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Acta Chim. Slov. 2007, 54, 638–641
Short communication
A Facile One-Pot Synthesis of Amino Furans Using
Trans-Cinnamaldehyde in the Presence
of Nucleophilic Isocyanides
Sakineh Asghari* and Mohammad Qandalee
Department of Chemistry, University of Mazandaran, P. O. Box 453, Babolsar, Iran
* Corresponding author: E-mail: s.asghari@umz.ac.ir
Received: 07-05-2007
Abstract
The 1 : 1 reactive intermediate generated by the addition of alkyl isocyanide to dialkyl acetylenedicarboxylates was trapped by trans-cinnamaldehyde to yield polyfunctionalized furan rings.
Keywords: Tert-butylisocyanide, dialkyl acetylenedicarboxylate, trans-cinnamaldehyde

1. Introduction
The development of reactions to produce hetero-cyclic compounds is of vital importance in organic synthesis, especially the heterocycles which can be found in naturally occurring products. A number of heterocyclic compounds such as furan, and pyran rings are found in natural systems. Furan rings, one example of five-mem-bered heterocycles, are found in a lot of naturally occurring products.1 The furan ring is not only present as key structural unit in naturally occurring products, but is also important in the pharmaceutical chemistry.2–4 Therefore, there has been interest in the synthesis of polyfunctional-ized furans, and some of the useful synthetic methods for
R
R´
yield of 4 (%)
Me Et
t-Bu
Me
Et
t-Bu
t-Bu t-Bu t-Bu Cya Cy Cy
65 60 68 58 72 68
furans have been reported, by many synthetic che-mists.5–12 The Paal–Knorr method,13 the Feist–Benary method,14 etc. are the most important methods for furan ring construction. Here, we wish to describe in detail the preparation of polyfunctionalized furan ring by reaction of alkyl isocyanides 1 with dialkyl acetylenedicarboxylate 2 in the presence of trans-cinnamaldehyde 3.
This three component reaction produces highly functionalized furans 4 in fairly good yields (Scheme 1).
2. Results and Discussion
On the basis of the well established chemistry of isocyanide,15–17 it is reasonable to assume that compound 4 results from the initial addition of the isocyanides to the acetylenic ester to form the zwitterionic intermediate 5, which attacks the carbonyl group of the trans-cinnamalde-hyde 3. Then, nucleophilic addition to the nitrile iminium moiety leads to the formation of the five-membered ring 6 which is aromatized to heterocyclic compound 4 by [1,5]-H shift (Scheme 2).
a Cy: cyclohexyl.
Scheme 1
4
Asghari and Qandalee:   A Facile One-Pot Synthesis of Amino Furans Using Trans-Cinnamaldehyde ...
Acta Chim. Slov. 2007, 54, 638–641
639
CO,R        O
t.            I -            O J
*-    R—N—C—C—C I C02R
H         Ph
RO,C.
R'—N=!
CO,R
^-       jj            Ph
H             [1,5]-H shift              //    \\
H    ----------------¦-
R1—N
H           Ph
Scheme 2
H          I*
The structure of 4a–f were deduced from their 1H and 13C NMR and IR spectra and their mass spectrometric data. The 1H NMR spectrum of 4a exhibited a sharp signal for tert-butyl (d = 1.5 ppm), two singlets for two met-hoxy groups (3.78 and 3.91 ppm), and a singlet for NH group (7.08 ppm) and two doublets for vinyl protons at about 6.88 and 7.07 ppm (3JHH = 16 Hz) showing E-geom-etry. The 13C NMR spectrum of 4a exhibited sixteen sharp lines in agreement with the proposed structure. The 1H and 13C NMR spectra of 4b and 4c are similar to that of 4a, except for the signals of alkoxy groups. The mass spectrum of 4a exhibited molecular ion peak at m/z 357(M+., 4%). Initial fragmentations involved loss or complete loss of the side chains of the furan system.
