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FOUNDATION REVIEW

COMPANION BOOKLET

MCAT
®

Organic Chemistry

MM3257A
ORGANIC CHEMISTRY 1

Foundation Review
FOUNDATION REVIEW

NOMENCLATURE

Alkanes, alkenes, alkynes


Hydrocarbons contain only carbon and hydrogen.

Alkanes
single bonds between atoms; general formula CnH2n+2 (noncyclic)
• Alkanes: only single bonds between atoms; known as “saturated”: They
have the maximum number of hydrogens possible.
• General formula for noncyclic alkanes: CnH2n+2, where n = 1, 2, …

Alkenes
one or more double bonds between carbon atoms; general formula CnH2n (noncyclic, one double bond)
• Alkenes: one or more double bonds between carbon atoms
• General formula for a noncyclic alkene with one double bond: CnH2n

Alkynes
one or more triple bond between carbon atoms; general formula CnH2n–2 (noncyclic, one triple bond)
• Alkynes: one or more triple bond between carbon atoms
• Alkenes and alkynes, as well as aromatic compounds (below), are considered “unsaturated.”
• General formula for a noncyclic alkyne with one triple bond: CnH2n–2
• Named by adding the suffix –ane, –ene, or –yne to a prefix indicating the number of carbon atoms.
These same prefixes are used in the naming of other organic compounds and are therefore important:

1 meth– methane
2 eth– ethane
3 prop– propane
4 but– butane
5 pent– pentane
6 hex– hexane
7 hept– heptane
8 oct– octane
9 non– nonane
10 dec– decane

1.
MCAT: ORGANIC CHEMISTRY

Naming conventions
If the carbon atoms form a ring, then the name is preceded by the prefix “cyclo–.”
• If the carbon atoms form a ring, then the name is preceded by the prefix “cyclo–”:
• Note that the structures are not necessarily the three-dimensional structures:
Cyclohexane, for example, is not really planar.

cyclopropane cyclohexane cycloheptene

• For alkenes and alkynes, we need to designate where the double or triple bond is
found if there is a possibility of ambiguity. This is done by giving the number of the
carbon atom at which the double or triple bond starts. Carbon atoms are numbered
from one end to the other, in a direction that would give the lower number for the
position of the double or triple bond:

7 5 4 3 2
H2C CH2 6 1

ethene 2-butene 3-heptyne

2.
FOUNDATION REVIEW

If the hydrocarbon is branched, then we base the name of the compound on the longest continuous chain.
• If the hydrocarbon is
branched, then we base the
name of the compound on
the longest continuous 8 7 6 5 4
chain. The other carbon CH3CH2CH2CH2CH CH2CH3
atoms (and their hydrogen
atoms) are treated as sub-
stituents. When used as
3 CH2
substituent groups, these
are known as alkyl groups
and we take the prefix giving
the number and add “–yl”: 2 CH2
methyl, ethyl, propyl, etc. For
example:
1 CH3

The longest chain in this molecule contains eight carbon atoms, so it is an octane. There is, however, an
ethyl group attached to the fourth carbon. (The carbon atoms in the longest chain are numbered to give
the lowest number possible for the positions of the substituents.) The molecule is therefore 4-ethyloctane.
• The same scheme is used if more than one substituent group is present.
When giving the full name, the substituent groups are listed alphabetically.
For substituent groups present more than once, we use di–, tri–, etc. These
are not considered when alphabetizing.

The molecule is 4, 4-diethyl-2-methyloctane. (The “e” in “ethyl” comes before


the “m” in “methyl.”)

3.
MCAT: ORGANIC CHEMISTRY

Functional groups

Functional groups often dictate the behavior of the molecule: the kind of reactions it undergoes, etc.
• More complicated molecules are classified according to the presence of certain
arrangements of atoms, known as functional groups.
• Functional groups often dictate the behavior of the molecule: the kind of reactions
it undergoes, etc. The most important ones:

Formula/Structure Class of molecule Example


RX haloalkanes CH3Br bromomethane
(X = a halogen atom: Cl, I, etc.) (methyl bromide)

ROH alcohols CH3CHOH 2-propanol

CH3

ROR ethers CH3CH2OCH3 methoxyethane


(ethyl methyl ether)

O O
RCHO aldehydes propanal
R H CH3CH2CH

O O
RCOR' ketones 3-pentanone
R R' CH3CH2CCH2CH3

O O
RCOOH carboxylic acids propanoic acid
R OH CH3CH2COH

O O
RCOOR' esters methyl ethanoate
R OR' CH3COCH3
O O
RCONR'R" R N R' amides butanamide
R"
CH3CH2CH2CNH2

O O O O
RCOOCOR' anhydrides propanoic anhydride
R O R' CH3CH2COCCH2CH3
• R, R’ and R” are groups attached to the functional groups. They are usually
alkyl groups, such as CH3, C2H5, etc., but can also be more complicated.
• Ar— is often used instead of R— if the group attached is an aromatic com-
pound, e.g., phenyl ring.
• In the table, the names in parentheses are common names. More examples of
common names are given below.

4.
FOUNDATION REVIEW

The naming process


• Step 1: Identify the principal functional group. Priority increases in the order:
alkane < alkene < alcohol < ketone < aldehyde < acyl halide < ester < carboxylic acid
• Step 2: After identifying the principal functional group, identify the carbon skeleton
(longest chain containing the principal functional group).
• Step 3: Number the carbon atoms in skeleton (principal functional group and sub-
stituents get lowest possible numbers).
• Step 4: Put substituents into alphabetical order by name

What is the correct IUPAC name of the following compound?


A: The longest carbon chain in this compound contains 6 carbons, and the highest priority group
is the hydroxy group –OH. The compound is therefore a hexanol. The position of the hydroxy
group on the carbon chain has to be specified and has to be assigned the lowest possible
number—hence the molecule is named 2-hexanol since it is attached to the #2 carbon:
H H H H
1 2 3 4 5 6
CH3 C C C C CH3

OH H CH3 Br
The other substituents on the carbon chain have to be specified, which are a bromine atom
and a methyl group. The bromine atom lies on carbon 5, and the methyl group lies on carbon
4. Listing the substituents in alphabetical order, the correct IUPAC name of the compound is
5-bromo-4-methyl-2-hexanol.

5.
MCAT: ORGANIC CHEMISTRY

Common names

Certain common names do not follow the rules of the IUPAC system but just need to be memorized.
For example:

IUPAC name Structure Common name


ethene CH2=CH2 ethylene
ethyne CH≡CH acetylene
O

H3 C C CH3
propanone acetone
O

H3 C C H
ethanal acetaldehyde
O

H3 C C OH
ethanoic acid acetic acid

Certain alkyl groups also have names commonly used as prefixes. For example:

CH3
CH3
H3 C C CH3
H3 C C C
H2
CH3 H3 C C C
H H2 CH3
tert-butyl
or t-butyl isobutyl neopentyl
• Hence common name for (CH3)2CHCH2Br is isobutyl bromide, etc.

