Ph3P + RO2CC CCO2R + O H N H O R¢ Ph3P+ C CHCO2R CO2R O H N– O R¢ H O N CHCO2R O R¢ C CO2R PPh3 2 N CO2R CO2R O R¢ 3 4 1 CH2Cl2 r.t. + a R = Me, R¢ = Me b R = Et, R¢ = Me c R = But, R¢ = Me d R = Me, R¢ = Ph e R = Et, R¢ = Ph f R = But, R¢ = Ph 5 PPh3 208 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 208–209† One-step Synthesis of Dialkyl 1,2-Dihydroquinoline- 2,3-dicarboxylates. A Vinyltriphenylphosphonium Salt Mediated Intramolecular Wittig Reaction† Issa Yavari,* Ali Ramazani and Abbas Ali Esmaili Chemistry Department, Tarbiat Modarres University, P.O.Box 14155-4838, Tehran, Iran Dialkyl 1,2-dihydroquinoline-2,3-dicarboxylates are formed in a one-pot reaction from amide derivatives of 2-aminobenzaldehyde, dialkyl acetylenedicarboxylates and triphenylphosphine in CH2Cl2 in high yields. Quinolines1 are interesting synthetic targets because they act as building blocks for a large number of natural products. In recent years there has been an increase in interest in the synthesis of quinoline compounds.This interest has resulted from the use of such compounds in a variety of biological and synthetic applications.2 While a number of synthetic methodologies for the quinoline ring system have been developed,3 the literature describing a novel one-pot cyclization method based on consecutive processes is rather scarce. Recently, we have established a heterocyclic synthesis using a novel approach to vinylphosphonium salts.4,5 Here we describe a facile one-pot synthesis of dialkyl 1,2-dihydroquinoline- 2,3-dicarboxylates (5) in high yields.Several examples are known in which an unsaturated heterocyclic compound is formed from a phosphorane connected to a carbonyl group by a chain containing a heteroatom. 6–10 Thus, quinoline 5 may be considered as the product of an intramolecular Wittig reaction. Such addition-cyclization products apparently result from the initial addition of triphenylphosphine to the acetylenic ester11,12 and concomitant protonation of the 1:1 adduct, followed by attack of the anion of the 2-aminobenzaldehyde derivative on the vinylphosphonium cation to form the phosphorane 4 which is then converted into quinolines.The essential structures of compounds 5a–f were deduced from their elemental analyses and their 1H and 13C NMR spectra. The molecular ion peak is very weak in the mass spectra of 5a–f accompanied by a stronger M+1 peak owing to the protonation of these molecules in the mass spectrometer.Initial fragmentations involve loss from one of the quinoline side chains. The 1H NMR spectrum of 5a displayed five single lines readily recognizable as arising from methyl (d 2.32), methoxy (d 3.61 and 3.88), N·CH (d 6.62) and olefinic CH (d 7.61) protons, along with a fairly complex multiplet in the aromatic region (see Experimental section). The noise-decoupled 13C NMR spectrum of 