The 1H NMR spectrum of 4d displayed a quintet for the cyclohexyl CH proton (d = 3.5 ppm), and methylene groups (1.72–1.74 and 1.76–1.77 and 2.02–2.03 ppm), methoxy (3.87 and 3.75 ppm), and NH proton (6.85 ppm), and vinyl protons (7.08 and 7.22 ppm). The 13C NMR spectrum of 4d exhibited eighteen sharp lines in agreement with the proposed structure. This spectrum indicated four signals for cyclohexyl (d = 24.3, 25.2, 33.42 and 51.03 ppm), two methoxy groups (51.5 and 51.9 ppm) and carbonyl groups (164.17 and 165.3 ppm). Partial assignment of these resonances for 4a–f is given in the experimental section. The structural assignments of 4a–f were supported by their IR spectra which have a strong absorption band at about 3320 cm–1 for NH groups and 1650– 1730 cm–1 for COO groups.
3. Conclusion
We have found a simple and efficient method for the preparation of some functionalized amino furans of potential interest. The one-pot nature of the present procedure makes it an acceptable alternative to previous multistep approaches.
The present method carries some advantages including mild and neutral reaction conditions without any activation or modification.
4. Experimental
Dialkyl acetylenedicarboxylates, alkylisocyanides and trans-cinnamaldehyde were obtained from Fluka (Buchs, Switzerland) and were used without further purification. Melting points were measured on an Electe-rothermal 9100 apparatus and are uncorrected. 1H and 13C NMR spectra were measured with a Bruker DRX-500 Avance spectrometer at 500 and 125.8 MHz, respectively. Mass spectra were recorded on a Finnigan-Matt 8430 mass spectrometer operating at an ionization potential of 70 eV. IR spectra were recorded on a Shimadzu IR-470 spectrometer. Elemental analysis were performed using a Heraeus CHN-O-Rapid analyzer.
General procedure for preparation of dialkyl 2-(tert-butylamino)-5-[(E)-2-phe- nyl-l-ethenyl]-3,4-furandi-carboxylate (exemplified by 4a)
To a magnetically stirred solution of trans-cinnamaldehyde (0.264 g, 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 -10 °C over 10 min. The mixture was allowed to stir at room temperature for 2 days. The solvent was removed under reduced pressure and the residue was purified by silica gel (Merck silica gel, 230-400 mesh) column chromatography using hexane:ethyl acetate (80:20) as eluent. The solvent was removed under reduced pressure, the products 4a-f were obtained as yellow powders or viscous oil (4d).
Dimethyl 2-(tert-butylamino)-5-[(E)-2-phenyl-l-ethenyl]-3,4-furandicarboxyl- ate (4a).
Yellow powder, m.p. 74-75 °C, yield 65%, IR (KBr) (v    , cm1): 1699-1657 (COO) and 3315 (NH); 1H NMR
v   max
(500 MHz, CDCl3): SH 1.50 (9H, s, CMe3), 3.78 and 3.91 (6H, 2s, 2 × OCH3), 6.88 (1H, d, 3JHH = 16 Hz, -CH=),
7.07  (1H, dd, 3JHH = 16 Hz and 4JHH = 0.87 Hz, -CH=),
7.08  (1H, s, NH), 7.23 (1H, t, 3JHH = 7.5 Hz, H ), 7.32 (2H, t, 3JHH = 7.5 Hz, Hmeta), 7.45 (2H, d, 3JHH = 7.5 Hz, H     );   13C   NMR   (125.8   MHz,   CDCl):   8    29.8
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Acta Chim. Slov. 2007, 54, 638–641
(NHCMe3), 51.1 and 52.0 (2 x OCH3), 52.8 (NCMe3), 87.6, 114.1, 145.5 and 162.3 (furan), 114.2 and 128.0 (-C=), 126.5 (C     ), 127.9 (C    ), 128.7 (C     ), 136.6
v                                       ortho                            para                            meta
(Cj so), 164.2 and 165.4 (2COO); MS: m/z (%): 357 (M+-, 4), 301 (M+- C4H8, 8), 269 [M+- (HNC4H9 + CH3 + H), 19], 237 [M+ - (2C02CH3 + 2H), 16], 181 [M+-(PhCH=CH + HNC4H9 + H), 37], 131 [M+ -(Ph + C4H9 + C02Me + OMe + 2H), 100], 103 (PhCH=CH+, 100), 77 (Ph, 100), 57 (C4H9, 100). Anal. Calcd for C20H23NO5 (357.4): C, 67.21; H, 6.48; N, 3.92. Found: C, 67.10; H, 6.41; N, 3.91.
