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Nutmeg and its Essential Oil

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From: [email protected]
Date: Sat, 25 Mar 1995 15:47:09 UTC
Subject: Safrole

After looking up Oil of Nutmeg in the Merck index (10th ed) I came up
with the following :
Oil of nutmeg, constit:
60-80% d-camphene (Bp 158.5-159.5 C), 8% d-pinene; dipentene,
d-borneol (Bp 212 C), l-terpineol, 6% geraniol (Bp 229-230 C),
safrole (Bp 232-234 C), 4% myristicin.
The chemicals of interest here are safrole and myristicin. Temperatures
are in degrees Celsius at 1atm pressure (760mm Hg). My question is :
What is the fraction of safrole in oil of nutmeg. My guess is 4-6% but
a corrected estimate is welcomed...
Oil of sassafras (constit appx 80% of safrole) is of course preferred but
nutmeg is so easily availble that it is at least worth checking this out.
V. Jones
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Author: Daniel R Haney
Email: [email protected]
Date: 1995/10/01
> filter off the crystallized trimyristin.
>Uh... wrong compound.
Crepitance. Trimyristin is CHAFF. You must separate it FIRST
to get at the tiny fraction containing the phenylics of interest.
> The one of interest here is myristicin, not
Yes, I know, ya' yung whippersnapper. The amusing Volatile Oil
Of Nutmeg is the leftover you get with an extraction+crystallization.
Volatile Oil components are less than 5% of the whole nutmeg weight
while the fat trimyristin is at least 25%. That's a lot of crap
to ignore for doctrinaire reasons.
Merck sez enough about the volatile oil to show that it is mostly
terpenes (oboy! let's eat it and belch like bandits) although
containing substantial safrole (hurrah!) and myristicin.
I know you guys want an elegant one-step to snag the oils. So
would I. But ethanol is cheep and this fat extraction requires
less energy than the steam distillation.

