One-pot synthesis of 2-amino-5,10-dihydro-5,10-dioxo-4-phenyl-4h-benzo[g] chromene derivatives catalyzed by ZnCl2

Article abstract of DOI:10.1080/00397911003642666

An efficient one-pot synthesis of 2-amino-5,10-dihydro-5,10-dioxo-4-phenyl- 4H-benzo[g]chromene derivatives has been achieved by the reaction of 2-hydroxynaphthalene-1,4-dione, cyanothioacetamide, and aromaticaldehyde in EtOH at room temperature catalyzed by ZnCl₂. The structures of the products were characterized by infrared, ¹H NMR, mass, and elemental analysis.

Full text of DOI:10.1080/00397911003642666

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One-Pot Synthesis of 2-Amino-5,10-
dihydro-5,10-dioxo-4-phenyl-4H-
benzo[g]chromene Derivatives Catalyzed
by ZnCl2
V. Srinivas a & V. Rajeswar Rao a
a Department of Chemistry, National Institute of Technology,
Warangal, India
Published online: 25 Feb 2011.
To cite this article: V. Srinivas & V. Rajeswar Rao (2011) One-Pot Synthesis of 2-Amino-5,10-
dihydro-5,10-dioxo-4-phenyl-4H-benzo[g]chromene Derivatives Catalyzed by ZnCl2 , Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
41:6, 806-811
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Synthetic Communications1, 41: 806–811, 2011
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911003642666
ONE-POT SYNTHESIS OF 2-AMINO-5,10-DIHYDRO-5,
10-DIOXO-4-PHENYL-4H-BENZO[g]CHROMENE
DERIVATIVES CATALYZED BY ZnCl2
V. Srinivas and V. Rajeswar Rao
Department of Chemistry, National Institute of Technology, Warangal, India
GRAPHICAL ABSTRACT
Abstract An efficient one-pot synthesis of 2-amino-5,10-dihydro-5,10-dioxo-4-phenyl-4H-
benzo[g]chromene derivatives has been achieved by the reaction of 2-hydroxynaphthalene-1,
4-dione, cyanothioacetamide, and aromaticaldehyde in EtOH at room temperature cata-
lyzed by ZnCl2. The structures of the products were characterized by infrared, 1H NMR,
mass, and elemental analysis.
Keywords Benzo[g]chromene; cyanothioacetamide; lawsone; one-pot synthesis; ZnCl2
INTRODUCTION
The chromene moiety often appears as an important structural component in
both biologically active and natural compounds. Chromene fragments occur in
alkaloids, flavonoids, tocopherols, and anthocyanins. Moreover, functionally substi-
tuted chromenes have played increasing roles in synthetic approaches to promising
compounds in the field of medicinal chemistry.[1–4]
Recently, the synthesis of particular groups of naturally occurring pyrano-
naphthoquinones, such as pentalongin,[5–7] dehydroherbarin,[8] several 1,3-disubstituted-
3,4-dehydropyranonaphthoquinones,[9] and 3-arylpyranonaphthoquinones[10,11] have
been reported. The biological activities of these compounds were investigated too.[12]
For example, pentalongin is a natural product, which is reported in Rwanda and Kenya
for the treatment of malaria and skin diseases. These compounds have been synthesized
via a multistep approach in the presence of transition-metal catalysts under sensitive
conditions.[8,9] These compounds were semisynthetically obtained from lapachol.[13]
Received August 27, 2009.
Address correspondence to Dr. V. Rajeswar Rao, Department of Chemistry, National Institute of
Technology, Warangal 506 004, A.P., India. E-mail: vrajesw@yahoo.com
806