Diethyl 2-(tert-butylamino)-5-[(E)-2-phenyl-l-ethenyl]-3,4-furandicarboxylate (4b).
Yellow powder, m.p. 84-86 °C, yield 60%, IR (KBr) (v    , cm"1): 1669-1712 (COO) and 3333 (NH); :H NMR
v   max
(500 MHz, CDC13): 8H 1.29 (3H, t, 3JHH = 7.1 Hz, CH3), 1.37 (3H, t, 3JHH = 7.1 Hz, CH3), 1.48 (9H, s, CMe3), 4.22 (2H, q, 3JHH = 7.1 Hz, OCH2), 4.34 (2H, q, 3JHH = 7.1 Hz, OCH2), 6.87 (IH, d, 3JHH = 16.1 Hz, -CH=), 7.07 (IH, d, 3JHH = 16.1 Hz, -CH=), 7.07 (IH, s, NH), 7.22 (IH, t, 3JHH = 7.5 Hz, H ara), 7.31 (2H, t, 3JHH = 7.5 Hz, Hmeta), 7.44 (2H, d, 3JHH = 7.5 Hz, Hortho); 13C NMR (125.8 MHz, CDC13): ôc 14.3 (CH3), 14.4 (CH3), 29.8 (CMe3), 52.8 (NCMe3), 59.6 (OCH2), 60.9 (OCH2), 87.9, 114.7, 145.1 and 162.2 (furan), 114.2 and 127.7 (-C=), 126.5 (Cortho), 127.5 (C    ), 128.6 (C    ), 136.7 (C    ), 163.9 and 165.0
 para                          meta                          ipso
(2 x COO); MS: m/z (%): 385 (M+-, 41), 329 (M+- - C4H8, 59), 283 [M+- (C02Et + Et), 44], 255 [M+- (2C2H5 + NHC4H9), 43], 238 [M+- (PhCH=CH + OC2H5 + H), 100], 131 [M+- (Ph + C4H9 + C02Et + OEt + 2H), 100], 103 (PhCH=CH+, 100), 77 (Ph+, 100), 57 (C4H9+, 100). Anal. Calcd for C22H27N05 (385.45): C, 68.55; H, 7.06; N, 3.63. Found: C, 68.40; H, 6.92; N, 3.61.
Di(tert-butyl)-2-(tert-butylamino)-5-[(E)-2-phenyl-l-ethenyl]-3,4-furandicarboxylate (4c).
Yellow powder, m.p. 124-126 °C, yield 68%, IR (KBr) (v    , cm"1): 1657-1699 (COO) and 3322 (NH); :H
 v   max
NMR (500 MHz, CDC13): ôH 1.46 (9H, s, NHCMe3), 1.51 (9H, s, OCMe3), 1.61 (9H, s, OCMe3), 6.92 (IH, s, NH), 6.81 (IH, d, 3JHH = 16 Hz, -CH=), 7.05 (IH, d, 3JHH = 16 Hz, -CH=), 7.22 (IH, t, 3JHH = 7.5 Hz, H ), 7.32 (2H, t, 3JHH = 7.5 Hz, Hmeta), 7.41 (2H, d, 3JHH = 7.5 Hz, Hortho); 13C NMR (125.8 MHz, CDC13): ôc 28.4 (NCMe3), 28.5 (OCMe3), 29.8 (OCMe3), 52.6 (NHCMe3), 80.1 (OCMe3), 81.4 (OCMe3), 90.0, 116.9, 144.1 and 161.8 (furan), 114.4 and 127.5 (-C=), 126.2 (Cortho), 126.5 (C ), 128.7 (Cmeta), 137.1 (Cj ), 162.3 and 164.4 (2 x COO); MS: m/z (%): 441 (M+', 7), 329 (M+-2C4H8, 100), 273 (M+- 3C4H8, 100), 255 [M+- (2C4H9 + NHC4H9), 37], 238 [M+- (C4H9 + OC4H9 + NHC4H9 + H), 30], 166 [M+- (2C02 C4H9 + NHC4H9 + H), 26], 131[M+- Ph + C4H9 + C02C4H9 + OC4H9 + 2H), 100], 103 (PhCH=CH+, 33), 77 (Ph+, 21), 57 (C4H9+, 100). Anal. Calcd for C26H35N05 (441.56): C, 70.72; H, 7.99; N, 3.17. Found: C, 70.61; H, 7.86; N, 3.09.
