In the chemical reaction process, reaction time, type of solvent, can easily affect the result of the reaction, thereby determining the yield and properties of the reaction product. An updated downstream synthesis route of 118-29-6 as follows. 118-29-6
200 mL of sulfuric acid were cooled to 0 0C. 48 g of 2,3,3 – trimethylindolenine were added to the sulfuric acid followed by the addition of 54 g of N-hydroxymethyl-phthalimide. The reaction mixture was stirred at room temperature for 7 days. The reaction mixture then was added to 500 g of crushed ice in a 2000-mL conical flask immersed in ice-salt bath. A solution of about 225 g of sodium hydroxide in 500 mL of water was cooled to 10 0C and then added dropwise to the magnetically stirred mixture in the conical flask. A white precipitate starts to form after addition of about half of the solution of sodium hydroxide. Addition of the sodium hydroxide is continued until the pH of the reaction mixture is strongly basic (pH > 12). The white solid is then filtered, washed with water (3×100 mL) and air- dried on a Buchner funnel for about 1 hour. The solid is then transferred to a 1000- mL one -neck round bottom flask, 300 mL of acetone is added and the mixture is stirred under reflux for 30 min. The flask is then cooled to 10 0C and the white product is filtered with suction on a Buchner funnel, washed with acetone (1 x50 mL), and air dried.The yield of the pure product is 70-75% (67-7O g). NMR: (DMSO-d6, 300 MHz) delta 1.33 (s, 6H, 2xCH3), 2.31 (s, 3H, CH3), 4.91 (s, 2H, CH2), 7.32 (dd, 3JH-H =8.7 Hz, 5Jn-H – 1.2 Hz, IH), 7.48 (dd, 5JH-H = 8.7 Hz, IH), 7.51 (dd, 5JH-H = 1.2 Hz, IH, 7.9-8.1 (m, 4H).; 6.1 2-(2, 3, 3-Trimethyl-3H-indol-5-ylmethyl)-isoindole-l, 3-dione, 1Sulfuric acid (420.0 mL, 7.879 mol; Sigma-Aldrich) was placed to the 1 L one -neck, round-bottom flask equipped with magnetic stirrer. The flask was cooled in ice-water bath and 2,3,3-trimethyl-3H-Indole, (100.0 g, 0.6280 mol; Sigma-Aldrich) was added to the sulfuric acid by drops during 45 min with stirring. The reaction mixture becomes a very viscous upon addition of 2,3,3-trimethyl-3H-indole, so stirring plate with adequate power and large magnetic stir bar is required. When addition of 2,3,3-trimethyl-3H-Indole was completed the ice bath was removed and 2- (hydroxymethyl)-lH-Isoindole-l,3(2H)-dione, (112 g, 0.632 mol; Aldrich) was added to the reaction mixture at once. The flask was closed with a glass stopper and the stirring was continued for 168 hours at room temperature. In about 12 hours all solid, 2-(hydroxymethyl)-lH-Isoindole-l,3(2H)-dione dissolved and clear brown solution formed.After 168 hours the content of the flask was poured into 4-L conical flask containing 1 kg of ice. The 4-L flask was immersed in ice-salt bath, equipped with mechanical stirrer. A cooled to 10 0C solution of 550g of NaOH in 1.5 L of water was slowly added to the reaction mixture at such rate that temperature inside of flask didn’t increase higher than 20 0C. The addition takes about 1 hour. The white precipitate formed was filtered on Buchner funnel with suction and dried on air for 12 hours.The crude 2-(2,3,3-Trimethyl-3H-indol-5-ylmethyl)-isoindole-l,3-dione was placed in conical 2 L flask, 1 L of acetone was added and the mixture was magnetically stirred with heating until acetone start to boil. The heating was reduced to maintain a very gentle boiling and the content of the flask was stirred for additional 10 min. Flask was cooled using ice-water bath and the separated crystals were filtered, washed with acetone and dried.
According to the analysis of related databases, 118-29-6, the application of this compound in the production field has become more and more popular.
Reference:
Patent; THE UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL; WO2008/157762; (2008); A2;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem