Regio- and diastereoselective synthesis of (E)-3-(2-aminochromen-4-yl)-6-aryl-substituted fulvenes

Article abstract of DOI:10.1515/znb-2016-0064

A practical base-catalyzed route was developed for the regio- and diastereoselective synthesis of (E)-3-aminochromene-6-aryl-disubstituted fulvenes in high yields up to 94% starting with the Michael addition of cyclopentadiene to 2-iminochromenes in the k

Full text of DOI:10.1515/znb-2016-0064

Z. Naturforsch. 2016; 71(9)b: 945–951
GRaemzgeiKooz-, Oanunr dŞahdiniaandsNteecdreet Coosşkeunl*ective synthesis
of (E)-3-(2-aminochromen-4-yl)-6-aryl-substituted
fulvenes
DOI 10.1515/znb-2016-0064
Received March 15, 2016; accepted May 3, 2016
protein kinase inhibitors, tumor antagonists, and
anticancer drugs [16–19].
We now report a new practical route to (E)-3-(2-amino-
chromen-4-yl)-6-aryl-substituted fulvenes in which we use
cyclopentadiene as a Michael donor in conjugate addition
reactions to 2-iminochromenes and convert these isomeric
Michael adducts into (E)-3,6-disubstituted fulvenes regio-
and diastereoselectively using a modified pyrrolidine-H2O
Abstract: A practical base-catalyzed route was developed
for the regio- and diastereoselective synthesis of (E)-3-
aminochromene-6-aryl-disubstituted fulvenes in high
yields up to 94% starting with the Michael addition of
cyclopentadiene to 2-iminochromenes in the key step.
Keywords: aminochromene; base catalysis; cyclopentadi- catalytic system [20, 21].
ene; fulvene; Michael addition.
2 Results and discussion
1 Introduction
First, we synthesized 2-iminochromenes (1a, b) according
to the previously reported methods, using malononitrile
and salicylaldehyde for 1a, and 2-hydroxy-1-naphtaldehyde
for 1b in 86% and 99% yield, respectively. The 2-imino-
chromenes were characterized using reported spectro-
scopic data and melting points [22].
The conjugate addition of cyclopentadiene (CpH) to
electrophilic 2-iminochromenes was the next key step
in our strategy. Although several nucleophiles such as
indole, nitromethane, or ethyl cyanoacetate were reported
in Michael additions to 2-iminochromenes [23, 24], CpH
was used for the first time in this manner. A series of
organocatalysts were investigated for this addition step,
and we obtained the best results using 10 mol% DBU in
methanol-water mixture (Table 1).
We obtained 2a and 2b as inseparable isomeric mix-
tures using the DBU-catalyzed conjugate addition reaction
(Fig. 2). The isomeric mixtures of 2a and 2b were easily
obtained by filtration and characterized by spectroscopic
methods and elemental analysis. The isomeric ratios were
determined by 1H NMR as 1:5 in the case of 2a, whereas it
was 1:1 in the case of 2b.
Finally, 2a and 2b were reacted with a series of aro-
matic aldehyde and cyclobutanone in MeOH-H2O (4:1)
using 40 mol% of pyrrolidine at 55°C (Fig. 3) to obtain the
targeted functionalized fulvenes. The products were easily
obtained by filtration without any further purification.
The reaction proceeded smoothly and in high yields in
Fulvenes are an interesting class of cyclic cross-conjugated
molecules that display a wide range of reactions with
nucleophiles, electrophiles, and various cycloaddition
partners [1–3]. Pentafulvenes serve as activated dienes
in Diels-Alder reactions and as synthetic precursors to
several biologically occurring compounds [4–6], whereas
6-substituted fulvenes (Fig. 1) are particularly interesting
and easily accessible starting materials for the synthesis
of novel substituted metallocenes [7–10].
These fulvene-derived metallocenes have been
proven to be bio-organometallic anticancer drugs that
offer a significant potential against a variety of cancer
cell lines. However, the diversity of fulvene precursors of
such metallocenes is quite limited [11–15]. As a result, we
have become interested in the synthesis of new and more
functionalized fulvenes, which may find further applica-
tion in both metallocene and chromene chemistry. It is
well known that chromene frameworks also have a wide
application area where they are used as mitogen-activated
*Corresponding author: Necdet Coşkun, Department of Chemistry,
Uludag University, Bursa 16059, Turkey,
e-mail: coskun@uludag.edu.tr
Gamze Koz: Department of Chemistry, Bursa Technical University,
Bursa 16190, Turkey
Onur Şahin: Scientific and Technological Research Application and
Research Center, Sinop University, Sinop 57000, Turkey
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946ꢀ ꢀG. Koz et al.: Synthesis of (E)-3-(2-aminochromen-4-yl)-6-aryl-substituted fulvenes
In addition, cyclic ketones such as cyclopentanone and
cyclohexanone failed to give fulvenes, whereas cyclobu-
tanone reacted to give 3e and 3l in 63% and 77% yield,
respectively.
The fulvenes 3a–l were characterized by elemen-
tal analysis and spectroscopic methods (1H NMR, 13C
NMR, and NOESY). The only product of the reactions
were 3,6-disubstituted fulvenes, and the formation of a
2,6-disubstituted product was not observed in any case.
The exocyclic fulvene double bond had E geometry in
all of the products except for 3a according to spectroscopic
Fig. 1:ꢀAtom numbering scheme in pentafulvene.
Table 1:ꢀThe organocatalysts investigated in conjugate addition of
CpH to 1a.
1
data. In the H NMR spectra, 2-H proton in the Cp ring of
the compound (Z)-3a has a broad singlet at 6.55 ppm,
whereas the signals of 4-H and 5-H appear as a 2H ddd
(Jꢀꢁ=ꢁꢀ11.8, 5.2, 1.7 Hz) at 6.27 ppm. The fulvenes proton 6-H
appears at 7.07 ppm also as a broad singlet. The irradia-
tion of the broad singlet at 6.55 ppm enhanced the doublet
of the 4-methoxyphenyl ring at 7.56 ppm by 4% but not
the signals of 5-H and 6-H. This confirmed the assigned
Z geometry as well as the 3,6-disubstitution of compound
3a. On the other hand, the 1H NMR spectra of compounds
3b–l have two characteristic doublets at 6.59–6.77 ppm
for 4-H and 5-H and a broad singlet at 6.36–6.48 ppm for
2-H, which is indicative of (E)-3,6-disubstituted fulvene
structures. The structure of 3f was ascertained by a crystal
structure determination but a poor data set made a satis-
factory refinement impossible.
10 mol% base
CN
NH
CN
NH
CpH
MeOH-H2O
r. t.
2
O
O
2a + isomer
1a
Base
ꢁ
Time (min)ꢁ
Yield (%)a
Pyrrolidine
Piperidine
DBU
ꢂ
ꢂ
ꢂ
60ꢂ
60ꢂ
30ꢂ
60ꢂ
64
76
80
67
Triethylaminebꢂ
aAll reactions were performed in MeOH-H2O (3:1) at room temperature.
bA sticky precipitate was obtained.
CN
R
NH
O
3 Conclusion
1a, b
We have developed a practical base-catalyzed method
for the regio- and diastereoselective synthesis of (E)-
10 mol% DBU
CpH
MeOH-H2O
r. t.
3-(2-aminochromen-4-yl)-6-aryl-disubstituted
fulvenes
in high yields up to 94%. We used CpH for the first time
as a Michael donor in conjugate addition reactions to
2-iminochromenes in the key step of our method. The
isomeric mixtures of the CpH Michael adducts were suc-
cessfully converted to the functionalized fulvenes using
catalytic amounts of pyrrolidine at 55°C in MeOH-H2O. A
set of 12 different 3,6-disubstituted fulvenes was prepared,
and all except one was determined to have E configuration
in the exocyclic fulvene double bond.
CN
CN
R
R
O
NH2
NH2
O
isomeric mixture
2a (80% yield)
2b (95% yield)
Fig. 2:ꢀDBU-catalyzed conjugate addition of CpH to
2-iminochromenes.
4 Experimental section
the cases of aromatic aldehydes having electron-donating All chemicals and solvents were used as received from
groups. As expected, aldehydes containing electron-with- commercial suppliers and used without any purifica-
drawing groups did not give the corresponding fulvenes. tion. Silica gel F254 (Merck 5554) precoated plates were
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ꢃ947
R'
R'CHO
40 mol% pyrrolidine
N
C
CN
CN
MeOH-H2O
55 °C
NH2
O
R
NH2
O
R
NH2
O
R
3 b−l
2
Fig. 3:ꢀRegio- and diastereoselective fulvene synthesis with a series of aromatic aldehydes and cyclobutanone.
used for thin layer chromatography. Infrared spectra were
recorded on a Thermo-Nicolet 6700 FTIR. UV/Vis spectra
were recorded at room temperature with a Cary 60 2.00
4.1 Synthesis of iminochromene Michael
adducts (2a, b)
spectrometer. NMR experiments were performed on a Pyrrolidine (15 mol%) was added to a suspension of
Varian Mercury Plus 400 MHz spectrometer at ambient aldehyde (5 mmol) and malononitrile (5 mmol) in MeOH-
temperature using TMS as internal standard. The ele- H2O (3:1, 5 mL). The reaction mixture was stirred at room
mental analyses were performed on a Costech ECS 4010 temperature for the specified time and checked with TLC.
analyzer. Melting points were determined in open glass The precipitated iminochromenes (1a, b) were filtered,
capillary tubes with an electrothermal digital melting washed with cold MeOH-H2O (3:1), and dried in a vacuum
point apparatus.
oven. 2-Iminochromenes were characterized using
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948ꢀ ꢀG. Koz et al.: Synthesis of (E)-3-(2-aminochromen-4-yl)-6-aryl-substituted fulvenes
reported spectroscopic data and melting points [19]. DBU mixture of two isomers): δꢀꢁ=ꢁꢀ7.91–7.76 (m, 6H), 7.52–7.41
(10 mol%) was added to a suspension of iminochromene (m,ꢀ4H), 7.21–7.18 (m, 2H), 6.35–6.10 (m, 6H), 5.17 (s, 1H),
(5 mmol) and freshly cracked cyclopentadiene (5 mmol) in 5.13 (s, 1H), 4.61 (bs, 4H), 2.96–2.62 (m, 4H). – 13C NMR
MeOH-H2O (3:1, 30 mL). The reaction mixture was stirred (400 MHz, CDCl3): δꢀꢁ=ꢁꢀ159.6, 159.3, 150.1, 148.2, 146.8,
at room temperature for 30 min and checked with TLC. 146.6, 134.9, 132.2, 131.99, 131.92, 131.22, 131.21, 130.9, 130.8,
The precipitated products were filtered, washed with cold 129.3, 129.2, 128.43, 128.41, 128.3, 127.2, 127.1, 125.12, 125.10,
MeOH-H2O (3:1), and dried in a vacuum oven. The prod- 123.5, 123.4, 120.1, 116.7, 116.6, 115.6, 114.9, 77.3, 77.2, 61.2,
ucts were obtained as a mixture of isomers forming a 60.4, 41.2, 40.7, 34.1, 33.4. C19H14N2O (286.3): calcd. C 79.70,
yellow precipitate.
H 4.93, N 9.78; found C 79.67, H 4.90, N 9.76.
4.1.1 2-Imino-2H-chromene-3-carbonitrile (1a)
4.2 Synthesis of fulvenes 3a–l
1
Yellow solid, 86% yield, m.p. 163–165°C (decomp). – H Aldehyde (0.15 mmol) and pyrrolidine (40 mol%) was
NMR (400 MHz, CDCl3, 25°C, TMS): δꢀꢁ=ꢁꢀ7.77 (s, 1H), 7.53 (td, added to a suspension of iminochromene Michael adduct
Jꢀꢁ=ꢁꢀ1.6, 8.0 Hz, 1H), 7.39 (dd, Jꢀꢁ=ꢁꢀ1.6, 8.0 Hz, 1H), 7.22 (td, (0.15 mmol) in MeOH-H2O (4:1, 2 mL). The reaction mixture
Jꢀꢁ=ꢁꢀ0.8, 8.0 Hz, 1H), 7.16 (d, Jꢀꢁ=ꢁꢀ8.4 Hz, 1H).
was stirred at 55°C for the specified time and checked with
TLC. The precipitated products were filtered, washed with
cold MeOH-H2O (3:1), and dried in a vacuum oven.
4.1.2 3-Imino-3H-benzo[f]chromene-2-carbonitrile (1b)
1
Green solid, 99% yield, m.p. 218–220°C (decomp). – H 4.2.1 (Z)-2-Amino-4-(3-(4-methoxybenzylidene)-
NMR (400 MHz, [D6]DMSO, 25°C, TMS): δꢀꢁ=ꢁꢀ9.11 (s, 1H),
8.76 (s, 1H), 8.42 (d, Jꢀꢁ=ꢁꢀ8.4 Hz, 1H), 8.14 (d, Jꢀꢁ=ꢁꢀ9.2 Hz, 1H),
7.97 (d, Jꢀꢁ=ꢁꢀ8.0 Hz, 1H), 7.69 (t, Jꢀꢁ=ꢁꢀ7.2 Hz, 1H), 7.54 (t, Jꢀꢁ=ꢁꢀ7.6
Hz, 1H), 7.33 (d, Jꢀꢁ=ꢁꢀ8.8 Hz, 1H).
cyclopenta-1,4-dien-1-yl)-4H-chromene-
3-carbonitrile (3a)
Yellow solid, 88% yield, 48 h, m.p. 147–149°C. – UV/Vis
(CH2Cl2): λmaxꢀꢁ=ꢁꢀ335 nm. – IR (ATR): νꢀꢁ=ꢁꢀ3457, 3332, 2189,
1
1648, 1599, 1512, 1401, 1256, 1175 cm–1. – H NMR (400
4.1.3 2-Amino-4-(cyclopenta-1,4-dien-1-yl)-
MHz, CDCl3, 25°C, TMS): δꢀꢁ=ꢁꢀ7.57 (d, Jꢀꢁ=ꢁꢀ8.8 Hz, 2H), 7.21
(td, Jꢀꢁ=ꢁꢀ1.6, 8.8 Hz, 1H), 7.15 (dd, Jꢀꢁ=ꢁꢀ1.2, 7.6 Hz, 1H), 7.09 (d,
Jꢀꢁ=ꢁꢀ1.2 Hz, 1H), 7.07 (s, 1H), 6.98 (dd, Jꢀꢁ=ꢁꢀ0.8, 8.4 Hz, 1H),
4H-chromene-3-carbonitriles (2a)
Yellow solid, 80% yield, m.p. 160°C (decomp). – IR (ATR): 6.94 (d, Jꢀꢁ=ꢁꢀ8.8 Hz, 2H), 6.55 (s, 1H), 6.27 (ddd, Jꢀꢁ=ꢁꢀ11.8, 5.2,
νꢀꢁ=ꢁꢀ3426, 3328, 2190, 1651, 1613, 1581, 1531, 1488, 1406, 1.7 Hz, 2H), 4.67 (bs, 3H), 3.86 (s, 3H). – 13C NMR (400 MHz,
1
1326, 1288, 1266, 1222, 1043 cm–1. – H NMR (400 MHz, CDCl3): δꢀꢁ=ꢁꢀ160.5, 159.8, 151.4, 148.7, 142.8, 138.3, 136.6,
CDCl3, 25°C, TMS; 5:1 mixture of two isomers): δꢀꢁ=ꢁꢀ7.23–7.18 132.3, 129.5, 129.4, 128.9, 128.3, 125.0, 121.5, 120.0, 116.3,
(m, 1H), 7.11–7.05 (m, 2H), 6.99–6.94 (m, 1H), 6.42–6.30 (m, 115.6, 114.3, 58.7, 55.4, 35.9. – C23H18N2O2 (354.4): calcd. C
2H), 6.19 (bs, 0.75H), 4.65 (bs, 0.4H), 4.62 (bs, 2H), 3.02 (d, 77.95, H 5.12, N 7.90; found C 77.92, H 5.10, N 7.89.
13
Jꢀꢁ=ꢁꢀ2.8 Hz, 2H), 3.01–2.68 (m, 0.4H). – C NMR (400 MHz,
CDCl3): δꢀꢁ=ꢁꢀ159.7, 159.5, 150.3, 148.8, 148.5, 148.3, 135.1,
132.9, 131.9, 131.7, 129.2, 129.0, 128.2, 128.1, 127.9, 125.4, 124.9, 4.2.2 (E)-2-Amino-4-(3-(3-methoxybenzylidene)-
124,8, 122.6, 121.9, 120.0, 116.3, 116.3, 109.9, 59.9, 59.2, 41.2,
40.2, 36.5, 35.6. – C15H12N2O (236.3): calcd. C 76.25, H 5.12, N
11.86; found C 76.11, H 5.09, N 11.84.
cyclopenta-1,4-dien-1-yl)-4H-chromene-
3-carbonitrile (3b)
Orange solid, 76% yield, 48 h, m.p. 176–178°C (decomp.).
– IR (ATR): νꢀꢁ=ꢁꢀ3451, 3334, 2194, 1657, 1602, 1577, 1512, 1487,
1
4.1.4 3-Amino-1-(cyclopenta-1,4-dien-1-yl)-1H-benzo[f]
1405, 1251, 1177, 1026 cm–1. – H NMR (400 MHz, CDCl3,
chromene-2-carbonitriles (2b)
25°C, TMS): δꢀꢁ=ꢁꢀ7.51 (d, Jꢀꢁ=ꢁꢀ8.8 Hz, 2H), 7.23–7.17 (m, 2H),
7.11–7.07 (m, 2H), 6.99 (d, Jꢀꢁ=ꢁꢀ8.0 Hz, 1H), 6.91 (d, Jꢀꢁ=ꢁꢀ8.8 Hz,
Light yellow solid, 95% yield, m.p. 195–197°C. – IR (ATR): 2H), 6.69 (d, Jꢀꢁ=ꢁꢀ4.0 Hz, 1H), 6.48 (d, Jꢀꢁ=ꢁꢀ5.2 Hz, 1H), 6.09 (s,
νꢀꢁ=ꢁꢀ3427, 3331, 2185, 1648, 1590, 1407, 1232, 1178, 1080, 1H), 4.64 (s, 1H), 4.61 (bs, 2H), 3.84 (s, 3H). – 13C NMR (400
1
1028 cm–1. – H NMR (400 MHz, CDCl3, 25°C, TMS; 1:1 MHz, CDCl3): δꢀꢁ=ꢁꢀ160.5, 159.7, 148.8, 146.4, 142.8, 138.2,
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ꢃ949
133.9, 132.2, 129.6, 129.4, 128.2, 124.9, 122.6, 121.9, 121.8, 115.6, 59.3, 35.7, 32.3, 32.2, 16.9. – C19H16N2O (288.3): calcd.
119.9, 116.3, 115.6, 114.2, 109.9, 59.1, 55.3, 35,5. – C23H18N2O2 C 79.14, H 5.59, N 9.72; found C 79.11, H 5.56, N 9.71.
(354.4): calcd. C 77.95, H 5.12, N 7.90; found C 77.95, H 5.10,
N 7.88.
4.2.6 (E)-3-Amino-1-(3-(2-methoxybenzylidene)-
cyclopenta-1,4-dien-1-yl)-1H-benzo[f]chromene-
4.2.3 (E)-2-Amino-4-(3-(4-methylbenzylidene)-
cyclopenta-1,4-dien-1-yl)-4H-chromene-
3-carbonitrile (3c)
2-carbonitrile (3f)
Orange solid, 88% yield, 24 h, m.p. 187°C (decomp.). – IR
(ATR): νꢀꢁ=ꢁꢀ3464, 3333, 2187, 1652, 1588, 1404, 1232 cm–1. – 1H
Orange solid, 74% yield, 24 h, m.p. 185°C (decomp.). – IR NMR (400 MHz, CDCl3, 25°C, TMS): δꢀꢁ=ꢁꢀ7.94 (d, Jꢀꢁ=ꢁꢀ8.4 Hz,
(ATR): νꢀꢁ=ꢁꢀ3458, 3347, 2189, 1655, 1605, 1575, 1404 cm–1. – 1H), 7.82 (d, Jꢀꢁ=ꢁꢀ8.0 Hz, 1H), 7.77 (d, Jꢀꢁ=ꢁꢀ8.8 Hz, 1H), 7.53–7.42
1H NMR (400 MHz, CDCl3, 25°C, TMS): δꢀꢁ=ꢁꢀ7.44 (d, Jꢀꢁ=ꢁꢀ8.0 (m, 3H), 7.39 (s, 1H), 7.30 (t, Jꢀꢁ=ꢁꢀ7.2 Hz, 1H), 7.20 (m, 1H), 6.95
Hz, 2H), 7.24–7.08 (m, 6H), 6.99 (d, Jꢀꢁ=ꢁꢀ8.0 Hz, 1H), 6.69 (d, (t, Jꢀꢁ=ꢁꢀ7.6 Hz, 1H), 6.86 (d, Jꢀꢁ=ꢁꢀ8.4 Hz, 1H), 6.53 (d, Jꢀꢁ=ꢁꢀ5.2 Hz,
Jꢀꢁ=ꢁꢀ4 Hz, 1H), 6.47 (d, Jꢀꢁ=ꢁꢀ5.6 Hz, 1H), 6.09 (s, 1H), 4.64 (s, 1H), 6.47 (d, Jꢀꢁ=ꢁꢀ5.6 Hz, 1H), 6.01 (s, 1H), 5.16 (s, 1H), 4.64
1H), 4.61 (bs, 2H), 2.37 (s, 3H). – 13C NMR (400 MHz, CDCl3): (s, 2H), 3.83 (s, 3H). – 13C NMR (400 MHz, CDCl3): δꢀꢁ=ꢁꢀ159.7,
δꢀꢁ=ꢁꢀ159.8, 148.9, 146.9, 143.9, 139.3, 138.4, 134.1, 133.9, 130.5, 158.3, 147.0, 146.9, 144.6, 133.9, 133.7, 132.2, 131.2, 131.1,
129.4, 129.3, 128.2, 124.9, 122.5, 122.2, 121.7, 119.9, 116.3, 58.9, 130.4, 129.3, 128.4, 127.2, 125.9, 125.2, 123.6, 122.4, 121.4,
35.5, 21.4. – C23H18N2O (338.4): calcd. C 81.63, H 5.36, N 8.28; 120.5, 120.2, 116.7, 114.8, 110.5, 59.9, 55.5, 33.3. – C27H20N2O2
found C 81.59, H 5.29, N 8.21.
(404.5): calcd. C 80.18, H 4.98, N 6.93; found C 79.99, H
4.96, N 6.87.
4.2.4 (E)-2-Amino-4-(3-(4-(dimethylamino)benzylidene)-
cyclopenta-1,4-dien-1-yl)-4H-chromene-
3-carbonitrile (3d)
4.2.7 (E)-3-Amino-1-(3-(3-methoxybenzylidene)-
cyclopenta-1,4-dien-1-yl)-1H-benzo[f]chromene-
2-carbonitrile (3g)
Orange solid, 62% yield, 24 h, m.p. 203°C (decomp.). – IR
(ATR): νꢀꢁ=ꢁꢀ3329, 2923, 2189, 1643, 1595, 1528, 1373, 1192 cm–1.
– 1H NMR (400 MHz, CDCl3, 25°C, TMS): δꢀꢁ=ꢁꢀ7.51 (d, Jꢀꢁ=ꢁꢀ8.8
Hz, 2H), 7.20 (m, 2H), 7.10 (d, Jꢀꢁ=ꢁꢀ7.6 Hz, 1H), 7.05 (s, 1H),
6.98 (d, Jꢀꢁ=ꢁꢀ8.4 Hz, 1H), 6.77 (dd, Jꢀꢁ=ꢁꢀ2.0, 5.2 Hz, 1H), 6.67
(d, Jꢀꢁ=ꢁꢀ9.2 Hz, 2H), 6.45 (d, Jꢀꢁ=ꢁꢀ5.2 Hz, 1H), 6.07 (s, 1H), 4.64
Orange solid, 92% yield, 48 h, m.p. 195°C (decomp.). – IR
(KBr): νꢀꢁ=ꢁꢀ3451, 3332, 2186, 1657, 1619, 1592, 1407, 1237 cm–1.
1
– H NMR (400 MHz, [D6]DMSO, 25°C, TMS): δꢀꢁ=ꢁꢀ8.04 (d,
Jꢀꢁ=ꢁꢀ8.8 Hz, 1H), 7.91 (m, 2H), 7.54 (t, Jꢀꢁ=ꢁꢀ7.2 Hz, 1H), 7.46 (t,
Jꢀꢁ=ꢁꢀ7.6 Hz, 1H), 7.34–7.29 (m, 2H), 7.21 (s, 1H), 7.11 (d, Jꢀꢁ=ꢁꢀ7.6
Hz, 1H), 7.05 (bs, 3H), 6.93 (d, Jꢀꢁ=ꢁꢀ8.0 Hz, 1H), 6.57 (d, Jꢀꢁ=ꢁꢀ4.4
Hz, 1H), 6.35 (d, Jꢀꢁ=ꢁꢀ5.2 Hz, 1H), 6.08 (s, 1H), 5.17 (s, 1H), 3.74
13
(s, 1H), 4.56 (bs, 2H), 3.03 (s, 6H). – C NMR (400 MHz,
CDCl3): δꢀꢁ=ꢁꢀ140.3, 139.7, 132.7, 132.6, 132.4, 129.4, 128.0, 124.9,
123.2, 122.9, 121.4, 120.1, 116.2, 111.9, 77.5, 77.4, 77.2, 59.6, 59.1,
40.1, 35.46. – C24H21N3O (367.2): calcd. C 78.45, H 5.76, N
11.44; found C 78.40, H 5.72, N 11.39.
13
(s, 3H). – C NMR (400 MHz, [D6]DMSO): δꢀꢁ=ꢁꢀ161.3, 159.8,
148.3, 147.2, 144.8, 138.5, 137.9, 135.4, 131.1, 130.8, 130.4,
129.8, 128.9, 127.6, 125.5, 123.8, 123.1, 122.2, 121.2, 121.1, 117.3,
115.6, 115.5, 115.3, 55.5, 55.3, 33.1. – C27H20N2O2 (404.5): calcd.
C 80.18, H 4.98, N 6.93; found C 80.08, H 4.95, N 6.90.
4.2.5 2-Amino-4-(3-cyclobutylidenecyclopenta-
1,4-dien-1-yl)-4H-chromene-3-carbonitrile (3e)
4.2.8 (E)-3-Amino-1-(3-(4-methoxybenzylidene)-
cyclopenta-1,4-dien-1-yl)-1H-benzo[f]chromene-
2-carbonitrile (3h)
Yellow solid, 63% yield, 24 h, m.p. 188°C (decomp.). – IR
(ATR): νꢀꢁ=ꢁꢀ3456, 3346, 2189, 1654, 1605, 1575, 1485, 1401,
1230 cm–1. – 1H NMR (400 MHz, CDCl3, 25°C, TMS): δꢀꢁ=ꢁꢀ7.19 Orange solid, 84% yield, 30 h, m.p. 206°C (decomp.). –
(t, Jꢀꢁ=ꢁꢀ7.2 Hz, 1H), 7.13 (d, Jꢀꢁ=ꢁꢀ7.2 Hz, 1H), 7.07 (t, Jꢀꢁ=ꢁꢀ7.2 Hz, IR (KBr): νꢀꢁ=ꢁꢀ3451, 3332, 2186, 1657, 1619, 1592, 1407, 1237
1H), 6.97 (d, Jꢀꢁ=ꢁꢀ8.0 Hz, 1H), 6.26 (s, 2H), 6.06 (s, 1H), 4.59 cm–1. – 1H NMR (400 MHz, [D6]DMSO, 25°C, TMS): δꢀꢁ=ꢁꢀ8.04
(bs, 3H), 3.08 (d, Jꢀꢁ=ꢁꢀ4.8 Hz, 4H), 2.14 (p, Jꢀꢁ=ꢁꢀ7.6 Hz, 2H). (d, Jꢀꢁ=ꢁꢀ8.4 Hz, 1H), 7.92–7.89 (m, 2H), 7.55–7.51 (m, 3H), 7.45
13
– C NMR (400 MHz, CDCl3): δꢀꢁ=ꢁꢀ160.1, 159.6, 148.8, 146.9, (t, Jꢀꢁ=ꢁꢀ7.6 Hz, 1H), 7.29 (d, Jꢀꢁ=ꢁꢀ9.2 Hz, 1H), 7.15 (s, 1H), 7.03
138.2, 129.4, 129.3, 128.1, 124.9, 122.0, 121.8, 120.0, 116.3, (s, 2H), 6.96 (d, Jꢀꢁ=ꢁꢀ8.8 Hz, 2H), 6.61 (d, Jꢀꢁ=ꢁꢀ4.4 Hz, 1H), 6.32
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950ꢀ ꢀG. Koz et al.: Synthesis of (E)-3-(2-aminochromen-4-yl)-6-aryl-substituted fulvenes
(d, Jꢀꢁ=ꢁꢀ5.2 Hz, 1H), 6.04 (s, 1H), 5.14 (s, 1H), 3.76 (s, 3H). – 13C Jꢀꢁ=ꢁꢀ8.4 Hz, 1H), 7.92–7.89 (m, 2H), 7.54–7.43 (m, 4H), 7.28 (d,
NMR (400 MHz, [D6]DMSO): δꢀꢁ=ꢁꢀ160.9, 160.5, 146.8, 146.7, Jꢀꢁ=ꢁꢀ9.2 Hz, 1H), 7.04 (s, 1H), 6.96 (s, 2H), 6.70 (d, Jꢀꢁ=ꢁꢀ8.8 Hz,
142.1, 138.4, 134.3, 132.4, 130.7, 130.5, 129.3, 128.9, 128.5, 2H), 6.64 (dd, Jꢀꢁ=ꢁꢀ1.6, 4.8 Hz, 1H), 6.27 (d, Jꢀꢁ=ꢁꢀ5.2 Hz, 1H),
127.2, 125.1, 123.6, 121.4, 121.2, 120.9, 116.9, 115.3, 114.6, 55.4, 5.99 (s, 1H), 5.11 (s, 1H), 2.96 (s, 6H). – 13C NMR (400 MHz,
55.2, 32.8. – C27H20N2O2 (404.5): calcd. C 80.18, H 4.98, N [D6]DMSO): δꢀꢁ=ꢁꢀ160.7, 151.2, 146.7, 145.1, 139.8, 139.2, 132.8,
6.93; found C 80.12, H 4.96, N 6.91.
132.5, 130.7, 130.5, 129.2, 128.5, 127.1, 125.2, 125.1, 123.8,
123.6, 123.5, 121.4, 120.7, 120.6, 116.8, 56.1, 55.7, 32.8. –
C28H23N3O (417.5): calcd. C 80.55, H 5.55, N 10.06; found C
80.49, H 5.51, N 10.01.
4.2.9 (E)-3-Amino-1-(3-(4-methylbenzylidene)-
cyclopenta-1,4-dien-1-yl)-1H-benzo[f]chromene-
2-carbonitrile (3i)
4.2.12 3-Amino-1-(3-cyclobutylidenecyclopenta-
1,4-dien-1-yl)-1H-benzo[f]chromene-
2-carbonitrile (3l)
Yellow solid, 94% yield, 30 h, m.p. 238°C (decomp.). – UV/
Vis (CH2Cl2): λmaxꢀꢁ=ꢁꢀ210 nm. IR (KBr): νꢀꢁ=ꢁꢀ3435, 3327, 2187,
1658, 1621, 1594, 1409, 1236 cm–1. – 1H NMR (400 MHz, [D6]
DMSO, 25°C, TMS): δꢀꢁ=ꢁꢀ8.04 (d, Jꢀꢁ=ꢁꢀ8.4 Hz, 1H), 7.92–7.89 Yellow solid, 77% yield, 24 h, m.p. 218–220°C (decomp.).
(m, 2H), 7.55–7.44 (m, 4H), 7.29 (d, Jꢀꢁ=ꢁꢀ9.2 Hz, 1H), 7.22–7.18 – IR (KBr): νꢀꢁ=ꢁꢀ3456, 3351, 2186, 1658, 1591, 1405, 1230 cm–1.
