Pharmaceutical Organic Chemistry
description
Transcript of Pharmaceutical Organic Chemistry
![Page 2: Pharmaceutical Organic Chemistry](https://reader035.fdocuments.net/reader035/viewer/2022062305/5681663d550346895dd9a6ac/html5/thumbnails/2.jpg)
Textbooks:
R. Fessenden and J. Fessenden, Organic Chemistry, PWS Publishers, Latest edition.
Optional reading : Joule and Smith, Heterocyclic
Chemistry, Van Nostrand Reinhold, Latest edition.
![Page 3: Pharmaceutical Organic Chemistry](https://reader035.fdocuments.net/reader035/viewer/2022062305/5681663d550346895dd9a6ac/html5/thumbnails/3.jpg)
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.
![Page 4: Pharmaceutical Organic Chemistry](https://reader035.fdocuments.net/reader035/viewer/2022062305/5681663d550346895dd9a6ac/html5/thumbnails/4.jpg)
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
![Page 5: Pharmaceutical Organic Chemistry](https://reader035.fdocuments.net/reader035/viewer/2022062305/5681663d550346895dd9a6ac/html5/thumbnails/5.jpg)
COURSE EVALUATION
Credits Type 15 Midterm I 115 Midterm II 225 Practical Exam 35 Term Activity* 420 + 20 Final exam 5
*Homework and Classroom Assignments and Discussion
![Page 6: Pharmaceutical Organic Chemistry](https://reader035.fdocuments.net/reader035/viewer/2022062305/5681663d550346895dd9a6ac/html5/thumbnails/6.jpg)
LEC. 1
Dr. Ebtehal al [email protected]
Pharmaceutical Organic Chemistry Part One: Classes and Mechanisims of Organic reactions
![Page 7: Pharmaceutical Organic Chemistry](https://reader035.fdocuments.net/reader035/viewer/2022062305/5681663d550346895dd9a6ac/html5/thumbnails/7.jpg)
Classes of Organic compuondsand functional group
A functional group is an atom or a group of atoms withcharacteristic chemical and physical properties. It is thereactive part of the molecule.
![Page 8: Pharmaceutical Organic Chemistry](https://reader035.fdocuments.net/reader035/viewer/2022062305/5681663d550346895dd9a6ac/html5/thumbnails/8.jpg)
![Page 9: Pharmaceutical Organic Chemistry](https://reader035.fdocuments.net/reader035/viewer/2022062305/5681663d550346895dd9a6ac/html5/thumbnails/9.jpg)
![Page 10: Pharmaceutical Organic Chemistry](https://reader035.fdocuments.net/reader035/viewer/2022062305/5681663d550346895dd9a6ac/html5/thumbnails/10.jpg)
![Page 11: Pharmaceutical Organic Chemistry](https://reader035.fdocuments.net/reader035/viewer/2022062305/5681663d550346895dd9a6ac/html5/thumbnails/11.jpg)
OReactions and Their MechanismsO There are four general types of organic reactions
OSubstitutions
OAdditions
![Page 12: Pharmaceutical Organic Chemistry](https://reader035.fdocuments.net/reader035/viewer/2022062305/5681663d550346895dd9a6ac/html5/thumbnails/12.jpg)
O Reactions and Their Mechanisms
OEliminations
O Rearrangements
![Page 13: Pharmaceutical Organic Chemistry](https://reader035.fdocuments.net/reader035/viewer/2022062305/5681663d550346895dd9a6ac/html5/thumbnails/13.jpg)
13
O Cleavage of Covalent Bonds
O Homolytic cleavage: each atom involved in the covalent bond receives one electron, resulting in formation of free radical
O Hetrolytic cleavage: both bonding electrons are retained by one of the atoms, resulting in formation of ionic species
![Page 14: Pharmaceutical Organic Chemistry](https://reader035.fdocuments.net/reader035/viewer/2022062305/5681663d550346895dd9a6ac/html5/thumbnails/14.jpg)
14
O Heterolysis of Bonds to Carbons: Carbanions and CarbocationsO Reaction can occur to give a carbocation or
carbanion depending on the nature of Z
![Page 15: Pharmaceutical Organic Chemistry](https://reader035.fdocuments.net/reader035/viewer/2022062305/5681663d550346895dd9a6ac/html5/thumbnails/15.jpg)
15
O Heterolysis of Bonds to Carbons: Carbanions and CarbocationsO Carbocations have only 6 valence electrons and
a positive charge
O Carbanions have 8 valence electrons and a negative charge
![Page 16: Pharmaceutical Organic Chemistry](https://reader035.fdocuments.net/reader035/viewer/2022062305/5681663d550346895dd9a6ac/html5/thumbnails/16.jpg)
O Organic chemistry terms for Lewis acids and bases
O Electrophiles (“electron-loving” reagents ): seek electrons to obtain a stable valence shell of electrons
O Are electron-deficient themselves e.g. carbocations
O Nucleophiles (“nucleus-loving” reagents): seek a proton or some other positively charged center
O Are electron-rich themselves e.g. carbanions
![Page 17: Pharmaceutical Organic Chemistry](https://reader035.fdocuments.net/reader035/viewer/2022062305/5681663d550346895dd9a6ac/html5/thumbnails/17.jpg)
1- Substitution reactions
![Page 18: Pharmaceutical Organic Chemistry](https://reader035.fdocuments.net/reader035/viewer/2022062305/5681663d550346895dd9a6ac/html5/thumbnails/18.jpg)
1. Substitution Reaction In this type of reaction one atom, ion,
or group is substituted for another.
Its two types:A. Nucleophilic Substitution
Reaction
B. Electrophilic Substitution Reaction
![Page 19: Pharmaceutical Organic Chemistry](https://reader035.fdocuments.net/reader035/viewer/2022062305/5681663d550346895dd9a6ac/html5/thumbnails/19.jpg)
A. 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)
![Page 20: Pharmaceutical Organic Chemistry](https://reader035.fdocuments.net/reader035/viewer/2022062305/5681663d550346895dd9a6ac/html5/thumbnails/20.jpg)
Substitution reactions
The SN1 Mechanism
![Page 21: Pharmaceutical Organic Chemistry](https://reader035.fdocuments.net/reader035/viewer/2022062305/5681663d550346895dd9a6ac/html5/thumbnails/21.jpg)
Nucleophilic Substitution Reaction of alkyl halide
SN1 reaction
unimolecular nucleophilic substitution, two-step mechanism
Step1: ionization and formation of R+
Step2: combination of R+
R X R+ + X-
Carbonium ion
slow
R+ + Nu: RNu:fast
![Page 22: Pharmaceutical Organic Chemistry](https://reader035.fdocuments.net/reader035/viewer/2022062305/5681663d550346895dd9a6ac/html5/thumbnails/22.jpg)
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
R X R+ + X-R----------X
transition statefrom one particle
Cont. SN1 reaction
![Page 23: Pharmaceutical Organic Chemistry](https://reader035.fdocuments.net/reader035/viewer/2022062305/5681663d550346895dd9a6ac/html5/thumbnails/23.jpg)
R X R+ + X-R----------X
transition statefrom one particle
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
Cont. SN1 reaction
![Page 24: Pharmaceutical Organic Chemistry](https://reader035.fdocuments.net/reader035/viewer/2022062305/5681663d550346895dd9a6ac/html5/thumbnails/24.jpg)
The SN1 Mechanism1)
2)
: :..
slow+
+ : Br :..
..
_
++ : fast
CH3 C CH3
CH3
Br
CH3 C CH3
CH3
CH3 C CH3
CH3
CH3 C CH3
CH3
Nu
Nu _
carbocation
![Page 25: Pharmaceutical Organic Chemistry](https://reader035.fdocuments.net/reader035/viewer/2022062305/5681663d550346895dd9a6ac/html5/thumbnails/25.jpg)
When weak Nu such as H2O or ROH is used the rate of SN1 reactionIs 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-
Cont. SN1 reaction
![Page 26: Pharmaceutical Organic Chemistry](https://reader035.fdocuments.net/reader035/viewer/2022062305/5681663d550346895dd9a6ac/html5/thumbnails/26.jpg)
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 2. CH3Br 3. CH2=CHCH2Br
CH2 C(CH3)21. 3.2.
Cont. SN1 reaction
Proplems
![Page 27: Pharmaceutical Organic Chemistry](https://reader035.fdocuments.net/reader035/viewer/2022062305/5681663d550346895dd9a6ac/html5/thumbnails/27.jpg)
Substitution reactions
The SN2 Mechanism
![Page 28: Pharmaceutical Organic Chemistry](https://reader035.fdocuments.net/reader035/viewer/2022062305/5681663d550346895dd9a6ac/html5/thumbnails/28.jpg)
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
![Page 29: Pharmaceutical Organic Chemistry](https://reader035.fdocuments.net/reader035/viewer/2022062305/5681663d550346895dd9a6ac/html5/thumbnails/29.jpg)
The Sn2 mechanism:
a) is a single step processb) involves no intermediatesc) involves only one transition state, which is of low polarityd) follows second order (bimolecular) kinetics. That is, rate=k[substrate][nucleophile]
![Page 30: Pharmaceutical Organic Chemistry](https://reader035.fdocuments.net/reader035/viewer/2022062305/5681663d550346895dd9a6ac/html5/thumbnails/30.jpg)
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-
![Page 31: Pharmaceutical Organic Chemistry](https://reader035.fdocuments.net/reader035/viewer/2022062305/5681663d550346895dd9a6ac/html5/thumbnails/31.jpg)
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)3COCH3 + NaCl
![Page 32: Pharmaceutical Organic Chemistry](https://reader035.fdocuments.net/reader035/viewer/2022062305/5681663d550346895dd9a6ac/html5/thumbnails/32.jpg)
Summary of SN1 & SN2 Mechanisms
SN2 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
![Page 33: Pharmaceutical Organic Chemistry](https://reader035.fdocuments.net/reader035/viewer/2022062305/5681663d550346895dd9a6ac/html5/thumbnails/33.jpg)
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
![Page 34: Pharmaceutical Organic Chemistry](https://reader035.fdocuments.net/reader035/viewer/2022062305/5681663d550346895dd9a6ac/html5/thumbnails/34.jpg)
R-CH2-X + Nu_
R-CH2-Nu + X_
substrate nucleophile product leaving group
Oxygen Nucleophiles (SN2)
O-H_
R-CH2-O-Halcoholhydroxide
R-CH2-X + _+ X
O-R_
R-CH2-O-RR-CH2-X + _+ X
etheralkoxide
O-C-R_
R-CH2-R-CH2-X + _+ X
estercarboxylateO
O-C-R
O
![Page 35: Pharmaceutical Organic Chemistry](https://reader035.fdocuments.net/reader035/viewer/2022062305/5681663d550346895dd9a6ac/html5/thumbnails/35.jpg)
Linkage with the life sciences
Information
Enrichment
![Page 36: Pharmaceutical Organic Chemistry](https://reader035.fdocuments.net/reader035/viewer/2022062305/5681663d550346895dd9a6ac/html5/thumbnails/36.jpg)
MEDICALL YSPEAKINGPharmacology 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.
![Page 37: Pharmaceutical Organic Chemistry](https://reader035.fdocuments.net/reader035/viewer/2022062305/5681663d550346895dd9a6ac/html5/thumbnails/37.jpg)
Chlorambucil