my two cents, eugenol to myristicin 43,5% yield total over 3 reactions.

5-formyleugenol bisulfite adduct:


Duff formylation:

in an 2L rbf,

4g Zinc metal was dissolved into 250ml 80% Acetic acid. (warming helps)

160g Hexamine solved in 250ml H2O was added.

100g Eugenol was added and the beaker was washed with 100ml 80% Acetic acid into the rbf.

the mixture was refluxed 3,5h via oilbath at 200°C (jeah stirring..)

300ml conc. HCl + 100ml H2O added and the mixture was refluxed 0.5h further.

after that 1000ml H2O was added.

when cool the mixture was extracted 3x with 500ml EtOAc

pooled extract where washed with brine and then dried using anhyd. MgSO4.

extract is stipped off solvent (there might be some acetic acid wich should be removed mostly too.)

residue is taken up in 300ml 96% EtOH.

to the EtOH solution was added an solution of 100g Sodium bisulfite in 200ml H2O under strong stirring.

an exotherm reaction takes place and the mixture was stirred for 1h.

the bisulfit adduct was filtered and washed 3x with 300ml 96% EtOH.

dried at 100°C. Yield: 127g 5-formyleugenol bisulfite adduct 69,7% (MW: 296.2687693g)

(this reaction was performed double this size and the bisulfite was formed in MeOH instead of EtOH wich resulted in 65,9% yield)


Myristicine:


Dakin oxidation:

60g of the above bisulfite adduct was added to an stirring mixture of

16,2g NaOH in 400ml H2O

after a short stirring 150ml 12% H2O2 was added in one go! (no ice bath or water bath)

left stirring 1h.

the reaction mixture was extracted with 2x60ml of DBM (no washings, no dryings)



Methylenation:

the DBM extract from above was slowly dripped into an stirred & refluxing mixture of

60g NaOH
150ml H2O
3,6g TBAI

the slower the better. if it drips let it drip, dont torture yourself in min maxxing this.

after addition the mixture refluxed another hour.


after that, a bunch of water was added and this was steam distilled.

about 4-5L destillate was collected and extracted with DCM (ofc u dont mix up your DBM & DCM extracts..)

extracts , dried and stipped off solvend.

the residue stood in an open beaker at 100°C for several hours and several days in the open at rt to get rid of the last solvent residues.

weight of the residue: 25,7g -> 66% yield.

this was later vac distilled to get a very lightly jellow colored clear liquid withotu any considerable loss of yield. only a very flat colored residue was left in the flask (thats why the myristicine was red after steam distilling.)




so, now people asking themselfes: could we technically use DCM in this preparation?

and my answer: PROBABLY YES!


i actually tried using dcm in this fashion but with only 2eq of NaOH... with resulted in a VERY slow reaction time BUT yielded somewhat around 10% myristicine! (also the myristicine was yellow not red after steaming)
this was before i realized the NaOH % matters in this reaction ALOT.

but this realization came after implemented DBM wich resulted in an good yield. so DCM never had a chance to shine..

so, with 30% NaOH and DCM it probably works too!


oh, there was only 1 spot on TLC








[Edited on 24-2-2026 by 0_Q]

[Edited on 24-2-2026 by 0_Q]