5.Determination of structure of terpenoid

Determination of Structure of Terpenoid

Prepared byDr. N.GOPINATHAN

ASSISTANT PROFESSORDEPARTMENT OF PHARMACEUTICAL CHEMISTRY

FACULTY OF PHARMACYSRI RAMACHANDRA UNIVERSITY

CHENNAI-116TAMILNADU

INDIA

General structural elucidation

• Determination of molecular formulae of a pure specimen – elemental analysis.

• If it is optically active, its specific rotation is measured. It helps to distinguish the two or more possible structure as in limonene and carvone.

• Analytical method• Synthetic• Physical• Knowledge of a molecular

rearrangement• Synthesis

Nature of oxygen atom

• Hydroxy group• Formation of acetates with acetic

anhydride

Benzoates with 3,5 dinitro benzoyl chloride

Formation of urethane with phenyl iso cyanate

Nature of OH is revealed by esterification rate primary > secondary > tertiary

Carbonyl group

Carbonyl group-It can be ascertained by oxidation to show whether it is a ketone

or aldehyde

Carbon less in number

CH2-C=O group

CH2-C=O groupin ring on oxidation it yield dicarboxylic acid without any loss of carbon atom

Methyl ketone –COCH3

• Detected by haloform reaction –oxidation- it yields acetic acid

COOH group

• Effervescence with sodiumbicarbonate.• Number of cooH group is estimated by

titrating with standard alkali• The point of attachment of COOH to

primary, secondary or tertiary is determined by rate of esterification.

• primary > secondary > tertiary.• Tertiary is difficult to esterify.

Isopropylidene It is determined by ozonolysis to acetone. The amount of acetone is estimated volumetrically and the number of isopropylidene group is determined

Isopropenyl

Presence of unsaturation is ascertained by addition product.

From number of consumption of H2 molecule the number of double bond can be estimated

The number of halogen consumed would give the amount of unsaturation

Markovnikoff’s rule

Tilden’s reagent

It forms crystalline product having sharp melting point and be used for identification and separation of terpenoids.C=C both are tertiary gives blue colour.One is tertiary and other is secondary gives colourless complex

Epoxide formation by treated with peracid

Presence of conjugated system can be determined by the Diel’s alder reaction

Number of rings

• From number of olefinic double bonds, nature of functional groups and molecular formula of terpenoid, It is possible to find out the molecular formula of the parent saturated hydrocarbon.

Example

• Citral C10H16O with two double bond and one carbonyl group. The molecular formula of the parent saturated hydrocarbon.

It is considere with acyclic general formulae thus citral must be Acyclic

From molecular refraction, the nature of carbon skeleton of sesquiterpenoids can be ascertained

Oxidative degradation product• Degrade the terpenoid to small fragments of known

structure it can be done by oxidation.• Ozonolysis• The reagent attack olefinic linkage of molecule to

form ozonide which upon decomposition by hydrolysis or catalytic reduction yield the corresponding carbonyl carbon.

• Ozonolysis locate position of double bond in a molecule.

• The formation of acetone and formaldehyde reveals the presence of isopropylidene and terminal double bond

Oxidation with nitric acidIt is a strong oxidising agent which drastically degrade the terpenoid to a mixture of aliphatic and aromatic acid

Haloform reaction

Hydroxylating agent – lead tetra acetate in hot acetic acid, peracid , Osmium tetra oxide, hydrogenperoxide, potassium per manganate etc It will form glycols

If double bond is in ring on oxidation yield ketoacid or dicarboxylic acid without loss of carbon atom.Alpha pinene on oxidation yield keto acid

Dehydrationwhen terpenoid with alcohol or ketonic group heated with dehydrating agent, these lose a molecule of water and converted into simple aromatic compound

When open chain terpenoids are dehydrated with dehydrating agent they yield cyclic compound

Dehydrogenation

• When terpenoid is heated with Zn, I, Br,S,Se and palladium they are converted into aromatic compound of known structure.

• If it is unknown which can be determined by synthesis.

• By this method the skeleton structure and position of side chain in original terpenoids can be determined.

Dehydrogenation

Synthetic method

Grignard reagent

By grignard reaction methyl, isopropyl can be introduced to carbonyl alpha terpineol a naturally occurring terpenoid tertiary alcohol can be prepared

Reformatsky reaction- alpha substituted ester treated with carbonyl [ aldehyde / ketone / ester ] in the presence of zinc to form beta hydroxy ester.later which is treated with dilute acid to yield beta hydroxy acid which may further converted to unsaturated acid or hydrocarbon

Physical methods

• UV- detection of conjugation.• IR• NMR• Mass spectroscopy• Optical rotation• X ray analysis• Knowledge about rearrangement• synthesis

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