University of Santo Tomas

Faculty of Pharmacy SCHOLIA TUTORIAL CLUB

ORGANIC CHEMISTRY

First Grading Period

Prepared by: Hajime Q. Nakaegawa

BS Biochemistry 2018

AY 2016-2017

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Outline of Topics to be discussed:

• Introduction to Organic Chemistry – Definition, Hydrocarbon and its Derivatives, Structural Formula Formats

• Nomenclature – How to name organic compounds.

• Carbon, Carbon, Carbon – Review on importance of carbon, principles involved, hybridization, bonds

• Isomers and Stereochemistry – definition, types and classifications

• Chirality of Molecules - Introduction, Stereoisomers, Conformational Isomers (Straight Chain and Cyclic, Orientations (Axial and Equatorial), Configurational Isomers, Meso Compounds

• Relative and Absolute Configuration – Meaning

• Structural Effects – Electron delocalization, resonance, CH hyperconjugation, LPD, inductive effect, steric effect, and angle strain

Lesson 1 Introduction to

Organic Chemistry Definition, Hydrocarbon and its

Derivatives, Structural Formula Formats

Organic Chemistry • Study of carbon and its compounds?

• Study of organic compounds? …duh.

• Study of hydrocarbon compounds and its derivatives

TWO THINGS INVOLVED IN ORGCHEM

1. HYDROCARBON 2. HYDROCARBON DERIVATIVES

Few more notes to consider:

• The building block of structural organic chemistry is

the tetravalent carbon atom

• With few exceptions, carbon compounds can be

formulated with four covalent bonds to each

carbon, regardless of whether the combination is

with carbon or some other element.

1. HYDROCARBONS • A hydrocarbon is an organic compound consisting

entirely of hydrogen and carbon ONLY.

1. HYDROCARBON

Aliphatic (R) Aromatic (Ar)

Uncyclic / Open Structure Factors to consider:

1. Should be cyclic (closed

structure / no terminal

point)

2. Planar (2D structure)

3. Has conjugated double

bond (alternating)

4. Follows Huckel’s Rule #pi e- = 4n + 2

Saturated Unsaturated

No pi bond

formation or all

are single

bonded

Ex. Alkanes

Contain pi bonds

/ has double or

triple bonds

Ex.

Alkenes/Alkynes

General Rule for knowing if its Aromatic or

Aliphatic. If the organic compound does NOT follow the four general factors of an

aromatic compound, then it’s

aliphatic.

2. Hydrocarbon

Derivatives

• Hydrocarbon derivatives are formed when there is a substitution of a functional group at one or more of these positions.

• Order of priority MUST be observed

Kekule Formulas • A Lewis structure in which bonded electron pairs in

covalent bonds are shown as lines.

• FYI: Kekulé was the first to suggest a sensible structure for

benzene. He said The carbons are arranged in a

hexagon, and he suggested alternating double and

single bonds between them.

Condensed Formula • To save space and time in the representation of

organic structures, it is common practice to use

"condensed formulas" in which the bonds are not

shown explicitly.

• In using condensed formulas, normal atomic

valences are understood throughout.

3D Structural Formula

• Sample:

• Acetone

• IUPAC Name:

2-propanone

Skeletal Formula • Also called the Line-Angle Formula

• It is represented in two dimensions, as on a page of

paper.

• A skeletal formula shows the skeletal

structure or skeleton of a molecule, which is

composed of the skeletal atoms that make up the

molecule.

Lesson 2 Nomenclature

HOW TO NAME ORGANIC

COMPOUNDS

Introduction • The primary goal of the International Union of Pure

and Applied Chemistry (IUPAC) naming system is to

create an unambiguous relationship between the

name and structure of a compound.

• With the conventions established by IUPAC, no two

distinct compounds have the same name. The

IUPAC naming system greatly simplifies chemical

naming.

STEPS IN NAMING

1. Identify the Longest Carbon Chain Containing the

Highest-Order Functional Group

• This will be called the parent chain and will be used to

determine the root of the name.

• Keep in mind that if there are double or triple bonds

between carbons, they must be included

• If one of the functional groups would provide a suffix for

the compound (for example, an alcohol, which will be

discussed later), then the parent chain must contain this

functional group.

