1. Pharmaceutical Organic Chemistry
211 PHC lect.1
Dr. Ebtehal S AlAbdullah

2. Textbooks:
R. Fessenden and J. Fessenden, Organic Chemistry, PWS Publishers, Latest edition.
Optional reading :
Joule and Smith, Heterocyclic Chemistry, Van Nostrand Reinhold, Latest edition.

3. Aim of the Course The Course is Designed to Provide the Students with:
Recognize the various classes and subclasses of organic compounds and how the chemical and physical properties influence their behavior.
Understand the chemical reactions unique to each class or subclass of organic molecules and their role in synthetic chemistry.
Recognize the different reaction mechanisms and their importance in synthesis.
Understand the stereochemistry of organic molecules and the stereochemical courses of organic reactions.
Understand the role of physicochemical properties, mechanisms, and stereochemistry of organic molecules in biology and pharmacy.

4. Topics to be covered: Three parts:
Part one: Classes and Mechanism of reactions
a- Subsitiution
b- addition
c- elimination
d- rearrangement
e- Free radicals
Part two: Stereochemistry
Part three: Heterocyclic chemistry

5. COURSE EVALUATION Credits Type 15 Midterm I 1 Midterm II 2 25
Practical Exam 3 5
Term Activity* 4
Final exam
*Homework and Classroom Assignments and Discussion

6. LEC. 1 Dr. Ebtehal al abdullah Pharmaceutical Organic Chemistry
Pharmaceutical Organic Chemistry
Part One:
Classes and Mechanisims of Organic reactions

7. Classes of Organic compuonds and functional group
A functional group is an atom or a group of atoms with
characteristic chemical and physical properties. It is the
reactive part of the molecule.

11. Reactions and Their Mechanisms
There are four general types of organic reactions
Substitutions
Additions

12. Reactions and Their Mechanisms Eliminations
Rearrangements

13. Cleavage of Covalent Bonds
Homolytic cleavage: each atom involved in the covalent bond receives one electron, resulting in formation of free radical
Hetrolytic cleavage: both bonding electrons are retained by one of the atoms, resulting in formation of ionic species

14. Heterolysis of Bonds to Carbons: Carbanions and Carbocations
Reaction can occur to give a carbocation or carbanion depending on the nature of Z

15. Heterolysis of Bonds to Carbons: Carbanions and Carbocations
Carbocations have only 6 valence electrons and a positive charge
Carbanions have 8 valence electrons and a negative charge

16. Organic chemistry terms for Lewis acids and bases
Electrophiles (“electron-loving” reagents ): seek electrons to obtain a stable valence shell of electrons
Are electron-deficient themselves e.g. carbocations
Nucleophiles (“nucleus-loving” reagents): seek a proton or some other positively charged center
Are electron-rich themselves e.g. carbanions

17. 1- Substitution reactions

18. Substitution Reaction In this type of reaction one atom, ion, or group is substituted for another.
Its two types:
Nucleophilic Substitution Reaction
Electrophilic Substitution Reaction

19. Nucleophilic Substitution Reaction
Q: What is nucleophilic substitution reaction?
A species which has ability to donates a pair of electrons is termed as a nucleophile.
A reaction in which Nu is substituted by another Nu
can occur by an: a. SN1 path
b. SN2 path
Most common reaction of alkyl halides (RX) and alcohols (ROH)

20. Substitution reactions
The SN1 Mechanism

21. Nucleophilic Substitution Reaction of alkyl halide
SN1 reaction
unimolecular nucleophilic substitution, two-step mechanism
Step1: ionization and formation of R+
Step2: combination of R+

22. Cont. SN1 reaction
The rate of chemical reaction is a measure of how fast the reaction
proceed,
It dose not depend on the conc. Of Nu-, depend on only conc. Of RX
It follow first order kinetic, depend only on reactant conc.(RX)
It is nuimolecular reaction [ because only one particle (RX) is involved
in the transition state of rate determining step

