Introduction

Multicomponent reactions are well established as a powerful tool for rapid construction of complex and structurally diverse compounds from relatively simple building blocks [1–3]. Simple procedures, high atom-economy, chemical efficiency, and convergence are typical features of such one-pot condensations of at least three different starting materials. Because of the remarkably high purity of libraries, multicomponent reactions are well-suited for both combinatorial chemistry and high-speed parallel synthesis, and therefore have high exploratory power [4, 5]. Isocyanide-based [6–10] multicomponent reactions, especially, have been emerging fields of interest in the last decade, but the construction of heterocycles via multicomponent reactions has also attracted interest recently [11–14].

Polysubstituted furans play an important role in organic chemistry, not only because of their presence as key structural units in many natural products [15] and in important pharmaceuticals [16] but also because of their use in synthetic chemistry as building blocks. For this reason the synthesis of polysubstituted furans continues to attract the interest of many synthetic chemists.

Although the trapping of the 1:1 intermediate formed between dialkyl acetylenedicarboxylates and isocyanides with aldehydes [17], aromatic anhydrides [18, 19], 1,3-diones [20], benzoyl chlorides [21], benzoyl cyanides [22], quinones [23], malimide, and succinimides [24] has been studied in detail by a number of research groups [6–10], trapping of the initial 1:1 intermediate formed with acetic or benzoic anhydride has not been reported.

Dimethyl acetylenedicarboxylate (DMAD) and isocyanides undergo a variety of cycloadditions with a third component containing a carbonyl group to form diverse heterocyclic scaffolds. For example the reaction of DMAD, an isocyanide, and phthalic anhydride derivatives produces benzofused spirolactones [18, 19]. We planned to test a similar reaction between DMAD, isocyanide, and acetic anhydride or benzoic anhydride for construction of iminolactone derivatives, which was also based on the work of Esmaili and Bodaghi [18] and Shaabani et al. [19]. In these experiments we found that the reaction was different. We now report a simple one-pot synthesis of 2,5-diaminofuran derivatives and highly functionalized enone compounds using alkyl isocyanides 1 and dialkyl acetylenedicarboxylates 2 in the presence of acetic anhydride (3a) or benzoic anhydride (3b) as trapping agents for the reactive zwitterionic intermediate. This three-component condensation reaction produces highly functionalized compounds 4 and 5 in fairly good yields (Scheme 1).

Scheme 1
scheme 1

 

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Results and discussion

The one-pot, three-component condensation reactions of alkyl isocyanides 1 with electron-deficient acetylenic esters 2 in the presence of acetic anhydride (3a) or benzoic anhydride (3b) proceeded spontaneously at room temperature in dichloromethane and was complete after 1 day, affording the corresponding dialkyl (E)-2-[(N-acyl-N-alkylamino)carbonyl]-2-butenedioates 4 and dialkyl 2-(N-acyl-N-alkylamino)-5-(alkylamino)-3,4-furandicarboxylates 5 in moderate to good yields. 1H NMR spectra of the crude reaction mixture clearly indicated the formation of compounds 4 and 5 even in 1:1:1 (isocyanide: DMAD: Ac2O) experiments. The structures of compounds 4a–4k and 5a–5k were deduced from their elemental analyses and their IR, 1H NMR, and 13C NMR spectroscopic data. For example, the 1H NMR spectrum of 4a exhibits a multiplet for the cyclohexyl ring (δ = 1.24–2.20 ppm) and four sharp singlets for the acetoxy group (δ = 2.39 ppm), two methoxy groups (δ = 3.67 and 3.84 ppm), and the vinylic proton (δ = 6.61 ppm). The E configuration of the carbon–carbon double bond in 4 is based on the chemical shift of the olefinic proton. The 13C NMR spectrum of 4a showed 15 distinct resonances in agreement with the proposed structure. Two signals (δ = 122.68 and 143.98) ppm are readily assigned to the olefinic carbon atoms.

