The over view of Organic chemistry

Points for discussion:(Brain Wash)!!

What is organic chemistry?
Why Medical students are studying the course?
Where its source? How you get it?

Every living organisms were/are made up of organic chemicals;

How and Why? For instance;
the proteins w/c make up our hair, skin, muscles, etc;
the DNA w/c controls our genetic heritage;
the foods w/c nourish us! and
 the medicines w/c we heal!!!
1
 Organic chemistry is…

So; anyone with a curiosity about life and living things,

anyone who wants to be a parts of many exciting developments,
now happening in medicines and biological sciences, must
understanding first about organic chemistry!!
Eg.,Look the following chemical structures those might be a
familiar with their NOMENCLATURE!!
 For chronic arthritis and mild-
to-moderate musculoskeletal
pain
 Used to treat a number of
bacterial infections
 used to relieve pain severe enough
Rofecoxin
to require opioid treatment
Oxycodone 2
 Hence; some alkaloids have biological properties!

 Ephedrine used to treat breathing

problems (as a bronchodilator),
nasal congestion (as a decongestant)

 Cocaine has a similar

psychomotor stimulant effect to
that of amphetamine and related
compounds.

Cocaine, is obtained from the coca bush Erythroxylon coca,

endemic to the upland rain forest areas of central South America.
3
 Cocaine;…

a small amount of cocaine in

the original Coca-Cola recipe,
although it was removed.
Cocaine itself is no longer used
as a medicine because it is too
addictive, but its anesthetic
properties provoked.

 The risk of overdose is compounded when it is used with

another dangerous substance like alcohol or other drugs.
 It caused as Cardiac arrest, Stroke, Respiratory arrest and
Sudden death.
4
 Indeed; Organic chemistry is…

 Regularly; we hear the term "organic" in everyday language

where it describes or refers to substances that are "natural".
 This is probably a result of the notion of early scientists that all
organic compounds came from living systems and possessed a
‘’vital force’’
 Thus, it describes the structures, properties, preparation, and
reactions of a vast organic compounds.
 Eg.,different types of organic compounds, but all have carbon
as their principal constituent atom.
 These carbon atoms form a C-skeleton or C-backbone that has
other bonded atoms like H, N, O, S, F, Cl, Br, I and etc. 5
 Energy levels and Atomic orbitals

 Each and every atom is composed of a nucleus that is made

out of protons and neutrons w/c are surrounded by electrons.
 These electrons are in continuous movement around the
nucleus. B/c atom is smallest unit of ordinary matter that
forms a chemical element.
 Therefore, no one can give a specific location for an electron in
an atom.
 To combat such problem; various scientists have introduced the
concept of “probability.”
 Thus; the most probable pathway that an electrons is most
likely to be moving is determined and this pathway is an orbital.6
 Cont’d…
 These orbitals are arranged according to the amount of energy
that electrons in these orbitals are composed of and is called
energy levels.
 These energy levels are named as K, L, M, N, etc. The energy
level that has the lowest energy is K.
 So, Electrons are filled to these energy levels according to the
ascending order of energy.
 The main d/ce b/n orbitals and energy levels is orbitals show the
most probable pathway of an electron that is in motion around
the nucleus whereas energy levels show the relative locations of
orbitals according to the amount of energy they possess.
7
 Cont’d…

 In the atomic level, the most accurate name for an orbital

is atomic orbital.
 The atomic orbital may exist in several shapes such as spherical
shape and dumbbell shape.
 There are fixed numbers of electrons
that each energy level can hold.
 This number depends on the number
of orbitals that each energy level is
comprised of.
1st energy level – 2; 2nd energy level – 8
3rd energy level – 8; 4th energy level – 8 8
In summary

9
10
 Exercise(1)
i) The energy of an electron in the first Bohr orbit of H atom is
-13.6 eV. The possible energy value(s) of the excited state(s) for
electrons in Bohr orbits of hydrogen is (are) :
a) -3.4 eV b) -4.2 eV c) -6.8 eV d) +6.8 eV
ii) With increase in principal quantum number, n, the energy
difference between adjacent energy levels in Hydrogen atom:
a) Increases b) Decreases c) Remains constant
d) Decreases for lower values of n and increases for higher
values of n.
iii) If the electron of a hydrogen atom is present in the first orbit,
the total energy of the electron is?
11
 Atomic orbital, What is it???
 An orbital is a three-dimensional region around the nucleus
where there is a high probability of finding an electron.