Dimethyl 2-(cyclohexylamino)-5-[(E)-2-phenyl-l-ethenyl]-3,4-furandicarboxy- late (4d).
Viscous oil, yield 58%, IR (KBr) (v    , cm"1):
 \ max
1671-1727 (COO) and 3350 (NH); :H NMR (500 MHz, CDC13): 8H 1.72-1.74 (4H, m, Cy), 1.76-1.77 (2H, m, Cy), 2.02-2.03 (4H, m, Cy), 3.50 (IH, q, 3JHH = 3.5 Hz, Cy), 3.75 and 3.87 (6H, 2s, 2 x OCH3), 6.85 (IH, s, NH), 7.08 (IH, d, 3JHH = 16 Hz, -CH=), 7.22 (IH, q, 3JHH = 16 Hz, -CH=), 7.25 (IH, t, 3JHH = 7.5 Hz, H ara), 7.32 (2H, t, 3JHH = 7.5 Hz, Hmeta), 7.44 (2H, d, 3JHH = 7.5 Hz, Hortho); 13C NMR (125.8 MHz, CDC13): ôc 24.3, 25.2, 33.4 and 51.0 (Cy), 51.5 and 51.9 (2 x OCH3), 86.8, 114.4, 145.2 and 161.9 (furan), 114.2 and 127.9 (-C=), 126.5 (Cortho), 127.8 (C ara), 128.6 (Cmeta), 136.7 (C; so), 164.1 and 165.3 (2 x COO); MS: m/z (%): 383 (M+-, 3), 279 [M+ -PhCH=CH+ + H), 8], 237 [M+- (2C02Me + 2H), 2), 167 [M+- (2C02Me + NHC6Hn), 82], 149 [M+ -(PhCH=CH+, + NHC4H9 + C02Me), 100], 103 (PhCH=CH+, 37), 77 (Ph+, 95), 72 (NC4H9+, 67). Anal. Calcd for C22H25N05 (383.43): C, 68.91; H, 6.57; N, 3.65. Found: C, 68.80; H, 6.49; N, 3.60.
Diethyl 2-(cyclohexylamino)-5-[(E)-2-phenyl-l-ethenyl]-3,4-furandicarboxylate (4e).
