Synthesis of 4H-chromene derivatives by reaction between alkyl isocyanides and dialkyl acetylenedicarboxylate in the presence of 6-hydroxyquinoline

Article abstract of DOI:10.1016/j.cclet.2011.01.005

The reactive intermediate generated by the addition of alkyl isocyanides to dialkyl acetylenedicarboxylate was trapped by 6-quinolinol to produce highlyfunctionalized 4H-chromenes in fairly good yields.

Full text of DOI:10.1016/j.cclet.2011.01.005

Available online at www.sciencedirect.com
Chinese Chemical Letters 22 (2011) 771–773
www.elsevier.com/locate/cclet
Synthesis of 4H-chromene derivatives by reaction between
alkyl isocyanides and dialkyl acetylenedicarboxylate
in the presence of 6-hydroxyquinoline
b
c
Bita Mohtat a, , Hoorieh Djahaniani , Issa Yavari ,
*
Masomeh G. Dehbalaei a, Saba A. Jam a
a Department of Chemistry, Islamic Azad University, Karaj Branch, Karaj, Iran
b Department of Chemistry, Islamic Azad University, East Tehran Branch Qiamdasht, Tehran, Iran
c Department of Chemistry, Islamic Azad University, Science and Research Branch, Tehran, Iran
Received 25 October 2010
Available online 17 April 2011
Abstract
The reactive intermediate generated by the addition of alkyl isocyanides to dialkyl acetylenedicarboxylate was trapped by 6-
quinolinol to produce highlyfunctionalized 4H-chromenes in fairly good yields.
# 2011 Bita Mohtat. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
Keywords: 4H-Chromene; Alkyl isocyanides; Acetylenic ester; 6-Hydroxyquinoline
Chromenes constitute a major class of naturally occurring compounds, and interest in their chemistry continues
unabated because of their usefulness as biologically active agents [1,2]. 2-Amino-4H-chromenes have been of interest
because of their biological activity [3] and some methods have been reported for their synthesis [4]. The first amino-
4H-chromenes synthesized via acetylenic esters and alkyl isocyanides was presented by Yavari et al. [5]. As part of our
current studies [6,7] on the development of new routes to heterocyclic and carboxylic systems, we now report an
efficient synthetic route to 2-amino-4H-chromenes using alkyl isocyanides and dialkyl acetylene-dicarboxylate in the
presence of 6-quinolinol (Scheme 1).
1. Experimental
Melting points were measured on an Electrothermal 9100 apparatus. Elemental analyses for C, H, and N were
performed using a Heraeus CHN-O-Rapid analyzer. IR spectra were measured on a Shimadzu IR-460 spectrometer. 1H
and 13C NMR spectra were measured with a Bruker DRX-300 AVANCE instrument with CDCl3 as solvent at 300.1
and 75.5 MHz, respectively.
* Corresponding author.
E-mail address: b.mohtat@jooyan.org (B. Mohtat).
1001-8417/$ – see front matter # 2011 Bita Mohtat. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
doi:10.1016/j.cclet.2011.01.005

[()TD$FIG]
772
B. Mohtat et al. / Chinese Chemical Letters 22 (2011) 771–773
CO2R'
H
N
CO2R'
R'O2C
R
OH
+
R
N
C
+
O
N
CO2R'
N
R
1
2
3
4
4
R' Yeild %
3
R'
R
1
a
a
b
a
b
c
t-Butyl
c-Hexyl
t-Butyl
c-Hexyl
1,1,3,3-tetra-Metylbutyl
Me
Et
Me
Me
Me
Et
88
73
94
80
75
90
b
c
d
e
f
1,1,3,3-tetra-Metylbutyl
t-Butyl
c-Hexyl
1,1,3,3-tetra-Metylbutyl
Et
Et
Scheme 1.
