Tin powder-promoted allylation and cyclization of 2-(benzylideneamino)isoindoline-1,3-diones
-
Nibras Ahmed Elaas
,
Ke-Hu Wang
and
Yulai Hu
Abstract
α-Methylene-γ-lactams were synthesized from readily available N-acylhydrazones by a tin-mediated Barbier-type reaction. The method avoids the use of toxic allylstannanes and the reaction proceeds smoothly under mild conditions.
Introduction
The addition of allylic organometallic compounds to imines is one of the most important methods for the preparation of homoallylic amines [1], [2], [3], [4], [5]. Many allylic organometallics such as allylic magnesium, zinc, boron, silane and stannane reagents have been used in such reactions [6], [7], [8], [9], [10], [11], [12], [13]. In particular, allylstannanes are stable toward heat, hydrolysis, oxygen, and are compatible with many functional groups [3], [4], [8], [9]. However, the application of allylstannanes in organic synthesis is restricted due to their toxicity and the formation of undesirable trialkyltin-containing by-products [14], [15]. Besides, Lewis acids or transition-metal catalysts are often needed in allylstannane-mediated allylation reactions [3], [4], [8], [9]. In 1981, Mukaiyama and Harada [16] reported for the first time the allylation reaction of carbonyl compounds with allylic halide in the presence of tin powder to give the corresponding homoallylic alcohols. Additional reactions of this type with imines have been investigated [17], [18], [19], [20], [21]. In this report, we describe a practical procedure for the preparation of homoallylic N-aminophthalimides and α-methylene-γ-lactams by the reactions of aromatic aldehydes and N-acylhydrazones derived from N-aminophthalimide in the presence of tin powder. The combination of tin powder and allylic bromide as an allylation system avoids the use of toxic allylstannane.
Results and discussion
Initially, a mixture of 1 equivalent of 2-(benzylideneamino)isoindoline-1,3-dione (1a, generated from benzaldehyde and N-aminophthalimide), 1.5 equivalents of 2-(bromomethyl)acrylate (2) and 2 equivalents of tin powder in ethanol was heated under reflux. After 2 h, product 3a was obtained in 32% yield, and a trace amount of cyclized derivative 4a was also detected (Scheme 1). Under optimized conditions, the use of 1 equivalent of 1a, 3 equivalents of 2 and 3.5 equivalents of tin powder in ethanol furnished the desired product 3a in 57% yield. The use of dichloromethane, tetrahydrofuran, methanol, toluene and 1,4-dioxane have been examined. The product 3a was obtained in a 36% yield after 2 h of heating in methanol under reflux. In the remaining solvents under similar conditions, the allylation reaction of 1a did not occur. These results show that ethanol is the optimized solvent for the allylation reaction of 1a. Then, the allylation reaction was examined using various substrates 1 (Scheme 1). It was found that substituted acylhydrazones 1 are allylated smoothly with reagent 2 in the presence of tin powder. The position of the substituent on the phenyl ring has little effect on the yield of the corresponding product 3. However, an attempted reaction of substrate 1 bearing an amino or nitro group on the phenyl ring did not afford the desired product 3, and a complex mixture was obtained.
The cyclized by-products 4a were observed in these allylation reactions (Scheme 1). Related α-methylene-γ-lactam units are important scaffolds found in some biologically active synthetic molecules and natural products [22], [23], [24], [25], [26]. It was found that prolonging the reaction time resulted in the formation of compounds 4 as the major products. For example, heating of the mixture of the substrates for 2 h furnished 3a in a 57% yield, and the subsequent heating for an additional 2 h furnished product 4a in an 83% yield. Afterwards, different substituted 2-(benzylideneamino)isoindoline-1,3-diones 1 were examined for the synthesis of α-methylene-γ-lactams 4 (Scheme 1). The results show that acylhydrazones 1 with an electron-donating or electron-withdrawing group on phenyl ring undergo the cyclization reactions smoothly to give the corresponding products 4 in good to excellent yields. Again, the attempted cyclization of acylhydrazones 1 bearing an amino or nitro group on the phenyl ring did not afford the corresponding products 4.
A possible mechanism that includes the literature data [27], [28] and our previous research results [18], [19], [20], [21] is shown in Scheme 2. Thus, substrate 1 undergoes a reaction with the intermediate product 5, to generate the intermediate product 6. Hydrolysis of compound 6 gives the observed product 3. On the other hand, cyclization of 6 generates compound 7, which is the precursor to the observed product 4.
Conclusion
Efficient methods for the synthesis of homoallylic amines and α-methylene-γ-lactams are described. In these reactions, a mixture of allylic bromide and tin powder is used to replace toxic allylic stannane.
Experimental
All reactions were performed in oven-dried glassware equipped with a magnetic stirring bar. Silica gel column chromatography was carried out using silica gel 60 (230–400 mesh). Analytical thin layer chromatography (TLC) was done using silica gel GF254. Compounds were visualized by exposure to ultraviolet light, phosphomolybdic acid solution, potassium permanganate solution or iodine vapor. Proton nuclear magnetic resonance (1H NMR) (600 MHz) and carbon-13 nuclear magnetic resonance (13C NMR) (150 MHz) spectra were recorded in deuterated chloroform (CDCl3). Melting points are uncorrected. Infrared (IR) spectra were recorded using KBr pellets. Substituted 2-(benzylideneamino)isoindoline-1,3-diones 1 were prepared as previously described [29], [30].
General procedure for the synthesis of compounds 3 and 4
A mixture of 1 (0.4 mmol, 1 equiv.), 2 (1.2 mmol, 3 equiv.) and Sn powder (1.4 mmol, 3.5 equiv.) in anhydrous ethanol (4 mL) protected from atmospheric moisture was stirred and heated under reflux for a period of time indicated below. After the formation of compound 3 or 4, as monitored by TLC, the mixture was cooled to room temperature. The solvent was removed under reduced pressure, the residue was treated with a saturated solution of ammonium chloride (4 mL), and the mixture was stirred for 15 min. The mixture was extracted with ethyl acetate (3×10 mL). The combined organic phases were dried (MgSO4) and concentrated. Purification of the residue by silica gel column chromatography using petroleum ether and ethyl acetate (5:1) as an eluent furnished pure product 3 or 4.
Ethyl 4-((1,3-dioxoisoindolin2yl)amino)-2-methylene-4 phenylbutanoate (3a)
Reaction time 2 h; white solid; yield 80 mg (57%); mp 81–82°C; 1H NMR: δ 7.76 (dd, J=5.4 Hz and 3.0 Hz, 2H), 7.68 (dd, J=5.4 Hz and 3.0 Hz, 2H), 7.44 (d, J=7.2 Hz, 2H), 7.29 (t, J=7.2 Hz, 2H), 7.23 (t, J=7.2 Hz, 1H), 6.19 (s, 1H), 5.57 (s, 1H), 4.66 (t, J=7.2 Hz, 1H), 4.21 (qd, J=7.2 Hz and 2.4 Hz, 2H), 2.83 (m, 2H), 1.28 (t, J=7.2 Hz, 3H); 13C NMR: δ 166.8, 166.6, 139.6, 136.8, 134.1, 130.1, 128.3, 128.1, 128.00, 128.0, 123.3, 62.3, 60.9, 38.6, 14.1; IR: ν 3430, 3289, 2974, 2920, 1798, 1721, 1628, 1461, 1380, 1192, 1079, 706 cm−1. ESI-HRMS. Calcd for C21H20N2O4Na, [M+Na]+: m/z 387.1315. Found: m/z 387.1312.
