2-(2-Propyn-1-yl)-1H-isoindole-1,3(2H)-dione

Beige to orange powder

8.4 mmol of bromopropyne and 8.4 mmol of phthalimide potassium salt were added to 10 mL of N, N-dimethylformamide. Further, 0.2 g of manganese dioxide solid was added. The reaction at a temperature of 28°C for 2h; After adding 100 mL of ethyl acetate, the organic layer was collected by washing with water. The organic layer was washed with a saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate and separated by a column. The eluent was selected by petroleum ether-ethyl acetate 5: 1 (v: v) to seperate and purify to obtain pure B.Preparation 2:; 2-Prop-2-ynyl-isoindole-1, 3-dione; A mixture of potassium phthalimide (10 grams, 54 mmol) and propargyl bromide (7.65 grams, 65 mmol) was heated in dimethyl formamide (DMF) (50 mL) at 80 °C for 8 hours. The reaction mixture was then poured into ice cold water. White solid obtained was filtered on a Buchner funnel and washed with water and dried (yield is 8.95 grams, 90percent). Melting Point : 138°C. 'H NMR (CDC13) : 6 7.95-7. 85 (m, 2H), 7.75-7. 68 (m, 2H), 4.46 (d, J = 2.5 Hz, 2H), 2.23 (t, J= 2. 5 Hz, 1H). IR (KBr, cm-1): 3294, 2925, 1771, 1725, 1397. CI-MS (m/z) : 186 (M++1), 148.Step 2: Preparation of acetylene 4: To an ice cold mixture of propargyl bromide (50 g of an 80percent solution in toluene, 336 mmol) in DMF (200 mL) under argon was added potassium phthalimide (64.7 g, 350 mmol) via a funnel. The runnel was rinsed with additional DMF (50 mL). The reaction mixture was allowed to warm to room temperature and then stirred overnight. After solids were removed from the mixture by filtration through Celite, the filtrate was concentrated under reduced pressure. The residue was partitioned between EtOAc and water and the combined organics were washed with water and saturated aqueous NaHCO32.3 g (271 mmol) 3-bromopropine are dissolved in 150 ml DMF and 50.3 g (271 mmol) phthalimide potassium salt are added under ice cooling. The suspension is warmed at 70° C. for eight hours. The mixture is concentrated under a vacuum and the residue is distributed between acetic acid ethyl ester and water. The organic phase is dried over sodium sulfate and the solvent is removed under vacuum. The residue is crystallized from acetic acid ethyl ester: Yield 36.4 g (72percent) colorless crystals.Propargyl bromide (1.3 mL, 17.4 mmol) is dissolved in DMF (30 mL) and potassium phtalimide (3.4 g; 18.4 mmol) is added. The mixture is refluxed for 5 h. After cooling at room temperature the mixture is diluted with diethyl ether, washed with water (3x50 mL), dried over NaPropargyl bromide (1 mL, 11.6 mmol) was added to a solution of phthalimide (1 g, 6.8 mmol) and K2CO3 (1.4 g, 10.2 mmol) in CH3CN (25 mL). The reaction mixture was heated at reflux for 48 h and the hot mixture was filtered and cooled at room temperature, the solid was washed with CH3CN (3 × 5 mL), the organic phases were combined and filtered through celite, the solvent was removed in vacuo and the product was purified by crystallisation to afford a white solid (1.12 g, 89percent); m.p. 142–143 °C (lit. 141–143 °C); 20 FTIR (ATR, cm–1): 2145, 1768, 1712, 1468, 1395; 1H NMR (300 MHz, CDCl3) δ 8.15 – 7.75 (m, 4H), 4.60 (dd, J = 2.5, 0.4 Hz, 2H), 2.36 (td, J = 2.5, 0.4 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ 166.9 (2 × C), 134.2 (2 × CH), 132.0 (2 × C), 123.5 (2 × CH), 77.0 (C), 71.4 (CH), 26.9 (CH2); MS [EI+] m/z (percent): 185 [M]+ (55), 157 [M – CO]+ (40), 129 [C8H4NO] (40), 102 [C7H2O] (60), 76 [C6H4] (100).To a 100 mL round-bottom flask containing vaniline (0.800 g, 5.26 mmol) dissolved in acetone (40 mL), it was added potassium carbonate (1.45 g, 10.5 mmol) and propargyl bromide (957 μL, 10.5 mmol). The resulting mixture was refluxed for 24 h. After cooling to room temperature, it was added to the mixture cold water and CH2Cl2. The layers were separated and the aqueous phase was extracted with ethyl acetate (three times with portions of 30 mL). The organic extracts were combined and the resulting organic layer was washed with brine (25 mL), dried with anhydrous sodium sulphate, filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluted with hexane-ethyl acetate (2:1 v/v). Compound 6 was obtained in 72percent yield (0.716 g, 3.77 mmol). The following data support the structure of compound 6.White solid. Mp 81.3-82.2 oC. TLC: Rf = 0.59 (hexane-ethyl acetate 2:1 v/v). 1H NMR (300 MHz, CDCl3) : 2.56 (t, 1H, J = 2.4 Hz), 3.92 (s, 3H, OCH3), 4.85 (d, 2H, J = 2.4 Hz), 4.85 (d, 1H, J = 8.1 Hz), 7.42-7.47 (m, 2H), 9.85 (s, 1H, CHO). 13C NMR (75 MHz, CDCl3) : 56.0, 56.5, 76.6, 77.4, 109.3, 112.4, 126.2, 130.8, 149.9, 152.0, 190.9 (CHO).General procedure: To a mixture of propargyl bromide (8.47 mmol) and secondary amine (16.94 mmol) in DMF, KPrepared by the method of Clayton (69percent):Phthalic anhydride (200 mg, 1 .35 mmol) was suspended in toluene (5 mL) and propargylamine (175 iL, 2.73 mmol) was added. The reaction mixture was heated underreflux (115°C) using Dean-stark apparatus. After 2 h the reaction was cooled to rt and concentrated in vacuo. The residue was dissolved in DCM (50 mL) and the organic phase washed with saturated aqueous sodium hydrogen carbonate (diluted 1 in 5, 50 mL). The aqueous layers were further extracted with DCM (2 x 20 mL) before passing through a phase separator cartridge (Biotage) and concentrated in vacuo. The resultingresidue was purified by flash column chromatography (Biotage Isolera Four, 25 g KP-Sil column, 10percent EtOAc I isohexane to 20percent EtOAc I isohexane)to afford the title compound as a white solid (150 mg, 0.81 mmol, 60percent).

Molecular Weight:185.18
XLogP3:1.4
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:185.047678466
Monoisotopic Mass:185.047678466
Topological Polar Surface Area:37.4
Heavy Atom Count:14
Complexity:301
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes