Overview of functional groups

2° Alcohol
Alkane
OH
Me Ketal
HO Ether
O
H OH H
Me
O O
OMe
O HO
O
HO
HO O Ester O
Me
O
O
Me
AcO
AcO
Ketone
Diene Me OH

3° Alcohol
Alkene

Altohyrtin C
Introduction to Organic Compounds: Alkane Structure
Introduction to Organic Compounds: Alkane Structure
 Alkanes and Alkyl Chains

H3C CH3 H3C CH3 CH3

H H3C H3C

methane ethane propane n-butane

H3C H3C n-butane and
H3C H3C isobutane are
methyl group ethyl group propyl group n-butyl group constitutional
isomers
H3C

H3C CH3
isomethane isoethane isopropane? isobutane

CH3
H3C
H3C
H3C
isomethyl group isoethyl group isopropyl group isobutyl group

H3C
H3C
N/A
CH3 H3C CH3

sec-butane tert-butane sec-butyl group tert-butyl group

Alkyl halides, alkyl alcohols, and alkyl amines

H3C CH3 H3C CH3 CH3

H H3C H3C

methane ethane propane n-butane

H3C H3C
Cl H3C Cl Cl H3C Cl
methyl chloride ethyl chloride propyl chloride n-butyl chloride

H3C H3C
OH H3C OH OH H3C OH
methyl alcohol ethyl alcohol propyl alcohol n-butyl alcohol

H3C H3C
NH2 H3C NH2 NH2 H3C NH2
methylamine ethylamine propylamine n-butylamine
 My name is Neo
H3C
H3C
H3C CH3
CH3
H3C CH3 H3C H3C
n-pentane isopentane neopentane

H3C
H3C
H3C
H3C H3C H3C
n-pentyl group isopentyl group neopentyl group

iso, sec, tert, neo...obviously the number of constitutional isomers increases with the number of carbons,
so that once we get to decane, there would be many names to remember.

fortunately, a method of systematic nomenclature was developed...

 Systematic Nomenclature

• When common names became to hard to keep track of, the International Union of Pure and
Applied Chemistry (IUPAC) devised a system for naming all organic compounds.
• Why you NEED to know nomenclature:
– It’s on the MCAT
– It’s useful for ordering chemicals
– A general knowledge of nomenclature facilitates discussion about organic chemistry
– It will be on the exams, but it is more important to be able to go from a name to a
structure than from a structure to a name.

• Why you DON’T NEED to know nomenclature:

– Very simple molecules are always referred to by their common names…eg acetone, not
dimethyl ketone.
– Very complex molecules get trivial names, eg Altohyrtin C
– Chemical databases are substructure searchable with graphical interfaces
 Systematic Nomenclature: Rule #1
Determine the number of carbons in the longest continuous carbon chain...this is the "parent"
hydrocarbon and forms the "last name" of the compound CH3

CH3
CH3 CH3
H3C H3C

4-methyloctane 4-propyloctane
octane

H3C nonane H3C

CH3 CH3
H3C octane H3C

4-pentyloctane 4-butylnonane

H3C
CH3
H3C decane

5-propyldecane
 Systematic Nomenclature: Rule #2

Substituent names appear before the parent name but both words are joined to form a single name.

The number of the carbon bearing the substituent is separated from the name with a hyphen.

Use the lowest possible number to indicate the position of a substitutent (this is a recurring theme).

CH3
CH3
H3C octane

4-methyloctane
5-methyloctane
 Systematic Nomenclature: Rule #3
If there is more than one substituent, substituents are listed alphabetically, NOT numerically

Use the lowest possible numbers.

