Molecular Catalysis
Facile dehydration of primary amides to nitriles catalyzed by lead salts: The
anionic ligand matters
a,
b
a,
b
a,
b
a,b,
Shixiang Ruan , Jiancheng Ruan , Xinzhi Chen , Shaodong Zhou
*
a
College of Chemical and Biological Engineering, Zhejiang Provincial Key Laboratory of Advanced Chemical Engineering Manufacture Technology, Zhejiang University,
Hangzhou, 310027, PR China
b
Institute of Zhejiang University - Quzhou, 78 Jiuhua Boulevard North, Quzhou, 324000, PR China
A R T I C L E I N F O
A B S T R A C T
Keywords:
The synthesis of nitrile under mild conditions was achieved via dehydration of primary amide using lead salts as
catalyst. The reaction processes were intensified by not only adding surfactant but also continuously removing
the only by-product, water from the system. Both aliphatic and aromatic nitriles can be prepared in this manner
with moderate to excellent yields. The reaction mechanisms were obtained with high-level quantum chemical
calculations, and the crucial role the anionic ligand plays in the transformations were revealed.
Catalytic dehydration of amide
Facile synthesis
Quantum chemical calculation
Process intensification
1
. Introduction
(O)Cl
2
[35], benzensulfonyl chloride [36], and trichloroacetyl chloride
[
37]. Unfortunately, these hydrants react with water to afford sto-
Nitriles constitutes an important class of raw materials or in-
chemical pollutional species. Both the laboratory and the industry needs
facile and clean dehydration of amides! Recent efforts on this topic focus
on catalytic dehydration of amides in the presence of hydrosilane. The
catalysts used are typically transition metals [38–52] or metal-free
species [53,54]. Though these methods permit the reaction to proceed
under neutral, mild conditions, stoichiometric dehydrants are still
required. Shi and coworkers [55] reported Pd-catalyzed decarbonylative
cyanation of amides to produce aryl nitriles – an important improve-
ment, while this protocol is not available for the synthesis of alkyl ni-
triles. Herein, we report a facile, simple protocol for the dehydration of
amides catalyzed by lead salts without using any dehydrant. It will be
shown later that the anionic component of the lead salt is crucial for the
reaction efficiency. The reaction mechanisms and the origins for the
experimental findings are revealed with quantum chemical calculations.
termediates that are widely employed in the production of polyamides,
pharmaceuticals, agrochemicals, dyes, pigments, and various fine
chemicals for their unique reactivity [1–5]. As the most known example,
adiponitrile is used to produce hexamethylene diamine, the raw mate-
rial of polyamide fiber [6–8]. In the past decades, various studies have
been reported for the synthesis of nitriles. Originally, stoichiometric
methods prevailed in both laboratories and industry, including
Rosenmund-von Braun reaction of aryl halides [9,10]. Schmidt reaction
of aldehydes [11], the diazotization of anilines with subsequent Sand-
meyer reaction [12], etc. However, due to (over) stoichiometric
amounts of the dehydration reagents used, the same amounts of wastes
are produced. Ammoxidation of olefins or alkanes seems to be a more
sustainable method, in which the olefins or alkanes react with oxygen
◦
and ammonia at 300ꢀ 550 C in the presence of a heterogeneous
fixed-bed catalyst [13–18]. However, this method is limited by harsh
reaction conditions.
2. Results and discussion
To obtain a facile method to produce nitriles, great efforts have been
made in developing more efficient catalytic systems [19–28]. The
dehydration of amides turns out to be a promising route to prepare the
corresponding nitriles [29]. However, classic dehydration of amides was
implemented using stoichiometric or excessive amount of dehydrants,
The dehydration of butanamide was chosen as the model reaction to
screening the reaction parameters (Scheme 1). The results are detailed in
Table 1.
To start with, the experiments were conducted in different solvents
(entries 1–6, Table 1). When the reaction was carried out in the hy-
drophilic solvent such as methanol (entry 1, Table 1), acetonitrile (entry
2 2 5 3 4 4
such as SOCl [30], P O [31] POCl [32], TiCl [33], NaBH [34], EtOP
*
Corresponding author at: College of Chemical and Biological Engineering, Zhejiang Provincial Key Laboratory of Advanced Chemical Engineering Manufacture
Received 11 September 2020; Received in revised form 1 November 2020; Accepted 9 November 2020
2
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