Terpenoids are a class of naturally occurring organic chemicals derived from five-carbon isoprene units. This document provides an introduction and overview of terpenoids, including their general properties, methods of isolation from plants, classification based on the number of isoprene units, and common analytical techniques used for structural elucidation such as determining functional groups, unsaturation, and the number of rings in the structure.
Study material for chemistry UG and PG students
Chapter No 05 Terpenoids, Study of natural product Chemistry of natural products, Pharmaceutical chemistry.
Study material for chemistry UG and PG students
Chapter No 05 Terpenoids, Study of natural product Chemistry of natural products, Pharmaceutical chemistry.
An approach for designing organic synthesis which involves breaking down of target molecule into available starting material by imaginary breaking of bonds (disconnection) and/or by functional group interconversion is known as disconnection approach or retrosynthesis or synthesis backward.
The C-X disconnection approach is mainly applicable to a carbon chain attached to any of the heteroatoms like O, N, or S. Here, a bond joins the heteroatom (X) to the rest of the molecule like a C-O, C-N, or C-S group. This point is good point to initiate a disconnection. This is called a ‘One-group’ C-X disconnection as one would need to identify only one functional group like ester, ether, amide etc. to make the disconnection.
How to choose a disconnection?
These are the few general strategy which are important points introduced which apply to the whole of synthetic design rather than one particular area. The main choice is between the various disconnection, even such a simple disconnection as the following alcohol can be disconnected.
We want to get back to simple starting materials and we shall do if we disconnect the bond which are:
Towards the middle of the molecule thereby breaking into two reasonably equal halves rather than chopping off one or two carbon atoms from the end and,
At a branch as this is more likely to give straight chain fragments and these are more likely to be available.
Disconnections very often take place immediately adjacent to, or very close to functional groups in the target molecule. This is pretty much inevitable, given that functionality almost invariably arises from the forward reaction.
A simple example is the weedkiller propanil used on rice fields. Amide disconnection gives amine obviously made from o-dichlorobenzene by nitration and reduction. All positions around the ring in o-dichlorobenzene are about the same electronically but steric hindrance will lead to dichloronitrobenzene being the major product
This compound was needed for some research into the mechanisms of rearrangements. We can disconnect on either side of the ether oxygen atom, but (b) is much better because (a) does not correspond to a reliable reaction: it might be hard to control selective alkylation of the primary hydroxyl group in the presence of the secondary one.
The disconnections we have made so far have all been of C–O, C–N, or C–S bonds, but, of course, the most important reactions in organic synthesis are those that form C–C bonds. We can analyze C–C disconnections in much the same way as we’ve analyzed C–X disconnections.
The Zeneca drug propranolol is a beta-blocker that reduces blood pressure and is one of the top drugs worldwide. It has two 1,2-relationships in its structure but it is best to disconnect the more reactive amine group first.
Arildone is a drug that prevents polio and herpes simplex viruses from ‘unwrapping’ their DNA, and renders them harmless.
Introduction, classification, isolation, purification, biological activity of alkaloids, general methods of structural determination of alkaloids, structural elucidation of Morphine, Reserpine and Emetine
Presented by Shikha Popali and Harshpal singh Wahi students from Gurunanak college of pharmacy, Nagpur in Department of pharmaceutical Chemistry. The explained topic is seful for every chemistry student and for others too
Alkaloids are a group of naturally occurring chemical compounds that mostly contain basic nitrogen atoms.
The term alkaloid was coined by Meissner, a German pharmacist, in 1819.
Alkaloids are cyclic organic compounds containing nitrogen in a negative state of oxidation with limited distribution among living organisms.
Most alkaloids contain oxygen in their molecular structure; those compounds are usually colorless crystals at ambient conditions.
Some alkaloids are colored, like berberine (yellow) and sanguinarine (orange).
Most alkaloids are weak bases, but some, such as theobromine and theophylline, are amphoteric.
Many alkaloids dissolve poorly in water but readily dissolve in organic solvents.
Most alkaloids have a bitter taste or are poisonous when ingested.
Penicillin, one of the first and still one of the most widely used antibiotic agents, is derived from the penicillium mold. In 1928 Scottish bacteriologist alexander fleming in a contaminated green mold penicillium notatum. He isolated the mold, grew it in a fluid medium, and found that it produced a substance capable of killing many of the common bacteria that infect humans. Australian pathologist howard florey and British biochemist ernst Boris chain isolated and purified penicillin in the late 1930s, and by 1941 an injectable form of the drug was available for therapeutic use.