Ethyl 4-((1,3-dioxoisoindolin-2-yl)amino)-4-(2-fluorophenyl)-2-methylenebutanoate (3b)
Reaction time 2.1 h; white solid; yield 46 mg (30%); mp 111–112°C; 1H NMR: δ 7.77 (dd, J=9.0 Hz and 3.6 Hz, 2H), 7.69 (m, 3H), 7.21 (m, 1H), 7.13 (t, J=7.2 Hz, 1H), 6.94 (m, 1H), 6.24 (s, 1H), 5.62 (s, 1H), 4.99 (t, J=6.6 Hz, 1H), 4.23 (q, J=7.2 Hz, 2H), 2.87 (m, 2H), 1.57 (s, 1H), 1.31 (t, J=7.2 Hz, 3H); 13C NMR: δ 166.6, 166.5, 135.9 (d, J=241.5 Hz), 134.1, 130.1, 129.4 (d, J=9.0 Hz), 129.3 (d, J=4.5 Hz), 128.1, 124.2 (d, J=3.0 Hz), 123.4, 120.0, 115.2 (d, J=22.5 Hz), 61.0, 56.0, 37.3, 14.1; IR: ν 3430, 3289, 2978, 2937, 1781, 1724, 1627, 1377, 1284, 1192, 1081, 882, 710 cm−1. ESI-HRMS. Calcd for C21H19FN2O4Na, [M+Na]+: m/z 405.1221. Found: m/z 405.1217.
Ethyl 4-(2-chlorophenyl)-4-((1,3-dioxoisoindolin-2-yl)amino)-2-methylenebutanoate (3c)
Reaction time 2.2 h; white solid; yield 92 mg (57%); mp 116–117°C; 1H NMR: δ 7.94 (d, J=7.8 Hz, 1H), 7.76 (dd, J=5.4 Hz and 3.0 Hz, 2H), 7.68 (dd, J=5.4 Hz and 3.0 Hz, 2H), 7.32 (t, J=7.2 Hz, 1H), 7.25 (d, J=7.8 Hz, 1H), 7.17 (t, J=7.2 Hz, 1H), 6.28 (s, 1H), 5.67 (s, 1H), 5.24 (t, J=6.6 Hz, 1H), 4.26 (q, J=6.6 Hz, 2H), 2.81 (m, 2H), 1.54 (br, 1H), 1.32 (t, J=7.2 Hz, 3H); 13C NMR: δ 166.8, 166.7, 136.6, 134.1, 130.1, 129.2, 128.9, 128.4, 127.0, 123.4, 61.07, 40.9, 37.6, 14.2; IR: ν 3429, 3289, 2978, 2928, 1789, 1720, 1628, 1464, 1377, 1192, 1074, 883, 705 cm−1. ESI-HRMS. Calcd for C21H19ClN2O4Na, [M+Na]+: m/z 421.0926. Found: m/z 421.0923.
Ethyl 4-(3-chlorophenyl)-4-((1,3-dioxoisoindolin-2-yl)amino)-2-methylenebutanoate (3d)
Reaction time 2.2 h; white solid; yield 60 mg (42%); mp 142–144°C; 1H NMR: δ 7.78 (dd, J=5.4 Hz and 3.0 Hz, 2H), 7.69 (dd, J=5.4 Hz and 3.0 Hz, 2H), 7.46 (s, 1H), 7.37 (d, J=7.2 Hz, 1H), 7.23 (m, 2H), 6.23 (s, 1H), 5.60 (s, 1H), 4.79 (s, 1H), 4.64 (t, J=6.6 Hz, 1H), 4.22 (q, J =6.6 Hz, 2H), 2.81 (dd, J=13.8 Hz and 7.2 Hz, 1H), 2.76 (dd, J=13.8 Hz and 7.2 Hz, 1H), 1.30 (t, J=6.6 Hz, 3H); 13C NMR: δ 166.7, 166.5, 141.9, 136.5, 134.2, 134.1, 130.0, 129.6, 128.3, 128.2, 128.1, 126.1, 123.4, 61.9, 61.0, 38.8, 14.1; IR: ν 3445, 3203, 2923, 2852, 1774, 1747, 1650, 1463, 1385, 1139, 1052, 914, 716 cm−1. ESI-HRMS. Calcd for C21H19ClN2O4Na, [M+Na]+: m/z 421.0926. Found: 421.0924.
