A green, efficient, and rapid procedure for the hydrogenation of nitroarenes to formanilides in water

Article abstract of DOI:10.1007/s00706-017-2071-0

Abstract: A green, efficient, and rapid procedure for the hydrogenation of nitroarenes to formanilides in Pd(TFA)₂/HCOOH system in water is described. Under optimized conditions, the reaction of most substrates is complete within 30?min with yields of 30–93%. Furthermore, this procedure is applied successfully for the modification of natural products, such as arctigenin, vindoline, and estrone. Graphical abstract: [Figure not available: see fulltext.].

Full text of DOI:10.1007/s00706-017-2071-0

Monatsh Chem
DOI 10.1007/s00706-017-2071-0
ORIGINAL PAPER
A green, efficient, and rapid procedure for the hydrogenation
of nitroarenes to formanilides in water
Yingying Wang1 Zhajun Zhan1 Yang Zhou2 Min Lei2
Lihong Hu3
•
•
•
•
Received: 9 August 2017 / Accepted: 9 October 2017
Ó Springer-Verlag GmbH Austria 2018
Abstract A green, efficient, and rapid procedure for the
hydrogenation of nitroarenes to formanilides in Pd(TFA)2/
HCOOH system in water is described. Under optimized
conditions, the reaction of most substrates is complete
within 30 min with yields of 30–93%. Furthermore, this
procedure is applied successfully for the modification of
natural products, such as arctigenin, vindoline, and estrone.
Graphical abstract
Keywords Formanilide Á Hydrogenation Á
Pd(TFA)2/HCOOH Á Green chemistry
Introduction
Formanilides are a class of important intermediates widely
used in the synthesis of industrial chemicals, drugs, dyes,
cosmetics, and food additives. Formylation of amines is an
important method for the synthesis of these compounds
[1–3]. In recent years, a number of formylation reagents
have been reported, such as formic acid-VB1 [4], formic
acid-DCC [5], formic acid-EDCI [6], formic acid-ZnCl2
[7], formic acid-PEG 400 [8], formic acid esters [9–11],
CDMT [12], chloral [13], and others [14–18]. In most
cases, amines are obtained by reduction of nitro com-
pounds. Therefore, the synthesis of formanilides via a
reduction-formylation process has a better atom economy
than a two-step process. Due to growing interest in atom
economy of the reaction, chemists have developed several
alternate and more efficient methods for this reduction-
formylation process, which includes the use of HCOONH4/
Au/TiO2 [19], HCOOH/AgPd@g-C3N4 [20], CH(OEt)3/b-
CD-TiO2 [21], HCOOH/Sn [22], HCOOH/Rh [23], P/I2/
HCOOH [24], and others [15–28]. Although a number of
Electronic supplementary material The online version of this
article (https://doi.org/10.1007/s00706-017-2071-0) contains supple-
mentary material, which is available to authorized users.
& Min Lei
mlei@simm.ac.cn
& Lihong Hu
lhhu@simm.ac.cn
1
College of Pharmaceutical Sciences, Zhejiang University of
Technology, Hangzhou 310032, People’s Republic of China
2
Shanghai Research Center for Modernization of Traditional
Chinese Medicine, Shanghai Institute of Materia Medica,
Chinese Academy of Sciences, Shanghai 201203, People’s
Republic of China
3
Jiangsu Key Laboratory for Functional Substance of Chinese
Medicine, Stake Key Laboratory Cultivation Base for TCM
Quality and Efficacy, School of Pharmacy, Jiangsu
Collaborative Innovation Center of Chinese Medicinal
Resources Industrialization, Nanjing University of Chinese
Medicine, Nanjing, People’s Republic of China
123

Y. Wang et al.
modified methods under improved conditions have been
reported, many of them suffer from drawbacks such as
unsatisfactory yields, high temperatures, and long reaction
times, and the use of corrosive, toxic, and/or relatively
expensive reagents. Therefore, searching for more green,
efficient, and facile method for the synthesis of for-
manilides is still highly desirable work.
reaction, a series of optimization experiments were per-
formed, and the results are summarized in Table 1.
