P. Tomkins et al. / Journal of Catalysis 371 (2019) 207–213
211
dehydrogenated pyrrolidine species must first be transformed back
to pyrrolidine which readily reacts with cyclohexanone to form the
final product.
ing six reducing equivalents to form pyridine, which cannot react
with cyclohexanone. In the presence of sodium formate, 92% of
phenol was converted and the corresponding N-cyclohexyl and
N-phenylpiperidine were formed in 55% and 24% yield,
respectively. In the absence of sodium formate, 84% of phenol
was converted and the corresponding N-cyclohexyl and N-phenyl-
piperidine were formed in 48% and 23% yield, respectively. Thus,
the possibility of the amine to rather easily be dehydrogenated
by aromatization to give six reducing equivalents explains the
rather similar result between the reaction in the presence and
absence of sodium formate. When 1,2,3,4-tetrahydroquinoline
was used as amine (Table 1), cyclohexanone was observed as main
product, which indicates that the condensation of this amine with
cyclohexanone is sterically challenging. The yield of the corre-
sponding substituted cyclohexylamine was 13% at 80% phenol con-
version in the presence of sodium formate and only negligible
amounts were formed at 39% conversion in the absence of sodium
formate. The low extent of amination can be explained by the
higher steric demand compared with the other amines. In the
absence of an added reductant the amination is likely less pro-
nounced, because there is a higher fraction of amine with a pyri-
dine moiety (66% vs. 39%), which cannot form substituted
amines. The degree of dehydrogenation is much lower than e.g.
for pyrrolidine, which indicates that the dehydrogenation of
1,2,3,4-tetrahydroquinoline is rather challenging, explaining the
larger difference in phenol conversion upon addition of sodium
formate. Summarizing, the N-heterocycles that can rather easily
be dehydrogenated induced higher rates in the conversion of phe-
nol towards cyclohexanone and subsequent amination towards the
aminated products.
These observations are valid, irrespective of the presence or
absence of sodium formate. However, there are subtle differences
between these two reactions, which can primarily be explained
by the number of reducing equivalents available in the reaction
mixture. After 10 h the amount of partially hydrogenated products
slightly decreased, if no sodium formate is present: Ph-H4Pyr
decreased from 61 mol% to 57 mol% and the concentration of
Cy-Pyr decreased from 24 mol% to 20 mol%. The completely
dehydrogenated product Ph-Pyr is more abundant at the end of
the reaction in the absence of sodium formate, with 11 mol%, than
in its presence (6 mol%).
These results confirm that the amination of phenol without
addition of a reductant can successfully proceed via an initial dehy-
drogenation of the amine. In this case, the dehydrogenated com-
pounds derived from pyrrolidine are stable and they are formed
readily. Thus, the reducing equivalents provided by pyrrolidine
play a more important role than the reducing equivalents available
from sodium formate, resulting in comparable rates for these two
reactions.
2.4. Reaction of phenol with other N-heterocycles
In a next step, the reactivity of other heterocycles was investi-
gated in the presence and absence of sodium formate (Table 1).
Indoline (Table 1, Entry 1) is easily dehydrogenated to indole, cor-
responding to generation of two reducing equivalents. After 16 h of
reaction, the reaction in the presence of 1.5 eq sodium formate
yielded 54% of N-cyclohexylindole at a phenol conversion of 61%,
while in the absence of sodium formate, 47% N-cyclohexylindole
was formed at 49% phenol conversion. The higher conversion in
the presence of sodium formate can easily be explained by more
reducing equivalents being available. Note that the reaction in
the absence of sodium formate provides exactly the maximum
yield (47 mol%) possible using 1.4 eq (or 140 mol%) of indoline,
taking into account that indoline dehydrogenation takes place,
while the cyclohexyl group is hardly dehydrogenated:
To evaluate in a more quantitative way the reactivity induced
by the different amine substrates, the phenol conversion was
assessed after 3 h, and plotted as in Fig. 4. The horizontal axis gives
the number of reducing equivalents, supposing full dehydrogena-
tion of the amines, and full conversion of sodium formate to CO2.
The dehydrogenation of the amine does not necessarily result in
the release of hydrogen gas; hydride species might as well be
adsorbed on the catalyst surface where they are available for
reducing the phenol. It has been demonstrated for the condensa-
tion and dehydrogenation of cyclohexylamine towards dipheny-
lamine that H2 gas may be accumulated in analogous conditions
3 indoline + phenol ! N-cyclohexylindole + 2 indole + H2O
This proves that indoline is an effective reductant in this
conversion.
Next, piperidine was investigated for the reaction (Table 1,
Entry 2). Each molecule of piperidine can be dehydrogenated yield-
90
CHA
Hept-NH2
Pyrrolidine
Indoline
1,2,3,4-H4-Quinoline
Piperidine
80
70
60
50
40
30
20
10
0
Table 1
Amination of phenol with different N-heterocycles (1.4 eq.) in the presence and
absence of sodium formate (1.5 eq) as reductant after 16 h of reaction. Reactions were
carried out using Pd/C (10 mol%) and a 0.2 M solution of phenol at 140 °C.
Entry
Amine
Yield of cyclohexyl-/phenylamine (Phenol
conversion)
With HCOONa
54a/- (61)
Without HCOONa
47a/- (49)
1
2
55/24 (92)
13/- (80)b
48/23 (84)
<1%/- (39)b
0
5
10
15
Reducing equivalents [eq]
3
Fig. 4. Comparison of phenol conversion after 3 h in the presence of different
amines. The number of reducing equivalents in the reaction mixture was calculated
by summing the amount that would be available from either sodium formate (0 and
1.5 eq. with respect to the phenol) and from complete dehydrogenation of the
amine to either the imine or the corresponding aromatic heterocycle. Reactions
were carried out using Pd/C (10 mol%) and a 0.2 M solution of phenol at 140 °C.
a
The corresponding indole is formed as main product.
Cyclohexanone was formed as main product.
b