Chemistry 52, Organic 2
Prerequisite: Chemistry 51
Grading Scheme
Recitation Grade:
100 pts average 75
Laboratory Grade
100 pts average 75
Lecture Exams
100 pts
Final
100 pts
Total
400 pts
Old exams and quizzes:
academic.brooklyn.cuny.edu/chem/howell/jhowell.htm
Safety: goggles, pregnancy
Cheating: F
jhowell@brooklyn.cuny.edu
Goals of the course:
1. Structure of organic molecules, relation of
structure to reactivity
2. Organic reaction patterns
3. Mechanism of reactions
4. Synthesis of organic compounds
5. Techniques of the trade
Scaling of Raw Grades for Recitation and Lab
1. Omit the student, B,
that dropped the course.
2. Get the average to 75
Multiply these sums by
4.9342
or
Note that student D was
absent from two labs and
will be low for that
reason. We will deal with
D later.
Multiply these sums by
0.49342
In both cases get the
same result…….
Now we have to spread the grades out so that there is a reasonable distribution about
the desired average of 75. This is done by expanding or contracting the set of grades
around the average so that the maximum turns out to be 95.
Now for the student D who is outside of the desirable limits (50 – 95). We move his
raw grade up to 70 so that D does not skew the scaling process. D receives a scaled
grade of about 51.
Trends
for
Relative
Acid
Strengths
Totally unionized in
aqueous solution
Aqueous Solution
Totally ionized in
aqueous solution.
Example
Recall
OH
CH3CH2OH
pKa = 9.95
Stronger acid
H2O + PhOH
phenol, PhOH
H3O+ + PhO-
Ka = [H3O+][PhO-]/[PhOH] = 10-9.95
ethanol, EtOH
H2O + EtOH
pKa = 15.9
Weaker acid
H3O+ + EtO-
Ka = [H3O+][EtO-]/[EtOH] = 10-15.9
Ethanol, EtOH, is a weaker acid than phenol, PhOH.
It follows that ethoxide, EtO-, is a stronger base than phenolate, PhO-.
For reaction PhOH + EtOStronger base
PhO- + EtOH where does equilibrium lie?
Weaker base.
K = 10-9.95 / 10-15.9 = 106.0
Query: What makes for strong (or weak) acids?
What affects acidity?
1. Electronegativity of the atom holding the negative charge.
Increasing
acidity.
CH3O - + H+
CH3OH
CH3NH2
CH3CH3
CH3NH - + H+
CH3CH2- + H+
Increasing
Increasingelectronegativity
basicity of
ofanion.
atom bearing negative
charge. Increasing stability
of anion.
2. Size of the atom bearing the negative charge in the anion.
Increasing
acidity.
CH3OH
CH3O - + H+; pKa = 16
CH3SH
CH3S - + H+; pKa = 7.0
Increasing
Increasingsize
basicity
of atom
of
holding
anion. negative charge.
Increasing stability of
anion.
What affects acidity? - 2
3. Resonance stabilization, usually of the anion.
Acidity
OH
O
O
O
O
Increasing
resonance
basicity of the
stabilization.
anion.
Increased
anion stability.
phenol, PhOH
CH3CH2OH
CH3CH2O - + H+
ethanol, EtOH
No resonance structures!!
Note that phenol itself enjoys resonance but charges are
generated, costing energy, making the resonance less
important. The more important resonance in the anion
shifts the equilibrium to the right making phenol more
acidic.
OH
OH
etc.
An example: competitive Bases &
Resonance
• Two different bases or two sites in the same molecule may compete
to be protonated (be the base).
Acetic acid can be protonated at two sites.
O
H
O
Pi bonding
electrons
converted to
non-bonding.
O
H
H+
O
H
acetic acid
Non-bonding
electrons
converted to
pi bonding.
Which conjugate acid is
favored?
H
O
O
H
O
O
H
+
H
H
The more stable one!
Which is that?
Recall resonance provides
additional stability by
moving pi or nonbonding electrons.
O
O
H
H
No valid resonance
structures for this
cation.
An example: competitive Bases &
Resonance
Comments on the importance of the resonance structures.
All atoms obey octet
rule!
H
O
H+
O
H
O
O
H
acetic acid
H
O
O
H
H
All atoms obey octet
rule!
O
O
The carbon is electron deficient – 6
electrons, not 8. Lesser importance
H
What affects acidity? - 3
4. Inductive and Electrostatic Stabilization.
Acidity.
H3CCH2OH
d+
H3CCH2O - + H+
d+
F3CCH2OH
Increasing anion stability.
Increasing anion
basicity.
F3CCH2O - + H+
Due to electronegativity of F
small positive charges build
up on C resulting in
stabilization of the anion.
Effect drops off with distance. EtOH pKa = 15.9
What affects acidity? - 4
5. Hybridization of the atom bearing the charge. H-A  H+ + A:-.
sp3
sp2
sp
Note. The NH2- is
more basic than
the RCC- ion.
Increasing Acidity of HA
Increasing Basicity of A-
More s character, more stability, more “electronegative”, H-A more
acidic, A:- less basic.
Know this order.
Example of hybridization Effect.
terminal alkyne
RCCH + LiCH2CH2CH2CH3
base
acid
RCCH + AgNO3
HCH2CH2CH2CH3 + RCCLi
AgCCR (ppt)
non-terminal alkyne
RCCR + LiCH2CH2CH2CH3
RCCR + AgNO3
NR
No Reaction
What affects acidity? - 5
O
H
H
H
6. Stabilization of ions by solvents (solvation).
O
H
H
O
O
R
+
Solvation provides
stabilization.
H
R
Comparison of alcohol acidities.
OH
OH
OH
H
O
pKa = 15.9
ethanol
17
propan-2-ol
18
H
2-methylpropan-2-ol
Crowding inhibiting solvation
Solvation, stability of anion, acidity
(CH3)3CO -,
crowded
Example
para nitrophenol is more acidic than phenol. Offer an explanation
OH
O
+ H
Why? Could be due to destabilization of the
unionized form, A, or stabilization of the
ionized form, B.
O
OH
+ H
N
N
O
O
A
O
O
B
The lower lies further to the right.
Examine the equilibrium for p-nitrophenol. How does the nitro
group increase the acidity?
O
OH
+ H
Examine both sides of
equilibrium. What does
the nitro group do?
First the unionized acid.
N
N
O
O
OH
O
O
A
O
O
B
N
N
N
O
O
C
Note carefully that in these resonance
structures charge is created: + on the O and –
in the ring or on an oxygen. This decreases
the importance of the resonance.
OH
OH
OH
N
O
O
O
O
Structure D occurs only due to the nitro
group. The stability it provides will
slightly decrease acidity.
D
Resonance structures A, B and C are comparable to those in the phenol itself and thus would
not be expected to affect acidity. But note the + to – attraction here
Now look at the anion. What does the nitro group do? Remember we are
interested to compare with the phenol phenolate equilibrium.
O
OH
+ H
N
N
O
O
A
O
O
B
N
N
N
O
O
O
O
C
In these resonance structures charge is not
created. Thus these structures are important
and increase acidity. They account for the
acidity of all phenols.
O
O
O
N
O
O
O
O
O
Structure D occurs only due to the nitro
group. It increases acidity. The greater
amount of significant resonance in the
anion accounts for the nitro increasing
the acidity.
D
Resonance structures A, B and C are comparable to those in the phenolate anion itself and thus
would not be expected to affect acidity. But note the + to – attraction here
Carboxylic Acid Structure
• The functional group of a carboxylic acid is a
carboxyl group.
O
C
O H
O
COOH
O H
CO2 H
Alternative repres entations for a carboxyl group
– The general formula for an aliphatic carboxylic
acid is RCOOH; that for an aromatic carboxylic acid
is ArCOOH.
Nomenclature - IUPAC
• IUPAC names:
drop the -e from the parent
alkane and add the suffix -oic acid.
O
HCOOH
CH3 COOH
Methan oic acid
(Formic acid )
Eth anoic acid
(Acetic acid)
OH
3-Methylbutanoic acid
(Isovaleric acid )
– If the compound contains a carbon-carbon
double bond, change the infix -an- to -en-.
O
O
O
OH
Propen oic acid
(A crylic acid)
OH
t rans-2-Butenoic acid
(Crotonic acid )
OH
t rans-3-Phen ylp ropen oic acid
(Cinnamic acid )
Nomenclature - IUPAC
• The carboxyl group takes precedence over
most other functional groups.
