Phenols and Phenolic ethers -...
Transcript of Phenols and Phenolic ethers -...
Importance• Phenols are very important antiseptic and germicidal agents
e.g. thymol, eugenol, …etc
• Most phenols & phenol ethers have powerful aromatic odour and flavour e.g. oil of clove & oil of anise
Isolation:
Phenols and Phenolic ethers
1. Fractional distillation
2. GCMS and HPLC
3. Fractional crystallization by cooling (for cryst. phenols)
4. Formation of phenolates (= phenates) with alkali which is water soluble.
• N.B.Phenolic ethers are neutral compounds and do not react with alkalis but generate phenols on heating with HI or HBr.
Separation of phenols based on their acidic property (Formation of phenolates)
• Phenols are weak acids.
• They are acidic enough to formwith dilute alkali watersoluble salts (phenolates)
• This property is used to separate phenols fromnon-phenolic constituents
Tests for identity• Phenolics give highly coloured compounds with FeCl3• Phenolics form a crystalline bromides with Br2 by substitution
reaction.• Phenols can be esterified with acid anhydrides, phenyl
isocyanate, benzoyl chloride or p-nitrobenzoyl chloride. (Like3ry alc., phenols are difficult to esterify so esterification requires3ry alc., phenols are difficult to esterify so esterification requires
the presence of an organic base such as pyridine.)
Estimation of Phenols•Phenol form water soluble salts with alkalies (using cassia flask).•Specific color reaction with specific reagents.•GC-MS and HPLC
Cassia flask method:Principle:Phenol formwater soluble salts with alkalis
Method: (using cassia flask).
• In a cassia flask, put known volume of oil.
• Add aq. KOHsolution and mix
• Phenol forms phenolate soluble salt in water and the nonphenolic part separatesas oily layer which can bephenolic part separatesas oily layer which can bemeasured in the graduated neck of cassia flask.
• N.B. KOH is preferred than NaOH because the
potassium salts of many phenols are more soluble thanthe corresponding sodium salts.
Monohydric phenol
• In oil of thyme family Labiatae• Colorless crystals• Aromatic thyme-like odor, pungent
taste
1-Thymol (3-hydroxy p-cymene)
• Isolated by: � By cooling the oil, thymol crystallizes.
� By fractional distillation.
� By 5% KOH → Phenolate→ acid treatment → phenol → steam distillation or extract with ether.
OH
Thymol
Synthesis1- From menthone:
O
Br2
Quinoline OH
2- From piperitone:
O
FeCl3
OH
3- From m-Cresol:
OH
+ CH3CHOHCH3
isopropyl alc OH
Identification & uses• Derivatization to phenylurethane and determination of
the melting points m.p. 106-107 ºC • Color reactions:
�Thymol/gl. Acetic acid + dps H2SO4 + one dp HNO3deep bluish green color
�Add few crystals of thymol to 3 ml NaOHand heat a pale red color is produced. Shake with 2 ml CHC13 to get reddish-color is produced. Shake with 2 ml CHC13 to get reddish-violet color in the organic layer
�Dissolving thymol in conc. H2SO4 gives violet color due toformation of thymol sulfonic acid.
Uses:– Local anesthetic, Antifungal, Anthelmentic– Mouthwashes, oral preparations, Antiseptic– Hepatoprotective, Antioxidant, free radical scavenger– Preparation of synthetic menthol, Immunostimulant
• obtained from the oil Thymus capitatusand other species of the family labiatae
2- Carvacrol:
OH
Carvacrol�Carvacrol preparation and chemicalproperties are similar to those of thymol with fewdifferences.�When carvacrol or thymol dissolved in conc. H2SO4,diluted and oxidized with KMnO , K CrO or Manganesediluted and oxidized with KMnO4, K2CrO4 or Manganesedioxide a yellow plates of thymoquine are produced .�Carvacrol and thymol give green color with FeCl3.�Thymoquine possesses hepatoprotctive activitycomparable with Silymarin and inhibits leucotrienes andthromboxane synthesis which could help in treatment ofcough.
Dihydric phenols and phenolic ethers
• Oil of clove, cinnamon Fam. Myrtaceae, Lauraceae
• Yellow oil, clove odor, burning spicy taste• Isolated by by shaking with 5% KOH,
separation of the non-phenolic part and
OH
OCH3
separation of the non-phenolic part and addition of dil. acid to the phenolic part and distillate eugenol.
• Identified by:– + % alc.FeCl3 blue color– Preparation of benzoate, phenylurethane
derivatives– + 3% aq. NaOH saturated with NaBr
rosettes of needles of sod. eugenateEugenol
Uses• Local anaethetic& antiseptic in toothache remedies• Spice & flavouring agent• Synthesis of vanillin (not practical)• Potential hypocholesterolemic agent
OH
OCH3
OH
OCH3
OAc
OCH3
CHO
OAc
OCH3
CHO
OH
OCH3
KOH HClAcetylation Oxid.
Heat
Eugenol Isoeugenol Vanillin
Monohydric phenolic ether
• Anise, fennel, star anise oils Fam. Umbelliferae
• Isolated by fractional distillation then crystallization at low temperature
OCH3
at low temperature• White crystalline• Sweet taste and odor • Uses:
– Flavoring mouthwashes, gargles– Flavoring in foods and beverages– Antioxidant
Anethole
Anethole has to be stored in well-closed colored container away from light why??
