DETERMINING ORGANIC MECHANISMS ORGANIC OXIDATION–REDUCTION PHENOLS & QUINONE DERIVATIVES

Step 1: Know Your Nomenclature Level 0 (no bonds to heteroatoms): alkanes The hydrogen of the hydroxyl group of a phenol is
If given compound names in a question stem or Level 1: alcohols, alkyl halides, amines particularly acidic because the oxygen-containing
passage, be able to draw them. If working with Level 2: aldehydes, ketones, imines anion is resonance-stabilized by the ring.
reaction diagrams, be able to name the compounds. Level 3: carboxylic acids, anhydrides, esters, OH O− O O O
amides −H + − −
Step 2: Identify the Functional Groups Level 4 (four bonds to heteroatoms): carbon +H+
What functional groups are in the molecule? Do dioxide −

these functional groups act as acids or bases? How Oxidation = loss of electrons, fewer bonds to hydrogens, Quinones and Hydroxyquinones
oxidized is the carbon? Are there functional groups more bonds to heteroatoms (O, N, halogens)
that act as good nucleophiles, electrophiles, or Treatment of phenols with oxidizing agents produces
leaving groups? This will help define a category of Reduction = gain of electrons, more bonds to quinones.
reactions that can occur with the given functional hydrogens, fewer bonds to heteroatoms OH O

groups. Na2Cr2O7

Oxidizing Agents H2SO4

Step 3: Identify the Other Reagents Good oxidizing agents have a high affinity for OH
p-benzenediol
O
1,4-benzoquinone

Are the other reagents acidic or basic? Are they electrons (such as O2, O3, and Cl2) or unusually high (hydroquinone)

specific to a particular reaction? Are they good oxidation states (like Mn7+ in permanganate, MnO4—, These molecules can be further oxidized to form a
nucleophiles or a specific solvent? Are they good and Cr6+ in chromate, CrO42—). class of molecules called hydroxyquinones. Many
oxidizing or reducing agents? hydroxyquinones have biological activity.
Reducing Agents O

Step 4: Identify the Most Reactive Functional Group(s) Good reducing agents include sodium, magnesium, OH

More oxidized carbons tend to be more reactive aluminum, and zinc, which have low electronegativities
to both nucleophile–electrophile reactions and and ionization energies. Metal hydrides are also good O

oxidation–reduction reactions. Note the presence of reducing agents, like NaH, CaH2, LiAlH4, and NaBH4,
protecting groups that exist to prevent a particular because they contain the H– ion. Ubiquinones
functional group from reacting. Ubiquinone is also called coenzyme Q and is a vital
electron carrier associated with Complexes I, II,
Step 5: Identify the First Step of the Reaction and III of the electron transport chain.
If the reaction involves an acid or a base: Ubiquinone can be reduced to ubiquinol, which can
protonation or deprotonation later be reoxidized to ubiquinone. This is sometimes
If the reaction involves a nucleophile: called the Q cycle.
nucleophile attacks electrophile, forming a bond
If the reaction involves an oxidizing or ALDEHYDES
reducing agent: most oxidized functional
group is oxidized or reduced, accordingly The dipole moment of aldehydes causes an elevation
of boiling point, but not as high as alcohols because
Step 6: Consider Stereoselectivity Oxidation there is no hydrogen bonding.
If there is more than one product, the major product PCC takes a primary alcohol to an aldehyde.
will generally be determined by differences in strain PCC
Synthesis
or stability between the two molecules. Products OH O
Oxidation of primary alcohols
with conjugation (alternating single and multiple Jones’s reagent, KMnO4, and alkali dichromate Ozonolysis of alkenes
bonds) are significantly more stable than those salts will convert secondary alcohols to ketones
without. Reactions
and primary alcohols to carboxylic acids.
OH O Reactions of enols (Michael additions)
ALCOHOLS Na2Cr 2O7
H2SO4 O O
Base
O O
+ H:Base

Higher boiling points than alkanes R R R — R

Tertiary alcohols cannot be oxidized without O O

Weakly acidic hydroxyl hydrogen breaking a carbon–carbon bond. O O R R
O
+ O + Base

Synthesis Reduction R R R — R
R R
O OH
Addition of water to double bonds
Nucleophilic addition to a carbonyl
SN1 and SN2 reactions LiAlH4
O O— OH
or H+
Reduction of carboxylic acids, aldehydes, NaBH4
H H H
ketones, and esters Nu —
Nu Nu