6.
FOUNDATION REVIEW

BONDING

Carbon
A carbon atom has four valence electrons; needs four more to complete octet.
• Organic chemistry is the study of carbon-containing compounds.
• Carbon has four valence electrons; needs four more to complete octet.
• Four different ways of doing this: (1) four single bonds, (2) one double and two
single bonds, (3) one triple and one single bond, (4) two double bonds.
• Geometry in each case is consistent with VSEPR theory:

(1)

C often drawn as C

109.5°

tetrahedral, sp3 hybridized

(2) 120°
C

trigonal planar, sp2 hybridized

(3), (4)
180°
C C

linear, sp hybridized

Hybridization
The valence orbitals of carbon—2s, 2px, 2py, 2pz—need to be recombined in different ways to generate
new orbitals that point in the right directions. This “mixing” of orbitals is known as hybridization.
• To form bonds that are oriented in the ways shown above, there must be an atomic orbital of carbon pointing in each
of the different directions.
• The valence orbitals of carbon—2s, 2px , 2py , 2pz—need to be recombined in different ways to generate new orbitals
that point in the right directions. This “mixing” of orbitals is known as hybridization.
• Can combine all four orbitals and come up with 4 orbitals that point to the corners of a tetrahedron. Orbitals are
called sp3 orbitals. Carbon atom becomes sp3 hybridized. Occurs when 4 single bonds formed. Case (1) above.
• Can combine 2s and two of the 2p orbitals to come up with 3 orbitals that point to the corners of a triangle. Orbitals
are called sp2 orbitals. Carbon atom becomes sp2 hybridized. Occurs when one double and two single bonds formed.
Case (2) above. Will have one 2p orbital that is unhybridized: points perpendicular to the plane of the triangle.
• Can combine 2s and one 2p orbital to come up with 2 orbitals that point to the corners of a triangle. Orbitals are
called sp orbitals. Carbon atom becomes sp hybridized. Cases (3) and (4) above. Will have two 2p orbitals unhybridized
that are perpendicular to each other and also perpendicular to either of the sp orbitals.
7.
MCAT: ORGANIC CHEMISTRY

Sigma and Pi bonds


Single bonds are sigma bonds.
• Sigma (σ) bonds are formed when one of the hybridized orbitals overlaps with an
orbital from another atom end-to-end.
• Single bonds are sigma bonds.
• If the two atoms that form a bond are both sp2 hybridized carbon atoms, one
orbital from each can form a single sigma bond, but their unhybridized p orbitals
can also interact to form a weaker bond known as the pi (π) bond.
• Because of the orientation of these p orbitals, they do not have end-to-end
overlap, but side-to-side:

Two bonds (one sigma, one pi) make up a double bond.


side-to-side overlap
of two p orbitals
(π bond) • The two bonds (one sigma, one pi) make up
a double bond.
• A double bond is stronger (and therefore
shorter) than a single bond, but not twice
as strong since the pi bond is weaker than
the sigma bond.
• A triple bond is made up of one sigma and
two pi bonds: each sp hybridized atom has
two p orbitals “left over.” In the diagram
end-to-end overlap of above, for example, there will be one more p
2 hybridized orbitals orbital perpendicular to the paper on each
(π bond) atom that can also interact to form a sec-
ond pi bond.
A triple bond is made up of one sigma and two pi bonds

8.
FOUNDATION REVIEW

Refer to the diagram:

4
H
H C C
H
H C C C H

1 2 H 3

What is the hybridization of the carbon atom labeled 1?


1. sp: the carbon forms a single bond and a triple bond.

What is the hybridization of the carbon atom labeled 2?


2. sp: the carbon forms a single bond and a triple bond.

What is the hybridization of the carbon atom labeled 3?


3. sp3: the carbon forms four single bonds.

What is the hybridization of the carbon atom labeled 4?


4. sp2: the carbon forms a double and two single bonds.

How many σ and π bonds are there in the molecule?


5. There are 8 single bonds, one double bond and one triple bond.
Each single bond gives a σ bond; a double bond gives one σ and
one π bond; a triple bond gives one σ and two π bonds. So there
is a total of 8 + 1 + 1 = 10 σ bonds, and 1 (from double bond) + 2
(from triple bond) = 3 π bonds in the molecule.

9.
FOUNDATION REVIEW

FUNCTIONAL GROUPS AND PHYSICAL PROPERTIES


• Different functional groups have different
polarities, which influence the strength of the
attraction between molecules. In the carbonyl
Polarity group, for example, there is a dipole moment
associated with the carbon-oxygen double
bond: the carbon has a partial positive and
the oxygen a partial negative charge.

δ–
O O O
= +
C C Cδ

• In order for a molecule to be polar, the individual bond dipoles


must not cancel
Hydrogen bonding
The families of molecules capable of participating in hydrogen bonding include alcohols, carboxylic
acids, amines with at least one hydrogen atom attached to nitrogen (–NHRR’), but NOT, for example,
ethers.

O R

R O

10.
MCAT: ORGANIC CHEMISTRY

Melting and boiling points and solubility


Melting and boiling points are influenced by hydrogen bonding, polarity, and molecular weights.
• The ability to hydrogen bond and high polarity generally increase the melting and boil-
ing points of a substance because of increased intermolecular attractions.
• In general, melting and boiling points also increase with increased molecular weights
(all else being the same); hence, for straight chain alkanes, the mp and bp increase
with each additional —CH2 group.
Solubility
Like dissolves like.
• Polar molecules dissolve in polar solvents (e.g. H2O, acetone); nonpolar
molecules dissolve in nonpolar solvents (e.g. hexane): “Like dissolves like.”

Protic solvents
Solvents capable of participating in hydrogen bonding are known as protic solvents (e.g. H2O, alcohols).
• Solvents capable of participating in hydrogen molecule are known as protic
solvents (e.g. H2O, alcohols). Aprotic solvents are those incapable of hydro-
gen-bonding; they may be polar or nonpolar. Acetone, CH3COCH3, is polar
and aprotic.

Which of the following is the most soluble in water: 1-pentanol, 1-propanol, butane, 1-
chloropropane, or diethylether?
A: 1-propanol: It can participate in hydrogen-bonding with the solvent
water molecules, unlike butane, chloropropane, and diethylether.
Compared to 1-pentanol, it has a shorter hydrocarbon “tail,” and
so has less of a nonpolar character.

11.
FOUNDATION REVIEW

ISOMERISM

Stereoisomers
Most Most
Different Similar

Structural Diastereomers Enantiomers Conformational


(including
geometric isomers)

ISOMERS
(Different compounds with the same molecular formula)

Structural/Constitutional isomers Stereoisomers


(different atomic connectivities) (different spatial arrangement of atoms)

Enantiomers Diastereomers Conformational


(nonsuperimposable (stereoisomers that are isomers
mirror images) not mirror images) (arise by
rotation about a
single bond)

Geometric isomers
(a subclass of diastereomers
involving arrangement of atoms
about a double bond)

Structural isomers
Same number of atoms of each kind (same molecular formula), but bonded differently
• Same number of atoms of each kind (same molecular formula), but bonded differently. E.g.,
straight-chain butane and isobutane both have formula C4H10, but their structures are differ-
ent. Condensed structural formulas, which are a hybrid between molecular formulas and draw-
ings of the actual structure, offer a way of distinguishing them: CH3CH2CH2CH3 vs. (CH3)3CH
Chemical and physical properties
They may have different functional groups, and therefore react in very different ways.
• Structural isomers can have differ-
They are also called constitutional isomers. ent functional groups, and therefore
react in very different ways. They are
also called constitutional isomers.
12.
• They are most similar to one another since we can interconvert
MCAT: ORGANIC CHEMISTRY among them by rotating about single bonds. They have the same
chemical properties (participate in the same kinds of reactions)
and physical properties (boiling point, melting point, density, etc.).
• In fact, at room temperature, single bonds rotate very rapidly, so
Conformational isomers individual conformational isomers cannot even be isolated.
They are most similar to one another since they can be interconverted by rotation about single bonds.