1.1. Typical procedure
To a magnetically stirred solutionof2 (2 mmol) and dimethylacetylenedicarboxylate(2 mmol)in10 mL CH2Cl2 was
added dropwise at À10 8C over 10 min tert-butyl isocyanide (2 mmol). The reaction mixture was then allowed to warm
up to room temperature and stand for 24 h. The solvent was removed under reduced pressure and the residuewas purified
by preparative TLC on silica gel (Merck silica gel DC-Fertigplatten 60/Kieselgur F254) 20 cm  20 cm plates using n-
hexane-AcOEt (3:1) as eluent.
Dimethyl 3-(tert-butylamino)-1H-pyrano[3,2-f ]quinoline-1,2-dicarboxylate (4a): Yellow powder, yield 0.65 g
(88%); mp: 87–91 8C. IR (neat) (nmax/cmÀ1): 3390 (NH), 1730 (C O), 1668 (C O). 1H NMR: d 1.55 (s, 3 CH3), 3.60 (3,
OCH3), 3.79 (s, OCH3), 5.35(s, CH), 7.51–7.54(m, 2 CH), 8.09 (d, 3J = 9.1 Hz, CH), 8.70 (d, 3J = 8.3 Hz, CH), 8.82 (brs,
NH), 8.88 (d, 3J = 4.2 Hz, CH). 13C NMR: d 31.0 (3 CH3), 38.6 (CH), 51.5 (OCH3), 52.8 (OCH3), 53.0 (C), 72.4 (C), 114.
5 (CH), 120.6 (C), 122.2 (CH), 126.9 (CH), 131.3 (CH), 132.7 (C), 146.3 (C), 147.7 (CH), 149.6 (C), 162.4 (C O), 170.0
(C O), 173.4(C). Anal. calcd. forC20H22N2O5 (370.4):C, 64.85;H, 5.99;N, 7.56%; Found:C, 64.66;H, 6.04;N, 7.51%.
Dimethyl 3-(cyclohexylamino)-1H-pyrano[3,2-f ]quinoline-1,2-dicarboxylate (4b): Yellow powder, yield 0.58 g
(73%); mp: 102–105 8C. IR (neat) (nmax/cmÀ1): 3419 (NH), 1738 (C O), 1675 (C O). 1H NMR d 1.28–2.10 (m, 5
CH2), 3.60 (s, CH3), 3.78 (s, CH3), 3.95 (m, CH), 5.33 (s, CH), 7.49–7.55 (m, 2 CH), 8.11 (d, 3J = 9.2 Hz, CH), 8.63
(brs, NH), 8.72 (d, 3J = 8.6 Hz, CH), 8.9 (d, 3J = 4.2 Hz, CH). 13C NMR d 24.5 (CH2), 24.6 (CH2), 25.5 (CH2), 33.6
(CH2), 33.9 (CH2) 38.3 (CH), 49.9 (CH), 51.1 (OCH3), 52.5 (OCH3), 71.1 (C), 114.0 (CH), 120.7 (C), 121.8 (CH)
126.6 (CH), 130.4 (CH), 132.8 (C), 145.6 (C), 147.6 (CH), 148.8 (C), 160.5 (C O), 169.5 (C O), 173.1(C). Anal.
calcd. for C22H24N2O5 (396.44): C, 66.65; H, 6.10; N, 7.07%; Found: C, 66.69; H, 6.03; N, 7.10%.