OCH3
light/air/heat
OCH3
OCH3
CHO
OCH3
AnetholeAnethaldehyde
oxidation
P-p’- dimethoxystilbene(photoanethole)
Viscid consistencyyellow
Identification
OCH3
CHCHCH3
OCH3
CHO
OCH3
COOH
K2Cr2O7 [ O ]
m.p. 184°C
1-
CHCHCH3 CHO COOH
Aisaldehyde Anisic acid
2- Preparation of nitroso derivatives m.p. 126°C
Safrole• Safrole is colorless liquid, isolated fromthe oil of
sassafras and star anise by fractional distillationfollowed by crystallization after cooling.
• Safrole like eugenol isomerise to isosafrole on heatingwith KOH.
• Safrole and isosafrole gave red color with conc.H22SO4.
• Safrole and isosafrole are antiseptic and oxidized toheliotropin (piperonal) which is more fragrant.
• Safrole and heliotropine are used in flavoring andscenting and as insect repellant O
O
H2C CH CH2
Safrol use as a flavor is restricted and no longerused because its carcinogenicity to liver and itspresence in some medicinally used volatile oils, asnutmeg oil, became a problem
Tricyclic phenols and phenolic ethers•Myristicin:
Source: It is constituent of the oil of nutmeg and mace.
Isolation: Fractional distillation of the myristica oil.
OO
H2C CH CH2
H3CO
the myristica oil.
Uses: CNS stimulant
Hallucinogenic agent
• Identification:On oxidation with KMnO4 gives
myristinic acid
(definite m.p. 208-210 ºC)
• .
H2C CH CH2
OOH3CO
O
COOH
OH3CO
KMnO4
MyristicinMyristinic acid
Tetrahydrophenolic ethers
• In parsley seed oil
• Long colorless needles with faint parsley odor
• Isolated by fractional distillation OCH3
O
O
• Isolated by fractional distillation then cooling
• Identification:1- Preparation of apiole tribromide, m.p. 80C.2- On oxidation with KMnO4 gives apiolic acid (definite m.p. 173 ºC)
• Uses:Diuretic
H3CO
ApioleParsley camphor
Dillapiole
• Dillapiole is a colorless oil.
• obtained from dill oil by fractional distillation.
• Dillapiole possesses a chemical charaterstics similarto those of apiol and myristicin.
O
OH3CO
H3CO
to those of apiol and myristicin.
• It possesses hypolipidemic and insect repellantactivity and could be used as a lactagouge.
• Apiole and dillapiole possess mild CNS activity.
• Apiole prevent the calculi formation in kidney whiledillapiole protect from gall bladder stones formation
Terpene Oxides1,4-Cineol• It is isolated from oil of cubeb by fractional distillation.
• Quantification and qualification of 1,4-Cineol by GC-MS and HPLC
Cineole
O
EstimationUses:Antiseptic & expectorant
2- 1,8-Cineol (Eucalyptol)Eucalyptol is expectorant, diuretic, antiseptic,antispasmodic, stimulant.Prevent calculus formation in kidney or even help in dissolving the already formedcalculus either in kidney or gall bladder.
O
Eucalyptol
Terpene PeroxideAscaridoleOccurrence: In Chenopodiumoil
Preparation: by fractional distillation under reduced pressure
(to avoid explosion)
Characters: viscous yellowliquid with nasty disagreableodour&taste.
Test: Givebloodredcolorwith Fe+2 + ammoniumthiocyanate.
Ascaridole
O
O
Test: Givebloodredcolorwith Fe+2 + ammoniumthiocyanate.
Uses:Anthelmintic for round & hook worms
Estimation:(Iodometrically: based on the oxidizing action ofperoxides), the oil + acidified KI solution & the liberated I2 is
titrated against standard Na2S2O3 solution.N.B.• Blank experiment should be carried out• Temperature must be low to avoid addition of I2 to the double
bond and volatilization of I2
Esters in volatile oils
• Esters are widely distributed in many essential oils. The mostcommon is the acetate. However oil of winter green is composedmainly of methyl salicylate.
• Esterssaponify with alkalis to give the corresponding alcohol andtheacidsalt,andthis is thebasisfor theirquantization.theacidsalt,andthis is thebasisfor theirquantization.
• The best methods for detection and isolation of esters seems to bethe GC/MS and HPLC.
• Esters isolated fromthe volatile oil can be classified according tothe acyl radical into:
Methyl Esters Containing Nitrogen-Canthranilate
Occurrence: in leaf oil of sweet orange
Isolation: due to the basic nitrogen, methyl anthranilate
• can be isolated by shaking with dilHCl or dil H2SO4
• The formed sulfate is crystallized on cooling,recrystallized from alcohol and the ester isrecrystallized from alcohol and the ester isregenerated by treatment with NaOH or KOH.
Identification:
• By physical examination of the characteristicblue-violetfluorescence
• Uses:
• Antifungal
COOCH3
NH2
Acids• Some essential oils contain few free acids e.g.
citronellic acid (in citronella oil and geraniumoil) Salicylic acid, and p-anisic acid and manyfree acids are detected in water of cohobationof many oils, most likely due to hydrolysis ofsome esters. Some of these acids are aliphatic,some esters. Some of these acids are aliphatic,alicyclic or aromatic.