Chemical and physical properties


They have the same chemical properties (participate in the same kinds of reactions) and physical
properties (boiling point, melting point, density, etc.)

Example
Common example of conformational isomers: butane.

CH3 CH3 CH HCH3


H3 C 3
H H H CH3
H H
H H H H H H H CH3
H H
CH3 H

staggered staggered eclipsed eclipsed


(anti) (gauche)

Newman projections
• The above structures are drawn in the convention known as Newman pro-
jections. We are looking down the molecule along a C-C bond: in this case
the bond between the second and third carbon atoms of butane.
• In the four conformational isomers above, the anti conformation is the
most stable, while the eclipsed conformation with the two methyl groups
right on top of each other is the least stable (most strained). This is
because of the repulsion between the electron clouds.
Cyclohexane
The boat vs. chair conformations of cyclohexane are also examples of conformational isomers.
• The boat vs. chair conforma-
tions of cyclohexane are also
examples of conformational
isomers. The chair conforma- repulsion between electron clouds
tion is more stable than the
boat conformation:
H H
H H

boat conformation

13.
FOUNDATION REVIEW
• There are actually two possible chair conformations, as can be seen if
the cyclohexane is substituted. For example, for methylcyclohexane:

axial H

H H equatorial H H
H C
H
H H H
H
H H H H
H C H H
H H H
H H
H
H H H H

axial

• The two are conformational isomers. The molecule with the methyl
group in the equatorial rather than the axial position (the left hand
side rather than the right hand side structure) is more stable
because repulsion between the methyl group and the hydrogen atoms
are minimized.
• If there is more than one substituent, the conformation with the
bulkier substituent at an equatorial position will be dominant:
H
CH3 H H
H H3 C H H C
H CH3
C H H H CH3
H H H H
H C H C
H H H CH3
H H H
H H H H CH3

What are the positions occupied by the bromine atom and the t-butyl group respectively in
the most stable conformation of trans-1-bromo-3-t-butyl-cyclohexane?
A: bromine: axial, t-butyl: equatorial. For trans-1,3-disubstituted cyclohexanes,
one substituent will be axial and one equatorial. (Compare this with the
case of trans-1, 2-disub-
stituted cyclohexanes C(CH3)3
shown earlier.) The confor-
mation with the bulky t- H
H
butyl group in the
equatorial position would Br
be much more favorable:

14.
MCAT: ORGANIC CHEMISTRY


If a molecule has an enantiomer, then it
Enantiomers is chiral. Chirality most commonly
Nonsuperimposable mirror images of each other; always come in pairs. arises when a carbon atom is bonded to
four different atoms or groups. Such a
carbon atom is known as a chiral center,
Chirality or stereocenter, or stereogenic center.
arises when a carbon atom is bonded to four different atoms or groups

K K

C C
M O O M
N N

mirror images
K K
rotate along C–K
C C
O M N O
N M

K K

not superimposable upon C becaused N and M interchanged!


C
M O N O
N M

• The two structures above are enantiomers. The car-


bon atom is a chiral center. (Note that the four
groups attached to the carbon are different: K, M, N,
O.) However, the following carbon atom does not have
four different groups and is thus not a chiral center:

K K

C C
M N N M
N N

mirror images
K K
• The two are not enantiomers: they rotate along C–K
are the exact same molecule.
C C
• Note that when trying to determine
whether two structures are super- N M M N
imposable, we cannot break bonds to N N
switch two groups. In fact, as we will As can be seen, this is
see in more detail, switching the positions of two sub-
identical to the
stituents would give the opposite configuration.
original molecule.

15.
FOUNDATION REVIEW

A compound that is identical to its mirror image is achiral. All compounds with a plane of symmetry
are achiral. A compound that is identical to its mirror image is achiral. All compounds with a plane of
symmetry are achiral. In the last example above, there is a plane of symmetry cutting across
C, K and M; the molecule is achiral.
Configuration about each chiral center is designated either R or S.
• Configuration about each chiral center is either R or S. Assignment is based on the pri-
ority of the substituent groups (groups attached to the chiral center): Heavier atoms
have higher priority (—OH over —CH3); if two groups have the same atom directly
attached then look at the next ones, etc. (—CH2CH3 over —CH3). The four groups will
thus be ranked 1, 2, 3, 4 in priority. Mentally reorient the molecule so that the #4 group
points to the back. If 1, 2, 3 are oriented clockwise, then configuration is R; if counter-
clockwise, then S.

lowest priority hydrogen at the back


H

HOOC CH3

third in priority

C with 3 C-O NH2


bonds, higher
priority than
H's of the N heavier than C: highest priority
methyl group.
•In the molecule shown above (the amino acid alanine), the priority decreases as one goes
clockwise from NH2 to COOH to CH3. The configuration is R. The one below is S:
The following molecule has the S configuration at its chiral (or stereogenic) center:

HOOC NH2

CH3

• Going from NH2 to COOH to CH3 now involves going counterclockwise.


Note that comparing R and S, we see that the S configuration has two
groups swapped (NH2 and CH3).
• If we do yet another swap—say, CH3 with COOH—we will get the R back.

16.
• This offers a shortcut to determining the configuration about a stereocenter
MCAT: ORGANIC CHEMISTRY
when the lowest priority group is not pointing towards the back. Instead of try-
ing to rotate the molecule mentally, we swap the lowest priority group with the
one pointing to the back. We then determine the configuration as usual, knowing
that the actual molecule will have the opposite configuration. For example:
Interchanging two substituent groups leads to a change in the configuration.

COOH H
swap H and COOH HOOC NH2
H NH2

CH3 CH3

This has an S configuration.


The original molecule must have
an R configuration.

Fischer projections
Fischer projections are often used to give stereochemical information. The convention is that horizontal
lines are bonds coming out of the plane, while vertical bonds are going back:

H H
(3) (1)
H3 C OH = H3 C OH R

CH2CH3 CH2CH3
(2)

CH3 CH3

H OH = H OH S

CH2CH3 CH2CH3

• Note that if a Fischer projection is rotated by 90°,


the configuration has changed!

17.
FOUNDATION REVIEW

CH3 CH3

H OH = H OH

CH2CH3 CH2CH3

opposite configurations

rotate 90°

H H

H3 CH2C CH3 = H3 CH2C CH3

OH OH

• But if Fischer projection rotated 180° it is the same configuration.

Optical activity
the ability to rotate plane-polarized light
• Enantiomers have identical chemical and physical properties in achiral environments, but dif-
fer in the way that they rotate plane-polarized light: One will rotate the polarization by an
angle of q, while an equimolar amount of its enantiomer will rotate the light by the same
amount in the opposite direction.
• This ability to rotate plane-polarized light is known as optical activity. Compounds that
rotate plane-polarized light (chiral compounds) are optically active.
• The human body is not an achiral environment: we react in different ways to enantiomers.

