Chemistry 52, Organic 2

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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_at_brooklyn.cuny.edu
2

• Goals of the course
• Structure of organic molecules, relation of
  structure to reactivity
• Organic reaction patterns
• Mechanism of reactions
• Synthesis of organic compounds
• Techniques of the trade

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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
Note that student D was absent from two labs and
will be low for that reason. We will deal with D
later.
or
Multiply these sums by 0.49342
In both cases get the same result.
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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.
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Trends for Relative Acid Strengths
Totally ionized in aqueous solution.
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Example
pKa 15.9 Weaker acid
pKa 9.95 Stronger acid
H2O PhOH H3O PhO-
H2O EtOH H3O EtO- Ka
H3OEtO-/EtOH 10-15.9
Ka H3OPhO-/PhOH 10-9.95
Ethanol, EtOH, is a weaker acid than phenol,
PhOH. It follows that ethoxide, EtO-, is a
stronger base than phenolate, PhO-. For reaction
PhOH EtO- PhO- EtOH where does
equilibrium lie?
Weaker base.
Stronger base
K 10-9.95 / 10-15.9 106.0
Query What makes for strong (or weak) acids?
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What affects acidity?
1. Electronegativity of the atom holding the
negative charge.
Increasing electronegativity of atom bearing
negative charge. Increasing stability of anion.
Increasing acidity.
2. Size of the atom bearing the negative charge
in the anion.
Increasing size of atom holding negative charge.
Increasing stability of anion.
Increasing acidity.
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What affects acidity? - 2
3. Resonance stabilization, usually of the anion.
Increasing resonance stabilization. Increased
anion stability.
Increasing basicity of the anion.
Acidity
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.
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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.
Pi bonding electrons converted to non-bonding.
Which conjugate acid is favored? The more stable
one! Which is that? Recall resonance provides
additional stability by moving pi or non-bonding
electrons.
No valid resonance structures for this cation.
Non-bonding electrons converted to pi bonding.
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An example competitive Bases Resonance
Comments on the importance of the resonance
structures.
All atoms obey octet rule!
The carbon is electron deficient 6 electrons,
not 8. Lesser importance
All atoms obey octet rule!
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What affects acidity? - 3
4. Inductive and Electrostatic Stabilization.
Increasing anion stability.
Increasing anion basicity.
Acidity.
d
d
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
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What affects acidity? - 4
Note. The NH2- is more basic than the RCC- ion.
5. Hybridization of the atom bearing the charge.
H-A ? H A-.
sp3 sp2 sp
More s character, more stability, more
electronegative, H-A more acidic, A- less
basic.
Increasing Acidity of HA
Increasing Basicity of A-
Know this order.
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Example of hybridization Effect.
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What affects acidity? - 5
6. Stabilization of ions by solvents (solvation).
Solvation provides stabilization.
Comparison of alcohol acidities.
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18
pKa 15.9
Crowding inhibiting solvation
(CH3)3CO -, crowded
Solvation, stability of anion, acidity
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Example
para nitrophenol is more acidic than phenol.
Offer an explanation
The lower lies further to the right.
Why? Could be due to destabilization of the
unionized form, A, or stabilization of the
ionized form, B.
B
A
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Examine the equilibrium for p-nitrophenol. How
does the nitro group increase the acidity?
Examine both sides of equilibrium. What does the
nitro group do? First the unionized acid.
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.
Structure D occurs only due to the nitro group.
The stability it provides will slightly decrease
acidity.
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
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Now look at the anion. What does the nitro group
do? Remember we are interested to compare with
the phenol phenolate equilibrium.
In these resonance structures charge is not
created. Thus these structures are important and
increase acidity. They account for the acidity
of all phenols.
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.
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
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Sample Problem
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Carboxylic Acid Structure

• The functional group of a carboxylic acid is a
  carboxyl group.
• The general formula for an aliphatic carboxylic
  acid is RCOOH that for an aromatic carboxylic
  acid is ArCOOH.

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Nomenclature - IUPAC

• IUPAC names drop the -e from the parent alkane
  and add the suffix -oic acid.
• If the compound contains a carbon-carbon double
  bond, change the infix -an- to -en-.

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Nomenclature - IUPAC

• The carboxyl group takes precedence over most
  other functional groups.

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Nomenclature - IUPAC

• Dicarboxylic acids add the suffix -dioic acid to
  the name of the parent alkane containing both
  carboxyl groups.

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Nomenclature - IUPAC

• If the carboxyl group is bonded to a ring, name
  the ring compound and add the suffix -carboxylic
  acid.
• Benzoic acid is the simplest aromatic carboxylic
  acid.
• Use numbers to show the location of substituents.

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Nomenclature-Common

• When common names are used, the letters
  ????????????etc. are often used to locate
  substituents.

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Physical Properties

• In the liquid and solid states, carboxylic acids
  are associated by hydrogen bonding into dimeric
  structures.

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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 CO and OH groups.

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Physical Properties

• Table 17.2

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Physical Properties

• Water solubility decreases as the relative size
  of the hydrophobic portion of the molecule
  increases.

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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.

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Acidity

• Electron-withdrawing substituents near the
  carboxyl group increase acidity through their
  inductive effect.

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Acidity

• The form of a carboxylic acid present in aqueous
  solution depends on the pH of the solution.

