Ir(bis-NHC)-Catalyzed Direct Conversion of Amines to Alcohols in Aqueous Glycerol

Article abstract of DOI:10.1002/ejoc.201900042

Sustainable catalytic conversion of amines to alcohols was realized in the presence of iridium catalysts and aqueous glycerol. Iridium catalysts involving bis-N-heterocyclic carbene (bis-NHC) show good reactivity and stability in the conversion of amines into alcohols in aqueous glycerol. The reaction was initiated with the dehydrogenation of amines and followed by hydrolysis and reduction. Iridium catalysts play dual roles in both the dehydrogenation and reduction steps. By employing glycerol as a solvent and hydrogen source, the final reduction was facilitated. The synthesis and characterization of various Ir(bis-NHC) complexes are described along with the catalytic reaction results of the amine into alcohol conversion.

Full text of DOI:10.1002/ejoc.201900042

DOI: 10.1002/ejoc.201900042
Communication
Ir Catalysis
Ir(bis-NHC)-Catalyzed Direct Conversion of Amines to Alcohols
in Aqueous Glycerol
[a]
[a]
[a]
[a]
[a]
Yeon-Joo Cheong, Seunghyeon Lee, Sang Joon Hwang, Woojin Yoon, Hoseop Yun,
and Hye-Young Jang*[
a]
Abstract: Sustainable catalytic conversion of amines to alco- by hydrolysis and reduction. Iridium catalysts play dual roles in
hols was realized in the presence of iridium catalysts and aque- both the dehydrogenation and reduction steps. By employing
ous glycerol. Iridium catalysts involving bis-N-heterocyclic carb- glycerol as a solvent and hydrogen source, the final reduction
ene (bis-NHC) show good reactivity and stability in the conver- was facilitated. The synthesis and characterization of various
sion of amines into alcohols in aqueous glycerol. The reaction Ir(bis-NHC) complexes are described along with the catalytic
was initiated with the dehydrogenation of amines and followed reaction results of the amine into alcohol conversion.
Introduction
Transition-metal-catalyzed borrowing hydrogen reactions, in
which alcohols undergo dehydrogenation to form carbonyl
compounds, followed by the nucleophilic addition of amines,
Scheme 1. Reaction between alcohols and amines.
and hydrogenation to afford amines (Scheme 1), have been em-
[
1,2]
ployed in the conversion of alcohols to amines.
to the conversion of alcohols to amines, the reverse reaction is glycerol is delivered to the metal center to generate hydrogen
In contrast
[
3]
[7]
rarely studied; KOH-mediated reaction at high temperature
gas or reduce organic compounds. In the iridium-catalyzed-
[
4]
and Ru-catalyzed direct conversion of amines to alcohols are conversion of amines to alcohols in glycerol, glycerol acts as a
a few examples. The conversion of amines to alcohols should hydrogen source generating iridium-hydrides for efficient re-
include the dehydrogenation of amines to form imines, which duction as well as a green solvent.
undergo hydrolysis to produce carbonyl compounds along with
Ir complexes possessing a bis-N-heterocyclic carbene (NHC)
the release of ammonia. Then, carbonyl compounds undergo ligand show excellent reactivity in the hydrogenation and trans-
hydrogenation to give alcohols. It is known that the conversion fer hydrogenation of various π-systems.[8–10] The reactivity and
of amines to alcohols is challenging, because 1) dehydrogen- stability of Ir-NHC catalysts in hydrogenation or transfer hyd-
ation of amines is slower than that of alcohols and 2) imines rogenation are increased with assistance from strong electron-
[
11]
formed via dehydrogenation undergo facile re-addition of donating carbene ligands. Considering the reaction of Ir(bis-
amines to induce transamination because of the high nucleo- NHC) complexes with alcoholic solvents to form Ir–H during
[
5]
philicity of amines. To promote the conversion of amines to transfer hydrogenation, Ir(bis-NHC) complexes may promote: 1)
alcohols, efficient catalysts facilitating the dehydrogenation of the dehydrogenation of amines to initiate the conversion of
amines and the reduction of intermediate carbonyl compounds amines to alcohols and 2) the reduction of intermediate alde-
are required.
hydes to produce alcohols to complete this conversion. In this
Bio-waste-derived glycerol is considered a renewable feed work, we present a catalytic protocol for the amine to alcohol
stock.[ Glycerol is non-toxic, non-volatile, biodegradable, and conversion, employing efficient iridium catalysts possessing var-
highly-functionalized with hydroxy groups, and a variety of ious bis-NHC ligands and a sustainable aqueous glycerol sol-
glycerol applications from chemical feedstocks to solvents have vent.