BENZO[g]CHROMENE DERIVATIVES
807
Scheme 1. Reaction of 2-hydroxynaphthalene-1,4-dione, cyanothioacetamide, and aromatic aldehydes.
Multicomponent reactions (MCRs), because of their productivity, simple
procedures, convergence, and facile execution, are some of the best tools in combi-
natorial chemistry. Therefore, the design of novel MCRs has attracted great
attention from research groups working in areas such as drug discovery, organic syn-
thesis, and materials science.[14–20]
As part of our continuing interest in the development of new synthetic methods
in heterocyclic chemistry and our interest in MCRs,[21,22] herein we describe an
efficient synthesis of 4H-benzo[g]chromene 4 via a three-component reaction.
2-Hydroxynaphthalene-1,4-dione (1), cyanothioacetamide (2), and aromaticalde-
hyde (3) were treated with ZnCl2 in ethyl alcohol at room temperature, which
resulted in the formation of 2-amino-5,10-dihydro-5,10-dioxo-4-phenyl-4H-benzo[g]
chromene derivatives (4) (Scheme 1). As shown in Table 1, we can see a series of 3
reacted with 1 and 2 to give the corresponding products 4 in good yields under the
same reaction conditions.
The structures of the products were deduced from their infrared (IR), 1H NMR,
and mass spectra. The mass spectra of these compounds displayed molecular ion
peaks at the appropriate m=z values. The 1H NMR spectrum of 4a consists of a singlet
for the NMe2 (d ¼ 3.07 ppm), a singlet for the CH of the pyran ring (d ¼ 8.05 ppm), a
multiplet for aromatic protons (d ¼ 7.85–7.90 ppm), two multiplets for quinone aro-
matic protons (d ¼ 7.95–7.98 and 8.00–8.05 ppm), a singlet for NH2 (d ¼ 9.15 ppm),
and another singlet for thioamide NH2 (d ¼ 9.70 ppm) protons.
The plausible mechanism for the formation of 4 is proposed in Scheme 2.
In conclusion, we have demonstrated a novel, one-pot, three-component
reaction that offers a facile and efficient route for the synthesis of 2-amino-5,10-
dihydro-5,10-dioxo-4-phenyl-4H-benzo[g]chromene derivatives. This method has
Table 1. The products 4
S. no.
Compound
Ar
1
2
3
4
5
6
7
8
9
4a
4b
4c
4d
4e
4f
p-N,N-Dimethylaminophenyl
Phenyl
p-Tolyl
4-Methoxyphenyl
o-Hydroxyphenyl
p-Hydroxyphenyl
o-Hydroxy-m-methoxyphenyl
3,4,5-Trimethoxyphenyl
2-Hydroxynapththyl
4g
4f
4h

808
V. SRINIVAS AND V. RAJESWAR RAO
Scheme 2. Mechanism of the reaction.
some advantages, such as milder conditions, simplicity of the reaction, easy workup
procedure, and good product yields.
EXPERIMENTAL
Melting points were determined in open capillaries with a Cintex melting-point
apparatus (Mumbai, India). Melting points are uncorrected, and CHNS analysis was
done on a Carlo Erba EA 1108 automatic elemental analyzer. The purity of the com-
pounds was checked by thin-layer chromotography (TLC) plates (E. Merek, Mumbai,
India), and IR spectra (KBr) were recorded on a BrukerWM-4(X) spectrometer
(577model). 1H NMR spectra were recorded on a Bruker WM 400-MHz spectrometer
in d ppm using tetromethylsilane (TMS) as internal standard. The NH protons were
exchanged with D2O. Mass spectra (EI-MS) were determined on a Perkin-Elmer
instrument (SCIEX API-2000, ESI) at 12.5 eV.
General Procedure for the Syntheses of 2-Amino-5,10-dihydro-5,10-
dioxo-4-aryl-4H-benzo[g]chromene (4)
A dry 25-mL round-bottom flask was charged with 2-hydroxynaphthlene-1,4-
dione 1 (1 mmol), cyanothioacetamide 2 (1 mmol), aromatic aldehyde 3 (1 mmol),
ZnCl2 (100 mg), and ethyl alcohol (10 mL). The mixture was stirred at room tem-
perature for 5 h and then poured into 200 mL water. The solid was filtered off and
washed with water. The crude product was purified by recrystallization from
methanol to give 4.

