a precursor of 6-fluoro-substituted dopamine.251... 

It is not unusual to observe no reaction between diazonium ions and metal complexes (equation 119). Furthermore, a common side reaction is simple oxidation of the starting complex. It is thus sometimes necessary to carefully choose the ligands on the metal and substituents on the diazonium... 

Such treatment of the CIDNP results produced serious objections. Lippmaa et al. (1973), investigating the same reaction, revealed a strong 15N, 13C, and H CIDNP effect. The 13C nuclei in the phenoxyl C6-ring of the azo dye were not polarized. At the same time, the polarization of 15N nuclei of the azo bond and 13C nuclei at positions 1 and 2 of the phenyl ring connected with the diazo link was an exact replica of the polarization of the same nuclei in the diazonium salt. This has led to the conclusion that the diazo component polarizes as a result of the side reactions and that it is the diazo component that brings it to the azo dye. Thus, the CIDNP effect does not support the ion radical mechanism presented earlier. Several explanations for the observed CIDNP effect have been proposed. We want to discuss one of them here because it seems to explain a whole range of interactions of diazonium salts with oxyanions, an interaction that is accompanied by a pronounced polarization of nuclei. 

Binks and Ridd164 have made a complete kinetic study of the reaction of indole with several diazotized amines (p-nitroaniline, p-chloroaniline, sulfanilic acid, and aniline). Only the reaction with p-nitrodiazonium salt exhibits a simple kinetic form (pseudo first-order reaction) in the other cases the kinetics appear to be due to the superposition of two reactions, a normal azo-coupling reaction and an autocatalytic side reaction that removes diazonium ions, but does not form azo compounds. 

For the diazocoupling reaction, an undesirable side reaction of the main product and a second diazonium salt to forming a bisazo product is well known [54], Thus in our case, the large specific interfacial area and short molecular diffusion distance played important roles in removing the main product from the aqueous phase to the organic phase, which allowed the undesirable side reaction to be avoided. 

The reaction is in principle catalytic in TTF, and this was demonstrated by monitoring the reaction when substoichiometric quantities of TTF were used. Complete conversion of the diazonium salts could be achieved when >20 mol% of TTF was used, but incomplete reaction was seen with lesser amounts of TTF. This indicates that TTF is not the perfect catalyst, and that side reactions slowly consume TTF during the reaction. 

The best general reagent for the reductive elimination of the diazonium group is hypophosphorus acid. Reduction proceeds readily at 0-5° with an aqueous solution of the reagent. The yields of hydrocarbons are in the range of 60-85%. Hydrochloric acid is recommended for the diazo-tization except in certain cases in which nuclear halogenation occurs as a side reaction when this acid is used. 

Problem 23.20 (a) Coupling of diazonium salts with primary or secondary aromatic amines (but not with tertiary aromatic amines) is complicated by a side reaction that yields an isomer of the azo compound. Judging from the reaction of secondary aromatic amines with nitrous acid (S. 23.10), suggest a possible structure for this by-product. 

Aromatie aryla m. Decomposition of an aqueous solution of a diazonium salt at pH 8 in the presence of an aromatic compound proceeds poorly because of the heterogeneity of the mixture and because of side reactions. The process is improved by aptotic diazotization with amyl nitrite in the presence of the substrate. ... 

The most frequently used competitive reaction is the diazo-coupling of 1-naphthol with diazotized sulphanilic acid at a pH = 9.9, in which a single coupled (desired) and double coupled (undesired) products are formed (if the side-reaction in which the bis-azo-dye is decomposed due to the presence of excess diazonium ions is disregarded) ... 

The Schieman reaction (J ) was cited by Schlesinger (j ) and by Licari and Crepeau (14) as the probable mechanism by which initiators for cationic polymerization are released by diazonium salts. Rutherford et al ( ) showed side reactions to be minimized when the diazonium salt is a hexafluorophosphate. 

---