The 1H NMR spectrum of 5b exhibits five sharp singlets for two tert-butyl groups (δ = 1.36 and 1.42 ppm), the acetoxy group (δ = 1.96 ppm), and two methoxy groups (δ = 3.77 and 3.84 ppm), and a broad signal (δ = 6.90 ppm) for the NH group. The 13C NMR spectrum of 5b showed 14 distinct resonances in agreement with the proposed structure. Four signals (δ = 85.91, 113.63, 139.66, and 159.61 ppm) are readily assigned to the furan carbon atoms. The mass spectra of compounds 4 and 5 displayed molecular ion peaks at appropriate m/z values.

A plausible mechanism for the formation of 4 is shown in Scheme 2. On the basis of the well-established chemistry of isocyanides [25–28] it is reasonable to assume that compound 4 results from initial addition of alkyl isocyanide 1 to the acetylenic ester and subsequent protonation of the 1:1 adduct 6 by acid from hydrolysis of the anhydride, followed by attack of the carboxylate anion of the positively charged ion 7 to form an imidoyl carboxylate 8, which undergoes rearrangement [29, 30] to produce the enone 4. Compound 4 is trapped by isocyanide to give the 2,5-diaminofuran derivative 5.

Scheme 2
scheme 2

 

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We extended our studies to various reaction conditions. The reaction in the presence of a 1:1 mixture of anhydride and the corresponding carboxylic acid or replacing the anhydride by carboxylic acid resulted in better yields of the products. When the solvent was carefully dried and the reaction was carried out under nitrogen atmosphere, the corresponding 2,5-dihydro-5-imino-2-alkylfuran-3,4-dicarboxylate 9 was obtained in 30–40% yields (Scheme 3). It is conceivable that the intermediate 6 adds to a carbonyl group of the anhydride which undergoes cyclization to 9. Furthermore, when few drops of water were added to the reaction mixture, the reaction proceeded smoothly to afford the desired products in good yields and reduced formation of 9.

Scheme 3
scheme 3

 

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In conclusion, the three-component reaction of alkyl isocyanides with electron-deficient acetylenic esters in the presence of acetic anhydride or benzoic anhydride provides a simple entry to the synthesis of 2,5-diaminofuran derivatives and polyfunctionalized enones of potential synthetic interest. This procedure has the advantage that, not only is the reaction performed under neutral conditions, but also the substances can be mixed without any activation or modification.

Experimental

Dialkyl acetylenedicarboxylates, alkyl isocyanides, and other reagents and solvents used in this work were obtained from Fluka (Buchs, Switzerland) and used without further purification. NMR spectra were recorded with a Bruker DRX-300 Avance instrument (299.9 MHz for 1H and 75.4 MHz for 13C) with CDCl3 as solvent. Chemical shifts are given in ppm (δ) relative to internal TMS, and coupling constants (J) are reported in Hertz (Hz). Melting points were measured with an Electrotherma1 9100 apparatus. Elemental analyses for C, H, and N were performed using a Heraeus CHN–O-Rapid analyzer. The results agreed favorably with the calculated values. Mass spectra were recorded with a Shimadzu QP-GC Mass 1100-EX spectrometer operating at an ionization potential of 70 eV. IR spectra were measured with Bruker Tensor 27 spectrometer.

General procedure

To a stirred solution of the anhydride (1 mmol) and dialkyl acetylenedicarboxylate (1 mmol) in 10 cm3 dichloromethane was added the isocyanide (2 mmol) in 2 cm3 dichloromethane at room temperature over 10 min via a syringe. The reaction mixture was stirred at room temperature for 24 h. The solvent was removed under reduced pressure and the residue was purified by silica gel column chromatography (Merck silica gel 60, 70–230 mesh) using hexane–ethyl acetate (8:2) as eluent.