1
(m, 3H), 7.04 (s, 2H), 6.60 (d, Jꢀꢁ=ꢁꢀ4.8 Hz, 1H), 6.33 (d, Jꢀꢁ=ꢁꢀ4.8 – H NMR (400 MHz, [D6]DMSO, 25°C, TMS): δꢀꢁ=ꢁꢀ7.98 (d,
13
Hz, 1H), 6.06 (s, 1H), 5.15 (s, 1H), 2.29 (s, 3H). – C NMR Jꢀꢁ=ꢁꢀ8.4 Hz, 1H), 7.91–7.87 (m, 2H), 7.52 (t, Jꢀꢁ=ꢁꢀ7.6 Hz, 1H), 7.45
(400 MHz, [D6]DMSO): δꢀꢁ=ꢁꢀ160.9, 147.4, 146.8, 146.7, 143.4, (t, Jꢀꢁ=ꢁꢀ7.2 Hz, 1H), 7.27 (d, Jꢀꢁ=ꢁꢀ8.8 Hz, 1H), 6.97 (s, 2H), 6.14
139.4, 138.5, 134.7, 133.6, 130.7, 130.5, 129.7, 129.4, 128.5, 127.2, (dd, Jꢁ=ꢁ 0.8, 4.8 Hz, 1H), 6.07 (d, Jꢁ=ꢁ 4.4 Hz, 1H), 5.93 (s, 1H),
125.1, 123.5, 121.6, 121.0, 120.9, 116.9, 115.1, 55.1, 32.7, 21.0. 5.07 (s, 1H), 2.97 (bs, 4H), 2.02 (p, Jꢀꢁ=ꢁꢀ7.6 Hz, 2H). – 13C NMR
– C27H20N2O (388.5): calcd. C 83.48, H 5.19, N 7.21; found C (400 MHz, [D6]DMSO): δꢀꢁ=ꢁꢀ160.7, 159.9, 147.8, 146.7, 137.8,
83.42, H 5.15, N 7.19.
130.7, 130.4, 129.5, 129.2, 128.5, 127.2, 125.1, 123.5, 121.7, 120.9,
116.9, 115.5, 113.9, 55.7, 32.9, 31.9, 31.8, 16.6. – C23H18N2O
(338.4): calcd. C 81.63, H 5.36, N 8.28; found C 81.60, H 5.32,
N 8.22.
4.2.10 (E)-3-Amino-1-(3-(3-methylbenzylidene)-
cyclopenta-1,4-dien-1-yl)-1H-benzo[f]chromene-
2-carbonitrile (3j)
5 Supporting information
Yellow solid, 86% yield, 24 h, m.p. 215°C (decomp.). –
IR (KBr): νꢀꢁ=ꢁꢀ3426, 3334, 2186, 1642, 1621, 1593, 1407, 1235
cm–1. – 1H NMR (400 MHz, [D6]DMSO, 25°C, TMS): δꢀꢁ=ꢁꢀ8.04
(d, Jꢀꢁ=ꢁꢀ8.4 Hz, 1H), 7.93–7.90 (m, 2H), 7.54 (t, Jꢀꢁ=ꢁꢀ8.0 Hz,
1H), 7.46 (t, Jꢀꢁ=ꢁꢀ7.6 Hz, 1H), 7.33–7.26 (m, 4H), 7.19–7.16 (m,
2H), 7.05 (s, 2H), 6.59 (d, Jꢀꢁ=ꢁꢀ5.2 Hz, 1H), 6.35 (d, Jꢀꢁ=ꢁꢀ4.8 Hz,
1
13
Full experimental details, H and C NMR spectra of all
compounds are given as Supporting Information available
online (DOI: 10.1515/znb-2016-0064).
Acknowledgments: G. K. acknowledges a BIDEB 2218-Post-
doctoral Fellowship from the Turkish Scientific and
Technological Research Council (TUBITAK). Prof. Ihsan
Erden of SFSU is gratefully acknowledged for helpful
discussions and the careful reading of the manuscript.
The Scientific and Technological Research Application
and Research Center (Sinop University, Turkey) is grate-
fully acknowledged for the use of the Bruker D8 QUEST
diffractometer.
13
1H), 6.07 (s, 1H), 5.16 (s, 1H), 2.29 (s, 3H). – C NMR (400
MHz, [D6]DMSO): δꢀꢁ=ꢁꢀ160.9, 147.7, 146.8, 144.1, 138.5, 138.2,
136.3, 134.8, 130.9, 130.8, 130.5, 130.1, 129.4, 128.9, 128.5,
127.6, 127.3, 125.2, 123.5, 121.9, 120.9, 116.9, 115.0, 109.7, 55.0,
32.7, 20.9. – C27H20N2O (388.5): calcd. C 83.48, H 5.19, N 7.21;
found C 83.40, H 5.11, N 7.19.
4.2.11 (E)-3-amino-1-(3-(4-(dimethylamino)benzylidene)-
cyclopenta-1,4-dien-1-yl)-1H-benzo[f]chromene-
2-carbonitrile (3k)
References
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1
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G. Koz et al.: Synthesis of (E)-3-(2-aminochromen-4-yl)-6-aryl-substituted fulvenesꢃ
ꢃ951
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