Phytochemistry I Lecture 4 PDF

Phytochemistry I Lecture 4 V.O. - Oxygenated compounds Alcohols, Phenols, Aldehydes, Ketones, Esters, Oxides, Peroxides 1 Alcohols in volatile oils 2  Alcohols in volatile oils ...

Phytochemistry I Lecture 4 V.O. - Oxygenated compounds Alcohols, Phenols, Aldehydes, Ketones, Esters, Oxides, Peroxides 1 Alcohols in volatile oils 2  Alcohols in volatile oils  Usually present together with their esters.  Mostly terpenoid or aromatic in nature. Classification 1. According to the type of alcoholic group into:  Primary (RCH2OH)  Secondary (R2CHOH)  Tertiary (R3COH) 2. According to the carbon skeleton into:  Aliphatic (Acyclic)  Alicyclic  Aromatic 3  b) according to their carbon skeleton: Aliphatic alcohols Alicyclic terpenoid alcohols Aromatic alcohols Saturated -Methyl alc. Benzyl alc. -Ethyl alc. Phenyl ethyl Monoterpenoid Sesquiterpenoid Unsaturated Monocyclic -Menthol Monocyclic Monoterpenoid -Bisabolol -Terpineol -Citronellol 1ry -Geraniol -Nerol -Farnesol Bicyclic Tricyclic -Borneol -Santalol 3ry -Linalool Sesquiterpenoid 3ry -Nerolidol 4  Alcohols in volatile oils - Examples ▪ Saturated: Methyl & ethyl alcohol Aliphatic alcohols ▪ Unsaturated: Acyclic monoterpenoids: Citronellol, nerol (Acyclic alcohols) geraniol & linalol Acyclic sesquiterpenoids: Nerolidol (in oil of neroli, 3ry alc.) Alicyclic Terpenoid ▪ Monoterpenoids: alcohols Monocyclic: Menthol (2ry alc.), Terpineol (3ry alc.) Bicyclic: Borneol & isoborneol (2ry alc.) ▪ Sesquiterpenoids: Tricyclic: Santalol (1ry alc.) Aromatic alcohols Benzyl alcohol, phenyl ethyl alcohol & cinnamyl alcohol 5  Alcohols in volatile oils - Isolation Fractional distillation By one of the following methods: 1. Fractional distillation under reduced pressure 2. Chromatography CC, HPLC, GLC, ……… 3. Counter current extraction 4. Formation of crystalline derivatives (Derivatization) 6  Alcohols in volatile oils - Reactions Isolation 1. Derivatization of terpenoid alcohols Identification Determination A. Reaction similar to terpenoid hydrocarbons: Addition reactions due to unsaturation e.g. hydration, hydrogenation, halogenation,…. B. Reactions due to the presence of functional alcoholic OH groups. - Reactivity is dependent on the type of alcoholic group (1ry, 2ry or 3ry).  Derivatives with definite & sharp m.p. (identification).  Reaction when complete is used for determination (quantitative). 7  Alcohols in volatile oils - Reactions 2. Dehydration reaction ▪ Removal of elements of water → Unsaturated hydrocarbons ▪ Used for 3ry alcohols (the most reactive) + catalyst e.g. acids, acid anhydrides or ZnCl2, gentle heat → unsaturated hydrocarbons ▪ 2ry alcohol needs more drastic conditions ▪ 1ry alcohol resist dehydration Exception: Geraniol , 1ry alcohol readily dehydrates. 3. Calcium chloride additive compounds Certain 1ry alcohols (R-CH2OH) + anhyd. CaCl2 in absolute ether or benzene → crystalline derivatives → regeneration by water → original alcohol (e.g. Geraniol & Benzyl alcohol). Used to separate geraniol from nerol and citronellol 8  Alcohols in volatile oils - Reactions 4. Esterification  The speed of the reaction differs from 1ry to 2ry to 3ry alcohols according to the reagent  Most common esters are the borates, acid phthalates & urethans (or carbamates). 1. Boric acid esters (borates) 1ry & 2ry alcohols react easily → borates, while 3ry alcohols do not react. The reaction is used mainly to separate 1ry & 2ry from 3ry alcohols. 2. Benzoates Only 1ry & 2ry alcohols react → benzoates. 9  Alcohols in volatile oils - Reactions 3. Phthalic acid esters (Phthalates) 1ry alcohols react under less drastic conditions than 2ry alcohols, 3ry alcohols do not react. Conditions: ▪ 1ry alc. + phthalic anhydride + D 100 o C (water bath) + dil. benzene → acid phthalates esters + dil. aqueous alkalis → water-soluble salts. ▪ 2ry alc. → higher temperature (120-130 o C). ▪ 3ry alc. → do not react ▪ Acid phthalates can be extracted with NaHCO3 & hydrolyzed with alc. alkalis (saponification, regeneration) → alcohol. ▪ Used for isolation, purification & identification of 1ry & 2ry alc. ▪ Quantitative for 1ry alcohols (determination). ▪ Used for separation of 1ry from 2ry & 3ry alc. O O O Alcoholic O Heat OR Na HCO3 ROH + O OR KOH OK ONa ROH OH ONa + Alcohol O O Saponification O O Phthalic Acid phthalate Sodium phthalate Sodium Alcohol