Racemic mixture
An equimolar mixture of a pair of enantiomers; will not rotate plane-polarized light (optically
inactive).
• An equimolar mixture of a pair of enantiomers is known as a racemic mixture.
It will not rotate plane-polarized light.
• Achiral compounds will also not rotate plane-polarized light.

18.
MCAT: ORGANIC CHEMISTRY

Diastereomers
The category of diastereomers covers all configurational stereoisomers that are not enantiomers.
• The category of diastereomers covers all configurational stereoisomers that are
not enantiomers. This can arise when double bonds are involved (see geometric
isomers below), or when there is more than one chiral center in the molecule.

Meso compounds
Meso compounds are compounds that possess chiral centers but are still nonetheless achiral. They have
a plane of symmetry and are diastereomers of the corresponding enantiomers. For example:

COOH
• Meso compounds are compounds
that possess chiral centers but are (R)
H OH
still nonetheless achiral. They have plane of
a plane of symmetry and are symmetry
diastereomers of the corresponding H OH
(S)
enantiomers. For example:
COOH
meso tartaric acid
(achiral)
diastereomers diastereomers
(not mirror images) (not mirror images)

COOH COOH

(R) (S)
H OH HO H
enantiomers (S)
(R)
HO H H OH

COOH COOH

19.
FOUNDATION REVIEW

Cis/trans designation
• The cis/trans designation is sometimes used for cyclic diastereomers:

H
=
H H H
Cl
Cl Cl Cl

cis -1, 2- dichlorocyclohexane

H
=
H Cl Cl
Cl
Cl H H

trans -1, 2- dichlorocyclohexane

Geometric isomers
Differ in the arrangement of groups around a double bond. They are not conformational isomers
because there is no free rotation about double bonds.
• The cis/trans designation is sometimes used for cyclic diastereomers:

20.
MCAT: ORGANIC CHEMISTRY

What kind of isomers are the following pairs of compounds?

(i) CH3CH2CH2OH and CH3OCH2CH3

(ii) H H H CH3
CH3 and CH3
CH3 H
H H H H

(iii)
H H H CH3
and

CH3 CH3 CH3 H

(iv)
H CH2CH3 H CH3
and

CH3 CH3 CH3 CH2CH3

(v)
Cl Cl
and
H CH2CH3
CH3CH2 CH3 H CH3

H H
(vi)
CH3 Cl CH3 Cl
and
CH3 Cl Cl CH3

H H

H H
(vii)
CH3 Cl Cl CH3
and
CH3 Cl Cl CH3

H H

A: (i) structural isomers (v) enantiomers


(ii) conformational isomers (vi) diastereomers
(iii) geometric isomers (vii) meso compounds: identical!
(iv) geometric isomers

21.
MCAT: ORGANIC CHEMISTRY

SUBSTITUTION REACTIONS

Ionic mechanisms: SN1 and SN2

S N1 CH 3

H 3C C Br C C Nuc

CH 3

+ Nuc

S N2
H
H H H H
H δ δ
Nuc C
Nuc C Br Nuc C Br

H
H H

Nucleophile vs. Electrophile


• Driving force is electrostatic attraction between molecules with different
charges or polarities. “Nuc” denotes the nucleophile which either bears a nega-
tive charge or at least contains a lone electron pair. Because of this, it “loves
nuclei,” which are positively charged. “SN” stands for substitution, nucleophilic.
• The species being attacked is the electrophile. The carbon atom either has a
positive charge or a partial positive charge because of a polar bond. Because of
this, it “loves electrons.”

SN1
rate = k[RX]; unimolecular reaction (hence “1” in SN1): 2-step mechanism proceeding through the
formation of a carbocation intermediate (rate-determining step)
• rate = k[RX]; unimolecular reaction (hence “1” in SN1): 2-step mechanism proceed-
ing through the formation of a carbocation intermediate (rate-determining step)
• How readily the reaction occurs depends on the stability of the carbocation
intermediate. The more stable the carbocation, the more readily the reaction
occurs.
• The carbocation is stabilized if the positive charge is delocalized or if there are
electron-donating groups around.

22.
FOUNDATION REVIEW
• Alkyl groups are electron-donating, so the more highly substituted
the substrate (the more alkyl groups instead of hydrogen atoms
attached to the central carbon), the more stable the carbocation:
Stability of carbocation/Reactivity:

CH 3 CH 3 H H

H3C C CH 3 H3C C H H3C C H H C H

X X X X

tertiary alkyl halide secondary alkyl halide primary alkyl halide methyl halide
(does not react via
S N1)
• A double bond or a phenyl group starting on an adjacent
carbon atom is also helpful in stabilizing the carbocation.
• Carbocation is formed when the leaving group departs:
solvolysis as an example of an SN1 reaction: usually a halide ion X –, Br –, I –, etc. (weak bases). But leav-
ing group may need to be protonated if the leaving group
is a strong base,
CH 3 e.g. —OH into —
O+H2 and departs
H 3C C Br C + Br– (slow; rate-determining step) as a neutral water
molecule.
CH 3
• The carbocation may
rearrange by the migration
of a hydrogen or even a methyl
+ CH3OH C OCH3 (fast) group to make it more substi-
C
H tuted (more stable):
C H3
C H3
C H3 C C H2 C C H2 C H3
C H3
C H3
C OCH3 C OCH3 + H+ (fast)

Reaction is favored by protic
H
solvents (water, alcohols,
etc.) which can stabilize the
carbocation intermediate.
• The nucleophile does not have to be strong. (The strength of a nucleophile
roughly parallels its basicity.) In fact, it is often just a solvent molecule, e.g.
H2O, CH3OH. When the solvent molecule acts as the nucleophile, the reaction is
known as solvolysis. Deprotonation needs to occur:

23.
MCAT: ORGANIC CHEMISTRY

SN2
Rate = k[RX][Nuc–]; bimolecular reaction: one-step process proceeding through a transition state.

Nucleophile attacks from the back as the leaving group departs in front. Reaction leads to inversion of
configuration:
• Reactivity is determined by the ease
with which the nucleophile can
approach the substrate. The less sub-
stituted the substrate, the less “steri-
cally hindered” it is, and the easier the
reaction. Order hence goes opposite to
that of SN1: methyl > primary > sec-
ondary > tertiary
• Weak bases as leaving groups
• Wants a strong nucleophile like the
hydroxide ion OH –. (Again, the
strength of a nucleophile is approxi-
mately correlated with its basicity.)

What is the product of a substitution reaction with RX as the substrate and each of the
following as the reagent? (i) NaOH/H2O (ii) R’OH (iii) NaCN/ethanol (iv) excess NH3.
A: (i) ROH (alcohol), (ii) R’OR (ether), (iii) RCN (nitrile), (iv) RNH2 (primary amine)

• Radicals (or free radicals) are species with unpaired electrons.


• The presence of peroxides, heat or light can cause radicals to be generated.
Radical mechanism The bond is said to cleave “homolytically.”
Radicals (or free radicals) are species with unpaired electrons.

initiation: Cl Cl 2 Cl

propagation: Cl + CH4 CH 3 + HCl

CH 3 + Cl Cl CH 3Cl + Cl

termination: 2 Cl Cl Cl

• This is an example of a radical chain mechanism


since it is a chain reaction. The driving force in each
step is the need of a species to have a full octet.