Penicillin's are beta lactam antibiotics and characterized by three fundamental structural requirements
The fused beta-lactam and thiazolidine ring structure.
free carboxylic acid group.
And one or more substituted acylamino side chain.
Penam nucleus: 7-oxo-l-thia-4-azabicyclo [3.2.0] heptane
Absolute configuration: 3-S, 5-R, 6-R.
Instrumental methods of characterization:
FTIR
MASS
C13-NMR
1H-NMR
FTIR: -
Penicillin G molecule and its IR spectra in D2 O and in DMSO. Spectra are characterized by the presence of three intense bands.
β- lactam CO stretching observe at 1761 cm-1 in D2O and 1762 cm-1 in DMSO solution.
Amide group is observe at 1640 cm-1 in D2O and 1674 cm-1 in DMSO solution.
Asymmetric stretching of carboxylate group is observe at 1601 cm-1 in D20 and 1615 cm-1 in DMSO solution.
A large red shift of amide , out of the frequency window, is observed upon proton exchange in DMSO.
Collision-Induced Dissociation (CID) technique
MASS:-
A high-resolution, hybrid tandem mass spectrometer was used to obtain CID spectra. The CID spectra were acquired by:
Mass selecting the precursor ions using the first mass spectrometer.
Injecting the ions into the first quadrupole (collision cell) where they undergo CID.
Mass-analyzing the fragment ions produced using the second quadrupole.
Argon was used as the collision gas, and the pressure in the collision cell was adjusted to attenuate the precursor ion intensity to 20-50% of the original intensity. The collision energy of the ions ranged from 160 to 180 eV. The mass spectra shown abundant fragmentations at m/z 160 and m/z 176 that were reported to arise from cleavage of the β-lactam ring.
protonated benzyl penicillin exhibits abundant fragment ions at m/z 160, m/z 176, m/z 217, m/z 128, and m/z 289. The most abundant CID fragment at m/z 160 and the molecular ion peak was observed at m/z 334.
C13-NMR: -
The four sp3 ring carbons give rise to resonances in the decreasing chemical shift order C-3, C-5, C-2 and C-6.
Chemical shift for C-2 is 64.9 ppm and the substituents attached with it are α-methyl 27.0 ppm and β-methyl 31.4 ppm. Chemical shift for C-3 is 73.6 ppm and 174.5 ppm for carboxylate functions (reflecting the smaller de-shielding influence of COOH over that of COO-). The chemic shift for C-5 is 67.2 ppm. The chemic shift for C-6 is 58.4 ppm.
The lactam group shows its chemical shift at 175.0 ppm
Amino group
An approach for designing organic synthesis which involves breaking down of target molecule into available starting material by imaginary breaking of bonds (disconnection) and/or by functional group interconversion is known as disconnection approach or retrosynthesis or synthesis backward.
The C-X disconnection approach is mainly applicable to a carbon chain attached to any of the heteroatoms like O, N, or S. Here, a bond joins the heteroatom (X) to the rest of the molecule like a C-O, C-N, or C-S group. This point is good point to initiate a disconnection. This is called a ‘One-group’ C-X disconnection as one would need to identify only one functional group like ester, ether, amide etc. to make the disconnection.
How to choose a disconnection?
These are the few general strategy which are important points introduced which apply to the whole of synthetic design rather than one particular area. The main choice is between the various disconnection, even such a simple disconnection as the following alcohol can be disconnected.
We want to get back to simple starting materials and we shall do if we disconnect the bond which are:
Towards the middle of the molecule thereby breaking into two reasonably equal halves rather than chopping off one or two carbon atoms from the end and,
At a branch as this is more likely to give straight chain fragments and these are more likely to be available.
Disconnections very often take place immediately adjacent to, or very close to functional groups in the target molecule. This is pretty much inevitable, given that functionality almost invariably arises from the forward reaction.
A simple example is the weedkiller propanil used on rice fields. Amide disconnection gives amine obviously made from o-dichlorobenzene by nitration and reduction. All positions around the ring in o-dichlorobenzene are about the same electronically but steric hindrance will lead to dichloronitrobenzene being the major product
This compound was needed for some research into the mechanisms of rearrangements. We can disconnect on either side of the ether oxygen atom, but (b) is much better because (a) does not correspond to a reliable reaction: it might be hard to control selective alkylation of the primary hydroxyl group in the presence of the secondary one.
The disconnections we have made so far have all been of C–O, C–N, or C–S bonds, but, of course, the most important reactions in organic synthesis are those that form C–C bonds. We can analyze C–C disconnections in much the same way as we’ve analyzed C–X disconnections.
