I am making a precursor for cyclization towards 5 ring heterocycles. Because of the possibility to do several things with a 1,4 diketone, I want to
attach a group to benzene (or benzene derivatives), so that the resulting compound is an 1,4 dicarbonyl chain attached to benzene ring. Or rather, the
carbon alpha to the benzene has ketone, while the delta atom is a terminal aldehyde. This must absolutely be the case since a true diketone would
produce a methyl group in a ring position that I want functionalized later on.
There are several possibilities, the one that seems most straightforward on paper is a friedel crafts of a carboxylchloride to benzene, with the
carboxylchloride consisting of four carbon atoms and at the terminus, including an aldehyde or a group that can easily be made into one.
Would the conditions of a friedel crafts reaction allow an aldehyde? If so, would a nitrile survive?
[Edited on 20-6-2006 by Cloner]DDTea - 20-6-2006 at 13:53
Friedel-Craft's acylations are not affected by Aldehyde's or nitriles or other functional groups (unless they're particularly basic..?) in the
reactant as far as I know...but if you're really concerned about the aldehyde, you might consider reducing the aldehyde of your 1,4-dicarbonyl to an
alcohol, reacting that via friedel-crafts, and then oxidizing it back to your aldehyde.Nicodem - 23-6-2006 at 06:37
Quote:
Would the conditions of a friedel crafts reaction allow an aldehyde? If so, would a nitrile survive?
Aliphatic aldehyde + acid (either H+ or other Lewis acid) results in disgusting tar. Nitriles often result in amides if the reaction is quenched with
water or whatever else if quenched with whatever else. Very nucleophilic benzene derivatives (like phenols) can get acylated by nitriles in the
presence of strong acids.
[Edited on 23-6-2006 by Nicodem]unionised - 24-6-2006 at 01:01
I seem to recall reacting succinic anhydride with toluene to get 4 (p methylphenyl) 4 oxo butyric acid.
This was part of a synthesis of methyl tetralone.
If you esterified that acid or converted it to the chloride and reduced it you could get to the aldehyde by reduction.
Any help?
This is the sort of thing http://www.orgsyn.org/orgsyn/prep.asp?prep=cv2p0081
When we did it as a student practical we used the less toxic toluene
[Edited on 24-6-2006 by unionised]Cloner - 26-6-2006 at 05:04
I have seen this reaction, but that acid group is the wrong sort of carbonyl. The follow-up reaction would be a paal knorr type heterocyclization
which isnt going to work on an acid. Are you sure that reducing this to an aldehyde can be accomplished in reasonable yield?unionised - 26-6-2006 at 10:11
I'm sure the reduction can be done.
(It's the Rosemund reduction if you go via the acid chloride.)
What I'm not sure about is selectively reducing that carbonyl but leaving the other intact.
You could probably protect the ketone, but that's starting to get messy.
Anyone else got any ideas?
