Family: Myristicaceae.

Oleum Macidis. Oleum Nucis moschati. - Macis- und MuskatnuBol. - Essence de Macis. Essence de Muscade.

Origin. The nutmeg tree Myristica fragrans, Houtt. (Myristica officinalis, L. fil.; M.moschata, Thbg.; M.aromatica, Lam.), which belongs to the family Myristicaceae is indigenous to the Moluccas, more particularly to the Banda and Sunda islands. By means of cultivation it has been distributed1) throughout these islands and in other parts of the world, e.g. Brazil and the West Indies. The fruits obtained from the Indian Archipelago are preferred. The principal ports of export at the present time are Batavia and Singapore.

For distilling purposes injured and imperfectly developed nutmegs which are not suitable as spice are used. The yield amounts to from 7 to 15 p.c. The mace or arillus of the nutmeg, which yields from 4 to 15 p. c. of oil, is rarely used for distillation. Commercially no distinction is made between nutmeg oil and mace oil.

1) The cultivation of the nutmeg tree in Java has been described by Gillavry in Rev. cult, coloniales 14 (1904), 342; Report of Schimmel & Co. October 1904, 66.

Properties of Nutmeg Oil. Nutmeg oil is a limpid, colorless liquid which thickens with age, owing to the absorption of oxygen, and which has the characteristic odor of nutmeg and a spicy taste. According to the condition of the raw material, the specific gravity of the distillate varies considerably, fluctuating between 0,865 and 0,925; aD + 8 and +30°; nD20o1,479 and 1,488; soluble in 0,5 to 3 vol. of 90 p. c. alcohol. When distilled in a fractionating flask, about 60 p. c. pass over up to 180°. When evaporated on a water bath, a good oil leaves but a slight residue. When making this test, it should be remembered that nutmeg oil evaporates but slowly. As has been observed by Schimmel & Co. in connection with their own distillates, 5 g. of oil require 12 to 15 hours before the residue becomes of constant weight. This residue amounts to from 1 to 11/2 p. c.

The properties of the oil distilled by de Jong1) from fresh nutmegs were as follows: d26o 0,940; aD26o + 10° 20'; boiling temperature: 155 to 175° 9,5 "p.c., 175 to~200° 3 p.c, 200 to 250°, 22 p.c, 250 to 280°, 27 p.c.

Properties of Oil of Mace. In all its properties oil of mace closely resembles nutmeg oil and cannot be distinguished from the latter. It is colorless or yellowish and later acquires a reddish color. It has an agreeable, yet strong, mace odor which in old oils becomes unpleasant and terebinthinate. Its aromatic taste, mild at first, later becomes pungent. d15o 0,890 to 0,930; aD 10 to 4 + 22°. With 2 to 3 vol. of 90 p.c. alcohol the oil forms a clear solution.

An oil distilled from fresh mace by de Jong1) had the following properties: d26o 0,942; aD26o + 7°; upon distillation 30,5 p.c. passed over between 155 and 180°, 15 p.c. between 180 and 200°, 20 p.c. between 200 and 250° and 27,5 p.c. between 250 and 285°.

Composition. Because of the similarity of mace and nutmeg oils no distinction is made between the two oils in commerce. Hence it is impossible to distinguish at the present time between a) Teysmannia, Batavia 1907, No. 8; Report of Schimmel & Co. October 1908, 89. the oils that have been investigated. For this reason the two oils are discussed together. Inasmuch as no difference in their composition has been revealed thus far, this method of procedure does not appear to be objectionable1).

Although numerous older investigations of these oils are on record2), a clear insight into their composition has been obtained only recently, more particularly through the investigations of O.Wallach3), F. W. Semmler4), H. Thorns6), F.B.Power and A. H. Salway6), and Schimmel & Co.7).

Arranged according to their boiling points, the following constituents have been isolated:

1. a-Pinene was found by Wallach3) in the lowest fraction (m.p. of nitrolbenzylamine 123°). It is an almost inactive mixture of d- and /-cr-pinene. As early as 1862 Schacht had isolated it, had named it "macene", and prepared the solid hydrochloride (pinene hydrochloride).

2. The presence of camphene was first established by Power and Salway who converted it into isoborneol (m.p. 207 to 212°; m.p. of phenylurethane 138o).

3. B-Pinene is present in small amounts only (m.p. of nopinic acid 126 to 1280)7).

4. Dipentene (m.p. of tetrabromide 124 to 125°)3)6)7).

5. p-Cymene. With the aid of concentrated sulphuric acid Wright had indicated the presence of this hydrocarbon. Inas1) K. T. Koller declares both oils identical (N. Jahrb. Pharm. 23 [1864], 136; Vierteljahrsschr. f. Pharm. 13, 507; Jahresb. f. Chem. 1864, 536).

2) John, Chemische Schriften 6 (1821), 61; Journ. f. Chem. u. Phys. von Schweigger und Meinecke 33 (1821), 250. - G.). Mulder, journ. f. prakt. Chem. 17 (1839), 102 and Liebig's Annalen 31 (1839), 71. - C. Schacht, Arch, der Pharm. 162 (1862), 106. - J. Cloez, Compt. rend. 58 (1864), 133. - J.H.Gladstone, Journ. chem. Soc. 25 (1872), 1; Jahresb. f. Chem. 1872, 816. - C.R.A.Wright, Journ. chem. Soc. 26 (1873), 549; Jahresb. f. Chem. 1873, 369. - Pharmaceutical Journ. HI. 4 (1873), 311.

3) Liebig's Annalen 227 (1885), 288 and 252 (1889), 105.