OH
O
OH
(R)-5-Hydroxyhexan oic
acid
O
O
OH
5-Oxohexan oic acid
O
H2 N
OH
4-Aminobutan oic acid
Nomenclature - IUPAC
– Dicarboxylic acids: add the suffix -dioic acid to the
name of the parent alkane containing both
carboxyl groups.
O
HO
O
OH
O
Eth an e dioic acid
(O xal i c aci d)
O
HO
O
OH
O
Bu tan e dioi c aci d
(Su ccin i c aci d)
HO
O
HO
OH
Propan e di oic acid
(Malon ic acid)
O
O
OH
HO
OH
O
Pe n tan e di oic acid
(Glu tari c aci d)
He xan edi oi c aci d
(Adi pic acid)
Nomenclature - IUPAC
– If the carboxyl group is bonded to a ring, name the ring
compound and add the suffix -carboxylic acid.
2
3
1
COOH
2-Cyclohexen ecarboxylic
acid
HOOC
COOH
t rans-1,3-Cyclopentan edicarboxylic
acid
– Benzoic acid is the simplest aromatic carboxylic acid.
– Use numbers to show the location of substituents.
COOH
COOH
OH
COOH
COOH
COOH
COOH
Benzoic 2-Hydroxyben zoic 1,2-Benzenedicarb oxylic 1,4-Ben zenedicarboxylic
acid
acid
acid
acid
(Salicylic acid )
(Ph thalic acid )
(Tereph thalic acid )
Nomenclature-Common
– When common names are used, the letters
detc. are often used to locate
substituents.
O
d  

5
1 OH
4 3 2
O
O
H2 N
OH
4-A min ob utanoic acid
(-A min obu tyric acid, GABA)
OH
NH2
(S)-2-Aminopropanoic acid
[(S)--Aminop ropionic acid;
L-alanine]
Physical Properties
• In the liquid and solid states, carboxylic acids are associated
by hydrogen bonding into dimeric structures.
Physical Properties
• Carboxylic acids have significantly higher boiling
points than other types of organic compounds of
comparable molecular weight.
– They are polar compounds and form very strong
intermolecular hydrogen bonds.
• Carboxylic acids are more soluble in water than
alcohols, ethers, aldehydes, and ketones of
comparable molecular weight.
– They form hydrogen bonds with water molecules
through both their C=O and OH groups.
Physical Properties
• Table 17.2
Molecu lar Boiling
Point
Weight
(°C)
(g/mol)
Solu bility
(g/100 g H 2 O)
Structu re
Name
CH3 COOH
CH3 CH2 CH2 OH
Acetic acid
1-Propan ol
60.1
60.1
118
97
CH3 CH2 CHO
Propan al
58.1
48
88.1
88.1
86.1
163
137
103
Infinite
2.3
Slight
CH3 ( CH2 ) 4 COOH Hexan oic acid 116.2
116.2
CH3 (CH2 ) 5 CH2 OH 1-Hep tanol
114.1
Hep tanal
CH3 ( CH2 ) 5 CHO
205
1.0
176
153
0.2
0.1
CH3 ( CH2 ) 2 COOH Butanoic acid
CH3 (CH2 ) 3 CH2 OH 1-Pentanol
Pentanal
CH3 ( CH2 ) 3 CHO
Infinite
Infinite
16
Physical Properties
– Water solubility decreases as the relative size of
the hydrophobic portion of the molecule
increases.
Acidity
• Carboxylic acids are weak acids.
– Values of pKa for most aliphatic and aromatic carboxylic
acids fall within the range 4 to 5.
• The greater acidity of carboxylic acids relative to alcohols
(both compounds that contain an OH group) is due to
resonance stabilization of the carboxylate anion.
••
••
••
O
C
CH3
C
O
••
••
••
O
••
••
••
CH3
O
••
T hese cont ribut ing st ructures are equivalent ;
t he carboxylat e anion is stabilized
by delocalization of t he negative charge
Acidity
– Electron-withdrawing substituents near the carboxyl group
increase acidity through their inductive effect.
