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Helvetica Chimica Acta – Vol. 94 (2011)
work-up and the high yields of the products make this procedure a useful addition to
the library of modern synthetic methods. Furthermore, this solid-state reaction (i.e.,
solvent-free reaction) has many advantages: reduced pollution, low costs, and
simplicity in process and handling. These factors are especially important for industrial
synthesis.
Experimental Part
General. Freshly distilled solvents were used, and anh. solvents were dried according to Perrin and
Armarego [14]. IR Spectra (KBr): Jasco 6300 FT-IR spectrometer. 1H- and 13C-NMR spectra (CDCl3):
BRUKER DRX-250 AVANCE spectrometer at 250.0 and 62.5 MHz, resp. Elemental analyses: Heraeus
CHN-O-Rapid analyzer. The samples were characterized with a scanning electron microscope (SEM)
(Philips XL 30) with gold coating.
Preparation of Silica Nanoparticles from Organic Laboratory Waste of Silica Gel HF254. Silica gel
HF254 residues (5 g) were heated at 5008 for 1 h. The sample was heated at reflux in 2m HCl for 24 h. The
mixture was filtered, and the residue was washed with dist. H2O for several times, until the filtrate was
free from acid. The acid-leached silica was dried in an oven at 1008 for 1 h and then heated in a furnace at
7008 for 2 h. The morphology and grain size of the silica NPs was investigated by SEM (Fig. 1).
General Procedure for the Synthesis of Isoindolinones 4. Silica nanoparticles (0.2 g) were added to a
mixture of 6-formyl-2,3-dimethoxybenzoic acid (1; 1 mmol), secondary amine (dibenzyl- or benzyl(i-
sopropyl)amine) (2; 1 mmol), and isocyanide 3 (1 mmol) at r.t., followed by 7 h of stirring. After
completion of the reaction, flash column chromatography (petroleum ether/AcOEt 5 :2) of the residue
gave 4.
2-Benzyl-N-(tert-butyl)-2,3-dihydro-4,5-dimethoxy-3-oxo-1H-isoindole-1-carboxamide (4a). Color-
1
less oil. IR: 3327, 2971, 1698, 1675, 1544, 1494, 1270. H-NMR: 1.13 (s, Me3C); 3.89, 4.12 (2s, 2 MeO);
2
4.46, 4.95 (AM, JAM ¼ 14.8, PhCH2); 4.63 (s, CH); 5.35 (s, NH); 7.08, 7.23 (2d, 3J ¼ 8.4, 2 CH of
isoindolone); 7.25 – 7.34 (m, 5 arom. H). 13C-NMR: 28.3 (Me3C); 46.5 (PhCH2); 51.4 (Me3C); 56.6, 62.5
(2 MeO); 64.7 (CH); 117.1, 117.7 (2 CH of isoindolone); 122.6, 134.5, 148.4, 153.1 (4 C of isoindolone),
128.0, 128.7, 129.0 (5 CH of Ph), 136.8 (C of Ph), 166.9 (2 C¼O of amides). Anal. calc. for C22H26N2O4: C
69.09, H 6.85, N 7.32; found: C 69.01, H 6.81, N 7.37.
2-Benzyl-N-cyclohexyl-2,3-dihydro-4,5-dimethoxy-3-oxo-1H-isoindole-1-carboxamide (4b). Color-
1
less oil. IR: 3292, 3084, 2976, 1695, 1677, 1490, 1268. H-NMR: 0.79 – 1.79 (2m, 5 CH2 of cyclohexyl);
2
3.57 – 3.69 (m, CH of cyclohexyl); 3.86, 4.06 (2s, 2 MeO); 4.25, 5.14 (AM, JAM ¼ 14.8, PhCH2); 4.70 (s,
3
3
CH); 5.74 (d, J ¼ 8.0, NH); 7.05, 7.21 (2d, J ¼ 8.2, 2 CH of isoindolone); 7.23 – 7.45 (m, 5 arom. H).
13C-NMR: 24.8, 24.8 (2 CH2(b) of cyclohexyl); 25.3 (CH2(g) of cyclohexyl); 32.5, 32.7 (2 CH2(a) of
cyclohexyl); 46.0 (PhCH2); 48.6 (CH of cyclohexyl); 56.6, 62.4 (2 MeO); 63.4 (CH); 117.0, 117.8 (2 CH of
isoindolone); 122.6, 134.2, 147.1, 153.1 (4 C of isoindolone); 128.0, 128.6, 129.0 (5 CH of Ph); 136.4 (C of
Ph); 166.9, 168.0 (2 C¼O of amides). Anal. calc. for C24H28N2O4: C 70.57, H 6.91, N 6.86; found: C 70.49,
H 6.95, N 6.89.
2-Benzyl-2,3-dihydro-4,5-dimethoxy-3-oxo-N-(1,1,3,3-tetramethylbutyl)-1H-isoindole-1-carboxamide
(4c). Colorless oil. IR: 3369, 3030, 2946, 1699, 1674, 1461, 1253, 1223. 1H-NMR: 0.77 (s, Me3C); 1.16, 1.27
(2s, Me2CNH); 1.59 (s, CH2CMe3); 3.89, 4.10 (2s, 2 MeO); 4.39, 5.04 (AM, 2JAM ¼ 14.5, PhCH2); 4.64 (s,
3
CH); 5.44 (s, NH); 7.08, 7.25 (2d, J ¼ 8.2, 2 CH of isoindolone); 7.26 – 7.42 (m, 5 arom. H). 13C-NMR:
28.0, 28.7 (Me2CCH2); 31.2 (Me3C); 31.3 (Me3C); 46.4 (PhCH2); 52.0 (Me3CCH2); 55.5 (Me2CCH2);
56.7, 62.4 (2 MeO); 64.7 (CH); 117.1, 118.0 (2 CH of isoindolone); 122.3, 134.3, 148.5, 152.9 (4 C of
isoindolone); 128.0, 128.7, 129.0 (5 CH of Ph); 136.6 (C of Ph); 168.3, 173.4 (2 C¼O of amides). Anal.
calc. for C26H34N2O4: C 71.21, H 7.81, N 6.39; found: C 71.27, H 7.77, N 6.33.
N-(tert-Butyl)-2,3-dihydro-4,5-dimethoxy-2-(1-methylethyl)-3-oxo-1H-isoindole-1-carboxamide
(4d). Colorless oil. IR: 3382, 2973, 2933, 1692, 1652, 1540, 1457, 1232. 1H-NMR: 1.22 (s, Me3C); 1.28, 1.34
(m, 2 Me2CH); 3.86, 4.05 (2s, 2 MeO); 4.37 (m, Me2CH); 4.77 (s, CH); 5.27 (s, NH); 7.05, 7.23 (2d, 3J ¼
8.0, 2 CH of isoindolone). 13C-NMR: 20.4, 20.6 (Me2CH); 28.3 (Me3C); 45.9 (Me2CH); 51.4 (Me3C);
56.6, 62.3 (2 MeO); 63.0 (CH); 117.0, 117.4 (2 CH of isoindolone); 123.3, 135.0, 146.8, 153.0 (4 C of