The principal constituent of the oil, the ascaridol4) C10H16O2 has a disagreeable, benumbing odor and a disagreeable taste; d15o 1,0079; aD - 4° 14'; nD20o1,4731; b.p. 83° (4 to 5 mm.). Under ordinary pressure this substance cannot be distilled, since it decomposes, even before the boiling point has been reached, with explosive"') violence which is frequently accompanied by a flame.
In his attempt to ascertain the constitution of ascaridol, E.K.Nelson6) used a product that had the following constants: b.p. 96 to 97° (8 mm.); d20o0,9985; aD + 0,7°; nD20o1,4719.
As ascertained by Nelson, ascaridol, when acted upon by a saturated solution of ferrous sulphate at ordinary temperature, is decomposed with the evolution of considerable heat and the formation of a combustible gas. As one of the reaction products, isopropyl alcohol was isolated from the viscid mass by distillation with steam. It was recognized as such by its oxi1) E. Kremers, Pharm. Review 25 (1907), 155.
2) Garrigues, Americ. Journ. Pharm. 26 (1854), 405.
3) Report of Schimmel & Co. April 1908, 109.
4) So called because of its action against Ascaridas.
5) Already observed by E. Kremers (loc. cit.). 6) Journ. Americ. chem. Soc. 33 (1911), 1404.
Fused with caustic alkali or boiled with sodium, the glycol is partly converted into a compound which is colored greenish-violet when exposed to the air. When acidulated and after ferric chloride has been added, steam drives over a substance which can be shaken out of its ethereal solution by caustic alkali with a violet color. When acidulated, there were obtained small amounts of orange-yellow crystals that melted at 164 to 166° and apparently were a-hydroxythymoquinone. With concentrated sulphuric acid these gave a purple-red color. Its aniline derivative crystallizes in dark-violet needles.
When the glycol is oxidized with permanganate solution, there results a mixture of volatile acids (acetic acid, butyric acid?) in addition to a dibasic acid C10H16O5 that is difficultly soluble in water, melts at 116,5 to 117° and which has been named ascari-dolic acid. Its silver salt is well-nigh insoluble in water. As shown by its behavior toward acetic acid anhydride, hydroxyl-amine or semicarbazide, its molecule contains neither a hydroxyl nor a ketone group. Its behavior during titration excludes the possibility of its being an anhydride or lactone. When heated beyond its melting point, methyl heptenone1) appears to be formed.
1) The formation of methyl heptenone when the acid C10H16O5 is distilled was unquestionably established by Schimmel & Co.
When oxidized the glycol yields another solid acid which melts at 186 to 187° and is dibasic. Nelson assigns to it the provisional formula C10H160„.
Basing his conclusions on the foregoing results, Nelson assumes that ascaridol is a peroxide of the following formula:
Wallach1), however, who examined ascaridol at about the same time, but who persued another course, arrived at somewhat different conclusions.
Suspended in water and in the presence of colloidal palladium, ascaridol adds with unprecedented rapidity 4 atoms of hydrogen. Hence, lest the heat generated during the reduction becomes too great, the addition of hydrogen must be regulated. Two products result that are easily separated: an oil readily volatile with water vapor, and a solid substance that is difficultly volatile. This is best extracted from the residue with chloroform after the bulk of the readily volatile substance has been distilled over. The solid reduction product is a new terpin, 1,4 terpin (lerpinene terpin). It consists of large prisms that melt at 116 to 117°. This terpin can exist in two stereoisomeric forms, one of which melts at 137° and was described by Wallach2) several years ago. The product melting at 116 to 117° evidently represents the second form. When 1,4 terpin is heated with oxalic acid, there results as principal product 1,4-cineol3) (b. p. 172°; d18o0,9010; nD18„ 1,4479) which when mixed with hydrogen bromide in acetic acid yields terpinene dihydrobromide melting at 58 to 59°. Upon prolonged heating with potassium permanganate there did not result an acid corresponding to cineolic acid, but a sparingly soluble acid melting at 157° and containing less oxygen. When 1,4 terpin is acted upon with oxalic acid there results, in addition to much 1,4 cineol, a small amount of an unsaturated alcohol. This alcohol could not be obtained in a pure state. However, it was possible to identify its oxidation product. For this purpose the reaction product of the terpin was distilled off with water vapor and oxidized at 0° with 1 p.c. potassium permanganate solution. The 1,4 cineol present was distilled off with water vapor. The residue contained a glycerol which, when heated with dilute sulphuric acid, yielded cymene and a ketone, 1-menthenone-3. Upon further oxidation, the two terpinenols yielded d-dihydroxy-a-methyl-d-isopropyladipic acid, which can readily be identified by conversion into its dilactone. As a matter of fact, it was possible to obtain a dilactone C10H14O4 melting at 72° by the corresponding treatment of the oxidation mixture. Thus was proved the presence of a terpinenol in the product obtained by the reaction of oxalic acid on terpin and the terpin itself characterized as a derivative of terpinene.
