Electrochemically induced chain transformation of salicylaldehydes and alkyl cyanoacetates into substituted 4H-chromenes

Article abstract of DOI:10.1016/j.tetlet.2006.08.053

Electrolysis of salicylaldehydes and alkyl cyanoacetates in ethanol in an undivided cell in the presence of sodium bromide results in the formation of substituted alkyl 2-amino-4-(1-cyano-2-alkoxy-2-oxoethyl)-4H-chromene-3-carboxylates in 85-95% yields.

Full text of DOI:10.1016/j.tetlet.2006.08.053

Tetrahedron Letters 47 (2006) 7629–7633
Electrochemically induced chain transformation
of salicylaldehydes and alkyl cyanoacetates into
substituted 4H-chromenes
Michail N. Elinson,* Alexander S. Dorofeev, Sergey K. Feducovich, Sergey V. Gorbunov,
Ruslan F. Nasybullin, Nikita O. Stepanov and Gennady I. Nikishin
N. D. Zelinsky Institute of Organic Chemistry, Leninsky prospect 47, 119991 Moscow, Russia
Received 5 June 2006; revised 9 August 2006; accepted 17 August 2006
Abstract—Electrolysis of salicylaldehydes and alkyl cyanoacetates in ethanol in an undivided cell in the presence of sodium bromide
results in the formation of substituted alkyl 2-amino-4-(1-cyano-2-alkoxy-2-oxoethyl)-4H-chromene-3-carboxylates in 85–95%
yields.
Ó 2006 Elsevier Ltd. All rights reserved.
The chromene (or benzopyran) moiety often appears as
an important structural component in both biologically
active and natural compounds. Chromene fragments
occur in alkaloids, flavonoids, tocopherols and antho-
cyanins.1 Moreover, functionally substituted chromenes
have played increasing roles in synthetic approaches to
promising compounds in the field of biomedicinal chem-
istry.2 The current interest in 4H-chromene derivatives
bearing a nitrile functionality arises from their potential
application in the treatment of human inflammatory
TNFa-mediated diseases, such as rheumatoid and psori-
atic arthritis, and of cancer therapy. Thus, the corre-
sponding (4H-chromen-4-yl)malononitriles were found
to inhibit mitogen-activated protein kinase-activated
protein kinase 2 (MK-2) and suppress the expression
of the TNFa in U937 cells.3 In the case of cancer ther-
apy, substituted alkyl (4H-chromen-4-yl)cyanoacetates
are a new class of small molecules that exhibit a binding
activity for the surface pocket of cancer implicated Bcl-2
protein and induce apoptosis or programmed cell death
in tumor cells.4
coumarins,5 or coumarin imines, which can be hydro-
lyzed to coumarins.5c
Nevertheless, synthetic approaches to the corresponding
4H-chromen-4-yl derivatives are known and employ the
reaction of salicylaldehydes with alkyl cyanoacetates
catalyzed by ammonium acetate,6 aluminum oxide,7
8
˚
molecular sieves 3 A or by potassium exchanged
layered zirconium phosphate under solvent-free condi-
tions.9 The catalysis with ammonium acetate requires
careful temperature control (5–10) °C to ensure product
selectivity and the yields of the desired product are in the
range of 40–80%.6 The application of solid phase catal-
7
8
˚
ysis using aluminum oxide or the molecular sieves 3 A
is more convenient and results in the formation of the
corresponding 4H-chromene derivatives in 50–85%
yields. The best yields (70–95%) of the corresponding
substituted 4H-chromenes were reported for the reac-
tion of salicylaldehydes with alkyl cyanoacetates using
potassium exchanged layered zirconium phosphate cata-
lyst under the solvent-free conditions, but this method
requires long reaction times (2–15 h) and a 60 °C reac-
tion temperature.9
The condensation of salicylaldehyde derivatives with
active methylene compounds in the presence of ammo-
nium acetate, pyridine, or piperidine usually leads to
Due to the extensive research on the electrochemistry of
organic compounds over the last three decades, electro-
synthesis has become a useful method in modern organic
chemistry.10 Additionally, electrochemical processes are
beneficial from the viewpoint of environmentally benign
organic synthesis as electricity is the most ecologically
Keywords: Electrocatalysis; Electrolysis; Electrocatalytic transforma-
tion; Salicylaldehydes; Alkyl cyanoacetates; 4H-chromenes.
*
Corresponding author. Tel.: +7 495 938 35 42; fax: +7 495 137 38
42; e-mail: elinson@ioc.ac.ru
0040-4039/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.08.053

7630
M. N. Elinson et al. / Tetrahedron Letters 47 (2006) 7629–7633
R1
Table 1. Electrocatalytic transformation of salicylaldehyde 1a and
R2
methyl cyanoacetate 2a into 4H-chromene 3aa,b,14
R1
R2
CN
NC
R3O
R3O
CN
NH2
electrolysis, 0.05-0.10 F/mol
R3OH
I (mA) Time (min) Electricity passed (F/mol) Yield (%)c
NC
NC
250
125
50
30
30
30
30
0.47
0.23
0.09
0.04
68
75
95
79
CN
N
Scheme 1.
20
a 10 mmol of salicylaldehyde 1a, 20 mmol of methyl cyanoacetate,
1 mmol of NaBr, 20 ml of EtOH, Fe-cathode (5 cm2), C-anode
(5 cm2), 20 °C.
R1
R1
COOR2
O
NC
COOR2
COOR2
b Melting point 3a: 121–123 °C, lit. melting point 120–122 °C.7 The
ratio of diastereoisomers was 2:1 (according to NMR data in
DMSO-d6).
NC
R2O
R2O
electrolysis, 0.2 F/mol
R2OH
NC
N
H
c Isolated yields.
Scheme 2.
Table 2. Electrocatalytic transformation of substituted salicylaldehydes 1a–e and alkyl cyanoacetates 2a,b into 4H-chromenes 3b–ja,14
Aldehyde
Alkyl cyanoacetate
4H-Chromene
Yield, %b
Ratio of isomersc
Mp °C found
Mp °C reported
1a
1b
1b
1c
1c
1d
1d
1e
1e
2b
2a
2b
2a
2b
2a
2b
2a
2b
3b
3c
3d
3e
3f
91
93
88
85
87
84
89
85
83
2:1
3:2
2:1
3:2
5:2
2:1
2:1
7:2
2:1
141–143
126–127
107–108
155–156
134–135
156–157
125–126
150–152
127–128
142–1436
—
104–1056
1569
—
3g
3h
3i
150–1537
126–1276
—
3j
—
a 10 mmol of salicylaldehyde, 20 mmol of alkyl cyanoacetate, 1 mmol of NaBr, 20 ml of EtOH, Fe-cathode (5 cm2), C-anode, (5 cm2), 20 °C.
b Isolated yields.
c According to 1H NMR data in DMSO-d6.
R3OOC
CN
O
C
COOR3
NH2
R1
R1
CN
electrolysis, 0.09 F/mol
EtOH, NaBr
H
2
+
COOR3
OH
O
R2
R2
2a,b
1a-e
3a-j
a R3 = Me
b R3 = Et
a R1 = R2 = H
a R1 = R2 = H, R3 = Me; b R1 = R2 = H, R3 = Et;
b R1 = Br, R2 = H
c R1 = NO2, R2 = H
d R1 = H, R2 = MeO
c R1 = Br, R2 = H, R3 = Me; d R1 = Br, R2 = H, R3 = Et;
e R1 = NO2, R2 = H, R3 = Me; f R1 = NO2, R2 = H, R3 = Et;
g R1 = H, R2 = MeO, R3 = Me; h R1 = H, R2 = MeO, R3 = Et;
COOR3
CN
O
C
NH2
R3OOC
H
O
OH
1e
3i,j
i R3 = Me, j R3 = Et
Scheme 3.

M. N. Elinson et al. / Tetrahedron Letters 47 (2006) 7629–7633
7631
rocatalytic chain cyclization of tetracyanocyclopropanes
in an undivided cell, by the action of alkoxide anions
generated at the cathode, into substituted 2-amino-4,
4-dialkoxy-1,5-dicyano-3-azabicyclo[3.1.0]hex-2-enes12
(Scheme 1).
H
H
COOR3
COOR3
COOR3
COOR3
NC
NC
H
O
H
O
NH2
NH2
Recently, we reported a similar stereoselective electro-
catalytic chain transformation of 3-substituted 2,2-dicy-
anocyclopropane-1,1-dicarboxylates into (1R,5R,6R)*-
6-substituted-4,4-dialkoxy-5-cyano-2-oxo-3-azabicyclo-
[3.1.0]hexane-1-carboxylates13 (Scheme 2).
erythro
threo
Scheme 4.
pure oxidative and reductive agent. Despite the signifi-
cant synthetic potential and ecological advantages, the
practical use of electrochemical procedures has often
been limited on account of technical complexity and
generally long processing times.
We now report the use of the electrocatalytic chain pro-
cedure for the preparation of 4H-chromenes 3a–j under
mild conditions by the combined electrolysis of salicyl-
aldehydes 1a–e and alkyl cyanoacetates 2a,b in ethanol
in an undivided cell (Tables 1 and 2; Scheme 3).
In the course of our studies on the electrochemical oxida-
tion of organic compounds in the presence of alkali metal
halides,11 we have developed a new type of electrochem-
ical transformation, namely, the electrocatalytic chain
transformation of organic compounds in an undivided
cell. The first example of this process involved the elect-
First, to evaluate the synthetic potential of the proce-
dure and to optimize the electrolysis conditions, the
electrocatalytic transformation of salicylaldehyde 1a
and 2 equiv of methyl cyanoacetate 2a into 4H-chro-
mene 3a was studied (Table 1).
-
COOR3
CN
O
O
COOR3
CN
R1
R1
R1
H
-
-HO
-
CH(CN)(COOR3)
+
OH
OH
OH
R2
R2
R2
-
HO
1
R1
COOR3
R1
COOR3
NH
CH2(CN)(COOR3)
-
CH(CN)(COOR3)
+
-
N
O
O
R2
R2
R3OOC
CN
R1
COOR3
-
EtO
EtOH
+
-
NH
O
The beginning of
new catalytic cycle
R2
R3OOC
CN
R1
COOR3
NH2
O
R2
3
Scheme 5.

7632
M. N. Elinson et al. / Tetrahedron Letters 47 (2006) 7629–7633
Research; Harborne, J. B., Ed.; Chapman & Hall: Lon-
don, 1988; (b) Iacobucci, G. A.; Sweeny, J. G. Tetrahedron
1983, 39, 3005–3038; (c) Bohm, B. A.; Choy, J. B.; Lee, A.
Y.-M. Phytochemistry 1989, 28, 501–504; (d) Gill, M.
Aust. J. Chem. 1995, 48, 1–26; (e) Parmar, V. S.; Jain, S.
C.; Bisht, K. S.; Jain, R.; Taneja, P.; Jha, A.; Tyagi, O. D.;
Prasad, A. K.; Wengel, J.; Olsen, C. E.; Boll, P. M.
Phytochemistry 1997, 46, 597–674; (f) Polyakov, V. V.
Chem. Nat. Compd. (Engl. Transl.) 1999, 1, 21–28.
Under the optimal conditions found (I = 50 mA,
current density = 10 mA/cm2, 0.09 F/mol electricity
passed, time = 30 min) the electrolyses of substituted
salicylaldehydes 1a–e and alkyl cyanoacetates 2a,b were
carried out in EtOH. The results are summarized in
Table 2.
1H and 13C NMR data showed that the 4H-chromenes
3a–j thus obtained were mixtures of two diastereoiso-
mers. From a thermodynamic point of view, the more
abundant isomer should have an erythro configuration
(Scheme 4).
2. For recent reports on biologically active chromene deriv-
atives see: (a) Sun, W.; Cama, L. J.; Birzin, E. T.; Warrier,
S.; Locco, L.; Mosley, R.; Hammond, M. L.; Rohrer, S. P.
Bioorg. Med. Chem. Lett. 2006, 16, 1468–1472; (b)
Stachulski, A. V.; Berry, N. G.; Low, A. C. L.; Moores,
S. L.; Row, E.; Warhurst, D. C.; Adagu, I. S.; Rossignol,
J.-F. J. Med. Chem. 2006, 49, 1450–1454; (c) Garino, C.;
Taking into consideration the above results and the data
on the chain electrocatalytic transformation of tetra-
cyanocyclopropanes12 and the electrocatalytic cycliza-
tion of 3-substituted 2,2-dicyanocyclopropane-1,
1-dicarboxylates,13 the following mechanism for the
electrocatalytic chain transformation of salicylaldehydes
1a–e and alkyl cyanoacetates 2a,b into 4H-chromenes
3a–j is proposed (Scheme 5).
´ ´
Bihel, F.; Pietrancosta, N.; Laras, Y.; Quelever, G.; Woo,
I.; Klein, P.; Bain, J.; Boucher, J.-L.; Kraus, J.-L. Bioorg.
Med. Chem. Lett. 2005, 15, 135–138; (d) Leahy, J. J. J.;
Golding, B. T.; Griffin, R. J.; Hardcastle, I. R.; Richard-
son, C.; Rigoreau, L.; Smith, G. C. M. Bioorg. Med.
Chem. Lett. 2004, 14, 6083–6087.
3. Anderson, D. R.; Hedge, S.; Reinhard, E.; Gomez, L.;
Vernier, W. F.; Lee, L.; Liu, S.; Sambandam, A.; Snider,
P. A.; Masih, L. Bioorg. Med. Chem. Lett. 2005, 15, 1587–
1590.
4. (a) Skommer, J.; Wlodkowic, D.; Ma¨tto¨, M.; Eray, M.;
Pelkonen, J. Leukemia Res. 2006, 30, 322–331; (b) Wang,
J. L.; Liu, D.; Zhang, Z.; Shan, S.; Han, X.; Srinvasula, S.
M.; Croce, C. M.; Alnemeri, E. S.; Huang, Z. Proc. Natl.
Acad. Sci. U.S.A. 2000, 97, 7124–7129.
5. (a) Horning, E. C.; Horning, M. G. J. Am. Chem. Soc.
1947, 69, 968–969; (b) Baker, W.; Howes, C. S. J. Chem.
Soc. 1953, 119–124; (c) Schiemenz, G. P. Chem. Ber. 1962,
95, 483–486; (d) Matsumura, S. Bull. Chem. Soc. Jpn.
1962, 35, 672–676; (e) Yasuda, H.; Midorikava, H. Bull.
Chem. Soc. Jpn. 1966, 39, 1754–1759; (f) Sakurai, A.;
Midorikava, H. J. Org. Chem. 1969, 34, 3612–3615.
6. Fujimoto, A.; Sakurai, A. Synthesis 1977, 871–872.
7. Roudier, J. F.; Foucaud, A. Synthesis 1984, 159–160.
8. Yu, N.; Aramini, J. M.; Germann, M. W.; Huang, Z.
Tetrahedron Lett. 2000, 41, 6993–6996.
9. Curini, M.; Epifano, F.; Chimichi, S.; Montanari, F.;
Nocchetti, M.; Rosati, O. Tetrahedron Lett. 2005, 46,
3497–3499.
10. (a) For references on advanced synthetic electrochemical
procedures, see Organic Electrochemistry, 4th ed.; Lund,
H., Ed.; Marcel Dekker.: New York, 2000; (b) Novel
Trends in Electroorganic Synthesis; Torii, S., Ed.; Springer:
Berlin, 1998.
11. For our first publication on synthetic electroorganic
methodology, see: (a) Nikishin, G. I.; Elinson, M. N.;
Makhova, I. V. Angew. Chem., Int. Ed. Engl. 1988, 100,
1716–1717; for recent papers, see (b) Elinson, M. N.;
Feducovich, S. K.; Starikova, Z. A.; Vereshchagin, A. N.;
Belyakov, P. A.; Nikishin, G. I. Tetrahedron 2006, 62,
3989–3996; (c) Elinson, M. N.; Feducovich, S. K.;
Starikova, Z. A.; Vereshchagin, A. N.; Gorbunov, S. V.;
Nikishin, G. I. Tetrahedron Lett. 2005, 46, 6389–6393; (d)
Elinson, M. N.; Feducovich, S. K.; Starikova, Z. A.;
Vereshchagin, Nikishin, G. I. Tetrahedron 2004, 60, 11743–
11749.
12. Elinson, M. N.; Feducovich, S. K.; Lizunova, T. L.;
Nikishin, G. I. Tetrahedron 2000, 56, 3063–3069.
13. Elinson, M. N.; Feducovich, S. K.; Starikova, Z. A.;
Vereshchagin, A. N.; Gorbunov, S. V.; Belyakov, P. A.;
Nikishin, G. I. Russ. Chem. Bull. 2006, 55, 106–111.
14. General electrolysis procedure. A solution of salicylalde-
hyde (10 mmol), alkyl cyanoacetate (20 mmol), and
cathode: 2EtOH þ 2e ! 2EtOꢀ þ H2
in solution:
3
CH2ðCNÞðCOOR3Þ þ EtOꢀ ! CHðCNÞðCOOR Þ þ EtOH
ꢀ
The ethoxide anion generated from the ethanol at the
cathode reacts with the alkyl cyanoacetate. Next, Knoe-
venagel condensation of the alkyl cyanoacetate anion
and salicylaldehyde takes place with the elimination of
a hydroxide anion,15 followed by the cyclization and
addition of the second alkyl cyanoacetate anion, which
gives the 4H-chromene 3 with regeneration of the ethox-
ide anion in the last stage; the ethoxide anion continues
the catalytic chain process by interaction with the next
molecule of alkyl cyanoacetate. Theoretically, the gener-
ation of a single ethoxide anion at the cathode is
sufficient for the full conversion of all the salicyalde-
hyde and alkyl cyanoacetate into the corresponding
4H-chromene.
Thus, a simple electrocatalytic system can produce, un-
der mild conditions, a direct transformation of salicylal-
dehydes 1 and alkyl cyanoacetates 2 into 4H-chromenes
3 in high yields. This electrocatalytic chain process is an
efficient and convenient method for the synthesis of
substituted cyano-functionalized 4H-chromenes. The
procedure utilizes inexpensive reagents, simple equip-
ment and an undivided cell, it is easily carried out and
the work-up is not complicated.
Acknowledgements
The authors gratefully acknowledge the financial sup-
port of the Russian Foundation for Basic Research
(Project No. 06-03-32068a).
References and notes
1. (a) For examples of natural compounds containing the
chromene fragment see: The Flavonoids—Advances in

M. N. Elinson et al. / Tetrahedron Letters 47 (2006) 7629–7633
7633
1
sodium bromide (1 mmol) in ethanol (20 ml) was electro-
lyzed in an undivided cell equipped with a magnetic stirrer,
a graphite anode and an iron cathode at an ambient
temperature under a constant current density 10 mA/cm2
(I = 50 mA, electrodes square 5 cm2) until the catalytic
quantity of electricity equal to 0.09 F/mol was passed. The
solution was then evaporated and the solid product was
crystallized directly from the reaction mixture with 3 ml of
cold ethanol–water solution (9:1). Further filtration gave a
pure crystalline product.
Minor diastereoisomer: H NMR (250 MHz, DMSO-d6):
d = 1.07 (t, J = 7.3 Hz, 3H, CH3), 1.16 (t, J = 7.3 Hz, 3 H,
CH3), 4.05–4.27 (m, 4H, 2OCH2), 4.33 (d, J = 3.0 Hz, 1H,
CH), 4.74 (d, J = 3.0 Hz, 1H, CH), 7.34 (d, J = 8.55 Hz,
1H, Ar), 7.91 (s, 2H, NH2), 8.26 (d, J = 8.5 Hz, 1H, Ar),
8.41 (s, 1H, Ar); 13C NMR (62.5 MHz, DMSO-d6):
d = 13.6, 14.3, 35.8, 45.9, 59.4, 62.2, 70.5, 116.3, 117.3,
122.8, 124.9, 125.1, 143.6, 154.5, 161.6, 164.8, 167.2.
Methyl 3-amino-1-(1-cyano-2-methoxy-2-oxoethyl)-1H-
benzo[f]chromene-2-carboxylate 3i: IR (KBr, cmꢀ1): m
3468, 3316, 2956, 2252, 1744, 1684, 1520, 1444, 1220, 1080.
Anal. Calcd for C19H16N2O5: C, 64.77; H, 4.58; N, 7.95.
Found: C, 64.61; H, 4.53; N, 7.81.
All compounds (3a–j) gave expected NMR (DMSO-d6)
and IR spectra. For new compounds satisfactory elemen-
tal analyses were obtained.
1
Methyl
2-amino-6-bromo-4-(1-cyano-2-methoxy-2-oxo-
Major diastereoisomer: H NMR (250 MHz, DMSO-d6):
ethyl)-4H-chromene-3-carboxylate 3c: IR (KBr, cmꢀ1): m
3428, 3312, 2956, 2252, 1744, 1688, 1524, 1436, 1232, 1024.
Anal. Calcd for C15H13BrN2O5: C, 47.26; H, 3.44; Br,
20.96; N, 7.35. Found: C, 47.13; H, 3.53; Br, 20.81; N,
7.19.
d = 3.64 (s, 3H, OCH3), 3.82 (s, 3H, OCH3), 4.23 (d,
J = 2.0 Hz, 1H, CH), 5.20 (d, J = 2.0 Hz, 1H, CH), 7.35
(d, J = 9.2 Hz, 1H, Ar), 7.52–8.08 (m, 7H, Ar, NH2); 13C
NMR (62.5 MHz, DMSO-d6): d = 33.7, 46.8, 50.9, 53.2,
70.3, 114.5, 116.0, 116.6, 121.5, 125.4, 128.2, 129.3, 130.1,
130.3, 130.9, 148.0, 162.9, 165.9, 168.0. Minor diastereo-
1
Major diastereoisomer: H NMR (250 MHz, DMSO-d6):
1
d = 3.65 (s, 3H, OCH3), 3.72 (s, 3H, OCH3), 4.40 (d,
J = 3.6 Hz, 1H, CH), 4.52 (d, J = 3.6 Hz, 1H, CH), 7.08
(d, J = 8.7 Hz, 1H, Ar), 7.18 (s, 1H, Ar), 7.57 (d,
J = 8.7 Hz, 1H, Ar), 7.91 (s, 2H, NH2); 13C NMR
(62.5 MHz, DMSO-d6): d = 36.0, 46.8, 50.9, 53.1, 70.7,
115.9, 116.2, 118.4, 124.2, 130.6, 132.2, 149.4, 162.2, 165.6,
167.5. Minor diastereoisomer: 1H NMR (250 MHz,
DMSO-d6): d = 3.57 (s, 3H, OCH3), 3.62 (s, 3H, OCH3),
4.26 (d, J = 3.0 Hz, 1H, CH), 4.55 (d, J = 3.0 Hz, 1H,
CH), 7.05 (d, J = 8.5 Hz, 1H, Ar), 7.52 (d, J = 8.5 Hz, 1H,
Ar), 7.62 (s, 1H, Ar), 7.89 (s, 2H, NH2); 13C NMR
(62.5 MHz, DMSO-d6): d = 36.3, 47.0, 50.8, 53.0, 69.9,
116.0, 116.1, 118.1, 122.9, 131.4, 132.0, 149.3, 162.5, 165.4,
167.7.
isomer: H NMR (250 MHz, DMSO-d6): d = 3.47 (s, 3H,
OCH3), 3.75 (s, 3H, OCH3), 4.31 (d, J = 3.7 Hz, 1H, CH),
5.24 (d, J = 3.7 Hz, 1H, CH), 7.52–8.08 (m, 8 H, Ar,
NH2); 13C NMR (62.5 MHz, DMSO-d6): d = 33.2, 46.1,
50.8, 52.9, 72.3, 114.0, 116.4, 116.7, 122.1, 125.2, 127.4,
128.9, 130.2, 130.4, 130.6, 148.8, 162.8, 165.7, 167.7.
