Synthesis of imines from amines in aliphatic alcohols on Pd/ZrO2 catalyst under ambient conditions

Article abstract of DOI:10.1039/c3ra44625e

Synthesis of imines from amines and aliphatic alcohols (C ₁-C₆) in the presence of base on supported palladium nanoparticles has been achieved for the first time. The catalytic system shows high activity and selectivity in open air at room temperature.

Full text of DOI:10.1039/c3ra44625e

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Synthesis of imines from amines in aliphatic
alcohols on Pd/ZrO2 catalyst under ambient
Cite this: RSC Adv., 2014, 4, 2601
conditions†
a
Wenjing Cui,ab Bao Zhaorigetu, Meilin Jia,a Wulan Aoa and Huaiyong Zhuc
Received 23rd August 2013
Accepted 28th October 2013
*
DOI: 10.1039/c3ra44625e
www.rsc.org/advances
Synthesis of imines from amines and aliphatic alcohols (C1–C6) in the Ru-catalyzed,10 Ir-catalyzed,11 Pd-catalyzed,12 Au-catalyzed,13 Cu-
presence of base on supported palladium nanoparticles has been catalyzed9,14 and base-catalyzed15 imines synthesis from amines
achieved for the first time. The catalytic system shows high activity and and alcohols were reported. However, these reactions are always
selectivity in open air at room temperature.
limited to aromatic (benzylic) alcohols and unsaturated (cin-
namyl, allylic and propargyl) alcohols, which can be oxidized
readily to corresponding aldehydes.12–14,15b,16 Aliphatic alcohols
are more difficult to activate than aromatic alcohols and
unsaturated alcohols. Several methods are available to synthe-
size imines from amines and aliphatic alcohols, but severe
drawbacks still remain. For example, Ru catalysts required high
temperature (reux), prolonged reaction periods (24–56 h) to
Imines, a kind of nitrogenated compounds, are used as lip-
oxygenase inhibitors, anti-inammatory agents and anti-cancer
agents in therapeutic applications as well as nucleophilic
addition reagents in organic reactions.1 Synthesis and applica-
tion of imines play a pivotal role in modern organic synthesis.2
Generally, condensation of amine and carbonyl compound
(aldehyde or ketone) is used for the synthesis of imines.3
However, owing to the unstable and reactive nature of the
electrophilic carbonyl compound, it is desirable to obtain
imines from more stable compounds.4 Oxidation of secondary
amines,1,5 self-coupling of amines6 and coupling of alcohols and
amines7 are alternative methods for imines synthesis. It
commonly requires higher temperature (around 100 ꢀC), O2
atmosphere as well as longer reaction time (>24 h) to produce
imines through oxidation of secondary amines.5a,8 The products
of self-coupling of amines are always limited to symmetric
imines.9 Coupling of alcohols and amines is the superior choice
as alcohols are much greener, more stable and readily available
starting materials. The possible reaction mechanism involves:
an alcohol is oxidized to the reactive carbonyl compound (key
step), which aerwards condenses with an amine to form an
unstable intermediate, hemiaminal, which nally transforms to
the imine by elimination of one molecule of water (Scheme 1).
form desired imines with moderate selectivity and yield.10b,17
A
recent Au/Pd alloy catalyst was employed to synthesize imines
under 60 ꢀC, however, only 58% yield of imine was obtained
aer 12 h. In this catalytic system, benzylamine and octanol
were used as substrates and dioxygen was necessary for the
oxidation.18 The coupling reactions of amines with aliphatic
alcohols were great challenges,10b,14,15,19 and to the best of our
knowledge, imines are synthesized from amines with smaller
and less reactive aliphatic alcohols (C1–C6) was not known yet.
We herein report an original and efficient method for
synthesis of imine by adding amine in aliphatic alcohol (C1–C6)
which acting as both reagent and solvent.