Ethyl 4-(4-chlorophenyl)-4-((1,3-dioxoisoindolin-2-yl)amino)-2-methylenebutanoate (3e)
Reaction time 2 h; white solid; yield 96 mg (60%); mp 108–109°C; 1H NMR: δ 7.77 (dd, J=8.4 Hz and 4.8 Hz, 2H), 7.69 (dd, J=8.4 Hz and 4.8 Hz, 2H), 7.39 (m, 2H), 7.25 (m, 2H), 6.21 (d, J=1.8 Hz, 1H), 5.57 (d, J=1.2 Hz, 1H), 4.66 (t, J=10.2 Hz, 1H), 4.22 (qd, J=10.8 Hz and 1.8 Hz, 2H), 2.78 (m, 2H), 1.55 (br, 1H), 1.30 (t, J=10.2 Hz, 3H); 13C NMR: δ 166.7, 166.5, 138.2, 136.6, 134.2, 133.7, 130.0, 129.4, 128.5, 128.2, 123.4, 61.6, 61.0, 38.8, 14.2; IR: ν 3441, 2924, 2854, 1797, 1224, 1666, 1458, 1373, 1115, 1080, 887 cm−1. ESI-HRMS. Calcd for C21H19ClN2O4Na, [M+Na]+: m/z 421.0926. Found: m/z 421.0923.
Ethyl 4-(4-bromophenyl) ((1,3dioxoisoindolin-2-yl)amino)-2-methylenebutanoate (3f)
Reaction time 2.1 h; white solid: yield 123 mg (69%); mp 106–107°C; 1H NMR: δ 7.76 (dd, J=5.4 Hz and 3.6 Hz, 2H), 7.68 (dd, J=5.4 Hz and 3.0 Hz, 2H), 7.41 (d, J=7.8 Hz, 2H), 7.33 (d, J=5.4 Hz, 2H), 6.21 (s, 1H), 5.57 (s, 1H), 4.65 (t, J=6.6 Hz, 1H), 4.22 (qd, J=7.2 Hz and 3.0 Hz, 2H), 2.77 (m, 2H), 1.54 (br, 1H), 1.30 (t, J=7.2 Hz, 3H); 13C NMR: δ 166.7, 166.5, 138.8, 134.2, 131.5, 130.0, 129.7, 128.7, 128.2, 123.4, 61.7, 61.0, 38.8, 14.2; IR: ν 3478, 3281, 2933, 2874, 1764, 1610, 1625, 1441, 1328, 1251, 1045, 945, 776 cm−1. ESI-HRMS. Calcd for C21H19BrN2O4Na, [M+Na]+: m/z 465.0420. Found: m/z 465.0416.
Ethyl 4-((1,3-dioxoisoindolinyl)amino)2-methylen4-(4-(trifluoromethyl)phenyl) butanoate (3g)
Reaction time 2.2 h; white solid; yield 92 mg (53%); mp 103–104°C; 1H NMR: δ 7.77 (dd, J=5.4 Hz and 3.0 Hz, 2H), 7.69 (dd, J=5.4 Hz and 3.0 Hz, 2H), 7.61 (d, J=7.8 Hz, 2H), 7.55 (d, J=7.8 Hz, 2H), 6.24 (s, 1H), 5.60 (s, 1H), 4.76 (t, J=6.6 Hz, 1H), 4.23 (m, 2H), 2.79 (m, 2H), 1.31 (t, J=7.2 Hz, 3H), 1.25 (s, 1H); 13C NMR: δ 166.7, 166.5, 144.0, 136.5, 134.3, 129.9, 128.4, 128.3, 125.3 (q, J=4.5 Hz), 123.4, 61.9, 61.1, 39.1, 14.2; IR: ν 3446, 3281, 2921, 2830, 1805, 1683, 1621, 1465, 1382, 1123, 1067, 879, 709 cm−1. ESI-HRMS. Calcd for C22H19F3N2O4Na, [M+Na]+: m/z 455.1189. Found: m/z 455.1187.
