Lanthanides Mediated Oxidative Cross Coupling of Benzylalcohol and Various Amines to Form Corresponding Imines

Article abstract of DOI:10.1002/zaac.201600201

Herein, a new and efficient approach towards the oxidative cross-coupling of benzylalcohol and various aromatic amines to form corresponding imines with high degree conversion (>80 %) and chemo-selectivity using lanthanide salts as pre-catalysts is presented. The catalyzed oxidative cross-coupling reaction using La(NO₃)₃·6H₂O as pre-catalyst displayed a broad substrate scope. The reaction afforded various substituted imines from the reaction of benzylalcohol with ample variety of amines in good yields.

Full text of DOI:10.1002/zaac.201600201

Journal of Inorganic and General Chemistry
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DOI: 10.1002/zaac.201600201
Lanthanides Mediated Oxidative Cross Coupling of Benzylalcohol and
Various Amines to Form Corresponding Imines
Jayeeta Bhattacharjee,[a] Mitali Sachdeva,[a] and Tarun K. Panda*[a]
Dedicated to Prof. Ashoka G. Samuelson on the Occasion of His 60th Birthday
Keywords: Lanthanides; Alcohols; Cross-coupling; Imines; Catalysis
Abstract. Herein, a new and efficient approach towards the oxidative The catalyzed oxidative cross-coupling reaction using La(NO3)3·6H2O
cross-coupling of benzylalcohol and various aromatic amines to form
corresponding imines with high degree conversion (Ͼ80%) and
as pre-catalyst displayed a broad substrate scope. The reaction afforded
various substituted imines from the reaction of benzylalcohol with
chemo-selectivity using lanthanide salts as pre-catalysts is presented. ample variety of amines in good yields.
drogenation of secondary amines have received much more
Introduction
attention and have been greatly studied because the starting
materials are readily available, and green molecular oxygen or
air can serve as the terminal oxidant. To create environmen-
tally benign processes, the development of catalytic systems
for these reactions has received much attention. From this
point of view, an oxidative cross coupling of alcohols and
amines ought to be the most direct, appropriate and efficient
way to produce imines due to their wide substrate scope. In the
cross-coupling of alcohols with amines, the only by-product is
water, and diverse symmetric and unsymmetric imines can be
easily synthesized choosing different starting substrates. More-
over, compared to carbonyl compounds, alcohols are less toxic,
readily available, more stable, inexpensive, and easier to han-
dle. Nevertheless, the selective oxidation of alcohols into alde-
Imines, also known as Schiff bases are versatile intermedi-
ates having widespread applications in laboratory and indus-
trial synthetic processes.[1] They are involved in organic syn-
thesis and extensively utilized in the synthesis of pharmaceuti-
cals, fragrances, fungicides, natural products, dyes, and agri-
cultural chemicals. They act as electrophiles in many important
organic transformations including addition, condensation, re-
duction, cyclization, cycloaddition, and aziridination reac-
tions.[2] Moreover, imines also serve as common ligands in the
field of coordination chemistry. Therefore, the efficient and
diverse synthesis of imines is a consistently demanding re-
search topic in the organic synthetic chemistry. Conventionally,
imines were synthesized from the condensation of aldehydes/
ketones with amines in the presence of an acid. During the
past decade, numerous efforts have been devoted to the direct hyde intermediates under mild conditions is the major chal-
synthesis of imines, in particular via one pot procedures
through an oxidative process to reduce the energy consump-
tion, waste emission, operating and purification steps.[3] Re-
cently, versatile alternative methods such as oxidation of sec-
ondary amines,[4] self-condensation of primary amines upon
oxidation,[5] oxidative coupling of alcohols and amines,[6] hy-
droamination of alkynes with amines,[7] and the partial hyd-
rogenation of nitriles followed by coupling with amines[8] have
been reported.
lenge for this type of reaction. The development of an effective
and general method for the synthesis of imines from alcohols
and amines is very prudent due to its potential versatility and
broad scope. Recently, quite a number of metal complexes,
including complexes of ruthenium,[9] osmium,[10] palla-
dium,[11] manganese,[12] iridium,[13] and copper[14] have been
reported to catalyze this reaction homogeneously.