Initially, 1 wt% Pd/ZrO2 catalyst was prepared according to
the literiture.20 TEM image (Fig. S1a†) shows that palladium
nanoparticles (Pd NPs) are spheroidal in shape and well-
dispersed on ZrO2 support. The particle size distribution is
within the region of ca. 2–8 nm with average size of 5 nm
(Fig. S1b†). The diffraction peaks of XRD characterization are
assigned to the baddeleyite ZrO2 phase. No crystal Pd can be
aInner Mongolia Key Laboratory of Green Catalysis, Inner Mongolia Normal
University, Hohhot, China. E-mail: wenjing_cui@126.com; zrgt@imnu.edu.cn; Fax:
+86 0471-4392036; Tel: +86 0471-4393099
bCollege of Chemical Engineering, Inner Mongolia University of Technology, Hohhot,
010051, China
cSchool of Chemistry, Physics and Mechanical Engineering, Queensland University of
Technology, Queensland, 4001, Australia
† Electronic supplementary information (ESI) available. See DOI:
10.1039/c3ra44625e
Scheme 1 Likely mechanism for synthesis of imines from amines and
alcohols.
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Table 2 The reaction of different alcohols with benzylaminea
detected, which conrmed Pd NPs are highly dispersed
(Fig. S2†). XPS information of the catalyst suggests that the Pd0
presented on the surface of the catalyst (Fig. S3†).
Subsequently, benzylamine (1a) and ethanol (2a) were used
as model compounds to investigate synthesis of N-ethyl-
idenebenzylamine (3aa) on 1 wt% Pd/ZrO2 under various
conditions and the results are summarized in Table 1. When the
reaction of 1a with 2a was carried out at 20 ꢀC, the yield of 3aa
was much lower (entry 1). Further increasing the temperature,
the yield was improved. The most efficient temperature was
30 ꢀC as the yield of desired imine was not further improved at
40 ꢀC (entries 2 and 3). The selectivity of 3aa was almost full, and
no other byproduct was detected in the reaction.
The effect of the base was also examined (entries 4–7). The
base was considered to be essential for the rst hydrogen
abstraction in the oxidation of alcohols21 and no product was
detected in the reaction without base. KOH and NaOH are the
most efficient bases for synthesis of imines. Other base, K2CO3
and Na2CO3, furnished the imine in lower yield. It appears that
the alkalinity of the base has signicant inuence on the
conversion of the benzylamine, while the excellent selectivity of
imine was always observed for each of bases. Furthermore, the
high reaction efficiency still remained when the amount of KOH
was reduced, so it was more cost effective to x the amount of
KOH to 0.1 mmol rather than any others (entries 8–10).
With the optimized reaction conditions, a series of aliphatic
alcohols and amines were tested to explore the scope and
limitation of the catalytic system (Table 2). The selectivity to
desired imine was incredible and no other reported products,
such as secondary amine and amide, were detected. The reac-
tion of benzylamine with primary aliphatic alcohols afforded
the products (3aa–ah) in good to excellent yields and the yields
of imines from benzylamine with linear primary aliphatic
alcohols (entries 1–6) are higher than that with branched
primary aliphatic alcohols (entries 7 and 8). However, the
Entry
1
2
Yieldb (%)
1
2
3
1a
1a
1a
CH3–OH (2b)
85
94
84
2a
4
5
6
1a
1a
1a
83
96
82
7
8
9
1a
1a
1a
77 (86)d
70 (83)d
10 (76)c,d
10
11
12
1a
1a
1a
12 (97)c
2 (97)c
0
13
14
15
2a
2a
2a
99e
99e
99e
16
2a
99e
Table 1 Optimization of the reaction conditionsa
17
18
2a
2a
99e
99e
19
20
2a
2a
99e
99e
Entry Base, x (mmol) Temp. (ꢀC) Yieldb (%) TON TOF (hꢁ1
)
1
2
3
4
5
6
7
8
9
10
KOH, 0.5
KOH, 0.5
KOH, 0.5
NaOH, 0.5
Na2CO3, 0.5
K2CO3, 0.5
KOH, 0
KOH, 0.3
KOH, 0.1
KOH, 0.05
20
30
40
30
30
30
30
30
30
30
57
94
94
93
23
75
0
94
92
87
606 165
1000 238
1000 270
989 220
21
22
2a
2a
99e
99e
245
63
798 167
0
0
1000 239
979 221
926 207
23
2a
31(43)d
a
a
Reaction conditions: 1 (1 mmol), 2 (10 mL), 1 wt% Pd/ZrO2 (10 mg),
Reaction conditions: 1a (1 mmol), 2a (10 mL), 1 wt% Pd/ZrO2 (10 mg),
base, air atmosphere, 30 ꢀC, 6 h. TON ¼ n (converted benzylamine)/n
(Pd); TOF (hꢁ1) ¼ TON at the rst hour. b Yield was determined by GC
analysis.