Ethyl 4-[(1,3-dioxoisoindolin-2-yl)amino]-2-methylene-4-(o-tolyl)butanoate (3h)
Reaction time 2.2 h; colorless crystals; yield 61 mg (40%); mp 86–87°C; 1H NMR: δ 7.78 (m, 3H), 7.68 (m, 2H), 7.23 (t, J=7.8 Hz, 1H), 7.13 (t, J=7.8 Hz, 1H), 7.07 (d, J=7.2 Hz, 1H), 6.17 (s, 1H), 5.57 (s, 1H), 5.03 (t, J=7.2 Hz, 1H), 4.71 (s, 1H), 4.19 (q, J=7.2 Hz, 2H), 2.78 (d, J=6.6 Hz, 2H), 2.32 (s, 3H), 1.26 (t, J=7.2 Hz, 3H); 13C NMR: δ 166.9, 166.6, 137.8, 136.8, 136.5, 134.1, 130.2, 130.1, 128.1, 127.5, 126.2, 123.3, 110.0, 60.9, 57.4, 38.5, 19.2, 14.1; IR: ν 3435, 3285, 2982, 2932, 1784, 1729, 1629, 1464, 1383, 1192, 1026, 887, 711 cm−1. ESI-HRMS. Calcd for C22H22N2O4Na, [M+Na]+: m/z 401.1472. Found: m/z 401.1471.
Ethyl 4-((1,3-dioxoisoindolin-2-yl)amino)-2-methylene-4-(m-tolyl)butanoate (3i)
Reaction time 2.3 h; colorless crystals; yield 61 mg (40%); mp 77–78°C; 1H NMR: δ 7.77 (dd, J=8.4 Hz and 4.8 Hz, 2H), 7.68 (dd, J=8.4 Hz and 5.4 Hz, 2H), 7.26 (d, J=4.8 Hz, 1H), 7.22 (d, J=5.4 Hz, 1H), 7.17 (dd, J=13.2 Hz and 7.8 Hz, 1H), 7.04 (m, 1H), 6.18 (d, J=4.8 Hz, 1H), 5.56 (d, J=4.8 Hz, 1H), 4.61 (dd, J=12.6 Hz and 6.6 Hz, 1H), 4.18 (m, 2H), 2.80 (m, 2H), 2.31 (s, 3H), 1.27 (t, J=7.2 Hz, 3H); 13C NMR: δ 166.8, 166.7, 139.5, 137.9, 136.9, 134.1, 130.1, 128.8, 128.6, 128.2, 127.9, 125.0, 123.3, 62.2, 60.9, 38.6, 21.4, 14.1; IR: ν 3468, 3289, 2974, 2928, 1781, 1720, 1624, 1464, 1377, 1192, 1076, 879, 705 cm−1. ESI-HRMS. Calcd for C22H22N2O4Na, [M+Na]+: m/z 401.1472. Found: m/z 401.1470.
Ethyl 4-((1,3-dioxoisoindolin-2-yl)amino)-2-methylene-4-(p-tolyl)butanoate (3j)
Reaction time 2.3 h; white solid; yield 152 mg (53%); mp 84–85°C; 1H NMR: δ 7.79–7.73 (m, 2H), 7.68 (m, 2H), 7.32 (d, J=7.8 Hz, 2H), 7.09 (d, J=7.8 Hz, 2H), 6.18 (s, 1H), 5.56 (s, 1H), 4.77 (br, 1H), 4.62 (t, J=7.2 Hz, 1H), 4.20 (q, J=7.2 Hz, 2H), 2.81 (dd, J=14.4 Hz and 7.2 Hz, 1H), 2.78 (dd, J=13.8 Hz and 6.6 Hz, 1H), 2.28 (s, 3H), 1.27 (t, J=7.2 Hz, 3H); 13C NMR: δ 166.7, 166.6, 137.6, 136.9, 136.5, 134.0, 130.0, 129.0, 127.8, 123.3, 62.0, 60.8, 38.5, 21.1, 14.1; IR: ν 3449, 3291, 2980, 2929, 1782, 1727, 1628, 1479, 1381, 1194, 1080, 885, 710 cm−1. ESI-HRMS. Calcd for C22H22N2O4, [M+H]+: m/z 379.1652, Found: m/z 379.1648.