Alcohols and Reactivity

° Aldehydes and ketones with NaBH4 or Aldol condensation
LiAlH4 Alcohols can be converted to mesylates or tosylates
to make them better leaving groups for nucleophilic An aldehyde acts both as nucleophile (enol form)
° Esters and carboxylic acids with LiAlH4
substitution reactions. and electrophile (keto form). One carbonyl forms an
enolate, which attacks the other carbonyl. After the
Reactions Mesylates (–SO3CH3) are derived from
aldol is formed, a dehydration reaction results in an
methanesulfonic acid.
Substitution reactions after protonation or leaving α,β-unsaturated carbonyl.
Tosylates (–SO3C6H4CH3) are derived from
group conversion O (reacts in
protonated
toluenesulfonic acid. O + OH
C form)
O
H
O O H
catalytic H H R −H2O

OH + HBr OH+2 + Br — Alcohols can be used as protecting groups for R

C
CH3 R
C
CH2 R
C
CH2
C
R R
C
C
C
R
H
carbonyls, as reaction with a dialcohol forms enol
H
aldol addition product aldol condensation
product
an unreactive acetal. After other reactions, the
Br — + OH2+ Br + H2O
protecting group can be removed with aqueous acid. Decarboxylation
O O O
O O O O
HO OH H 2O C
+
cat. H+ LiAIH4 cat. H O

OH O
NaI
+ O S O + —
SO3 O O O O OH OH
I
LiAIH4 OH
ClSO2

tosyl chloride

OH
 CARBOXYLIC ACIDS CARBOXYLIC ACID DERIVATIVES
Carboxylic acids have pKa values around 4.5 due Carboxylic acid derivatives contain three bonds to Amides
to resonance stabilization of the conjugate base. heteroatoms (O, N, halides, and so forth). As such,
Electronegative atoms increase acidity with inductive they can be interconverted through nucleophilic acyl Formation from an anhydride
effects. Boiling point is higher than alcohols because substitution by swapping leaving groups. O O O– O

of the ability to form two hydrogen bonds. Carboxylic acid derivatives can be ranked based on
NH3 +
O + O
H3N
descending reactivity:
Synthesis Acyl halides are the most reactive
Oxidation of primary alcohols with KMnO4 Anhydrides O O
O– O
+
O Carboxylic acids and esters +
O
KMnO 4 NH2 OH
OH OH
Amides are the least reactive H2N
H

A reaction that proceeds down the order of reactivity can

Hydrolysis of nitriles Formation from an ester
occur spontaneously by nucleophilic acyl substitution.
O

CH3Cl CH3CN CH3COH + NH+4

A reaction that proceeds up the order of reactivity requires
special catalysts and specific reaction conditions.
Reactions Hydrolysis (requires acid)
Anhydrides
Formation of soap by reacting carboxylic acids with Synthesis via dehydration of two carboxylic acids
NaOH; arrange in micelles
O

O—Na +

nonpolar tail polar head

Intramolecular formation of a cyclic anhydride
Nucleophilic acyl substitution O O

Ester formation OH
Reduction to an amine
O + H2O
O
OH
LiAlH4
O
O NH2 NH2
ortho-phthalic acid phthalic anhydride

Esters

Reduction to alcohols Transesterification

NITROGEN-CONTAINING COMPOUNDS

Hydrolysis
OH
OH
+ OH
+
O
O
H2O O O OH H
H + H

Strecker Synthesis O H2O

+OH
+ + +
H3O
Decarboxylation Reagents: aldehyde, ammonium chloride (NH4Cl), OH OH
OH

O potassium cyanide (KCN)

C
O R O H NH+3
NH3
NH+3 Reduction
H
R O
+
R OH O

LAH +
O OH OH
proton
transfer

NH2 NH2
Saponification
−
CN R NH+2 −H2O O O
+
R R OH 2
N –
RC O RC O Na+
N NH+ OH+2
H2N + O O HO
H H2N H2O H2N
–
NH RC O NaOH RC O Na+ + HO
CYCLIC CARBOXYLIC ACID DERIVATIVES R R R
O O HO
proton
–
transfer
O Na+
Lactams RC O RC
OH OH OH triacylglycerol soap glycerol
Cyclic amides are called lactams. These are named H2N
proton
transfer H2N H2O H2 N
OH OH+2
according to the carbon atom bound to the nitrogen:
+
NH+3 NH2 NH 2
R R R
β-lactams contain a bond between the β-carbon and PHOSPHORUS-CONTAINING COMPOUNDS
the nitrogen, γ-lactams contain a bond between the −NH3