Results and discussion
To further improve the efficiency of this green synthetic
approach, various catalysts such as Pd(OAc)2, PdCl2,
Pd(TFA)2, and Pd(PPh3)4 have been applied to improve
this transformation. As shown in Table 1, both 2a and 3a
were formed in all cases. Only moderate yields (43–59%)
of desired product 2a were obtained in the presence of
Pd(OAc)2, PdCl2, and Pd(PPh3)4 as catalysts. Under similar
reaction conditions, 99% yield of 2a was obtained cat-
alyzed by Pd(TFA)2 (Table 1, entry 3). These results
clearly indicated that Pd(TFA)2 was a more effective cat-
alyst than others.
In connection with our ongoing research for the devel-
opment of simple and efficient methods for organic
synthesis [29–32], we now report a green, efficient, and
practical method for the one-pot synthesis of formanilides
from nitroarenes via a reduction-formylation process
(Scheme 1). Initially, we carried out the reaction of
nitrobenzene (1a) and HCOOH using Pd(OAc)2 as catalyst,
PPh3 as ligand in water. After stirring for 60 min at 80 °C,
the desired product N-phenylformamide (2a) was obtained
in 52% yield. To further improve the efficiency of this
Then, the amount of catalyst and ligand was also opti-
mized. The conversion of 1a was low (43%) resulting from
the decrease amount of Pd(TFA)2 (0.5 mol%) as well as
ligand PPh3 (1 mol%). The yields of 2a and 3a were
roughly equal in the presence of 1 or 3 mol% Pd(TFA)2
(Table 1, entries 6 and 7). Hence, 5 mol% of Pd(TFA)2
was most suitable for this one-pot reduction-formylation
process. Furthermore, this model reaction was also carried
out at different reaction times and the results revealed that
Scheme 1
Table 1 Optimization of the reaction conditions
Entry
[Pd]/mol%
PPh3/mol%
Time/min
Yield/%a
1a
2a
3a
1
Pd(OAc)2 (5)
PdCl2 (5)
10
10
10
0
60
60
60
60
60
60
60
10
20
30
40
50
1
11
0
52
47
46
1
2
43
3
Pd(TFA)2 (5)
Pd(PPh3)4 (5)
Pd(TFA)2 (0.5)
Pd(TFA)2 (1)
Pd(TFA)2 (3)
Pd(TFA)2 (5)
Pd(TFA)2 (5)
Pd(TFA)2 (5)
Pd(TFA)2 (5)
Pd(TFA)2 (5)
99
4
1
59
40
12
42
42
11
2
5
1
57
10
1
31
6
2
48
7
6
48
8
10
10
10
10
10
3
80
98 (92b)
9
0
10
11
12
0
98
2
0
99
1
0
99
1
Conditions: 1a (2.0 mmol), [Pd], PPh3, 1 cm3 HCOOH, 1 cm3 H2O, 80 °C
a
Yields were determined by LC–MS
b
Isolated yield
123

A green, efficient, and rapid procedure for the hydrogenation of nitroarenes to formanilides…
Table 2 Synthesis of formanilides
Entry
Ar
Time/min
Product 2
Yield/%a
M.p./°C
1
C6H5 (1a)
20
20
2a
2b
2c
2d
2e
2f
92
80
92
92
30
77
50
72
60
93
90
92
65
0
Oil (oil [33])
2
2-CH3C6H4 (1b)
3-CH3C6H4 (1c)
4-CH3C6H4 (1d)
2-ClC6H4 (1e)
3-ClC6H4 (1f)
54.2–56.1 (53 [34])
Oil (oil [35])
3
20
4
20
Oil (oil [33])
5
60
75.7–77.4 (76–78 [36])
46.3–46.8 (45–50 [37])
104.5–104.9 (101 [38])
Oil (oil [33])
6
150
20
7
4-ClC6H4 (1g)
2-FC6H4 (1h)
2g
2h
2i
8
20
9
3-CNC6H4 (1i)
4-HOOCC6H4 (1j)
4-CH3OC6H4 (1k)
4-HOC6H4 (1l)
Indol-4-yl (1m)
Imidazol-2-yl (1n)
60
146.6–148.6 (147 [39])
267.3–268.1 (266 [40])
Oil (oil [33])
10
11
12
13
14
20
2j
20
2k
2l
20
136.6–137.6 (136–138 [41])
Colorless gum
60
2m
2n
120
–
Conditions: 1 (2.0 mmol), Pd(TFA)2 (5 mol%), PPh3 (10 mol%), 1 cm3 HCOOH, 1 cm3 H2O, 80 °C
a
Isolated yields
the reaction could be completed within 20 min with the
yields in 98 and 92% with determined by LC–MS or iso-
lated, respectively (Table 1, entry 9).
