Photoinduced direct hydration of dipyridylacetylenes in acidic aqueous solution

Article abstract of DOI:10.1039/d0cc01351j

Photoinduced direct hydration of dipyridylacetylenes (DPAs) in acidic aqueous solution was achieved upon UV irradiation at room temperature. This is a catalyst-free reaction with moderate-to-good yields, and asymmetric dipyridylacetylenes afford the corresponding Markovnikov addition products.

Full text of DOI:10.1039/d0cc01351j

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DOI: 10.1039/D0CC01351J
COMMUNICATION
Photoinduced Direct Hydration of Dipyridylacetylenes in Acidic Aqueous
Solution
a
a
a
a
Ya Li, Zimu Su, Haijun Hao, and Junpeng Zhuang *
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
a) PDDA reaction of phenylethynylpyridine
Photoinduced direct hydration of dipyridylacetylenes (DPAs) in
acidic aqueous solution was achieved upon UV irradiation at room
temperature. This is a catalyst-free reaction with moderate-to-
good yields, and asymmetric dipyridylacetylenes afford the
corresponding Markovnikov addition products.
N
1. hv, 1M aqueous HCl solution
N
2. Neutralization
N
N
The hydration of alkyne derivatives is a straightforward and
environmentally benign synthetic method for constructing
carbonyl compounds, which is crucial for organic syntheses.
b) This work, photoinduced hydration reaction of DPA
1
O
1
. hv, 1M aqueous HCl solution
The traditional synthesis of carbonyl compounds from carbon-
carbon triple bonds is usually accomplished via Markovnikov
N
N
2. Neutralization
N
2
addition catalyzed by mercury salts. Due to the high toxicity of
Scheme 2 Photoreactions of phenylethynylpyridines and DPAs in 1M aqueous HCl
solution
mercury salts, many transition metal catalysts have reportedly
3
-8
9-12
13, 14
been explored for this reaction, including Au, Ag,
Co,
1
5, 16
17-19
20-22
23-26
27, 28
29
0, 31
from alkynes remains highly desirable.
Cu,
Fe,
Pd,
Pt,
Rh
and Ti . Brønsted acids
3
Besides the common metal-catalyzed hydration reaction, the
photoirradiation-promoted hydration reactions of alkynes
can also catalyze the hydration of alkynes.
However, despite being efficient, these transition metal
catalysts suffer from some obvious drawbacks, such as reaction
temperatures exceeding 100 °C, expensive noble metal salts,
and sometimes high catalyst loadings. Thus, the search of a low-
toxicity, inexpensive, and mild protocol to synthesize ketones
a) Typical approch
2
7, 28
16
catalyzed by rhodium complexes
reported (Scheme 1b).
or CuCl have also been
We are interested in developing new photochemical method
with low cost, facile synthesis, and environmental friendliness.
3
2, 33
We previously reported that phenylethynylpyridine
derivatives can be converted to triaryl naphthalenes with
medium yield via photo-dehydro Diels-Alder (PDDA)
mechanism upon irradiation with a 250-W high-pressure
O
Metal or Bronsted acid
R
R'
R'
Harsh condition
Expensive catalyst
R
3
2
mercury lamp in 1 M aqueous HCl solution.
The PDDA
reaction of 3-arylynones and arylacetylenes to construct
naphthalene derivatives has been intensively studied by Wessig
b) Visible light promoted
3
4-37
and coworkers.
However, when we used di(pyridin-4-
O
Rh complex or CuCl
yl)acetylene 1a to conduct the same reaction, 1,2-di(pyridin-4-
yl)ethone 2a was produced in 86% yield and no PDDA product
was generated. Di(pyridyl)ethones have been reported to
synthesize 3-heteroaryl-2-pyridones which have high affinity for
the benzodiazepine binding site of human GABAA receptor ion
channels and naphthyridines which act as protein kinase D
R
R
Visible light
Scheme 1 Different approaches for hydration of alkynes.
a. Department of Organic Chemistry, College of Chemistry, Beijing University of
Chemical Technology, Beijing 100029, P. R. China. E-mail:
zhuangjp@mail.buct.edu.cn
Electronic Supplementary Information (ESI) available: [General procedures,
synthesis and characterization of compounds, and computational details]. See DOI:
0.1039/x0xx00000x
3
8, 39
inhibitors.
