One-pot synthesis of substituted 4H-chromenes by three-component reaction of alkyl isocyanides, dialkyl acetylenedicarboxylates, and N-aryl-3- hydroxynaphthalene-2-carboxamide

Article abstract of DOI:10.1080/00397911.2010.520184

The reactive intermediate generated by the reaction of alkyl isocyanides and dialkyl acetylenedicarboxylates was trapped by N-aryl-3-hydroxynaphthalene- 2-carboxamide for the preparation of substituted 4H-chromenes in good yields. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397911.2010.520184

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One-Pot Synthesis of Substituted 4H-
Chromenes by Three-Component
Reaction of Alkyl Isocyanides, Dialkyl
Acetylenedicarboxylates, and N-Aryl-3-
hydroxynaphthalene-2-carboxamide
Alireza Hassanabadi a , Mohammad H. Mosslemin b , Mohammad
Anary-Abbasinejad b & Maryam Ghasemi b
a Department of Chemistry, Islamic Azad University, Zahedan Branch,
Zahedan, Iran
b Department of Chemistry, Islamic Azad University, Yazd Branch,
Yazd, Iran
Accepted author version posted online: 30 Jun 2011. Version of
record first published: 16 Jun 2011
To cite this article: Alireza Hassanabadi, Mohammad H. Mosslemin, Mohammad Anary-Abbasinejad
& Maryam Ghasemi (2011): One-Pot Synthesis of Substituted 4H-Chromenes by Three-Component
Reaction of Alkyl Isocyanides, Dialkyl Acetylenedicarboxylates, and N-Aryl-3-hydroxynaphthalene-2-
carboxamide, Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 41:24, 3714-3719
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Synthetic Communications1, 41: 3714–3719, 2011
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2010.520184
ONE-POT SYNTHESIS OF SUBSTITUTED
4H-CHROMENES BY THREE-COMPONENT REACTION
OF ALKYL ISOCYANIDES, DIALKYL
ACETYLENEDICARBOXYLATES, AND
N-ARYL-3-HYDROXYNAPHTHALENE-2-CARBOXAMIDE
Alireza Hassanabadi,1 Mohammad H. Mosslemin,2
Mohammad Anary-Abbasinejad,2 and Maryam Ghasemi2
1Department of Chemistry, Islamic Azad University, Zahedan Branch,
Zahedan, Iran
2Department of Chemistry, Islamic Azad University, Yazd Branch,
Yazd, Iran
GRAPHICAL ABSTRACT
Abstract The reactive intermediate generated by the reaction of alkyl isocyanides and
dialkyl acetylenedicarboxylates was trapped by N-aryl-3-hydroxynaphthalene-2-
carboxamide for the preparation of substituted 4H-chromenes in good yields.
Keywords Acetylenic esters; alkyl isocyanides; N-aryl-3-hydroxynaphthalene-2-carboxa-
mide; multicomponent reactions; substituted 4H-chromenes
INTRODUCTION
Chromenes often appear as important components in both biologically active
and natural compounds. Benzopyran fragments are widely found in natural alka-
loids, flavonoids, tocopherols, and anthocyanins.[1,2] Isocyanides, by virtue of their
carbenic character, react readily with most common multiple bonds.[3–5] The reaction
of isocyanides with electron-deficient acetylenic compounds leads to a zwitterionic
intermediate, which may then be trapped by various electrophiles.[6] These reactions
are of interest for the synthesis of functionalized heterocyclic ring systems.[7] The
reaction between alkyl isocyanides and dialkyl acetylenedicarboxylates has been
carried out in the presence of different organic acidic compounds to trap the
Received June 23, 2010.
Address correspondence to Alireza Hassanabadi, Department of Chemistry, Islamic Azad
University, Zahedan Branch, P.O. Box 98135-978, Zahedan, Iran. E-mail: ar_hasanabadi@yahoo.com
3714

N-ARYL-3-HYDROXYNAPHTHALENE-2-CARBOXAMIDE
3715
zwitterionic intermediate.[8–20] In the presence of alcohols, keteneimine and
unsaturated iminoesters were obtained as the main products.[9] The reaction between
isocyanides and dimethyl acetylenedicarboxylate (DMAD) in the presence of
naphthols and phenols respectively yields benzochromene[10] and chromene deriva-
tives.[11] Similar products were reported for the reaction of DMAD, cyclohexyl iso-
cyanide, and 4-hydroxycoumarins.[21] In the course of our work on the reaction
between isocyanides and acetylenic esters in the presence of organic acids,[21–24] here
we report the results of our study on the reaction between alkyl isocyanides and
dialkyl acetylenedicarboxylates in the presence of N-aryl-3-hydroxynaphthalene-2-
carboxamide. The three-component reaction between alkyl isocyanides 1 and
acetylenic esters 2 in the presence of N-aryl-3-hydroxynaphthalene-2-carboxamide
3 produces dialkyl 3-alkylamino-5-arylcarbamoyl-1H-benzo[f]chromene-1,2-
dicarboxylates 4a–e in excellent yields (Scheme 1).
The structures of compounds 4a–e were deduced from their elemental analyses
and their infrared (IR), 1H NMR, and 13C NMR spectra. The mass spectra of these
compounds displayed molecular ion peaks at appropriate m=z values.
The 1H NMR spectrum of compound 4a exhibited two single sharp lines
readily recognized as arising from methoxy (d ¼ 3.63 and 3.79 ppm) and methine
(d ¼ 5.42 ppm) protons, along with multiplets (d ¼ 7.16–8.29 ppm) for aromatic pro-
tons. Two single signals were observed at 8.35 and 8.57 ppm and disappeared after
addition of a few drops of D2O to CDCl3 solution of compound 4a. These signals
are related to NH protons. The NCH proton appeared as a multiplet at 3.71 ppm,
and the signals related to methylene groups of cyclohexyl moiety were observed as
multiplets at 0.86–1.93 ppm. The 13C NMR spectrum of compound 4a showed 28
distinct signals in agreement with the proposed structure; The IR spectrum of
Scheme 1. Reaction of alkyl isocyanides and dialkyl acetylenedicarboxylates in the presence of N-aryl-3-
hydroxynaphthalene-2-carboxamide.

3716
A. HASSANABADI ET AL.
Scheme 2. Suggested mechanism for the formation of compound 4.
compound 3a also supported the suggested structure; strong absorption bands were
observed at 3465, 1741, and 1662 cmꢀ1 respectively for the NH, ester, and amide
groups.
The formation of compounds 4 can be rationalized as shown in Scheme 2. The
reaction starts with nucleophilic attack of alkyl isocyanide on dialkyl acetylenedi-
carboxylate and subsequent protonation by N-aryl-3-hydroxynaphthalene-2-carbox-
amide. The addition of conjugate anion of N-aryl-3-hydroxynaphthalene-2-
carboxamide on the positively charged intermediate 6 leads to keteneimine 7, which
then cyclizes to product 4.
In summary, reactions reported here provide simple entries to the synthesis
of dialkyl 3-alkylamino-5-arylcarbamoyl-1H-benzo[f]chromene-1,2-dicarboxylates.
The present method has the advantage that the reaction is performed under neutral
conditions and the substances can be mixed without any activation or modification.
EXPERIMENTAL
Melting points were determined with an Electrothermal 9100 apparatus.
Elemental analyses were performed using a Costech ECS 4010 CHNS-O analyzer
at the analytical laboratory of the Islamic Azad University, Yazd branch. Mass spec-
tra were recorded on a Finnigan-MAT 8430 mass spectrometer operating at an ioni-
zation potential of 70 eV. IR spectra were recorded on a Shimadzu IR-470
spectrometer. 1H and 13C NMR spectra were recorded on Bruker DRX-500 Avance
spectrometer at solution in CDCl3 using tetramethylsilane (TMS) as internal stan-
dard. The chemicals used in this work purchased from Fluka (Buchs, Switzerland)
and were used without further purification.
General Procedure for Preparation of Compounds 4a–e
A mixture of dialkyl acetylenedicarboxylate (1 mmol) in 5 mL ethyl acetate was
added dropwise at room temperature to a magnetically stirred solution of N-aryl-3-
hydroxynaphthalene-2-carboxamide (1 mmol) and alkyl isocyanide (1 mmol) in

N-ARYL-3-HYDROXYNAPHTHALENE-2-CARBOXAMIDE
3717
10 mL ethyl acetate. The reaction mixture was then stirred for 24 h at reflux tempera-
ture. The solvent was removed under reduced pressure, and the residue was purified
by silica-gel column chromatography using hexane-ethyl acetate as eluent. The sol-
vent was removed under reduced pressure to afford the product.
Selected Data
Dimethyl 3-cyclohexylamino-5-phenylcarbamoyl-1H-benzo[f]chromene-
1,2-dicarboxylates (4a). Yellow powder, yield: 91% mp 101–104 ꢁC. IR (KBr)
(nmax=cmꢀ1): 3465 (NH), 1741 and 1662 (C O). Anal. calcd. for C30H30N2O6: C,
70.02; H, 5.88; N, 5.44. Found: C, 70.15; H, 5.92; N, 5.52%. MS, m=z (%): 514
=
1
(Mþ., 11). H NMR (500 MHz, CDCl3, Me4Si): d 0.88–1.92 (10 H, m, 5 CH2),
3.63, and 3.79 (6 H, 2 s, 2 OCH3), 3.71 (1 H, m, NCH), 5.42 (1 H, s, CH),
7.16–8.29 (10H, m, aromatic protons), 8.34 and 8.57 (2H, s, 2NH). 13C NMR
(125.8 MHz, CDCl3, Me4Si): d 24.47, 24.64, 25.66, 34.06, and 34.47 (5 CH2), 38.63
and 50.80 (2 CH), 51.52 and 52.87 (2 OCH3), 72.46 and 115.94 (2 C), 120.40,
124.02, 124.83, 125.18, 126.40, 129.26, 129.60, 129.80, 130.49, 131.59, 132.56,
138.34, 144.54, 160.72 (naphthol and phenyl moieties), 163.86, 169.73, 173.81
=
(3C O).
Dimethyl
3-t-butylamino-5-phenylcarbamoyl-1H-benzo[f]chromene-
1,2-dicarboxylates (4b). Yellow powder, yield: 94% mp 194–196 ꢁC. IR (KBr)
(nmax=cmꢀ1): 3450 (NH), 1738, 1669 (C O). Anal. calcd. for C28H28N2O6: C,
68.84; H, 5.78; N, 5.73. Found: C, 68.81; H, 5.73; N, 5.86%. MS, m=z (%): 488
=
1
(Mþ., 8). H NMR (500 MHz, CDCl3, Me4Si): d 1.28 (9 H, s, CMe3), 3.51, and
3.65 (6 H, 2 s, 2 OCH3), 5.32 (1 H, s, CH), 7.09–8.24 (10H, m, aromatic protons),
8.83 and 10.76 (2H, s, 2NH). 13C NMR (125.8 MHz, CDCl3, Me4Si): d 30.57
(3CH3 of t-butyl), 38.51 (CH), 51.88 (C of t-butyl), 53.01 and 53.24 (2 OCH3),
72.5 and 114.79 (2 C), 120.50, 124.17, 124.70, 126.88, 127.72, 128.94, 129.25,
129.58, 129.78, 130.55, 131.48, 139.83, 144.52, 161.99 (naphthol and phenyl moi-
=
eties), 163.86, 169.64, 173.46 (3C O).
Dit-Butyl 3-cyclohexylamino-5-phenylcarbamoyl-1H-benzo[f]chromene-
1,2-dicarboxylates (4c). Yellow powder, yield: 89% mp 68–70 ꢁC, IR (KBr)
(nmax=cmꢀ1): 3410 (NH), 1736, 1685 (C O). Anal. calcd. for C36H42N2O6: C,
=
72.22; H, 7.07; N, 4.68. Found: C, 72.38; H, 7.19; N, 4.76%. MS, m=z (%): 598
(Mþ., 20). 1H NMR (500 MHz, CDCl3, Me4Si): d 0.82 and 1.47 (18 H, 2 s, 6
CH3), 1.12–2.01 (10 H, m, 5 CH2), 3.77 (1 H, m, N-CH), 5.92 (1 H, s, CH),
6.92–8.05 (10H, m, aromatic protons), 8.23 and 9.48 (2H, s, 2NH). 13C NMR
(125.8 MHz, CDCl3, Me4Si): d 25.13, 25.31, 25.99, 32.96, and 33.21 (5 CH2), 27.33
and 28.46 (6 CH3 of t-butyl groups), 48.25 and 49.38 (2 CH), 82.84 and 83.01 (2 C
of t-butyl groups), 83.98 and 116.77 (2 C), 118.17, 121.64, 123.60, 124.36, 125.31,
128.02, 129.35, 129.51, 130.19, 130.86, 136.32, 137.89, 154.62, 167.09 (naphthol
=
and phenyl moieties), 167.45, 168.78, 170.78 (3C O).
Dimethyl
3-t-butylamino-5-o-tolylcarbamoyl-1H-benzo[f]chromene-
1,2-dicarboxylates (4d). Yellow powder, yield: 90%; mp 95–97 ꢁC. IR (KBr)
(nmax=cmꢀ1): 3425 (N–H), 1742, 1673 (C O). Anal. calcd for C29H30N2O6: C,
=