Scheme 2
To gauge the scope of these conditions, several
nitroarenes were examined under the optimized conditions
(Table 2). As shown in Table 2, methyl substituted sub-
strates at ortho, meta, or para position reacted smoothly
to give the corresponding products in good to excellent
yields (80–92%) (Table 2, entries 2–4). However, only
low-to-medium yields (30–77%) of the desired products
were obtained when using chloro substituted substrates
(Table 2, entries 5–7). Further study revealed that these
substrates easily undergo a dechlorination side reaction
under similar conditions which led to the decrease of
yields. Moreover, both nitroarenes having electron
donating (CH3–, HO–, and CH3O–) or withdrawing (F–,
NC–, and HOOC–) substituents reacted proceeded
smoothly to give the corresponding products in yields
ranging from 60 to 93% (Table 2, entries 2–4, 8–12). In
addition, heterocyclic compounds 4-nitroindole (1m) and
2-nitroimidazole (1n) were also selected for the synthesis
of formanilides. The results showed that 1m could reacted
to form 2m in 65% yield (Table 2, entry 12), however no
product 2n was observed under similar conditions
(Table 2, entry 14).
As shown in Scheme 2, the reaction also carried out
using 3,5-dinitrobenzoic acid (1o) as starting material
under similar reaction conditions. The reaction proceeded
smoothly and completed within 20 min to form desired
product 2o in 94% yield.
Furthermore, this reaction was also applied to natural
products (Scheme 3). At first, arctigenin, vindoline, and
estrone were chosen as starting materials, and 3-nitroarcti-
genin (4a), 15-nitrovindoline (5a), and 2-nitroestrone (6a)
[42] were synthesized by nitration (See Electronic Supple-
mentary Information, ESI). Then, the reaction of 4a, 5a, or
6a was carried out under standard conditions for
60–100 min. The corresponding products 4b, 5b, or 6b were
obtained in 50, 50, and 65% yields, respectively.
On the basis of the experimental results, a possible
mechanism for the formation of formanilide derivatives is
123

Y. Wang et al.
Scheme 3
presented in Scheme 4. Initially, addition of 1 and formic
acid on Pd-Cat led to the formation of key intermediate
palladium hydride complex B. A new hydrido palladium
complex C is formed from B by releasing carbon dioxide.
Upon reduction elimination, complex C gave the inter-
mediate D with regeneration of Pd-Cat. Then, nitroso
compound is formed from D by intramolecular dehydra-
tion. D is further hydrogenated under similar catalytic
process to afford amine 3. At last, 3 reacts with formic acid
to form product 2 by dehydration.
solutions. Optimization reactions were determined by LC–
MS (Waters LCMS/SQD ? UPLC H-class spectrometer).
HR-ESI–MS were determined on a Micromass Q-Tof
Global mass spectrometer and ESI–MS were run on a
Bruker Esquire 3000 Plus Spectrometer. TLC was per-
formed on GF254 silica gel plates (Yantai Huiyou Inc.,
China).
