Here’s that reference GC_MS was looking for on Friedel-Crafts acylation using only Zn metal as a catalyst, I finally found it in my library (thanks Chimimanie
!). It looks incredibly easy; if this works on benzodioxole with yields in the same range as the other substrates listed, it could be another route to isosafrole, but it would much more interesting (and easier) to make Methylone, which is only one step away from the propiophenone. Even if it doesn't work on benzodioxole it should be a great way to acylate 1,4-dimethoxybenzene. The amounts of solvent used are a bit high, but I'm sure they could be reduced if the reaction was done on a larger scale:
ZINC PROMOTED REGIOSELECTIVE FRIEDEL-CRAFTS ACYLATION OF ELECTRON RICH ARENES
Synthetic Communications 28 (12), 2203–2206 (1998)
H.M. Meshram, Gondi Sudershan Reddy, M. Muralidhar Reddy and J.S. Yadav
Indian Institute of Chemical Technology, Hyderabad-500 007, IndiaAbstract: A simple and convenient zinc promoted selective Friedel-Crafts acylation is described. The inexpensive metal grade catalysis and minimum waste effluent are the important features of the procedure.
The general experimental is as follows: A solution of acid chloride (4 mmol in 50 mL toluene) was stirred with activated zinc (4 mmol) at RT for 15 minutes. To this was added a toluene solution of arene (4 mmol in 30 mL) and the mixture was heated to 70
oC for stipulated time (see table). The completion of the reaction was followed by TLC. The used up catalyst was removed by filtration, filtrate washed with sodium bicarbonate (10%) and organic phase dried over sodium sulfate. The evaporation of solvent gave essentially pure product in good yield. If necessary the further purification can be done by passing through a small bed of neutral alumina using hexane:ethylacetate (80:20) as eluent.
The method selectively and efficiently proceeds with active arenas. However, the efforts failed to acylate benzene, chlorobenzene and toluene in the identical condition. Further, it was observed that increasing the alky chain on benzene facilitates the reaction (entry – 9, 10, 11, 12). This finding supports the selectivity of this method for electron donating substrates. We presume that the electrophilic character of acyl chlorides is enhanced by the zinc which in turn reacts at the electron rich position of arenes. This effect may be explained by assuming that the polar groups complex efficiently to the zinc surface
9. Though the reaction proceeds 0.5 eq. of zinc, the rate of the reaction is enhanced by employing 1 eq. of zinc. It is important to note that the unused zinc is recovered at the end of the reaction, which can be reused again after activation.
Table:
Arenes Acid chlorides Time/h Yielda 1a 2a 6 90
1a 2b 5 91
1a 2c 7 85
1a 2d 8 89
1b 2a 6 90
1b 2b 6 93
1b 2c 7 85
1b 2a 6 90
1c 2b 7 83
1c 2c 7 80
1c 2d 6 93
1d 2b 7 89
1d 2c 8 92
1d 2d 7 94
[Note from Kinetic: All acyl groups go in the 4-position]
Arenes:1a. Anisole
1b. N-2,6-dichlorophenyl aniline
1c. Isobutyl benzene
1d. Thiophene
Acyl chlorides:2a. Pivaloyl chloride
2b. Palmitoyl chloride
2c. p-Chlorobenzoyl chloride
2d. [Rather large acyl chloride with no trivial name]
a: Yields are obtained after column chromatography purification.
References: [Also look quite interesting IMHO]
1. Olah, G.A. ‘Friedel-Crafts Chemistry’, Wiley Interscience, New York and London, 1973
2. Khalikar, B.M.; Borkar, S.D. Tetrahedron Lett. 1997, 38, 1641. b) Izumi, J; Mukaiyama, T. J. Chem. Soc. Chem. Commun, 1996, 183.
3. Izumi, J; Mukaiyama, T. Chem. Lett. 1996, 739 and references cited therein.
4. Clark, J.H.; Keybett , A.P.; MaCquarrie, B.J.; Barlow, S.J.; Landon, P. J. Chem. Soc. Chem. Commun. 1989, 1353.
5. Poul, V.; Sudalai, A.; Daniel, T.; Srinivasan, K.V. Tetrahedron Lett. 1994, 35, 2601. b) Chiche, B.; Finiels, A.; Gauphier, C.; Gauphier, P.; Graille, J.; Piock, D. J. Org. Chem. 1988, 51, 2128. c) Sreekumar, R.; Raghavakaimal Padmakumar. Synth. Comm. 1997, 27, 777.
6. Furstner, A.; Synthesis, 1989, 571 and references cited therein. b)Angew Chem. Int. 1997, 36(3), 186 (Copper), 35(2) 2333 (Titanium).
7. Yadav, J.S.; Srinivas, D.; Reddy, G.S.
[A busy bee, one of the authors in Post 407575
(Chimimanie: "Well chief if you ask me", Novel Discourse)]; Himabindu, K. Tetrahedron Lett. (accepted).
8. Meshram, H.M. Tetrahedron Lett. 1993, 34, 2521. b) Meshram, H.M.; Srinivas, D.; Yadav, J.S. Tetrahedron Lett. (accepted).
9. Coates, G.E.; Ridley, D. J. Chem. Soc., 1965, 1870. b) Rao, S.A.; Chao, T.; Schipor, I.; Knochel. P. Tetrahedron, 1992, 48, 2025.