Dragging my flu-ridden carcass around the house,

-DrH
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Author: Daniel R Haney
Email: [email protected]
Date: 1995/10/01
I have come perilously close to a chemical prick-waving
match with you and sincerely apologize. As evidence of
earnest good intent, I am passing on the fruits of my
studies on NUTMEG for the edification of all.
On nutmeg, the Encyclopedia Britannica sez:
"Nutmeg and mace contain 7 to 14 percent essential oil,
the principal components of which are pinene, camphene,
and diterpene, all having the empirical formula C10H16.
Nutmeg on expression yeilds about 24 to 30 percent fixed
oil called nutmeg butter, or oil of mace, the principal
component of which is trimyristin..."
On volatile oil of NUTMEG, Merck 11th sez:
(skipping the reference to steam distillation)
"...Constit. 60-80% d-camphene, about 8% d-pinene;
dipentene, d-borneol, l-terpineol, about 6% geraniol,
safrol, about 4% myristicin. The myristicin fraction
with its more than 25% content of elemicin is supposed
to be responsible for the purported hallucinogenic
properties of nutmeg seed: Shulgin, "Nature" 197, 4865,
(1963)"
Sorta figured Shulgin would turn up in there. More later.
The elemicin is not listed or indexed as such in Merck 11th,
but is the 3,4,5 trimethoxy substituted phenylallene.
Neither safrole nor myristicin is there in SUBSTANTIAL amounts,
only SIGNIFICANT amounts. Useless for preparative intents,
useful for scents and flavorings.
100MG OF MYRISTICIN...
4% of 10% (average 7,14) is 0.4%, that is to say, myristicin is .4%
the weight of whole nutmeg. 25 grams of whole nutmeg contains 100 mg
of the myristicin fraction. I'd rather brew beer.
UBER ALCOHOL EXTRACTION:
>...What percentage of oils can be extracted out this way?
Nearly all of them that can be had along with a lot of stuff
you don't want. Solvent extraction is so thorough the the nutmeg
is pale when you are done.
>I was always under the impression that steam
>distillation was much more effective at squeezing the non-miscible
>non-volatiles out.
MY CONJECTURE:
The steam distillation is industrially feasible because of the
mechanical simplicity of equipment and lower physical handling.
The alcohol extraction is fast but requires more handling and so is
better applied to small scale,i.e., benchtop. I guess it depends
on what amount you want to produce.
By example, stearic acid is produced by both methods depending
upon the cheapness of fuel and labor. The results differ
primarily in the last 3% of stuff that is NOT stearic acid such
as proteins, inorganics, unsaturated fats, and funky esters.
Stearic acid is used in vast quantity to make soaps, creams,
and lotions. [end digresssion]
Shulgin's listing of the 10 essential oils follows. I have
renamed them from IUPAC to trivial allylbenzenes to reflect
the ring substitution of a sibling phenalkylamine.
estragole: 4-methoxy allylbenzene
methyleugenol: 3,4-dimethoxy allylbenzene
safrole: 3,4-methylenedioxy allylbenzene
myristicin: 5-methoxy 3,4-methylenedioxy allylbenzene
croweacin: 2-methoxy 3,4-methylenedioxy allylbenzene
elemicin: 3,4,5-trimethoxy allylbenzene
asarone: 2,4,5-trimethoxy propenylbenzene
apiole: 2,5-dimethoxy 3,4-methylenedioxy allylbenzene
dillapiole: 2,3-dimethoxy 4,5-methylenedioxy allylbenzene
???: 2,3,4,5-tetramethoxy allylbenzene
Jason keeps mentioning inorganic salts in nutmeg. While my
first impulse was to ignore that as insignificant, there is
no avoiding inorganic matter entrained in the nutmeg extracts.
All woody/nutty materials contain significant inorganics.
This has been recognized historically -
Rock maple is awfully hard stuff in part because of the silicates
in it. Makes a nice solid body guitar, too. Chews up saw blades.
Stradivari treated wood with brine to leach out the inorganics
as well as the water-soluble rosins and so got a lighter, more
resonant material with extended high frequency response.
I have no exact information as to the disposition of inorganics
in nutmeg or wood so if anyone else knows some figures, speak up.
Good Cheer,
Daniel R. Haney
ps: Hah! The old fart's brain isn't entirely rusted shut.
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I got curious enough about nutmeg to do some reading. Nutmeg contains
a variety of allylbenzenes (double bond between beta and gamma carbons),
all very similar to psychedelic amphetamines. I tried drawing the
compounds, but they're difficult in ASCII. The compounds all have the
allylbenzene in common, the differ in their substitutions at the 3,4,5
positions of the benzene ring. The compounds and their concentrations
from (1):
compound substitutions concentration
-------- ------------- -------------
myristicin 3-methoxy, 4,5-methylenedioxy 4.0%
safrole 3,4-methylenedioxy 0.6%
eugenol 3-methoxy, 4-hydroxyl 0.2%
elemicin 3,4,5-trimethoxy *
methyleugenol 3,4-dimethoxy *
----
*-mentioned in (4) and stated as being previously included with
the myristicin portion incorrectly.
Weil's (1) paper gives a broad history of nutmeg use as food and as
narcotic, and gives a summary of research into the pharmacological
effects of nutmeg. Some of the more interesting work cited is that by
Alexander Sulgin (3,4). Unfortunately some of the cited work is from an
unpublished paper, and the library didn't have the journal another
article was in (3) so I only saw excerpts.
The descriptions of the experience mentioned by Weil are consistent
with pyschedelic amphetamine experiences, although the initial phase
of an excitment and distorted perception is often followed by
narcosis, the effects sometimes reported as lasting days. There are a
wide variety of other toxic effects reported (infrequently, death) with
enough frequency to make it clear why this is not a widely abused
substance.
The psychedelic component is examined by Shulgin who concludes that
the hallucinogenic action is mainly from the myristicin and related
components. He notes that only know mechanism of metabolism of any of
the compounds is the detoxification of safrole to piperonylic acid.
This reaction show the capacity to oxidize an olefinic side chain.
He uses this fact to speculate on a possible pharmacologic mechanism
(quoted from Weil):
"Shulte suggests that, if this degradative process is `applicable to
myristicin, or especially to elemicin, a theoretical intermediate, a
vinyl alcohol, could undergo transamination producing the known
psychotomimetic drug, 3,4,5-trimethoxy amphetamine (TMA). The recent
description of the new, synthetic hallucinogen -
3-methoxy-4,5-methylenedioxy amphetamine (MMDA)-which might be
derived by an analogous process from myristicin, itself, is even more
suggestive of a psychotropic function for this component of nutmeg.'"
References
----------
1. Weil, Andrew (1965). Nutmeg as a Narcotic. 19(3), 194-217.
2. Truitt, Edward and others (1961). The Pharmacology of Myristicin; A
Contribution to the Psychoparmacology of Nutmeg. 2(4), 205.
3. Shulgin, Alexander T. (1963). Concerning the pharmacology of nutmeg.
Mind 299-303.
4. Shulgin, Alexander T. (1964). Composition of the myristicin fraction
from oil of nutmeg. Nature, 197:4865, p.379.