General procedure for the synthesis of compounds
2a–2m
In conclusion, we have demonstrated a green, efficient,
and simple procedure for the hydrogenation of nitroarenes
into formanilides in Pd(TFA)2/HCOOH system in water.
This procedure is also suitable for the modification of
natural products. The main advantages of this methodology
are: (a) the use of relatively non-toxic reagents and sol-
vents; (b) short reaction times; (c) operational simplicity;
(d) good yields of products.
A mixture of nitroarene 1 (2.0 mmol), 1.0 cm3 HCOOH,
33 mg Pd(TFA)2 (0.1 mmol, 5 mol%), and 52 mg PPh3
(0.2 mmol, 10 mol%) in 1.0 cm3 water was sealed and
heated to 80 °C for an appropriate time (Table 2). After
completion of the reaction, the mixture was cooled to room
temperature and diluted with 20 cm3 DCM. The solid was
removed by filter, and the filtrate was washed with 20 cm3
water and 20 cm3 brine. The organic layer was dried over
Na2SO4, filtered, and concentrated under reduced pressure.
The residue was purified by column chromatography on
silica gel to afford product 2a–2m.
Experimental
Melting points were measured by a WRS-1B micromelting
point apparatus. NMR spectra were recorded on a Bruker
AMX 400 instrument using solvent peaks as CDCl3
N-(1H-Indol-4-yl)formamide (2m, C9H8N2O)
Yield: 65%; colorless gum; 1H NMR (400 MHz, CD3OD):
d = 8.73 (s, 0.5H, cis), 8.37 (s, 1H, trans), 7.64 (d,
123

A green, efficient, and rapid procedure for the hydrogenation of nitroarenes to formanilides…
Scheme 4
J = 7.6 Hz, 1H, trans), 7.31–7.16 (m, 3H, trans), 7.07 (td,
J = 7.8, 4.1 Hz, 1.5H, cis), 6.84 (d, J = 7.6 Hz, 0.5H, cis),
6.58 (dd, J = 0.8 Hz, 1H, trans), 6.57 (dd, J = 0.8 Hz,
0.5H, cis) ppm; 13C NMR (101 MHz, CD3OD):
d = 165.74, 161.83, 138.87, 138.46, 130.40, 130.09,
125.88, 125.30, 122.69, 122.56, 122.41, 121.72, 112.35,
110.72, 110.04, 109.51, 99.47, 99.19 ppm; MS (ESI): m/
z = 161 ([M ? H]?); HRMS (ESI): calcd for C9H9N2O
[M ? H]? 161.0709, found 161.0706.
(0.4 mmol, 20 mol%) in 1.0 cm3 water was sealed and heated
to 80 °C for 20 min. After completion of the reaction, the
mixture was cooled to room temperature and diluted with
20 cm3 DCM. The solid was removed by filter, and the filtrate
was washed with 20 cm3 water and 20 cm3 brine. The organic
layer was dried over Na2SO4, filtered, and concentrated under
reduced pressure. The residue was purified by column
chromatography on silica gel to afford the product 2o in
94% yield. Gray solid; m.p.: [300 °C; 1H NMR (400 MHz,
DMSO-d6): d = 13.10 (s, 1H), 10.42 (s, 2H), 8.29 (s, 2H), 8.13
(s, 2H), 7.94 (s, 2H) ppm; 13C NMR (101 MHz, DMSO-d6):
d = 167.07, 166.93, 162.99, 162.59, 160.23, 160.10, 139.98,
139.03, 132.76, 132.12, 115.42, 113.83, 113.33, 112.31 ppm;
3,5-Diformamidobenzoic acid (2o, C9H8N2O4)
Amixture of nitroarene 1o (2.0 mmol), 1.0 cm3 HCOOH,
66 mg Pd(TFA)2 (0.2 mmol, 10 mol%), and 104 mg PPh3
123

Y. Wang et al.
MS (ESI): m/z = 209 ([M ? H]?); HRMS (ESI): calcd for
C9H9N2O4 [M ? H]? 209.0557, found 209.0553.
