DBU-catalyzed synthesis of novel 2-Amino-3-nitrile-4H-chromenes

Article abstract of DOI:10.1515/znb-2017-0040

A simple method via the base-catalyzed Michael addition of nitroalkanes to 2-iminochromenes was developed, which leads to the production of highly functionalized 2-Amino-3-nitrile-4H-chromenes in good yields.

Full text of DOI:10.1515/znb-2017-0040

Z. Naturforsch. 2017; aop
Gamze Koz* and Ömer Koz
DBU-catalyzed synthesis of novel 2-amino-3-
nitrile-4H-chromenes
https://doi.org/10.1515/znb-2017-0040
in the Michael addition of nitroalkanes to unsaturated
carbonyl compounds [22–26]. However, there is no
report on the DBU-catalyzed Michael additions to
Received February 10, 2017; accepted June 2, 2017
Abstract: A simple method via the base-catalyzed Michael
addition of nitroalkanes to 2-iminochromenes was devel-
oped, which leads to the production of highly functional-
ized 2-amino-3-nitrile-4H-chromenes in good yields.
2-iminochromenes.
2
Results and discussion
Keywords: base catalyst; iminochromene; Michael addi-
tion; nitroalkane.
First, wesynthesizedandcharacterized2-iminochromenes
(
1a–g) according to previously reported methods using
Dedicated to: This paper is dedicated to Professor Necdet Coşkun on
the pyrrolidine catalyzed reaction of appropriate alde-
hydes and malononitrile in methanol [27–31].
the occasion of his 57th birthday.
Then we investigated a series of base catalysts and
solvents for the addition of nitroalkanes to 2-imino-
chromenes. We selected the addition of nitromethane to
1
Introduction
1
a as a test reaction (Table 1).
The chromene moiety often appears as an important
The catalytic system 20 mol% DBU-MeOH/H O was
2
structural component in both biologically active and determined as the optimum for this addition reaction.
natural compounds. It widely occurs in natural alka- Finally, we assessed the scope of the reaction using
loids, flavonoids, tocopherols and anthocyanins [1–4]. nitroalkanes, and various 2-iminochromenes and a series
Moreover, in recent years, functionalized chromenes of functionalized 2-amino-3-nitrile-4H-chromenes (2a–g,
have played an increasing role in the field of medici- 3a–g) were obtained successfully with good yields (Fig. 2).
nal chemistry [5–7]. Among different types of chromene All of the new 2-amino-3-nitrile-4H-chromenes were fully
1
systems, 2-amino-4H-chromenes are of particular utility characterized using spectroscopic methods (IR, H NMR,
1
3
as they belong to privileged medicinal scaffolds serving
C NMR, HRMS) while the spectroscopic data of the
for the generation of small-molecule ligands with highly known compounds were checked with literature data. In
pronounced spasmolytic, diuretic, anti-coagulant and the course of the nitroethane addition, the products were
anti-anaphylactic activities [8–11]. Due to their numerous obtained as a 1:1 mixture of diastereomers except for 3c
applications, some catalytic methods have been reported and 3g which were obtained as only one diastereomer.
for the synthesis of 2-amino-3-nitrile-4H-chromenes [12–
We also applied our optimized conditions to the
1
6]. However, the general approach for their synthesis is one-pot synthesis of 2-amino-3-nitrile-4H-chromenes [32],
a cascade Michael-cyclization sequence of 2-(E)-2-nitrovi- but the substrate scope was very narrow and the reaction
nylphenols and malononitrile using a variety of catalysts times were very long, up to 24 h (Fig. 3).
(
Fig. 1) [17–20].
In the course of our studies on the asymmetric syn-
thesis of chromene heterocycles [21], we developed a prac- 3 Conclusions
tical 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) catalyzed
method for the synthesis of 2-amino-4-(nitroalkyl)-4H- We have developed a practical method for the synthesis
chromene-3-carbonitriles. DBU is a well-known catalyst of medicinally privileged 2-amino-3-nitrile-4H-chromenes
using DBU as a Brønsted base in aqueous media. This
catalyst proved to be efficient for the Michael addition of
*
Corresponding author: Gamze Koz, Department of Chemistry,
nitroalkanes to electrophilic 2-iminochromenes. A series
Bursa Technical University, 16310 Bursa, Turkey,
e-mail: gamzedkoz@gmail.com
of highly functionalized 2-amino-3-nitrile-4H-chromenes
(
14 examples) were synthesized successfully using this
Ömer Koz: Department of Chemistry, Bursa Technical University,
16310 Bursa, Turkey
catalytic system.
