Transition metal/Br?nsted acid cooperative catalysis enabled facile synthesis of 8-hydroxyquinolines through one-pot reactions of ortho-aminophenol, aldehydes and alkynes

Article abstract of DOI:10.1039/c8ra07212d

A convenient and straightforward three-component one-pot strategy has been developed for the synthesis of 8-hydroxyquinoline derivatives. Under the cooperative catalysis of silver(i) triflate and trifluoroacetic acid, ortho-aminophenol reacted with a range of aldehydes and alkynes under mild reactions, affording the corresponding 8-hydroxyquinoline derivatives with good to excellent yields. These transformations exhibited exceptional substrate generality and functional group compatibility.

Full text of DOI:10.1039/c8ra07212d

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Transition metal/Brønsted acid cooperative
catalysis enabled facile synthesis of 8-
Cite this: RSC Adv., 2018, 8, 33968
hydroxyquinolines through one-pot reactions of
ortho-aminophenol, aldehydes and alkynes†
*
*
Shuyan Yu,
Jingxin Wu, Hongbing Lan, Hanwen Xu, Xiaofei Shi, Xuewen Zhu
*
and Zhigang Yin
A convenient and straightforward three-component one-pot strategy has been developed for the synthesis
of 8-hydroxyquinoline derivatives. Under the cooperative catalysis of silver(I) triflate and trifluoroacetic acid,
ortho-aminophenol reacted with a range of aldehydes and alkynes under mild reactions, affording the
corresponding 8-hydroxyquinoline derivatives with good to excellent yields. These transformations
exhibited exceptional substrate generality and functional group compatibility.
Received 29th August 2018
Accepted 24th September 2018
DOI: 10.1039/c8ra07212d
rsc.li/rsc-advances
nucleophilic addition of acetylide-[M] B to iminium A. That is,
under the cooperative catalysis of transition metal and
Introduction
Brønsted-acid, 8-hydroxyquinoline might be efficiently gener-
ated through one-pot reaction of ortho-aminophenol, aldehyde
and alkyne (Scheme 1). Suitable catalyst match was considered
to be crucial for this transformation.
As a privileged scaffold, 8-hydroxyquinoline has been found in
many natural products and drug candidates with remarkable
biological and pharmaceutical activities.1–9 Moreover, 8-
hydroxyquinolines have been gaining attention in metallocene
complex catalyzed transformations, in which they are utilized as
effective multidentate ligands.10–21 In view of the remarkable
importance of this class of heterocyclic compounds, the eld of
8-hydroxyquinoline synthesis is continuously gaining attention.
Although 8-hydroxyquinolines could be prepared by hydrolysis
of 8-haloquinolines22 or 8-aminoquinolines,23 the latter two
quinolone derivatives were not easily accessible. The classical
Skraup's procedure for quinoline derivatives suffered from
harsh reaction conditions and poor yields.24–26 The Friedlander
reaction was limited due to the instability of 2-amino-
benzaldehyde, which is mostly in situ generated by reduction of
2-nitrobenzaldehyde derivatives.27,28 In the last 20 years,
transition-metal or Brønsted-acid catalysis toward quinoline
derivatives have been extensively studied.29–36 What's confusing
is that 8-hydroxyquinolines were rarely involved in these
reports.37–40 Considering the importance in pharmacology and
functional materials chemistry, the development of more facile
and economic synthetic approached for 8-hydroxyquinolines is
highly desirable.
Results and discussion
To establish proof of concept, we carried out the reaction of
ortho-aminophenol 1, benzaldehyde 2a and phenylacetylene 3a
as the archetypal. Our study began with the evaluation of
different metal catalyst in the presence of one equivalent of TFA
(Table 1, entry 1–6). We were pleased to nd that the reaction
with AgOTf as alkye-philic catalyst could generate the desired 8-
hydroxyquinoline compound 4a in 72% yield with benzylamine
5a as the byproduct41 (entry 1). Other Brønsted acid were also
examined (entry 7–9). Suitable strength of acidity proved to be
crucial for the multicomponent transformation. TFA seemed to
be the best. Control experiments indicated the necessity of the
both catalysts. Without the participation of TFA, no product
could be obtained. And the reaction got obviously suppressed in
Initially 8-hydroxyquinoline was envisioned to arise from
hydroarylation-cyclization of propargylamine C followed by
oxidation/aromatization, which might to be formed through
Material and Chemical Engineering College, Zhengzhou University of Light Industry,
Zhengzhou 450002, Henan, People's Republic of China
† Electronic supplementary information (ESI) available. CCDC 1864450 and
1864452. For ESI and crystallographic data in CIF or other electronic format see