2-(3-Methylene-2-oxo-5-phenylpyrrolidin-1-yl)isoindoline-1,3-dione (4a)
Reaction time 4 h; white solid; yield 106 mg (83%); mp 168–169°C; 1H NMR: δ 7.83 (dd, J=2.4 Hz and 1.8 Hz, 1H), 7.77 (dd, J=4.8 Hz and 2.4 Hz, 1H), 7.72 (m, 2H), 7.47 (d, J=7.2 Hz, 2H), 7.33 (t, J=7.2 Hz, 2H), 7.29 (t, J=7.2 Hz, 1H), 6.28 (s, 1H), 5.58 (s, 1H), 5.17 (t, J=7.2 Hz, 1H), 3.40 (dd, J=17.4 Hz and 8.4 Hz, 1H), 2.92 (m, 1H); 13C NMR: δ 166.0, 165.1, 163.7, 138.2, 135.1, 134.7, 134.5, 130.1, 129.8, 128.8, 128.8, 127.4, 124.1, 123.7, 119.6, 61.0, 35.0. IR: ν 3078, 3038, 2897, 1788, 1743, 1673, 1462, 1342, 1277, 1224, 1078 cm−1. ESI-HRMS. Calcd for C19H15N2O3, [M+H]+: m/z 319.1077. Found: m/z 319.1075.
2-(5-(2-Fluorophenyl)-3-methylene-2-oxopyrrolidin-1-yl)isoindoline-1,3-dione (4b)
Reaction time 4 h; white solid; yield 117 mg (87%); mp 170–171°C; 1H NMR: δ 7.86 (m, 1H), 7.80 (m, 1H), 7.74 (m, 2H), 7.69 (td, J=7.8 Hz and 1.8 Hz, 1H), 7.27 (m, 1H), 7.17 (td, J=7.8 Hz and 0.6 Hz, 1H), 7.01 (m, 1H), 6.30 (t, J=2.4 Hz, 1H), 5.60 (t, J=2.4 Hz, 1H), 5.54 (dd, J=8.4 Hz and 6.0 Hz, 1H), 3.47 (dd, J=17.4 Hz and 8.4 Hz, 1H), 2.93 (m, 1H); 13C NMR: δ 166.1, 165.0, 163.9, 161.0 (d, J=246.0 Hz), 134.7, 134.6, 134.6, 130.0 (d, J=7.5 Hz), 130.1, 129.8, 128.5 (d, J=3.0 Hz), 125.6 (d, J=12.0 Hz), 124.7 (d, J=4.5 Hz), 124.1, 123.9, 120.0, 115.5 (d, J=6.0 Hz), 54.1, 33.3; IR: ν 3099, 3019, 2928, 1791, 1742, 1656, 1493, 1347, 1267, 1225, 1105 cm−1. ESI-HRMS. Calcd for C19H13FN2O3Na, [M+Na]+: m/z 359.0802. Found: m/z 359.0804.
2-(5-(3-Chlorophenyl)-3-methylene-2-oxopyrrolidin-1-yl)isoindoline-1,3-dione (4c)
Reaction time 7 h; white solid; yield 71 mg (50%); mp 104–105°C; 1H NMR: δ 7.85 (m, 1H), 7.82 (dd, J=4.8 Hz and 1.8 Hz, 1H), 7.74 (m, 2H), 7.45 (s, 1H), 7.41 (d, J=7.2 Hz, 1H), 7.29 (m, 2H), 6.29 (s, 1H), 5.60 (s, 1H), 5.12 (t, J=7.8 Hz, 1H), 3.41 (dd, J=17.4 Hz and 7.8 Hz, 1H), 2.87 (m, 1H); 13C NMR: δ 165.9, 165.1, 163.7, 140.5, 134.8, 134.6, 134.5, 130.2, 130.1, 129.7, 129.0, 127.7, 125.4, 124.2, 123.8, 120.1, 119.8, 60.5, 34.9; IR: ν 3055, 2937, 2686, 1791, 1740, 1666, 1413, 1350, 1272, 1221, 1076 cm−1. ESI-HRMS. Calcd for C19H13ClN2O3Na, [M+Na]+: m/z 375.0507. Found: m/z 375.0510.