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ꢀꢀꢀꢀꢁꢀG. Koz and Ö. Koz: DBU-catalyzed synthesis of novel 2-amino-3-nitrile-4H-chromenes
NO2
CN
was added. The precipitated product was filtered and
washed with cold MeOH and dried under vacuum.
NO2
catalyst
NCCH2CN
OH
O
NH2
4
.1.1 2-Imino-2H-chromene-3-carbonitrile (1a)
Fig. 1:ꢀGeneral method for the synthesis of
-amino-3-nitrile-4H-chromenes.
2
1
Yellow solid, 86% yield, m.p. 163–165°C (decomp.). – H
NMR (400 MHz, CDCl , 25°C, TMS): δꢀ=ꢀ7.77 (s, 1H), 7.53 (td,
Jꢀ=ꢀ1.6, 8.0 Hz, 1H), 7.39 (dd, Jꢀ=ꢀ1.6, 8.0 Hz, 1H), 7.22 (td,
Jꢀ=ꢀ0.8, 8.0 Hz, 1H), 7.16 (d, Jꢀ=ꢀ8.4 Hz, 1H).
3
Table 1:ꢀBase-catalyzed Michael addition of nitromethane to 1a.
NO2
CN
NH
CN
CH3NO2
O
O
NH2
4.1.2 2-Imino-8-methoxy-2H-chromene-3-carbonitrile (1b)
1
a
2a
1
Pale yellow solid, 82% yield, m.p. 173–174°C. – H NMR
Base
Solvent
Timea
(min)
Catalyst Yield (%)b
loading (%)
(
(
400 MHz, [D ]DMSO, 25°C, TMS): δꢀ=ꢀ8.93 (s, 1H), 8.32
6
catalyst
1
3
s, 1H), 6.92–7.38 (m, 3H), 3.86 (s, 3H). – C NMR (75 MHz,
DBU
DBU
DBU
DBU
Toluene
ꢂꢃ
ꢆꢃ
ꢄꢃ
ꢅꢅ
8ꢃ
8ꢆ
9ꢇ
8ꢄ
ꢅꢈ
88
89
[
D ]DMSO, 25°C, TMS): δꢀ=ꢀ161.91, 151.41, 146.37, 124.51,
6
Methanol
ꢄꢃ
ꢄꢃ
ꢆꢃ
ꢆꢃ
ꢆꢃ
ꢆꢃ
ꢆꢃ
1
22.82, 118.12, 115.59, 104.78, 55.29.
MeOH:H O (ꢇ:ꢄ)
ꢆꢃ
ꢆ
MeOH:H O (ꢇ:ꢄ)
ꢄꢃ
ꢆ
c
DABCO
MeOH:H O (ꢇ:ꢄ)
ꢄ8ꢃ
ꢄꢆꢃ
ꢂꢃ
ꢆ
Et N
MeOH:H O (ꢇ:ꢄ)
ꢂ
ꢆ
4
.1.3 6-Hydroxy-2-imino-2H-chromene-3-carbonitrile (1c)
Piperidine
Pyrrolidine MeOH:H O (ꢇ:ꢄ)
MeOH:H O (ꢇ:ꢄ)
ꢆ
ꢂꢃ
ꢆ
1
Dark green-brown solid, 91% yield, m.p. >260°C. – H NMR
a
All reactions were performed at room temperature.
b
(400 MHz, [D ]DMSO, 25°C, TMS): δꢀ=ꢀ9.75 (br s, 1H), 8.61 (s,
Isolated yield.
6
c
13
DABCO (1,4-diazabicyclo[2.2.2]octane).
1H), 8.31 (s, 1H), 7.04–6.39 (m, 3H). – C NMR ([D ]DMSO,
6
7
5 MHz, 25°C, TMS): δꢀ=ꢀ153.4, 152.1, 146.9, 146.8, 121.4,
1
17.5, 116.3, 113.8, 104.1, 23.6.
4
Experimental section
All reagents were obtained from commercial sources and
were used without further purification. Silica gel F254 (Merck
4
.1.4 6-Bromo-2-imino-2H-chromene-3-carbonitrile (1d)
5554) precoated plates were used for thin layer chromatog-
1
Pale yellow solid, 88% yield, m.p. 184°C. – H NMR
raphy. Infrared spectra were recorded on a NICOLET-IS50
(
400 MHz, CDCl , 25°C, TMS): δꢀ=ꢀ7.84–7.83 (br, 1H), 7.71–
1
13
3
FTIR. H NMR and C NMR spectra were carried out using
a 400 MHz Bruker NMR spectrometer at ambient tempera-
ture. HRMS analyses were performed on Agilent 6540 UHD
accurate mass Q-TOF LC/MS. Melting points were recorded
with an electrothermal digital melting point apparatus.
The 2-iminochromenes 1a–g were synthesized by previ-
ously reported methods and characterized using melting
point and NMR data [27–31]. Compounds 2a–g, 3a, 3b and
7
.69 (m, 1H), 7.63–7.62 (m, 1H), 7.54 (s, 1H), 7.06–7.05 (br,
1
3
1
1
H). – C NMR (CDCl , 75 MHz, 25°C, TMS): δꢀ=ꢀ152.7, 143.8,
36.7, 136.5, 131.9, 131.7, 130.9, 117.9, 116.8, 113.8.
3
4
.1.5 6-tert-Butyl-2-imino-2H-chromene-3-carbonitrile
1e)
(
3
d were characterized using melting point and NMR data
Yellow solid, 75% yield, m.p. 129°C. IR (ATR): νꢀ=ꢀ3302,
of previous reports [17–19, 32–34].
3
032, 2952, 2228, 1651, 1616, 1577, 1377, 1209, 1121, 847,
−1
1
8
15 cm . – H NMR (400 MHz, CDCl , 25°C, TMS): δꢀ=ꢀ7.69
3
(
s, 1H), 7.57 (s, 1H), 7.47 (d, Jꢀ=ꢀ5.6 Hz, 1H), 6.98 (d, Jꢀ=ꢀ5.6 Hz,
H), 1.25 (s, 9H). – C NMR (CDCl , 75 MHz, 25°C, TMS):
4
.1 General procedure for the synthesis
of 2-iminochromenes (1a–g)
1
3
1
3
δꢀ=ꢀ154.0, 152.0, 147.7, 146.1, 131.6, 125.3, 116.7, 115.7, 114.6,
To a solution of aromatic aldehyde (5 mmol) and malon- 105.1, 34.5, 31.2. – HRMS ((+)-ESI): m/zꢀ=ꢀ227.2341 (calcd.
onitrile (5 mmol) in MeOH (4 mL) piperidine (30 mol%) 227.1139 for C H N O, [Mꢀ+ꢀH] ).
+
14
14
2
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G. Koz and Ö. Koz: DBU-catalyzed synthesis of novel 2-amino-3-nitrile-4H-chromenesꢉꢁꢀꢀꢀꢉ3
R'
NO2
CN
CN
NH
2
0 mol% DBU
R'CH2NO2
MeOH/H2O
r. t.
R
O
R
O
NH2
1
a−g
2 a−g, R' = H
3
a−g, R' = CH3
NO2
CN
NO2
CN HO
NO2
CN
O
NH2
O
NH2
O
NH2
OCH3
2
a
2b
94% yield
10 min.
2c
82% yield
20 min.
9
2% yield
0 min.
1
NO2
CN
NO2
NO2
NO2
CN
t-Bu
Br
CN t-Bu
CN
O
NH2
O
NH2
O
NH2
O
NH2
t-Bu
2
d
2e
86% yield
20 min.
2f
2g
96% yield
20 min.
8
9% yield
0 min.
91% yield
40 min.
3
NO2
CN
NO2
NO2
NO2
CN HO
CN Br
CN
O
NH2
O
NH2
O
NH2
O
NH2
OCH3
3
a
3b
80% yield
15 min.
3c
76% yield
40 min.
3d
92% yield
40 min.
9
8% yield
0 min.
1
NO2
NO2
CN
NO2
CN
t-Bu
CN
t-Bu
O
NH2
O
NH2
O
NH2
t-Bu
3f
90% yield
50 min.
3
e
3g
85% yield
40 min.
8
6% yield
5 min.
1
Fig. 2:ꢀDBU-catalyzed Michael addition of nitroalkanes to 2-iminochromenes.
4
.1.6 6,8-Di-tert-butyl-2-imino-2H-chromene-3-
4.1.7 3-Imino-3H-benzo[ꢀfꢀꢀ]chromene-3-carbonitrile (1g)
carbonitrile (1f)
1
Dark green solid, 99% yield, m.p. 218–220°C. – H NMR
Pale yellow solid, 83% yield, m.p. 156–158°C (decomp.). – (400 MHz, CDCl , 25°C, TMS): δꢀ=ꢀ8.48 (s, 1H), 8.06 (d,
3
1
H NMR (400 MHz, CDCl , 25°C, TMS): δꢀ=ꢀ7.78 (d, Jꢀ=ꢀ1.6 Hz, Jꢀ=ꢀ5.1 Hz, 1H), 7.98 (d, Jꢀ=ꢀ5.4 Hz, 1H), 7.86 (d, Jꢀ=ꢀ4.8 Hz,
3
1
H), 7.61 (bs, 1H), 7.56–7.55 (d, Jꢀ=ꢀ2.4 Hz, 1H), 7.19–7.19 (d, 1H), 7.71–7.67 (m, 2H), 7.55 (t, Jꢀ=ꢀ4.5 Hz, 1H), 7.24 (s, 1H).