Dimethyl (E)-2-[(N-acetyl-N-cyclohexylamino)carbonyl]-2-butenedioate (4a, C15H21NO6)

Pale yellow oil; 0.244 g (78%); IR (KBr): \( \bar{v} \) = 1,710, 1,685 (C=O), 1,645 (C=C), 1,300, 1,250 (C–O) cm−1; 1H NMR (300 MHz, CDCl3): δ = 1.24–2.20 (10H, m, 5 CH2), 2.39 (3H, s, CH3CO), 3.74 (1H, m, NCH), 3.67, 3.84 (6H, 2s, 2 OCH3), 6.61 (1H, s, C=CH) ppm; 13C NMR (75.4 MHz, CDCl3): δ = 25.2, 25.4, 26.7, 29.2, 29.8 (5 CH2), 25.4 (CH3CO), 52.3 and 53.0 (2 OCH3), 60.1 (NCH), 122.7 (C=CH), 143.9 (C=CH), 163.2 (NCO), 165.0, 166.7 (2 CO2CH3), 174.2 (CH3 CON) ppm; MS: m/z (%) = 311 (M+, 0.4), 170 (3), 155 (3), 86 (17), 84 (40), 60 (35), 43 (100).

Dimethyl 2-(N-acetyl-N-cyclohexylamino)-5-(cyclohexylamino)-3,4-furandicarboxylate (5a, C22H32N2O6)

Yellow oil; 0.04 g (10%); IR (KBr): \( \bar{v} \) = 3,288 (NH), 1,750, 1,712 (C=O), 1,294, 1,170 (C–O) cm−1; 1H NMR (300 MHz, CDCl3): δ = 1.12–2.30 (20H, m, 10 CH2), 3.10 (3H, s, CH3CO), 3.20–3.45 (2H, m, 2 NCH), 3.87, 3.89 (6H, 2s, 2 OCH3), 6.91 (1H, br s, NH) ppm; 13C NMR (75.4 MHz, CDCl3): δ = 23.2, 24.4, 25.1, 25.2, 25.5, 25.5, 26.2, 28.2, 29.8, 30.1, 31.1 (10 CH2, CH3CO), 52.7, 52.9 (2 OCH3), 53.5, 60.9 (2 NCH), 89.2 (furan-C4), 118.2 (furan-C3), 135.7 (furan-C5), 161.7 (furan-C2), 161.7, 162.4 (2 CO2CH3), 173.2 (C=O) ppm; MS (M+ = 420).

Dimethyl (E)-2-[(N-acetyl-N-tert-butylamino)carbonyl]-2-butenedioate (4b, C13H19NO6)

Yellow oil; 0.028 g (10%); IR (KBr): \( \bar{v} \) = 1,710 and 1,685 (C=O), 1,645 (C=C), 1,300 and 1,250 (C–O) cm−1; 1H NMR (300 MHz, CDCl3): δ = 1.60 (9H, s, NCMe3), 2.12 (3H, s, CH3CO), 3.98, 3.99 (6H, 2s, 2 OCH3), 6.34 (1H, s, C=CH) ppm; 13C NMR (75.4 MHz, CDCl3): δ = 25.4 (CH3CO), 28.7 (NCMe 3), 52.9, 53.1 (2 OCH3), 123.0 (C=CH), 144.1 (C=CH), 163.3 (NCO), 165.2, 166.7 (2 CO2CH3), 173.8 (CH3 CON) ppm; MS (M+ = 285).

Dimethyl 2-(N-acetyl-N-tert-butylamino)-5-(tert-butylamino)-3,4-furandicarboxylate (5b, C18H28N2O6)

Yellow powder; 0.296 g (80%); IR (KBr): \( \bar{v} \) = 3,285 (NH), 1,737, 1,710, 1,651 (C=O), 1,367, 1,296 (C–O) cm−1; 1H NMR (300 MHz, CDCl3): δ = 1.36 (9H, s, CMe 3), 1.42 (9H, s, CMe 3), 1.96 (3H, s, CH3CO), 3.77, 3.84 (6H, 2s, 2 OCH3), 6.90 (1H, br s, NH) ppm; 13C NMR (75.4 MHz, CDCl3): δ = 24.5 (CH3CO), 28.1, 29.7 (2 CMe 3), 51.2, 52.3 (2 OCH3), 52.7, 60.2 (2 CMe3), 85.9 (furan-C4), 113.6 (furan-C3), 139.7 (furan-C5), 159.6 (furan-C2), 163.3, 165.1 (2 CO2CH3), 172.5 (C=O) ppm; MS (M+ = 368).

