Piperonal synthesis

Bushroot · Fri Aug 26, 2005 3:15 pm

I performed the whole procedure in 1 day. Results are far from ideal, but I'm working on improvement.

1. Chloromethylation of benzodioxole
Procedure based on britih patent GB 1538214.
Saturation with HCl gas did not increase yield in british experiments, so the aqueous 38% HCl can be used.

In the RB flask with rubber bibb and thermometer in it was placed:

12g of catechol methylene ether (benzodioxole)
17 ml GAA
20 ml HCl 38%
3g phosphoric acid
and 10g formalin (big excess, my mistake - 3g would be enough)

Rm was mixed for 4 hours with temp rising from -5 to 20C
Rm cooled, oil (~15 mls) separated,
acidic layer extracted with 3 х 8 ml of MeCl2
pooled extracts and oil was washed with water, 10% soda, again water.
solvent vacuum distilled
yielding 12 mls of yellowish oil

2. Piperonil chloride formilation

In 100mls flask (250ml should be used) with reflux condenser, with mag stirring
was placed:

The crude product from above reaction
20g of HMTA (hexamethylenetetramine)
30 mls of GAA
30 mls of water

Rm was refluxed at 130С for 2 hours,
the colour of rm changed from yellow to wine-red
after 2 hours 10 mls of HCl was added
and refluxing continued for 15 minutes more
rm was then cooled, diluted with 100 mls of cold water
Dark red oil ws separated (approx 5 mls),
water/acid extracted with 3 x 17 mls of benzene
Combined oil and extracts were washed with water

The combined extracts were then mixed with
12g of Na2S2O5 (sodium pyrosulfite) in 15 mls of water

The next day volumnous percipitate was filtered, which weighted 3,5 grams
5 mg probe was mixed with 5 mg NaOH and 1 ml H2O. Weak smell appeared which was much like vanillin\benzaldehyde but much more pleasant.

The pure aldehyde yield was 2g (13% only)

less formalin should be used in first rxn.
more HCl should be used in hydrolizing HMTA complex.

anime · Fri Aug 26, 2005 8:22 pm

Next time try to oxidize the halide to the aldehyde, you can use vanadium pentoxide as a catalyst with hydrogen peroxide, the yields are generally in the 70-90% range.

Don't you love the smell of the benzyl chloride?

64bandil · Busy Bee

I've been looking into that particular reaction, but thought of bromomethylation to avoid gassing. It seems that your procedure stays clear of that.

However - if you are doing chloromethylations, why not make MDP2P in a single step extra?

Take your purified benzodioxole-methylchloride (you probably need to distill it), make the grignard and react it with n,n-dimethylacetamide and hydrolyse. That ought to yield MDP2P in really high yields. If you get the chloromethylation to work in high yields - the world suddenly doesnt need safrole to produce bulk MDP2P Wink

Regards
Bandil

Bushroot · Sat Aug 27, 2005 3:01 pm

anime
thanks for advice, I'll try it as soon as I get my hands on Vanadium Oxide! It's too exotic so I seriously doubt I ever will... Maybe You send me some? LOL

64bandil
A friend of mine tried to make a grignard reaction with piperonyl chloride obtained as above, but he failed. He couldn't completely purify the piperonyl chloride by vac distillation (dunno why, maybe some paraformaldehyde distills along with main product, sounds shit to me Very Happy

) and the Grignard reaction started but several minutes after the chloride's surface was covered by white stuff and reaction ceased...
I don't have that elemental magnesium turnings so I can't try. Anyway it's quite attractive to make the new route to MDMA without any suspicious reagents.