1) Liebig's Annalen 392 (1912), 59.
2) Berl. Berichte 40 (1907), 577.
3) Liebig's Annalen 366 (1907), 197.
The oil, together with the terpin that resulted upon the reduction of ascaridol, contained saturated and unsaturated constituents. The product was, therefore, further reduced in the presence of palladium and the last traces of unsaturated compound were removed by potassium permanganate. An alcohol C10H19OH (b.p.207to208°; dl9o0,9080; nD 1,4656) results, which when heated with zinc chloride yields a hydrocarbon (b. p. 173,5 to 175,5°; d19o 0,821; nD19o 1,4558; mol. refr. found 45,67, computed for C10H18/=45,63). These figures agree well with those for menthene. Presumably, however, the product is a mixture.
The results communicated above justify the assumption that ascaridol adds 4 atoms of hydrogen with the formation of 1,4 terpin (II). Provided that no re-arrangement of the atoms has taken place during the reduction to 1,4 terpin, formula I may be assumed for ascaridol.
Wallach suspects that the acid C10H16O6 melting at 186 to 187", obtained by Nelson from ascaridol has the formula C10H18O6 and that it is identical with a-dihydroxy-a-methyl-a-isopropyl-adipic acid. Wallach regards the formulas proposed by Nelson for ascaridol and ascaridolglycol as of little probability.
(I) Ascaridol according to Wallach. (11) 1,4-Terpin.
In order to ascertain the approximate amount of ascaridol present, Schimmel & Co.1) fractionated several oils that showed great variation in their physical constants. They obtained the following results: Normal American oil (d15o 0,9708) contained 62 to 65 p.c. of ascaridol and about 22 p.c. of cymene. A light oil (d15o 0,9426) contained but 45 to 50 p.c. of ascaridol and as much as about 38 p.c. of hydrocarbons. The high percentage of the latter accounts for its lack of solubility. An oil distilled by Schimmel & Co. contained 65 to 70 p.c. ascaridol and only about 20 p.c. hydrocarbons (cymene). In spite of the high percentage of the readily soluble principal constituent, this oil was sparingly soluble. An explanation for this anomaly was found in the large percentage of resinous residue that remained upon fractionation. In the case of this oil it amounted to 12,5 p.c, whereas in the oils just mentioned it amounted to only 4 p.c. and 6 p.c, respectively.
An observation, made during the oxidation of an ascaridol obtained by fractional distillation, seems to indicate the presence of safrol in American wormseed oil. The acids obtained upon treatment with permanganate (see above) yielded upon vacuum distillation a residue from which homopiperonylic acid (m. p. 127 to 128°) and piperonylic acid (m.p. 226 to 228°) could be obtained.
l) Report of Schimmel & Co. April 1908, 118.
Physiological action. In North America the American worm-seed oil is used very successfully as anthelmintic. According to H. Bruning1) ascaridae become lifeless after a short time in water, sodium chloride solution, or Ringer's solution of 38° C. to which some ascaridol or wormseed oil has been added, whereas in the control experiments the animals continued to move about for a long period. Even in solution of 1:5000 a paralysing, narcotizing action results within two hours. However, when the animals are transferred to a non-poisonous solution, they regain their mobility after a short time. Basing his conclusions on extended experimental studies and on a series of successful treatments on patients afflicted with worms, Bruning regards American wormseed oil as an anthelmintic equal, if not superior, in its effect to santonin. Varying with the age, the dose for children is from 8 to 15 drops, mixed with sugar water three times during the forenoon. If a medicine dropper be used 0,5 to 1,0 g. of pure oil is taken. This is followed by a cathartic, such as castor oil, Pulv. Curettes, or a similar preparation, at intervals of an hour.
According to W. Salant2) American wormseed oil produces temporary excitement, then general paralysis and coma. If a dose of 0,2 cc. per kg. body weight be administered into the stomach, death results after 24 to 48 hours. The active constituent of the oil, the ascaridol, is twice as active. It lowers the blood pressure.