Di-tert-butyl (E)-2-[(N-acetyl-N-tert-butylamino)carbonyl]-2-butenedioate (4c, C19H31NO6)

Pale yellow oil, 0.114 g (30%); IR (KBr): \( \bar{v} \) = 1,720, 1,691 (C=O), 1,658 (C=C), 1,251, 1,245, 1,180 (C–O) cm−1; 1H NMR (300 MHz, CDCl3): δ = 1.26, 1.49, 1.50 (27H, 3s, 3 CMe3), 2.49 (3H, s, CH3CO), 6.58 (1H, s, C=CH) ppm; 13C NMR (75.4 MHz, CDCl3): δ = 25.5 (CH3CO), 27.7, 28.3 (2 CMe 3), 28.8 (NCMe 3), 60.6 (NCMe3), 82.3, 83.2 (2 CMe3), 122.5 (C=CH), 144.2 (C=CH), 163.2 (NCO), 165.2, 166.7 (2 CO2CMe3), 174.2 (CH3 CON) ppm.

Di-tert-butyl 2-(N-acetyl-N-tert-butylamino)-5-(tert-butylamino)-3,4-furandicarboxylate (5c, C24H40N2O6)

Orange powder, 0.272 g (60%); IR (KBr): \( \bar{v} \) = 3,350 (NH), 1,732, 1,710, 1,690 (C=O), 1,603 (C=C), 1,367, 1,260 (C–O) cm−1; 1H NMR (300 MHz, CDCl3): δ = 1.38, 1.40, 1.52, 1.53 (36H, 4s, 4 CMe 3), 1.99 (3H, s, CH3CO), 6.45 (1H, s, NH) ppm; 13C NMR (75.4 MHz, CDCl3): δ = 24.4 (CH3CO), 28.2, 28.3, 28.6, 29.8 (4 CMe 3), 52.4, 60.0 (2 NCMe3), 80.4, 82.1 (2 OCMe3), 87.6 (furan-C4), 115.5 (furan-C3), 138.3 (furan-C5), 159.2 (furan-C2), 161.8, 164.48 (2 CO2CMe3), 172.9 (C=O) ppm; MS: m/z (%) = 452 (0.2), 143 (5), 98 (5), 77 (7), 71 (16), 58 (68), 43 (100).

Diethyl (E)-2-[(N-benzoyl-N-tert-butylamino)carbonyl]-2-butenedioate (4d, C20H25NO6)

Pale yellow powder; m.p.: 115–117 °C; 0.348 g (93%); IR (KBr): \( \bar{v} \) = 1,739, 1,722 (C=O), 1,668 (C=C), 1,598, 1,451 (Ph), 1,259, 1,174 (C–O) cm−1; 1H NMR (300 MHz, CDCl3): δ = 1.24 (3H, t, 3 J HH = 7.2 Hz, CH3), 1.28 (3H, t, 3 J HH = 7.2 Hz, CH3), 1.60 (3H, s, CMe3), 4.10 (2H, q, 3 J HH = 7.0 Hz, OCH 2 CH3), 4.20 (2H, q, 3 J HH = 7.0 Hz, OCH 2 CH3), 6.40 (1H, s, C=CH), 7.41 (2H, dd, 3 J HH = 7.4 Hz, 3 J HH = 7.5 Hz, 2 CHmeta), 7.56 (1H, t, 3 J HH = 7.4 Hz, CHpara), 7.81 (2H, d, 3 J HH = 7.6 Hz, 2 CHortho) ppm; 13C NMR (75.4 MHz, CDCl3): δ = 13.8, 14.1 (2 CH2 CH 3 ), 28.5 (CMe 3), 59.8 (CMe3), 61.5, 62.2 (OCH2), 128.5 (C=CH), 128.6 (2 CHmeta), 130.6 (2 CHortho), 134.1 (CHpara), 135.9 (Cipso), 141.7 (C=CH), 162.6 (NCO), 162.6, 163.5 (2 CO2Et), 175.2 (PhCON) ppm; MS: m/z (%) = 375 (M+, 0.2), 122 (21), 105 (44), 77 (100), 52 (86), 39 (28).