13
13
Jꢀ=ꢀ2.4 Hz, 1H), 1.45 (9H, s), 1.33 (9H, s). – C NMR (CDCl ,
– C NMR (CDCl , 75 MHz, 25°C, TMS): δꢀ=ꢀ154.3, 141.4,
3
3
7
5 MHz, 25°C, TMS): δꢀ=ꢀ162.7, 150.6, 148.1, 146.9, 137.4, 135.5, 130.1, 129.3, 129.2, 128.9, 126.3, 120.9, 116.2, 114.9,
25.3, 123.7, 118.4, 115.7, 114.6, 35.0, 34.6, 31.2, 29.8. 111.2, 104.2.
1
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ꢀꢀꢀꢀꢁꢀG. Koz and Ö. Koz: DBU-catalyzed synthesis of novel 2-amino-3-nitrile-4H-chromenes
NO2
CHO
OH
CN
2
0 mol% DBU
MeOH/H2O
8
2% yield
NCCH2CN
3 2
CH NO
8h
O
NH2
OCH3
OCH3
2b
NO2
trace
12h
HO
CHO
HO
CN
2
0 mol% DBU
MeOH/H2O
NCCH2CN
3 2
CH NO
OH
O
NH2
2c
Fig. 3:ꢀDBU-catalyzed one-pot synthesis of 2-amino-3-nitrile-4H-chromenes.
1
3
3
H), 3.41 (s, 2H). – C NMR (CDCl , 600 MHz, 25°C, TMS):
4
.2 General procedure for the Michael
addition of nitroalkanes to
3
δꢀ=ꢀ161.7, 147.8, 138.9, 125.5, 119.7, 119.0, 118.6, 111.8, 80.1,
6.1, 54.2, 34.9.
5
2
-iminochromenes (2a–g, 3a–g)
The corresponding 2-iminochromene (1a–g) (0.30 mmol)
was added to the mixture of a 20 mol% DBU and nitrometh-
ane (0.90 mmol) in methanol:water (5:1, 5 mL). The result-
ing suspension was stirred at room temperature until
the addition was completed. The solvent was removed
under vacuum and the product was extracted with
dichloromethane:water. The organic phase was dried with
Na SO , filtered, and dichloromethane fraction was evapo-
4
.2.3 2-Amino-6-hydroxy-4-(nitromethyl)-4H-chromene-
-carbonitrile (2c)
3
White crystal, 82% yield, m.p. 165°C (decomp.). – IR
ATR): νꢀ=ꢀ3450, 3333, 2190, 1652, 1615, 1580, 1539, 1498,
(
−1
1
1
427, 1220 cm . – H NMR (400 MHz, [D ]DMSO, 25°C,
6
TMS): δꢀ=ꢀ9.45 (s, 1H), 7.01 (s, 2H), 6.87–6.84 (d, Jꢀ=ꢀ8.8 Hz,
2
4
1
1
H), 6.71–6.68 (dd, Jꢀ=ꢀ2.8, 8.8 Hz, 1H), 6.65 (d, Jꢀ=ꢀ2.8 Hz,
H), 4.74–4.69 (dd, Jꢀ=ꢀ5.2, 12.4 Hz, 1H), 4.63–4.58 (dd,
rated under vacuum. The crude product was purified with
column chromatography (1:3 ethyl acetate:hexane) to give
the addition product.
1
3
Jꢀ=ꢀ5.6, 12.4 Hz, 1H), 4.22–4.19 (t, Jꢀ=ꢀ5.2 Hz, 1H). – C NMR
400 MHz, [D ]DMSO, 25°C, TMS): δꢀ=ꢀ162.4, 153.9, 142.1,
(
1
6
20.0, 119.9, 116.8, 115.8, 113.5, 80.7, 49.5, 34.9.