3718
A. HASSANABADI ET AL.
69.31; H, 6.02; N, 5.57. Found: C, 69.20; H, 6.05; N, 5.60%. MS, m=z (%): 502 (Mþ.,
10).1H NMR (500 MHZ, CDCl3, Me4Si): d 1.24 (9 H, s, CMe3), 2.30 (3 H, s, CH3),
3.48, and 3.67 (6 H, 2 s, 2 OCH3), 5.48 (1 H, s, CH), 7.11–8.29 (9 H, m, aromatic
protons), 8.89 and 10.37 (2H, s, 2NH). 13C NMR (125.8 MHz, CDCl3, Me4Si): d
18.23 (CH3), 30.52 (3CH3 of t-butyl), 38.58 (CH), 51.67 (C of t-butyl), 53.03 and
53.29 (2 OCH3), 72.64 and 114.98 (2 C), 123.24, 124.11, 124.79, 126.08, 126.43,
127.30, 129.14, 129.32, 129.85, 130.47, 131.12, 131.75, 132.40, 136.19, 144.88,
=
160.38 (naphthol and phenyl moieties), 163.71, 169.53, 173.41 (3C O).
Diethyl 3-cyclohexylamino-5-o-tolylcarbamoyl-1H-benzo[f]chromene-
1,2-dicarboxylates (4e). Yellow powder, yield: 91%; mp 80–82 ꢁC. IR (KBr)
(nmax=cmꢀ1): 3420 (N–H), 1748, 1681 (C O). Anal. calcd. for C33H36N2O6: C,
71.20; H, 6.52; N, 5.03. Found: C, 71.23; H, 6.60; N, 4.97%. MS, m=z (%): 556
=
(Mþ., 8).1H NMR (500 MHZ, CDCl3, Me4Si): d 0.82–1.90 (10 H, m, 5 CH2), 1.18
3
and 1.35 (6 H, 2 t, JHH ¼ 7.1 HZ, 2 CH3), 2.33 (3 H, s, CH3), 3.68 (1 H, m,
NCH), 4.05–4.31 (4 H, m, 2 OCH2), 5.41 (1 H, s, CH), 7.13–8.34 (9H, m, aromatic
protons), 8.36 and 8.60 (2H, s, 2NH). 13C NMR (125.8 MHz, CDCl3, Me4Si): d
14.59 and 15.12 (2 CH3), 18.37 (CH3), 24.58, 24.63, 25.67, 34.29, and 34.38 (5
CH2), 38.92 and 50.79 (2 CH), 60.02 and 61.58 (2 OCH2), 78.66 and 116.22 (2 C),
123.39, 124.20, 124.64, 126.02, 126.40, 127.40, 129.15, 129.38, 129.86, 130.53,
131.14, 131.64, 132.58, 136.11, 144.82, 160.76 (naphthol and phenyl moieties),
=
163.81, 169.44, 173.49 (3C O).
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