23. * Only benzylic, allylic and 3°R+ undergo SN1
Cont. SN1 reaction
The rate-determinig step in SN1 reaction involves the formation of R+,
So, increasing the stability of R+ will increase the rate of the reaction
C6H5CH2+, CH2=CHCH2+, (CH3)3C+, (CH3)2CH+, CH3CH2+, CH3+
Decresing the stability of R+, decreasing SN1 rate of RX
* Only benzylic, allylic and 3°R+ undergo SN1

24. The SN1 Mechanism
carbocation

25. When weak Nu such as H2O or ROH is used the rate of SN1 reaction
Cont. SN1 reaction
When weak Nu such as H2O or ROH is used the rate of SN1 reaction
Is in the following order
C6H5CH2X > CH2=CHCH2X > 3° RX
When a strong Nu as CN- is used,
3° RX undergo SN1 reaction exclusively, where as
C6H5CH2OH or CH2=CHCH2OH
C6H5CH2X or
CH2=CHCH2X C6H5CH2CN or CH2=CHCH2CN
SN1
H2O or ROH
SN2
CN-

26. Cont. SN1 reaction Proplems
Q1: List the following carbocation in order of increasing stability
Q2: Which of the following compounds is more reactive toward SN1
reaction. Explain why
1. C6H5CH2Br CH3Br CH2=CHCH2Br

27. Substitution reactions
The SN2 Mechanism

28. Nucleophilic Substitution Reaction of alkyl halide
SN2 reaction
bimolecular nucleophilic substitution, one-step mechanism, which
involves a transition state.
Nu attacks from back-side.
Bimolecular reaction, because both Nu and RX are involved in the
transition state.
Transition state

29. The Sn2 mechanism:
a) is a single step process
b) involves no intermediates
c) involves only one transition state, which is of low polarity
d) follows second order (bimolecular) kinetics. That is,
rate=k[substrate][nucleophile]

30. Increase the steric hindrance around the halogenated carbon Decreases
Cont. SN2 reaction
The rate of second order, because it is proportional to conc. Of Nu & RX
Increase the steric hindrance around the halogenated carbon Decreases
the rate of SN2 reaction.
3° RX are too hindered to undergo SN2 reaction.
CH3X RCH2X R2CHX
increasing steric hindrance , decreasing SN2 rate
CH3X…… most reactive
2 ° [R2CHX ]…… react slowly
3 ° [R3X ] …….no react by SN2
When strong Nu as CN- is used, the SN2 rate in the following order
benzylic halide > Allylic halide > Methyl halide
** CH3X and RCH2X (1° RX) undergo SN2 exclusively, irrespective of the
strength of Nu-

31. Q: Outline all steps in the mechansim of each of the following reaction:
1. C6H5CH2Br + NaCN C6H5CH2CN + NaBr
2. C6H5CH2Br + H2O C6H5CH2OH + HBr
3. (CH3)3CCl CH3O-Na (CH3)3COCH NaCl

32. Summary of SN1 & SN2 Mechanisms
A bimolecular reaction
Back-side attack
2ed order in rate
Inversion of configuration
CH3X > 1oRX > 2oRX
SN1
A unimolecular reaction
An ionization reaction
1st order in rate
No inversion of configuration
3oRX > 2oRX

33. Summary of SN1 & SN2 Mechanisms
Benzylic and allylic undergo both type of substitution
SN1 & SN2 Mechanisms
Depending on the strength of Nu
if weak Nu ……… SN1
if strong Nu ………. SN2

35. Linkage with the life sciences
Information Enrichment

36. MEDICALL YSPEAKING Pharmacology and Drug Design
Pharmacology is the study of how drugs interact with biological systems, including the mechanisms that explain drug action.
Pharmacology is a very important field of study because it serves as the basis for the design of new drugs.

37. Chlorambucil