5a showed 15 distinct resonances in agreement with the dihydroquinoline structure.Partial assignments of these resonances are given in the Experimental section. The 1H and 13C NMR spectra of 5b–f are similar to those of 5a, except for the ester groups and the amide moiety, which exhibit characteristic signals with appropriate chemical shifts (see Experimental section). The structural assignments made on the basis of the 1H and 13C NMR spectra of compounds 5a–f were supported by measurement of their IR spectra.The carbonyl region of the spectrum exhibited three distinct absorption bands for each compound (see Experimental section). Of special interest is the ester absorption at 1691–1714 cmµ1 for these compounds. Conjugation with the carbon–carbon double bond appears to be a plausible factor in the reduction of these bands.13 In conclusion, vinyltriphenylphosphonium salts have been shown to be useful precursors for a new and efficient synthetic route to 1,2-dihydroquinoline derivatives.The one-pot nature of the present procedure makes it an alternative to multistep approaches.14–16 Further applications of this type of addition-cyclization to the synthesis of interesting heterocycles will be reported in due course. Experimental Melting points were measured on an Electrothermal 9100 apparatus and are uncorrected. Elemental analyses were performed using a Heraeus CHN-O-rapid analyser. IR spectra were recorded on a Shimadzu IR-460 spectrometer. 1H and 13C NMR spectra were measured with JEOL EX-90A spectrometer at 90 and 22.6 MHz, respectively.Mass spectra were recorded on a Finnigan- Matt 8430 mass spectrometer operating at an ionization potential of 70 eV. Preparation of Anilides 2a and 2d.·Compounds 2a and 2d were prepared by known methods17 and identified as follows. 2p- Formylacetanilide 2a: white crystals, mp 68–69 °C. dH (CDCl3) 2.23 (3 H, s, CH3CON), 7.1–7.7 (3 H, m, arom.), 8.71 (1 H, d, J 8.1 Hz, 3-H), 9.88 (1 H, s, CHO), 11.1 (1 H, brs, CONH).dC (CDCl3) 25.00 (CH3), 119.35, 122.49, 135.71 and 135.73 (4 CH), 121.27 (C2), 140.61 (C1), 169.07 (CON), 195.22 (CHO). 2p-Formylbenzanilide 2d: white crystals, mp 70–71 °C. dH (CDCl3) 7.1–8.1 (8 H, m, arom.), 8.94 (1 H, d, J 8.1 Hz, 3-H), 9.96 (1 H, s, CHO), 12.0 (1 H, brs, CONH). dC (CDCl3) 119.27, 122.44, 135.63 and 135.65 (4 CH), 121.43 (C2), 140.57 (C1), 126.96 and 128.35 (2 CH of benzoyl, ortho and meta), 131.65 (CH of benzoyl, para), 133.72 (ipso-C of benzoyl), 165.24 (CON), 195.29 (CHO).*To receive any correspondence. †This is a Short Paper as defined in the Instructions for Authors, Section 5.0 [see J. Chem. Research (S), 1997, Issue 1]; there is therefore no corresponding material in J. Chem. Research (M).J. CHEM. RESEARCH (S), 1997 209 Preparation of Dialkyl 1,2-Dihydroquinoline-2,3-dicarboxylates 5.