Dimethyl 3-(2,4,4-trimethylpentan-2-ylamino)-1H-pyrano[3,2-f ]quinoline-1,2-dicarboxylate (4c): Yellow pow-
der, yield 0.80 g (94%); mp: 118–122 8C; IR (neat) (nmax/cmÀ1): 3408 (NH), 1739 (C O), 1674 (C O). 1H NMR d
1.02 (s, 3 CH3), 1.56 (s, CH3), 1.58 (s, CH3), 1.85 (d, 3J = 14.9 Hz, CH), 1.92 (d, 3J = 14.9 Hz, CH), 3.56 (s, CH3) 3.77
(s, CH3), 5.34 (s, CH), 7.50–7.54 (m, 2 CH), 8.10 (d, 3J = 9.1 Hz, CH), 8.71 (d, 3J = 8.6 Hz, CH), 8.88 (brs, NH), 8.90
3
(d, J = 4.1 Hz, CH). 13C NMR d 31.4 (3 CH3), 31.5 (CH3), 31.6 (CH3), 31.7 (C), 38.2 (CH), 51.1 (OCH3), 52.4
(OCH3), 53.3 (CH2), 56.2 (C), 71.7 (C), 114.2 (CH), 120.3 (C), 121.9 (CH), 126.6 (CH), 130.8 (CH), 132.6 (C),
145.7(C), 147.3 (CH), 149.1 (C), 161.8 (C O), 169.6 (C O), 173.0(C). Anal. calcd. for C24H30N2O5 (426.51): C,
67.59; H, 7.09; N, 6.57%; Found: C, 67.64; H, 6.92; N, 6.54%.
Diethyl 3-(tert-butylamino)-1H-pyrano[3,2-f ]quinoline-1,2-dicarboxylate (4d): Yellow powder, yield 0.64 g
(80%); mp: 95–99 8C; IR (neat) (nmax/cmÀ1): 3390 (NH), 1730 (C O), 1668 (C O).1H NMR d 1.12 (t, 3J = 7.1 Hz,
CH3), 1.32 (t, 3J = 7.1 Hz, CH3), 1.52 (s, 3 CH3), 4.03 (m, OCH2), 4.23 (m, OCH2), 5.29 (s, CH), 7.42–7.51 (m, 2 CH),
8.03 (d, 3J = 9.1 Hz, CH), 8.71 (d, 3J = 8.4 Hz, CH), 8.82 (brs, NH), 8.88 (d, 3J = 4.2 Hz, CH). 13C NMR d 14.1 (CH3),
14.7 (CH3), 30.6 (3 CH3), 38.3 (CH), 52.6 (C), 59.5 (OCH2), 61.1 (OCH2), 72.1 (C), 114.0 (CH), 120.2 (C), 121.7
(CH), 126.6 (CH), 130.9 (CH), 132.3 (C), 146.0 (C), 147.2 (CH), 149.2 (C), 161.8 (C O), 169.2 (C O), 172.8 (C).
Anal. calcd. for C22H26N2O5 (398.45); C, 66.32; H, 6.58; N, 7.03%; Found: C, 66.28; H, 6.65; N, 7.00%.
Diethyl 3-(cyclohexylamino)-1H-pyrano[3,2-f ]quinoline-1,2-dicarboxylate (4e): Yellow powder, yield 0.64 g
1
(75%); m.p.: 107–110 8C; IR (neat) (nmax/cmÀ1): 3254 (NH), 1729 (C O), 1671 (C O). H NMR d 1.12 (t,

[()TD$FIG]
B. Mohtat et al. / Chinese Chemical Letters 22 (2011) 771–773
773
CO R'
2
H
CO R'
2
O
R'O C
2
N
R'O C
2
R'O C
2
N
CO R'
+
2
H
O
C
N
4
C
N
R
N
C
N
HO
R
5
R
6
7
Scheme 2.
3J = 7.1 Hz, CH3), 1.33 (t, 3J = 7.1 Hz, CH3), 1.28–2.09 (m, 5 CH2), 3.90 (m, CH), 4.05 (m, OCH2), 4.25 (m, OCH2),
3
3
5.30 (s, CH), 7.46–7.53 (m, 2 CH), 8.08 (d, J = 9.1 Hz, CH) 8.68 (brs, NH), 8.75 (d, J = 8.5 Hz, CH), 8.87 (d,
3J = 4.0 Hz, CH). 13C NMR d 14.1 (CH3), 14.7 (CH3), 24.5 (2CH2), 25.5 (CH2), 33.6 (CH2), 33.9 (CH2), 38.5 (CH),
49.9 (CH), 59.4 (OCH2), 61.1 (OCH2), 71.3 (C), 114.0 (CH), 120.7 (C), 121.6 (CH), 126.6 (CH), 130.5 (CH), 132.8
(C), 145.7 (C), 147.5 (CH), 148.9 (C), 160.4 (C O), 169.2 (C O), 172.9(C). Anal. calcd. for C24H28N2O5 (424.49): C,
67.91; H, 6.65; N, 6.60%; Found: C, 67.94; H, 6.61; N, 6.64%.
Diethyl 3-(2,4,4-trimethylpentan-2-ylamino)-1H-pyrano[3,2-f ]quinoline-1,2-dicarboxylate (4f): Yellow powder,
yield 0.82 g (90%); mp: 135–140 8C; IR (neat) (nmax/cmÀ1): 3445 (NH), 1732 (C O), 1670 (C O). 1H NMR d 1.02 (s,
3 CH3), 1.11 (t, 3J = 7.1 Hz, CH3), 1.33 (t, 3J = 7.1 Hz, CH3), 1.55 (s, CH3), 1.57 (s, CH3), 1.84 (d, 3J = 14.9 Hz, CH),
4.04 (m, OCH2), 4.23 (m, OCH2), 7.44–7.53 (m, 2 CH), 8.08 (d, 3J = 9.1 Hz, CH), 8.75 (d, 3J = 8.4 Hz, CH), 8.84 (brs,
NH), 8.90 (d, 3J = 4.2 Hz, CH). 13C NMR d 14.1 (CH3), 14.7 (CH3), 31.4 (3 CH3), 31.5 (2 CH3), 31.7 (C), 38.5 (CH),
53.3 (CH2), 56.1 (C), 59.4 (OCH2), 61.1 (OCH2), 71.9 (C), 114.1 (CH), 120.2 (C), 121.7 (CH), 126.6 (CH), 130.8
(CH), 132.6 (C), 145.8 (C), 147.2 (CH), 149.1 (C), 161.6 (C O), 169.2 (C O), 172.7 (C). Anal. calcd. for
C26H34N2O5 (454.56): C, 68.70; H, 7.54; N, 6.16%; Found: C, 68.73; H, 7.50; N, 6.18%.
2. Result and discussion
The structure of 4a was determined on the basis of its elemental analyses, 1H and 13C NMR and IR spectroscopic
data. The 1H NMR spectrum of 4a exhibited four singlets identified as tert-butyl (d 1.55), methoxy (d 3.60 and 3.79)
and methine (d 5.35), quinolinol moiety appeared at (d 7.51–8.88). The NH proton resonance at d 8.85 disappeared
after addition of D2O to the CDCl3 solution of 4a. The 13C NMR spectrum of 4a showed 18 distinct resonances in
agreement with the proposed structure. The a-carbon atom of this polarized system appears at d 173.4, while and the b-
carbon at d 72.4. Partial assignment of these resonances is given in the experimental.
A possible explanation is proposed in Scheme 2. On the basis of the well established chemistry of isocyanides [8–
11] it is reasonable to assume that compounds 4 result from nucleophilic addition of alkyl isocyanides to the acetylenic
system and subsequent protonation of the 1:1 adduct by the OH-acid. Then, the positively charged ion 5 is attacked by
the anion of the OH-acid to form ketenimine 6. Such an addition product may tautomerize and then cyclize, under the
reaction conditions employed, to produce 4.
3. Conclusion
The present method carries the advantage that not only is the reaction performed under neutral conditions, but also
the starting materials and reagents can be mixed without any activation or modification.
References
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[5] I. Yavari, H. Djahaniani, F. Nasiri, Tetrahedron 59 (2003) 9409.
[6] I. Yavari, M.A. Abbasinejad, A. Alizadeh, Z. Hossaini, Tetrahedron 59 (2003) 9409.
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