 The Heisenberg uncertainty principle states that both the

precise location and the momentum of an atomic particle
cannot be simultaneously determined; as stated below:

 This can make sense of this by imagining that the more carefully
one tries to measure position, the more disruption there is to the
system, resulting in changes in momentum. 12
 Cont’d

 This means, we never say precisely where an electron is but we

can only describe its probable location(i.e.,∆x)

 Thus, it says that an electron occupies a 1s atomic orbital, we

mean, there is a greater than 90% probability that the electron
is in the space defined by the sphere.

13
 Cont’d

 An electron in a 1s atomic orbital can be anywhere within the

1s sphere, but a 2s atomic orbital has a region where the
probability of finding an electron falls to zero.(i.e., node).
 Hence, a node is a place where there is zero probability of
finding an electron
 So 2s electron can be found anywhere within the 2s sphere
including the region of space defined by the 1s sphere except
in the node. To understand why nodes occur, we need to
remember that electrons have both particle like and wavelike
properties and b/c a node is a consequence of the wavelike
properties of an electron. 14
For instance; Cont’d

15
 Further illustration

 An electron behaves like a standing wave, but unlike the wave

created by a vibrating guitar string; it is three dimensional.
 This means that the node of a 2s atomic orbital is actually a
surface a spherical surface within the 2s atomic orbital.

 Unlike s-atomic orbitals that resemble spheres, p atomic

orbitals have two lobes.

16
 Cont’d
 Based on the above nodal lobes, there are three degenerate
p atomic orbitals.

 Hence, degenerate orbitals are orbitals that have the same

energy and is zero probability of finding an electron in the
nodal plane of the p orbital.
 Therefore, p orbital has the approximate shape of a pair of
lobes on opposite sides of the nucleus, or a somewhat
17
In summary, atomic orbital is represented as:

s Orbitals (l=0)

p Orbitals (l=1)

d Orbitals (l=2)

18
 Shapes of sub shell orbitals.
 The s subshell electron density distribution is spherical and the
p subshell has a dumbbell shape.
 The d and f orbitals are more complex.
 These shapes represent the three-dimensional regions within
which the electron is likely to be found.

19
 Question (1)

i) What are basic characteristic that happen

to s orbitals as n increases?
ii) What are the shapes of s, p, and d orbitals
respectively?
iii) Describe the properties of an electron associated
with each of the following four quantum
numbers: n, l, ml, and ms.
iv) Consider the orbitals shown here in outline;

20
 Cont’d…
a. What is the maximum number of electrons contained in an
orbital of type (x)? of type (y)? of type (z)?
b. How many orbitals of type (x) are found in a shell with n = 2?
How many of type (y)? How many of type (z)?
c. Write a set of quantum numbers for an electron in an orbital of
type (x) in a shell with n = 4. of an orbital of type (y) in a shell
with n = 2. of an orbital of type (z) in a shell with n = 3.
d. What is the smallest possible n value for an orbital of type (x)?
of type (y)? of type (z)?
e. What are the possible l and ml values for an orbital of type (x)?
of type (y)? of type (z)?
21
 The Nature of Chemical Bonds

Why do atoms bond together?

 How can bonds be described electronically?

atoms bond together because the compound that results is

more stable and lower in energy than the separate atoms.
Hence, energy must be put into the system to break a bond.
Making bonds always releases energy, and breaking bonds
always absorbs energy
 electronic properties of atoms

an electron octet in an atom’s outermost shell, or valence

22
 For examples

A special stability to the noble-gas elements in group VIIIA of the

periodic table: Ne (2, 8); Ar (2, 8, 8); Kr (2, 8, 18, 8).
Where as, alkali metals, w/c achieves a noble gas configuration
they under go e-s lost from s orbital to form a cation;
In addition; the halogens also achieves a noble gas
configuration by gaining a p electron to fill their valence shell and
form an anion.
Therefore; the combinations of two ions are held together in
compounds form an electrostatic attraction, i.e., an ionic bond

23
 Exercise
i) How, do elements makes chemical bonding near
the middle and right hand side of the periodic
table form bonds?
ii) What was/is the fundamental concept of electron-
dot structures in the sense of covalent bond?

iii) State the bonding system in carbon compounds

and narrate the theory of molecular orbital and
valance bonding accordingly?

24
 Hybridization of Atomic Orbitals
 The phenomenon of mixing up of atomic orbitals of similar
energies and formation of equivalent number of entirely new
orbitals of identical shape and energy.
 AOs on a single atom mix to form new, hybrid orbitals.
 Eg. hybrid orbitals have characteristics of both s and
p orbitals,
 It provides a means of explaining observed bond angles in
organic molecules.
 It is considered to an important evolutionary force since it may
lead to an increase of the intraspecific genetic diversity of the
participating populations; 25
 Cont’d
 Thus, it is the creation of new species, species extinction
through genetic assimilation and the generation of highly
invasive genotypes.
 Important points for hybridization
 The number of hybrid orbitals generated is equal to
the number of pure atomic orbitals that participate in
hybridization process.
 Hybridization concept is not applicable to isolated atoms.
 It is used to explain the bonding scheme in a molecule.
 Covalent bonds is polyatomic molecules are formed by the
overlap of hybrid orbitals or of hybrid orbitals with unhybridized
26
 Types of Hybridization

i) sp3-hybridization: The combination of one s and three p-

orbitals to form four hybrid orbitals of equal energy.
 For instance: Methane (CH4) molecule.
 Carbon has, outside its nucleus, 6e-s and therefore the ground
state electronic configuration of carbon is:

 This, however, represent the ground state of the carbon atom

in which only two unpaired electrons are available for bond
formation with other atoms. 27
 Cont’d
 at first sight carbon might appear to be only divalent;

 A typical C-H has a bond strength of 100 Kcal/mol.

 From this estimated excite; (400kJ/mol-97kJ/mol) is 300kJ/mol;

w/c is net the energy. 28
 In this case;

 In the excited state carbon has four unpaired electrons and

can form four bonds with hydrogen.
 What is the nature of the four C-H bonds in methane?
 Since excited carbon uses two kinds of orbitals (2s and 2p) for
bonding purpose, we might expect methane to have two kinds
of C-H bonds.

 The valence orbitals of a carbon atom are neither s or p but a

hybrid or mixture of orbitals.

29
 In addition;

 Since three p orbitals are mixed with one s-orbital, we call the
hybrid orbitals sp3 meaning that each of them has one-fourth s-
character and three fourth p-character.
 Each bond in CH4 is formed by overlap of an sp3 hybrid orbital
of carbon with a 1s orbital of hydrogen. These four bonds point
to the corners of a tetrahedron

Bond strength = 104 Kcal/mol

 The tetrahedral shape of an sp3 hybridized carbon.

30
 Question (2)

1) Describes in detail and draw the hybridization features of

Ethane (C2H6).
i) sp2-hybridization: The combination of one s and two p-orbitals
to form three hybrid orbitals of equal energy.
 For example: BF3 Molecule

 These sp2 hybridized orbitals are oriented at an angle of 120°.

 When three sp2 hybridized orbitals of B overlaps with three p
orbitals of fluorine, three σ -bonds are formed with bond angle
31
120°. The shape of BF molecule is trigonal planar.
 Question(3)

1) Describes the hybridization of Ethylene (C2H4) in

details and support with its diagram.
iii) sp-hybridization: The combination of one s and one p orbitals to
form two hybrid orbitals of equal energy.