Formula: CH3 COOH ClCH2 COOH
Cl2 CHCOOH
Name: Acetic
Chloroacetic D ich loroacetic
acid
acid
acid
pKa :
4.76
2.86
1.48
Increasin g acid strength
Cl3 CCOOH
Trich loroacetic
acid
0.70
Acidity
– The form of a carboxylic acid present in aqueous
solution depends on the pH of the solution.
O
O
O
O
OHOH
R- C-OH
R- C-OH + R- C-O RC-O
H+
H+
predom inant
present in equal
predominant
species when t he
concent rat ions when
species when
pH of the
t he pH of t he
t he pH of t he
solut ion is
solut ion is equal t o
solut ion is 7.0
2.0 or less
t he pKa of t he acid
or great er
Reaction with Bases
• Carboxylic acids, whether soluble or insoluble
in water, react with NaOH, KOH, and other
strong bases to give water-soluble salts.
COOH
+
NaOH
-
H2 O
Be n z oi c aci d
(slight ly soluble
in wat er)
COO Na
+
+
H2 O
S odiu m ben z oate
(60 g/100 m L water)
• They also form water-soluble salts with
ammonia and amines.
COOH + NH3
Be nz oi c acid
(slight ly soluble
in wat er)
-
H2 O
COO NH4
+
Amm oni um be nz oate
(20 g/100 m L water)
Reaction with Bases
• Carboxylic acids react with sodium
bicarbonate and sodium carbonate to form
water-soluble salts and carbonic acid.
– Carbonic acid, in turn, breaks down to carbon
dioxide and water.
CH3 COOH + NaHCO3
H2 CO3
CH3 COOH + NaHCO3
+
CH3 COO Na + H2 CO3
CO2 + H2 O
-
CH3 COO Na
+
+ CO2 + H2 O
• Reaction with bases
– The acid-base
properties of
carboxylic acids allow
an easy separation of
carboxylic acids from
water-insoluble
nonacidic
compounds.
Preparation
• Carbonation of Grignard reagents
– Treatment of a Grignard reagent with carbon
dioxide followed by acidification gives a carboxylic
acid.
O
Mg Cl + C
O
C arbon di oxi de
O
C-O
-
[ Mg Cl] +
A m agn e s iu m carboxyl ate
HCl
H2 O
O
C-OH + Mg 2 +
C yclope ntan e carboxyl ic acid
Oxidation
Primary alcohol
Na Cr O
RCH2OH 2 2 7
RCH=O
Na2Cr2O7
RCO2H
Na2Cr2O7 (orange)  Cr3+ (green)
Actual reagent is H2CrO4, chromic
acid.
Secondary
R2CHOH
Na2Cr2O7
R2C=O
KMnO4 (basic) can also be
used. MnO2 is produced.
Tertiary
R3COH
NR
The failure of an attempted
oxidation (no color change) is
evidence for a tertiary alcohol.
Oxidation: Aldehyde  Carboxylic
Recall from the discussion of alcohols.
Milder oxidizing reagents can also be used
Ag(NH3)2+
RCHO
RCO2- + Ag
Tollens Reagent test for
aldehydes
Haloform Reaction, overall
O
O
CH3
CX3
CO2-
X2
NaOH
O
CH3
 methyl
NaOH
+ HCX3
The last step which produces the
haloform, HCX3 only occurs if there is
an  methyl group, a methyl directly
attached to the carbonyl.
If done with iodine then the formation of
iodoform, HCI3, a bright yellow
precipitate, is a test for an  methyl
group (iodoform test).
Example…
OH
OH
Na2Cr2O7
acid
HO
CH2OH
O
CO2H
Oxidation using PCC
Primary alcohol
RCH2OH
PCC
Stops here, is not oxidized to
RCH=O carboxylic acid
Secondary
R2CHOH
PCC
R2C=O
Periodic Acid Oxidation
OH
O
OH
HIO4
glycol
O
+
HIO3
two aldehydes
OH
O
O
HIO4
HO
O
+
aldehydes
carboxylic acid
O
O
O
HO
HIO4
O
+
OH
carboxylic acid
HIO3
carboxylic acid
OH
O
O
2 HIO4
+ 2 HIO3
HO
O
OH
OH
O
HIO3
Hydrolysis of Nitriles, RCN
Work on mechanism of hydrolysis
Methanol to Acetic Acid
• Acetic acid is synthesized by carbonylation of
methanol.
– The carbonylation is exothermic.
