2.6.5.5 Phenol Volatile Oils
The important drugs containing phenol volatile oils are, namely: Clove oil, Myrcia oil (Bay oil), Organum oil, Pinetar, Thyme etc., In fact, they essentially owe their value in the pharmaceutical domain almost exclusively by virtue of their antiseptic and germicidal properties of their phenolic constituents. A good many of them are employed as popular flavouring agents, for instance: oil of anise, clove and sassafras.2.6.5.5.1 General Methods of Isolation
Mostly phenols are weak acids. Hence, they react with dilute alkali solutions (3-5% w/v) to result into the formation of corresponding water-soluble salts known as ‘phenolates’. This specific characteristic property usually offers, a convenient method for carrying out the separation of phenolic components from the non-phenolic ones. To affect the separation, therefore, the volatile oils or fractions are subjected to treatment with dilute alkaline solutions with vigorous shaking. Once the two layers get separated, the water-soluble salts are decomposed by acidification carefully and the phenols thus generated (or liberated) are isolated either by means of steam-distillation or by extraction with ether.Note
1. Thymol and carvacrol may be steam-distilled from alkaline solution without previous acidification.
2. Several phenols may be isolated by chilling the oil as such or its fraction to a very low temperature (–20 to –30°C) whereby these compounds normally separate in crystalline form.
2.6.5.5.2 General Properties of Terpene Phenols
There are several characteristic features of terpene phenols which not only help them in their separation but also aid in their identification as stated below:1. Bromine Reaction: Phenols react with bromine evolving the corresponding HBr. The resulting bromides are usually crystalline in nature and sparingly water-soluble. Hence, they may be separated easily and identified accordingly.
2. Reaction with Ferric Chloride: Phenols react with dilute aqueous solutions of ferric chloride (FeCl3) (0.1-0.2% w/v) to give rise to intense coloured reactions, which attributes to the specific colour-tests.
3. Formation of Phthaleins: Several phenols react with phthalic anhydride to form their
corresponding phthaleins.
4. Most phenols react with specific reagents, such as: acetic anhydride, benzoyl chloride, phenyl isocyanate and p-nitrobenzoyl chloride to give characteristic reaction products that also help in their identifications.
2.6.5.5.3 Classification The terpene phenols
are classified into the following categories, namely:(i) Monohydric phenols and
(ii) Dihydric phenols.
The above categories of phenols shall be discussed briefly as under:
2.6.5.5.3.1 Monohydric Phenols
The typical examples of monohydric phenols are: carvacrol, eugenol, thymol.
The typical examples of monohydric phenols are: carvacrol, eugenol, thymol.
A. Carvacrol
Chemical Structure 2-Methyl-5-(1-methylethyl)-phenol.
Occurrence It occurs in the essential oil origanum (Origanum vulgare Linn., Family: Labiatae); oil of thyme (Thymus serphyllum Linn., and T. vulgaris Linn., Family: Labiatae); oil of marjoram and oil of summer savory.
Characteristic Features It is a liquid oil having strong thymol odour. Its physical properties are as follows: d2040.976; bp760 237-238°C; mp ~ °C; n20D 1.52295.
It is practically insoluble in water and freely soluble in alcohol and ether.
Uses
1. It is mostly employed as a disinfectant.
2. It is also used as an anthelmintic (Nematodes).
B. Eugenol Please see section 5.2.6.1.4.3 in this chapter.
C. Thymol Please see section 5.2.1.4 in this chapter.
2.6.5.5.3.2 Dihydric Phenols The various dihydric phenols found in natural products are namely:
Catechin (catechol). A few of these constituents shall be dealt with here under:
A. Catechin (Catechol)
Chemical Structure (2R-trans)-2-(3, 4-Dihydroxyphenyl)-3, 4-dihydro-4H-1-benzopyran-3, 5, 7-triol.
Occurrence It is a flavonoid found primarily in higher woody plants as (–)-catechin along with (–)-epicatechin (cis-form). It is also found in catechu (gambir and acacia), mahogany wood etc. Besides, it occurs in a variety of medicinal-plants, such as: Argimonia eupatoria L., (Rosaceae)-agrimony; Areca catechu L., (Arecaceae)-areca-nut, betel-nut palm; Camellia sinensis (L.) Kuntze (Theaceae)-tea; Catha edulis Vahl (Celastaceae)-khat; Cola acuminata (Beauv.) Schott & Endl. (Sterculaceae)-kola nuts, cola, guru; Caratadegus oxyacantha L. (Rosaceae)-hawthorn; Ephedra gerardiana Wall. ex Stapf (Ephedraceae)-Paskistani ephedra; Eucalyptus globulus Labill. (Myrataceae)-eucalypt, tasmanium bluegum; Leonurus cardiaca L., (Lamiaceae)-motherwort; Malus sylvestris Mill., (Rosaceae)-apple; Paullinia cupana Kunth. ex H.B.K. (Sapindaceae)-guarana, ubano, Brazilian cocoa; Polygonum aviculare L., (Polygunaceae)-prostrate knotweed; Rheum officanaleBail. (Polygonaceae)-Chinese rhubarb, Canton rhubarb, Shensi rhubarb; Santolina chamaecyparissus L. (Asteraceae)-Lavendar-cotton; Solidago virgaureae L. (Asteraceae)-European goldenrod, woundwort; Uncaria gambir (Hunter) Roxo. (Rubiaceae)-gombir, pale catechu; Vanilla planifolia Andr. (Orchidaceae)-vanilla.
Isolation The areca nut or kola nut is cut into small chips mechanically and filled into the extractors. The steam is passed through the drug profusely to affect maximum extraction. The crude extract is filtered and concentrated under vacuum. The concentrated extract is chilled in deep-freezer when catechin separates as its hydrated product (mp: 93-96°C) and its anhydrous product (mp: 175-177°C).
Characteristic Features Its needles obtained from water and acetic acid give rise to its hydrate form having m.p. 93-96°C, whereas its anhydrous form registers mp 175–177°C, and [α]18D+ 16° to + 18.4°. The physical parameters of l-form and dl-form are stated below.
Note Catechin is called catechol (flaran) to distinguish it from catechol (pyrocatechol q.v).
Identification
1. Catechin on being treated with HCl yields phluroglucinol, that burns along with lignin to produce purple or magnata colour. The tannin extract is taken on the tip of a match-stick, dipped in HCl and burnt in the blue-flame of the Bunsen-burner.
2. It reacts with vanillin and HCl to produce a pink or red colour.
Uses
1. It is used as an antidiarrheal agent.
2. It is also employed for dycing and tanning.
B. Protocatechuic Acid
Chemical Structure 3,4-Dihydroxybenzoic acid.
Occurrence It is found in the dried fruit of Illicium verum Hook. f. (Magnoliaceae)-star anise, Chinese anise; in the leaves and seeds of Perilla frutescens (L.) Britt. (Lamiaceae)-beef-steak plant, perilla, wild coleus; and in the timbers of Tabebuia Spp. (Bignoniaceae)-Pao D’Arco. However, minute amounts are found in wheat grains and also in wheat seedlings.
Characteristic Features It is white to brownish crystalline powder. It undergoes discolouration on exposure to air. Its mp ~ 200°C and d 1.54. It is soluble in 50 parts of water and freely soluble in ether and alcohol.