Substituent numbers separated by hyphens on both sides if necessary

If two substituents are the same, prefixes di, tri, tetra, etc are used, but ignored for alphabetization

Prefixes iso, neo, and cyclo are NOT ignored for alphabetization

CH3
CH3
CH3
H3C octane

4-methyl-6-ethyloctane

3-ethyl-5-methyloctane

CH3 CH3
CH3
H3C
CH3
2,2,4-trimethylpentane
 Sidenote: Isooctane

CH3 CH3
CH3
H3C
CH3

2,2,4-trimethylpentane
(aka isooctane)

What is the Octane Rating?

Why are branched alkanes considered more desirable for use as gasoline?

Can linear alkanes be converted to branched alkanes?

George Olah developed "superacid" catalysts that perform this process, and for his work he was
awarded the Nobel Prize in 1994.

Superacids

Linear Alkanes, low octane rating Branched Alkanes, higher octane rating
 Systematic Nomenclature: Rules #4 & 5
If both directions lead to the same numbers, maximize the number of LOW numbers

CH3 CH3
CH3
H3C
CH3
2,2,4-trimethylpentane

2,4,4-trimethylpentane

If the same substituent numbers are obtained in both directions, the first group cited alphabetically gets the
lower number...ie minimize number AND alphabetical position

CH3
CH3
H3C octane

CH3
4-methyl-5-ethyloctane

4-ethyl-5-methyloctane
 Systematic Nomenclature: Rules #6 & 7

If a compound has two or more chains of the same length, the parent hydrocarbon is the chain with the
greatest number of substituents

CH3
H3C

H3C CH3
3-ethyl-2-methylhexane (2 substituents)

3-isopropylhexane (1 substituent)

Isopropyl and tert-butyl are acceptable, though non-IUPAC, names for substituents, but IUPAC names are
generally preferred

In the event that a substituent has substituents of its own, parentheses are used

CH3
CH3
H3C octane

H3C CH3
4-isopropyl-5-methyloctane

4-methyl-5-(1-methylethyl)octane
 Cycloalkanes
H2
H2
H2 C
C
C H2C CH2 H2C CH2
H2C CH2
H2C CH2 H2C CH2 H2C CH2
H2 C CH2
C
H2

cyclopropane cyclobutane cyclopentane cyclohexane

•If the molecule is unsubstituted name = Me

Me
“cyclo” + parent alkane

•if the molecule is substituted, then the

parent alkane is the ring, unless the methylcyclobutane
pentylcyclopbutpane
substituent is larger (more carbons) 1-cyclobutylpentane

•If the ring has two substituents, they are

Me
cited in alphabetical order, first one Me
getting number “1”

1-ethyl-2-methyl-cyclopentane
 Alkyl Halides

• R refers to any alkyl group…X refers to any halogen, so an alkyl halide = RX

a primary a secondary a tertiary

carbon carbon carbon

R Br R Br
R Br C C
C H R
H H R R

• Alkyl halides are named just like substituted alkanes using the substituent prefixes "fluoro,"
"chloro," "bromo," and "iodo." (don't worry about astatine!)
Me
Me
Br
3-bromooctane
 Ethers
a symmetrical an unsymmetrical
ether ether

R R R R'
O O

Ethers are named by their respective alkyl chains in alphabetical order followed by the word
"ether." Di-, tri-, sec-, tert- are used as previously described.

Me O
Me
ethyl methyl ether

IUPAC nomenclature employs alkoxy group substituents

CH3 = methyl CH3O = methoxy

CH3CH2 = ethyl CH3CH2O = ethoxy

Me
Me
O Me 4-isopropoxyoctane

Me
 Alcohols
a primary a secondary a tertiary
alcohol alcohol alcohol

R OH R OH
R OH
R
R R

Alcohols are generally named by the alkyl substituent followed by the word "alcohol."