• Keep in mind that the highest-priority functional group

(with the most oxidized carbon) will provide the suffix.

2. Number the Chain

• As a convention, the carbon numbered 1 will be the

one closest to the highest-priority functional group.

• If the functional groups all have the same priority,

numbering the chain should make the numbers of the

substituted carbons as low as possible.

3. Name the Substituents • Substituents are functional groups that are not part of

the parent chain.

• A substituent’s name will be placed at the beginning of

the compound name as a prefix, followed by the name

of the longest chain.

4. Assign a Number to Each

Substituent

• Pair the substituents that you have named to the

corresponding numbers in the parent chain.

• Multiple substituents of the same type will get both the

di–, tri–, and tetra– prefixes that we have previously

noted and also a carbon number designation—even if

they are on the same carbon.

5. Complete the Name • Names always begin with the names of the substituents

in alphabetical order, with each substituent preceded by its number.

• Note: Prefixes like di–, tri–, and tetra– as well as the hyphenated prefixes like n– and tert– are ignored while alphabetizing.

• Nonhyphenated roots that are part of the name, however, are included; these are modifiers like iso–, neo–, or cyclo–.

• The numbers are separated from each other with commas, and from words with hyphens.

• Finally, we finish the name with the name of the backbone chain, including the suffix for the functional group of highest priority.

Example

PRACTICE EXERCISE

Answer Key

• View Practice Questions pg.55

Lesson 3 Carbon, carbon,

carbon… Review on importance of carbon,

principles involved, hybridization,

bonds

Why Carbon? • Molecules with carbon are ORGANIC.

• Carbon dioxide and molecules without carbon are

INORGANIC.

• FACTORS WHY CARBON IS IMPORTANT

• 1. They are versatile. Can form up to four bonds (single,

double, or triple) in rings or in chains

• 2. Bonds formed are high in energy. Ex. Diamond

• Functional groups in organic molecules

o Are LESS stable than the carbon backbone but

are more likely to participate in chemical reactions

o Determine the characteristics and chemical

reactivity of organic molecules.

Principles involved • 1. Aufbau Principle - electron will successfully occupy the

available electrons in increasing energy. German term

meaning building up

• In short, lowest energy first.

• 2. Hund’s Rule of Multiplicity – When there are more than

one orbital at a particular energy level, only one electron

will fill each orbital until each has one electron. After this,

pairing will occur with the addition of one electron to

each orbital.

• In short, degenerate orbitals must have 1 electron first

• 3. Pauli’s Exclusion Principle (by Wolfgang Pauli) – In a

given atom, no two electrons can have the same set of

four quantum numbers, therefore each orbital can only

hold two electrons.

• In short, two electrons only and must be of opposite spin.

Hybridization • All atoms undergo hybridization red + white = pink…

• PURPOSE OF HYBRIDIZATION? Form equivalent orbitals

(orbitals with the same shape)

Lesson 4 Isomers and

Stereochemistry Definition, types and classifications

Stereochemistry • the branch of chemistry concerned with the three-

dimensional arrangement of atoms and molecules and

the effect of this on chemical reactions.

• Branch of chemistry that studies isomers (duh), and a

property of a compound to have isomers.

• IMPORTANT NOTES TO TAKE:

- We need at least one sp3-hybridized carbon

- To represent molecules as 3D objects.

ISOMERS • Isomers - each of two or more compounds with the

same molecular formula but a different arrangement of

atoms in the molecule and different properties.

• They can differ in:

a. ARRANGEMENT OF BONDS – refers to actual bonds

between atoms, isomers with a different connectivity of

their atoms

b. CONFIGURATION – refers to the permanent spatial

positions of two isomers with the same attachments.

Two configurational isomers are never identical to each

other.

c. CONFORMATION – refers to temporary spatial positions,

and two conformational isomers can be identical at

one point.

ISOMERS Red means ‘difference in’

Structural / Constitutional Isomers

Arrangement

Skeletal

Stereoisomers Spatial position

Positional Functional

Attachment Placement

of functional group

Actual functional group

Configurational Conformational

tetrahedral Unsaturated/cyclic

Geometric

Enantiomers Diastereomers

Mirror images Non Mirror images

Optical Isomers

Permanent

spatial

difference

Temporary

spatial

difference

Flowchart of Isomer Relationship

Exercise 1 2

3

6

4

5

7 8

Answer Key 1. Positional Isomers – because they differ in the

placement of their functional groups

2. Functional Isomers – one is aldehyde, another is ketone

3. Enantiomers – they are optical and mirror images

4. Geometric Isomers - there is a restricted rotation of the double bond due to the pi bond which means they don't readily interconvert

5. Skeletal Isomers

6. Positional Isomers – because they differ in the placement of their functional groups

7. Diastereomers

8. Diastereomers

Lesson 5 Chirality of Molecules Introduction, Stereoisomers, Conformational

Isomers (Straight Chain and Cyclic, Orientations (Axial and Equatorial),

Configurational Isomers, Meso Compounds

Introduction • Stereoisomers – have the same molecular formula and

connectivity of atoms in their molecules, but different 3D

orientation of their atoms in space.

• Enantiomers – (1)non superimposable mirror images, (2)

the term itself always refers to pairs, and (3) majority of

biomolecules and one-half of the used medications

used in human medicine exhibit enantiomerism

• The most common cause of enantiomerism is a carbon

bonded to four different groups.

Conformational vs Configuration

• Conformational isomers or conformers differ in

rotation around single (σ) bonds

• Configurational isomers can be interconverted only

by breaking bonds.

Conformational Isomers • Conformational isomers are, in fact, the same molecule,

only at different points in their natural rotation around single (σ) bonds.

• While double bonds hold molecules in a specific position (as explained with cis–trans isomers later), single bonds are free to rotate.

• Conformational isomers arise from the fact that varying degrees of rotation around single bonds can create different levels of strain.

• Conformations are easy to see when the molecule is depicted in a Newman projection, in which the molecule is visualized along a line extending through a carbon–carbon bond axis.

Straight-Chain

Conformations

• For butane, the most stable conformation occurs when the two methyl groups (containing C-1 and C-4) are oriented 180° (duh) away from each other.

• WHY 180?? In this position, there is minimal steric repulsion between the atoms’ electron clouds because they are as far apart as they can possibly be.

• Thus, the atoms are “happiest” BECAUSE they are in their lowest-energy state. Because there is no overlap of atoms along the line of sight (besides C-2 and C-3), the molecule is said to be in a staggered conformation.

• Specifically, it is called the anti conformation because the two largest groups are antiperiplanar (in the same plane, but on opposite sides) to each other.

• This is the most energetically favorable type of staggered conformation. (parang sa pagmamahal lang yan)

• The other type of staggered conformation, called gauche (means unsophisticated or awkward), occurs when the two largest groups are 60° apart.

• When the two methyl groups directly overlap each other with 0° separation, the molecule is said to be totally eclipsed and is in its highest-energy state. Totally eclipsed conformations are the least favorable, energetically, because the two largest groups are synperiplanar (in the same plane, on the same side)

Nothing I can say A total eclipse of the

heart

Cyclic Conformations • Cycloalkanes can be either fairly stable compounds, or fairly

unstable—depending on ring strain. Ring strain arises from three factors: angle strain, torsional strain, and nonbonded strain (sometimes referred to as steric strain).

• Angle strain results when bond angles deviate from their ideal values by being stretched or compressed.

• Torsional strain results when cyclic molecules must assume conformations that have eclipsed or gauche interactions.

• Nonbonded strain (van der Waals repulsion) results when nonadjacent atoms or groups compete for the same space.

• Nonbonded strain is the dominant source of steric strain in the flagpole interactions of the cyclohexane boat conformation.

Conformations of Cycloalkanes • To alleviate the strain, cycloalkanes attempt to adopt various

nonplanar conformations.

• Cyclobutane puckers into a slight “V” shape.

• Cyclopentane adopts what is called an envelope

conformation.

• Cyclohexane exists mainly in three conformations called the

chair, boat, and twist- or skew-boat forms.

• The most stable conformation of cyclohexane is the chair

conformation, which eliminates all three types of strain.

Axial-Equatorial Orientation

• The hydrogen atoms that are perpendicular to the

plane of the ring (sticking up or down) are called

axial, and those parallel (sticking out) are called

equatorial.