Although these results are encouraging, there are still some
drawbacks associated with these types of reactions such as the
use of organic solvents as the reaction medium, the use of
expensive metal complexes, and high catalyst loadings. These
reactions are also limited to activated (benzylic) alcohols and
a maximum turnover number of 50 are reported. The limited
availability of these metals and their high cost makes it highly
demanding to search for more economical and environmental
friendly alternatives. The development of nonprecious metal
catalysts would be a significant progress from the perspective
of cost, abundance, and sustainable chemistry.
Among the various methodologies for imine formation,
mainly three approaches – cross coupling of alcohols with
amines, self-coupling of primary amines, and oxidative dehy-
* Dr. T. K. Panda
E-Mail: tpanda@iith.ac.in
[a] Department of Chemistry
Indian Institute of Technology
Hyderabad 502285, Telangana, India
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/zaac.201600201 or from the au-
thor.
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para position, overcame the steric inhibition of methyl group
at ortho position (Table 2, entry 10).
Results and Discussion
Herein, the synthesis of imines using lanthanide salts to cat-
To study the effect of groups present at para position of the
anilines, 4-methylanline and 4-iodoaniline were employed as
substrates for this catalytic reaction. It has to be noted that
yields of 84% and 80% were obtained with 4-methylaniline
and 4-iodoaniline, respectively (Table 2, entries 8 and 9). The
reaction of cyclohexylamine and 3-methoxy aniline with benz-
ylalcohols also showed a high degree of conversion to yield
respective imines under optimum conditions (Table 2, entries
11 and 12). To further validate the scope of this reaction and
to study the effect of various groups, anilines bearing electron
releasing groups were also examined. It was found that 2,6-
dimethylaniline gave only 15% yield on reaction with benzyl
alcohol (Table 2, entry 13). The coupling between p-meth-
oxybenzylalcohol yielded 45% of product N under similar
condition (Table 2, entry 14). The substantial decrease in yield
assumed to be due to the presence of electron donating group
on para position of benzyl to reduce the electrophilicity of
the bezyl alcohol.[14a,15] Furthermore, no imine formation took
place when Dipp-NH2 and Mes-NH2 were investigated as sub-
strates for the reaction with benzylalcohol (Table 2, entries 16
and 17). This is presumably because of the steric hindrance of
the bulky electron donating groups. However, sluggish reactiv-
ity was observed with aliphalic alcohol such as ethanol with
benzylamine (Table 2, entry 15).
The mechanism for the lanthanide salts catalyzed oxidative
cross coupling of benzylalcohol with various amines is unclear.
In contrast to the reported transition metal based catalyst,
where formation of metal hydrides plays a crucial role,[9–12]
the existence of a lanthanide hydride in the reaction medium
can be ruled out due to its extreme reactivity in the aerobic
condition. Thus, the formation of a lanthanide hydroxyl cluster
by the reaction of lanthanide salt, potassium hydroxide under
aerobic condition, which eventually catalyzes the benz-
ylalcohol to benzaldehyde is assumed. The aldehyde couples
with the amine leading to imine formation. However, attempts
to isolate any of the intermediates were failed.
alyze the oxidative cross coupling of alcohols and amines is
described. Initially, the coupling reaction of benzylalcohol and
benzylamine was investigated in the presence of various com-
mercially available lanthanide salts as precatalysts and 1.0
equivalent of KOH in toluene at 90 °C for 19 h in an O2 atmo-
sphere (Scheme 1).
Scheme 1. Lanthanide salts mediated preparation of imines by the oxi-
dative cross coupling of alcohols with amines.
The reaction went smoothly to afford the corresponding
imines in 90–99% yield with the full conversion of the starting
material when different types of lanthanides were used as cata-
lysts for the transformation (Table 1, entries 1–4). All lantha-
nide salts showed similar activity for oxidative cross coupling
reaction. However, no imine formation was noticed in the ab-
sence of catalyst (Table 1, entry 5).
Table 1. Catalyst screening for oxidative cross coupling reaction.a)
Entry
Alcohol
Amine
Catalyst
Yieldb) /%
1
2
3
4
5
PhCH2OH
PhCH2OH
PhCH2OH
PhCH2OH
PhCH2OH
PhCH2NH2
PhCH2NH2
PhCH2NH2
PhCH2NH2
PhCH2NH2
LaCl3·6H2O
ErCl3·6H2O
La(NO3)3·6H2O 99
La(OAc)3·6H2O 90
None
99
99
0
a) Reaction conditions: 5 mol% of catalyst, 1 mmol of benzylalcohol,
1.5 mmol of benzylamine, 1 mL toluene, 19 h, 90 °C, O2 atmosphere.
1
All compounds were characterized by H and 13C NMR spectroscopy
using CDCl3 as NMR solvent. b) Yields are calculated by 1H NMR
spectroscopy on the basis of the amount of alcohol.
Conclusions
Encouraged by these promising results and the efficiency
of lanthanide salts as catalysts, the scope of this reaction was
extended for the synthesis of other imines with various
amine substrates. 5 mol% of hydrated lanthanum nitrate
[La(NO3)3·6H2O] was used as the catalyst as optimum condi-
tion to evaluate a variety of substituted anilines for imine for-
mation with benzylalcohol (Table 2). The reaction of benzyla-
mine and unsubstituted aniline with benzylalcohol gave 99%
yield (Table 2, entries 1 and 2). Anilines containing halogen
atoms as electron withdrawing groups at ortho position pro-
duced excellent yields (91–96%) (Table 2, entries 3–5). How-
ever, 2-methylaniline showed slightly less conversion (84%)
due to steric crowding at ortho position (Table 2, entry 6). The
combination of methyl group and methoxy group, i.e. the 2-
methyl-4-methoxy aniline was converted to corresponding im-
A new, simple and efficient catalytic system for the oxidat-
ive cross coupling of alcohols with amines to form the corre-
sponding imines was developed. Lanthanide salts proved to be
the effective and versatile catalysts for synthesis of imines.
The major advantages of this method are its general applica-
bility, giving good yields of corresponding imines with various
amines, easy transformation, and low toxicity. The reaction
was performed at atmospheric pressure of molecular oxygen,
which is considered as an abundant and green oxidant.
Experimental Section
General Information: All reactions were performed in air without
any special precautions, unless stated otherwise. Chemicals and sol-
vents were of analytical grade, purchased from Sigma Aldrich and
ine in 99% yield as the electron donating methoxy group at were used without purification. 1H NMR (400 MHz) and 13C{1H}
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Table 2. Catalyzed oxidative cross coupling of alcohols and amines to form imines.a)
a) Reaction conditions: 5 mol% of catalyst, 1 mmol of benzylalcohol, 1.5 mmol of benzylamine, 1 mL toluene, 19 h, 90 °C, O2 atmosphere. All
1
1
compounds were characterized by H and 13C NMR spectroscopy using CDCl3 as NMR solvent. b) Yields are calculated by H NMR spec-
troscopy on the basis of the amount of alcohol.
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400 spectrometer. Amines were distilled over CaH2 prior to use. NMR
solvent (CDCl3) was purchased from Alfa Aesar and distilled over
molecular sieves.
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General Procedure for the Cross Coupling of Alcohols and Amines
to form Imines: In a typical experiment, benzylalcohol (1.0 mmol),
amine (1.0 mmol), catalyst (5 mol%), KOH (53 mg, 1.0 mmol), and
toluene (1 mL) were placed in a 10 mL glass tube. Subsequently, the
reaction mixture was stirred in an oxygen atmosphere at 90 °C for 19
h before it was quenched by NH4Cl (2 mL, sat. aq.). The layers were
separated and the aqueous layer was extracted with ethyl acetate. The
combined organic layers were dried using Na2SO4 and concentrated in
vacuo. The product was characterized by 1H and 13C NMR spec-
troscopy (Supporting Information). The yield of product was analyzed
using 1H NMR spectroscopy and calculated based on the amount of
alcohol.
Supporting Information (see footnote on the first page of this article):
1H and 13C NMR spectra of A–N.
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Acknowledgements
This work is supported by the Ministry of New and Renewable Energy
(MNRE), India under project no. 103/209/2013-NT, dated: 29th Sep-
tember, 2014. The instrumental facilities were provided by the Indian
Institute of Technology Hyderabad (IITH). J. B. thanks UGC, India
for her PhD fellowship.
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Received: June 9, 2016
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J. Bhattacharjee, M. Sachdeva, T. K. Panda* ................. 1–5
Lanthanides Mediated Oxidative Cross Coupling of Benz-
ylalcohol and Various Amines to Form Corresponding Imines
Z. Anorg. Allg. Chem. 0000, 0–0
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