24.
FOUNDATION REVIEW

ELIMINATION REACTIONS

E1:
CH 3
CH 3 H CH 3
H
H 3C C Br H C C C C + H+
H CH 3 H CH 3
CH 3

E2:
Base Base
H H H H H H

H C C H C C
H C C H
H H
H Br H Br

+ H-Base + Br –

E1
unimolecular elimination reaction. Proceeds through formation of carbocation intermediate.
Rate = k[RX] • Same rate-determining step as S 1 reaction. Therefore same consid-
N
erations in terms of reactivity (same solvent effect, etc.) Also means
that it is hard to preferentially have one reaction occur: What makes
one reaction go would also facilitate the other.
E2
bimolecular elimination reaction. One-step (concerted) mechanism via a transition state.
• bimolecular elimination reaction. One-step (concerted) mechanism via a transition state.
• Steric effects not as important as in SN2 because the base does not have to get too close.
• Therefore, to favor E2 over SN2, can use a large, bulky base.

Dehydration
Dehydration of alcohols is a special case of an elimination reaction.
• Dehydration of alcohols is a
special case of an elimination
reaction. The reaction takes H+
C C C C + H2O
place when an alcohol is heated ∆
under acidic conditions. The
leaving group is the –OH group, H OH
which is protonated by the acid
catalyst and leaves as a water (∆ represents heat)
molecule (hence the name dehydration). Extrac-
tion of a proton in the second step regenerates
the acid catalyst. The net reaction is:
• In general, elimination is an important
way to synthesize alkenes: We start
with either an alcohol or a haloalkane.
25.
FOUNDATION REVIEW

• Recall definition of Brønsted-Lowry acids: proton donors.


• An organic compound is acidic if it donates a proton easily.
ACIDS AND BASES • The ease of proton donation is determined by the stability of the conju-
gate base: the anion that is left behind after the proton leaves. (More
specifically, the lone pair of electrons left behind needs to be stabilized.)
An organic compound is acidic if it donates a proton easily.

The ease of proton donation is determined by the stability of the conjugate base.

The general factors affecting the stability of the conjugate base fall into three broad categories: (1)
resonance effects, (2) inductive effects, and (3) hybridization.

Resonance effects
• Delocalization of the lone pair of electrons stabilizes the anion, making the com-
pound more acidic.
• For example, p-nitrophenol is more acidic than phenol itself because the nitro
group can help delocalize the electron pair:

O O

N O N O

O O

vs.

• While resonance effects involve delocalization of electrons via π bonds,


Inductive effects inductive effects are those that are exerted through sigma bonds.
• Electronegative groups or atoms near the proton to be removed help
stabilize the conjugate base, making the compound more acidic.

Electronegative groups or atoms near the proton to be removed help stabilize the conjugate base,
making the compound more acidic.

Three considerations of the effect of electronegative groups:


a. The closer the electron-withdrawing group is to the carboxylic group (or other acid functionality),
the stronger the acid.

H H H δ– H H H δ–
O O

H C C C C more stable than H C C C C


δ – δ–
O O
H H Cl H Cl H

26.
MCAT: ORGANIC CHEMISTRY

b. The more electronegative the electron-withdrawing group, the stronger the acid.

H H δ– H H δ–
O O

F C C C more stable than H3 CO C C C




H H H H

c. The larger the number of electron-withdrawing groups, the stronger the acid.

Cl H δ– H H δ–
O O

Cl C C C more stable than Cl C C C



O
δ –

Cl H H H

Hybridization
• This effect is used to explain why a terminal alkyne is more acidic than
an alkene or alkane:
R C C H R C C pKa ~ 22

R H R
C C C C pKa ~ 40

H H H H

H H H H
R C C H R C C pKa ~ 60

H H H H
• This is due to the fact that electrons in an sp orbital are more stable
(at a lower energy) than ones in an sp 2 orbital, which are in turn more
stable than ones in an sp 3 orbital.
• An organic base contains a lone pair of electrons. The most common
example of an organic base is an amine (or ammonia).
• The more reactive the lone pair of electrons (the less stabilized it is),
the more basic the compound is.

27.
ORGANIC CHEMISTRY 2

Foundation Review
MCAT: ORGANIC CHEMISTRY

Aromatics, delocalization, and conjugation

Delocalization
Electrons in π bonds can be delocalized (i.e., not limited to the region between the two atoms but spread
out farther) if there is another π bond or another p orbital one atom removed. One can always draw
resonance Lewis structures in these cases:

O O

There are two π bonds in the molecule above, each containing two electrons. But each pair of electrons
is not confined to the region between two atoms; the electrons are instead delocalized. Another example:

i.e.:

or, more three-dimensionally:

Conjugation or delocalization of electrons makes a molecule more stable.


• Conjugation or delocalization of electrons usually make a
molecule more stable.
• Aromatic compounds are a special class of molecules that are
made extra stable by delocalization. They are planar, cyclic, and
have (4n + 2) π electrons, where n is some nonnegative integer
(0, 1, 2, etc.)
• Benzene is the most common example of an aromatic compound
(6 π electrons, i.e. n = 1).
28.
FOUNDATION REVIEW

OVERVIEW OF REACTION TYPES

Substitution Br OH

Elimination Br

Addition Br

Rearrangement

Substitution
• replacement of functional group.

Elimination
• functional group(s) removed. Formation of a π bond.

Addition
• π bond is destroyed. Formation of σ bond(s) to another group or other groups.

Rearrangement
• molecule rearranged to make new isomeric structure.
• Each of these types of reactions can happen via a variety of mechanisms.
This classification just looks at the net outcome of the reaction.

29.
MCAT: ORGANIC CHEMISTRY

ADDITION REACTIONS
• π electrons are more reactive than electrons in σ bonds.

Markovnikov addition

H H CH 3
H CH 3 CH 3

C C H C C H C C CH 3

H CH 3 CH 3
E E Nu

E Nu
(such as H+ ) (such as Br–)

The addition of an electrophile generates a carbocation. The need for the carbocation to be stabilized
dictates which end of the double bond the electrophile is added to:

H3C H
primary carbocation:
H C C H not stable
H3C H

C C H

H H
H3C H
secondary carbocation:
more substituted,
H Br H C C H hence more stable

• The two parts of the molecule that is added (the E+ in the first step
and the Nu– in the second step) are often two halves of the same
molecule. For example: HBr (H+ and Br–).
• Note that the halide has added to the more substituted carbon atom.

30.
FOUNDATION REVIEW

Anti-Markovnikov addition
radical mechanism

H CH 3 H CH 3
H CH 3

C C H C C CH 3 H C C CH 3

H CH 3
Br Br H
Br
H Br
+ Br

• Note that the two halves of the molecule add in the reverse configuration as in the ionic
mechanism above. (The halogen is on the less substituted carbon now.) This is because we
add the bromine first, but still want to form the more stable secondary carbon radical.

