Ascaridole

α-Terpinene and ascaridole

Ascaridole was the first, and for a long time only, discovered naturally occurring organic peroxide. It was isolated from Chenopodium oil and named by Hüthig in 1908. He found that when heated to between 130° and 150 °C "there occurs, with sudden boiling in which the temperature momentarily rises to about 250°, a decomposition of an explosive character, occasionally accompanied by ignition. At the same time a very disagreeable skatol-like odour, difficult to define, is observed. In the course of the examination it was found that during the decomposition a gas is split off." He determined its chemical formula as C₁₀H₁₆O₂.^[2] Hüthig also noted the indifference of ascaridole to aldehydes, ketones or phenols that characterized it as non-alcohol. When reacted with sulfuric acid, or reduced with zinc powder and acetic acid, ascaridole formed cymene.^[3][4] A detailed study was done by E. K. Nelson in 1911. He described the decomposition as apparently a molecular rearrangement, and found that it reacts with sulfuric, hydrochloric, nitric, or phosphoric acids. Nelson showed that the new substance contained neither a hydroxyl nor a carbonyl group and that upon reduction with iron(II) sulfate it formed a glycol, now known as ascaridole glycol, C₁₀H₁₈O₃. The glycol is more stable than ascaridole and has a higher melting point of about 64 °C, boiling point of 272 °C, and density of 1.098 g/cm³. Nelson also predicted the chemical structure of ascaridole which was almost correct, but had the peroxide bridge not along the molecular axis, but between the other, off-axis carbon atoms.^[5] This structure was corrected by Otto Wallach in 1912.^[6][7][8]

The first laboratory synthesis was demonstrated in 1944 by Günther Schenck and Karl Ziegler and might be regarded as mimicking the natural production of ascaridole. The process starts from α-terpinene which reacts with oxygen under the influence of chlorophyll and light. Under these conditions singlet oxygen is generated which reacts in a Diels–Alder reaction with the diene system in the terpinene.^[8][9][10] Since 1945, this reaction has been adopted into the industry for large-scale production of ascaridole in Germany. It was then used as an inexpensive drug against intestinal worms.^[11]

Ascaridole is a colorless liquid that is soluble in most organic solvents. It is toxic and has a pungent, unpleasant smell and taste. Like other pure, low molecular weight organic peroxides, it is unstable and prone to violent decomposition when heated to a temperature above 130 °C or treated with organic acids. When heated, it emits fumes which are poisonous and possibly carcinogenic.^[1][6][12] Ascaridole (organic peroxide) is forbidden to be shipped as listed in the US Department of Transportation Hazardous Materials Table 49 CFR 172.101.^[13]

The specific flavor of the Chilean tree boldo (Peumus boldus) primarily originates from ascaridole. Ascaridole is also a major component of epazote (or Mexican tea, Dysphania ambrosioides, formerly Chenopodium ambrosioides)^[14][15] where it typically constitutes between 16 and 70% of the plant's essential oil.^[16][17] The content of ascaridole in the plant depends on cultivation and is maximal when the nitrogen to phosphorus ratio in the soil is about 1:4. It also changes through the year peaking around the time when the plant seeds become mature.^[18]