Dimethyl (E)-2-[(N-benzoyl-N-tert-butylamino)carbonyl]-2-butenedioate (4e, C18H21NO6)

Pale yellow crystals; m.p.: 130–132 °C; 0.295 g (85%); IR (KBr): \( \bar{v} \) = 1,726, 1,689 (C=O), 1,650 (C=C), 1,603, 1,585, 1,435 (Ph), 1,210, 1,179 (C–O) cm−1; 1H NMR (300 MHz, CDCl3): δ = 1.63 (9H, s, CMe3), 3.66, 3.77 (6H, 2s, 2 OCH3), 6.46 (1H, s, C=CH), 7.42 (2H, dd, 3 J HH = 7.5 Hz, 3 J HH = 7.5 Hz, 2 CHmeta), 7.51 (1H, t, 3 J HH = 7.4 Hz, CHpara), 7.80 (2H, d, 3 J HH = 7.4 Hz, 2 CHortho) ppm; 13C NMR (75.4 MHz, CDCl3): δ = 28.4 (CMe 3), 52.5, 52.8 (2 OCH3), 59.9 (CMe3), 128.5 (C=CH), 128.6 (2 CHmeta), 130.6 (2 CHortho), 134.2 (CHpara), 135.8 (Cipso), 141.1 (C=CH), 162.3 (NCO), 163.0, 163.8 (2 CO2Me), 175.2 (PhCON) ppm; MS: m/z (%) = 347 (M+, 0.1), 171 (18), 105 (100), 77 (56), 57 (10), 41 (9).

Dimethyl 2-(N-benzoyl-N-tert-butylamino)-5-(tert-butylamino)-3,4-furandicarboxylate (5e, C23H30N2O6)

Yellow paste; 0.052 g (12%); IR (KBr): \( \bar{v} \) = 3,328 (NH), 1,730, 1,705, 1,682 (C=O), 1,608 (C=C), 1,251, 1,210 (C–O) cm−1; 1H NMR (300 MHz, CDCl3): δ = 1.37, 1.42 (9H, 2s, 2 CMe 3), 3.74, 3.79 (6H, 2s, 2 OCH3), 6.90 (1H, s, NH), 7.42 (2H, dd, 3 J HH = 7.3 Hz, 3 J HH = 7.4 Hz, 2 CHmeta), 7.60 (1H, t, 3 J HH = 7.3 Hz, CHpara), 7.80 (2H, d, 3 J HH = 7.3 Hz, 2 CHortho) ppm; 13C NMR (75.4 MHz, CDCl3): δ = 28.1, 29.7 (2 CMe 3), 51.2, 52.3 (2 OCH3), 52.4, 60.3 (2 NCMe3), 85.2 (furan-C4), 114.1 (furan-C3), 128.5 (CHpara), 130.2 (2 CHortho), 133.8 (2 CHmeta), 136.9 (Cipso), 138.1 (furan-C5), 159.0 (furan-C2), 163.3, 164.4 (2 CO2Me), 175.2 (C=O) ppm; MS (M+ = 430).

Diethyl 2-(N-acetyl-N-tert-butylamino)-5-(tert-butylamino)-3,4-furandicarboxylate (5f, C20H32N2O6)

Colorless crystals; m.p.: 108–110 °C; 0.336 g (85%); IR (KBr): \( \bar{v} \) = 3,352 (NH), 1,732, 1,670 (C=O), 1,463 (C=C), 1,216 (C–O) cm−1; 1H NMR (300 MHz, CDCl3): δ = 1.28 (3H, t, 3 J HH = 7.1 Hz, CH3), 1.29 (3H, t, 3 J HH = 7.2 Hz, CH3), 1.36 (9H, s, CMe 3), 1.40 (9H, s, CMe 3), 1.96 (3H, s, CH3CO), 4.27 (2H, q, 3 J HH = 7.2 Hz, OCH2), 4.41 (2H, q, 3 J HH = 7.1 Hz, OCH2), 6.90 (1H, s, NH) ppm; 13C NMR (75.4 MHz, CDCl3): δ = 14.1, 14.3 (2 CH 3 CH2), 24.5 (CH 3 CO), 28.1, 29.7 (2 CMe 3), 52.6, 60.2 (2 CMe3), 59.8, 61.4 (2 OCH 2 CH3), 86.1 (furan-C4), 114.0 (furan-C3), 139.0 (furan-C5), 159.5 (furan-C2), 163.1, 164.7 (2 CO2Et), 172.6 (C=O) ppm; MS: m/z (%) = 143 (35), 125 (8), 98 (15), 81 (16), 56 (39), 53 (57), 43 (100).