IUPAC demands that alcohols are named by dropping the "e" from the name of the parent
alkane and replacing it with "ol"...therefore alkanes become alkanols:

Me OH
OH Me OH
Me
Me
methyl alcohol ethyl alcohol isopropyl alcohol
methanol ethanol isopropanol
For alcohols derived from larger carbon chains, the position is designated by a number in
one of 2 ways: either before the name of the parent hydrocarbon or immediately before the
suffix "ol" separated by hyphens:

Me Me 3-pentanol or
OH pentan-3-ol
 Alcohols, cont’d
The parent hydrocarbon of a compound with a functional group suffix is the longest chain
that contains the suffix. The parent hydrocarbon is numbered such that the functional
group suffix gets the lowest possible number.

Me OH 2-ethyl-1-hexanol or
Me OH 2-ethyl-hexan-1-ol
Me
Me
the heptyl chain does not contain the functional group, but the hexyl chain does...

If there is a substituent and a functional group suffix, the functional group suffix gets the
lowest possible number.

Me OH 4,4-dimethyl-2-pentanol
Me
Me Me
Me
If the same number for the functional group suffix
is obtained in both directions, the substituent gets OH Me
the lowest possible number.
Me Me OH
Substituents are listed in alphabetical order.
2-methyl-4-heptanol 3-methyl-cyclohexanol
Cyclic alcohols have an implied 1-position, so it is 6-methyl-4-heptanol 5-methyl-cyclohexanol
not necessary to mention it.
 Amines

a primary a secondary a tertiary

amine amine amine

R H R R R R
N N N
H H R

R NH2 R NH2
R NH2
R
R R

a primary a primary a primary

amine attached to amine attached to amine attached to
a primary carbon a secondary carbon a tertiary carbon
 Amines, cont’d

Amines, unlike alkyl halides, alcohols, and ethers, have common names that are one word .

NH2 OH
Me Me
propylamine propyl alcohol

Amines are named like ethers, ie the names of the alkyl substituents followed by the word
"amine," in analogy to ethers.

Me N Me
Me O Me
Me
triethylamine diethyl ether

IUPAC naming involves replacing the "e" at the end of the parent hydrocarbon with "amine," in
analogy to alkanols...alkanes become alkanamines. Substituents are listed alphabetically and
designated with either a number or "N" to indicate their attachment to either the parent
hydrocarbon or the nitrogen.

Me Me
4-bromo-N,N-dimethyl-2-pentanamine
Br N
Me Me
 Properties of Organic Molecules
Forces: From weakest to strongest...

1) van der Waal's forces (VDW). This attractive force results from induced dipole-dipole
interactions, due to the Heisenberg uncertainty principle, the locations of the electron density
in a molecule is not fixed. At any instant a local minimum of electron density will result in a
small positive charge (δ+) charge and a concommitant small negative charge (δ-).

VDW forces hold alkanes together...as a result, the boiling point (bp) of alkanes are lower
than other compounds of similar molecular weight. Branching decreases bp due to reduced
contact area.
Me Me
Me
Me
Me Me Me Me Me
pentane: bp=36 isopentane: bp=28 neopentane: bp=10
 Properties of Organic Molecules
Forces, cont’d

2) Dipole-dipole interactions. Molecules with dipoles are attracted to each other when their dipoles are
misaligned. Dipole-dipole interactions are stronger than VDW forces, so as a result, molecules with a
dipole moment will have higher bps than those without.

dipole-
δ+ dipole
interaction
δ-
O O
δ-
δ+
tetrahydrofuran cyclopentane
bp=65 bp=49
Sidenote: Why are general anesthetics administered as gases?
Examples of compounds used for general anesthetics:
H H H H Et2O H H H
Me O H H
H H EtCl
H O diethyl ether H O ethyl vinyl ether H H
H H
H bp = 35 ÞC H H (VinamarTM) H Cl ethyl chloride
H H

Cl H Cl
Br F Br O H OCH3
H F Cl Cl
Cl CF3 H
Cl F F F H F F
2-bromo-2-chloro-1,1,1-trifluoromethane 2,2-dichloro-1,1-difluoroethyl methyl ether
(halothane, FluothaneTM), bp = 50 ÞC (methoxyflurane, PenthraneTM)

