THE CHEMISTRY OF ESSENTIAL OILS

I. THE CHEMISTRY OF ESSENTIAL OILS

Early in his history, man evinced a great deal of interest in the preservation of the fragrant exhalation of plants, and those who were later to be called chemists occupied themselves with separating the essence of the perishable plants. It was probably observed that heating of the plant caused the odoriferous principle to evaporate and that upon condensation and subsequent cooling, droplets united and formed a liquid consisting of two layers water and oil. While, in such primitive experiments, the water from the plant is used to carry over the oils, additional water or steam was later introduced in "stills" to obtain better yields and quality.

In early work, therefore, we find the term "essential oil" or "ethereal oil" defined as the volatile oil obtained by the steam distillation of plants. With such a definition, it is clearly intended to make a distinction between the fatty oils and the oils which are easily volatile. Their volatility and plant origin are the characteristic properties of these oils, and it is for thi reason more satisfactory to include in our definition volatile plant oils obtained by other means than by direct steam distillation. 1 - 2 Bitter almond and mustard oil, obtained by enzymatic action, followed by steam distillation; lemon and orange oil isolated by simple pressing, and certain volatile oils obtained by extraction are, therefore, included among the essential oils.

In the early stages of development of organic chemistry, the chemical investigation of oils was limited to the distillation of a great number of plants, and the oils which were obtained in this way were used to compose perfumes according to recipes, some of which are still used at the present time; e.g., the can de Cologne prepared in 1725 by Johann Maria Farina in Cologne.

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1 Thomas, "Athcrische Ole," in Klein, "Handbuch der Pflazenanalyse" Vol. Ill, 1 (1932), 454.

2 Rosenthaler, Pharm. Ada Helv. 10 (1944), 213.

Gradually with the advance of science came improvements in the methods of preparing the oils, and parallel with this development a better knowledge of the constituents of the oils was gained. It was found that the oils contain chiefly liquid and more or less volatile compounds of many classes of organic substances. Thus, we find acyclic and isocyclic hydrocarbons and their oxygenated derivatives. Some of the compounds contain nitrogen and sulfur. Although a list of all the known oil components would include a variety of chemically unrelated compounds, it is possible to classify a large number of these into four main groups, which are characteristic of the majority of the essential oils, i.e. :

1. Terpenes, related to isoprene or isopentene;

2. Straight-chain compounds, not containing any side branches;

3. Benzene derivatives ;

4. Miscellaneous.

Representatives of this last group are incidental and often rather specific for a few species (or genera) and they contain compounds other than those belonging to the three first groups (Fig. 2.1).

FIG. 2.1. Natural occurring volatile Sulfur and Nitrogen containing compounds.

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³ Mannich and Fresenius, Arch. Pharm. 274 (1936), 461.

For example, the mustard oils, containing allyl isothiocyanate, are found in the family of the Cruciferae; allyl sulfides in the oil of garlic. The oil from Ferula asafoetida L., belonging to the family of the Umbelliferae, gained reputation from its active component, secondary butyl propenyl disulfide, competitor of the odoriferous principles of the skunk, primary n-butyl mercaptan and dicrotyl sulfide.⁴ The more pleasant smelling orange blossom and jasmine perfume betrays the presence of small amounts of anthranilates and indole, both compounds related to the amino acid, tryptophane.

Although it is possible to list a considerable number of such singular cases, the most characteristic group present in many essential oils contains hydrocarbons, as a rule of the formula C₁₀H₁₆ and a group of oxygen-containing compounds with the empirical formula H₁₀O₁₆ and C₁₀H₁₈O. The classical book of Wallach indicates the names of these two types of compounds in its title "Terpene und Campher." The English word "terpene" and the German "Terpen" are derived from the German word "Terpentin," English "turpentine" and French "trebenthine." The name "Terpen" is commonly attributed to Klkule*, who is said to have introduced it as a generic term for hydrocarbons CioHie to take the place of such words as Terebene, Camphene, etc.^5,6 The name "camphor" formerly was used to indicate the crystalline oxygen compounds, such as thyme camphor (C. Neumann, 1719) and peppermint camphor (Gaubius, 1770) ; these are now known respectively as thymol and menthol. The name "camphor" is at present limited to a specific compound and its more general meaning, covering the oxygenated derivatives, has been taken over by the term "terpene." With an increase in our knowledge, this broadened definition in its turn became too narrow and had to be modified to cover new and more distantly related compounds. Not all terpenes are represented by the formula C₅H₈ ; there exist compounds which contain less hydrogen, still others which are more saturated. We also find terpenes, like santene (C₉H₁₄), which have only 9 carbon atoms. The close resemblance to and probable connection with the C₁₀ compounds through the terpene acid, santalic acid, make it impractical to omit such a compound from the terpene literature.

