In a 250 mL RBF was prepared mixture of 5-hydroxyvanillin (3.4 g, 20 mMol), grinded K2CO3 (5.8 g, 42 mMol) and DMSO (35 mL).
Reflux condenser was set in, the reaction flask was placed in a glycerol bath and heating with stirring was started.
Temperature of the bath was set at 125°C, and then to the reaction mixture was added CH2Cl2 (3.6 mL, 56.3 mMol) right through
the top of the condenser, in one portion. After 45 minutes there was added another small portion of CH2Cl2 (1 mL, 15.7 mMol; for
a total of 72 mMol) and heating was continued for another 105 minutes (i.e. total time of heating was 150 minutes).
After that, still hot reaction mixture was poured into a beaker containing 200 mL of cold water. Reaction flask was washed with another 40 mL of water
and this wash was added to the same beaker. Resulting suspension was basified with solution of 2 g KOH in 10 mL H2O, stirred for one minute
and filtered. Solid mass on the filter was washed with water (3 x 20 mL) and dried. There was obtained 3.5 g of very crude brown-colored product.
This crude product was transfered into a 500 mL RBF and there was also added 190 mL of petroleum ether (fraction of 70-100°C). This mixture was
boiled with stirring for about 10 minutes, and then boiling solvent was decanted into a heat-proof container. This operation was repeated with 50 mL
of boiling petroleum ether decanting in the same container.
Combined petroleum extracts was boiled to dissolve all of the precipitate and let cool slowly to RT°, then it was extra-cooled in a freezer for
several hours. Precipitate was filtered out, washed with 5 mL of petroleum ether and dried. There was obtained 2.71 g of yellow crystalline powder
with a smell of DMSO-decomposition compounds. Mp. 125.5-128° (fast heating; I think the main impurity was DMSO).
Said obtained product was recrystallized from 40 mL of boiling IPA, filtered, product on the filter was washed with two small portions of cold IPA and
dried.
There was obtained 2.48 g (68%) of myristicinaldehyde. Mp. 130-132°C.
Yellowish crystalline powder with no smell at RT°. However, it has a sweet aroma if you melt it.
Recrystallization trial from mixture of DCM and petroleum ether (1.7 to 1 by volume; p. ether was added by drops into DCM solution of the product
until solution becomes cloudy, then heated until it's clear again) have failed to raise purity of the final product.
I did a couple experiments with this procedure on the same scale but changing various conditions, here's what I found:
1) Addition of 0.5 grams of grinded KI doesn't affect the yield.
2) Swapping DMSO for N-methylpyrrolidone leads to purer aldehyde product that doesn't require recrystallization from alcohol (just the
extraction with boiling petroleum ether is enough, it gave almost colorless crystalline aldehyde with no smell and with mp of 129-131°).
3) Application of an inert atmosphere doesn't seem to change anything (almost the same yield and purity was obtained).
4) Yield was always 60-70% of the theoretical.
I also measured solubility of myristicinaldehyde in various solvents:
Water: insoluble (RT°); ~0.65 g in 100 mL (at boiling)
Petroleum ether (fr. 70-100°): insoluble (-18°); insoluble but seems to form somewhat oversaturated solutions (RT°)
IPA: very low (RT°)
EtOH (95%): very low (RT°)
DCM: <1 g in 6 mL (20°), >1 g in 6 mL (at boiling)
EtOAc: >0.2 g in 6 mL (RT°); very crude product right after reaction have poorer solubility than purified aldehyde.
I think that slight solubility of myristicinaldehyde in boiling water gives an opportunity to use it in the first purification stage instead of
petroleum ether, as safer and cheaper alternative.
Overall, I'm pretty satisfied with this simple procedure for methylenation of dihydroxybenzaldehydes and I'm also too lazy to make any further
improvements , but it could definitely use some optimization.
[Edited on 28-3-2019 by bipolar]bipolar - 3-4-2019 at 02:09
to the reaction mixture was added CH2Cl2 (3.6 mL, 56.3 mMol) right through the top of the condenser, in one
portion.
Forgot to tell you. Be careful when scaling this up - addition of DCM will cause extreme boiling, especially the first portion of it.laserlisa - 3-4-2019 at 02:47
Really nice writeup. Thanks for sharing.
Did you make the 5-hydroxyvanillin yourself? Im interested in efficient procedures for making that compound.bipolar - 3-4-2019 at 03:01
, but it could definitely use some optimization.