anhydride monoester monoester Potassium phthalate 10  Alcohols in volatile oils - Reactions 4. Carbamic acid esters (carbamates or urethanes) ▪ Esters of carbamic acid (NH2-COOH), generally formed with 1ry & 2ry alcohols. ▪ 3ry alcohols are rapidly dehydrated under the reaction conditions. ▪ Esters of N-substituted carbamic acid are known as N-substituted urethans. H N=C=O N COOR NH2 ROH + COOH Carbamic acid Alcohol Phenyl isocyanate Phenyl urethan Geraniol & nerol can be identified through formation of diphenyl urethan derivatives, which have different m.p. Geraniol derivative, m.p. 82.2 oC Nerol derivative, m.p. 52 - 53 oC 11 12  I. Acyclic Monoterpenoid Alcohols – 1. Citronellol Source 6 * d-form: oil of citronella. 8 CH2OH CH2OH l-form : in oil of geranium (35 - 40 %) & oil of rose (20 - 35 %) 2 −Citronellol -Citronellol Properties Terpinolene form Limonene form 1. Optically active liquid 2. With rose-like odor 3. Stable, its stability is due to the presence of only one double bond in the molecule (≠ geraniol & nerol, 2 double bonds). Uses In perfume, cosmetic & soap industries to impart a rose-like odor. As substitute for rose oil. Insect repellent. 13 I. Acyclic Monoterpenoid Alcohols – 2. Geraniol & Nerol Z Z E E α-Nerol α-Geraniol β -Nerol β-Geraniol (Z isomer) (E isomer) (Z isomer) (E isomer) Terpinolene form Limonene form Source Geraniol & its esters geranium (40 - 50 %) Nerol & its esters Oils of neroli *(generally occur with geraniol & its esters) 14 I. Acyclic Monoterpenoid Alcohols – 2. Geraniol & Nerol Properties - Optically inactive (c.f. citronellol & linalool) - liquids with rose-like odor (similar to citronellol) - reactive (2 double bonds → degradation) hot mineral acids cold, dil mineral acids + (dehydration) (hydration) Dipentene Geraniol Terpin hydrate Terpineol 15  Isolation of geraniol -Add anhydrous CaCl2 to the oil CaCl2-adduct (solid in nature, like cake) -Extract with organic solvent (ether) remove constituents other than geraniol -Wash adduct with warm water regenerate geraniol -Steam distill to collect geraniol Anhydrous CaCl2 Geraniol Geraniol.CaCl2 warm water 16 I. Acyclic Monoterpenoid Alcohols – 2. Geraniol & Nerol Separation of geraniol from nerol & other alcohols Geraniol is usually present in oils together with nerol & citronellol, it can be separated by formation of : 1- Separation of Geraniol from Nerol + Anhydrous CaCl2 Geraniol forms adduct (≠ Nerol easily oxidized to the aldehyde, Citral) Does not form a complex with anhydrous CaCl2 2- Separation of Geraniol from Citronellol As acid phthalate silver salts & Fractional crystallization of the derivatives produced. 17 I. Acyclic Monoterpenoid Alcohols – 2. Geraniol & Nerol Identification Geraniol & Nerol can be identified from each other through the formation of their diphenyl urethan derivatives, which have different melting points. 1. Geraniol derivative, m.p. 82.2 o C 2. Nerol derivative, m.p. 52 - 53 o C Uses 1. Geraniol & its esters are used in perfume, cosmetic & soap industries for compounding rose scents. 2. As substitute for rose oil. 18  I. Acyclic Monoterpenoid Alcohols – 3. Linalol (Linalool) Source HO * d-form: oils of coriander, nutmeg & sweet orange l-form: oils of lavender & bergamot Linalyl acetate: oils of lavender & bergamot Properties (+) Linalol -Optically active liquid. 3ry alc -Lavender-like odor. Lavender -Highly unstable, (double bonds, 3ry alc. gp.) -Easily dehydrated to monoterpene H.C. + traces of acid Geraniol (1ry alc) + glacial acetic acid Geraniol, Nerol, Terpeniol Coriander fruit + cold dil. H2SO4 Terpin hydrate + Chromic acid (oxidation) Citral 19  I. Acyclic Monoterpenoid Alcohols – 3. Linalol (Linalool) Uses ♣ Linalol & its acetate ester are widely used in perfume, cosmetics, soap & flavor industries to impart a lavender-like odor. ♣ As a substitute for lavender oil ♣ Antirheumatic. 20 21  II. A. Monocyclic monoterpenoid alcohols - Menthol Source *  Most common isomer is l-menthol. *  It is present in oil of peppermint (Mentha * piperita, Labiatae or Lamiaceae) 50 - 65 %. Menthol  in Japanese mint oil (Mentha arvensis) up to 75 -90 %. Structure Mentha arvensis Menthol has 3 centers of asymmetry, it is optically active and exists as 8 optically active isomers (23 = 8). Mentha piperita 22  II. A. Monocyclic monoterpenoid alcohols - Menthol Isolation from Japanese mint oil (75 - 90 %) by successive cooling & filtration to collect the deposited crystals of menthol Semi-synthesis Semi-synthetic dl-menthol is obtained by catalytic reduction of thymol or pulegone + H2 or OH O OH Cu chromite Thymol Pulegone Menthol 23  Menthol - Isolation Peppermint oil cooling at 15 oC, centrifuge Menthol-crystals Liquid oil cooling at 5 oC, centrifuge Menthol-crystals Liquid oil cooling at -10 oC, centrifuge Menthol-crystals Liquid oil (Menthone + Menthol) NH2OH.HCl Oxime + Menthol ether dil.H2SO4 ethereal layer aqueous layer (Menthol) (Oxime) 24 Menthol - Reaction 25  II. A. Monocyclic monoterpenoid alcohols - Menthol Properties  Needle crystals.  Powerful peppermint-like odor & a cooling taste. Tests for identification Crystals in conc H2SO4 + 1drop Vanillin/H2SO4 → orange-yellow color + few drops of H2O → violet color. Pharmacological action & uses Local action: antipruritic (anti-itching), counter irritant, mild local anesthetic & antiseptic. Systemic action: heart depressant , carminative & gastric sedative. Flavoring agent in mouthwashes & toothpastes, in candies, chewing gums & cigarettes. 26 27 II. A. Monocyclic monoterpenoid alcohols – 2. -Terpineol 28 ▪ Terpeniol is considered as a key substance in semi-synthesis of several hydrocarbons & certain oxygenated monoterpenoids. 29 Terpineols 30 31  II. B. Bicyclic monoterpenoid alcohols - Borneol & isoborneol Source * * OH * * H Borneol occurs as d- or l- isomer, free or as H OH ester mainly the acetate. Borneol Isoborneol d-Borneol (or Borneo camphor) with camphor-like odor: oils of Dryobalanops camphora & D. oblongifolia l- Borneol: oils of citronella, coriander, valarian root & Pinus pallustris. Bornyl acetate is the main constituent of pine needle oils (up to 40 %). Isoborneol is not a natural constituent (an artifact during preparation of oils rich in borneol) unstable to dehydrating agents (e.g. ZnCl2/benzene) 32  II. B. Bicyclic monoterpenoid alcohols - Borneol & isoborneol Isolation  Distilled pine needle oil is saponified (hydrolysis of esters) → fractional distillation (removal of hydrocarbons).  Fraction boiling between 205 - 215 o C cooled → crystals of borneol.  Remaining borneol isolated as acid phthalate. Semi-synthesis  From  -pinene  From camphor: By reduction in presence of catalyst Cl HCl gas Isomerization Cl OH KOH Na amalgum/alc. Molecular (reduction) -10oC Rearangement -Pinene Pinene Bornyl Borneol Camphor hydrochloride chloride 33 II. B. Bicyclic monoterpenoid alcohols - Borneol & isoborneol 34 35 36 III. Monocyclic sesquiterpenoid alcohols - α-Bisabolol 37  IV. Tricyclic sesquiterpenoid alcohols - α-Santalol Source 1ry alc Main constituent of East-Indian sandal wood oil Isolation Sandal wood oil is first treated with KOH (to remove phenolic constituents), then fractional CH2OH distillation → α-santalol −Santalol Properties Tricyclic sesquiterpenoid 1ry alcohol Viscid liquid, yellow in color odor of sandalwood. Uses Medicinal & odoriferous values of sandalwood are due to santalol content of the volatile oil. 38  V. Aromatic alcohols Aromatic alcohols common in volatile oils are benzyl, phenyl ethyl & cinnamyl alcohols. CH2OH CH2CH2OH CH=CHCH2OH 1. Benzyl alcohol Benzyl alcohol Phenyl ethyl alcohol Cinnamyl alcohol Source Benzyl alcohol occurs mainly in the form of its esters.  Benzyl benzoate & benzyl cinnamate: balsam Peru, balsam Tolu & storax  Benzyl acetate: oils of jasmine Isolation 1. By fractional distillation of the saponified oils. 2. By formation of a complex with anhydrous CaCl2 in Jasmine ether & regeneration by treatment with warm water. 39  V. Aromatic alcohols - 1. Benzyl alcohol Uses Benzyl alcohol, mainly as its aliphatic esters, is widely used in perfume & cosmetic industries to give synthetic flowers odor e.g. jasmine, gardenia, & tuberose. As diluent & fixative (due to its low volatility) in perfume mixtures. As antimicrobial pharmaceutical aid (similar to phenols). ▪ On bad storage (exposure to air & light) → bitter almond odor (benzaldehyde) → crystalline deposit (benzoic acid). 40  V. Aromatic alcohols - 2. Phenyl ethyl alcohol Source Oils of rose, neroli, geranium & hyacinth Properties & Uses Liquid with a rose-like odor. Antimicrobial pharmaceutical aid, preservative In flavor & perfume industries, especially those of rose-scented perfumes. CH2CH2OH Rose Hyacinth 41 42