An ideal anesthetic is an easily volatilized inhalant that can dissolve in the bloodstream (an aqueous
solution) to circulate to the brain. Chemical properties are dictated by the strength of intermolecular
forces between molecules. For these compounds, only weak dipole-dipole interactions exist (no
hydrogen-bonding), therefore, they have a high vapor pressure and can easily change from liquid to gas.
The distribution of anesthetic is a collection of equilibrium processes:
Fat

The equilibrium of
Blood
Tissues with anesthetic between the
Inhaled gas Alveoli high blood flow blood and the brain
Stream
(including brain)
tissue determines the
level of unconsciousness
of the patient.
Sleketal
Muscle
 Properties of Organic Molecules, cont’d

3) Hydrogen Bonds. Molecules with functional

groups that contain hydrogen attached to either
oxygen or nitrogen can hydrogen-bond to each
other, and thus have much higher boiling
points.

Hydrogen bonding is an important attribute of

many organic molecules and is responsible for
many biological effects in living systems

Hydrogen bonding is strongest when the

hydrogen-bearing atom is more electronegative:
the OH in an alcohol engages in stronger
hydrogen bonding than the NH of an amine.

H H
O
H H N C H
H H H H
water ammonia methane
bp=100 bp= -33 bp= -167
 Hydrogen Bonding: As It Applies to Biology

α-helix

Proteins are shaped

by hydrogen bonding β-sheet

N R5
H
H R4 O
N
N
H O
3 O 2
R R
N H
O R1 O R3 O R5 H
N
H H H
N N N O O
N N N N R1
H H H
O R2 O R4 O O

Linear Structure

alpha helix
Hydrogen Bonding: the origin of life
DNA is also held together by hydrogen bonding
 Melting Point and Solubility:
Two important properties for lab work, Lab Experiment #1

Melting Point:
Neutral organic molecules are attracted to each other by weak forces…therefore they
have relatively low melting points, up to 200 ºC. NaCl (held together by strong, ionic
forces) has a very high melting point.
The melting point serves as an index of purity, since impurities will alter the melting
point of a compound.

Solubility:
“Like dissolves like”…Neutral organic molecules are generally soluble in non-polar
solvents
More hydrocarbon sidechains make a molecule less polar…methanol is very polar
and dissolves in water, while octanol is immiscible with water.
 Sidenote: Why won’t water relieve the burning sensation
of a chili pepper?

O
O CH3
H3C N
H CH3
HO

capsaicin - the pungent ingredient in red and green chili pepers

(measured in Scoville Heat Units)

Remember the common expression of “like dissolves like”?

The organic, non-polar structure of capsaicin makes this compound practically insoluble in
water, but freely soluble in oil, fats and alcohols, i.e. organic solvents. Therefore, water
cannot “cool” or dilute the burning sensation because it cannot dissolve the capsaicin.

Using chemical intuition, the burning sensation of a chili pepper is more effectively
alleviated with something containing fat (like sour cream or whole milk) or something
containing alcohol (like beer or tequila).

http://www.chilepepperinstitute.org/
 Sidenote: LogP & cLogP
Me
[Drug]octanol O-Na+
P=
[Drug]water O
MeO
Naproxen sodium
(Alleve) cLogP = 2.67

octanol O Me
N
Me
water

Benadryl
cLogP = 3.45

A high Log[P] means that the drug, or potential drug, has a high concentration
in octanol, and is therefore more soluble in human tissue.
Since Log[P] is difficult to measure, a computer-based prediction of Lop[P], or
calculated Log[P] is often used as an approximation…this is called cLogP.
 Alkanes Exhibit Well-Defined Conformational
Preferences
Alkanes (and alkyl chains) are flexible, but still have conformational preferences
that are predictable. 6-membered rings also have distinct preferences, so that they
all behave, to a certain extent, like cyclohexane.
Like all functional groups, the concepts learned from the simplest possible case
extrapolate to more complicated cases
H H
H H OH H
C Cyclic Ether H
H C C H
Me Alkane
C H
H C
H C C H H
H C H
H HO
H H O Ethane
OH H
Cyclohexane

H H H H
H 60º
H H H perspective drawings
H H H H
staggered eclipsed
conformation conformation

H HH
H H 60º
Newman projections
H H H H
H H
H
Conformations of Alkanes: C-C bond rotation
H H H H
H 60º
H H H perspective drawings
H H H H
staggered eclipsed
conformation conformation
H HH
H H 60º
Newman projections
H H H H
H H
H
 Conformations of Butane: eclipsed, gauche & anti
Me H Me
Me H
butane H
Me H

A B C D E F

Me Me Me HMe Me HMe Me
Me H H H H Me

H H H H H H H H H Me H H
H H Me H H H
H Me H
Me-Me eclipsed gauche Me-H eclipsed anti Me-H eclipsed gauche
0º 60º 120º 180º 240º 300º
4.5 kcal 0.9 kcal 3.8 kcal 0.0 kcal 3.8 kcal 0.9 kcal
 Ethane/Butane comparison…Does Any of This
Generalize?
Ethane Butane Alkane
Me Me RR
highest
4.5 kcal/mol
H H H H
H H H H

HMe HR

3.8 kcal/mol higher

HH H H H H
Me H R H
2.9 kcal/mol
H H
H H

Me R
Me H R H
lower
0.9 kcal/mol
H H H H
H H
H Me R
H H H H H H
0.0 kcal/mol 0.0 kcal/mol lowest
H H H H H H
H Me R
 Torsional strain approximation

HH Eclipsed Ethane: 2.9 kcal

3 H-H eclipsing interactions = 2.9 kcal
1 H-H eclipsing interaction = 0.93 kcal...
H H
H H or 1 kcal for approximation purposes
HMe

H H
Me H
Me Me Me-Me Eclipsed Butane: 4.5 kcal
2 H-H eclipsing interaction = 2.0 kcal
1 Me-Me eclipsing interaction = 2.5 kcal Me-H Eclipsed Butane: 3.8 kcal
H H (ie 4.5 - 2.0 = 2.5) 1 H-H eclipsing interaction = 1.0 kcal
H H
2 Me-H eclipsing interactions = 2.8 kcal
ie 3.8- 1.0 = 2.8
Me 1 Me-H eclipsing interaction = 1.4 kcal
Me H Gauche Butane: 0.9 kcal
1 Me-Me gauche interaction = 0.9 kcal
H H
H

How about propane?

Me HMe
H H 1 Me-H eclipsing interaction: 1.4 kcal
no offending interactions:
2 H-H eclipsing interactions: 2x1.0 kcal
0.0 kcal
H H H H approximate torsional strain = 3.4 kcal
H H
H observed torsional strain = 3.4 kcal!
 Alkanes & Cycloalkanes

H H H H H H H
CH3CH2CH3 H H Me Me
H H
H H H
propane H H
sp3 hybridized, 109.5°

H H H H
CH2CH2CH2 H H
H H
cyclopropane H H
H H
sp3 hybridized, 60°???

H H H H H H H
Me
CH3(CH2)4CH3 H H Me
4 H 4 H
H H H
hexane H H
sp3 hybridized, 109.5°

H H H H
H H H H
H H H H
CH2(CH2)4CH2 H H
H H
cyclohexane H H H H
H H H H
sp3 hybridized, 120°???
 Ring Strain

H
methane
If we assume planar H H bond angle =109.5º
H
cycloalkanes, then....

cyclopropane cyclobutane cyclopentane cyclohexane cycloheptane

bond angle = 60º bond angle =90º bond angle =108º bond angle = 120º bond angle = 128.6º
 Why IS cyclohexane strain free?
109.5°
H H

H H

H H H H H H
H HH H
H H H H
H H
H H H H H H
H H
H H H H
HH H H HH
H H

H HH H
H H

H H H
H H
H
ethane analogy:
H HH H
H H H H
0.0 kcal/mol 2.9 kcal/mol 0.0 kcal/mol
H H H H H H
H H
H H
 Conformational Analysis: how to draw cyclohexane

1. Draw 2 parallel lines

2. Add two "v's"; note legs of v's are parallel with each other

A
A
3. Add axial substituents...all are parallel and vertical E
A
A A E
E E
A
E
A
A E
A
A
A A

4. Add equatorial substituents...3 pairs, each parallel

with a pair of lines from steps #1 and #2
E E
E
E

E E E
E
E
E
Practice Drawing Cyclohexane Chairs
Chair Flip Results in Change from Equatorial to Axial

R is EQUATORIAL R is AXIAL

H H H R
H H
H Chair FLIP H
H H
H R H H
H H
H H
HH HH
H H

H HH
H
R
H
H
H
H R
H
H
 Cyclohexane is Strain-free: Chair conformation
A
E
A A A
E E E

E E
E
A A
E
A
H H H H H "Flagpole
H H H E E H H
H A A H Interactions"
H H H H
H H
H H AE AE H H
H H
 Substituted Cyclohexanes

1,3-diaxial interaction...approx 1.7 kcal

H H CH3 H H
H H H
H
H 3 H H
H H 1 H
H H H H H CH3
H H H
3H H
H
H H H H H H
H H
H
H H H
H CH3
H CH3
H H
H H
H H
H H
H H

Me
CH3
Me H
H
H H
H
H H

Gauche Butane: 0.9 kcal H

1 Me-Me gauche interaction = 0.9 kcal H

A 1,3-diaxial interaction is equivalent to two gauche interactions…1.8 kcal/mol

 A-values: A useful measure of steric demand

1,3-diaxial interaction

H R H H
H H
H H
H K H A values are simply the energy
H H H R difference between axial and
H −∆G H
H H equatorial conformations ("A" is
Remember ∆G = -RTln[K] used to specify ∆G for this
H H H H
H H
particular case)
R K "A" value A = -∆G(Ax to Eq)
A = ∆G(Eq to Ax)
H 1 0
H Question can be reversed...instead
H 18 1.7 of wondering what the equilibrium of
H cyclohexane is, we can ask which of
CH3 two groups is more sterically
H 21 1.8 demanding? Answer: compare A
H values
Me
CH3
H 35 2.2 CO2Na
CH3
CH3
CH3 R
4800 4.9 R = CN (0.2)
CH3 R = Cl (0.5)
 Disubstituted Cyclohexanes
1.7 kcal/mol
H CH3 H H
H H
H H
H H
H H H3C CH3
H H
H H
H3C H H H
HH
1.7 kcal/mol more stable conformer (-3.4 kcal)

1.7 kcal/mol
H 1.7 kcal/mol H
CH3 H3C
H H
H H
H H
H3C H H CH3
H H
H same H
HH H
energy
H
HH

H H3C CH3 H
CH3 1.7 kcal/mol 2.2 kcal/mol
H H
H H
H3C H H
H H CH3
H3C H H
H H
HH H H
HH

more stable conformer (2.2-1.7 = -0.5 kcal)

 Summary: Torsional, ring (angle), and steric strain
Torsional Strain: Electron Cloud repulsion between Vicinal Substituents
H HH H vicinal
H H H
60º H
Newman projections H
H H H H H
H H H
H
geminal

Ring Strain: Bond Angles Bend Higher or Lower than Hybridization Defines

Me Me

sp3 hybridized, 109.5° sp3 hybridized, 60°???

Steric Strain: Neighboring Groups Forced Too Close Together

H CH3 H H
H H
H H
H H
H H H CH3
H H
H H
HH H H
HH