CH3 OH + CO
O
CH3 COH H° = -138 kJ(33 kcal )/mol
– The Monsanto process uses a soluble rhodium(III)
salt and HI to catalyze the reaction.
Mechanism for Monsanto Process: methanol to acetic acid.
Product
Complicated process. Let’s look in some detail.
Reactant
Mechanism for Monsanto Process: methanol to acetic acid.
First. Look at the Rh
complexes
•Tetra coordinate complex
•Iodide negative, CO
neutral. Thus Rh(I)
•Hexa coordinate complex
•Iodide negative, CO
neutral, CH3CO negative.
Thus Rh(III).
•Hexa coordinate complex
•Iodide negative, CO
neutral, CH3 negative. Thus
Rh(III). Rh oxidized.
•Penta coordinate complex
•Iodide negative, CO
neutral, CH3CO negative.
Thus Rh(III).
Some Inorganic Chemistry:
Oxidative addition-reductive elimination
Mn+ + X-Y
M(n+2)+
X-
YH
Ph3P
Cl
Ox. Addn
Ir
I
CO
PPh3
Vaska’s compound
+ H2
Reduc. Elim.
Ph3P
Ir
III
Cl
H
PPh3
CO
Very important in activation of hydrogen
Insertion-deinsertion
M-X + L
M-L-X
O
(CO)5Mn-C-CH 3
(CO)5Mn-CH 3 + CO
Very important in catalytic C-C bond forming reactions
(polymerization, hydroformylation)
Also known as migratory insertion for mechanistic reasons
CH3
OC
Mn
OC
CO
CO
CO
H3C CO
H3C
C
CO
O
Mn
OC
CO
CO
CO
C
CO
O
Mn
OC
CO
CO
Mechanism for Monsanto Process: methanol to acetic acid.
Second: Look at the
reactions
Reductive Elimination.
•Tetra coordinate complex
•Rh(I)
Oxidative Addition.
•Hexa coordinate complex
•Rh(III).
•Hexa coordinate complex
•Rh(III).
•Rh(III).
Insertion Reaction, Migratory Insertion
Reduction of Carboxylic Acids
• The carboxyl group is very resistant to reduction.
– It is not affected by catalytic hydrogenation under
conditions that easily reduce aldehydes and ketones to
alcohols, and reduce alkenes and alkynes to alkanes. Nor is
it reduced by NaBH4.
• Lithium aluminum hydride reduces a carboxyl group to a 1°
alcohol.
– reduction is carried out in diethyl ether, THF, or other
nonreactive, aprotic solvent.
O
COH
1 . LiAlH4
2 . H2 O
CH2 OH + LiOH + Al(OH) 3
4-Hydroxymeth ylcyclopenten e
Selective Reduction
– Carboxyl groups are not affected by catalytic reduction
under conditions that reduce aldehydes and ketones.
O
O
OH
OH + H2
5-O xoh e xanoi c aci d
O
Pt
OH
25°C , 2 atm
5-H ydroxyh e xan oi c aci d
(racemic)
– Nor are carboxyl groups reduced by NaBH4.
O
C6 H5
O
OH
OH
1 . Na BH 4
2 . H2 O
5-O xo-5-ph e n yl pe ntan oic acid
C6 H5
O
OH
5-H ydroxy-5-ph e n yl pen tan oi c acid
(racemic)
Fischer Esterification
• Esters can be prepared by treating a carboxylic
acid with an alcohol in the presence of an acid
catalyst, commonly H2SO4, ArSO3H, or gaseous
HCl.
O
H2 SO 4
+
OH
HO
Ethanoic acid
Ethanol
(Ace tic acid) (Ethyl al cohol )
O
+ H2 O
O
Ethyl e thanoate
(Ethyl ace tate )
Fischer Esterification
• Fischer esterification is an equilibrium
reaction.
– By careful control of experimental conditions, it is
possible to prepare esters in high yield.
– If the alcohol is inexpensive relative to the
carboxylic acid, it can be used in excess to drive
the equilibrium to the right.
– Alternatively, water can be removed by azeotropic
distillation .
Mechanism of Fischer Esterification.
Consists of two parts
Acid catalyzed addition
of alcohol to the
carbonyl group.
Acid catalyzed elimination
of water to re-establish the
carbonyl group.