The Zeneca drug propranolol is a beta-blocker that reduces blood pressure and is one of the top drugs worldwide. It has two 1,2-relationships in its structure but it is best to disconnect the more reactive amine group first.
Arildone is a drug that prevents polio and herpes simplex viruses from ‘unwrapping’ their DNA, and renders them harmless.
Introduction, classification, isolation, purification, biological activity of alkaloids, general methods of structural determination of alkaloids, structural elucidation of Morphine, Reserpine and Emetine
Presented by Shikha Popali and Harshpal singh Wahi students from Gurunanak college of pharmacy, Nagpur in Department of pharmaceutical Chemistry. The explained topic is seful for every chemistry student and for others too
Alkaloids are a group of naturally occurring chemical compounds that mostly contain basic nitrogen atoms.
The term alkaloid was coined by Meissner, a German pharmacist, in 1819.
Alkaloids are cyclic organic compounds containing nitrogen in a negative state of oxidation with limited distribution among living organisms.
Most alkaloids contain oxygen in their molecular structure; those compounds are usually colorless crystals at ambient conditions.
Some alkaloids are colored, like berberine (yellow) and sanguinarine (orange).
Most alkaloids are weak bases, but some, such as theobromine and theophylline, are amphoteric.
Many alkaloids dissolve poorly in water but readily dissolve in organic solvents.
Most alkaloids have a bitter taste or are poisonous when ingested.
Penicillin, one of the first and still one of the most widely used antibiotic agents, is derived from the penicillium mold. In 1928 Scottish bacteriologist alexander fleming in a contaminated green mold penicillium notatum. He isolated the mold, grew it in a fluid medium, and found that it produced a substance capable of killing many of the common bacteria that infect humans. Australian pathologist howard florey and British biochemist ernst Boris chain isolated and purified penicillin in the late 1930s, and by 1941 an injectable form of the drug was available for therapeutic use.
Penicillin's are beta lactam antibiotics and characterized by three fundamental structural requirements
The fused beta-lactam and thiazolidine ring structure.
free carboxylic acid group.
And one or more substituted acylamino side chain.
Penam nucleus: 7-oxo-l-thia-4-azabicyclo [3.2.0] heptane
Absolute configuration: 3-S, 5-R, 6-R.
Instrumental methods of characterization:
FTIR
MASS
C13-NMR
1H-NMR
FTIR: -
Penicillin G molecule and its IR spectra in D2 O and in DMSO. Spectra are characterized by the presence of three intense bands.
β- lactam CO stretching observe at 1761 cm-1 in D2O and 1762 cm-1 in DMSO solution.
Amide group is observe at 1640 cm-1 in D2O and 1674 cm-1 in DMSO solution.
Asymmetric stretching of carboxylate group is observe at 1601 cm-1 in D20 and 1615 cm-1 in DMSO solution.
A large red shift of amide , out of the frequency window, is observed upon proton exchange in DMSO.
Collision-Induced Dissociation (CID) technique
MASS:-
A high-resolution, hybrid tandem mass spectrometer was used to obtain CID spectra. The CID spectra were acquired by:
Mass selecting the precursor ions using the first mass spectrometer.
Injecting the ions into the first quadrupole (collision cell) where they undergo CID.
Mass-analyzing the fragment ions produced using the second quadrupole.
Argon was used as the collision gas, and the pressure in the collision cell was adjusted to attenuate the precursor ion intensity to 20-50% of the original intensity. The collision energy of the ions ranged from 160 to 180 eV. The mass spectra shown abundant fragmentations at m/z 160 and m/z 176 that were reported to arise from cleavage of the β-lactam ring.
protonated benzyl penicillin exhibits abundant fragment ions at m/z 160, m/z 176, m/z 217, m/z 128, and m/z 289. The most abundant CID fragment at m/z 160 and the molecular ion peak was observed at m/z 334.
C13-NMR: -
The four sp3 ring carbons give rise to resonances in the decreasing chemical shift order C-3, C-5, C-2 and C-6.
Chemical shift for C-2 is 64.9 ppm and the substituents attached with it are α-methyl 27.0 ppm and β-methyl 31.4 ppm. Chemical shift for C-3 is 73.6 ppm and 174.5 ppm for carboxylate functions (reflecting the smaller de-shielding influence of COOH over that of COO-). The chemic shift for C-5 is 67.2 ppm. The chemic shift for C-6 is 58.4 ppm.
The lactam group shows its chemical shift at 175.0 ppm
Amino group
Natural products and chemical products differ in several ways, including their origin, composition, production methods, and potential applications. Here are some key differences between the two:
Origin:
Natural Products: These are derived from natural sources, such as plants, animals, microorganisms, or minerals. Examples include herbal remedies, essential oils, and food products.