2-Nitroestrone (6a)
Amixture of 191 mg phenylselenium chloride (1.0 mmol),
170 mg AgNO3 (1.0 mmol) and 20 cm3 MeCN was stirred
at rt for 10 min. Then, 170 mg estrone (1.0 mmol) was
added and the mixture was stirred for 3 h. After completion
of the reaction as monitored by TLC, the mixture was
concentrated under reduced pressure. Then, 20 cm3 DCM
was added, and washed with 20 cm3 water and 20 cm3
brine. The organic layer was dried over Na2SO4, filtered,
and concentrated under reduced pressure. The residue was
purified by column chromatography on silica gel to afford
the product 6a in 75% yield [43].
3-Nitroarctigenin (4a, C21H13NO8)
Amixture of 372 mg arctigenin (1.0 mmol), 8 cm3 Ac2O,
and 4 cm3 AcOH was stirred and cooled to -10 °C. Then,
a mixed acid (0.1 cm3 HNO3 and 4 cm3 AcOH) was added
dropwise to the mixture, and stirred at -10 °C for 1.5 h.
After completion of the reaction as monitored by TLC,
30 cm3 DCM was added, and washed with sat. aq. Na2CO3
(2 9 30 cm3) and 30 cm3 brine. The organic layer was
dried over Na2SO4, filtered, and concentrated under
reduced pressure. The residue was purified by column
chromatography on silica gel to afford the product 4a in
50% yield. Orange solid; m.p.: [ 300 °C; 1H NMR
(400 MHz, CDCl3): d = 10.56 (s, 1H), 6.90 (s, 1H), 6.70
(d, J = 8.0 Hz, 1H), 6.51 (d, J = 8.0 Hz, 1H), 6.48 (s,
1H), 4.17 (t, J = 8.4 Hz, 1H), 3.82–3.67 (m, 10H),
2.88–2.74 (m, 2H), 2.61 (d, J = 7.2 Hz, 2H), 2.57–2.50
(m, 1H), 2.41 (q, J = 8.0 Hz, 1H), 1.23–0.68 (m, 1H) ppm;
13C NMR (101 MHz, CDCl3): d = 178.07, 150.09, 149.17,
148.04, 145.29, 133.26, 129.94, 128.84, 120.57, 119.06,
115.99, 111.66, 111.37, 77.40, 77.08, 76.76, 71.33, 56.69,
55.87, 55.85, 46.31, 41.01, 38.26, 33.92 ppm; MS (ESI):
m/z = 418 ([M ? H]?); HRMS (ESI): calcd for
C21H24NO8 [M ? H]? 418.1496, found 418.1503.
General procedure for the synthesis of compounds
4b, 5b, and 6b
A mixture of 4a, 5a, or 6a (2.0 mmol), 1.0 cm3 HCOOH,
33 mg Pd(TFA)2 (0.1 mmol, 5 mol%), and 52 mg PPh3
(0.2 mmol, 10 mol%) in 1.0 cm3 water was sealed and
heated to 80 °C for an appropriate time as shown above.
After completion of the reaction, the mixture was cooled to
room temperature, and diluted with 20 cm3 DCM. The
solid was removed by filter, and the filtrate was washed
with 20 cm3 water and 20 cm3 brine. The organic layer
was dried over Na2SO4, filtered, and concentrated under
reduced pressure. The residue was purified by column
chromatography on silica gel to afford the product 4b, 5b,
or 6b.
15-Nitrovindoline (5a, C25H31N3O8)
Amixture of 456 mg vindoline (1.0 mmol), 1.2 cm3 Ac2O,
and 0.5 cm3 AcOH was stirred and cooled to 0 °C. Then,
0.1 cm3 HNO3 was added and the mixture was stirred for
5 min. A mixed acid (0.05 cm3 H2SO4 and 1 cm3 AcOH)
was added dropwise to the mixture, and stirred at 0 °C for
10 min. After completion of the reaction as monitored by
TLC, 30 cm3 DCM was added, and washed with sat. aq.
