Diazonium compound

"Diazo process" redirects here. For the reproduction of prints using the diazo chemical process, see Whiteprint.

Benzenediazonium cation

Diazonium compounds or diazonium salts are a group of organic compounds sharing a common functional group [R−N⁺≡N]X⁻ where R can be any organic group, such as an alkyl or an aryl, and X is an inorganic or organic anion, such as a halide. The parent compound, where R is hydrogen, is diazenylium.

Structure and general properties

Arene derivatives

According to X-ray crystallography the C−N⁺≡N linkage is linear in typical diazonium salts. The N⁺≡N bond distance in benzenediazonium tetrafluoroborate is 1.083(3) Å, which is almost identical to that for dinitrogen molecule (N≡N).

The linear free energy constants σ_m and σ_p indicate that the diazonium group is one of the most strongly electron-withdrawing substituents known. Thus, the diazonio-substituted phenols and benzoic acids have greatly reduced pK_a values compared to their unsubstituted counterparts. The pK_a of phenolic proton of 4-hydroxybenzenediazonium is 3.4, versus 9.9 for phenol itself. In other words, the diazonium group raises the ionization constant K_a (enhances the acidity) by a million-fold. This also causes arenediazonium salts to have decreased reactivity when electron-donating groups are present on the aromatic ring.

The stability of arenediazonium salts is highly sensitive to the counterion. Benzenediazonium chloride is dangerously explosive, whereas benzenediazonium tetrafluoroborate has been described as shock insensitive.

Alkane derivatives

Alkanediazonium salts are generally synthetically unimportant due to their extreme and uncontrolled reactivity toward S_N2/S_N1/E1 substitution or elimination. These cations are, however, of theoretical interest for study of these reactions. Furthermore, methyldiazonium carboxylate is believed to be an intermediate in the methylation of carboxylic acids by diazomethane, a common transformation.

Methylation with diazomethane

With the exception of methyldiazonium, loss of N₂ is both enthalpically accessible and entropically favorable:

[CH₃N₂]⁺ → [CH₃]⁺ + N₂, ΔH = +43 kcal/mol

[CH₃CH₂N₂]⁺ → [CH₃CH₂]⁺ + N₂, ΔH = +11 kcal/mol

For ethyl and higher primary alkanediazonium species, dediazotization takes place rapidly at room temperature and is rendered irreversible by loss of N₂. For secondary and tertiary alkanediazonium species, the enthalpic change is calculated to be close to zero or negative, with minimal activation barrier. Hence, secondary and (especially) tertiary alkanediazonium species are either unbound species or, at best, extremely fleeting intermediates.

The aqueous pK_a of methyldiazonium ([CH₃N₂]⁺) is estimated to be <10.

Preparation

See also: Nitrosation

The process of forming diazonium compounds is called "diazotation", "diazoniation", or "diazotization". The reaction was first reported by Peter Griess in 1858, who subsequently discovered several reactions of this new class of compounds. Most commonly, diazonium salts are prepared by treatment of aromatic amines with nitrous acid and additional acid. Usually the nitrous acid is generated in situ (in the same flask) from sodium nitrite and the excess mineral acid (usually aqueous HCl, H₂SO₄, p-H₃CC₆H₄SO₃H, or H[BF₄]):

ArNH₂ + HNO₂ + HX → [ArN₂]⁺X⁻ + 2 H₂O

Sample of benzenediazonium tetrafluoroborate

Chloride salts of diazonium cation, traditionally prepared from the aniline, sodium nitrite, and hydrochloric acid, are unstable at room temperature and are classically prepared at 0–5 °C. However, one can isolate diazonium compounds as tetrafluoroborate or tosylate salts, which are stable solids at room temperature. It is often preferred that the diazonium salt remain in solution, but they do tend to supersaturate. Operators have been injured or even killed by an unexpected crystallization of the salt followed by its detonation.

Due to these hazards, diazonium compounds are often not isolated. Instead they are used in situ. This approach is illustrated in the preparation of an arenesulfonyl compound:

Alternatively, an easily prepared diazo cation can transfer the diazotation to another amine through a triazene intermediate (compare diazo transfer).

Reactions

Arenediazonium salts are highly versatile reagents. After electrophilic aromatic substitution, diazonium chemistry is the most frequently applied strategy to prepare aromatic compounds.

In general, two reactions are possible for diazonium salts: reductive additions to arenes ("diazo coupling") and hydrazines, and substitution. The latter case is no simple S_N1 or S_N2 reaction, characterized instead by aryl radicals and cations.

