Synthesis of polyfunctionalized amino furans with long conjugated aromatic systems using nucleophilic aromatic isocyanide

Article abstract of DOI:10.1155/2012/931293

Polyfunctionalized amino furans with long conjugated aromatic systems have been synthesized by three component reaction of aldehydes, acetylenic esters and aromatic nucleophilic isocyanide.

Full text of DOI:10.1155/2012/931293

ISSN: 0973-4945; CODEN ECJHAO
E-Journal of Chemistry
http://www.ejchem.net
2012, 9(2), 791-795
Synthesis of Polyfunctionalized Amino
Furans with Long Conjugated Aromatic Systems
Using Nucleophilic Aromatic Isocyanide
MOHAMMAD QANDALEEa*, MASOUD MOKHTARYb,
SAKINEH ASGHARIc, and MEHRDAD MEHRZADId
aDepartment of biology, Garmsar Branch
Islamic Azad University, Garmsar, Iran
bDepartment of Chemistry, Rasht Branch
Islamic Azad University, PO Box 41325-3516, Rasht, Iran
cDepartment of Organic Chemistry, Faculty of Chemistry,
University of Mazandaran, Babolsar, 47415, Iran
dDepartment of Chemistry, Ayatollah Amoli Branch,
Islamic Azad University, Amol, Iran
qandalee@gmail.com
Received 25 October 2011; Accepted 29 December 2011
Abstract: Polyfunctionalized amino furans with long conjugated aromatic
systems have been synthesized by three component reaction of aldehydes,
acetylenic esters and aromatic nucleophilic isocyanide.
Keywords: 2,6-Dimethylphenyl isocyanide, Acetylenic esters, Aldehydes, Amino furans.
Introduction
Polysubstituted furans are key structures in a lot of naturally occurring products and
pharmaceutical compounds1. Because of this importance, synthesis of such compounds
attracted great attentions. The nucleophilic character of isocyanide with a formally divalent
carbon atom has made it as one of the compounds with an extraordinary functional group
which is very important species in the synthesis of heterocycles like furans2,3. Recently, we
considered the chemiluminescene properties of polyfunctionalized conjugated furans4,5. In
this work we have used aromatic isocyanide to synthesize new furans with longer aromatic
conjugated systems. The structure shows that three aromatic rings are attached by amine and
olefin groups. Therefore, we expect higher chemiluminescence activities in these
compounds (Scheme1).

792 MOHAMMAD QANDALEE et al.
Me
E
E
H
R
Me
CH2Cl2
r.t.
N+ C
+
O
+
E
E
R
O
N
H
Me
4
2
3
1
Me
R
E
Yield, % of 4
4
a
Ph
Ph
C
C
H
CO2Me
86
H
C
H
C
H
CO2Et
80
77
b
c
Ph
CO2Me
H
H
Me
Me
Ph
CO2Et
70
85
d
e
CO2Me
O
Scheme 1. Synthesis of compound 4.
Experimental
Dialkyl aceylenedicarboxylates, alkylisocyanide and cinnamaldehyde were purchased from
fluka (Buchs, Switzerland) and were used without further purification. Melting points were
1
measured on a thermo scientific apparatus. H and 13C NMR spectra were measured with a
Bruker DRX-400 Avance spectrometer at 400 and 100.6 MHz, respectively. Mass spectra
were recorded on a Agilent Technology (HP) 5973 mass spectrometer operating at an
ionization potential of 70 eV. IR spectra were recorded on a FT-IR Bruker (WQF-510)
spectrometer.
General procedure for the preparation of compound 4
To a magnetically stirred solution of cinnamaldehyde (2 mmol) and dialkyl acetylenedi-
carboxylate (2 mmol) in CH2Cl2 (10 mL), dropwise, 2 mmol of alkyl isocyanide in CH2Cl2
(4 mL) was added at room temperature. The mixture was stirred at room temperature for
24 h. The solvent was removed under reduced pressure and the residue was purified by silica
gel (Merck silica gel, 230-240 mesh) column chromatography using hexane:ethyl acetate
(80:20) to afford pure products.
Results and Discussion
On the basis of the extraordinary properties of isocyanide6-17, it is reasonable to assume that
the reaction starts by Micheal addition of isocyanide to the acetylenic ester to form the
zwitterionic intermediate 5, which attacks the carbonyl group of the aldehyde 3. Then,
nucleophilic addition to the nitrile iminium moiety leads to the formation of the five-
membered ring 6 which is aromatized to functionalized furan 4 by [1,5]-H shift (Scheme 2).

Synthesis of Polyfunctionalized Amino Furans with long Conjugated 793
Me
Me
Me
E
C
H
N+
C
+
N+
C
C
E
E
E
O
R''
Me
1
2
5
3
E
E
Me
E
E
E
E
C
H
[1,5]-H shift
N+
H
H
H
Me
H
H
Me
HN
N
O
O
-O
Ph
H
Me
H
Ph
Ph
Me
Me
6
4
Scheme 2. Proposed mechanism for the formation of compound 4.
Spectroscopic data
Dimethyl 2-(2,6-Dimethyl-phenylamino)-5-[(E)-2-phenyl-1-ethenyl]-3,4-furan
dicarboxylate (4a)
o
Yellow powder, m.p. 117-119 C, yield 86%, IR (KBr) (νmax, cm-1): 1662-1712 (C=O) and
1
3311 (NH); H NMR (400 MHz, CDCl3): H 2.32 (6H, s, 2 CH3), 3.89 and 3.96 (6H, 2s, 2
3
3
OCH3), 6.67 (1H, d, CH=CH, JHH =16.4 Hz), 7.08 (1H, d, CH=CH, JHH =16.4 Hz), 7.19
(3H, m, Ph), 7.22 (1H, t, JHH =7.2 Hz, Hpara), 7.32 (2H, t, 3JHH =7.2 Hz, Hmeta), 7.40 (2H, d,
3
3JHH =7.2Hz, Hortho), 8.36 (1H, s, NH); 13C NMR (400 MHz, CDCl3): C 18.50 (2 CH3), 51.4
and 52.1 (2 OCH3), 87.83, 113.91, 145.93 and 160.62 (furan), 114.01 and 128.01 (C=C
alkene), 126.59 (Cortho), 127.23 (Cpara), 128.51 (Cmeta), 136.43 (Cipso), 128.64 (Cortho), 128.82
(Cpara), 134.10 (Cmeta), 135.26 (Cipso), 164.04 and 165.44 (2 CO); MS: m/z (%): 59
(COOCH3, 7), 77 (Ph, 25), 103 (PhCH=CH+, 54), 285 (M+ -[(CH3)2PhNH+], 32), 341
(M+ -[2 OCH3 + H], 45), 374 (M+ -2 CH3, 78), 404 (M+, 100), Anal. Calcd for C24H23NO5
(405.42): C, 71.10; H, 5.71; N, 3.45. Found: C, 71.17; H, 5.74; N, 3.47.
Diethyl 2-(2,6-Dimethyl-phenylamino)-5-[(E)-2-phenyl-1-ethenyl]-3,4-furan
dicarboxylate (4b)
o
,
Yellow powder, m.p. 128-130 C, yield 80%, IR (KBr) (νmax cm-1): 1660-1710 (C=O) and
1
3
3276 (NH); H NMR (400 MHz, CDCl3): H 1.39 (3H, t, JHH =7.2 Hz, CH3), 1.44 (3H, t,
3JHH =7.2 Hz, CH3), 2.32 (6H, s, 2 CH3), 4.35 (2H, q, 3JHH =7.2 Hz, OCH2), 4.42 (2H, q, 3JHH
3
3
=7.2 Hz, OCH2), 6.66 (1H, d, CH=CH, JHH =16 Hz), 7.08 (1H, d, CH=CH, JHH =16 Hz),
3
3
7.20 (3H, m, Ph), 7.22 (1H, t, JHH =7.2 Hz, Hpara), 7.33 (2H, t, JHH =7.2 Hz, Hmeta), 7.40
3
(2H, d, JHH =7.2 Hz, Hortho), 8.38 (1H, s, NH); 13C NMR (400 MHz, CDCl3): C 14.36 and
14.48 (2 CH3), 18.58 (2 CH3Ph), 60.07 and 61.15 (2 OCH2), 88.09, 113.93, 145.53 and
160.51 (furan), 114.55 and 128.38 (C=C alkene), 126.53 (Cortho), 127.16 (Cpara), 127.91
(Cmeta), 136.53 (Cipso), 128.50 (Cortho), 128.65 (Cpara), 134.19 (Cmeta), 135.23 (Cipso), 163.77
and 165.10 (2 CO); MS: m/z (%): 103 (PhCH=CH+, 59), 265 (M+ -[PhCH=CHfuran], 91),
313 (M+ -[(CH3)2PhNH2 + H], 39), 342 (M+ -2 CH3CH2OH, 38), 361 (M+ -COOCH2CH3,
82), 434 (M+, 100), Anal. Calcd for C26H27NO5 (433.47): C, 72.04; H, 6.27; N, 3.23. Found:
C, 72.10; H, 6.31; N, 3.25.

