Pharmaceutical Organic Chemistry-I (BP202T) B. PHARM. FIRST YEAR (Second Sem.)
Pharmaceutical Organic Chemistry-I (BP202T) B. PHARM. FIRST YEAR (Second Sem.)
Pharmaceutical Organic Chemistry-I (BP202T) B. PHARM. FIRST YEAR (Second Sem.)
(BP202T)
B. PHARM. FIRST YEAR (Second Sem.)
Answer book
Of
SECTION-A
Ans:
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PHARMACEUTICAL ORGANIC CHEMISTRY-I (BP202T)
Of these two rearrangement examples, hydride shift leads to a tertiary carbocation whereas alkyl
shift leads to a secondary carbocation. Because a tertiary carbocation is more stable than a
secondary carbocation, the hydride shift is favored in preference to the alkyl shift.
Any C–H or C–C bond adjacent to a carbocation may shift (including C–C bonds that are part of
a ring), but only C–C and C–H bonds can migrate during carbocation rearrangement.
The most common carbocation rearrangements involve a carbocation rearranging into a more
stable carbocation, such as 2o → 3o with resonance. (So use these rearrangements with impunity.)
Rearrangements that transform a carbocation into another of apparently equal stability are less
common, but they do occur.
Rearrangement to a less stable carbocation is very unusual, but also does occur.
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PHARMACEUTICAL ORGANIC CHEMISTRY-I (BP202T)
3. Aromatic Compounds
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PHARMACEUTICAL ORGANIC CHEMISTRY-I (BP202T)
They are a special type of compounds which contain benzene and other ring related compounds.
Similar to alicyclic, they can also have heteroatoms in the ring. Such compounds are called
heterocyclic aromatic compounds. Some of the examples are as follows:
(a) Benzenoid aromatic compounds
Solution:
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PHARMACEUTICAL ORGANIC CHEMISTRY-I (BP202T)
SECTION-B
Q2a. Give the reaction and mechanism of elimination reaction with suitable examples.
Solution:
In 1, 2-elimination, e.g. dehydrohalogenation of alkyl halide, the atoms are removed from adjacent
carbons. This is also called b-elimination, because a proton is removed from a beta-carbon.
Characteristics of an E1 Reaction
Kinetics – First order
Mechanism – Two steps
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PHARMACEUTICAL ORGANIC CHEMISTRY-I (BP202T)
Dehydrohalogenation of sec- and ter- alkyl halides undergo both E1 and E2 reactions. However, prim-
halides undergo only E2 reactions.
They cannot undergo E1 reaction because of the difficulty of forming primary carbocations.
E2 elimination is stereospecific,
The E2 reaction is the most effective for the synthesis of alkenes from primary alkyl halides.
ALKANES
General formula- CnH2n+2 where n=1, 2, 3. 4………etc.
Alkanes are relatively inert because of strong C-C and C-H bond hence these are called as Paraffin’s
(Latin-Parumaffinis means little affinity)
Halogenation:
When the substitution of alkane hydrogen by a halogen atom under the influence of UV light or
250-4000C.
Chlorination is a typical example of a broad class of organic reactions known as substitution.
A chlorine atom has been substituted for a hydrogen atom of methane, and the hydrogen atom thus
replaced is found combined with a second atom of chlorine.
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PHARMACEUTICAL ORGANIC CHEMISTRY-I (BP202T)
Solution:
(i) DIELS ALDER REACTION
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PHARMACEUTICAL ORGANIC CHEMISTRY-I (BP202T)
Example-
CH2
+
CH2
Ethene
Cyclohexene
Buta-1,3-diene
1. Diene: A conjugated diene, either open chain or cyclic is required for the reaction.
The presence of electron releasing groups (+I) increase the reactivity of diene.
Cis-diene undergoes the reaction, while Trans- Diene does not. Examples of Diene:
2. Dienophile (diene loving): any unsaturated species which tend to react with diene is called
Dienophile. Examples:
The presence of electron withdrawing group (-I effect) increase the reactivity of Dienophile.
Examples:
O
O
H2C C Cl H2C C C CH3
H2C C CH O O H H
H Chloro-ethene But-3-en-2-one
O
Propenal
Furan-2,5-dione
(acrolein) (vinyl chloride)
(maleic anhydride)
Mechanism of reaction:
CH2
CH2
HC
+ (Adduct)
CH2
HC
CH2
Ethene
Cyclohexene
Buta-1,3-diene
(ii) Saytzeff Rule (Zaitsev Rule): According to this rule, major product is the most substituted alkene, i.e.,
the most stable alkene. Thus, the major product is obtained by elimination of H+ from that β-carbon which
has the least number of hydrogen. Product of the reaction in this case is known as Saytzeff product.
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PHARMACEUTICAL ORGANIC CHEMISTRY-I (BP202T)
SECTION C
Q3a. Explain the addition of HBr to propylene in accordance with Markonikov’s and anti-
Markonikov’s rule with mechanism.
Solution:
Electrophilic addition to symmetrical and unsymmetrical 𝝅 bonds
When the same substituents are at each end of the double or triple bond, it is called symmetrical.
Unsymmetrical means different substituents are at each end of the double or triple bond.
Electrophilic addition of unsymmetrical reagents (HX, H2O or ROH) to unsymmetrical double or
triple bonds follows Markovnikov’s rule.
MARKOVNIKOV'S RULE
In the ionic addition of an acid to the carbon-carbon double bond of an alkene, the hydrogen of the acid
attaches itself to the carbon atom that already holds the greater number of hydrogen. This statement is
generally known as Markovnikov's rule.
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PHARMACEUTICAL ORGANIC CHEMISTRY-I (BP202T)
The modern Markovnikov rule states that, in the ionic addition of an unsymmetrical reagent to a double
bond, the positive portion of the adding reagent adds to a carbon atom of the double bond to yield the
more stable carbocation as an intermediate.
For example, Alkenes are converted to alkyl halides by the addition of HX (HCl, HBr or HI). Addition
of HX to unsymmetrical alkenes follows Markovnikov’s rule.
addition of hydrogen bromide (HBr) to propene yields 2-bromopropane as the major product.
Mechanism. The double bond p electrons attack the electrophile. Protonation of the double bond yields a
secondary carbocation inter mediate. The bromine nucleophile attacks the carbocation to form 2 -
bromopropane.
Addition of HBr to 1-butene yields a chiral molecule. The reaction is regioselective and a racemic
mixture is formed.
In the absence of peroxides, hydrogen bromide 'adds to alkenes in agreement with Markovnikov's rule;
in the presence of peroxides, the direction of addition is exactly reversed.
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PHARMACEUTICAL ORGANIC CHEMISTRY-I (BP202T)
When HBr is added to alkenes in the presence of free radical initiators, e.g. hydrogen peroxide (HOOH)
or alkyl peroxide (ROOR).
For example, 2-methyl propene reacts with HBr in the presence of peroxide (ROOR) to form 1-bromo-
2-methyl propane, which is an anti-Markovnikov product.
Radical additions do not proceed with HCl or HI.
1. Initiation The oxygen–oxygen bond is weak, and is easily homolytically cleaved to generate two
alkoxy radicals, which in turn abstract hydrogen to generate bromine radicals.
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PHARMACEUTICAL ORGANIC CHEMISTRY-I (BP202T)
3. Termination Any two radicals present in the reaction mixture can combine in a termination step, and
end the radical chain reaction. Thus, radical reactions produce a mixture of products.
Solution:
For example-
Addition of HX to a conjugated diene forms 1,2- and 1,4-products because of the resonance
stabilized allylic carbocation intermediate.
When 1, 3-butadiene is treated with bromine under similar conditions, there is obtained not only the
expected 3,4-dibromo-l-butene, but also l,4-dibromo-2- butene.
Treatment with HCl yields not only 3-chloro-l-butene, but also l-chloro-2-butene.
Hydrogenation yields not only 1-butene but also 2-butene,
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PHARMACEUTICAL ORGANIC CHEMISTRY-I (BP202T)
At higher temperatures, the major product is formed by 1,4-addition. Themore slowly formed
thermodynamic product is more stable andpredominates at higher temperatures.
In fact, when a mixture containing mainly the 1,2-product is heated, the1-4-addition product
becomes the major product at equilibrium:
Q. 4a. Explain Chain OR Positional and Functional isomerism with suitable example.
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PHARMACEUTICAL ORGANIC CHEMISTRY-I (BP202T)
Solution: Chain Isomerism: It occurs when carbon atoms are linked to the main chain in different
ways. For example:
Positional Isomerism: It occurs when functional groups are attached on different positions on a carbon
chain. For example:
Functional isomerism: It is a very interesting form of isomerism where the compounds are different due
to different arrangements of atoms leading to different functional groups. As functional groups are usually
the reactive centre of a molecule this leads to entirely different properties. For example:
Q. 4b. Discuss the free radical addition reaction of conjugated diene with suitable example.
Solution: Free-radical addition to conjugated dienes
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PHARMACEUTICAL ORGANIC CHEMISTRY-I (BP202T)
5(a). What are diene? Classified with suitable examples. Explain stability of conjugated diene
over isolated diene.
A diene is a hydrocarbon chain that has two double bonds that may or may not be adjacent to each
other. The arrangements of these double bonds can have varying effects on the compounds reactivity
and stability.
Diene is used, with two numbers to indicate the positions of the two double bonds. This system is
easily extended to compounds containing any number of double bonds.
Examples
Dienes are divided into two important classes according to the arrangement of the double bonds.
1. Double bonds that alternate with single bonds are said to be conjugated;
2. Double bonds that are separated by more than one single bond are said to be isolated.
3. Contain cumulated double bonds; these compounds are known as allenes.
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PHARMACEUTICAL ORGANIC CHEMISTRY-I (BP202T)
OZONOLYSIS OF ALKENES
Ozone (O3) is the triatomic form of oxygen.
It is a neutral but polar molecule that can be represented as a hybrid of its two most stable Lewis
structures.
Ozone is a powerful electrophile and undergoes a remarkable reaction with alkenes in which both
the σ and π components of the carbon–carbon double bond are cleaved to give a product referred
to as an ozonide.
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PHARMACEUTICAL ORGANIC CHEMISTRY-I (BP202T)
The two-stage reaction sequence is called ozonolysisand is represented by the general equation
Each carbon of the double bond becomes the carbon of a carbonyl group.
Ozonolysis has both synthetic and analytical applications in organic chemistry. In synthesis,
Ozonolysis of alkenes provides a method for the preparation of aldehydes and ketones.
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