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⁴Stevens, J. Am. Chem. Soc. 67 (1945), 407.

⁵Gildemeister and Hoffmann, "Die Atherischen Ole," 2cl Ed., Vol. I (1910), 90.

⁶ Kremers and collaborators, "Phytochemical Terminology," J. Ain. Pharm. Assocn. 22 (1033), 227.

At the present time, therefore, we use the term terpene both in its broadest sense to designate all compounds which have a distinct architectural and chemical relation to the simple C₅H₈ molecule, and in a more restricted sense to designate compounds with 10 carbon atoms derived from C₁₀H₁₆ . When confusion with the general designation is possible, members of the C₁₀ group are often referred to as monoterpencs. Compounds having a more distant connection with the terpenes, but still containing features which link them with terpene structures, are sometimes called terpenoids or iso-prenoids in analogy with the term steroids, which includes not only sterols, but many more remotely connected relatives. ^7,8,9,10

Characteristic for many of these oil constituents is their instability an the ease with which intramolecular rearrangements occur. These propertie have been a great hindrance to the study of these compounds. Anothe drawback in the analysis of these oils is that most of the compounds ar liquids so that thorough fractionation is necessary to separate the constituents which boil within a restricted temperature range. Since in the early stages of research it was difficult to define sharply the isolated fraction, a great number of terpenes were named after the plant from which they were obtained.

Order was brought into this chaos by Wallach, who saw clearly that the first task in the study of the oils was the identification of the terpenes with the help of crystalline derivatives, this being the only practical way we possess at present to identify chemical substances with certainty. Based on Wallach's investigation, about 500 compounds have since been isolated and characterized in the essential oils. After a general idea was obtained of the great number of distinct chemical compounds in oils, Wallach started the second part of his working program, i.e., studies of the relationship between the terpenes and the camphors. By reason of their fundamental nature and the clear presentation of the problems they involved, these studies provided great stimulus not only to his contemporaries Semmler, Harries, Tilden and others but had a pronounced influence on the development of chemistry as a whole. The establishment of the constitution and the relationship of the terpenes revealed a certain regularity in their structures. As early as 1869 Berthelot had discovered how the hydrocarbons C₁₀H₁₆, C₁₅H₂₄, and C₂₀H₃₂ are related to the hydrocarbon isoprene (C₆H₈) isolated by Williams^11,12 a few years before. However, it was through the combined work of the aforementioned investigators that this hypothesis was established on a firm basis.

The compounds which we find in the monoterpene series can be figuratively divided into 2 isopentene chains; such a hypothetical combination gives substances of the empirical formula C₁₀H₁₆ . If three of these isopentene units can be recognized in the molecule, the name sesquiterpene is given. In the course of time there have been added diterpenes derived from C₂₀H₃₂, triterpenes, C₃₀H₄₈, and tetraterpenes, C₄₀H₆₄ and finally polyterpenes with an indefinitely large number of these units (Fig. 2.2).

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7 Kremers, ibid.

8 Gildemeister and Hoffmann, "Die Xtherischen Ole," 3d Ed., Vol. I, 15.

9 Ruzicka, Ann. Review Biochem. I (1932), 581.

10 Fieser and Fieser, "Organic Chemistry," Heath Co. (1944).

11 Kremers and collaborators, "Phytochemical Terminology” J. Am. Pharm. Assocn. 22 (1933), 227.

12 Williams, Jahresber. (1860), 495.

A saturated acyclic hydrocarbon with 10 carbon atoms would have the formula C₁₀H₂₂, possessing 6 II atoms more than a compound C₁₀H₁₆. This lower hydrogen content may be caused by the occurrence of double bonds, by ring structure, or by both, giving rise to acyclic, monocyclic and bicyclic representatives, with 3, 2 and 1 double bond, respectively. We have, therefore, the following possibilities for a molecule with the formula (monoterpene) :