794 MOHAMMAD QANDALEE et al.
Dimethyl 2-[(2,6-dimethylphenyl)amino]-5-[(E)-1-methyl-2-phenylvinyl]-3,4-furan
dicarboxylate (4c)
o
,
Yellow powder, m.p. 125-127 C, yield 77%, IR (KBr) (νmax cm-1): 1675-1735 (C=O) and
3305 (NH); 1H NMR (400 MHz, CDCl3):H 2.02(3H, s, CH3), 2.32 (6H, s, 2 CH3), 3.86 and
3
3.93 (6H, 2s, 2 OCH3), 6.67 (1H, s, CH=CH), 7.15 (3H, m, Ph), 7.22 (1H, t, JHH =7.6 Hz,
3
3
Hpara), 7.32 (2H, t, JHH =7.6 Hz, Hmeta), 7.34 (2H, d, JHH =7.6 Hz, Hortho), 8.07 (1H, s, NH);
13C NMR (400 MHz, CDCl3): C 14.27 (CH3), 18.49 (2 CH3), 51.47 and 52.71 (2 OCH3),
88.56, 113.80, 142.90 and 159.30 (furan), 124.84 and 128.14 (C=C alkene), 126.16 (Cortho),
126.78 (Cpara), 127.19 (Cmeta), 136.91 (Cipso), 128.46 (Cortho), 129.23 (Cpara), 134.10 (Cmeta),
135.23 (Cipso), 164.86 and 166.20 (2 CO); MS: m/z (%): 59 (COOCH3, 7), 121( (CH3)2
PhNH2, 82), 267 (M+ -[2 CH3COOH + HOCH3], 25), 328 (M+ -[2 CH4 + COOCH3], 34),
388 (M+ -OCH3, 54), 419 (M+, 100), Anal. Calcd for C25H25NO5 (419.45): C, 71.58; H, 6.00;
N, 3.33. Found: C, 71.64; H, 6.04; N, 3.34.
Diethyl 2-[(2,6-dimethylphenyl)amino]-5-[(E)-1-methyl-2-phenylvinyl]-3,4-furan
dicarboxylate (4d)
o
,
Yellow powder, m.p. 126-128 C, yield 70%, IR (KBr) (νmax cm-1): 1675-1739 (C=O) and
1
3
3315 (NH); H NMR (400 MHz, CDCl3): H 1.36 (3H, t, JHH =7.2Hz, CH3)3, 1.41 (3H, t,
3JHH =7.2 Hz, CH3), 2.04(3H, s, CH3), 2.32 (6H, s, 2 CH3), 4.32 (2H, q, JHH =7.2 Hz,
OCH2), 4.39 (2H, q, 3JHH =7.2Hz, OCH2), 6.67 (1H, s, CH=CH), 7.15 (3H, m, Ph), 7.23 (1H,
3
3
t, JHH =7.6 Hz, Hpara), 7.31 (2H, t, 3JHH =7.6 Hz, Hmeta), 7.34 (2H, d, JHH =7.6 Hz, Hortho),
8.10 (1H, s, NH); 13C NMR (400 MHz, CDCl3): C 14.13 and 14.30 (2 CH3), 14.42 (CH3),
18.51 (2 CH3), 59.99 and 61.77 (2 OCH2), 88.75, 114.20, 142.58 and 159.33 (furan), 124.98
and 128.13 (C=C alkene), 125.83 (Cortho), 126.71 (Cpara), 127.10 (Cmeta), 136.99 (Cipso),
128.44 (Cortho), 129.23 (Cpara), 134.20 (Cmeta), 135.17 (Cipso), 164.58 and 165.78 (2 CO); MS:
m/z (%): 77 (Ph, 14), 105 (Ph(CH3)2, 25), 121 ( (CH3)2PhNH2, 100), 299 (M+ -2
CH3CH2COOH, 19), 373 (M+ - CH3CH2COOH, 4), 402 (M+ -3 CH3, 30), 447 (M+, 70),
Anal. Calcd for C27H29NO5 (447.50): C, 72.46; H, 6.52; N, 3.13. Found: C, 72.51; H, 6.54;
N, 3.14.
Dimethyl 2-(2,6-Dimethyl-phenylamino)-5-furyl-3,4-furan dicarboxylate (4e):
o
,
Yellow powder, m.p. 140-142 C, yield 85%, IR (KBr) (νmax cm-1): 1675-1737 (C=O) and
1
3311 (NH); H NMR (400 MHz, CDCl3): H 2.30 (6H, s, 2 CH3), 3.87 and 3.95 (6H, 2s, 2
3
4
3
OCH3), 6.38 (1H, dd, JHH =3.5Hz, JHH =1.6 Hz, CH), 6.46 (1H, d, JHH =3.5 Hz, CH) 7.15
(3H, m, Ph), 7.37 (1H, d, 3JHH =1.6 Hz, CH) 8.12 (1H, s, NH); 13C NMR (400 MHz, CDCl3):
C 18.47 (2 CH3), 51.48 and 52.54 (2 OCH3), 87.76 (CN=C), 107.80 and 111.28 (2 CH),
112.32 (OC=C), 127.24 and 128.47 (Ph), 134.02 (C), 135.31 and 135.39 (Ph), 142.69 (CH),
143.76 (C), 159.99(C), 164.49 and 165.06 (2 CO); MS: m/z (%): 168 ( M+ -C12H12NO, 85),
265 (M+ -[COOCH3 + 3 CH3], 91), 339 (M+ -2 CH3, 92), 369 (M+ ,100), Anal. Calcd for
C20H19NO6 (369.35): C, 65.03; H, 5.18; N, 3.79. Found: C, 65.09; H, 5.21; N, 3.81.
Conclusion
We studied the synthesis of polyfunctionalized furans with longer conjugated aromatic
systems that can show chemiluminescence activities by a three component reaction under
the neutral conditions.

Synthesis of Polyfunctionalized Amino Furans with long Conjugated 795
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