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       Synthesis of propenylbenzenes from propiophenones - by Psychokitty
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Anyway, I may have some good news for you guys. A friend of mine recently sent 
me a detailed lab experiment that was once a part of the Organic Chemistry 
program at some college in the US. In it is the synthesis of 4-methoxypropenyl- 
benzene from 4-methoxypropiophenone. My friend had apparantly e-mailed the 
chemistry teacher from that college who wrote up the experiment and he gave him 
a little more information than what was available in lab note book. Here is that 
information:

Experimental:

In a small Erlenmeyer flask, weigh out 2.16 g. of anisole and dissolve it in 5 
ml of methylene chloride. Cover and set aside. Quickly weigh out and transfer 
3.3 g of FeCl3 into a 50 mL round bottom flask with a magnetic stirrer and 
cover. With stirring, first add 25 mL of methylene chloride, then slowly add 2.0 
mL of propionyl chloride (careful, smelly and toxic. Use the glass pipette in 
the hood). Put a Claisen head adapter on the round bottom flask, then place a 
separatory flask and a bent vacuum adapter on the Claisen head (see the drawing 
below). Transfer the anisole solution to a separatory funnel (the small one), 
which will serve as an addition funnel. Put a stopper in the bent vacuum 
adapter, run a hose to an inverted liquid funnel which is just above a beaker 
full of water (this will scub the HCl vapors). With stirring, add the anisole 
solution over a 2-4 min period (about 1 drop per 3-5 sec). The reaction is 
exothermic and evolves HCl, so you must be very careful not to add the solution 
too fast. After the addition, let it stir for another 20 min. Add 5 mL of water 
dropwise (use the sep funnel again) to quench the reaction and stir for 5 min. 
Transfer the contents of the flask with water (50 mL) and methylene chloride (10 
mL). Shake vigorously, then separate the organic layer from the aqueous layer. 
Wash the aqueous layer with another 10 mL of methylene chloride, combine the 
organic layers, and wash the organic layer with 50 mL of 0.25 M NaOH. Dry the 
organic layer with Na2SO4, add 0.25 g of activated charcoal (add more if it does 
not seem sufficient for the removal of most of the colored impurities), and 
swirl for several minutes. Filter the mixture through a bed of Celite (vacuum 
filtration). Use a little methylene chloride to wash the filter cake. Put the 
organic solution in a tarred beaker in the back of the hood until next week. 
Obtain a weight, IR and NMR.

Reduction of the Ketone

Experimental:

Dissolve the ketone (2 g) in ethanol (10 mL) in a 50 mL round bottom flask with 
a magnetic stirrer. Add NaBH4 (0.4 g) over a period of 15 min. The reaction may 
be mildly exothermic, so do not add the hydride reagent too fast. After stirring 
for 15 min, add 10 mL of water, heat to reflux for 5 min, and cool to room 
temperature (this destroys most of the excess sodium borohydride). Wash the 
reaction mixture into a separatory funnel with additional water (25 mL) and 
diethyl ether (50 mL). Shake, separate the organic layer and wash the aqueous 
layer again with ether (25 mL). Combine the organic layers, wash with water (25 
mL), separate, and dry the organic layer over Na2SO4. Allow the organic solution 
to evaporate in the back of the hood in a tared flask until next week. After 
weighing your product, obtain an IR and NMR.

Dehydration of the Alcohol.

Experimental:

In a 50 mL round bottom flask, add 0.5 g of alcohol, a magnetic stirrer, and 25 
mL of a 1.5 M solution of KH2SO4. Set up a distillation apparatus on top of your 
round bottom flask (your lab notebook has a schematic for distillation set-ups) 
and distill off approximately 20 mL of liquid. This procedure not only drives 
the dehydration reaction to completion but it also purifies your product by 
steam distillation. Transfer the distillate to a separatory funnel, extract the 
aqueous phase twice with ether (2 tms 15 mL), dry the ether solution over 
Na2SO4, and evaporate the ether solution in a tared beaker in the hood in a warm 
sand bath (if you can't deal with the sample this week, make sure you cover up 
the flask with aluminum foil so that the anethole does not evaporate; it is 
fairly volatile). As before, get a weight, IR and NMR.

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So what do you think? My guess is that anisole could be replaced easily with 
benzodioxole or even benzene. Of course, if you already have propiophenone, you 
could jump directly to the second step. As for the very last part of the 
reaction, I would substitute heating the P-1-Pol with dry KH2SO4 rather than use 
the aqueous KH2SO4 solution like the proceedure describes.

Also, if one cared to form the benzoyl acetate first from the propiophenone and 
then reduce to the diol, I suppose step two could be used to effect this 
reaction as well -- in lieu of the traditional and expensive catalytic reduction 
using Pt/C or whatever.

For more information on this specific reaction, refere to the following citation:
"Iron (III) Chloride as a Lewis Acid in the Friedel-Crafts Acylation Reaction" 
taken from Journal of Chemical Education -- Ahhh, SHIT! The article is right in 
front of me, but it doesn't indicate which volume it comes from. Oh, well. I 
know where to find the reference again. I'll get it to you guys soon.

BTW, according to my friend, the professor indicated that only the last part 
tended to produce low yields (by student, 30-50%; by the professor, 50-70%) and 
that the first and second steps were high-yielding. 

If anyone wants another high yielding equally simple alternative to the first 
step in the above reaction, refer to "2,5-dimethoxy-n-propyl- either 
phenethylamine or amphetamine" in PIHKAL. There he uses 1,4-dimethoxybenzene in 
Friedel-Crafts fashion using AlCl3 and propionyl chloride in methylene chloride 
to form in about an hour the desired propiophenone. This method is probably 
easily adapted to using both benzodioxole and benzene itself.

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