Ethyl 3-amino-1-(1-cyano-2-ethoxy-2-oxoethyl)-1H-benzo-
[f]chromene-2-carboxylate 3j: IR (KBr, cmꢀ1): m 3456,
3328, 2976, 2256, 1740, 1676, 1516, 1464, 1228, 1076.
Anal. Calcd. for C21H20N2O5: C, 66.31; H, 5.30; N, 7.36.
Found: C, 66.19; H, 5.37; N, 7.18.
Major diasteroisomer: 1H NMR (250 MHz, DMSO-d6):
d = 1.26 (t, J = 7.3 Hz, 3H, CH3), 1.29 (t, J = 7.3 Hz, 3H,
CH3), 3.85–4.28 (m, 5H, 2OCH2, CH), 5.22 (d, J = 1.8 Hz,
1H, CH), 7.34 (d, J = 9.2 Hz, 1H, Ar), 7.50–8.10 (m, 7H,
Ar, NH2); 13C NMR (62.5 MHz, DMSO-d6): d = 13.9,
14.4, 33.5, 46.7, 59.2, 62.1, 71.0, 114.8, 116.1, 116.6, 121.6,
125.3, 128.1, 128.9, 129.1, 130.1, 130.9, 147.9, 162.8, 165.3,
167.6. Minor diasteroisomer: 1H NMR (250 MHz,
DMSO-d6): d = 0.99 (t, J = 7.3 Hz, 3H, CH3), 1.34 (t,
J = 7.3 Hz, 3H, CH3), 3.85–4.28 (m, 5H, 2OCH2, CH),
5.25 (d, J = 3.7 Hz, 1H, CH), 7.50–8.10 (m, 8H, Ar, NH2);
13C NMR (62.5 MHz, DMSO-d6): d = 13.3, 14.3, 33.2,
46.2, 59.3, 62.0, 72.3, 114.1, 116.5, 116.7, 122.1, 125.1,
127.3, 128.8, 129.3, 130.0, 130.6, 148.7, 162.6, 165.2,
167.4.
Ethyl
2-amino-4-(1-cyano-2-ethoxy-2-oxoethyl)-6-nitro-
4H-chromene-3-carboxylate 3f: IR (KBr, cmꢀ1): m 3428,
3316, 2992, 2260, 1740, 1692, 1520, 1472, 1228, 1040.
Anal. Calcd for C17H17N3O7: C, 54.40; H, 4.57; N, 11.20.
Found: C, 54.26; H, 4.62; N, 11.07.
1
Major diastereoisomer: H NMR (250 MHz, DMSO-d6):
d = 1.23 (t, J = 7.3 Hz, 3H, CH3), 1.28 (t, J = 7.3 Hz, 3H,
CH3), 4.05–4.27 (m, 4H, 2OCH2), 4.47 (d, J = 3.7 Hz, 1H,
CH), 4.75 (d, J = 3.7 Hz, 1H, CH), 7.39 (d, J = 9.1 Hz,
1H, Ar), 7.93 (s, 2H, NH2), 8.02 (s, 1H, Ar), 8.28 (d,
J = 9.1 Hz, 1H, Ar); 13C NMR (62.5 MHz, DMSO-d6):
d = 13.8, 14.2, 36.0, 46.9, 59.5, 62.5, 70.7, 116.0, 117.6,
121.8, 124.2, 125.3, 143.4, 154.6, 161.5, 165.0, 166.9.
15. Patai, S.; Israeli, Y. J. Chem. Soc. 1960, 2025–2030.