DOI: 10.1039/c8ra07212d
Scheme 1 Possible synthetic pathway for 8-hydroxyquinoline.
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Table 1 Optimization of reaction conditionsa
Entry
TM
BA
Solvent
Time/h
Yieldb (4a) [%]
Yieldb (5a) [%]
1
2
3
4
5
6
7
8
AgOTf
AgOAc
Cu(OTf)2
Pd(OAc)2
PdCl2
Ph3PAuCl
AgOTf
AgOTf
AgOTf
AgOTf
—
TFA
TFA
TFA
TFA
TFA
TFA
TfOH
PTSA
H3PO4
—
TFA
TFA
TFA
TFA
TFA
TFA
TFA
TFA
TFA
TFA
TFA
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
Toluene
MeCN
THF
DMF
DCE
8
12
8
10
10
12
8
8
8
10
14
5
1
1
6
2
4
6
5
5
72
Complex
63
—
Complex
Complex
38
23
12
15
70
50
—
—
9
43
10
11
12c
13d
14e
15f
16g
17g
18g
19h
20i
21j
No reaction
68
80
96
95
75
94
80
14
10
—
—
16
—
10
12
—
AgOTf
AgOTf
AgOTf
AgOTf
AgOTf
AgOTf
AgOTf
AgOTf
AgOTf
74
No reaction
No reaction
Sluggish reaction
2
a
Conditions: 1 (1.1 mmol, 1.1 equiv.), 2a (1 mmol, 1 equiv.), 3a (1.2 mmol, 1.2 equiv.), TM (transition metal, 5 mol%), BA (Brønsted acid, 100 mol%)
in 4.0 mL solvent under atmosphere at 80 ꢀC for 8 h. b Isolated yield based on 2a. c TFA (400 mol%). d AgOTf (5 mol%) and TFA (400 mol%). e AgOTf
f
g
h
(1 mol%) and TFA (400 mol%). AgOTf (1 mol%) and TFA (200 mol%). AgOTf (0.5 mol%) and TFA (400 mol%). AgOTf (0.5 mol%) and TFA
(400 mol%) at 60 ꢀC. AgOTf (0.5 mol%) and TFA (400 mol%) at 100 ꢀC. j AgOTf (0.5 mol%) and TFA (400 mol%) at 60 ꢀC.
i
the absence of silver (entry 10 and 11). Unexpectedly, when the effectively in the one-pot cascade reactions to give 8-hydrox-
ratio of TFA increased to 400 mol%, 8-hydroxyquinoline yquinoline derivatives 4l–q in acceptable yields. Aliphatic
compound 4a was collected with higher yield along with greatly aldehyde and heteroaromatic aldehyde were effective
reduced reaction time (entry 12 and 13). To our delight, when substrates, generating 4r and 4s in 93% and 87% yield respec-
AgOTf decreased to 0.5 mol%, a parallel yield was also observed tively. The reactions proceeded smoothly for aryl alkynes with
(entry 14–16). Solvent and temperature optimization revealed either electron-withdrawing or electron-donating substituents
that other medias are not suitable in terms of yield comparable present on the aromatic ring to afford the desired products in
ꢀ
to that in DCE at 80 C (entry 17–21).
moderate to excellent yields (4t–4v). Electron density provided
With the optimized reaction conditions in hand (Table 1, certain impact on the reactions, and those with electron-
entry 16), we examined the AgOTf/TFA system for one-pot releasing group gave a slightly low yield. Alkyl alkyne was also
synthesis of 8-hydroxyquinoline derivatives from ortho-amino- an effective substrate. 8-Hydroxyquinoline derivative 4w was
phenol 1, various aldehydes 2 and alkynes 3. Table 2 illustrates collected in nearly equivalent yield. The structures of obtained
the wide generality and substrate scope of this tandem reaction. compounds were characterized by NMR spectrum and further
To our delight, satisfactory yields were observed for all substrate conrmed by single-crystal X-ray diffraction analysis of
examined. For the variation on aromatic aldehyde, different compound 4c and 4e.
electron-donating or electron-withdrawing substituents at
either the para-, meta- or ortho-position on the aryl group were
all tolerated to yield 4a–q in high yields. Aromatic aldehydes
with electron-donating group afforded better results than those
Experimental section
Materials and methods
with electron-withdrawing group (4a–d vs. 4e–f). Notably,
strongly electron-decient p-nitrobenzaldehyde gave a complex
reaction, without desired product identied. Comparing with
electron effect, the steric hindrance exerted less inuence on
these transformations. It should be noted steric crowded
aromatic aldehydes with multiple substituents could work
All chemicals were obtained from commercial suppliers and
used without further purication. Melting points were
1
measured using a TY-60 microscopic apparatus. H NMR and
13C NMR spectra were recorded with Bruker 400M or 600M
instruments. Chemical shis were measured relative to tetra-
methylsilane (0.00 ppm) as internal standard.
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Table 2 Synthesis of 8-hydroxyquinoline derivatives from amino-
aldehydes and alkynes, thus enabling the vast expansion of
substituent architectures on 8-hydroxyquinoline framework.
phenol, aldehydes and alkynesa,b
Conflicts of interest
There are no conicts to declare.
Acknowledgements
We are grateful to the support from the National Natural
Science Foundation of China (21602207), the Foundation of
Henan Educational Committee (17A150022) and the Doctoral
Research Fund of Zhengzhou University of Light Industry
(2014BSJJ009).
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