b
KOH (0.1 mmol), air atmosphere, 30 ꢀC, 6 h. Yield was determined
by GC analysis. 10 mg Au–Pd/ZrO2. Reaction time 12 h. Reaction
time 3 h.
c
d
e
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reaction of benzylamine with secondary aliphatic alcohols only decreasing the selectivity of imines which were synthesized
gave the corresponding imines (3ai–ak) in lower yields under from carbonyls and amines. Therefore, we further inferred the
the same conditions (entries 9–11). Firstly, this is attributed to high imine selectivity in our reaction system depended on the
the steric hindrance of secondary alcohols, so it makes difficult low concentration of carbonyls which were generated by alco-
to oxidize secondary alcohols into ketones. In addition, ketones hols and consumed readily in situ with amine.
react with amines more slowly to form ketimines than alde-
In conclusion, we developed a one-pot method for the direct
hydes do.7b The reaction using tertiary alcohol (tert-butyl synthesis of imines catalyzed by 1 wt% Pd/ZrO2 at 30 ꢀC under
alcohol) was also examined, however, it resulted in no reaction air atmosphere. This is a general, efficient and versatile access
(entry 12). It was obviously because tertiary alcohol had no a-H to formation of imines from amines with short-chain aliphatic
and can not be oxidized.
alcohols (C1–C6). For one advantage, the environmentally
Apart from Pd/ZrO2 catalyst, Au/ZrO2 and Au–Pd/ZrO2 alloy benign method occurs under ambient conditions (30 ꢀC and
catalysts were also used in above reactions (Table S1†). To our using air as the economic oxidant) and achieves high yield to
delight, Au–Pd/ZrO2 catalyst was much more active than Pd/ imine. In order to achieve high yield of ketimines from amines
ZrO2 in the reactions of benzylamine and secondary aliphatic with secondary alcohols which are relatively restricted, Au–Pd
alcohols, and the yields of ketimines were largely improved alloy catalyst was introduced and better results were obtained.
(Table 2, entries 9–11). The signicant enhancement of the For another, the selectivity to desired imine was excellent and
catalytic activity can be explained by the electronic heteroge- no other reported products were detected. The full selectivity
neity (Pd in the alloy NPs expresses more electropositive prop- can be explained that oxidation of alcohols to the correspond-
erties and Au expresses more electronegative properties18), ing aldehydes which were only present in small amounts and
which can lead to enhancement the interaction between the consumed in situ, consequently, such side reactions can be
alloy NPs and the reactant molecules.22
Next, the reactions of various amines with ethanol were also underway.
diminished. Deeper mechanistic study of this method is
investigated (Table 2, entries 13–23). Substituted benzylamine
We gratefully acknowledge the nancial supports from the
with 4-chloro (1b), 4-methyl (1c), 4-methoxy (1d), 3-methoxy (1e) National Natural Science Foundation of China (no. 20966008)
and 2-methoxy (1f) groups reacted well with ethanol to afford and Opening Project of Natural Science Foundation of Inner
the products (3ba-3fa) in 99% yields aer 3 h (entries 13–17). It Mongolia (no. 2010KF02).
seems that both the electron donating and electron with-
drawing substituents on benzylamine can facilitate the reac-
tion. Similarly, treatment ethanol with 2-phenylethylamine (1g),
Notes and references
a-methylbenzylamine (1h), aminodiphenylmethane (1i) or
cyclohexylamine (1j) also led to form the desired imines in 99%
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reaction of low nucleophilic aniline (1l) with ethanol, never-
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