Herein we report a facile and catalyst-free
photochemical approach to construct carbonyls from carbon-
carbon triple bond by direct hydration of DPAs in acidic aqueous
solution.
†
1
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Journal Name
Table 1 Photoinduced hydration reaction conditions investigation. a
Table 2 Scope of photoinduced hydration of alkynes a
View Article Online
DOI: 10.1039/D0CC01351J
O
0.1 M acid aqueous solution
N
O
N
N
1. hv, 1M acidic aqueous solution
N
hv
Ar
Ar'
Ar'
Ar
1a
2a
2
. Neutralization
1
2
Entry
1
Acid
HCl
HCl
HCl
Temp(°C)
Yield(%)c
25
25
90
25
25
90
86
0
0
80
86
75
Yield(%)c
Entry
1
2
Time(h)
b
2
3
O
1a
N
N 1a
N
2a
2b
1
78
b
N
4
5
6
2
H SO
4
O
N
2a
7
7
1
80
0
1b
CH
CH
3
SO
SO
3
H
H
N
N
N
3
3
N
3a
a
1c
1d
Reaction condition: 1a (0.1 mmol) dissolving in 2 mL of acidic aqueous
N
solution at room temperature upon UV irradiation for 10 h (long irradiation
O
time due to higher substrate concentration). In the dark. c Yields were
b
4a
N
O
2d
N
N
72
N
O
1
determined by the H NMR spectra using pyrazine as an internal standard.
O
O
O
O
5a
6b
N
N
1e
N
2e
1
4
74
30
N
O
O
The investigation of reaction conditions was performed by
using 1a as a model substrate. The feasibility of the hydration
reaction is summarized in Table 1. After careful investigation of
various solvents and solution pH, we found that DPA in 0.1 M
aqueous HCl solution at room temperature gave the best results
upon UV irradiation.
The application of UV irradiation is crucial for achieving an
efficient transformation. Compound 1a does not react without
UV irradiation in 0.1 M aqueous HCl solution either at room
temperature or at 90 ºC (entries 2 and 3; Table 1). Replacing HCl
O
F
F
N
N
F
1f
N
N
3f
OH
Cl
Cl
O
N
7b
8b
N
N
1g
1h
4
4
41
0
N
Cl
Cl
Br
N
N
Br
O
N
9b
N
O
1i
4
4
4
0
F
with H
obtained using CH
entry 5). Conducting the reaction at 90 °C instead of at room
2
SO
4
resulted in lower yield (entry 4). The reactivity
F
O
0b
11b
N
2j
36
38
1
N
N
1j
N
3
SO H was almost the same as that using HCl
3
(
F
F
O
N
N
N
1k
2k
N
temperature resulted in lower conversion (entry 6), mainly due
to the formation of by-products.
Based on the reaction conditions mentioned above, the acid
species and solution acidity had less effect on the yield. We used
O
O
O
O
Cl
Cl
O
2b
3b
4b
1l
N
2l
1
1
1
N
N
N
4
4
4
4
35
37
50
51
N
Br
Br
O
O
1
M aqueous HCl solution for the DPAs that have better
solubility (1a–1e), and aqueous CH SO solution of
concentration 1 M or more for the rest of the DPAs having F, Cl,
Br, OCH , CN substituents at the meta position.
N
N
2m
N
1m
N
3
3
H
NC
N
NC
N
2n
3o
N 1n
3
F
OH
N
15b
The generality of the hydration protocol was determined by
evaluating 15 symmetric and asymmetric dipyridylacetylenes,
which were conveniently synthesized by Pd-catalyzed
Sonogashira coupling between pyridyl halide and
triethylsilylacetylene (see Supporting Information). As shown
in Table 2, we successfully isolated 10 hydration products by
using this photoinduced nucleophilic addition reaction.
N
N 1o
N
a
Reaction conditions: 1(1 mmol), 1 M HCl aqueous solution (30 mL) at room
b
c
temperature under UV light irradiation (250-W Hg lamp). Acid was CH
3
SO
3
H.
Isolated yield.