 Example: In BeF2 Molecule the sp-hybridized orbitals of Be

overlap with the half-filled orbitals of two fluorine atoms to give
a linear shape.

32
Cont’d

33
Additional Illustration

34
 Question (4)

1) Explain and describes the detail hybridization of

Ethyne (C2H2)
2) Locate the types of hybridization and identify the
functional groups in the following molecules.

35
 sp3d-hybridization

 The combination of one s, three p and one d-orbitals to form five

hybrid orbitals of equal energy.
 Example: PCl5 molecule

 Therefore, the geometry of PCl5 is trigonal bipyramidal.

36
 Question (5)

1) Describe and explain the shape and detail

hybridization of SF4 and I3- molecules.
i) sp3d2-hybridization
 The combination of one s, three p and two d-orbitals to form six
hybrid orbitals of equal energy.

37
 Question (6)

i) Describes the shape and hybridization diagrammatic

representation of SbCl52-

ii) What is the hybridization of As in ASF5 molecules?

iii) What is the hybridization of central atom in the ClO3-

iv) Consider the hydrocarbon drawn below.

a) What is the hybridization of at each carbon atom

in the molecules?
b) How many ᵟ bonds are there in the molecule?
38
Summary

39
Cont’d…,

40
Factors influencing electron availability

 Inductive Effect;
 Resonance /Mesomeric
Effect;
 Steric Effect;
 Electromeric Effect;
 Hyperconjugative Effect;
 Tautomerism;

41
 Dipole moment; what ?

 It is the product of the magnitude of the

charge and the distance between the
centers of the positive and negative
charges.

For instance;

42
 Cont’d…

From above examples, two idea can be stated.

 it is not possible to measure the dipole moment of an
individual bond within a molecule;
 It can measure only the total moment of the molecule, which is
the vectorial sum of the individual bond moments
 The dipole moment can be reflected under cyclic structures as
follow:

43
 How does dipole moment depend on
electronegativity?

 EN is the ability of an atom to draw electrons to itself. w/c

means it is the tenancy of an atom to pull electrons towards it.
 A dipole is the uneven sharing of electrons between two atoms
engaging in a covalent bond.
 Dipoles can be determined by comparing the electronegativity
of the bonded atoms.
 Eg., methanol molecule the oxygen pulls electrons away from
the carbon making the carbon electron deficient.

44
 Inductive effect

 It is s an effect that occurs when the σ-bond in a molecule is

polarized.
 This is carried out through the chain of atoms in a molecule,w/c
effect of the transmission of unequal sharing of the bonding
electron a, leading to a permanent dipole in a bond;
 The effect on electron density in one portion of a molecule due
to EWG or EDG where emphasized.
 Has two types
i) Negative inductive effect or -I effect
ii) Positive inductive effect +I effect
45
 Negative inductive effect

 It is formed when an EN atom, such as a halogen, introduced to

a chain of atoms (generally, carbon atoms),
 It results unequal sharing of electrons generates a positive
charge which is transmitted through the chain.
 This causes a permanent dipole to arise in the molecule
wherein the electronegative atom holds a negative charge, and
the corresponding effect is the electron-withdrawing inductive
effect or the -I effect.
 For instance: Chloroacetic
acid is a stronger acid than
acetic acid. 46
 For examples

Positive Inductive effect

 It is formed when a chemical species with the tendency to
release or donate electrons, such as an alkyl group,
 is also introduced to a carbon chain, the charge is relayed
through the chain.

47
 Question(1)

1) Why alkyl groups are showing positive inductive

effect?
Application of Inductive effects

i) Stability of carbonium ions:

It increases with increases in number of alkyl group due to their
+ I effect; The alkyl group release an electrons to carbon, bearing
positive charge and thus stabilizes the ions.