6]
been reported because of these attractive attributes. In particu-
lar, glycerol has been used as a reducing agent in metal-cata-
lyzed transfer hydrogenation, where a hydrogen atom from
Results and Discussion
We began optimizing the conversion of 4-methoxy benzyl-
III
[
a] Department of Energy Systems Research, Ajou University
Suwon 16499, South Korea
amines 1a to 4-methoxy benzyl alcohols 1b with Crabtree's Ir
complex A (Table 1). The reactions of 1a (1 mmol) with catalyst
A (0.35 mol-%) and KOH (1 equiv.) in a solvent mixture of glyc-
E-mail: hyjang2@ajou.ac.kr
https://sites.google.com/ajou.ac.kr/ajouom
Supporting information and ORCID(s) from the author(s) for this article are
available on the WWW under https://doi.org/10.1002/ejoc.201900042.
erol (1 mL) and H O (0.5 mL) at 120 °C to 150 °C to afford 1b
2
with 55 % to 62 % yields, respectively (entries 1–3). The reaction
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Communication
1
of entry 1 (Table 1) was monitored by H NMR, showing clear iridium metal ion in compounds B–E was determined by the
conversion of amines to alcohols (see supporting information). analogy of the NMR spectra of A and X-ray crystallographic data
During the reaction, trace amount of amides and imines de- (Figure 1). Single crystals of C and D were obtained via slow
rived from the reaction of aldehydes and amines were observed evaporation of acetone/hexane mixture solutions at –20 °C. Irid-
1
by H NMR, but they were not isolated (see supporting informa- ium catalysts B–D were examined for the conversion of amines
tion). Upon changing the amount of KOH, the yield was in- to alcohols to form 1b at yields of 72 %, 68 %, and 68 %, respec-
creased to 70 % (entries 4–6). Next, other inorganic bases and tively. Complex E involving a wingtip-modified bis-NHC ligand
an organic base were examined; they showed a good yield of participated in this reaction to afford 1b with 58 % yield.
1
b with NaOH (entries 7–10). The effect of solvents was also
investigated (entries 11–16). Without water, the yield of 1b de-
creased slightly (55 %, entry 11). In the absence of an alcoholic
solvent, the reaction did not proceed to form 1b (entry 12).
Propylene glycol (PG), ethylene glycol (EG), 1,3-propandiol (PD),
and 2-propanol (IPA) were employed to show low yields of 1b
(
entries 13–16). Glycerol showed the best result in this reaction.
Presumably, glycerol delivers hydrogen to iridium catalysts in a
[
12]
more efficient manner than other alcoholic solvents.
absence of iridium catalysts, the reaction did not proceed (entry
7).
In the
1
Table 1. Optimization of the conversion of amines to alcohols.
Scheme 2. Comparison of the reactivities of various Ir(NHC) complexes.
Entry
Base (equiv.) Solvent (mL)
Temp [°C]
Yield %[a]
1
2
3
4
5
6
7
8
9
KOH (1)
KOH (1)
KOH (1)
Glycerol/H
Glycerol/H
Glycerol/H
Glycerol/H
Glycerol/H
Glycerol/H
Glycerol/H
Glycerol/H
Glycerol/H
Glycerol/H
2
2
2
2
2
2
2
2
2
2
O (1:0.5)
O (1:0.5)
O (1:0.5)
O (1:0.5)
O (1:0.5)
O (1:0.5)
O (1:0.5)
O (1:0.5)
O (1:0.5)
O (1:0.5)
120
130
150
120
120
120
120
120
120
120
120
120
120
120
120
120
120
58
55[
62[
57
63
70
73
30
67
43
55
0
b]
b]
KOH (0.5)
KOH (1.5)
KOH (2.0)
NaOH (2.0)
NaOH (2.0)
KOtBu (2.0)
DBU (2.0)
KOH (2.0)
KOH (2.0)
KOH (2.0)
KOH (2.0)
KOH (2.0)
KOH (2.0)
KOH (2.0)
10
11
12
13
14
15
16
17
Glycerol (1)
O(0.5)
PG/H O (1:0.5)
EG/H O (1:0.5)
O (1:0.5)
O (1:0.5)
O (1:0.5)
H
2
2
5
10
0
2
PD/H
IPA/H
2
2
0
N.R.[
c]
Glycerol/H
2
[
a] Isolated Yield. [b] Reaction time: 8 h. [c] No iridium catalyst. PD (1,3-
propanediol), IPA (2-propanol) Reaction conditions: 1a (1 mmol), A (3.5 μmol),
and bases in the indicated solvent were heated for 16 h.
Figure 1. (a) X-ray structure of complex C and (b) X-ray structure of complex
D.[
13]
Using the conditions optimized for the conversion of 1a to
The scope of this transformation involving alcohol formation
1
b, shown in Table 1, various iridium complexes modified on from amines was examined (Figure 2). The compounds 3- and
anionic ligands and wingtips were examined (Scheme 2). The 2-methoxy substituted benzylamines participated in this reac-
complex A reported by Crabtree was prepared as described pre- tion to form desired alcohols 2b (70 %) and 3b (69 %), respec-
[
10a,10b]
viously.