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Author: Jacob W Smith
Email: [email protected]
Date: 1995/10/02
Myristicin constitutes about two thirds of the aromatic ether
fraction, but it cannot account entirely for the psychoactivity
of nutmeg. Those occurring at more than 10 mg per 20 g are myristicin
(210 mg), elemicin (70 mg), safrole (39 mg), methyleugenol (18 mg),
and methylisoeugenol (11 mg). A 400-mg dose of myristicin, almost twice
the amount present in 20 gm of nutmeg (20 gm being assumed to be the
quantity required to produce psychotropic effects) produces only mild
effects.
Schultes and Hofmann. The Botany and Chemistry of Hallucinogens. p. 121.
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Author: Jason Kennerly
Email: [email protected]
Date: 1995/10/01
Roughly 60g of nutmeg powder was extracted into acetone. The acetone was
allowed to sit like that on a shelf for a few days and...
Something precipitated! white stuff! What is it? I'm *guessing* this has
something to do with the fatty acids, but does it? What the hell is the
stuff. I saved it, i'm pretty damn curious as to what it is.... I know
its not likely to be anything useful, but does this type of thing happen
often?

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Composition of the Myristicin Fraction from Oil of Nutmeg
Alexander T. Shulgin
Nature, Vol. 197, No. 4865, p. 379 (1963)
The aromatic ether fraction of oil of nutmeg has been previously shown to
consist of eugenol (Ia), isoeugenol (IIa) safrole (Ic) and myristicin (Id).
Vacuum distillation yields a fraction (bp 109-112°C @1 mmHg; 60g from
1000g of "W.I." oil of nutmeg (George Lueders and Co)) which consisted of
a substance heretofore accepted both clinically and pharmacologically as
the single compound, myristicin (Id).
3 (I) 3 (II)
\___ \___
/ \ KOH/EtOH / \
4--< O >--CH2--CH==CH2 ==========> 4--< O >--CH2==CH2-CH3
\___/ \___/
/ /
5 5
---------------------------
3 4 5
---------------------------
a OCH3 OH H
b OCH3 OCH3 H
c O--CH2--O H
d O--CH2--O OCH3
e OCH3 OCH3 OCH3
---------------------------
The isomerization of this fraction with alcoholic potassium hydroxide
yielded (trans) isomyristicin (IId), isolated by crystallization of the
distilled reaction mixture. The mother liquors of this isolation.
On analysis by vapour phase chromatography, provided the first indication of
the complexity of the above "myristicin" fraction. Of the four peaks observed,
No. 1 was easily identified as methyl isoeugenol (IIb) by its infra-red
spectrum and direct comparison to a commercial sample. Peak No. 3 was to a
large extent trans-isomyristicin not removed by crystallization. The remaining
two peaks were isolated using a Beckman Megachrome preparative V.P.C.
instrument using a substrate of silicone 710, on firebrick at 220°C.
The presence of a methylenedioxy group (by nuclear magnetic resonance) and the
absence of absorption in the 963-967 cm-1 region of the infra-red spectrum of
peak 2 strongly suggested that the isomer might be cis-isomyristicin. That
trans-propenyl aromatic ethers possess a characteristic absorption band in the
above region (which is transparent for the cis-isomer) has been shown for
isosafrole, anethol, isoeugenol, methylisoeugenol and asarone. Further, it has
been shown recently that the cis-isomer of the stereoisomeric pairs invariably
precedes the trans-isomer during vapour chromatography. This peak was verified
as cis-isomyristicin by its conversion to trans-isomyristicin (IId) and its
synthesis from myristicin, both with alcoholic potassium hydroxide. The fourth
peak was also isolated by preparative chromatography and showed the absence of
a methylenedioxy group, but the presence of a strong band at 957 cm-1.
Isoelemicin (IIe) was synthesized by the potassium hydroxide isomerization of
elemicin and was found to possess an identical infra-red spectrum. Methyl
isoeugenol may be assumed to be in the propenyl form in the original sample of
nutmeg distillate. There is an unresolved peak at this identical time in the
original "myristicin" fraction and a search for the logical precursor methyl
eugenol, has been unsuccessful.
The implied presence of elemicin (Ie) in the original myristicin fraction was
confirmed by the successful separation of it from myristicin by low-temperature
chromatography (108°C, silicone 'SF-96'). Repeated fractional distillation was
ineffective in increasing the myristicin content of this constant boiling
fraction over 70 percent. Consequently in assigning chemical and biological
properties to the substances as isolated from nutmeg, allowance must be made
for this congeneric contaminant.
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