·The typical process, exemplified for the preparation of 5a, is described below. Preparation of 5a. To a magnetically stirred solution of triphenylphosphine (0.262 g, 1 mmol) and 2p-formylacetanilide 2a (0.161 g, 1 mmol) in CH2Cl2 (3 ml) was added dropwise a mixture of dimethyl acetylenedicarboxylate (0.142 g, 1 mmol) in CH2Cl2 (2 ml) at µ10 °C over 10 min.The reaction mixture was then allowed to warm up to room temperature and stirred for 24 h. The solvent was removed under reduced pressure and the residue was purified by silica gel (Merck silica gel 60, 230–400 mesh) column chromatography using diethyl ether–hexane (1:1) as eluent.The solvent was removed under reduced pressure to afford the product (0.26 g, mp 137–138 °C, 90%) which was recrystallized from ethanol (95%) to yield dimethyl N-acetyl-1,2-dihydroquinoline-2,3-dicarboxylate (5a) as white crystals (0.24 g), mp 138–139 °C; vmax/cmµ1 (KBr) 1740 and 1714 (2 C�O, ester), 1668 (C�O, amide); dH (CDCl3) 2.32 (3 H, s, CH3CON), 3.61 and 3.88 (6 H, 2 s, 2 OCH3), 6.62 (1 H, s, NCH), 7.1–7.5 (4 H, m, arom.), 7.61 (1 H, s, 4-H); dC (CDCl3) 22.23 (CH3CON), 51.78 (NCH), 52.29 and 52.69 (2 OCH3), 124.36, 125.87, 129.00, 130.35 and 134.09 (5 CH), 126.03, 127.21 and 136.41 (3 C), 164.88, 169.24 and 169.68 (3 C�O); m/z 290 (3%, MH+, 230 (12%, MH+µCO2µCH4), 188 (100% MH+µCO2CH3µ CH3CO), 128 (27%, MH+µ2CO2CH3µCH3CHO) [Found: C, 63.8; H, 6.1; N, 4.1%.Calc. for C15H15NO5 (289.29): C, 62.28; H, 5.23; N, 4.84%]. Selected data for 5b. White crystals (0.28 g), mp 113–114 °C, yielded 87%; vmax/cmµ1 (KBr) 1735 and 1709 (2 CO�O, ester), 1665 (C�O, amide); dH (CDCl3) 1.12 (3 H, t, J 7.0 Hz, CH3 of ester), 1.37 (3 H, t, J 7.5 Hz, CH3 of ester), 2.33 (3 H, s, CH3CON), 3.80–4.31 (2 H, 2 dq, J 7.0 and µ10.7 Hz, OCH2 of ester), 4.35 (2 H, q, J 7.5 Hz, OCH2 of ester), 6.60 (1 H, s, NCH), 7.1–7.5 (4 H, m, arom.), 7.59 (1 H, sm, 4-H); dC (CDCl3) 13.97 and 14.29 (2 CH3 of 2 Et), 22.36 (CH3 of CH3CON), 52.12 (NCH), 61.24 and 61.65 (2 OCH2), 124.40, 125.75, 128.88, 130.14 and 133.65 (5 CH); 126.15, 127.94 and 136.54 (3 C); 164.51, 168.71 and 169.64 (3 C�O); m/z 318 (2%, MH+), 244 (17%, MH+µCO2Et), 202 (100%, MH+µ CO2EtµCH3CO), 174 (45%,H3COµCO2EtµCH2 �CH2), 128 (25%, MH+µ2CO2EtµCH3CHO) [Found: C, 63.8; H, 6.1; N, 4.1%.Calc. for C17H19NO5 (317.34): C, 64.34; H, 6.04; N, 4.41%]. Selected data for 5c. Viscous colourless oil (0.35 g), yield 94%; vmax/cmµ1 (CCl4) 1732 and 1702 (2 C�O, ester), 1670 (C�O, amide); dH (CDCl3) 1.29 and 1.57 (18 H, 2 s, 2 But), 2.32 (3 H, s, CH3CON), 6.38 (1 H, s, NCH), 7.1–7.4 (4 H, m, arom.), 7.45 (1 H, s, 4-H); dC (CDCl3) 27.81 and 28.18 (6 CH3, 2 But), 52.73 (NCH), 81.48 and 82.30 (2 C, 2 But), 124.36, 125.46, 128.60, 129.82 and 132.30 (5 CH), 126.32, 128.60 and 136.62 (3 C), 163.78, 167.81 and 169.56 (3 C�O); m/z 374 (2%, MH+), 272 (4%, MH+µCO2µ Me3CH), 230 (7%, MH+µCO2ButµCH3CO), 174 (100%, MH+µCO2ButµCH3CO, CH2�CMe2) [Found: C, 68.3; H, 7.3; N, 4.2%.Calc. for C21H27NO5 (373.45): C, 67.54; H, 7.29; N, 3.75%].Selected data for 5d. White crystals (0.29 g), mp 160–161 °C, yield 83%; vmax/cmµ1 (KBr) 1740 and 1705 (2 C�O, ester), 1645 (C�O, amide); dH (CDCl3) 3.63 and 3.89 (6 H, 2 s, 2 OCH3), 6.46 (1 H, s, NCH), 6.7–7.6 (9 H, m, arom.), 7.69 (1 H, s, 4-H); dC (CDCl3) 52.59 and 52.73 (2 OCH3), 53.50 (NCH), 125.01, 125.14, 129.78, 131.04 and 134.22 (5 CH of quinoline), 128.27 and 129.04 (2 CH of benzoyl, ortho and meta), 128.80 (CH of benzoyl, para), 134.30 (ipso-C of benzoyl), 126.37, 129.05 and 137.35 (3 C of quinoline), 164.84, 169.11 and 169.44 (3 C�O); m/z 352 (4%, MH+), 294 (10%, MH+µCO2µCH4), 156 (15%, MH+µCO2CH3µOCH3, C6H5CHO), 128 (20%, MH+µ2 CO2CH3µC6H5CHO) 105 (100%, C6H5CO+) [Found: C, 67.7; H, 4.9; N, 3.6%.Calc. for C20H17NO5 (351.36): C, 68.37; H, 4.88; N, 3.99%]. Selected data for 5e. White crystals (0.33 g), mp 76-5–78 °C, yield 88%; vmax/cmµ1 (KBr) 1730 and 1691 (2 C�O, ester), 1665 (C�O, amide); dH (CDCl3) 1.14 (3 H, t, J 7.2 Hz, CH3 of ester), 1.37 (3 H, t, J 7.0 Hz, CH3 of ester), 3.80–4.31 (2 H, 2 dq, J 7.2 and µ10.8 Hz, OCH2 of ester), 4.35 (2 H, q, J 7.0 Hz, OCH2 of ester), 6.43 (1 H, s, NCH), 6.7–7.6 (9 H, m, arom.), 7.66 (1 H, s, 4-H); dC (CDCl3) 13.93 and 14.29 (2 CH2CH3), 53.51 (NCH), 61.24 and 61.69 (2 OCH2), 125.12, 125.13, 129.66, 131.00 and 134.42 (5 CH of quinoline), 128.31 and 129.04 (2 CH of benzoyl, ortho and meta), 128.72 (CH of benzoyl, para), 133.77 (ipso-C of benzoyl), 127.01, 129.05 and 137.39 (3 C of quinoline), 164.47, 168.62 and 169.56 (3 C�O); m/z 380 (3%, MH+), 306 (100%, MH+µ2 CH2�CH2µH2O), 279 (15%, MH+µCO2EtµCH2�CH2), 105 (C6H5CO+) [Found: C, 69.0; H, 5.7; N, 3.4%.Calc. for C22H21NO5 (379.42): C, 69.65; H, 5.58; N, 3.69%]. Selected data for 5f. White crystals (0.41 g), mp 128.5–130 °C, yield 95%; vmax cmµ1 KBr 1735 and 1699 (2 C�O, ester), 1647 (C�O, amide); dH (CDCl3) 1.32 and 1.56 (18 H, 2 s, 2 But), 6.24 (1 H, s, NCH), 6.7–7.5 (9 H, m, arom.), 7.53 (1 H, s, 4-H).dC (CDCl3) 27.81 and 28.06 (6 CH3, But), 54.28 (NCH), 81.36 and 82.28 (2 C, 2 But), 124.85, 125.05, 129.29, 130.80 and 132.38 (5 CH of quinoline), 128.23 and 128.84 (2 CH of benzoyl, ortho and meta), 128.39 (CH of benzoyl, para), 134.70 (ipso-C of benzoyl), 125.30, 128.85 and 137.35 (3 C of quinoline), 163.62, 167.65 and 169.48 (3 C�O); m/z 436 (2%, MH+), 334 (100%, MH+µCO2µMe3CH), 306 (15%, MH+µ2 CH2�CMe2µH2O), 278 (50%, MH+µCO2 µMe3CHµCH2�CMe2), 156 (10%, MH+µCO2ButµOBut µC6H5CHO), 105 (25%, C6H5CO+), 174 (100%, MH+µ CO2ButµCH3CO, CH2�CMe2 [Found: C, 71.3; H, 6.8; N, 3.4%.Calc. for C26H29NO5 (435.52): C, 71.70; H, 6.71; N, 3.22%]. Received, 3rd December 1996; Accepted, 19th February 1997 Paper E/6/08156H References 1 J. D. 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