-------------------------------------------------------------------------------- Nutmeg and its Essential Oil -------------------------------------------------------------------------------- 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 -------------------------------------------------------------------------------- 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 -------------------------------------------------------------------------------- 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. -------------------------------------------------------------------------------- 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. -------------------------------------------------------------------------------- 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. -------------------------------------------------------------------------------- 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? -------------------------------------------------------------------------------- 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. --------------------------------------------------------------------------------