For interesting results allowing C(Ar)–N(noncyclic amides) coupling and not
described in the Sect. 2.2, see the following [150–164].
2.3 Coupling Reactions of Aryl Halides with NH 3
Anilines and their derivatives are important building blocks both for the fine and
commodity chemistry. Aniline is traditionally produced in a huge scale (>6 million
tons/year) from the hydrogenation of nitrobenzene, which requires very hard
conditions (300–600
C) in the presence of a transition metal catalyst. The nitrobenzene itself is synthesized from benzene under hard acidic conditions in a
mixture of water, nitric acid and sulfuric acid [198]. More sophisticated aniline
derivatives have been mainly prepared, particularly in the past decade, via the
palladium-catalyzed C–N bond formation resulting from the coupling of aryl
halides with ammonia surrogates (for recent reviews on arylation of ammonia by
Pd or Cu catalysts, see, e.g., [199–201]). However these efficient methods require a
deprotection step to obtain anilines and consequently result in the production of
unwanted side products. Therefore, the development of alternative processes for the
production of anilines and derivatives is of great importance, particularly in terms
of sustainable development. One possibility could be the direct use of ammonia as
the nitrogen source [199–201]. Indeed NH 3 is one of the simplest and cheapest bulk
chemicals and its use would allow reducing the amounts of waste. The latter has
however been rarely involved as a reagent in a catalytic process because of, for
example, its strong ability to coordinate transition metals, thus leading to an
inactivation of the catalyst. Another potential problem is the selectivity of the
reaction with the possible formation of diarylamines, the anilines formed in a
catalytic process being usually more reactive than NH 3 [202]. A punctual example
has been reported in 1999 by Vedej et al. in an intermediate step for the synthesis of
substituted isoquinolines [203]. A coupling between ammonia and a substituted aryl
bromide was obtained in the presence of an almost stoichiometric amount of
copper. As another limitation, the reaction was performed in 5 days under high
pressure in liquid NH 3 . Another protocol involving catalytic amount of copper was
later reported by a researcher at Merck [204] (for a more recent example of
Cu-catalyzed coupling between aryl halides and liquid ammonia, see also the
[205]). As drawbacks, the reaction was performed under pressure with liquid
ammonia and the scope was mainly limited to activated aromatic or heteroaromatic
bromide. Moreover, the presence of ethylene glycol being necessary for the success
of the reaction, the method encounters in all cases problems with the selectivity
because of competitive C–O arylation of the alcoholic solvent. After 2006,
palladium catalysts appeared as serious candidates for the coupling involving aryl
halides and NH 3 . The efficient direct synthesis of aniline derivatives has thus been
reported from ammonia and, depending on the method, aryl bromides, aryl
chlorides, or aryl tosylates [202, 206–209]. Drawbacks regarding these catalytic
systems include the use of toxic and expensive metal and sophisticated supporting
ligands and the use of strong bases and ammonia pressure in some cases. Finally,
184
F. Monnier and M. Taillefer
described in the Sect. 2.2, see the following [150–164].
2.3 Coupling Reactions of Aryl Halides with NH 3
Anilines and their derivatives are important building blocks both for the fine and
commodity chemistry. Aniline is traditionally produced in a huge scale (>6 million
tons/year) from the hydrogenation of nitrobenzene, which requires very hard
conditions (300–600
C) in the presence of a transition metal catalyst. The nitrobenzene itself is synthesized from benzene under hard acidic conditions in a
mixture of water, nitric acid and sulfuric acid [198]. More sophisticated aniline
derivatives have been mainly prepared, particularly in the past decade, via the
palladium-catalyzed C–N bond formation resulting from the coupling of aryl
halides with ammonia surrogates (for recent reviews on arylation of ammonia by
Pd or Cu catalysts, see, e.g., [199–201]). However these efficient methods require a
deprotection step to obtain anilines and consequently result in the production of
unwanted side products. Therefore, the development of alternative processes for the
production of anilines and derivatives is of great importance, particularly in terms
of sustainable development. One possibility could be the direct use of ammonia as
the nitrogen source [199–201]. Indeed NH 3 is one of the simplest and cheapest bulk
chemicals and its use would allow reducing the amounts of waste. The latter has
however been rarely involved as a reagent in a catalytic process because of, for
example, its strong ability to coordinate transition metals, thus leading to an
inactivation of the catalyst. Another potential problem is the selectivity of the
reaction with the possible formation of diarylamines, the anilines formed in a
catalytic process being usually more reactive than NH 3 [202]. A punctual example
has been reported in 1999 by Vedej et al. in an intermediate step for the synthesis of
substituted isoquinolines [203]. A coupling between ammonia and a substituted aryl
bromide was obtained in the presence of an almost stoichiometric amount of
copper. As another limitation, the reaction was performed in 5 days under high
pressure in liquid NH 3 . Another protocol involving catalytic amount of copper was
later reported by a researcher at Merck [204] (for a more recent example of
Cu-catalyzed coupling between aryl halides and liquid ammonia, see also the
[205]). As drawbacks, the reaction was performed under pressure with liquid
ammonia and the scope was mainly limited to activated aromatic or heteroaromatic
bromide. Moreover, the presence of ethylene glycol being necessary for the success
of the reaction, the method encounters in all cases problems with the selectivity
because of competitive C–O arylation of the alcoholic solvent. After 2006,
palladium catalysts appeared as serious candidates for the coupling involving aryl
halides and NH 3 . The efficient direct synthesis of aniline derivatives has thus been
reported from ammonia and, depending on the method, aryl bromides, aryl
chlorides, or aryl tosylates [202, 206–209]. Drawbacks regarding these catalytic
systems include the use of toxic and expensive metal and sophisticated supporting
ligands and the use of strong bases and ammonia pressure in some cases. Finally,
184
F. Monnier and M. Taillefer