Anti addition of halogens


Proceeds via an ionic mechanism as in the case of Markovnikov addition. But the intermediate is a
cyclic ion:

R Br
R R R R
R
C C C C + Br– C C
R R R R R
Br Br R
Br Br

Referred to as anti addition because the two halves add on opposite sides.

Hydrogenation
• Catalytic hydrogenation on a metal surface: takes place on a
surface such as Pt or Pd.-
• One H atom is added on each end of a double bond. Compound
becomes saturated.
• Syn addition because the two H atoms add from the same side
of the alkene.
• Alkynes are completely saturated to alkanes under hydrogena-
tion on a catalytic palladium or platinum surface.

31.
MCAT: ORGANIC CHEMISTRY

ELECTROPHILIC AROMATIC SUBSTITUTIONS


• Alkenes and alkynes undergo electrophilic addition. Aromatic compounds, however, do not want to give
up their stability and so want to reform the conjugated double bond. They thus undergo addition and
then elimination, resulting in net substitution and maintaining their aromaticity:
Aromatic compounds undergo addition and then elimination, resulting in net substitution and
maintaining their aromaticity:

H H H

H E H E
H H
(addition) H (elimination)
+ E+ + H+

H H H H H H

H H
H

Different substituents can be attached to the benzene ring by varying the electrophilic reagent used in
the reaction.

Process Reagent Attacking electrophile Product

Halogenation Cl2/FeCl3 Cl+ C6H5Cl (chlorobenzene)

Halogenation Br2/FeBr3 Br+ C6H5Br (bromobenzene)

Nitration HNO3(conc)H2SO4(conc) NO2+ C6H5NO2 (nitrobenzene)

H2SO4(fuming) SO3 (benzenesufonic


Sulfonation C6H5SO3H acid)

Friedel-Crafts Alkylation RX/AlCl3 R+ C6H5R (alkylbenzene)

Friedel-Crafts Acylation RCOCl/AlCl3 RCO+ C6H5COR (phenyl ketone)

32.
FOUNDATION REVIEW

A substituent activates or deactivates the ring towards further substitution. It also affects where the next
substituent will add relative to itself:
• Once a substituent is attached to the benzene ring, it can activate or deactivate the
ring towards further substitution. It can also affect where the next substituent will
add relative to itself:
X

ortho ortho

meta meta

para
X X X

Y
ortho meta para
• ortho/para activating substituents either possess a lone pair of electrons or
can donate electrons through induction. Such activators include –NH2, –OH,
–OR, –R.
• ortho/para deactivating substituents include the halogens: –Cl, –Br, –I, –F.
• meta deactivators possess a positively-polarized atom directly attached to the
ring. Such groups include: –NO2, –C+N, –COOH, –SO3H, –CHO, –COR.
• In general, activators are o/p-directing and electron-donating. Deactivators are
meta-directing and electron-withdrawing. Halogens are the exceptions: they are
deactivators but o/p-directors.

What is/are the MAJOR product(s) of the following reaction?

NO2

HNO3(conc)

H2SO4(conc)

A: The nitro group is a meta-directing deactivator:


NO 2

NO 2

33.
MCAT: ORGANIC CHEMISTRY

OXIDATION AND REDUCTION

General scheme
The more bonds to oxygen a carbon atom has, the more oxidized it is. The fewer bonds to oxygen, the
more reduced.
• The more bonds to oxygen a carbon atom has, the more oxidized it is. The fewer
bonds to oxygen, the more reduced.
• Alkanes contain no C–O bond. Alcohols contain 1 C–O bond. Aldehydes and ketones
have a carbon-oxygen double bond which is considered equivalent to two C–O bonds.
Carboxylic acids are considered to have three C–O bonds: one C=O bond for the car-
bonyl group and one C–O bond to the hydroxy group.

OXIDATION

ALCOHOL ALDEHYDE / KETONE ACID

REDUCTION

Oxidizing and reducing agents


• reducing agents cause compounds to be reduced: e.g. LiAlH4 , NaBH4
• oxidizing agents cause compounds to be oxidized: e.g. PCC, KMnO4 , K2Cr2O7 , H2CrO4.
Note the presence of a transition metal in a high oxidation state.

OH O

Na2 Cr2O 7, H2 SO4 , H2O

cyclohexanol cyclohexanone

OH
O
NaBH4
R C H
C ethanol
R H
H

aldehyde primary alcohol

34.
FOUNDATION REVIEW
• Since formation of a C–O bond in an oxidation process means that another
bond has to be broken, we may encounter a “dead end.” For example, oxidizing
a tertiary alcohol would mean
that a C–C bond has to be bro- CH 3 H3C
ken. The strength of a C–C H2 CrO4 C O
bond prevents this from hap- H3C C OH
pening, so tertiary alcohols H3C
cannot be easily oxidized: CH 3

Ease of reduction:

aldehyde > ketone > ester > carboxylic acid

NaBH 4

LiAlH 4

• LiAlH4 (lithium aluminum hydride, often abbrevi-


ated LAH) is a stronger reducing agent than
NaBH4 (sodium borohydride). NaBH4 can only
reduce aldehydes and ketones, while LAH can
reduce esters and carboxylic acids as well:

35.
MCAT: ORGANIC CHEMISTRY

THE CARBONYL GROUP: OVERVIEW

Characteristics
The carbon atom in the carbonyl group bears a partial positive charge. In addition to affecting the
physical properties of the compound, it is also susceptible to attack by a nucleophile.
• Recall that the carbon atom in the carbonyl group bears a partial
positive charge. In addition to affecting the physical properties of the
compound, it is also susceptible to attack by a nucleophile.
NUCLEOPHILIC ADDITION TO CARBONYLS:
OH

n)
tio R C R'
ro 1
na
(p ath
to
p

– O Nu
O

+ R C R'
C
R R'
pa isp

Nu O O
th lac
(d

2 em

Nu C
R C R'
en

R Nu
t)

Nu

• There are 2 ways to complete the addition process: protonate, or kick out
leaving group. Path 2 is actually a substitution. (In the case of path 2, R’
obviously cannot be an alkyl group, but needs to be a good leaving group.)
• Example of nucleophiles: OH –, OR –, amines, R-MgX (Grignard reagents),
H2O, ROH. The latter two are weak nucleophiles and need acid catalysis.
• In acid-catalyzed conditions, the carbonyl oxygen may first be protonated,
but the net result is generally the same. For example:

OH OH
O OH OH
H+ –H+
R R' R R'
R R' R R' R R'
Nuc H Nuc

H-Nuc
• A Grignard reagent contains an alkyl group acting as a nucleophile (R–). The
net effect is the addition of an R group to a carbonyl to form (after acid
work-up) an alcohol. If the starting carbonyl is an aldehyde, the alcohol is
secondary. If the starting carbonyl is a ketone, the alcohol is tertiary.

36.
FOUNDATION REVIEW

ALDEHYDES AND KETONES

Nomenclature
ends in –al or –one
• In numbering the carbon atoms, the carbonyl carbon should be given the
lowest number possible: The carbonyl carbon in an aldehyde is always
going to be carbon #1, so the number does not need to be given.