Diethyl (E)-2-[(N-benzoyl-N-cyclohexylamino)carbonyl]-2-butenedioate (4g, C22H27NO6)

Colorless crystals; m.p.: 114–116 °C; 0.362 g (90%); IR (KBr): \( \bar{v} \) = 1,735, 1,690 (C=O), 1,660 (C=C), 1,601, 1,579 (Ph), 1,185, 1,120 (C–O) cm−1; 1H NMR (300 MHz, CDCl3): δ = 1.30 (3H, t, 3 J HH = 7.2 Hz, CH3), 1.34 (3H, t, 3 J HH = 7.2 Hz, CH3), 1.83–2.40 (10H, m, 5 CH2), 3.50 (1H, m, NCH), 4.22 (2H, q, 3 J HH = 7.2 Hz, OCH2), 4.28 (2H, q, 3 J HH = 7.2 Hz, OCH2), 6.43 (1H, s, C=CH), 7.42 (2H, dd, 3 J HH = 7.4 Hz, 3 J HH = 7.5 Hz, 2 CHmeta), 7.50 (1H, t, 3 J HH = 7.4 Hz, CHpara), 7.80 (2H, d, 3 J HH = 7.4 Hz, 2 CHortho) ppm; 13C NMR (75.4 MHz, CDCl3): δ = 13.9, 14.0 (2 CH3), 25.2, 26.4, 26.4, 26.4, 29.3 (5 CH2), 60.4, 61.5 (2 OCH2), 62.2 (NCH), 128.5 (2 CHmeta), 128.6 (2 CHortho), 130.6 (C=CH), 134.6 (CHpara), 135.5 (Cipso), 142.7 (C=CH), 162.7 (NCO), 164.3, 165.9 (2 CO2Et), 175.1 (PhCON) ppm; MS: m/z (%) = 401 (M+, 0.1), 123 (4), 122 (19), 105 (71), 77 (82), 52 (100).

Dimethyl (E)-2-[(N-benzoyl-N-cyclohexylamino)carbonyl]-2-butenedioate (4h, C20H23NO6)

Pale yellow paste; 0.299 g (80%); IR (KBr): \( \bar{v} \) = 1,741, 1,695 (C=O), 1,658 (C=C), 1,594, 1,460 (Ph), 1,279, 1,150 (C–O) cm−1; 1H NMR (300 MHz, CDCl3): δ = 1.51–2.40 (10H, m, 5 CH2), 3.45 (1H, m, NCH), 3.76, 3.82 (6H, 2s, 2 OCH3), 6.55 (1H, s, C=CH), 7.45 (2H, t, 3 J HH = 7.6 Hz, 2 CHmeta), 7.60 (1H, t, 3 J HH = 7.4 Hz, CHpara), 8.15 (2H, d, 3 J HH = 7.5 Hz, 2 CHortho) ppm; 13C NMR (75.4 MHz, CDCl3): δ = 25.4, 26.3, 26.5, 29.3 (5 CH2), 52.4, 53.0 (2 OCH3), 60.4 (NCH), 128.5 (C=CH), 128.6 (2 CHmeta), 130.6 (2 CHortho), 135.3 (CHpara), 135.5 (Cipso), 142.5 (C=CH), 163.2 (NCO), 164.6, 165.8 (2 CO2Me), 175.2 (PhCON) ppm; MS: m/z (%) = 373 (M+, 0.2), 122 (21), 105 (100), 77 (78), 52 (96).