48
 ii) Stability of free radicals

In the same way, the stability

of free radicals increases with
increases in number of alkyl
groups

iii) Stability of carbanions;

However it is decreases as the number of alkyl groups
increases; since the electro donating alkyl groups destabilize the
carbanions by increasing electron density.

49
 iv) Acidity and basicity Strength

EWG groups (-I) decreases the +ve charges on the carboxylate

ions and thus by stabilize it.
Hence the acidity strength increase when –I is present; but +I
decreases acidity.

 The reason for the increased acidity of the above compounds is

that the EN of halogen atoms stabilize the negatively charged
conjugate base
50
 In addition;

Exercise :Order the following

structure based on the
increasing acidity strength? 51
 Strength of Base!

EDG like alkyl groups increase the basic strength of amines;

whereas EWD groups like Aryl groups decrease the strength of
basic natures.
Thus, alkyl amines are stronger Lewis base than NH3, and aryl

amines are weaker than NH3. For instance (1) CH3NH2,

NH3,C6H5NH2.

52
 v) Reactivity of carbonyl groups!

The +I groups increases the e-s density at carbonyl groups.

Hence their reactivity towards NU- decreases.
For instance: formaldehyde is more reactive than acetaldehyde
and acetone towards nucleophilic addition reactions
 For instances;

Exercise: Why Inductive effect is less influencing than other

effects like resonance effects and hyperconjugation effects?
Support your answer with Example!
53
 Resonance Effects

 The polarity induced in a molecule by the interaction of a lone

pair of electrons with a pi bond or the interaction of two pi
bonds in nearby atoms.
 It is also the process whereby p-electrons can be delocalized
by exchanging double bonds and single bonds.
 This delocalization of positive and negative charges lead to
relatively stable captions and anions, respectively.
 For instance:

54
 Cont’d…
 Furthermore, the withdrawal effect or releasing effect of electrons attributed
to a particular substituent through the delocalization of π or pi-electrons.
 This can be seen by drawing various canonical structures is also a
resonance effect or mesomeric effect.
 For instance;

55
 Comparison

Inductive effect Resonance effect

 Sigma bonds move the  It is based on conjugation

electrons  The effect of resonance
 The inductive effect is defines the impact on a
created by the passage of molecule’s stability caused
an electrical charge across by the interaction of pi bond
a chain of atoms electrons
 The polarization of bonds  The existence of single and
causes the inductive effect double bonds together
 The degree of inductive causes the resonance
impact is affected by the effect
electronegativity values of  The resonance effect is
atoms. affected by the number of
double bonds and their
order

56
 Cont’d…

 are resonance contributors/forms

 no rapid interconversion
 not in equilibrium
 any of them does not exist in reality (hypothetical structures)
 the hybrid is more stable than any of the resonance forms

57
 Basic Rules of Resonance
1) Individual resonance forms are imaginary, not real
2) Resonance forms differ only in the placement of their  or non-
bonding electrons.
 Neither the position nor the hybridization of any atom changes
from one resonance form to another.

58
Other examples;…

59
 Resonance;…

3)The atoms covered by delocalized must be lie on the same

plane (planar).

 The larger tert-butyl groups twist the structure and prevent the
double bonds from lying in the same plane.
 All cannonical forms must have the same number of unpaired
electrons

4) Different resonance forms don´t have to be equivalent.

 The actual structure of the resonance hybrid is closer to the
more stable form than the less stable form 60
 Cont’d…

 Those cannonical forms which have more covalent bonds have

more contribution.

61
 Cont’d…
 Charge separation has less contribution;

 Large (+) or (-) charge decrease stability results less

contribution.

 Negative charge should reside on more electronegative atom

and positive charge on less electronegative atom.

62
 Cont’d;…

 Here is identical charge on adjacent atom is notfavarable,

5) Resonance forms must be valid Lewis structures

and obey normal rules of valence.

 a resonance form is like any other structure. The octet rule still
applies.

6)Resonance hybride is more stable than any individual

resonance form. 63
 Exercise
1) Consider the following benzene substituents:

Then, arrange based on the acidity strength and explain your reason?