BENZO[g]CHROMENE DERIVATIVES
809
Data
2-Amino-4-(4-(dimethylamino)phenyl)-5,10-dihydro-5,10-dioxo-4H-
benzo[g]chromene-3-carbothioamide (4a). Compound 4a was obtained in 85%
yield. Mp 204–205 ꢀC; IR (KBr) n: 3301 (NH2 stretching of CSNH2), 3158 (NH2),
1
1641 (quinone C O), 1280 (C S) cmꢁ1; H NMR (400 MHz, DMSO-d6) (d ppm):
3.07 (6H, s, NMe2), 7.85–8.03 (8H, m, ArH), 8.05 (1H, s, CH of pyran ring), 9.15
(2H, s, NH2), 9.70 (2H, s, NH2). Anal. calcd. for C22H19N3O3S: C, 65.17; H, 4.72;
N, 10.36; S, 7.91. Found: C, 65.12; H, 4.80; N, 10.39; S, 7.98.
=
=
2-Amino-5,10-dihydro-5,10-dioxo-4-phenyl-4H-benzo[g]chromene-3-
carbothioamide (4b). Compound 4b was obtained in 90% yield. Mp 174–175 ꢀC;
=
IR (KBr) n: 3318 (NH2 stretching of CSNH2), 3202 (NH2), 1624 (quinone C O),
1277 (C S) cmꢁ1; H NMR (400 MHz, DMSO-d6) (d ppm): 7.65–8.03 (9H, m,
1
=
ArH), 8.05 (1H, s, CH of pyran ring), 9.78 (2H, s, NH2), 10.10 (2H, s, NH2). Anal.
calcd. for C20H14N2O3S: C, 66.28; H, 3.89; N, 7.73; S, 8.85. Found: C, 66.24; H, 3.84;
N, 7.77; S, 8.89.
2-Amino-5,10-dihydro-5,10-dioxo-4-p-tolyl-4H-benzo[g]chromene-3-
carbothioamide (4c). Compound 4c was obtained in 89% yield. Mp 126–127 ꢀC;
=
IR (KBr) n: 3356 (NH2 stretching of CSNH2), 3290 (NH2), 1638 (quinone C O),
1281 (C S) cmꢁ1; H NMR (400 MHz, DMSO-d6) (d ppm): 2.40 (3H, s, CH3),
1
=
7.83–8.03 (8H, m, ArH), 8.05 (1H, s, CH of pyran ring), 9.58 (2H, s, NH2), 10.10
(2H, s, NH2). Anal. calcd. for C21H16N2O3S: C, 67.00; H, 4.28; N, 7.44; S, 8.52.
Found: C, 67.10; H, 4.31; N, 7.48; S, 8.55.
2-Amino-5,10-dihydro-4-(4-methoxyphenyl)-5,10-dioxo-4H-benzo[g]-
chromene-3-carbothioamide (4d). Compound 4d was obtained in 90% yield.
Mp 181–182 ꢀC; IR (KBr) n: 3396 (NH2 stretching of CSNH2), 3316 (NH2), 1640
1
(quinone C O), 1259 (C S) cmꢁ1; H NMR (400 MHz, DMSO-d6) (d ppm): 3.87
(3H, s, OCH3), 7.17–8.03 (8H, m, ArH), 8.05 (1H, s, CH of pyran ring), 9.50 (2H,
s, NH2), 10.00 (2H, s, NH2). Anal. calcd. for C21H16N2O4S: C, 64.27; H, 4.11; N,
7.14; S, 8.17. Found: C, 64.22; H, 4.15; N, 7.17; S, 8.19.
=
=
2-Amino-5,10-dihydro-4-(2-hydroxyphenyl)-5,10-dioxo-4H-benzo[g]-
chromene-3-carbothioamide (4e). Compound 4e was obtained in 88% yield. Mp
ꢀ
=
207–208 C; IR (KBr) n: 3422 (NH2 stretching of CSNH2), 1609 (quinone C O),
1271 (C S) cmꢁ1; H NMR (400 MHz, DMSO-d6) (d ppm): 6.25 (1H, s, OH),
1
=
7.40–8.03 (8H, m, ArH), 9.00 (1H, s, CH of pyran ring), 9.80 (2H, s, NH2), 10.35
(2H, s, NH2). Anal. calcd. for C20H14N2O4S: C, 63.48; H, 3.73; N, 7.40; S, 8.47.
Found: C, 63.44; H, 3.77; N, 7.45; S, 8.49.
2-Amino-5,10-dihydro-4-(4-hydroxyphenyl)-5,10-dioxo-4H-benzo[g]-
chromene-3-carbothioamide (4f). Compound 4f was obtained in 92% yield.
ꢀ
=
Mp > 300 C; IR (KBr) n: 3326 (NH2 stretching of CSNH2), 1587 (quinone C O),
1274 (C S) cmꢁ1; H NMR (400 MHz, DMSO-d6) (d ppm): 7.83–8.03 (8H, m,
1
=
ArH), 8.05 (1H, s, CH of pyran ring), 8.98 (2H, s, NH2), 10.10 (2H, s, NH2),
10.60 (1H, s, OH). Anal. calcd. for C20H14N2O4S: C, 63.48; H, 3.73; N, 7.40; S,
8.47. Found: C, 63.50; H, 3.77; N, 7.44; S, 8.50.