Dimethyl 2-(N-benzoyl-N-cyclohexylamino)-5-(cyclohexylamino)-3,4-furandicarboxylate (5h, C27H34N2O6)

Yellow paste; 0.048 g (10%); IR (KBr): \( \bar{v} \) = 3,340 (NH), 1,730, 1,685 (C=O), 1,600 (C=C), 1,215 (C–O) cm−1; 1H NMR (300 MHz, CDCl3): δ = 1.10–2.25 (20H, m, 10 CH2), 3.15–3.45 (2H, m, 2 NCH), 3.72, 3.81 (6H, 2s, 2 OCH3), 6.80 (1H, br s, NH) 7.44 (2H, t, 3 J HH = 7.6 Hz, 2 CHmeta), 7.64 (1H, t, 3 J HH = 7.4 Hz, CHpara), 8.10 (2H, d, 3 J HH = 7.5 Hz, 2 CHortho) ppm; 13C NMR (75.4 MHz, CDCl3): δ = 23.2, 24.4, 25.1, 25.2, 25.5, 25.5, 26.2, 29.8, 30.1, 31.1 (10 CH2), 52.7, 53.1 (2 OCH3), 53.6, 60.9 (2 NCH), 88.7 (furan-C4), 114.7 (furan-C3), 130.1 (CHpara), 130.2 (2 CHortho), 133.8 (2 CHmeta), 135.7 (furan-C5), 136.9 (Cipso), 159.9 (furan-C2), 161.8, 162.6 (2 CO2CH3), 173.2 (C=O) ppm; MS: m/z (%) = 143 (4), 122 (22), 105 (54), 77 (100), 76 (22), 53 (18), 52 (96).

Dimethyl (E)-2-[(N-cyclohexyl-N-isobutyrylamino)carbonyl]-2-butenedioate (4i, C17H25NO6)

Pale yellow paste; 0.264 g (78%); IR (KBr): \( \bar{v} \) = 1,725, 1,700 (C=O), 1,678 (C=C), 1,254, 1,055 (C–O) cm−1; 1H NMR (300 MHz, CDCl3): δ = 1.10–1.90 (10H, m, 5 CH2), 1.16 (6H, d, 3 J HH = 6.8 Hz, Me 2CH), 2.55 (1H, hept, 3 J HH = 6.8 Hz, Me2CH), 3.65 (1H, m, NCH), 3.80, 3.92 (6H, 2s, 2 OCH3), 6.55 (1H, s, C=CH) ppm; 13C NMR (75.4 MHz, CDCl3): δ = 19.2 (Me 2CH), 23.4, 23.9, 25.4, 26.3, 26.5, 29.3 (5 CH2 and Me2 CH), 51.0 (NCH), 51.7, 52.2 (2 OCH3), 122.2 (C=CH), 142.6 (C=CH), 159.7 (NCO), 160.5, 162.1 (2 CO2Me), 171.0 (Me2CHCON) ppm; MS (M+ = 339).

Dimethyl 5-(cyclohexylamino)-2-(N-cyclohexyl-N-isobutyrylamino)-3,4-furandicarboxylate (5i, C24H36N2O6)

Yellow oil; 0.045 g (10%); IR (KBr): \( \bar{v} \) = 3,295 (NH), 1,745, 1,720 (C=O), 1,250, 1,170 (C–O) cm−1; 1H NMR (300 MHz, CDCl3): δ = 1.10–2.30 (26H, m, 10 CH2 and Me 2CH), 2.60 (1H, hept, Me2CH), 3.20–3.45 (2H, m, 2 NCH), 3.81, 3.88 (6H, 2s, 2 OCH3), 6.89 (1H, br s, NH) ppm; 13C NMR (75.4 MHz, CDCl3): δ = 21.8, 23.2, 24.4, 25.1, 25.2, 25.5, 25.5, 26.2, 29.8, 30.1, 31.1 (10 CH2 and Me 2CH), 42.2 (Me2 CH), 52.9, 53.3 (2 OCH3), 53.3, 60.4 (2 NCH), 89.5 (furan-C4), 118.4 (furan-C3), 135.6 (furan-C5), 161.7 (furan-C2), 161.7, 162.3 (2 CO2CH3), 173.9 (C=O) ppm; MS (M+ = 448).

