u/ConsiderationTop4247

Hello! I’m looking for some advice on a reaction that’s been giving me a lot of trouble. I’m attempting a Friedel–Crafts acylation of an indole with a substituted naphthoyl chloride. The naphthoic acid starting material has a nitro group on the opposite ring relative to the acid chloride. I have tried this reaction 15 times under a range of conditions and I haven’t been able to push the yield above ~15%.

Current procedure:

1. Convert the naphthoic acid to the acid chloride using oxalyl chloride (monitor to full conversion), then remove excess reagent completely by rotovap.
2. Resuspend the crude acid chloride in DCM.
3. Add the indole substrate dropwise.
4. Add AlCl3 (I've tried zero eq up to 5)
5. Run the reaction at various temperatures (–70 °C up to 40 °C) and for different reaction times (an hour to overnight).

Workup:

1. Quench by adding the reaction mixture dropwise into ice water (also tried saturated NaHCO₃ solution)
2. Back extract with DCM

I have tested to make sure the AlCl3 is active and it seems to work great. I always form a little product but I have never had yield above 15%. I am thinking about changing solvent systems but I want to see if there is any other ideas. ANY ideas will be greatly appreciated.