O O O

H C H H C CH3 H C CH2CH2Br

methanal ethanal 3-bromopropanal


(formaldehyde) (acetaldehyde)

O O

H3C C CH2CH2CH2CH3 H3C C CH2CH CH2

2-hexanone 4-penten-2-one

Synthesis
usually by oxidation of alcohols

Key reactions
Oxidation/reduction

Nucleophilic addition
• Addition of strong nucleophiles such as HO –, RO –, CN –, Grignard reagents.
(Note that reduction can be considered addition of the hydride ion H –.)

37.
MCAT: ORGANIC CHEMISTRY

Keto-enol tautomerism
O
OH

H
keto form enol form

• The two are constitutional isomers: the hydrogen atom is in a different


position. The keto form is so-named because it is a ketone; the enol form
gets its name from the presence of the alkene and the alcohol function-
ality. Interconversion between the two, known as keto-enol tautomeriza-
tion, can be either acid- or base-catalyzed.
• Usually the keto form is more thermodynamically stable, so the equilib-
rium lies to the left.
• Keto-enol tautomerization can occur because the proton shown above
can be abstracted relatively easily (i.e. it is acidic, see below).

What is the product of the following reaction?

O
H2O
CH3 + CH3CH2CH2MgBr

A: A tertiary alcohol: 2-phenyl-2-pentanol. In this question, the nucleophile is


the negatively-polarized alkyl portion of the Grignard reagent
CH3CH2CH2MgBr. The addition of water ensures that the magnesium salt
is converted to a tertiary alcohol:

O O– Mg +
δ –
δ δ + –
C CH3 + CH3CH2CH2 MgB C CH2CH2CH3
CH3
H2O
OH

C CH2CH2CH3+
CH3
Tertiary

38.
FOUNDATION REVIEW

CARBOXYLIC ACIDS AND CARBOXYLIC ACID DERIVATIVES

Nomenclature
carboxylic acids: ends in “–oic acid”

O O O

HO C CH2CHCH2CH3 HO C CHCH3 HO C CH2CH CH2

CH3 OH

3-methylpentanoic acid 2-hydroxypropanoic acid 3-butenoic acid

C OH

benzoic acid

The name of the carboxylic acid is used as a starting point in the naming of the acid derivatives:

Acyl halides:
O
O
C Cl
Cl C CH2CH2CH2CH3

pentanoyl chloride benzoyl chloride

Anhydrides:

O O O O

C O C H3C C O C CH3

benzoic anhydride ethanoic anhydride


Esters:

O O CH3

H3C C OCH2CH2CH3 H3CH2C C O C CH3

CH3

propyl ethanoate t-butyl propanoate

39.
MCAT: ORGANIC CHEMISTRY

Synthesis of carboxylic acids

oxidation of aldehydes and primary alcohols

oxidative cleavage of alkenes with vinylic protons

carbonation of Grignard reagents

O O
O C O +
H
R MgX
R O R OH

carboxylate carboxylic
acid

40.
FOUNDATION REVIEW

Synthesis of carboxylic acid derivatives


• The substitution pathway offers a means of converting between different car-
boxylic acid derivatives.
• In general, a more basic nucleophile can displace a less basic leaving group, but
not the other way round:

O O

NH2– + + Cl–

Cl NH2

O O

Cl– + + NH2–

NH2 Cl

• Since substitution consists of an addition and then an elimination, we need


to have a leaving group. The halogen in an alkanoyl halide (or acyl halide) is a
good leaving group (in the form of a halide ion: Cl–, Br–). Alkanoyl halides are
thus reactive and can be transformed into the other compounds relatively
easily. In water, it will form a carboxylic acid (H2O as nucleophile). In alcohol, it
will form an ester (ROH as nucleophile).
• Alkanoyl chlorides can themselves be synthesized by reacting carboxylic acids
with SOCl2.
• Esters can be converted into carboxylic acids through hydrolysis. Depending
on whether the reaction is carried out under acidic or basic conditions, the
attacking nucleophile is either a H2O or OH–.
acidic conditions: RCOOR’ + H2O → RCOOH + R’OH
basic conditions: RCOOR’ + NaOH → RCOO–Na+ + R’OH

When carried out under basic conditions, the reaction is known as saponifica-
tion and the product is in the form of the carboxylate anion. Acid work-up is
necessary to get the acid.
• Esterification is the reverse process: a carboxylic acid is converted into an
ester. It is acid-catalyzed with an alcohol molecule R’OH as the nucleophile.
The net reactions is: RCOOH + R’OH → RCOOR’ + H2O.

41.
MCAT: ORGANIC CHEMISTRY

Key reactions of carboxylic acids

Formation of sodium salts


deprotonation in the presence of a base to form carboxylate salts. Long-chain carboxylic acids aggregate
to form micelles in polar solvents.
• Deprotonation in the presence of a base to form carboxylate salts. Long-chain car-
boxylic acids aggregate to form micelles in polar solvents, which have hydrophobic
interiors but have their charged “heads” exposed to the solvent. Remember “like
dissolves like”! + Na+
Na
Na+
–OOC COO–
Na+ COO–
–OOC COO– Na+
COO– Na+
–OOC
Na+ COO–

OOC Na+
–OOC COO–
Na+
Na+ Na+

cross section of a micelle

Decarboxylation
RCOOH → RH + CO2; reverse of the carbonation reaction

Nucleophilic acyl substitution


as in the synthesis of the carboxylic acid derivatives

42.
ORGANIC CHEMISTRY 3

Foundation Review
FOUNDATION REVIEW

SEPARATION TECHNIQUES

Distillation
used to separate a mixture of liquids of different volatility (different boiling points). If we heat the
mixture and cause it to vaporize, the vapor or gas phase will be more concentrated in the more volatile
compound. If we trap this vapor and recondense it, we have a new mixture that has a higher proportion
of the more volatile compound.
• Mixture of liquids of different volatility (different boiling points). If we heat the mixture
up and cause it to vaporize, the vapor or gas phase is going to be more concentrated in
the more volatile compound (the one with the lower boiling point). If we trap this vapor
and recondense it, we have a new mixture that has a higher proportion of the more
volatile compound. Can repeat the process until we end up with a liquid that is predomi-
nantly the more volatile compound.
Filtration
used to separate a solid from a liquid. Usually done by passing the mixture through filter paper.
• Used to separate a solid from a liquid. Usually done by passing the mixture through
filter paper. The liquid goes through but the solid cannot. Can apply a vacuum on the
other side to pull the liquid through more rapidly (vacuum filtration).

Extraction
separation of a mixture of liquids by dissolving them in solvents of different polarity

The usual set-up involves two liquids in a separatory funnel. One is the organic layer or phase and the
other is the aqueous layer. • Separation of a mixture of liquids by dissolving them in different sol-
vents (of different polarity).
• Usual set-up: two liquids in a separatory funnel. One is called the
“organic layer”: usually a nonpolar liquid like an ether or an alkane. The
other is the aqueous layer whose pH can be adjusted.
• Recall “like dissolves like”: highly polar and charged species will dissolve
in the aqueous layer. Nonpolar species will dissolve in the organic layer.
Chromatography
key aspect: stationary vs. mobile phase
• Strength of attraction differs; some compounds adhere to the stationary phase
more strongly than others.
• Thin layer chromatography: sample of mixture swept up by a solvent as it seeps up a
plate. Different compounds will move up different distances in a particular time.
• Gas chromatography and column chromatography: the compound with a lower affin-
ity for the stationary phase will move through quicker and will come off sooner

43.
MCAT: ORGANIC CHEMISTRY

SPECTROSCOPY

Mass spectroscopy
When bombarded with high-energy electrons, molecules break up into fragments that are often charged.