Di-tert-butyl (E)-2-[(N-acetyl-N-cyclohexylamino)carbonyl]-2-butenedioate (4j, C21H33NO6)

Liquid oil; 0.316 g (80%), IR (KBr): \( \bar{v} \) = 1,717, 1,695 (C=O), 1,650 (C=C), 1,282, 1,210 (C–O) cm−1; 1H NMR (300 MHz, CDCl3): δ = 1.12–1.90 (10H, m, 5 CH2), 1.45, 1.50 (18H, 2s, 2 CMe3), 2.41 (3H, s, CH3CO), 3.56 (1H, m, NCH), 6.54 (1H, s, C=CH) ppm; 13C NMR (75.4 MHz, CDCl3): δ = 25.4 (CH3CO), 24.1, 25.2, 26.4, 26.7, 29.2, 29.3 (5 CH2), 27.8, 27.9 (2 CMe 3), 60.4 (NCH), 82.2, 83.2 (2 CMe3), 126.8 (C=CH), 143.7 (C=CH), 161.7 (NCO), 163.6, 167.7 (2 CO2CMe3), 173.9 (CH3 CON) ppm; MS: m/z (%) = 156 (2), 142 (3), 95 (2), 60 (18), 59 (24), 58 (100), 56 (20), 44 (16), 43 (62), 41 (66).

Diethyl (E)-2-[(N-acetyl-N-cyclohexylamino)carbonyl]-2-butenedioate (4k, C17H25NO6)

Yellow oil; 0.169 g (50%); IR (KBr): \( \bar{v} \) = 1,726, 1,684 (C=O), 1,643 (C=C), 1,305, 1,250 (C–O) cm−1; 1H NMR (300 MHz, CDCl3): δ = 1.20–1.95 (10H, m, 5 CH2), 1.23, 1.26 (6H, 2t, 2 CH3) 2.34 (3H, s, CH3CO), 3.65 (1H, m, NCH), 4.17, 4.22 (4H, 2q, 3 J HH = 7.2 Hz, 2 OCH2), 6.56 (1H, s, C=CH) ppm; 13C NMR (75.4 MHz, CDCl3): δ = 13.9, 14.1 (2 CH3), 25.2, 25.4, 25.4, 26.4, 29.3, 29.85 (5 CH2 and CH3CO), 60.4 (NCH), 61.4, 62.2 (2 OCH2), 123.6 (C=CH), 142.7 (C=CH), 162.7 (NCO), 164.3, 165.9 (2 CO2Et), 175.1 (CH3 CON) ppm; MS: m/z (%) = 339 (M+, 0.2), 170 (8), 143 (16), 98 (14), 69 (13), 67 (16), 60 (28), 56 (48), 53 (100).

Diethyl 2-(N-acetyl-N-cyclohexylamino)-5-(cyclohexylamino)-3,4-furandicarboxylate (5k, C24H36N2O6)

Yellow paste; 0.112 g (25%); IR (KBr): \( \bar{v} \) = 3,235 (NH), 1,742, 1,723 (C=O), 1,244, 1,167 (C–O) cm−1; 1H NMR (300 MHz, CDCl3): δ = 1.12–2.30 (26H, m, 10 CH2 and 2 CH3), 3.14 (3H, s, CH3CO), 3.15–3.40 (2H, m, 2 NCH), 4.23 (2H, q, 3 J HH = 7.4 Hz, OCH2), 4.45 (2H, q, 3 J HH = 7.4 Hz, OCH2), 6.92 (1H, br s, NH) ppm; 13C NMR (75.4 MHz, CDCl3): δ = 14.2, 14.3 (2 CH3), 23.2, 24.4, 25.1, 25.2, 25.5, 25.5, 26.2, 28.1, 29.8, 30.1, 31.1 (10 CH2 and CH3CO), 53.5, 60.9 (2 NCH), 59.7, 61.2 (2 OCH2), 86.2 (furan-C4), 114.1 (furan-C3), 139.2 (furan-C5), 159.5 (furan-C2), 162.9, 163.8 (2 CO2CH3), 172.6 (C=O) ppm; MS (M+ = 448).