2) Arrange the following structures according to increasing their stability and

justify why?

3) Explain which benzene species is more reactive towards to electrophilic

NO2 OH
substitutions reactions?

and
64
 Reactions Intermediates
 In Organic chemistry, a reactive intermediate or an intermediate is:
 a short-lived,
 high energy,
 highly reactive molecule; that results from homolytic and Heterolytic
bond fission.

 There are various important reaction intermediates which used in organic

reactions:
 free radicals,
 carbocations,
 carbonions, carbenes,
 benzyne and nitrenes.

65
 Carbocation
 An organic species which has a carbon atom bearing only six electrons in its
outermost shell and has a positive charge.
 The positively charged carbon of the carbocation is sp2 hybridized.
 The unhybridized p-orbital remains vacant.
 They are highly reactive and act as reaction intermediate.
 They are also carbonium ion.
 It is formed an intermediate species, as a result of the loss of two valence
electrons, normally shared electrons, from a carbon atom that already has
four bonds.
 For instance:

66
 Carbocation Stability
 The stability order of carbocations bearing only alkyl groups is

Cation stability is influenced by FOUR factors:

i) Hyperconjugation: is the delocalization of sigma electrons or lone pairs of

electrons into nearby empty or partially filled p- or pi-orbitals.
 It is caused by the overlapping of a sigma-bonding orbital or an orbital
containing a lone pair with a neighbouring pi-orbital or p-orbital.
 Increasing the number of alkyl substituents increases the stability of the
carbocation.
 This is due to orbital overlap between the σ bond and the empty p orbital
on the sp2 carbon.
67
 Cont’d…
 When an alkyl group is attached to an unsaturated system such as double
bond or a benzene ring, the order of inductive effect is actually reversed.

ii) Inductive Effects:

 Neighbouring alkyl groups contain electrons that are polarizable, and these
can shift towards the positive charge.
 However, that carbocations with higher substitution are always more stable
than those with less substitution.
 This as EDG can stabilize a carbocation, EWG act to destabilize
68
 For instances
 Carbonyl groups are electron-withdrawing by inductive effects, due to the
polarity of the C=O double bond. Consider the following two structures:
 W/c one is more stable?

 The difference in stability can be explained by considering the electron-

withdrawing inductive effect of the ester carbonyl and affected due to
Inductive effects.
 the effect decreases with distance and In 2 nd structure, the positive charge is
closer to the carbonyl group, thus the destabilizing electron-withdrawing
effect is stronger than it is 1st structure.
 This causes Carbonyl groups are electron-withdrawing by inductive effects,
due to the polarity of the C=O double bond.
69
 Exercise

A) In which of the structures below is the carbocation expected to be more

stable? Explain.

iii) Resonance Effects: Conjugation with a multiple bond or lone pairs of

electrons increase the stability of a carbocation.
 Eg.; allylic and benzylic systems are more stable than their saturated
counterparts.

70
 Cont’d…

 heteroatoms such as oxygen and

nitrogen are more electronegative
than carbon.
 heteroatoms are
electron withdrawing groups by
induction, they are
electron donating groups by
resonance, and it is this resonance
effect which is more powerful

 In the more stable carbocations, the heteroatom acts as an electron

donating group by resonance: in effect, the lone pair on the heteroatom is
available to delocalize the positive charge.
71
 Exercise

 State which carbocation in each pair below is more stable, or if they are
expected to be approximately equal. Explain your reasoning.

72
 Carbanions
 Hypothetical reaction C H + B C + B H

 Depend on C-H bond acidity

 Carbanions are bases and as well as nucleophiles.

 Geometry
C C

sp3 hybridized
hybridization of C is sp2
Pyramidal
Planar
can conjugate

 If the carbanion is derived from strong acid, the equilibrium

shifts toward the anion (weak base), which is stable.

73
 For instance
Compound pKa
CH4 43
CH6 37
stability of carbanioin and the acicity
Ph3C-H 33 of the molecule is increased
HC CH 25
O
20
C
CH3

N C CH2 C N 12

CH2(NO2)2 4

 Generation
1) a group attached to carbon cleaves without its electrons

R H R + H
H Li
e.g. + CH2CH2CH2CH2 Li
(n - BuLi )
phenyllithium 74
 Cont’d…

2) Decarboxylation O
-CO2
R C O R
75
 Cont’d…
H O O H O H
O -CO2
e.g. N C C O N C N C
O O
H H
O H
stablized by resonance
3) A negative ion adds to a C=C or C

+ Y C C
Y

 Stability of Carbanion

 Electron withdrawing groups

 Increased in s-character
 Formation of aromatic character
e.g. + B

H H
H 76
H
 Reaction of carbanions
a) Nucleophilic addition
O H2O
Nu M + C Nu C OM Nu C OH

tetrahedral intermediate
b) Grignard reaction

77
 c) Aldol condensation

 It is the condensation reaction of aldehydes and ketones

 It can be catalyzed either by a base or an acid
i) Base catalyzed
 ketone or aldehyde having -hydrogen
O O
OH
e.g. 2 CH3 C H H C CH CH CH3
 Mechanism

78
ii) Acid catalyzed
Cont’d…
O O CH3
e.g. 2 H3C C CH3 HCl H3C C CH C CH3 + H2 O
4-methyl-3-penten-2-one

 Mechanism

79
d) The Knovennagel condensation

 The condensation of carbon acid compounds with aldehydes to

afford α, β - unsaturated compounds.
Z H Z and Z' may be CHO, COR, CO2H, COOR,
C
Z' H CN, NO2, SOR, SO2R or similar -M groups.
R
Z H C O Z' Z
B Z 1) R
C C
Z' H Z' H 2) H2O
R R

 To prevent the formation of mixed products, use aldehyde lack

of α- hydrogen.
O O O
CH3 C C CH3
C H CH2 Et3N CH C
e.g.
+ C OEt
C O 0°C
O 80
EtO
 The Claisen Condensation Reaction

 Ester at least two -hydrogens undergo a reaction similar to

the aldol condensation to yield a β – keto ester.

 Mechanism

81
 Therefore;

 esters which have only one α-hydrogen do not undergo the

reaction.
Exercise (1)
1) Show the detail mechanism of the following reaction

a)

b) Show the detail reaction mechanism and complete the products?

82
 Mixed Claisen condensations

 Mixed Claisen reactions are successful only when one of the

two ester components has no α hydrogen and thus can’t form
an enolate ion.

 Example; Ethyl benzoate and ethyl formate are the two

common esters lacking ɑ hydrogens that are used in the
crossed Claisen condensation.

83
Mixed Claisen condensations cont’d…

e.g

 Exercise(2) show the detail reaction mechanism.

84
 The Dieckmann Cyclization:

 Intramolecular Claisen Condensations

 The Dieckmann condensation is the intrachemical chemical

reaction of diesters with base to give β-keto esters

 It can be carried out with diester and the reaction works best on
1, 6-diesters and 1, 7-diesters.
 Examples:
 Possible reaction mechanism:

85
 Possible Mechanism

 The cyclic β-keto ester produced in a Dieckmann cyclization

can be further alkylated and decarboxylated by a series of
reactions.
1)

86
 Exercise (3)
1)

2)

87
 Mechanism
O O O
OH CH C
H3C C CH2 H H3C C CH2 H2C CH3

O
H3C C CH2 + H 2O

O O O
H H O O
CH3 C CH2-CH2 CH C CH3 H3 C C CH2 CH2 CH2 C CH3 + OH

C6H5
O C6H5 O
O O O CH
OH CH CH
C6H5 CH CH C C6H5 CH
2)
C O
C O C6H5
C6H5

O H3O+

C6H5
O
enolate anion CH
CH2
C O

88
C6H5
 Cont’d…
H3O+
CO2Et Na OEt 1) Na OEt heat
2) O O O + CO2 + EtOH
CO2Et 2) C6H5CH2Br
EtO2C CH2C6H5 CH2C6H5
CO2Et

 The Michael Addition Reaction

 It is a conjugate additions of enolate anion to α, β –

unsaturated carbonyl compounds.
O O
-
C 1) OH
C O
R' CR2 H O R' CR2 CH CH
2 2 C R
2) H2C CH C R