Acyclic.................... No ring        3 double bonds

Monocyclic ..............One ring        2 double bonds

Bicyclic ....................Two rings       1 double bond

Tricyclic ......................Three rings      No double bonds

All these structural variations of the same empirical formula are found in the constituents of volatile plant oils. A chemical shorthand, developed by terpene chemists, has been introduced to show more clearly the principal structural details. This greatly simplified way of writing formulas consists in assuming a carbon atom at a place where valency lines end, or form an angle. As many C's and H's as feasible are omitted and only double bonds and substituents, such as hydroxyl and amino groups, are written in full (Fig. 2.3). Others prefer to indicate all end groups such as methyl and methylene groups in full.

 FIG. 2.3. Abbreviated formulas of Terpenes.

As examples of the acyclic terpenes with 3 double bonds, we find ocimene and myrcene. In the frequently occurring acyclic alcohols geraniol and linalool, in the aldehydes citronellal and citral, and in dehydrogeranic acid we see several stages of oxidation and reduction of this type of terpene hydrocarbons (Fig. 2.4). Many of these compounds can be converted into

 FIG. 2.4. Oxidation Stages of Acyclic Terpenes.

each other with great ease. Geraniol, the chief constituent of rose and geranium oil, is easily converted into the monocyclic alcohol α-terpineol, the chief constituent of the oil of hyacinth, and into linalool, which as acetate constitutes the characteristic component of lavender oil.

Geraniols of variant origin have variant constants and odors, due to the presence of isomers. The double bond between carbon atoms 2 and 3 makes the existence of cis- and Jrans-isomers possible, and the relative ease of ring formation permits one to distinguish between these forms, which have been called nerol and geraniol according to their origin. The double bond near the terminal carbons is another source of isomerism. Thus geraniol, nerol and other compounds with similar structure, such as citronellol and rhodinol, and citronellal and rhodinal, consist of varying quantities of isomers containing the double bond, between either carbon atoms 7 and 8, or 6 and 7, resulting in a further source of variation in the constants of the oil constituents (Fig. 2.5).

 FIG. 2.5. Isomerism of Geraniol.

Most of these compounds easily form cyclic derivatives under the influence of acids, and the formulas are usually written intentionally in such a way as to indicate where the ring closure takes place. A saturated monocyclic terpene has the formula C₁₀H₂₀ and is called menthane. If the compound has the empirical formula C₁₀H₁₆ , there must be 2 double bonds, since the ring occurs in the place of one of the 3 double bonds present in aliphatic terpenes. Such hydrocarbons are called menthadienes, and the method of indicating the position of the double bond given by Baeyer makes use of the Greek capital letter A (delta), and an index number indicating the carbon atom from which the double bond starts. If the double bond is in the side chain, then it will be necessary to indicate toward which carbon atom the double bond goes. This number is placed in brackets behind the number of the first carbon atom, as is indicated in Fig. 2.6. ¹³

We find many representatives of this class of menthadienes among the terpene fractions in essential oils. For example, dipentene, formed by the

When the purified fractions are characterized by preparation of crystalline derivatives, and when these are compared by melting point and mixed melting point with the known derivatives, there remain always some fractions which cannot be characterized in this way. In, such cases, chemical degradations of the molecules have to be applied. The principle involved in these degradations consists of breaking up the molecule into smaller parts until the pieces have become so simple that they can be recognized. For this purpose, oxidation with ozone, potassium permanganate and chromium trioxide is often used. Sometimes several of these degradations may be necessary before the pieces obtained are small enough to be identified. On the basis of these degradations, a possible structure is postulated and attempts are made to confirm this structure by synthesis. This work has been carried out on about 500 constituents of essential oils. One-fifth of this number is made up of monoterpenes, and only a start has been made on the investigations of sesqui- and higher terpenes. In view of the greatly increased possibility of structural isomerism, every time 5 carbons are added to a molecule we may look forward to the addition to our present knowledge of a great number of the higher terpene homologues when a more extensive survey is made.