Chemical Products: These are synthesized in laboratories or chemical factories. They are typically created through chemical reactions and processes.
Composition:
Natural Products: They often contain a complex mixture of naturally occurring compounds, and their composition can vary based on the source and environmental factors. These products may contain a combination of chemicals produced by living organisms.
Chemical Products: They are typically composed of pure or well-defined chemical compounds. Their composition is consistent and can be precisely controlled.
Production Methods:
Natural Products: Obtained through extraction, purification, or isolation processes from natural sources. The methods may involve techniques like distillation, solvent extraction, or fermentation.
Chemical Products: Synthesized through chemical reactions involving various reagents and catalysts in controlled laboratory conditions. These reactions are typically reproducible.
Purity:
Natural Products: May contain impurities or variations in composition due to the natural source. Purity levels can vary significantly.
Chemical Products: Can be highly purified, with known and consistent chemical compositions.
Safety and Regulation:
Natural Products: May be subject to fewer regulations, leading to potential variability in safety and efficacy. Some natural products may also have potential side effects or interactions with medications.
Chemical Products: Typically subject to rigorous safety testing and regulatory oversight, which helps ensure a certain level of safety and efficacy.
Environmental Impact:
Natural Products: May have a lower environmental impact if sourced sustainably, but overharvesting or unsustainable practices can lead to ecological harm.
Chemical Products: The production of chemicals can have environmental consequences, including the generation of waste and pollution. However, sustainable and green chemistry practices aim to mitigate these impacts.
Applications:
Natural Products: Often used in traditional medicine, cosmetics, food, and some pharmaceuticals. They are favored for their perceived natural and holistic qualities.
Chemical Products: Widely used in various industries, including pharmaceuticals, plastics, agriculture, and electronics. They can be designed for specific purposes and are essential in modern manufacturing and technology.
It's important to note that both natural and chemical products have their own advantages and disadvantages, and the choice between them often depends on factors like safety, efficacy, cost, sustainability,
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In this PDF you'll be able to learn and understand the drug Menthol in a very subtle and easy way.
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2. CONTENTS
Introduction
General proprties
Isolation
Classification
Isoprene rule
General methods of structural elucidation
Structural elucidation of some drugs
3. INTRODUCTION
The term terpene was given to the compounds isolated from
terpentine, a volatile liquid isolated from pine trees.
Terpenes are the hydrocarbons having the general formula
(CH8)n.
The term terpenoids represents these hydrocarbons as well as
their hydrogenated and dehydrogenated derivatives.
Therefore,terpenoids have the general formula (C5)n.
Thus, all terpenes are terpenoids but all terpenoids are not
terpenes.
There are many different classes of naturally occuring
compounds.
Terpenoids also form a group of naturally occuring compounds
majority of which occur in plants, a few of them have also
been obtained from other sources.
Terpenoids are volatile substances which give plants and
flowers their fragrance.
They occur widely in the leaves and fruits of higher plants,
conifers, citrus and eucalyptus.
4. GENERAL PROPERTIES
Physical properties:
Terpenoids are colourless liquid.
Soluble in organic solvents and insoluble in water.
Most of the terpenoids are optically active.
Volatile in nature.
Boiling point 150° – 180° C.
Chemical properties:
The are unsaturated compounds.
They undergo addition reaction with hydrogen, halogen acids
to form addition products like NOCl, NOBr and hydrates.
They undergo polmerization and dehdrogenation in the ring.
On thermal decomposition, terpenoid gives isoprene as one of
the product.
5. ISOLATION OF TERPENOIDS
i) Isolation of essential oils from plant parts method
a) Steam distilation
b) Solvent extraction
c) Maceration
d) Adsorption in purified fats/ Enfluerage
ii) Separation of terpenoid from essential oils
a) Chemical methods
b) Physical methods
7. B) SOLVENT EXTRACTION
• Solvents like hexane and ethanol is used to isolate
essential oils.
• It is used for the plant parts have low amount of essential oil
.
• Plant material are treated with the solvent, it produces a
waxy aromatic compound called a "concrete.“
• Then it mixed with alcohol, the oil particles are released.
• Then it passess through a condenser then it separated out.
• This oil is used in perfume industry or for aromatherapy
purposes
8.
9. C) MACERATION
Advantage: More plant’s essence is captured.
• In this method the plant material is converted into
moderately coarse powder.
• Plant material is placed in a closed vessel.
• To this solvent is added.
• The mixture is allowed to stand for 1 week,
then the liquid is strained.
• Solid residue is pressed to recover any remaining
liquid.
• Strained and expressed liquids are mixed
10.
11. D) ENFLEURAGE
• The fat is warmed to 500C on glass plates.
• Then the fat is covered with flower petals and it kept for
several days until it saturated with essential oils.
• Then the old petals are replaced by fresh petals ,it repeated.
• After removing the petals, the fat is treated with ethanol when
all the
oils present in fat are dissolved in ethanol.
• The alcoholic distillate is then fractionally distilled under
reduced pressure to remove the solvent.
• Recently the fat is replaced by coconut charcoal, due to
greater
stability and higher adsorptive capacity.
12. II SEPARATION OF TERPENOID FROM
ESSENTIAL OILS
a) CHEMICAL METHOD:
Essential oils containing terpenoid hydrocarbon
+ nitrosyl chloride in chloroform form crystalline
adduct of hydrocarbons.
Essential oil containing alcohols
13. Terpenoid containing aldehyde and ketone treated
with NaHSO3, phenyl hydrazine or semicarbazone.
After separation it is decomposed to get terpenois.
b) PHYSICAL METHOD :
Fractional distillation
Chromatography
14. FRACTIONAL DISTILLATION:
During fractional distillation of essetial oils,
monoterpenoid hydrocarbons get initially
distilled followed by their oxgenated
derivatives.
Distillation of residue under reduced pressure
gives sesquiterpenoids.
15. CHROMATOGRAPHY
In this, essential oils are allowed to flow through
alumina/silica which is used as an adsorbent with the
principle of separation being adsorption chromatography.
Different classes of terpenoids show different
chromatograms.
These are again subjected to chromatography where the
individual terpenoids finally get separated.
Vapour phase/gas chromatography, partition
chromatography, counter current separation are
commonly used for the separation of individual
terpenoids.
16. ISOPRENE RULE
• In 1887, Wallach proposed the isoprene rule.
• “It states that the skeleton structures of all terpenoids are built up
of isoprene units or 2-methyl 1,3-butadiene”.
CH2= CH(CH3)-CH=CH2
• The isoprene rule derived from the following facts:
a) The empirical formula of almost all terpenoids is C5H8.
b) The thermal decomposition of all terpenoids gives isoprene as
one of the products. Eg: Rubber on destructive distillation yields
isoprene as the products.
17. The isoprene rule has been confirmed by the following
facts:
i) Isoprene, when heated to 2800C yield a (dipentene).
ii) Isoprene may be polymerized to yield a rubber like product
Polymerisation (C5 H8)n
( Rubber polyterpenoid)
n C5 H8
18. SPECIAL ISOPRENE RULE
This rule proposed by Ingold in 1925.
According to this rule “the isoprene units in terpenoids are joined
by head to tail linkage or 1,4- linkage ( The branched end of
isoprene unit was considered as head and other end as the tail).
19. VIOLATIONS OF ISOPRENE RULE
• Carbon content of certain terpenoids are not a multiple
of five.
Eg: Cryptone, a naturally occurring ketonic terpenoid
contains nine carbon atoms , it cannot be divided into
two isoprene units.
Cryptone
20. • In certain terpenoids isoprene rule is violated.
• Eg: Lavandulol is composed of two isoprene units are
linked through C3 and C4.
21. CLASSIFICATION OF TERPENOIDS
The terpenoids have general formula(C5H8)n . Based on the value of
‘n’ the terpenoids are classified into following:
22. Terpenoids are classified based on the number of rings present
in the terpenoids.
• Acyclic terpenoids
• Monocyclic terpenoids
• Bicyclic terpenoids
• Tricyclic terpenoidsc
• Tetracyclic terpenoids
24. iii) Bicyclic monoterpenoids:
The size of the first ring (six membered) in terpenoid is same in
all these terpenoids but the size of second ring is varies. On the
basis of the size of second ring, bicyclic monoterpenoids are
further divided into three classes.
a) It containing 6+3-membered rings (Eg:Carane)
b) Itcontaining 6+4- membered rings (Pinane)
32. GENERAL METHODS OF STRCTURAL
ELUCIDATION OF TERPENOIDS
1. Analytical method
2. Synthetic method
3. Physical method
4. Molecular rearrangement
5. Synthesis
33. 1) ANALYTICAL METHOD
a) Molecular formula
b) Nature of the oxygen atom
c) Unsaturation
d) Number of rings
e) Oxidative degradation products
f) Dehydrogenation
35. b) NATURE OF OXYGEN ATOM
i) Hydroxyl group
ROH + ( CH3CO)2O ROCOCH3 + CH3COOH
Acetate
36. Nature of hydroxyl group is revealed by the rate of esterification.
Primary alcohols undergo esterification more readily than secondary and
tertiary alcohols.
ii) Carbonyl group:
Carbonyl group :Aldehyde or Ketone
38. iv) C- alkyl group
The important C- alkyl group is C- CH3 group.
It is determined by Kuhn-Roth method
iii) Carboxyl group
• If terpenoid soluble in NH3 and gives effervescence with NaHCO3,
it indicate the presence of –COOH group.
• Number of –COOH group is estimated by titration against a
standard alkali.
Whether the –COOH group is attached to a 10, 20 or
30 carbon atom is ascertained from the esterification of acids in the
following order.
Tertiary ˂ secondary ˂ Primary
39. C) UNSATURATION
• It is determined by the formation of addition products with reagents
like hydrogen, halogen, halogen acids, per acids and nitrosyl
chloride.
Eg: Cadinene undergo hydrogenation to form tetrahydro
cadinene, it indicate that cadinene contains 2 double bond.
40. D) NUMBER OF RINGS
The number of rings is determined from the following table showing
the relation between general formula of compound and types of
compounds.
41. The molecular formula of citral is C10H16O, it contain 2 double bonds and
one oxygen atom as carbonyl group.
Molecular formula of parent hydrocarbon is C10H16O ≡ C10H16 + 4H (for
2 double bond) + 2H (for carbonyl oxygen) ≡C10H22.
The molecular formula C10H22 corresponds to Cn H2n+2 (general formula
of acyclic terpenoid), so citral is an acyclic terpenoid
42. e) Oxidative degradation products
Ozone:
Terpenoid react with ozone to form ozonide it undergo decomposition
either hydrolysis or catalytic reduction yields carbonyl compounds.
Nitric acid
react with nitric acid to form aromatic acid and aliphaticTerpenoids
acid.
43. f) Dehydration
•Terpenoid containing alcoholic or ketonic groups are heated with
dehydrating agents (potassium bisulphate, zinc chloride) to form
simple aromatic compound with loss of water.
g) Dehydrogenation
α-terpeneol to dipentene.
44. 2) SYNTHETIC METHOD
1) Catalytic Hydrogenation
• When aromatic compounds undergo catalytic hydrogenation to form
synthetic terpenoids.
• Eg: Menthol is prepared from thymol an aromatic compound by
catalytic hydrogenation
45. 2) GRIGNARD REACTIONS
• In grignard reagent, methy or isopropyl groups are introduced into
compound having carbonyl groups to synthesise large number of
terpenoids.
3) Reformatsky reactions
• In this reaction - halogen substituted ester is treated with a carbonyl
compound to form - hydroxyl ester. It is then treated with dil.acid
yield - hydroxyl acid which further coverted to an unsaturated acid
or a hydrocarbon.
46. 3) PHYSICALMETHOD
• UV spectroscopy:
• It is used for the detection of conjugation in terpenoids
• IR spectroscopy:
• Used for detecting the presence of a hydroxyl group, an oxo
group.
• Used for distinguish between cis and trans isomer.
• Used for quantitative measurements (determination of no: of
methyl group).
• NMR spectroscopy:
• Used for identifying double bonds and determing the nature of
endgroups in terpenoid.
• No: of rings present in terpenoid
• Orientation of methyl group in terpenoid
• Presence of –OH group
47. • 4) MOLECULAR REARRANGEMENT
• Molecular rearrangement is used when the degradation
reaction gives various products.
• 5) SYNTHESIS
• Structure elucidated by the above physical and analytical
method is confirmed by its synthesis.
48. STRUCTURAL ELUCIDATION OF
CITRAL
• Constitution of citral
a) Molecular formula: C10H16O
b) Presence of two double bond:
Citral is treated with bromine or hydrogen, it forms citral
tetrabromide. It indicate the presence of two double bond.
C10H16O
Br2
C10H16O.Br4
49. Citral on ozonolysis yield acetone, laevulaldehyde and gyoxal. It
indicate that citral is an acyclic compound containing two double bond.
c) Presence of an aldehyde group:
Formation of an oxime with hydroxylamine indicates the presence of
an oxo group in citral.
• Citral on reduction with Na/Hg it gives an alcohol called geraniol
and on oxidation with silver oxide to yield a Geranic acid
with same number of carbon atom as citral.
• Indicate that oxo group in citral is an aldehyde group.
50. d) Citral as an acyclic compound:
• Formation of above products shows that citral is an acyclic
compound containing two double bonds.
