Selective aerobic oxidation of halides and amines with an inorganic-ligand supported zinc catalyst

Article abstract of DOI:10.1039/c8dt03003k

A practical, efficient and environmentally benign catalytic protocol for the oxidative cross-coupling reaction of halides with amines, oxidative self-coupling of amines and oxidation of halides was developed with inorganic-ligand supported ZnPOM (NH₄)₄[ZnMo₆O₁₈(OH)₆] using molecular oxygen. This method mainly utilizes an inorganic polymolybdate ligand to support the Zn²⁺ ion, avoiding the use of complicated organic ligands.

Full text of DOI:10.1039/c8dt03003k

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Selective aerobic oxidation of halides and amines
with an inorganic-ligand supported zinc catalyst†
Cite this: DOI: 10.1039/c8dt03003k
Jingjing Wang,‡a Yongyan Zhai,‡a Ying Wang,‡a Han Yu,*a,c Wenshu Zhao*b and
Received 23rd July 2018,
Accepted 21st August 2018
c
Yongge Wei
*
DOI: 10.1039/c8dt03003k
rsc.li/dalton
A
practical, efficient and environmentally benign catalytic
Catalytically active, stable complexes involving low-valence
protocol for the oxidative cross-coupling reaction of halides with metal ions supported/coordinated by metal oxides are poten-
amines, oxidative self-coupling of amines and oxidation of tial candidates. Many of these inorganic-ligand coordinated
halides was developed with inorganic-ligand supported ZnPOM complexes contain well-dispersed metal ions bound with the
(NH4)4[ZnMo6O18(OH)6] using molecular oxygen. This method inorganic scaffold via a variable number of metal–oxygen
mainly utilizes an inorganic polymolybdate ligand to support the bonds, thus providing complexes which are more stable than
Zn2+ ion, avoiding the use of complicated organic ligands.
organometallic catalysts. Inspired by this idea, polyoxo-
metalates (POMs),6 types of discrete metal-oxo clusters, are
considered to be inorganic alternatives to synthesize classical
transition-metal complexes. The catalytic function of POMs
has attracted much attention because of their multiple active
sites, including protons, oxygen atoms, and metals allows for
“fine-tuning” of their redox activities and acidic properties at
the atomic or molecular levels. Recently, our group reported
firstly that the Anderson-type POMs can be used as the
inorganic-ligand supported metal catalysts for highly efficient
aerobic oxidation of aldehydes to carboxylic acids in water, or
the oxidation of amines to imines under mild conditions.7
Herein, we report an efficient and environmentally friendly
transformation from organic halides to aldehydes/ketones and
imines to amines using an inorganic-ligand supported zinc cata-
lyst, (NH4)4[ZnMo6O18(OH)6] (1) (Fig. 1b) (for characterization
see the ESI†). Catalysis is performed under mild conditions with
molecular oxygen as the terminal oxidant, and it shows good
Zinc metal is abundant in the Earth’s crust and it has a certain
biological relevance as an essential trace element in humans.1
Recently, great progress in the use of cheaper and low toxicity
zinc complexes to replace precious metal catalysts (e.g. Rh, Pd,
Ir, Ru, etc.) has been made in modern chemistry. In 2008,
Nicholas and co-workers reported that benzylic and allylic C–H
bonds are successfully converted to related secondary amines
in good yields.2 In 2012, the Wu group reported a general and
efficient zinc catalyzed oxidation of benzyl alcohol to alde-
hydes which are important intermediates for fragrances and
many drugs.3 The examples impressively show the potential of
zinc catalysts in oxidation chemistry. In general, the catalytic
effect can only be produced by the interaction of the metal
center with organic ligands which often suffer from severe pro-
blems including cost, toxicity, air/moisture sensitivity and
being commercially unavailable (Fig. 1a).4 Moreover, it is
difficult to separate the catalyst from the reaction system.
Therefore, developing an efficient, stable, and recyclable zinc
catalytic system is of great significance.5
aSchool of Chemical and Environmental Engineering, Shanghai Institute of
Technology, Shanghai 201418, P.R. China. E-mail: scihanyu@163.com,
yonggewei@mail.tsinghua.edu.cn
bLonghua Hospital Shanghai University of Traditional Chinese Medicine, 725 South
Wanping Road, Shanghai 200032, P. R. China. E-mail: Wenshuzhao005@163.com
cKey Lab of Organic Optoelectronics & Molecular Engineering of Ministry of
Education, Department of Chemistry, Tsinghua University, Beijing 100084,
P.R. China
†Electronic supplementary information (ESI) available: Experimental con-
ditions, supplementary table and NMR spectra. See DOI: 10.1039/c8dt03003k
‡Contributed equally to this work.
Fig. 1 Catalytic systems.
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Table 1 Investigation of the substrate scope on the cross-coupling of
halides and aminesa
stability and reusability. And the catalytic oxidation could
readily be scaled up to the gram-scale with little loss of cata-
lytic activity.
Imines, known as Schiff bases, are key synthetic intermedi-
ates in the synthesis of biologically and fragrances, agricultural
chemicals and pharmaceuticals.8 In recent years, the cross-
coupling reaction of alcohols with amines has been one of the
most popular synthesis approaches due to its use of green
molecular oxygen as the terminal oxidant and water being the
only by-product.9 But alcohols are mainly obtained by the
hydrolysis of halogenated hydrocarbons both in the laboratory
and in industry.10 From the point of view of atom economy, we
present here an inorganic-ligand supported zinc-catalyst for
the oxidative cross-coupling reaction of halides with amines
and oxidation reactions of various halides with oxygen acting
as the sole oxidant (Scheme 1).
Initially, we selected benzylamine and benzyl chloride as
model substrates for the oxidative cross-coupling reaction and
gained N-benzylidenebenzylamine 3a with 32% yield and 47%
selectivity (Table S1,† entry 1). By screening the solvent, aceto-
nitrile is the best solvent with 89% yield and 90% selectivity
(Table S1,† entries 1–9). Moreover, both shortening and
prolonging the reaction time have an impact on the yield
a Reaction conditions: 1.0 mol% cat. 1, 1.0 mmol amines, 1.0 mmol
halides, O2 (1 atm, balloon), 2.0 mL MeCN, and 60 °C for 24 h.
b Determined by GC and confirmed by GC-MS.
(Table S1,† entries 10 and 11). 60 °C is the optimum reaction 3a). When coupling with benzylamine, benzyl chloride with
temperature (Table S2,† entries 1–3). When taking electron-donating substituents generally resulted in higher
ZnSO4·7H2O, (NH4)6Mo7O24·4H2O as the catalyst alone or in yields than substrates bearing electron-withdrawing substitu-
the absence of a catalyst, no desired product was detected ents, probably due to the higher nucleophilicity of the former
(Table S2,† entries 4–6). 1.0 mol% is the optimal catalyst (compounds 3b–3f). The reaction of benzylamine with hetero-
loading (Table S2,† entries 7 and 8). Switching from a pure cyclic functionalized chloride such as 3-(chloromethyl)pyridine
oxygen atmosphere to air under the same atmospheric and 2-(chloromethyl)thiophene produced the corresponding
pressure also led to 18% yield (Table S2,† entry 9). When the imines in 88% and 89% yields, respectively (compounds 3g
reaction was carried out under a nitrogen atmosphere, a very and 3h). In view of more challenging aliphatic chloride,
low yield was obtained (<10%), implying a stoichiometric (chloromethyl)cyclohexane and 1-chloropentane gave the corre-
oxidation reaction (Table S2,† entry 10).
sponding imines in 86% and 80% yields, respectively (com-
With the optimal conditions in hand, the general applica- pounds 3i and 3j). Switching from benzylamine to other
bility for the oxidative coupling reaction of various amines and amines, the catalytic coupling of benzyl chloride with aniline
halides was examined, as shown in Table 1. Benzyl chloride, under analogous reaction conditions yielded 90% of the
benzyl bromide and benzyl iodide were smoothly cross- corresponding imines (compound 3k). Benzyl chloride with
coupled with benzylamine to yield N-benzylidenebenzylamine aniline substrates containing both electron-donating and elec-
with a yield of 93%, 94% and 89%, respectively (compound tron-withdrawing groups also has good tolerance (compounds
3l and 3m). Both cyclic and aliphatic amines reacted efficiently
with benzyl chloride to produce the imine products in excel-
lent yields (compounds 3n–3p). Notably, the most challenging
coupling of aliphatic chlorides and aliphatic amines was also
promoted by catalyst (1) to afford the corresponding imines,
albeit in relatively lower but reasonable yields (compound 3q).
Inspired by this study, we next checked the applicability of
this aerobic protocol in the synthesis of symmetrical imines
under the optimal conditions (Table S3†). This reaction is very
well tolerated. Benzylamines which have electron-donating or
-withdrawing substituents were converted into their corres-
ponding products with high yields by a zinc catalyst (Table 2,
compounds 5a–5p). However, benzylamines with electron-
donating groups (compounds 5h–5j) showed more efficiency
than those with electron-withdrawing groups (compounds
Scheme 1 Oxidation of halides to aldehydes or ketones and amines to
imines.
5b–5g). In addition, the benzylamine having a methyl group at
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Table 2 Investigation of the substrate scope on oxidative coupling
reactions and the self-coupling of aminesa
Table 3 Investigation of substrate scope on the oxidation of benzyl
halidesa
a Reaction conditions: 1.0 mol% cat. 1, 1.0 mmol halides, O2 balloon,
2.0 mL MeCN/H2O (1 : 1), and 60 °C for 12 h. b Determined by GC and
confirmed by GC-MS. Values in parentheses are the isolated yields.
a Reaction conditions: 1.0 mol% cat. 1, 1.0 mmol amines, O2 (1 atm,
balloon), 2.0 mL MeCN, and 60 °C for 24 h. b Determined by GC and
confirmed by GC-MS. Values in parentheses are the isolated yields.
On the whole, the former has a lower impact than the latter on
yield, probably because the latter increases the electron cloud
an ortho position (compound 5j) showed a slight decrease in density on the aromatic ring, which the latter have the pres-
product yield in comparison to the para isomer (compound 5i) ence of the electron donating group. Moreover, we discover
owing to steric hindrance. Heterocyclic amine compounds that this reaction has a certain steric effect. Among the para-,
such as furan-2-ylmethanamine and thiophene-methylamine meta- and ortho-substituents, the para-substituent shows a
were also examined (compounds 5k and 5l) and gave modest slightly better yield (compounds 7b, 7e, 7f, 7d and 7g).
yields. It was found that inert 1-butylamine can also be con- Despite this, 2-(chloromethyl)-1,3,5-trimethylbenzene afforded
verted to related imine (compound 5m). Secondary dibenzyla- 2,4,6-trimethylbenzaldehyde in 90% yield (compound 7l).
mine also yielded the corresponding imine with moderate 2-(Chloromethyl)naphthalene produced the corresponding pro-
yield (compound 5n). To our satisfaction, 1,2,3,4-tetrahydro- ducts in good yields (compound 7n). What’s more, as for inert
quinoline was also successfully converted to the corresponding cyclic or aliphatic halides, we also obtained the corresponding
imine in 85% yield, which is an important pharmaceutical aldehyde products in moderate yields (compounds 7o and 7p).
intermediate (compound 5o). Moreover, dibenzylamine was Notably, this may be accompanied by by-products of the
converted to N-benzylidenebenzylamine with 90% yield (com- corresponding acid. Moreover, we conducted secondary benzyl
pound 5p). These results suggest that the inorganic-ligand halide oxidation to ketones (compounds 7q–7y). Secondary
supported zinc catalyst is promising to promote the oxidative benzyl chlorides with electron-withdrawing groups (–Cl, –F) or
coupling reactions of various amines.
an electron-donating group (–CH3) provided good yields (com-
To demonstrate the general applicability of the inorganic- pounds 7r–7t). The heterocyclic secondary benzyl chloride also
ligand supported zinc catalyst, various primary and secondary generated related ketones in good yields (compounds 7u–7w).
halides were investigated to produce aldehydes or ketones In addition, 2-(chloromethyl)naphthalene and chlorodiphenyl-
under the optimal reaction conditions (Table S4†). As depicted methane gave 90% and 85% yields of the corresponding
in Table 3, various primary and secondary halides react to give desired ketones (compounds 7x and 7y).
the desired products in good yields (compounds 7a–7y). No
On the basis of the above experiments and existing litera-
matter what electron-withdrawing or electron-donating sub- ture,11 we propose a plausible mechanism, as shown in Fig. 2.
strates, all gave related aldehyde or ketone products. Aryl In the first step Zn-POM activates oxygen molecules to form
halides possessing electron-withdrawing substrates such as the peroxo intermediates B.12 The active component B is then
4-F, 4-Cl, 4-Br, and 4-NO2 provided excellent yields, respectively subjected to the reaction path producing compound C with a
(compounds 7b–7h). But aryl halides with electron-rich groups high oxidation state that is from the heterolytic cleavage of the
like –CH3, –OCH3, –C(CH3)2, and –CN produced 95%, 95%, O–O bond. Subsequently the amine substrate reacts with C to
92%, and 93% yields, respectively (compounds 7i–7k and 7m). generate active intermediate D, which can further form the
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but also conveniently-recoverable because of heterogeneous
reaction. In addition, compared with precious metals such as
rhodium, ruthenium and palladium, the inorganic ligand cata-
lysts avoid the use of toxic, air and water-sensitive organic
ligands. Hence, we believe that inorganic ligand-modified
heteropolyacids still have great potential as heterogeneous cat-
alysts in organic synthesis. This work is currently underway in
our laboratory.
Conflicts of interest
Fig. 2 Proposed mechanism for the formation of aldehydes, ketones
and imines.
There are no conflicts to declare.
NH-imine intermediate. In other words, the amine substrate is
activated under the action of the catalyst and then dehydro-
Acknowledgements
genated to afford the NH-imine intermediate. The unstable We are grateful for the National Natural Science Foundation of
intermediate was decomposed by the release of NH3, followed China (No. 21471087, 21631007 and 21225103), the Doctoral
by coupling with another amine substrate, forming the final Fund of Ministry of Education of China No. 20130002110042,
imine product and completing the catalytic cycle. Similar to the Tsinghua University Initiative Foundation Research
the halide oxidation process and the oxidative coupling of Program No. 20131089204, and the State Key Laboratory of
halides with amine substrates, the alcohol substrate derived Natural and Biomimetic Drugs K20160202. The start-up fund
from the hydrolysis of halides can also coordinate with the of Shanghai Institute of Technology is also gratefully
active substance C to produce the active intermediate E, which acknowledged.
in turn gives the aldehyde intermediate. If there is no other
substance in the system, dehydes are formed. But in addition
to halides, if there are amines in the reaction system, conden-
sation can occur to produce an asymmetric imidized product.
Notes and references
According to the above assumption of the mechanism, the key
to the success of the catalytic reaction is the formation of inter-
mediate C. Furthermore we detected the presence of aldehydes
in the course of the experiment by GC-MS, and this also veri-
fied the reliability of the mechanism.
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