2-(5-(4-Chlorophenyl)-3-methylene-2-oxopyrrolidin-1-yl)isoindoline-1,3-dione (4d)
Reaction time 4 h; white solid; yield 129 mg (91%); mp 191–192°C; 1H NMR: δ 7.84 (dd, J=6.6 Hz and 3.0 Hz, 1H), 7.80 (dd, J=5.4 Hz and 2.4 Hz, 1H), 7.74 (dd, J=5.4 Hz and 3.6 Hz, 2H), 7.41 (d, J=8.4 Hz, 2H), 7.30 (d, J=8.4 Hz, 2H), 6.29 (s, 1H), 5.59 (s, 1H), 5.14 (t, J=7.2 Hz, 1H), 3.40 (dd, J=16.8 Hz and 7.8 Hz, 1H), 2.87 (m, 1H); 13C NMR: δ 165.9, 165.1, 163.7, 136.8, 134.8, 134.7, 134.7, 134.6, 130.1, 129.7, 129.0, 128.8, 124.2, 123.8, 120.0, 60.3, 35.0; IR: ν 3092, 2964, 2932, 1792, 1742, 1656, 1493, 1345, 1260, 1224, 1091 cm1. ESI-HRMS. Calcd for C19H13ClN2O3Na, [M+ Na]+: m/z 375.0507. Found: m/z 375.0503.
2-(3-Methylene-2-oxo-5-(o-tolyl)pyrrolidin-1-yl)isoindoline-1,3-dione (4e)
Reaction time 8 h; white solid; yield 55 mg (41%); mp 125–126°C; 1H NMR: δ 7.82 (dd, J=6.0 Hz and 3.0 Hz, 1H), 7.79 (dd, J=5.4 Hz and 2.4 Hz, 1H), 7.72 (dd, J=5.4 Hz and 3.0 Hz, 2H), 7.22 (t, J=8.4 Hz, 1H), 7.09 (s, 1H), 7.00 (d, J=7.8 Hz, 1H), 6.82 (dd, J=8.4 Hz and 2.4 Hz, 1H), 6.27 (s, 1H), 5.58 (s, 1H), 5.17 (t, J=7.2 Hz, 1H), 3.81 (s, 3H), 3.39 (dd, J=16.8 Hz and 7.8 Hz, 1H), 2.88 (m, 1H); 13C NMR: δ 166.1, 165.1, 163.7, 159.9, 139.9, 135.0, 134.7, 134.5, 130.2, 129.7, 124.1, 123.7, 119.7, 119.6, 115.0, 111.7, 60.9, 55.3, 35.1; IR: ν 3060, 2931, 2641, 1795, 1739, 1660, 1403, 1361, 1282, 1220, 1081 cm−1. ESI-HRMS. Calcd for C20H16N2O3Na, [M+Na]+: m/z 355.1053. Found: m/z 355.1058.
