Org Prep Daily

October 24, 2006

1-Boc-2-(5′-indolyl)-4,5-dihydroimidazole

Filed under: procedures — milkshake @ 2:12 pm

amidines.gif

P2S5 0.55g was added to a mixture of 5-cyanoindole 10.00g (70.34mmol) in neat ethylene diamine 90mL in a pressure glass flask (H2S gas evolution), the flask was closed, mixture sonicated for 10 min and the obtained homogennous mixture was stirred at 120C for 14 hours (overnight). The amine was evaporated on highvac (30 to 0.5Torr, RT to 30C), the residue was suspended in a mixture of dichloromethane 150mL and water 50mL, the mixture was heated to reflux, stirred for 10 min, cooled, diluted with hexane 200mL, stirred for 15 min. The solids were collected by filtration, washed with hexane 200mL and then with ice-cold water (50mL), dried by suction and on highvac. Y=12.011g (92%) of a off-white solid. 1H(d6-DMSO, 400MHz): 11.274(br s, 1H), 8.009(br d, 1.2Hz, 1H), 7.645(dd, 8.6Hz, 1.6Hz, 1H), 7.389(m, 1H), 7.368(m, 1H), 6.741(br s, 1H), 6.479(br d, 3.1Hz, 1H), 3.589(s, 4H)

The indolylimidazoline from the previous step 11.910g (64.30mmol) was suspended in acetone 100mL, solid Boc anhydride 15.28g (70 mmol) was added followed by additional acetone 20mL (to wash the funnel). With vigorous stirring, water 150mL was slowly added over 10 min period, followed by 15% aq. NaOH 15mL. The stirring was continued overnight (13 hours), the formed precipitate was collected by filtration, washed thoroughly with a mixture water+acetone 3:1 (100mL), dried by suction and on highvac. Y=15.208g (83%) of a white crystalline solid

1H(d6-DMSO, 400MHz): 11.194(br s, 1H), 7.660(m, 1H), 7.368(m, 2H), 7.206(dd, 8.6Hz, 2.0Hz, 1H), 6.467(m, 1H), 3.885(m, 2H), 3.795(m, 2H), 1.149(s, 9H)

P2S5 catalyst is not essential for the nitrile reaction, for example 5-cyanooxindole 0.886g (5.602mmol) with 5.5mL of ethylenediamine at 105C in 5 h provided 0.851g (75.5%) of the corresponding imidazoline-oxindole. (After purification on silica 35g in chloroform/MeOH+aq. NH3 10:1 mixture, using a gradient from 10 to 35% of the MeOH+NH3 mix)

3 Comments »

  1. What would be nice is that you put the reference where the reaction is taken from !
    Thanks in advance !

    Comment by Max — October 25, 2006 @ 4:52 am

  2. and also for all procedure in your website !

    Comment by Max — October 25, 2006 @ 4:53 am

  3. The problem is that I often don’t have the original reference and I am too lazy to search for it in Scifinder/Beilstein. In this case, the first step was from some paper but I remember vaguely that I modified the workup so that the product would precipitate from the mix, skipping the extraction/evaporation in workup. The Boc protection was my own, I think. I did this experiment few years ago and the only thing that remains from this work now is the procedure. (I promise that I will be putting in the original references whenever I have it. )

    Comment by milkshake — October 25, 2006 @ 9:36 am


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