Na2CO3 (2 9 30 cm3) and 30 cm3 brine. The organic layer
was dried over Na2SO4, filtered, and concentrated under
reduced pressure. The residue was purified by column
chromatography on silica gel to afford the product 5a in
3-Formamidoarctigenin (4b, C22H25NO7)
1
Yield: 50%; white solid; m.p.: 119.4–124.6 °C; H NMR
(400 MHz, CDCl3): d = 8.42 (s, 1H), 7.66 (s, 2H), 6.74 (d,
J = 8.1 Hz, 1H), 6.59 (dd, J = 8.1, 1.7 Hz, 1H), 6.51 (dd,
J = 9.2, 1.7 Hz, 2H), 6.02 (s, 1H), 3.86 (s, 1H), 3.84 (s,
3H), 3.82 (s, 3H), 3.80 (s, 3H), 3.04–2.87 (m, 2H),
2.60–2.52 (m, 3H), 2.52–2.43 (m, 1H), 1.25–1.06 (m, 1H)
ppm; 13C NMR (101 MHz, CDCl3): d = 178.81, 178.55,
161.65, 159.05, 149.08, 148.99, 147.98, 147.72, 147.22,
146.90, 134.06, 133.64, 130.51, 130.27, 129.77, 129.42,
124.75, 124.05, 120.74, 120.67, 114.46, 111.84, 111.79,
111.31, 111.23, 110.89, 108.03, 107.96, 71.47, 71.31,
56.20, 56.15, 55.91, 55.87, 55.84, 50.79, 46.65, 41.02,
40.92, 38.26, 34.78, 34.55 ppm; MS (ESI): m/z = 416
([M ? H]?); HRMS (ESI): calcd for C22H26NO7
[M ? H]? 416.1704, found 416.1700.
1
85% yield. Light yellow solid; m.p.: [ 300 °C; H NMR
(400 MHz, CDCl3): d = 7.82 (s, 1H), 5.97 (s, 1H), 5.90
(dd, J = 10.0, 4.8 Hz, 1H), 5.32 (s, 1H), 5.26 (d,
J = 10.4 Hz, 1H), 3.98 (s, 4H), 3.80 (s, 3H), 3.55–3.39
(m, 2H), 2.87 (d, J = 16.0 Hz, 1H), 2.81 (s, 3H), 2.79 (s,
1H), 2.67–2.58 (m, 1H), 2.40–2.22 (m, 2H), 2.07 (s, 3H),
1.69–1.59 (m, 1H), 1.13–1.04 (m, 1H), 0.57 (t, J = 7.4 Hz,
3H) ppm; 13C NMR (101 MHz, CDCl3): d = 171.52,
170.58, 158.22, 157.32, 129.97, 129.92, 124.59, 124.43,
121.71, 91.31, 83.01, 79.18, 77.35, 77.0 3, 76.71, 75.77,
66.66, 56.60, 52.52, 52.17, 51.26, 50.79, 43.74, 42.81,
36.28, 31.09, 20.99, 7.53 ppm; MS (ESI): m/z = 502
([M ? H]?); HRMS (ESI): calcd for C25H32N3O8
[M ? H]? 502.2184, found 502.2190.
