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				Nutmeg and its Essential Oil
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From: an89433@anon.penet.fi
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: DrHaney@world.std.com
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: DrHaney@world.std.com
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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Author: Jacob W Smith
Email: smit0262@gold.tc.umn.edu
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: jkenner@cello.gina.calstate.edu
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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