Crowfjord - 19-7-2016 at 14:33
O-propyl eugenol (3-methoxy-4-propoxy-allylbenzene)
O-propyl eugenol was prepared directly from clove oil and n-propyl bromide (1-bromopropane) with potassium hydroxide in ethanol/methanol mixture.
Reagents
28 g clove oil (steam distilled)
95 mL ethanol (Kleen Strip Green Denatured ethanol)
75 mL methanol + extra for rinsing(Heet)
11.60 g potassium hydroxide, assumed ~85% KOH (Photo formulary)
24.9 g 1-bromopropane (prepared from n-propanol, sodium bromide, and sulfuric acid)
80 mL dichloromethane (DCM - distilled from Zip-Strip paste paint remover)
50 mL 2.5% (w/w) aqueous KOH
Distilled water
Calcium chloride (CaCl2)
Experimental
In a 250 mL beaker, 28 g clove oil was dissolved in 95 mL ethanol plus 10 mL methanol. 11.60 g ~85% KOH was dissolved in 60 mL methanol and added
to the eugenol solution. The combined solution was added to a 355 mL swing-top beer bottle, rinsing the last bits out of the beaker with 5 mL
methanol. 24.9 g 1-bromopropane was added, the bottle clamped shut and swirled to mix.
The bottle was heated in an 80° C water bath until the formed sediment reached a constant height, about 3 hours. The reaction mixture was allowed
to cool to ambient temperature, standing overnight.
The formed potassium bromide was vacuum filtered, washing with methanol. The total volume of the filtrate was ~300 mL; this was diluted to ~1000
mL with distilled water (dense brown oil separates) and extracted four times with 20 mL DCM. Additional dilution with water failed to precipitate
more oil. The organic extracts were pooled and washed with 50 mL 2.5% KOH, with 50 mL, and finally 25 mL distilled water. The DCM extract was dried
over CaCl2.
The DCM was distilled off, applying vacuum via aspirator at the end with a warm water bath and strong magnetic stirring until bubbling ceased. The
residue, weighing 22.93 g, mostly solidified in the freezer (-11° C) and melted at ~5° C. The mixture was again frozen and the remaining brown
liquid poured off. The crystals were allowed to melt, refrozen, and the remaining liquid once again poured off. This increased the melting point to
6° C. The final product was light brown and weighed 18.51 g. The odor is similar to clove, but slightly sweeter and softer.
Discussion
While polar aprotic solvents such as dimethylformamide or N-methyl-2-pyrrolidone (NMP) are typically used for SN2 alkylations such as this, ethanol
was used as the solvent due to wide availability and low cost. There is also precedent in the literature of the use of ethanol as solvent in
propylation of eugenol1. Methanol was used as cosolvent, due to insufficient quantity of ethanol on hand.
Assuming the clove oil was 85% eugenol, the final yield was approximately 62%.
Reference
1 JACS, 1899, 21 (11) pp 955-957
O-propyl isoeugenol (3-methoxy-4-propoxy-propenylbenzene)
Reagents
18.5 g O-propyl eugenol (as prepared above)
15 mL n-propanol
21.6 g ~85% KOH
Distilled water
Experimental
18.5 g O-propyl eugenol and 15 mL n-propanol were combined in a 250 mL RBF with a magnetic stir bar. 21.6 g ~85% KOH were ground with a mortar and
pestle and added to the solution and the mixture was heated to reflux with stirring. Two liquid layers formed. 5 mL propanol was added ~20 minutes
into reflux, and another 5 mL at 3 hours. The mixture remained biphasic, and was heated for a total of 6.5 hours, allowing to stand overnight at
ambient temperature.
After cooling overnight, the entire mixture had solidified to a pale brown-orange mass and the joint had seized, despite a generous use of silicone
grease. 50 mL of distilled water were added, the mixture was heated until all dissolved/melted, and poured through the condenser into a 250 mL
beaker. The flask and condenser were rinsed with a little n-propanol and the condenser was easily removed from the flask. 25 mL distilled water was
added to the reaction solution, stirred well and allowed to cool and separate to a brown upper organic layer and a yellowish aqueous layer. The
mixture was transferred to a 1000 mL beaker and with magnetic stirring another 200 mL distilled water was added. The formed white crystals were
filtered, washing generously with distilled water. The total filtrate had a volume of ~600 mL. Extraction of the filtrate with DCM gave, upon
evaporation, a very small amount of oily residue, perhaps 2 mL. This was discarded.
The crystalline material was placed on a coffee filter and air-dried, then dried further over CaCl2 for several days. TLC analysis (1:1
ethyl acetate:VM&P naphtha, visualized with iodine) gave a single spot with Rf = 0.79, and a melting range of 48°-51° C (lit: 54°
C1). The yield was 15.18 g, 82%. The odor of the product is very different from the starting material, similar to the smell of the sap of
pine, spruce, or fir, with floral tones.
Discussion
Propanol was chosen as the medium for the isomerization reaction due to lack of diethanolamine, butanol, or pure ethanol on hand, for which
literature precedent of similar reactions exist. In addition, the higher boiling point of n-propanol over ethanol or isopropanol was attractive as
this could potentially bring the reaction to completion in a more timely manner. Since no corresponding literature to the use of n-propanol in
allylbenzene isomerization could be found, the above procedure was devised.
Although TLC showed only one spot, the product was likely contaminated by trace starting material, as evidenced by the depressed melting point and
some oily residue absorbed by the filter on which product was dried. The chosen solvent system may not have sufficiently separated the propenyl and
allyl isomers.
Reference
1 Atti della Accademia Nazionale dei Lincei, Classe di Scienze Fisiche, Matematiche e Naturali, Rendiconti (1912), 21(I), pp 42-6
Side note: The joint was actually found to be seized early on in the reaction, as I had wanted to take samples and test for reaction completeness as
it progressed. The reaction was stopped at 6.5 hours because the cooling water was getting warm, and it was time for bed so I couldn't keep adding
ice. Several methods were attempted to separate the flask and condenser to no avail, and at one point in trying to pull the two pieces apart, I
slipped and hit myself in the chest quite hard with the flask. I seem to have bruised or cracked a rib; it has been three weeks and it still has not
healed. Let this serve as a reminder to pull away from oneself when trying to separate stuck glassware!
[Edited on 19-7-2016 by Crowfjord]
[Edited on 20-7-2016 by Crowfjord]