15-Formamidovindoline (5b, C26H33N3O7)
1
Yield: 50%; white solid; m.p.: 209.3–209.9 °C; H NMR
(400 MHz, CDCl3): d = 9.77 (s, 1H, trans), 8.35 (s, 1H,
trans), 8.08 (s, 1H, cis), 7.63 (s, 1H), 6.11 (s, 1H), 5.85 (dd,
J = 10.2, 4.5 Hz, 1H), 5.41 (s, 1H), 5.23 (d, J = 10.2 Hz,
1H), 3.87 (s, 3H), 3.78 (s, 3H), 3.71 (s, 1H), 3.49–3.37 (m,
2H), 2.84 (d, J = 16.1 Hz, 1H), 2.77 (s, 1H), 2.67 (s, 3H),
2.62–2.49 (m, 1H), 2.39–2.23 (m, 2H), 2.16 (s, 1H), 2.06
123

A green, efficient, and rapid procedure for the hydrogenation of nitroarenes to formanilides…
10. Kisfaludy L, Laszlo O (1987) Synthesis 19:510
(s, 3H), 1.59 (dq, J = 14.7, 7.2 Hz, 1H), 1.06 (dd,
J = 14.2, 7.4 Hz, 1H), 0.52 (t, J = 7.4 Hz, 3H) ppm;
13C NMR (101 MHz, CDCl3): d = 172.19, 172.03, 171.19,
171.03, 162.48, 158.64, 158.50, 152.21, 151.38, 149.66,
149.52, 130.75, 130.56, 124.68, 124.36, 123.96, 119.66,
117.94, 115.52, 114.40, 94.39, 93.63, 83.77, 83.68, 80.08,
79.94, 76.77, 76.55, 67.19, 66.72, 56.29, 53.74, 53.47,
52.70, 52.60, 52.06, 51.82, 51.37, 51.28, 44.43, 44.33,
43.26, 43.20, 39.41, 39.16, 31.35, 31.22, 21.50, 8.09,
7.99 ppm; MS (ESI): m/z = 500 ([M ? H]?); HRMS
(ESI): calcd for C26H34N3O7 [M ? H]? 500.2391, found
500.2386.
11. Duezek W, Deutsch J, Vieth S, Niclas HJ (1996) Synthesis 28:37
12. Luca LD, Giacomelli G, Porcheddu A, Salaris M (2004) Synlett
15:570
13. Blicke FF, Lu C-J (1952) J Am Chem Soc 74:3933
14. Strazzolini P, Giumanimi AG, Cauci S (1990) Tetrahedron
46:1081
15. Reddy PG, Kumar GDK, Baskaran S (2000) Tetrahedron Lett
41:9149
16. Mihara M, Ishino Y, Minakara S, Komatsu M (2003) Synthesis
35:2317
17. Desai B, Danks TN, Wagner G (2005) Tetrahedron Lett 46:955
18. Hosseini-Sarvari M, Sharghi H (2006) J Org Chem 71:6652
19. Lou X-B, He L, Qian Y, Liu Y-M, Cao Y, Fan K-N (2011) Adv
Synth Catal 353:281
20. Baig RBN, Verma S, Nadagouda MN, Varma RS (2016) Green
Chem 18:1019
21. Kakroudi MA, Kazemi F, Kaboudin B (2014) RSC Adv 4:52762
22. Hrvatin P, Skyes HG (1997) Synlett 8:1069
23. Wei Y, Wu J, Xue D, Wang C, Lin Z, Zhang Z, Chen G, Xiao J
(2014) Synlett 25:1295
24. Du X, Zheng M, Chen S, Xu Z (2006) Synlett 17:1953
25. Lin IJB, Chang C-S (1992) J Mol Catal 73:167
26. Kamal A, Reddy KS, Prasad BR, Babu AH, Ramana AV (2004)
Tetrahedron Lett 45:6517
27. Pratap TV, Baskaran S (2001) Tetrahedron Lett 42:1983
28. Karimi B, Mansouri F, Vali H (2015) ChemPlusChem 80:1750
29. Xiao C, Wang Z, Lei M, Hu L (2017) Tetrahedron 73:204
30. Ma F, Lei M, Hu L (2016) Org Lett 18:2708
31. Sun G, Lei M, Hu L (2016) RSC Adv 6:28442