Different compounds fragment in characteristic ways. The sizes of the fragments therefore help us
determine the molecular weight, formula and structural moieties of the original molecule.
• Molecules are bombarded with high-energy electrons, causing them to break up into fragments.
• Some of these fragments are charged, so their movement can be affected by applying an external electric field.
• The charged fragments are directed by an electric field to a detector. The more massive the fragment, the
longer the time it takes for it to reach the detector.
• Molecules from different compounds break up in characteristic ways. Therefore the sizes of the fragments, as
determined by the time taken to reach the detector, help us determine the molecular weight, formula and
structural moieties (e.g. methyl group) of the original molecule
Infrared (IR) spectroscopy
• IR radiation excites chemical bonds, causing them to bend or stertch faster.
The molecule absorbs the energy carried by the IR radiation and ascend to a
higher energy level where the vibrational motion is more rapid.
• Different chemical bonds absorb light of different energies. The precise wave-
lengths or frequencies of IR radiation where absorption occurs therefore tell
us what bonds/functional groups are present:

Bond/Functional Group Frequency (cm–1)


C=O 1630–1780
N–H 3300–3500
O–H (in alcohol) 3590–3650
C=C 1620–1680
C≡C 2100–2260
• The values given above are not precise because the rest of
the molecule and other effects such as the solvent also
influence the frequency of IR light absorbed.

44.
FOUNDATION REVIEW

Nuclear magnetic resonance spectroscopy (1H NMR)


• The proton NMR spectrum of an organic molecule tells us something about
its structure: the different “types” of protons it has, how many of each
type, and sometimes even what other kinds of functionalities (benzene
rings, alcohol, etc.) are present.

How many different types of protons does each of the following molecules have?
A: (i) Two types: (ii) Five types:
(i) (a) (ii) (a) (c)
CH 3
H3C H

H3C CH 2OH
(b) (b) (b) (d) (e)
Note that the protons of the
two methyl groups are no longer
CH 3 (a) equivalent since they are cis to
different groups on the other
(a) the 6 methyl ones on the two ends end of the double bond.
(b) the four hydrogens directly attached
to the benzene ring

(iv) Three types


(iii) Four types
(iv)
(iii) Cl
O (a) (a)
H H H H
H3C CH 3
Cl C C C C C H
H H H H
(a) (b) (c) (d)
(b) (b)
(c)

45.
• Each type of proton gives a peak or a small cluster of peaks at a particular posi-
tion in an NMR spectrum. The position (x-axis scale) is known as chemical shift
MCAT: ORGANIC CHEMISTRY and is given in terms of ppm. Lower ppm is to the right.
• Protons of alkanes appear at low ppm (~1–3 ppm). If close to an electronegative
atom (alkyl halides, ethers, etc.) they will be more “downfield” (higher chemical
shift, more to the left): ~3–4 ppm.
Each type of proton gives a peak or a small cluster of peaks at a particular position in an NMR
spectrum. The position (x-axis scale) is known as chemical shift and is given in terms of ppm. Lower
ppm is to the right.

The actual number of peaks in the cluster is the “splitting pattern”: It tells us the number of protons
attached to neighboring carbon atoms. From this we can deduce the overall arrangement or locations of
the different types of protons. • Vinylic protons (protons directly attached to a carbon atom in a C=C bond)
appear ~5–6 ppm.
• Acetylenic protons (RC=CH) appear ~2.5–3 ppm.
• Aromatic protons ~7–9 ppm.
• Aldehyde protons (RCHO) appear ~9.5 ppm.
• Ketone protons (RCOCH3) appear ~2–2.6 ppm.
• The actual number of peaks in the cluster is the “splitting pattern”: It tells us
the number of protons attached to neighboring carbon atoms. From this we can
deduce the overall arrangement or locations of the different types of protons

singlet no protons on C CH3


neighboring carbons

neighboring carbon
C

protons
doublet one proton on one proton H C CH3 giving
neighboring carbon signal
C

two protons H
two protons on protons
triplet neighboring carbon H C CH3 giving
signal
neighboring carbon
C

If there are n protons on an adjacent carbon atom, then the cluster contains (n + 1) peaks.
• Note also that splitting is “reciprocal”: In the example shown above for the doublet case,
the one proton gives a signal that contains 4 peaks (a quartet) because of the 3 methyl
protons.
• The number of peaks does NOT tell us the number of protons that generate the signal. In
the examples above, there are three protons in the methyl group in each case.
• The number of protons giving the signal is given by the area under the peaks

46.
FOUNDATION REVIEW

BIOLOGICAL MOLECULES

Amino acids and proteins

NH2

R C COOH

an amino acid

Amino acids
the nature of the R group is what distinguishes different amino acids.

Proteins
Proteins are made up of many amino acids linked together by peptide bonds. The formation of a
peptide bond involves the loss of a water molecule as the amine functional group comes together with
the carboxylic acid functional group on another amino acid:

R1 NH2 R1 O NH2
H O
HOOC C N + C C R2 HOOC C N C C R2
H
H HO
H H H H

+ H2O

Carbohydrates
Carbohydrates are “hydrates of carbon”: i.e., they have the general formula Cn(H2O)m.
• The two cyclic forms shown differ in the stereochemistry at carbon-1 (whether
the hydroxide group is axial or equatorial). The two cyclic forms are known as
anomers, even though it is really just an example of diastereomers.

47.
MCAT: ORGANIC CHEMISTRY

Naming conventions

If n = m, then the carbohydrates are monosaccharides.

n = m = 3: a triose; n = m = 4: a tetrose; n = m = 5: a pentose; n = m = 6: a hexose

In addition to classifying a monosaccharide by the number of carbon atoms it contains, we can also
classify it by whether it contains an aldehyde or a ketone functional group:

O H CH2 OH
C C O
CH2 OH
HO C H H C OH
C O
H C OH H C OH
CH2 OH
H C OH HO C H

CH2 OH CH2 OH

a ketotriose an aldopentose a ketohexose

Hexose
In solution, hexoses tend to exist in a cyclic form rather than the straight chain form shown above:

(6)
HOH2 C
H (1) O O
C HO
HO (1)
H OH
OH
HO H OH
+
H OH (6)
HOH2 C
H OH O
HO
CH2OH HO OH
(6)
(1)
OH

The two cyclic forms shown differ in the stereochemistry at carbon-1 (whether the hydroxide group is
axial or equatorial). The two cyclic forms are known as anomers.

48.
FOUNDATION REVIEW

Disaccharides
Two monosaccharides come together to form a disaccharide. Again, the bond is formed with the
elimination of a water molecule.

Sucrose, for example, is a disaccharide made up of the two hexoses glucose and fructose:

HOH2 C
CH2 OH HO O
HOH2 C O
O H CH2 OH
HO
+ H OH O H
HO CH2 OH OH + H2 O
HO O H OH
OH CH2 OH
OH OH H
OH H

Polysaccharides
This polymerization process can go on, forming polysaccharides. Starch and cellulose are examples of
polysaccharides.

49.