Complexes B–D containing benzoate, p-OH tively. Compounds 4-methyl and 4-Cl substituted benzylamines
benzoate, and o-OH benzoate, and complex E containing a were transformed to alcohols 4b and 5b with 51 % and 60 %
[
10c]
modified NHC ligand
were prepared in a manner analogous yields, respectively. Piperonylamine was subjected to reaction
to the synthesis of A. The coordination mode of ligands on conditions to afford 6b with 67 % yield. N-phenylethane-1,2-
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Communication
diamine participated in the reaction to form desired alcohol amount of deuterium of 1b, the α-hydrogens of 1b are specu-
product 7b with 22 % yield. (1S,2S)-1,2-diphenyl ethylenedi- lated to have come from glycerol. Subsequent to the dehydro-
amine was subjected to reaction conditions to form pyrazine 8b genation of glycerol, it could be transformed to lactate, which
[
15]
with 50 % yield. Instead of alcohol formation, vicinal diamines was observed in this reaction.
The reaction in a mixture of
1
8
18
16
underwent facile cycloaddition with pyruvic aldehyde which is glycerol and H O formed the mixture of O- and O-labelled
[
14]
formed from glycerol.
1b, suggesting that KOH and H O are the oxygen source of 1b
2
(Equ. 4).
Scheme 3. Control experiments.
Conclusion
This work describes the successful Ir-catalyzed conversion of
amines to alcohols. Ir(bis-NHC) catalysts show great activity in
the conversion of amines to alcohols with the assistance of
glycerol as a hydrogen source and solvent, in which the conven-
tional dehydrogenation-reductive amination of alcohols was
suppressed. Various anion-modified and wingtip-modified irid-
ium complexes were examined to show good yields of alcohol
formation. According to mechanistic studies using deuterated
amines, the α-hydrogens of alcohols are derived from α-hydro-
gens of glycerol.
Figure 2. Substrate scope.
The proposal of the reaction mechanism is based on control
experiments (Scheme 3). A mixture of 1a and 4-methyl benzyl
alcohol was subjected to the optimized conditions, resulting in
the formation of 1b (72 % yield) and the decomposition of 34 %
of 4-methyl benzyl alcohol (Equ. 1). This result implies that the
conversion rate of amines to alcohols is fast enough to form
alcohols as a major product of this reaction, but the decomposi-
tion of alcohols was unavoidable. To probe the destination of Experimental Section
alcohols, alcohol 1b was exposed to standard conditions in the
presence of aniline for reductive amination (Equ. 2). The ex-
pected reductive amination of oxidized alcohols (aldehydes) oc-
Representative Procedure for Iridium Complexes: A mixture of
3,3′-methylene-bis(1-methyl-1H-imidazol-3-ium) iodide (300 mg,
0.694 mmol), [Ir(COD)Cl]2 (233 mg, 0.347 mmol), KI (230 mg,
curred at a very low yield (2 %). These results also indicate that 1.39 mmol) and sodium acetate (342 mg, 2.78 mmol) was stirred in
iridium catalyst A promotes the conversion of amines to alco- MeCN (15 mL, 0.05
M) for 16 h with reflux. The gradient column
hols, not vice versa. Next, the reaction mechanism involving the chromatography (CH
Cl /acetone, 8:2) gave A as an orange solid in
2
2
40 % yield.
borrowing hydrogen concept was investigated. If the borrowing
hydrogen mechanism is the major pathway, deuterium of Representative Procedure for Catalytic Reactions: 4-Methoxy-
deuterio-1a should remain in deuterio-1b (Equ. 3). Based on the benzylamine (1a) (130 μL, 1 mmol), KOH (112 mg, 2 mmol), iridium
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Communication
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Acknowledgments
This study was supported by the next generation carbon
upcycling project (No. 2017M1A2A2043141) through NRF
funded by the Ministry of Science and ICT, Ajou University, and
the Human Resources Program in Energy Technol-
ogy (No. 20154010200820) of the Korea Institute of Energy
Technology Evaluation and Planning (KETEP), which receives fi-
nancial resources from the Ministry of Trade, Industry & Energy,
Republic of Korea.
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Keywords: Iridium · Dehydrogenation · Amines ·
Alcohols · Glycerol
[
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Received: January 10, 2019
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Ir Catalysis
Iridium catalysts including biscarbene
ligands were employed to transform
amines into alcohols with an assist-
ance of aqueous glycerol. The synthe-
sis and characterization of various
Ir(bis-NHC) complexes are described.
Y.-J. Cheong, S. Lee, S. J. Hwang,
W. Yoon, H. Yun, H.-Y. Jang* ........... 1–5
Ir(bis-NHC)-Catalyzed Direct Conver-
sion of Amines to Alcohols in Aque-
ous Glycerol
DOI: 10.1002/ejoc.201900042
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© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim