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 SN1 or SN2 reaction, characterized instead by
aryl radicals and cations. 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: : The deep colors of the dyes reflects their extended
conjugation. A popular azo dye is
aniline yellow, produced from
aniline. : 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 () 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 . For example, low-valent metal complexes add with diazonium salts. Illustrative complexes are and the chiral-at-metal complex .
Displacement of the group Arenediazonium cations undergo several reactions in which the 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 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, 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 , benzenediazonium chloride heated with
copper(I) dissolved in HCl or HBr yields
chlorobenzene or
bromobenzene, respectively: : The copper salt can be formed
in situ from copper powder, at the cost of a biaryl
byproduct (see ): : :
Potassium iodide does not require the copper catalyst: :
Fluorobenzene is produced by thermal decomposition of
benzenediazonium tetrafluoroborate. The conversion is called the . : The traditional Balz–Schiemann reaction has been the subject of many modification, e.g. using hexafluorophosphate(V) () and hexafluoroantimonate(V) () in place of tetrafluoroborate (). The inertness of fluoroanions allows the diazotization to be performed simultaneous with anion introduction, e.g. with
nitrosonium hexafluoroantimonate(V) ().
By a hydroxyl group Phenols are produced by heating aqueous solutions of arenediazonium salts: : This reaction goes by the German name
Phenolverkochung ("cooking down to yield phenols"). The phenol formed may react with the diazonium salt and hence the reaction is carried in the presence of an acid which suppresses this further reaction. A Sandmeyer-type hydroxylation is also possible using and in water.
By inorganic anions Nitrobenzene can be obtained by treating benzenediazonium fluoroborate with
sodium nitrite in presence of copper. Alternatively, the diazotisation of the aniline can be conducted in presence of cuprous oxide, which generates cuprous nitrite in situ: :
Nucleophilic aromatic substitution of
haloarenes can rarely introduce
cyanide moieties, but such compounds can be easily prepared from diazonium salts. Illustrative is the preparation of
benzonitrile using the reagent
cuprous cyanide: : Diazonium salts cannot be converted directly to thiols. But in the
Leuckart thiophenol reaction, displacement of benzenediazonium chloride with
potassium ethylxanthate gives an intermediate xanthate ester that hydrolyzes to
thiophenol: : :
By carbanion equivalents In the , benzenediazonium chloride reacts with compounds containing
activated double bonds to produce phenylated products: : Two research groups reported in 2013. Goossen reported the preparation of a complex from CuSCN, , and . In contrast, Fu reported the trifluoromethylation using Umemoto's reagent (
S-trifluoromethyldibenzothiophenium tetrafluoroborate) and Cu powder (Gattermann-type conditions). They can be described by the following equation: : The bracket indicates that other ligands on copper are likely present but are omitted. A
formyl group, –CHO, can be introduced by treating the aryl diazonium salt with formaldoxime (), followed by hydrolysis of the aryl aldoxime to give the aryl aldehyde. This reaction is known as the .
Biaryl coupling One aryl group can be coupled to another using arenediazonium salts. For example, treatment of
benzenediazonium chloride with benzene (an aromatic compound) in the presence of sodium hydroxide gives
diphenyl: : This reaction is known as the
Gomberg–Bachmann reaction. A similar conversion is also achieved by treating benzenediazonium chloride with
ethanol and copper powder. Alternatively, a pair of diazonium cations can be coupled to give
biaryls. This conversion is illustrated by the coupling of the
diazonium salt derived from
anthranilic acid to give
diphenic acid (). In a related reaction, the same diazonium salt undergoes loss of and to give
benzyne.
By hydrogen Arenediazonium cations reduced by
hypophosphorous acid,
ethanol,
sodium stannite or alkaline
sodium thiosulphate give the unsubstituted arene: : : : An alternative way suggested by Baeyer & Pfitzinger is to replace the diazo group with H is: first to convert it into hydrazine by treating with then to oxidize it into hydrocarbon by boiling with cupric sulphate solution.
Borylation A
Bpin (pinacolatoboron) group, of use in
Suzuki-Miyaura cross coupling reactions, can be installed by reaction of a diazonium salt with
bis(pinacolato)diboron in the presence of benzoyl peroxide (2 mol %) as an initiator: Alternatively similar borylation can be achieved using transition metal carbonyl complexes including dimanganese decacarbonyl. :
Grafting reactions In a potential application in
nanotechnology, the diazonium salts 4-chlorobenzenediazonium tetrafluoroborate very efficiently functionalizes
single wall nanotubes. In order to
exfoliate the nanotubes, they are mixed with an
ionic liquid in a
mortar and pestle. The diazonium salt is added together with
potassium carbonate, and after grinding the mixture at
room temperature the surface of the nanotubes are covered with chlorophenyl groups with an efficiency of 1 in 44 carbon atoms. These added
substituents prevent the tubes from forming intimate bundles due to large
cohesive forces between them, which is a recurring problem in nanotube technology. It is also possible to functionalize
silicon wafers with diazonium salts forming an
aryl monolayer. In one study, the silicon surface is washed with
ammonium hydrogen fluoride leaving it covered with silicon–hydrogen bonds (hydride passivation). The reaction of the surface with a solution of diazonium salt in
acetonitrile for 2 hours in the dark is a spontaneous process through a
free radical mechanism: So far, grafting of diazonium salts on metals has been accomplished on
iron,
cobalt,
nickel,
platinum,
palladium,
zinc,
copper, and
gold surfaces. Also grafting to diamond surfaces has been reported. One interesting question raised is the actual positioning on the aryl group on the surface. An
in silico study demonstrates that in the
period 4 elements from titanium to copper the
binding energy decreases from left to right because the number of d-electrons increases. The metals to the left of iron are positioned tilted toward or flat on the surface favoring metal to carbon
pi bond formation and those on the right of iron are positioned in an upright position, favoring metal to carbon
sigma bond formation. This also explains why diazonium salt grafting thus far has been possible with those metals to right of iron in the
periodic table. ==Biochemistry==