4
0
The fluoro-substituted symmetric DPAs 1f and mono-fluoro-
substituted DPA 1o were transformed to the nucleophilic
The unsubstituted 1a and 1b were efficiently converted to the substitution products 3f and 3o, respectively, in which one F
corresponding ketones 2a and 2b in 78% and 80% yields, group was substituted with a OH group in 30% and 51% yields,
respectively (entries 1-2; Table 2). However, the irradiation of respectively (entries 6 and 15), and no hydration products were
di(pyridin-2-yl)acetylene 1c resulted in complex products and isolated. We found that this substitution reaction does not
no hydration product could be isolated. Symmetric DPAs with occur in the absence of UV light, which confirms that UV light is
CH
3
, COOCH
3
, and Cl substituents at the meta position gave the also a crucial factor for this nucleophilic substation reaction.
Then, we explored the selectivity of asymmetric DPAs
entries 4, 5, and 7). However, symmetric DPAs with Br and hydration reactions. For these asymmetric DPAs 1j–1n, one of
corresponding hydration products in 72%, 74%, and 41% yields
(
CH O substituents did not give the corresponding hydration the substituents is an electron-donating group (CH ) and the
3
3
products (entries 8 and 9). We tried changing the solvents and other is an electron-withdrawing group (F, Cl, or Br), or the
acid species, but still could not isolate the desired hydration electronegativity values of the two substituents differ greatly
products.
(CN and H, F and COOCH , etc.). Only one hydration product
3
could be isolated for each asymmetric substrate (entries 10-14).
2
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Compared with the NMR spectra of the products obtained from similar, but the photochemical behaviors of 1gVieawnAdrtic1lehOnalirnee
symmetric DPAs, the hydration products of asymmetric DPAs totally different. Br is a heavy atom, and DitOiIs: 1r0e.p10o3r9t/eDd0CthCa0t13t5h1eJ
follows Markovnikov's rule, and the carbonyl moiety is formed heavy atom effect will facilitate the intersystem crossing and
4
1
adjacent to the pyridine ring with the electron-donating increase the formation of triplet state of organic compounds.
substituent.
We think the heavy atom effect of Br atoms changes the excited
The isolated yield in aqueous CH
3
SO
3
H solution was low behavior of 1h and leads to the difference between 1g and 1h.
(30%~40%) which limited the application of this hydration Although 1f bearing F groups should be able to undergo
reaction. Even for the reaction of 1a in 1M HCl solution, TLC hydration, we could only isolate the nucleophilic substitution
monitoring showed that there was no obvious byproduct. After products, perhaps because the substitution reaction has a
the total consumption of 1a, the isolated yield of 2a was only smaller activation energy gap than the addition reaction.
around 80%. We think the reactant and product are not very
Next, the reaction mechanism was investigated. First, the
stable in acidic aqueous solution upon UV irradiation due to hydration of 1a was conducted in the presence of 2 equivalents
unselective decomposition especially in more concentrated of 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) as a radical
CH SO H solution. If the solution was irradiated for more than 4 scavenger, with no change in yield. Therefore, this
3 3
hours, the yield would decrease gradually. Therefore, the photoinduced hydration reaction did not proceed via a free-
+
solution was usually irradiated for about 4 hours.
radical pathway. Moreover, we found that increasing H
Based on the experimental results, there was no significant concentration reduced the yield; therefore, this reaction
substituent effect on the hydration reaction. Since this reaction involves nucleophilic addition of H
2
O, rather than electrophilic
+
was triggered upon UV irradiation, the behavior of the excited addition of H . A plausible mechanism for this reaction is shown
state of the DPAs should play an important role in elucidating in Scheme 3. Initially, the protonated DPA was excited to the S1
the mechanism. Therefore, the theoretical calculation of the excited state upon irradiation, and the carbon-carbon triple
Mulliken charge values of the carbon-carbon triple bonds of bond became more electron deficient than in the ground state.
protonated DPAs in ground and excited states were carried out Subsequent addition of a H
using Gaussian 09 package at B3LYP/6-31+G(d,p) level of theory triple bond generated an enol intermediate, which
Table 3). tautomerized to generate the ketone product. For asymmetric
The Mulliken charge values of the alkynyl carbon atoms in DPAs, the H O molecule preferentially attacked the alkynyl
2
O molecule to the carbon-carbon
(
2
excited states are apparently higher than those in the ground carbon atom adjacent to the pyridine ring bearing with
state, indicating that the carbon-carbon triple bonds of the electron-donating group, resulting in the Markovnikov addition
protonated DPAs in aqueous solution are more electron- product.