4) Berl. Berichte 23 (1890), 1803; 24 (1891), 3818. 5) Ibidem 36 (1903), 3446.

°) Journ. chem. Soc. 91 (1907), 2037. The oil examined by P. and S. had been specially distilled for this investigation from unlimed Ceylon nutmegs. It had the following properties: d15o 0,8690; aD+ 38°4'; A.V. 0,81; E.V. 315; soluble in 3 parts of 90 p.c. alcohol.

7) Report of Schimmel & Co. April 1910, 80.

much, however, as this method is not reliable in the presence of terpenes, the proof was first established by Schimmel & Co.1) who prepared p-hydroxy isopropyl benzoic acid (m.p. 155 to 156°) from the corresponding fraction without previous treatment.

6. d-Linalool (oxidation to citral, m.p. of citrylnaphthocin-choninic acid 200°)2).

7. Terpinenol-4. The alcohol which occurs in fraction 205 to 215° yields terpinene (m.p. of dihydrochloride 50 to 52°) when heated with concentrated formic acid. When oxidized with dilute permanganate it yields a glycerol melting at from 112 to 115° which, upon boiling with hydrochloric acid, loses water and yields p-cymene and carvenone. This identifies the original alcohol with terpinenol-41) (See vol.1, p. 382). In agreement with this result is an observation by Power and Salway who, upon the oxidation of a corresponding fraction with chromic acid mixture, obtained a diketone, the dioxime of which melted at 140°. The diketone which thus results from terpinenol-4 is identical with a-dimethylacetonylacetone. This same compound, the dioxime of which melts at 137°, was obtained by Wallach3) upon further oxidation of the glycerol from terpinenol-4, mentioned above, to a-dihydroxy-«-methyl-«'-/sopropyladipinic acid.

8. Borneo/. In the oxidation liquid of fraction 205 to 215° mentioned under 7, Power and Salway found camphor (m.p. of semicarbazone 238°) the formation of which is probably due to borneol present in the original oil.

9. u.-Terpineol (m.p. of dipentene dihydriodide 80°; oxidation to the ketolactone C10H16O3 which melted at 62 to 63°)2).

Hence, it would appear that the alcohol described as myristicol by Wright4) and which boiled between 212 and 218o was a mixture of a-terpineol, borneol and terpinenol-4.

10. Geraniol2) (m.p. of diphenyl urethane 81 to 82°).

11. Safro/2) (oxidation to piperonal, m.p. 34 to 35°).

12. An aldehyde with the odor of citral and characterized merely by its B-naphthocinchoninic acid melting at 248°.

1) Report of Schimmel & Co. April 1910, 80.

2) Footnote 6, p. 410.

3) Terpene und Campher, Leipzig 1909, p. 486. Report of Schimmel & Co. October 1908, 179. 4) Loc. cit.

13. Myristicin1), C11H1303, 4-allyl-6-methoxy-1,2-methylene dihydroxy benzene, is contained in the highest boiling fraction of the oil. Wright2) first assigned to it the formula C10H13O2 and Semmler8) regarded it originally as a butenyl derivative of the formula C12H14034). The constitutional formula, the properties and derivatives of this interesting phenol ether are recorded in vol. I, p. 489.

In the saponification liquor of the oil the following acids have been found:

14. Formic acid (Ba-salt)5).

15. Acetic acid (Ba-salt)5).

16. Butyric acid5).

17. Caprylic acid (n-Octylic acid) (Ag-salt)5).

18. A non volatile, monocarboxylic acid C12H17Oco2 that melts at 84 to 85° and is insoluble in water5).

19. Myristic acid, m.p. 54°, occurs both free and as ester. According to the duration of the distillation the oil contains more or less. Occasionally it separates in crystalline form1). Upon evaporation of the oil it remains behind.

Of phenols Power and Sal way5) found the following:

20. Eugenol (m. p. of benzoate 69°; m. p. of diphenyl ure-thane 107 to 108 ).

21. \soeugenol (m. p. of benzoate 105°).

As to the quantitative composition of oil of nutmeg, Power and Sal way record the following percentages:

Eugenol and isoeugenol (about 0,2 p. c), d-pinene and d-camphene (abt. 80 p.a), dipentene (abt. 8 p.c), d-linalool, d-borneol, i-ferpineol and geraniol (abt. 6 p.c), small amounts of a new alcohol (terpinenoI-4), traces of a citral-like aldehyde, safrol (abt. 0,6 p.c), myristicin (abt. 4 p.c), myristic acid free (abt. 0,3 p.c.) and small amounts as esters, finally small amounts of formic acid, acetic acid, butyric acid, octoic acid and a new monocarboxylic acid C13H1803 all as ester.

1) This should not be confounded with "myristicin", the stearoptene of John and Mulder, which occasionally crystallizes out of old oils and which, as Fluckiger (Pharmaceutical Journ. III. o [1874], 136) has shown, consists of myristic acid.

2) Footnote 2, p. 410.

3) Berl. Berichte 23 (1890), 1803; 24 (1891), 3818.

4) Ibidem 36 (1903), 3446.

5) Footnote 6, p. 410.

As Power and Salway point out, these figures may not have any general import since they must vary considerably according to the conditions of the material employed. From the low specific gravity and the exceptionally high rotation it must be supposed that Power and Salway worked with an oil particularly rich in terpenes. Many of the nutmeg oils presumably have a larger content of oxygenated constituents than recorded above.

Physiological Action. Toxic action has been observed repeatedly as the result of the use of large amounts of nutmeg. According to the experiments made by Power and Salway1) this is doubtless due to the volatile oil, more particularly to the myristicin. The poisonous character of the latter had already been ascertained experimentally by F. Jurss-).