O O
1) OH- O
1) H3C C CH3 H3C C CH2 CH2 CH2 C CH3
O
2) H2C CH C CH3

89
 Mechanism
O O O
OH CH C
H3C C CH2 H H3C C CH2 H2C CH3

O
H3C C CH2 + H 2O

O O O
H H O O
CH3 C CH2-CH2 CH C CH3 H3 C C CH2 CH2 CH2 C CH3 + OH

C6H5
O C6H5 O
O O O CH
OH CH CH
C6H5 CH CH C C6H5 CH
2)
C O
C O C6H5
C6H5

O H3O+

C6H5
O
enolate anion CH
CH2
C O

90
C6H5
 Free Radicals

 A radicals is a seven electron intermediate that adopts a flat,

sp2 structure despite the fact that it has four electron groups;
the lone electron resides in a half-filled p-orbital.

 This sp2 structure allows radicals to delocalize

the single electron through resonance.

 Radical alkyl intermediates are stabilized by similar physical

processes to carbocations: as a general rule, the more
substituted the radical center is, the more stable it is.

91
 Exercise (1)

1) State which carbon radical (free radical) in each pair below is more stable or
if they are expected to have comparable stability. Explain your reasoning.

92
 Free Radicals, Cont’d
 It is unstable compound;
 obtained by hemolytic processes

 occur in gas phase or in the non – polar solution

 radicals are unselective in their reaction.
 Once initiate, radicals follow chain reactions

93
 Formation of free radicals

i) Thermolysis
ii) For bonds require energy < 40 Kcal/mol (~165 KJ/mol

For instance

94
 Cont’d…
ii) Photolysis
•usually visible light and UV light are used
E  h UV 400 nm = ~ 300 KJ / mol
c UV 300 nm = ~ 400 KJ / mol
h UV 200 nm = ~ 600 KJ / mol


95
 Note that….

 Photolysis has more advantages than thermolysis due to

 Break strong bond which is not break at reasonable

temperature of thermolysis.
 Photolysis with a certain wavelength radiation can affect only
the bond which has the same energy order as the radiation.
Stability of free radicals
A) An alkyl group when attached with a trivalent carbon, it is
electron releasing

 it reflects the relative ease of radical formation,

96
 B)Hyperconjugation

 The more hyperconjugation of bonds, the more stable that

radical.

C) Steric relief gained

 Conjugate double bond enhances the stability of radicals by

delocalizing the radical through resonance.

97
 For instance;

Radical Reactions
 Addition of HBr:- the most important reactions of radicals

98
 Carbenes

 singlet and triplet

 Electron spin resonance (ESR) spectroscopy is used to detect

the two:-
- singlet – diamagnetic
- triplet – paramagnetic
 triplet carbine is less than the singlet by 8 kcal/mol of energy.
 They are differ in reactivity. 99
Cont’d…

100
 Generation

i) α – elimination – the common method

 For example

ii) Disintegration of compounds containing certain types of bonds

101
 Photolysis of a ketene

H H
e.g. C N N hv or C the deriving force is the formation
+ N N
H pyrolysis H of stable N2 molecule
diazomethane

 Reactions

102
 For instance,

 Since carbine is an electron deficient, so it would like to add on

the more electron rich double bond (the most substituted).

103
Cont’d…

104
 2) Insertion

 If no bond that carbine react, it inserts in the existing bonds.

 Mechanism

 Insert between Hydrogen and Carbon

 No synthetic use because difficult to control
105
 3) Rearrangement reactions

 This rearrangement of acyl carbenes to ketenes called the

Wolff rearrangement

106