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Reaction with Bases

• Carboxylic acids, whether soluble or insoluble in
  water, react with NaOH, KOH, and other strong
  bases to give water-soluble salts.
• They also form water-soluble salts with ammonia
  and amines.

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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.

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• Reaction with bases
• The acid-base properties of carboxylic acids
  allow an easy separation of carboxylic acids from
  water-insoluble nonacidic compounds.

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Preparation

• Carbonation of Grignard reagents
• Treatment of a Grignard reagent with carbon
  dioxide followed by acidification gives a
  carboxylic acid.

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Oxidation
Primary alcohol
Na2Cr2O7
Na2Cr2O7
RCH2OH RCHO
RCO2H
Na2Cr2O7 (orange) ? Cr3 (green) Actual reagent
is H2CrO4, chromic acid.
Secondary
Na2Cr2O7
KMnO4 (basic) can also be used. MnO2 is produced.
R2CHOH R2CO
Tertiary
The failure of an attempted oxidation (no color
change) is evidence for a tertiary alcohol.
R3COH NR
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Oxidation Aldehyde ? Carboxylic
Recall from the discussion of alcohols.
Milder oxidizing reagents can also be used
Tollens Reagent test for aldehydes
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Haloform Reaction, overall
The last step which produces the haloform, HCX3
only occurs if there is an a methyl group, a
methyl directly attached to the carbonyl.
a methyl
If done with iodine then the formation of
iodoform, HCI3, a bright yellow precipitate, is a
test for an a methyl group (iodoform test).
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Example
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Oxidation using PCC
Primary alcohol
Stops here, is not oxidized to carboxylic acid
PCC
RCH2OH RCHO
Secondary
PCC
R2CHOH R2CO
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Periodic Acid Oxidation
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Hydrolysis of Nitriles, RCN
Work on mechanism of hydrolysis
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Methanol to Acetic Acid

• Acetic acid is synthesized by carbonylation of
  methanol.
• The carbonylation is exothermic.
• The Monsanto process uses a soluble rhodium(III)
  salt and HI to catalyze the reaction.

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Mechanism for Monsanto Process methanol to
acetic acid.
Reactant
Product
Complicated process. Lets look in some detail.
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Mechanism for Monsanto Process methanol to
acetic acid.

• Tetra coordinate complex
• Iodide negative, CO neutral. Thus Rh(I)

First. Look at the Rh complexes

• 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).

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Some Inorganic Chemistry Oxidative
addition-reductive elimination
-
-
Ox. Addn
Reduc. Elim.
Very important in activation of hydrogen
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Insertion-deinsertion
Very important in catalytic C-C bond forming
reactions (polymerization, hydroformylation)
Also known as migratory insertion for mechanistic
reasons
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Mechanism for Monsanto Process methanol to
acetic acid.
Second Look at the reactions

• Tetra coordinate complex
• Rh(I)

Reductive Elimination.
Oxidative Addition.

• Hexa coordinate complex
• Rh(III).

• Hexa coordinate complex
• Rh(III).

• Rh(III).

Insertion Reaction, Migratory Insertion
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Association-Dissociation of Lewis bases
D(FOS) 0 D(CN) 1 D(NVE) 2
A Lewis base is a neutral, 2e ligand L (CO,
PR3, H2O, NH3, C2H4,) in this case the metal is
the Lewis acid
For 18-e complexes, dissociative mechanisms
only For lt18-e complexes dissociative and
associative mechanisms are possible
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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.

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Selective Reduction

• Carboxyl groups are not affected by catalytic
  reduction under conditions that reduce aldehydes
  and ketones.
• Nor are carboxyl groups reduced by NaBH4.

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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.

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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 .

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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)
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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.
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Can use diazomethane to form methyl esters.

• Diazomethane, CH2N2
• A potentially explosive, toxic, yellow gas is a
  hybrid of two contributing structures.
• Treating a carboxylic acid with diazomethane
  gives a methyl ester.

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Diazomethane Mechanism

• Esterification occurs in two steps.
• Step 1 Proton transfer to diazomethane.
• Step 2 Nucleophilic displacement of N2.

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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.

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Acid Chlorides

• Acid chlorides are most often prepared by
  treating a carboxylic acid with thionyl chloride.

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Acid Chlorides Mechanism

• Two steps.
• Step 1 Reaction with SOCl2 transforms OH, a poor
  leaving group, into a chlorosulfite group, a good
  leaving group.

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Acid Halides

• Step 2 Attack of chloride ion gives a
  tetrahedral carbonyl addition intermediate, which
  collapses to give the acid chloride.

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Decarboxylation

• Decarboxylation The loss of CO2 from a carboxyl
  group.
• Most carboxylic acids require a very high
  temperature for thermal decarboxylation.

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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.

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Mechanism Thermal decarboxylation of a ?-ketoacid

• Thermal decarboxylation of a ?-ketoacid involves
  rearrangement of six electrons in a cyclic
  six-membered transition state.

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Decarboxylation of Malonic Acid

• Decarboxylation occurs if there is any carbonyl
  group beta to the carboxyl.
• Malonic acid and substituted malonic acids.

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Mechanism of Malonic Acid Decarboxylation

• Thermal decarboxylation of malonic acids also
  involves rearrangement of six electrons in a
  cyclic six-membered transition state.

Same as earlier mechanism, except that have OH
here