• The axial–equatorial orientations alternate around the

ring; that is, if the wedge on C-1 is an axial group, the

dash on C-2 will also be axial, the wedge on C-3 will

be axial, and so on.

• Cyclohexane can undergo a chair flip in which one chair form is converted to the other.

• In this process, all axial groups become equatorial, and all equatorial groups become axial.

• All dashes remain dashes, and all wedges remain wedges. This interconversion can be slowed if a bulky group is attached to the ring;

• tert-butyl groups are classic examples of bulky groups on the MCAT. For substituted rings, the bulkiest

• group will favor the equatorial position to avoid nonbonded strain (flagpole interactions) with axial

• groups in the molecule

Cis and trans

• If both groups are located on the same side of the

ring, the molecule is called cis; if they are on

opposite sides of the ring, it is called trans

Cis/trans vs E/Z • In simple compounds with only one substituent on

either side of the immovable bond, we use the

terms cis and trans. For more complicated

compounds with polysubstituted double bonds,

(E)/(Z) nomenclature is used instead.

Configurational Isomers • Unlike conformational isomers that interconvert by

simple bond rotation, configurational isomers can only

change from one form to another by breaking and

reforming covalent bonds.

• The two categories of configurational isomers are

enantiomers and diastereomers.

• Both enantiomers and diastereomers can also be

considered optical isomers because the different

spatial arrangement of groups in these molecules

affects the rotation of plane-polarized light.

• An object is considered chiral if its mirror image

cannot be superimposed on the original object.

• This implies that the molecule lacks an internal plane

of symmetry.

• Two molecules that are nonsuperimposable mirror images of each other are called enantiomers.

• Molecules may also be related as diastereomers. These molecules are chiral and share the same

• connectivity, but are not mirror images of each other. This is because they differ at some (but not all) of

• their multiple chiral centers.

Polarized and Optical Activity

• Optical activity refers to the rotation of this plane-polarized light by a chiral molecule.

• At the molecular level, one enantiomer will rotate plane-polarized light to the same magnitude but in the opposite direction of its mirror image (assuming concentration and path lengths are equal).

• A compound that rotates the plane of polarized light to the right, or clockwise, is dextrorotatory (d-) and is labeled (+).

• A compound that rotates light toward the left, or counterclockwise, is levorotatory (l-) and is labeled (–). The direction of rotation cannot be determined from the structure of a molecule and must be determined experimentally.

Polarizer

Diastereomers • Diastereomers are non-mirror-image configurational

isomers.

• Diastereomers occur when a molecule has two or

more stereogenic centers and differs at some, but

not all, of these centers.

• This means that diastereomers are required to have

multiple chiral centers. For any molecule with n

chiral centers, there are 2n possible stereoisomers.

Meso compound • For a molecule to have optical activity, it must not

only have chiral centers within it, but must also lack

a plane of symmetry.

• Thus, if a plane of symmetry exists, the molecule is

not optically active, even if it possesses chiral

centers. This plane of symmetry can occur either

through the chiral center or between chiral centers.

• A molecule with chiral centers that has an internal

plane of symmetry is called a meso compound.

• As shown in this image, D- and L-tartaric acid are both optically active, but meso-tartaric acid has a plane of symmetry and is not optically active.

• This means that even though meso-tartaric acid has two chiral carbon atoms, the molecule as a whole does not display optical activity.

• Meso compounds are essentially the molecular equivalent of a racemic mixture.

Lesson 6 Relative and Absolute

Configuration Meaning

• The configuration of a stereoisomer refers to the spatial

arrangement of the atoms or groups in the molecule.

• The relative configuration of a chiral molecule is its

configuration in relation to another chiral molecule

(often through chemical interconversion).

• We can use the relative configuration to determine

whether molecules are enantiomers, diastereomers, or

the same molecule.

• Absolute conformation of a chiral molecule describes

the exact spatial arrangement of these atoms or

groups, independent of other molecules.

(E) and (Z) nomenclature • (E) and (Z) nomenclature is used for compounds with

polysubstituted double bonds.

• Using the Cahn–Ingold–Prelog priority rules, priority is

assigned based on the atom bound to the double-

bonded carbons.

• The alkene is named (Z) (German: zusammen,

“together”) if the two highest-priority substituents on

each carbon are on the same side of the double

bond and (E) (entgegen, “opposite”) if they are on

opposite sides.

The simple priority rules • The higher the atomic number, the higher the

priority. If the atomic numbers are equal, priority is determined by the next atoms outward; again, whichever group contains the atom with the highest atomic number is given top priority.

• If a tie remains, the atoms in this group are compared one-by-one in descending atomic number order until the tie is broken.

• Z = “z”ame sid; E = “e”pposite side

• View Practice Questions pg.103

Lesson 7 Structural Effects

Structural Effects • Effect of the structure on STABILITY and REACTIVITY of the

organic compound.

• 1. Electron Delocalization

• A. pi electron delocalization

• B. sigma (σ) electron delocalization / CH hyperconjugation

• C. Lone pair delocalization

• 2. Inductive Effect

• A. Electron Attracting or Withdrawing Inductive Effect

• B. Electron Repelling or Donating Inductive Effect

• 3. Steric Effect

• 4. Angle Strain

1. Electron Delocalization • Electrons belonging to certain molecules are not attached

to a particular atom or bond in that molecule.

• These electrons are said to be "delocalized" because they

do not have a specific location (are not localized); they

cannot be drawn in a simple Lewis structure. Rather, they

exist in orbitals that include several atoms and/or bonds.

• You can imagine these orbitals as clouds surrounding parts

of the molecule.

• Delocalization gives molecules resonance stability, stronger

acidiy and based on the resonance stability, we can

determine the range of absorbtion of ultraviolet and visible

light of a molecule in the light spectrum.

• The actual structure with delocalized electrons is called a

resonance hybrid.

Molecular Orbital Theory • Delocalization is characteristic of the molecular

orbital theory concerning the structure of atoms.

• Rather than the lone pair of electrons contained in specific bonds (as in the valence-bond theory), the MO (molecular-orbital theory) theorizes that electrons exist in orbitals that are spread over the entire molecule.

• The MO theory explains molecules such as ozone and benzene, which cannot be drawn satisfactorily with one Lewis structure, and are therefore described as resonance hybrids. Molecular orbitals solve this issue through the concept of delocalized electrons.

A. Pi electron delocalization (Resonance)

• The delocalized electrons mainly come from a pi

bond. Recognize that a conjugated diene is

actually a sp2 system, and will demonstrate

resonance.

B. Sigma pi delocalization (CH hyperconjugation)

• Delocalized electrons come from a sp3 hybridized

carbon.

C. Lone pair delocalization

• The delocalized electrons mainly come from a lone

pair, most often from a nitrogen or oxygen atom.

2. Inductive Effect • An inductive effect is an electronic effect due to the

polarization of σ bonds within a molecule or ion. This

is typically due to an electronegatvity difference

between the atoms at either end of the bond.

• The more electronegative atom, the more it pulls

the electrons in the bond towards itself creating

some bond polarity

• Basis here is the polarity.

• Three considerations:

• 1). electronegativity, 2). bonding order and charge

and 3). position within a structure.

Electron attracting or Withdrawing Inductive Effect

• Has a Negative inductive effect (-I)

• Electrons are draw on towards atoms with:

• 1. Excess positive charges

• 2. Electronegative atoms

• 3. Atoms with increased electronegativity due to

more electrons

Electron donating inductive effect

• Has a positive inductive effect (+I)

• Electrons are repelled by:

• 1. Less electronegative atoms (ex. C)

• 2. Negatively charged functional groups

3. Steric Effect • Electrical instability caused by closing in of electron

dense atoms.

• Atoms in molecules occupy certain amounts of

space. If they are brought too close to each other,

their electron clouds may repel each other causing

a steric strain that may affect the reactivity of the

molecule.

4. Angle Strain • Electrical instability in atoms closing in with small

angles in cyclic compounds.

• Atoms in cyclic molecules share a certain angle

between each other. The ideal is 109.5 degrees. As

the goes farther or lower than that, the repelling

effect of electrons on each other increases.

END Failure is the opportunity to begin again, more

intelligently.