Compare with the
mechanism for formation of a
hemiacetal (next)
hemiacetal formation in Acid
Protonation of
carbonyl (making the
oxygen more
electronegative)
Attack of the (poor)
nucleophile on (good)
electrophile.
Deprotonation
Overall, we have added
the alcohol to the
carbonyl.
Can use diazomethane to form methyl esters.
• Diazomethane, CH2N2
– A potentially explosive, toxic, yellow gas is a
hybrid of two contributing structures.
H C N N:
:
:
+
+
H C N N:
H
H
– Treating a carboxylic acid with diazomethane gives
a methyl ester.
O
RCOH
+
ether
CH2 N 2
Di az ome th an e
O
RCOCH3 + N 2
A m e th yl e ste r
Diazomethane Mechanism
• Esterification occurs in two steps.
Step 1: Proton transfer to diazomethane.
O
O
R C O H +
+
–
CH2 N N
R C O:
A carboxylate
anion
+
CH3 N N
Methyldiazonium
cation
Step 2: Nucleophilic displacement of N2.
O
+
R C O:– + CH3 N N
SN 2
+
O
R C O CH3 + N N
Acid Chlorides
• The functional group of an acid halide is a
carbonyl group bonded to a halogen atom.
– Among the acid halides, acid chlorides are by far
the most common and the most widely used.
O
- C- X
O
CH3 CCl
Fu n ction al grou p
of an acid hal ide
A cetyl
ch loride
O
C-Cl
Be n z oyl
ch loride
Acid Chlorides
– Acid chlorides are most often prepared by treating
a carboxylic acid with thionyl chloride.
O
OH
Bu tanoic acid
O
+ SOCl2
+ SO2 + HCl
Cl
Th ionyl ch loride Butanoyl chlorid e
Acid Chlorides Mechanism
• Two steps.
Step 1: Reaction with SOCl2 transforms OH, a poor
leaving group, into a chlorosulfite group, a good
leaving group.
O
O
R- C-O- H + Cl-S- Cl
O
O
R C O S Cl + H- Cl
A chlorosulfite
group
Acid Halides
Step 2: Attack of chloride ion gives a tetrahedral
carbonyl addition intermediate, which collapses to
give the acid chloride.
O
R
C
O
O
S
Cl
+
Cl
-
O R
C
O
O
S
O
Cl
Cl
A tetrahedral carbonyl
addition intermediate
R- C- Cl
+
SO2
+
Cl
-
Decarboxylation
• Decarboxylation: The loss of CO2 from a
carboxyl group.
– Most carboxylic acids require a very high
temperature for thermal decarboxylation.
O
R-C-OH
decarboxylation
heat
R-H + CO2
Decarboxylation
• Exceptions are carboxylic acids that have a
carbonyl group beta to the carboxyl group
– This type of carboxylic acid undergoes
decarboxylation on mild heating.
O
O
warm
 
OH
3-Oxobu tan oic acid
(Acetoacetic acid)
O
+
Acetone
CO2
Mechanism: Thermal decarboxylation of a -ketoacid
– Thermal decarboxylation of a -ketoacid involves
rearrangement of six electrons in a cyclic sixmembered transition state.
H
O
H
O
O
O
(1)
+
O
O
+
C
CO2
O
(A cyclic six-membered
transition state)
Enol of
a ketone
HO
on ly th is carboxyl
has a C=O beta to it.
(2)
O

O

A ketone
O
O
OH
HO
O
Oxalos uccinic acid
O
OH + CO2
HO
O
-Ketoglutaric acid
Decarboxylation of Malonic Acid
– Decarboxylation occurs if there is any carbonyl
group beta to the carboxyl.
– Malonic acid and substituted malonic acids.
O
O
140-150°C
HOCCH2 COH
Prop anedioic acid
(Malon ic acid )
O
CH3 COH + CO2
Mechanism of Malonic Acid Decarboxylation
– Thermal decarboxylation of malonic acids also
involves rearrangement of six electrons in a cyclic
six-membered transition state.
O
HO
H
O
O
(1)
O
HO
H
O
+ C
O
(2)
A cyclic six-membered
Enol of a
transition s tate
carb oxylic acid
Same as earlier mechanism, except that have OH here
O
HO
A carb oxylic
acid
+ CO2