• Corresponding saturated hydrocarbon of citral (molecular Formula
C10H22) corresponds to the general formula CnH2n+2 for acyclic
compounds, indicating that citral must be an acyclic compound.
e) Carbon skeleton of citral
• Citral is heated with potassium hydrogen sulphate, it gives p-
cymene (known compound).
•Formation of p-cymene and product obtained from the ozonolysis
reveals that C-skeleton (I) of citral is formed by the joining of two
isoprene units in the head to tail fashion.
•Formation of p-cymene also reveals the position of methyl and
isopropyl group in citral.
51. f) Oxidation
• Citral undergo oxidation with KMnO4 followed by chromic acid yield
acetone, oxalic acid and laevulic acid. These reactions are only
explained if the citral has structure (II).
52. SUPPORT FOR THE STRUCTURE (II)
• Verley found that citral on boiling with aqueous potassium
carbonate yielded 6-methyl hept-5-ene-2-one and
acetaldehyde.
• The formation of these can only be explained on the basis of
proposed structure of citral (II) if it undergoes cleavage at α,β-
double bond.
• Further methylheptenone undergo oxidation yields acetone and
laevulic acid.These can be only explained on the basis of
structure (II).
53. CONFIRMATION SYNTHESIS OF CITRAL BY BARBIER-
BOUVEAULT-TIEMANN’S SYNTHESIS
• In this synthesis methyl heptenone is converted to geranic ester by
using Reformatsky’s reaction. Geranic ester is then converted to citral
by distilling a mixture of calcium salts of geranic and formic acids.
54. ISOMERISM OF CITRAL
• Two geometrical isomers occur in nature
• Two isomers are differ in the arrangement of aldehyde group about
double bond in 2,3 position. One is cis-citral or Neral and other is
trans- citral or geranial.
55. STRUCTURAL ELUCIDATION OFMENTHOL
1) Molecular formula: C10H20O
2) Menthol forms esters readily with acids it means that it possess an
alcoholic group.
Menthol then oxidized to yield ketone, menthone (C10H18O) it
indicate that the alcoholic group is secondary in nature.
3) On dehydration followed by dehydrogenation it yields p-cymene. It
indicate the presence of p-cymene skeleton (p-menthane skeleton) in two
componds.
56. 4) Menthone on oxidation with KMnO4 yields ketoacid C10H18O3.
It possess one keto group and one carboxyl group and is called
ketomenthylic acid.
• It readily oxidized to 3-methyladipic acid. These reactions can be
explained by considering the following structure of menthol.
57. • Menthol was converted to p-Cymene [1-methyl-4-
isopropylbenzene], which was also obtained by dehydrogenation of
pulegone.
• Pulegone on reduction yields menthone which on further reduction
gives menthol.
58. SYNTHESIS
• Finally the structure of menthone and menthol have been confirmed
by the synthesis given by Kotz and Hese from m-cresol.
59. STRUCTURAL ELUCIDATION OF
CAMPHOR
CONSTITUTION OF CAMPHOR-
• Molecular formula - C10H16O.
• Presence of keto group
It form oxime with hydroxylamine
When camphor is distilled with iodine it
yields cavacrol.
I2
60. • Presence of –CH2CO group.
When camphor is treated with amyl nitrite and hydrochloric acid, it yields iso nitroso
camphor
• Presence of six membered ring
61. • 6. Nature of carbon frame in camphor.
when camphor is oxidized with nitric acid, it yields a crystalline dibasic acid , camphoric acid
as a camphoric acid possesses the same number of carbon atom as camphor , it means that
group must be present in one of the ring of camphor. Further camphoric acid is dicarboxlic
acid and its molecular refraction reveals that it is also saturated. Thus during the conversion
camphor into camphoric acid , there occur the opening of ring containing the keto group
and therefore camphoric acid must be monocyclic compound.
When camphoric acid is further oxidized with nitric acid , camphoric acid is obtained.
62. STRUCTURAL ELUCIDATION OF PHYTOL
• Introduction:-
• It is a kind of diterpene which comes under the “acyclic diterpene” category.
• Phytol is an acyclic diterpene alcohol and a constituent of chlorophyll.
• It is obtained from alkaline hydrolysis of chlorophyll, which is then converted to
phytanic acid and stored in fats.
• It is commonly used as a precursor for the manufacture of synthetic forms of
vitamin E and vitamin K1.
• It is an optically active compound which boils at 145°C at 0.03mm pressure.
• Molecular Formula: C20H40O
• Melting Point: < 25 °C
PHYTOL
63. STRUCTURAL ELUCIDATION
• Molecular formula: C20H40O
• Presence of double bond :
When it is catalytically hydrogenated, it adds on one mole of hydrogen to form
dihydrophytol indicating that phytol contains one double bond.
• Presence of primary alcoholic group :
Phytol on oxidation with chromic acid yields monocarboxylic acid called phytenic acid
which has same no. of C- atom indicating the presence of primary alcoholic group.
• Ozonolysis of phytol :
on ozonolysis it yields glycoaldehyde and a saturated ketone
64. • Structure of saturated ketone may be written as follows :
Structure of saturated ketone is confirmed by its synthesis from ketone(I):
65. STRUCTURAL ELUCIDATION OF
RETINOL
• It is a kind of diterpene which comes under the “Monocyclic diterpene” category.
• It is also called Vitamin A
• Vitamin A is the fat soluble vitamin, is a group of unsaturated nutritional organic
compounds that includes retinol, retinal, retinoic acid, and several provitamin A
carotenoids (most notably beta- carotene).
• All forms of vitamin A have a beta-ionone ring to which an isoprenoid chain is attached,
called a retinyl group.
Molecular Formula: C20H30O
66.
67. STRUCTURAL ELUCIDATION
• Molecular formulae : C20H30O
• Double bond present:
It consumes 5 hydrogen molecules during hydrogenation in presence of Pd catalyst, that
means 5 double bonds are present in the structure.
68. • Isoprene Units Confirmation: The oxidation of Vit.A with Pot. Permagnate gives 2
molecules of Acetic acid which indicates 2 Isoprene units are present in structure.
• Methyl group: The oxidation of Vit.A in the presen e of CrO3 which gives 3 molecules
of Acetic acid. It means, 3 methyl groups are present.
69. • Hydroxy(–OH) group:
presence of –OH group can be determined by the formation of acetates with
acetic anhydride.
Upon Oxidation, Retinol converts to Retinal(aldehyde) and then converts to Retinoic
acid. It means, there is primary alchohol present in structure.
70. • Beta-Ionone Nucleus:
Ozonolysis of retinol gives geronic acid which can directly obtained by ozonolysis of
beta-Ionone.It confirms the basic nucleus of beta-Ionone is present in structure.
71. STRCTURAL ELCIDATION OF TAXOL
Introduction:
• It is a type of Complex diterpene.
• Taxol, a diterpenoid natural product first isolated from Taxus brevifolia, is one of
today’s better known
anticancer drugs.
• The paclitaxel molecule consists of a tetracyclic core called baccatin III and an amide
tail.
• The core rings are conveniently called (from left to right) ring A (a cyclohexene),
ring B (a cyclooctane), ring C (a cyclohexane) and ring D (an oxetane).
• MOLECULAR FORMULAE – C47H51NO14
72. Nature of O atom:
• Presence of alcoholic group:
75. STRUCTURAL ELUCIDATION OF
SQUALENE
• Squalene is a natural 30-carbon organic compound originally obtained for
commercial purposes primarily from shark liver oil (hence its name, as
Squalus is a genus of sharks), although plant sources (primarily vegetable
oils) are now used as well, including amaranth seed, rice bran, wheat
germ, and olives. Yeast cells have been genetically engineered to produce
commercially useful quantities of "synthetic" squalane, which is similar to
squalene.
76. STRUCTURAL ELUCIDATION
• Molecular formulae: C30H50
• Presence of double bonds :
The molecular formulae of fully saturated squalene was found to be
perhydrosqualene with 6H₂ molecule.
• Absence of conjugated double bonds in squalene:
Squalene fails to undergo reduction whwn treated with Na – metal amd amyl alcohol
which indicates absence of conjugated double bonds
• Oxidation of squalene with chromyl chloride:
On oxidation with CrO₂Cl₂ in CCl₄ gives Formaldehyde , Acetaldehyde ,Succinic acid
• Ozonolysis of squalene :
77. STRUCTRAL ELUCIDTION OF
CROTENOIDS
• Carotenoids are the group of non-nitrogenous , yellow , red or orange pigments that are
universally distributed in living things.
• These are also called tetraterpenoids , that are produced by plants and algae as well
as several bacteria and fungi.
• There are over 600 known carotenoids
• They split into 2 classes xanthophyll and carotenes
• Tetraterpenoids contain 40 C atoms
• General structure of carotenoid is a polyene chain consisting of 9-11 double bonds
and possibly terminating in rings
78. ALPHA & BETA CAROTENOIDS
• About 600- 700 different carotenoids are known of which α & β carotene are the
most prominent
• Β carotene is the most known carotenoid and the most often naturally occurring
carotene also known as provitamin A