Yellow powder, m.p. 66-68 °C, yield 72%, IR (KBr) (v    , cm"1): 1669-1704 (COO) and 3311 (NH); :H NMR
v   max
(500 MHz, CDC13): ôH 1.30 and 1.37 (6H, 2t, 3JHH = 7 Hz and 3JHH = 7.5 Hz, 2 x CH3), 1.61-1.63 (4H, m, Cy), 1.76-1.78 (2H, m, Cy), 2.02-2.03 (4H, m, Cy), 3.73 (IH, q, 3JHH = 3.5 Hz, Cy), 4.22 and 4.33 (4H, 2q, 3JHH = 7 Hz and 3JHH = 7.5 Hz, 2 x OCH2), 6.87 (IH, s, NH), 6.85 (IH, d, 3JHH = 16 Hz, -CH=), 7.07 (IH, d, 3JHH = 16 Hz, -CH=), 7.22 (IH, t, 3JHH = 7.5 Hz, H ara), 7.31 (2H, t, 3JHH = 7.5 Hz, Hmeta), 7.44 (2H, d, 3JHH = 7.5 Hz, Hortho); 13C NMR (125.8 MHz, CDC13): ôc 14.3 and 14.4 (2 x CH3), 24.5, 25.4, 33.4 and 51.4 (Cy), 59.6 and 60.9 (2 x OCH2) 87.0, 115.0, 144.8 and 161.9 (furan), 114.2 and 127.7 (-C=), 126.4 (Cortho), 127.4 (C ara), 128.7 (Cmeta), 136.8 (C    ), 163.8 and 164.9 (2 x COO); MS: m/z (%): 411
 ipso
(M+-, 21), 366 (M+- - C2H5, 3), 329 [M+- (C6Hn + H), 2), 255 [M+ - (2C2H5 + NHC6Hn), 11], 238 [M+ +1 -(NHC6Hn + OEt + Et + H), 24], 210 [M+ - (PhCH=CH+ + NHC6Hn), 10], 131[M+ -(Ph + C6Hn + C02Et + OEt + 2H), 100], 103 (PhCH=CH+, 57), 83 (C6Hn+, 33), 77 (Ph+, 59). Anal. Calcd for C24H29N05 (411.49): C, 70.05; H, 7.10; N, 3.40. Found: C, 69.92; H, 6.98; N, 3.25.
Di(tert-butyl)-2-(cyclohexylamino)-5-[(E)-2-phenyl-l-ethenyl]-3,4-furandicarb-oxylate (4f).
Yellow powder, m.p. 93-95 °C, yield 68%, IR (KBr) (v    , cm"1): 1664-1713 (COO) and 3329 (NH); :H NMR
v   max
(500 MHz, CDC13): ôH 1.55 and 1.75 (18H, 2s, 2 x CMe3), 1.43-1.46 (4H, m, Cy), 1.52-1.55 (2H, m, Cy), 2.02-2.03 (4H, m, Cy), 3.10 (IH, q, 3JHH = 3.5 Hz, Cy), 6.98 (IH, s, NH), 6.82 (IH, d, 3JHH = 16 Hz, -CH=), 7.20 (IH, d, 3JHH = 16 Hz, -CH=), 7.21 (IH, t, 3JHH = 7.5 Hz, H ara), 7.32
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(2H, t, 3JHH = 7.5 Hz, Hmeta), 7.45 (2H, d, 3JHH = 7.5 Hz, Hortho); 13C NMR (125.8 MHz, CDC13): dc 24.4 and 24.4 (2 x CMe3), 27.9, 28.4, 33.5 and 51.4 (Cy), 56.2 and 58.5 (2 x OCMe3), 80.1, 115.1, 143.8 and 161.5 (furan), 114.4 and 127.5 (-C=), 126.2 (Cortho), 126.8 (C ), 128.7 (Cmeta), 137.1 (Cj ), 164.1 and 164.3 (2 x COO); MS: m/z (%): 467 (M+', 3), 355 (M+' - 2C4H8, 70), 255 [M+ -(2C4H9 + NHC6Hn), 9), 238 [M+ - (C4H9 + HOC4H9 + NHC6Hn), 26], 167 [M+ - (2C02C4H9 + NHC6Hn), 73], 149 [M+ - (Ph + C6Hn + C02C4H9 + C4H9), 100], 131[M+ - (Ph + C6Hn + C02C4H9 + OC4H9 + 2H), 100], 103 (PhCH=CH+, 38), 83 (C6Hn+, 100), 77 (Ph+, 16.2). Anal. Calcd for C28H37N05 (467.59): C, 71.92; H, 7.97; N, 2.99. Found: C, 71.80; H, 7.90; N, 2.94.
5. References
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Povzetek
Reaktivni intermediat, ki nastane pri adiciji alkil izocianida na dialkil acetilendikarboksilate (v razmerju 1:1) je bil us-pe{no cikliziran s trans-cimetaldehidom pri ~emer so nastali polifunkcionalizirani derivati furana.
Asghari and Qandalee:   A Facile One-Pot Synthesis of Amino Furans Using Trans-Cinnamaldehyde ...