4
.2.1 2-Amino-4-(nitromethyl)-4H-chromene-3-
carbonitrile (2a)
4
.2.4 2-Amino-6-bromo-4-(nitromethyl)-4H-chromene-3-
carbonitrile (2d)
1
Yellow crystal, 92% yield, m.p. 143–144°C. – H NMR
400 MHz, CDCl , 25°C, TMS): δꢀ=ꢀ7.47–7.43 (m, 2H), 7.32–
(
7
3
1
White crystal, 89% yield, m.p. 181–182°C. – H NMR
.28 (t, Jꢀ=ꢀ8 Hz, 1H), 7.16–7.14 (d, Jꢀ=ꢀ8 Hz, 1H), 4.93–4.89
(
400 MHz, CDCl , 25°C, TMS): δꢀ=ꢀ7.70 (d, Jꢀ=ꢀ2.4 Hz, 1H),
3
(
dd, Jꢀ=ꢀ5.2, 12.4 Hz, 1H), 4.81–4.77 (dd, Jꢀ=ꢀ5.2, 12.4 Hz, 1H),
7
.57–7.54 (dd, Jꢀ=ꢀ2.4, 8.8 Hz, 1H), 7.07–7.05 (d, Jꢀ=ꢀ8.8 Hz, 1H),
13
4
.45–4.42 (t, Jꢀ=ꢀ5.2 Hz, 1H), 3.44 (s, 2H). – C NMR (CDCl ,
3
4
1
.95–4.91 (dd, Jꢀ=ꢀ5.2, 12.4 Hz, 1H), 4.78–4.74 (dd, Jꢀ=ꢀ4.8,
6
00 MHz, 25°C, TMS): δꢀ=ꢀ161.7, 149.3, 129.6, 127.9, 125.7,
13
2.8 Hz, 1H), 4.41–4.39 (t, Jꢀ=ꢀ4.8 Hz, 1H), 3.37 (s, 2H). – C
1
18.6, 116.9, 109.9, 80.1, 54.2, 34.7.
NMR (CDCl , 600 MHz, 25°C, TMS): δꢀ=ꢀ161.3, 148.4, 132.7,
3
130.6, 120.7, 118.6, 118.2, 118.1, 79.6, 34.5, 29.7.
4
.2.2 2-Amino-8-methoxy-4-(nitromethyl)-4H-
chromene-3-carbonitrile (2b)
4.2.5 2-Amino-6-tert-butyl-4-(nitromethyl)-4H-
chromene-3-carbonitrile (2e)
1
Yellow crystal, 94% yield, m.p. 166–167°C. – H NMR
1
(
400 MHz, CDCl , 25°C, TMS): δꢀ=ꢀ7.24–7.19 (t, Jꢀ=ꢀ8 Hz, 1H), White crystal, 86% yield, m.p. 121–123°C. – H NMR
3
7
.14–7.12 (dd, Jꢀ=ꢀ1.2, 8.4 Hz, 1H), 6.98–6.97 (d, Jꢀ=ꢀ7.6 Hz, (400 MHz, CDCl , 25°C, TMS): δꢀ=ꢀ7.30 (d, Jꢀ=ꢀ5.6 Hz, 1H),
3
1
H), 4.88–4.84 (dd, Jꢀ=ꢀ5.2, 12 Hz, 1H), 4.76–4.72 (dd, 7.10 (s, 1H), 6.95 (d, Jꢀ=ꢀ5.6 Hz, 1H), 4.99 (bs, 2H), 4.60 (dd,
Jꢀ=ꢀ5.2, 12 Hz, 1H), 4.41–4.38 (t, Jꢀ=ꢀ5.2 Hz, 1H), 3.92 (s, Jꢀ=ꢀ3.2, 8 Hz, 1H), 4.46 (dd, Jꢀ=ꢀ5.2, 8 Hz, 1H), 4.36–4.34
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G. Koz and Ö. Koz: DBU-catalyzed synthesis of novel 2-amino-3-nitrile-4H-chromenesꢉꢁꢀꢀꢀꢉ5
1
3
−1
1
(
t, Jꢀ=ꢀ4 Hz, 1H), 1.27 (s, 9H). – C NMR (CDCl , 600 MHz, 703 cm . – H NMR (400 MHz, CDCl , 25°C, TMS): δꢀ=ꢀ7.09–
3 3
2
5°C, TMS): δꢀ=ꢀ162.0, 148.7, 146.9, 126.5, 124.5, 119.0, 117.9, 7.05 (m, 2H), 6.89–6.87 (m, 2H), 6.69 (d, Jꢀ=ꢀ5.2 Hz, 1H), 6.53
(d, Jꢀ=ꢀ5.2 Hz, 1H), 5.16 (bs, 2H), 5.12 (bs, 2H), 4.69–4.65
m, 1H), 4.53–4.49 (m, 1H), 4.38 (d, Jꢀ=ꢀ2.8 Hz, 1H), 4.17 (d,
1
16.2, 80.5, 53.5, 35.1, 34.4, 31.2.
(
Jꢀ=ꢀ4.0 Hz, 1H), 3.87 (s, 6H), 1.55 (d, Jꢀ=ꢀ4.4 Hz, 3H), 1.33 (d,
1
3
4
.2.6 2-Amino-6,8-di-tert-butyl-4-(nitromethyl)-4H-
Jꢀ=ꢀ4.4 Hz, 3H). – C NMR (400 MHz, CDCl , 25°C, TMS):
3
chromene-3-carbonitrile (2f)
δꢀ=ꢀ162.8, 162.3, 147.6, 147.4, 139.6, 139.3, 125.4, 125.3, 120.8,
1
19.4, 119.3, 119.2, 119.1, 118.5, 111.8, 111.6, 87.8, 86.1, 55.9,
1
White crystal, 91% yield, m.p. 115°C. – H NMR (400 MHz, 54.0, 52.6, 40.5, 40.4, 29.6, 14.9, 12.8.
[
D ]DMSO, 25°C, TMS): δꢀ=ꢀ7.23 (d, Jꢀ=ꢀ2 Hz, 1H), 7.15 (bs,
H), 4.68–4.63 (dd, Jꢀ=ꢀ6.4, 12 Hz, 1H), 4.62–4.57 (dd, Jꢀ=ꢀ6,
6
3
1
2 Hz, 1H), 4.25–4.22 (t, Jꢀ=ꢀ6 Hz, 1H), 1.36 (s, 9H), 1.25 (s, 4.2.10 2-Amino-6-hydroxy-4-(nitroethyl)-4H-chromene-
13
9
H). – C NMR (400 MHz, [D ]DMSO, 25°C, TMS): δꢀ=ꢀ162.1,
3-carbonitrile (3c)
6
1
46.1, 145.9, 136.2, 122.9, 122.6, 119.7, 119.6, 81.0, 49.7, 35.5,
3
4.5, 34.1, 31.0, 29.9.
Yellow solid, 76% yield, m.p. 115°C (decomp.). – IR (ATR):
−1
νꢀ=ꢀ3399, 3341, 2958, 2929, 2852, 2181, 1731, 1274, 744 cm .
1
–
H NMR (400 MHz, [D ]DMSO, 25°C, TMS): δꢀ=ꢀ9.48 (bs,
6
4
.2.7 3-Amino-1-(nitromethyl)-1H-benzo[f]chromene-
1H), 7.12 (bs, 2H), 6.87 (d, Jꢀ=ꢀ5.6 Hz, 1H), 6.69 (d, Jꢀ=ꢀ5.6 Hz,
1H), 6.60 (s, 1H), 4.72–4.68 (m, 1H), 4.13 (d, Jꢀ=ꢀ3.2 Hz, 1H),
2
-carbonitrile (2g)
1
3
1
.28 (d, Jꢀ=ꢀ4.4 Hz, 3H). – C NMR (400 MHz, [D ]DMSO,
6
1
Yellow crystal, 96% yield, m.p. 157–159°C. – H NMR 25°C, TMS): δꢀ=ꢀ163.5, 153.9, 142.5, 120.5, 116.8, 115.7, 113.7,
(
400 MHz, [D ]DMSO, 25°C, TMS): δꢀ=ꢀ8.09–8.06 (d, 86.9, 47.8, 40.3, 28.9, 13.5. – HRMS ((+)-ESI): m/zꢀ=ꢀ262.1945
6
+
Jꢀ=ꢀ8.8 Hz, 1H), 8.00–7.98 (d, Jꢀ=ꢀ8 Hz, 1H), 7.96–7.94 (d, (calcd. 262.0783 for C H N O , [Mꢀ+ꢀH] ).
1
1
11
3
4
Jꢀ=ꢀ9.2 Hz, 1H), 7.68–7.67 (t, Jꢀ=ꢀ7.2 Hz, 1H), 7.56–7.53 (t,
Jꢀ=ꢀ8 Hz, 1H), 7.25–7.23 (m, 3H), 4.99–4.97 (t, Jꢀ=ꢀ4.4 Hz, 1H),
1
3
4
.75 (d, Jꢀ=ꢀ4.4 Hz, 2H). – C NMR (400 MHz, [D ]DMSO, 4.2.11 2-Amino-6-bromo-4-(nitroethyl)-4H-chromene-3-
6
2
5°C, TMS): δꢀ=ꢀ162.2, 147.8, 130.6, 129.9, 129.4, 128.7, 127.6,
25.2, 122.2, 119.7, 116.5, 111.9, 79.7, 50.4, 32.4.
carbonitrile (3d)
1
White solid, 92% yield, m.p. 179°C (decomp.). – IR (ATR):
νꢀ=ꢀ3438, 3323, 3276, 3191, 2923, 2855, 2193, 1648, 1598,
−1
1
4
.2.8 2-Amino-4-(nitroethyl)-4H-chromene-3-
1033, 827 cm . – H NMR (400 MHz, [D ]DMSO, 25°C,
6
carbonitrile (3a)
TMS): δꢀ=ꢀ7.54–7.49 (m, 4H), 7.32 (bs, 2H), 7.30 (bs, 2H),
7.04 (d, Jꢀ=ꢀ5.6 Hz, 1H), 7.01 (d, Jꢀ=ꢀ6.0 Hz, 1H), 4.89–4.85
Yellow solid, 98% yield, m.p. 159°C (decomp.). – IR (ATR): (m, 1H), 4.84–4.81 (m, 1H), 4.31 (d, Jꢀ=ꢀ2.8 Hz, 1H), 4.20 (d,
−1
1
νꢀ=ꢀ3432, 3320, 3199, 2199, 1636, 1539, 1418, 759 cm . – H Jꢀ=ꢀ2.0 Hz, 1H), 1.42 (d, Jꢀ=ꢀ4.4 Hz, 3H), 1.29 (d, Jꢀ=ꢀ4.0 Hz,
1
3
NMR (400 MHz, [D ]DMSO, 25°C, TMS): δꢀ=ꢀ7.36–7.33 (m, 3H). – C NMR (400 MHz, [D ]DMSO, 25°C, TMS): δꢀ=ꢀ162.9,
6
6
2
7
H), 7.29 (d, Jꢀ=ꢀ4.8 Hz, 1H), 7.25 (bs, 2H), 7.24 (bs, 2H), 162.7, 149.13, 149.11, 131.9, 131.7, 130.9, 130.8, 130.7, 122.4,
.21–7.15 (m, 3H), 7.08–7.04 (m, 2H), 4.83–4.79 (m, 1H), 122.2, 120.2, 119.5, 118.3, 118.1, 116.2, 116.1, 87.5, 86.5, 48.3,
.78–4.75 (m, 1H), 4.25 (d, Jꢀ=ꢀ3.2 Hz, 1H), 4.20 (d, Jꢀ=ꢀ2.8 Hz, 48.13, 48.10, 14.7, 13.4.
4
1
3
1
H), 1.35 (d, Jꢀ=ꢀ4.4 Hz, 3H), 1.21 (d, Jꢀ=ꢀ4.0 Hz, 3H). – C
NMR (400 MHz, [D ]DMSO, 25°C, TMS): δꢀ=ꢀ163.1, 162.9,
6
1
49.8, 149.7, 129.1, 128.4, 128.2, 124.73, 124.70, 120.2, 119.8, 4.2.12 2-Amino-6-tert-butyl-4-(nitroethyl)-4H-
1
19.7, 119.3, 116.1, 115.9, 87.3, 86.9, 49.1, 48.3, 40.4, 39.9, 39.8,
chromene-3-carbonitrile (3e)
14.1, 13.5.
Yellow solid, 86% yield, m.p. 130–132°C. – IR (ATR):
νꢀ=ꢀ3479, 3326, 2957, 2905, 2201, 1636, 1545, 1533, 1430,
−1
1
4
.2.9 2-Amino-8-methoxy-4-(nitroethyl)-4H-chromene-
1386, 1362, 1277, 821 cm . – H NMR (400 MHz, CDCl , 25°C,
3
3
-carbonitrile (3b)
TMS): δꢀ=ꢀ7.30 (m, 2H), 7.10 (s, 1H), 6.97–6.91 (m, 3H), 5.03
(
bs, 2H), 4.99 (bs, 2H), 4.70–4.68 (m, 1H), 4.54–4.49 (m,
Yellow solid, 80% yield, m.p. 165°C (decomp.). – IR (ATR): 1H), 4.38 (d, Jꢀ=ꢀ2.4 Hz, 1H), 4.18 (d, Jꢀ=ꢀ4.4 Hz, 1H), 1.56
νꢀ=ꢀ3394, 3055, 2987, 2196, 1651, 1583, 1551, 1265, 736, (d, Jꢀ=ꢀ4.4 Hz, 3H), 1.31 (d, Jꢀ=ꢀ4.4 Hz, 3H), 1.28 (s, 9H), 1.26
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6
ꢀꢀꢀꢀꢁꢀG. Koz and Ö. Koz: DBU-catalyzed synthesis of novel 2-amino-3-nitrile-4H-chromenes
13
(
s, 9H). – C NMR (400 MHz, CDCl , 25°C, TMS): δꢀ=ꢀ162.9, Prof. Mehmet İşleyen was gratefully acknowledged for
3
1
1
62.5, 148.7, 148.5, 147.8, 147.6, 126.3, 126.2, 125.0, 124.7, HRMS analyses.