deficient in the excited state. Therefore, the nucleophilic
To further demonstrate the synthetic utility of our protocol,
addition of a H O molecule to the carbon-carbon triple bond is gram-scale hydration of 1a was investigated (scheme 4). To our
2
much easier in the excited state. The Mulliken charge values of delight, 2a was obtained in 74% isolated yield under optimized
protonated 1c, 1h, and 1i are −0.129, −0.078, and −0.347 conditions in 4 h. This result demonstrates the good scalability
(
entries 3, 8, and 9; Table 3), respectively, which are the three of the present method.
smallest values obtained. These results are in accordance with In summary, an effective photoinduced green protocol has
the experimental observation that no hydration product was been developed for the hydration of DPAs in acidic aqueous sol-
isolated from 1c, 1h, and 1i. The calculated Mulliken charge
values of protonated 1g and 1h (Table 3, entries 7 and 8) are
H C
*
3
H C
+
3
H , H2O
+ -
HN
NH
Cl
HN
NH
Cl
Table 3 Calculated Mulliken charge values of carbon-carbon triple bonds of protonated
PDAs in ground and excited states at B3LYP/6-31+G(d,p) level of theory.
H2O
Ground
state(S
Excited
H C
3
Protonated DPAs
Entry
Ar or R
+
-
H+, H O
2
H , H2O
NH
Cl
0
)
state (S
1
)
HN
O+
1
2
HN
-0.096
-0.081
0.008
H
H
0.020
Ar
Ar
HN
H C
3
H C
3
NH Keto-enol tautomerism
Cl
NH
Cl
HN
HN
3
-0.195
-0.129
NH
OH
O
4
5
6
7
8
9
CH3
-0.010
0.101
0.093
0.220
0.027
-0.071
-0.078
-0.347
Scheme 3 The proposed reaction mechanism
COOCH3
R
O
F
-0.075
-0.172
-0.166
-0.431
1 M HCl aqueous solution (150 mL)
N
HN
NH
R
N
N
Cl
Br
N
hv, 4 h, r.t.
1a
2a
1.00 g, 5.55 mmol
0.806 g, 4.11 mmol
OCH3
Yield: 74%
Scheme 4 Scaled-up reaction for photoinduced hydration of 1a.
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J. Name., 2013, 00, 1-3 | 3
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Journal Name
ution at room temperature. Theoretical calculations have 21.
revealed that excitation of protonated DPAs reduce the
X. B. Li, G. B. Hu, P. Luo, G. Tang, Y. X. Gao, PV.ieXw. XAruticalenOdnYlin.e
F. Zhao, Adv. Synth. Catal., 2012, 3D54O,I:21402.170-3294/3D20.CC01351J
C. X. Xu, W. Y. Du, Y. Zeng, B. Dai and H. Guo, Org. Lett.,
2
2
2
2
2.
3.
4.
5.
electron density of the carbon-carbon triple bond, facilitating
nucleophilic attack of H O. In addition, the hydration of
asymmetric DPAs follows the Markovnikov’s rule.
2
014, 16, 948-951.
2
O. Israelsohn, K. P. C. Vollhardt and J. Blum, Journal of
Molecular Catalysis A: Chemical, 2002, 184, 1-10.
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Conflicts of interest
F. Trentin, A. M. Chapman, A. Scarso, P. Sgarbossa, R. A.
There are no conflicts to declare.
Michelin, G. Strukul and D. F. Wass, Adv. Synth. Catal.,
2
012, 354, 1095-1104.
2
2
2
2
3
3
3
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6.
7.
8.
9.
0.
1.
2.
3.
4.
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X. Liu, L. H. Liu, Z. K. Wang and X. F. Fu, Chem. Commun.,
Acknowledgements
We thank the National Natural Science Foundation of China for
financial support (20902008). The theoretical calculation is
supported by CHEMCLOUDCOMPUTING of BUCT.
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