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Organic Chemistry
MM3257A
ORGANIC CHEMISTRY 1
Foundation Review
FOUNDATION REVIEW
NOMENCLATURE
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.
• 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
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.
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:
CH3
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
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:
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°
(2) 120°
C
(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
8.
FOUNDATION REVIEW
4
H
H C C
H
H C C C H
1 2 H 3
9.
FOUNDATION REVIEW
δ–
O O O
= +
C C Cδ
O R
R O
10.
MCAT: ORGANIC CHEMISTRY
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
ISOMERS
(Different compounds with the same molecular formula)
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.
Example
Common example of conformational isomers: butane.
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
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.
HOOC CH3
third in priority
HOOC NH2
CH3
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
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
17.
FOUNDATION REVIEW
CH3 CH3
H OH = H OH
CH2CH3 CH2CH3
opposite configurations
rotate 90°
H H
OH OH
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
H
=
H Cl Cl
Cl
Cl H H
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
(ii) H H H CH3
CH3 and CH3
CH3 H
H H H H
(iii)
H H H CH3
and
(iv)
H CH2CH3 H CH3
and
(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
21.
MCAT: ORGANIC CHEMISTRY
SUBSTITUTION REACTIONS
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
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
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)
initiation: Cl Cl 2 Cl
CH 3 + Cl Cl CH 3Cl + Cl
termination: 2 Cl Cl Cl
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
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.
Electronegative groups or atoms near the proton to be removed help stabilize the conjugate base,
making the compound more acidic.
H H H δ– H H H δ–
O O
26.
MCAT: ORGANIC CHEMISTRY
b. The more electronegative the electron-withdrawing group, the stronger the acid.
H H δ– H H δ–
O O
Oδ
–
Oδ
–
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
Oδ
–
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
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.:
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.
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
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.
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.
NO2
HNO3(conc)
H2SO4(conc)
NO 2
33.
MCAT: ORGANIC CHEMISTRY
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
REDUCTION
OH O
cyclohexanol cyclohexanone
OH
O
NaBH4
R C H
C ethanol
R H
H
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:
NaBH 4
LiAlH 4
35.
MCAT: ORGANIC CHEMISTRY
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
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
O O
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
O
H2O
CH3 + CH3CH2CH2MgBr
O O– Mg +
δ –
δ δ + –
C CH3 + CH3CH2CH2 MgB C CH2CH2CH3
CH3
H2O
OH
C CH2CH2CH3+
CH3
Tertiary
38.
FOUNDATION REVIEW
Nomenclature
carboxylic acids: ends in “–oic acid”
O O O
CH3 OH
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
Anhydrides:
O O O O
C O C H3C C O C CH3
O O CH3
CH3
39.
MCAT: ORGANIC CHEMISTRY
O O
O C O +
H
R MgX
R O R OH
carboxylate carboxylic
acid
40.
FOUNDATION REVIEW
O O
NH2– + + Cl–
Cl NH2
O O
Cl– + + NH2–
NH2 Cl
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
Decarboxylation
RCOOH → RH + CO2; reverse of the carbonation reaction
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:
44.
FOUNDATION REVIEW
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
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
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
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
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
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.