19.6, 119.2, 118.9, 116.5, 116.0, 115.7, 88.1, 86.2, 54.1, 52.5,
4
0.7, 40.6, 34.4, 34.3, 31.2, 31.1, 15.0, 12.3. – HRMS ((+)-ESI):
+
m/zꢀ=ꢀ302.2785 (calcd. 302.1460 for C H N O , [Mꢀ+ꢀH] ).
16
19
3
3
References
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1] V. S. Parmaxr, S. C. Jain, K. S. Bisht, R. Jain, P. Taneja, A. Jha,
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[
[
[
[
[
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3
–
C NMR (400 MHz, CDCl , 25°C, TMS): δꢀ=ꢀ162.7, 162.2,
3
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–
HRMS ((+)-ESI): m/zꢀ=ꢀ358.3628 (calcd. 358.2086 for
+
C H N O , [Mꢀ+ꢀH] ).
2
0
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3
3
ꢊ] A. A. Patchett, R. P. Nargund, Annu. Rep. Med. Chem. 2000,
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Catal. 2008, 350, 5ꢊ1.
4
.2.14 3-Amino-1-(nitroethyl)-1H-benzo[ꢀfꢀꢀ]chromene-2-
1
carbonitrile (3g)
[
[
Yellow solid, 85% yield, m.p. 139°C (decomp.). – IR (ATR):
νꢀ=ꢀ3332, 3194, 2926, 2193, 1723, 1654, 1586, 1542, 1418, 1236,
[
−1
1
7
39 cm . – H NMR (400 MHz, [D ]DMSO, 25°C, TMS):
6
δꢀ=ꢀ8.13 (d, Jꢀ=ꢀ5.6 Hz, 1H), 8.01 (d, Jꢀ=ꢀ5.2 Hz, 1H), 7.99 (d,
Jꢀ=ꢀ6.0 Hz, 1H), 7.34 (t, Jꢀ=ꢀ4.8 Hz, 1H), 7.57 (t, Jꢀ=ꢀ5.2 Hz,
1
1
H), 7.39 (bs, 2H), 7.29 (d, Jꢀ=ꢀ6.0 Hz, 1H), 5.10 (d, Jꢀ=ꢀ1.2 Hz, [15] M. N. Elinson, A. I. Ilovaisky, V. M. Merkulova, P. A. Belyakov, A.
1
3
O. Chizhov, G. I. Nikishin, Tetrahedron 2010, 66, 4043.
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23, 33ꢊ.
H), 4.93–4.89 (m, 1H), 1.16 (d, Jꢀ=ꢀ4.4 Hz, 3H). – C NMR
[
[
[
[
(
400 MHz, [D ]DMSO, 25°C, TMS): δꢀ=ꢀ163.2, 147.9, 130.7,
6
1
30.2, 129.2, 128.8, 127.9, 125.4, 119.5, 116.6, 112.6, 84.1, 47.7,
3
7.7, 15.9, 11.5. – HRMS ((+)-ESI): m/zꢀ=ꢀ296.2281 (calcd.
96.0991 for C H N O , [Mꢀ+ꢀH] ).
+
2
16
13
3
3
[
20] K. Hu, A. Lu, Y. Wanga, Z. Zhou, C. Tang, Tetrahedron: Asymme-
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[
[
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given as Supplementary Information available online
https://doi.org/10.1515/znb-2017-0040).
2
(
[
2
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G. Koz and Ö. Koz: DBU-catalyzed synthesis of novel 2-amino-3-nitrile-4H-chromenesꢉꢁꢀꢀꢀꢉ7
[
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Supplemental Material: The online version of this article offers
supplementary material (https://doi.org/10.1515/znb-2017-0040).
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Z. Naturforsch.ꢉ
ꢉ2017 | Volume x | Issue x(b)
Graphical synopsis
Gamze Koz and Ömer Koz
DBU-catalyzed synthesis of novel
2-amino-3-nitrile-4H-chromenes
https://doi.org/10.1515/znb-2017-0040
Z. Naturforsch. 2017; x(x)b: xxx–xxx
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