810
V. SRINIVAS AND V. RAJESWAR RAO
2-Amino-5,10-dihydro-4-(2-hydroxy-3-methoxyphenyl)-5,10-dioxo-4H-
benzo[g]chromene-3-carbothioamide (4g). Compound 4g was obtained in 89%
yield. Mp 110–111 ꢀC; IR (KBr) n: 3402 (NH2 stretching of CSNH2), 1587 (quinone
1
C O), 1274 (C S) cmꢁ1; H NMR (400 MHz, DMSO-d6) (d ppm): 3.98 (3H, s,
OCH3), 6.23 (1H, s, OH), 7.38–8.00 (7H, m, ArH), 8.98 (1H, s, CH of pyran ring),
8.80 (2H, s, NH2), 10.38 (2H, s, NH2). Anal. calcd. for C21H16N2O5S: C, 61.76; H,
3.95; N, 6.86; S, 7.85. Found: C, 61.71; H, 3.91; N, 6.89; S, 7.89.
=
=
2-Amino-5,10-dihydro-4-(3,4,5-trimethoxyphenyl)-5,10-dioxo-4H-
benzo[g]chromene-3-carbothioamide (4h). Compound 4h was obtained in 91%
yield. Mp 192–193 ꢀC; IR (KBr) n: 3394 (NH2 stretching of CSNH2), 1577 (quinone
1
C O), 1271 (C S) cmꢁ1; H NMR (400 MHz, DMSO-d6) (d ppm): 3.82 (3H, s,
OCH3), 7.70–8.00 (6H, m, ArH), 8.08 (1H, s, CH of pyran ring), 9.56 (2H, s,
NH2), 10.08 (2H, s, NH2). Anal. calcd. for C23H20N2O6S: C, 61.05; H, 4.46; N,
6.19; S, 7.09. Found: C, 61.12; H, 4.49; N, 6.15; S, 7.10.
=
=
2-Amino-5,10-dihydro-4-(2-hydroxynaphthalen-1-yl)-5,10-dioxo-4H-
benzo[g]chromene-3-carbothioamide (4i). Compound 4i was obtained in 90%
yield. Mp 180–181 ꢀC; IR (KBr) n: 3429 (NH2 stretching of CSNH2), 1587 (quinone
C O), 1271 (C S) cmꢁ1; 1H NMR (400 MHz, DMSO-d6) (d ppm): 7.50–8.00 (10H,
m, ArH), 8.10 (1H, s, CH of pyran ring), 9.40 (2H, s, NH2), 10.72 (2H, s, NH2),
10.80 (1H, s, OH). Anal. calcd. for C24H16N2O4S: C, 67.28; H, 3.76; N, 6.54; S,
7.48. Found: C, 67.23; H, 3.79; N, 6.59; S, 7.51.
=
=
ACKNOWLEDGMENT
We thank the University Grants Commission, New Delhi (F. No. 32-201=2006
(SR)), for financial support.
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