Reductive additions

Diazo coupling

The first and still main use of diazonium salts is azo coupling, which is exploited in the production of azo dyes. In some cases water-fast dyed fabrics are simply immersed in an aqueous solution of the diazonium compound, followed by immersion in a solution of the coupler (the electron-rich ring that undergoes electrophilic substitution). In this process, the diazonium compound is attacked by, i.e., coupled to, electron-rich substrates. When the coupling partners are arenes such as anilines and phenols, the process is an example of electrophilic aromatic substitution:

[ArN₂]⁺ + Ar'H → ArN₂Ar' + H⁺

The deep colors of the dyes reflects their extended conjugation. A popular azo dye is aniline yellow, produced from aniline. Naphthalen-2-ol (beta-naphthol) gives an intensely orange-red dye. Methyl orange is an example of an azo dye that is used in the laboratory as a pH indicator..

Another commercially important class of coupling partners are acetoacetic amides, as illustrated by the preparation of Pigment Yellow 12, a diarylide pigment.

To hydrazines

Diazonium salts can be reduced with stannous chloride (SnCl₂) to the corresponding hydrazine derivatives. This reaction is particularly useful in the Fischer indole synthesis of triptan compounds and indometacin. The use of sodium dithionite is an improvement over stannous chloride since it is a cheaper reducing agent with fewer environmental problems.

Metal complexation

In their reactions with metal complexes, diazonium cations behave similarly to NO⁺. For example, low-valent metal complexes add with diazonium salts. Illustrative complexes are [Fe(CO)₂(PPh₃)₂(N₂Ph)]⁺ and the chiral-at-metal complex Fe(CO)(NO)(PPh₃)(N₂Ph).

Displacement of the N₂ group

Arenediazonium cations undergo several reactions in which the N₂ group is replaced by another group or ion. The process is a formal nucleophilic aromatic substitution reaction, and the basis of the Sandmeyer Reaction, the Gomberg-Bachmann reaction and the Schiemann reaction.

The N+2 group is extremely fragile, and displacement can be initiated by:

• organic reduction at an electrode
• mild reducing agents such as ascorbic acid (vitamin C)
• gamma radiation from solvated electrons generated in water
• photoinduced electron transfer
• reduction by metal cations, most commonly a cuprous salt.
• anion-induced dediazoniation; a counterion such as iodine gives electron transfer to the diazonium cation forming the aryl radical and an iodine radical
• solvent-induced dediazoniation with solvent serving as electron donor.

Nevertheless, N₂ departure is also somewhat reversible, as indicated by the isotope scrambling of the nitrogen atoms.

In many applications, the diazonium salt is produced in situ, to avoid premature reaction. In the so-called Craig method, 2-aminopyridine reacts with sodium nitrite, hydrobromic acid, and excess bromine to 2-bromopyridine.

By halides

In the Sandmeyer Reaction, benzenediazonium chloride heated with copper(I) dissolved in HCl or HBr yields chlorobenzene or bromobenzene, respectively:

[C₆H₅N₂]⁺ + CuCl → C₆H₅Cl + N₂ + Cu⁺

The copper salt can be formed in situ from copper powder, at the cost of a biaryl byproduct (see § Biaryl coupling):

2 Cu + 2 [C₆H₅N₂]⁺ → 2 Cu⁺ + (C₆H₅)₂ + 2 N₂ (initiation)

[C₆H₅N₂]⁺ + HX → C₆H₅X + N₂ + H⁺ (Cu⁺ catalysis)

Potassium iodide does not require the copper catalyst:

[C₆H₅N₂]⁺ + KI → C₆H₅I + K⁺ + N₂

Fluorobenzene is produced by thermal decomposition of benzenediazonium tetrafluoroborate. The conversion is called the Balz–Schiemann reaction.

[C₆H₅N₂]⁺[BF₄]⁻ → C₆H₅F + BF₃ + N₂

The traditional Balz–Schiemann reaction has been the subject of many modification, e.g. using hexafluorophosphate(V) ([PF₆]⁻) and hexafluoroantimonate(V) ([SbF₆]⁻) in place of tetrafluoroborate ([BF₄]⁻). The inertness of fluoroanions allows the diazotization to be performed simultaneous with anion introduction, e.g. with nitrosonium hexafluoroantimonate(V) ([NO]⁺[SbF₆]⁻).