2-(3-Methylene-2-oxo-5-(m-tolyl)pyrrolidin-1-yl)isoindoline-1,3-dione (4f)
Reaction time 8 h; white solid; yield 85 mg (64%); mp 152–153°C; 1H NMR: δ 7.83 (m, 1H), 7.79 (dd, J=4.8 Hz and 1.2 Hz, 1H), 7.72 (m, 2H), 7.26 (d, J=4.2 Hz, 2H), 7.16 (m, 1H), 7.10 (d, J=7.2 Hz, 1H), 6.27 (s, 1H), 5.57 (s, 1H), 5.14 (t, J=7.2 Hz, 1H), 3.38 (dd, J=17.4 Hz and 7.8 Hz, 1H), 2.89 (m, 1H), 2.32 (s, 3H); 13C NMR: δ 166.1, 165.2, 163.7, 138.5, 138.2, 135.2, 134.6, 134.4, 130.2, 129.8, 129.5, 128.7, 128.1, 124.4, 124.1, 123.7, 119.5, 60.9, 35.1, 21.3; IR: ν 3040, 2925, 2691, 1878, 1733, 1605, 1418, 1349, 1279, 1221, 1080 cm−1. ESI-HRMS. Calcd for C20H16N2O3Na, [M+Na]+: m/z 355.1053. Found: 355.1049.
2-(3-Methylene-2-oxo-5-(p-tolyl)pyrrolidin-1-yl)isoindoline-1,3-dione (4g)
Reaction time 8 h; white solid; yield 54 mg (40%); mp 183–184°C; 1 H NMR: δ 7.83 (dd, J=7.2 Hz and 3.0 Hz, 1H), 7.78 (dd, J=8.4 Hz and 4.8 Hz, 1H), 7.72 (m, 2H), 7.34 (d, J=7.8 Hz, 2H), 7.13 (d, J=7.8 Hz, 2H), 6.27 (s, 1H), 5.57 (s, 1H), 5.13 (t, J=6.6 Hz, 1H), 3.37 (dd, J=16.8 Hz and 7.8 Hz, 1H), 2.90 (m, 1H), 2.30 (s, 3H); 13C NMR: δ 166.0, 165.1, 163.7, 138.7, 135.3, 135.1, 134.6, 134.4, 130.2, 129.8, 129.4, 127.4, 124.1, 123.7, 119.5, 60.8, 35.1, 21.1; IR: ν 3038, 3006, 2922, 1802, 1743, 1658, 1423, 1350, 1279, 1222, 1078 cm−1. ESI-HRMS. Calcd for C20H17N2O3, [M+H]+: m/z 333.1239. Found: m/z 333.1230.
2-(5-(4-Methoxyphenyl)-2-methylene-3-oxopyrrolidin-1-yl)isoindoline-1,3-dione (4h)
Reaction time 10 h; white solid; yield 93 mg (66%); mp 146–147°C; 1H NMR: δ 7.83 (dd, J=7.2 Hz and 2.4 Hz, 1H), 7.78 (dd, J=6.0 Hz and 1.8 Hz, 1H), 7.72 (m, 2H), 7.37 (d, J=8.4 Hz, 2H), 6.84 (d, J=9.0 Hz, 2H), 6.27 (s, 1H), 5.57 (s, 1H), 5.12 (t, J=7.2 Hz, 1H), 3.76 (s, 3H), 3.36 (dd, J=16.8 Hz and 7.8 Hz, 1H), 2.90 (m, 1H); 13C NMR: δ 165.9, 165.1, 163.7, 159.9, 135.3, 134.6, 134.4, 130.1, 129.9, 129.8, 128.8, 124.1, 123.7, 119.4, 114.1, 60.5, 55.2, 35.1; IR: ν 3100, 2965, 2931, 1796, 1737, 1610, 1515, 1338, 1252, 1222, 1076 cm−1. ESI-HRMS. Calcd for C20H16N2O4Na, [M+Na]+: m/z 371.1002. Found: m/z 371.0999.
Acknowledgment
This study was supported by the National Natural Science Foundation of China (Funder Id: 10.13039/501100001809, Grants 21462037 and Funder Id: 10.13039/501100001809, 21662030), the Key Laboratory Polymer Materials of Gansu Province (Northwest Normal University) and the Key Laboratory of Eco-Environment-Related Polymer Materials (Ministry of Education, China).
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Articles in the same Issue
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- Preliminary Communications
- Microwave-assisted synthesis of γ-thiolactams from ethyl isocyanoacetate
- Microwave-assisted synthesis of isoindolinones via Pd-mediated tandem coupling reactions
- Research Articles
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