32. Chen F, Lei M, Hu L (2014) Green Chem 16:2472
33. Chiang K-H, Lu S-H, Yen W-P, Uramaru N, Tseng W-S, Chang
T-W, Wong FF (2016) Heteroatom Chem 27:235
34. Quintanilla-Licea R, Colunga-Valladares JF, Caballero-Quintero
2-Formamidoestrone (6b, C19H23NO3)
1
Yield: 65%; white solid; m.p.: 232.7–233.3 °C; H NMR
(400 MHz, CDCl3): d = 9.60 (s, 1H), 9.46 (s, 1H), 8.22 (s,
1H), 7.94 (s, 1H), 6.55 (s, 1H), 2.72–2.71 (m, 2H), 2.43
(dd, J = 18.8, 8.4 Hz, 1H), 2.25–2.00 (m, 3H), 1.948–1.89
(m, 2H), 1.78–1.75 (m, 1H), 1.5–1.35 (m, 6H), 0.82 (s, 3H)
ppm; 13C NMR (101 MHz, CDCl3): d = 221.80, 160.32,
146.27, 136.37, 132.58, 123.01, 119.45, 119.35, 50.83,
48.48, 44.22, 38.62, 36.37, 32.00, 29.29, 26.89, 26.39,
22.02, 14.32 ppm; MS (ESI): m/z = 314 ([M ? H]?);
HRMS (ESI): calcd for C19H24NO3 [M ? H]? 314.1751,
found 314.1744.
Acknowledgements This work was supported by the National Nat-
ural Science Foundation of China (Grant: 81473110), Special Fund
for Strategic Pilot Technology Chinese Academy of Sciences
(XDA12040303), Shanghai Science and Technology Support Pro-
gram (13431900401).
´
A, Rodrıguez-Padilla C, Tamez-Guerra R, Gomez-Flores R,
Waksman N (2002) Molecules 7:662
´
35. Chen Z, Cao Y, Tian Z, Zhou X, Xu W, Yang J, Teng H (2017)
Tetrahedron Lett 58:2166
36. Habibi D, Sahebekhtiari H, Nasrollahzadeh M, Taghipour A
(2013) Lett Org Chem 10:209
37. Rosowsky A, Forsch RA, Queener SF (1995) J Med Chem
38:2615
38. Surmiak E, Neochoritis CG, Musielak B, Twarda-Clapa A,
References
1. Chancellor T, Morton C (1994) Synthesis 26:1023
2. Aleiwi BA, Mitachi K, Kurosu K (2013) Tetrahedron Lett
54:2077
3. Lv H, Xing Q, Yue C, Lei Z, Li F (2016) Chem Commun
52:6545
4. Lei M, Ma L, Hu L (2010) Tetrahedron Lett 51:4186
5. Waki J, Meinhofer J (1997) J Org Chem 42:2019
6. Chen FMF, Benoiton NL (1979) Synthesis 11:709
7. Shekhar AC, Kumar AR, Sathaiah G, Paul VL, Sridhar M, Rao
PS (2009) Tetrahedron Lett 50:7099
8. Das B, Krishnaiah M, Balasubramanyam P, Veeranjaneyulu B,
Nandankumar D (2008) Tetrahedron Lett 49:2225
9. Yale HL (1971) J Org Chem 36:3238
¨
Kurpiewska K, Dubin G, Camacho C, Holak TA, Domling A
(2017) Eur J Med Chem 126:384
´
39. Pace V, de la Vega-Hernandez K, Urban E, Langer T (2016) Org
Lett 18:2750
40. Sekiya M, Takayama S, Ito K, Suzuki J, Suzuki K, Terao Y
(1972) Chem Pharm Bull 20:2661
41. Shirini F, Mazloumi M, Seddighi M (2016) Res Chem Intermed
42:1759
42. Mostafa YA, Kralt B, Rao PPN, Taylor SD (2015) Bioorg Med
Chem 23:5681
43. Ali H, Lier JE (1991) J Chem Soc Perkin Trans 1:269
123