γ-carbon and the nitrogen, and so forth. Phosphoric acid is a phosphate group or inorganic
OH+ O phosphate (Pi). At physiologic pH, inorganic
+ H2N
H2N
OH
−H
OH phosphate includes both hydrogen phosphate
O R R (HPO2–
4 ) and dihydrogen phosphate (H2PO4 ).
–
N N O N O N O
H H H H Pyrophosphate (PPi ) is P2O4–7 , which is released
β-lactam γ-lactam δ-lactam ε-lactam Gabriel (Malonic-Ester) Synthesis during the formation of phosphodiester bonds
Reagents: potassium phthalimide, diethyl in DNA. Pyrophosphate is unstable in aqueous
Lactones bromomalonate solution, and is hydrolyzed to form two
O O O
molecules of inorganic phosphate.
Cyclic esters are called lactones. These are named CO2C2H5 CO2C2H5 CO2C2H5

O O 4–
− + base
N K + Br C H N C H N C −

not only based on the carbon bound to the oxygen,

SN2
CO2C2H5 CO2C2H5 CO2C2H5
O O O
but also the length of the carbon chain itself. potassium
phthalimide
diethyl
bromomalonate P P
O O O O
O
O O
CO2H
O
−
CO2
− O
R–Br
S N2
O O
+ O CO2C2H5
H3O , ∆
O + NaOH

O
H3N C R
−CO2
+ H2N C R
H2O, ∆ N C R
Nucleotides with phosphate groups, such
O H O CO2 − CO2C2H5
O O
−
O ATP, GTP, and those in DNA, are referred to as
α-acetolactone β-propiolactone γ-butyrolactone δ-valerolactone organic phosphates.
 PURIFICATION METHODS SPECTROSCOPY
Extraction separates dissolved substances based Distillation separates liquids based on boiling point, Infrared spectroscopy measures molecular vibrations
on differential solubility in aqueous vs. organic which depends on intermolecular forces. Types are of characteristic functional groups.
solvents. simple, fractional, and vacuum. Functional Group Wavenumber (cm–1) Vibration

Alkanes 2800 — 3000 C H

thermometer 1200 C C
Alkenes 3080 — 3140 C H
1645 C C
condenser
vacuum adapter
Alkynes 2200 C C
3300 C H
Aromatic 2900 — 3100 C H
clamp to vacuum source 1475 — 1625 C C
water outlet clamp Alcohols 3100 — 3500 O H (broad)
water inlet
distilling flask Ethers 1050 — 1150 C O
receiving flask Aldehydes 2700 — 2900 (O)C H
1700 — 1750 C O
ice bath
heat source Ketones 1700 — 1750 C O
Carboxylic acids 1700 — 1750 C O
vacuum distillation
2800 — 3200 O H (broad)
Amines 3100 — 3500 N H (sharp)

UV spectroscopy involves passing ultraviolet

light through a chemical sample and plotting
absorbance vs. wavelength. It is most useful for
studying compounds containing double bonds and
heteroatoms with lone pairs.
Filtration separates solids from liquids.
1H–NMR is a form of nuclear magnetic resonance.

Type of Proton Approximate Chemical Shift (ppm)

Downfield from TMS
RCH3 0.9
Column RCH2 1.25
R3CH 1.5
–CH=CH 4.6–6
Column packing –C≡CH 2–3
Ar–H 6–8.5
–CHX 2–4.5
residue –CHOH/–CHOR 3.4–4
RCHO 9–10
filter paper RCHCO– 2–2.5
–CHCOOH/–CHCOOR 2–2.6
–CHOH–CH2OH 1–5.5
ArOH 4–12
to vacuum trap –COOH 10.5–12
glass projection to
hold up packing
–NH2 1–5

Ha Hb
clean filter flask deshielding b Cl C O C Hb

shielding Cl Hb

TMS
filtrate
a

vacuum filtration fractional distillation

Simple distillation can be used to separate two liquids

Chromatography uses a stationary phase and a with boiling points below 150°C and at least 25°C apart. 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0

mobile phase to separate compounds based on δ (ppm)

Vacuum distillation should be used when a liquid to

polarity and/or size. When analyzing an NMR spectrum, look for:
be distilled has a boiling point above 150°C. To prevent
degradation of the product, the incident pressure is Types of protons: corresponds to the number
solvent front
lowered, thereby lowering the boiling point. of peaks seen in the spectrum
Fractional distillation should be used when two Position of peaks: the further left-shifted
liquids have boiling points less than 25°C apart. By (downfield) the peak, the more deshielded
Y
introducing a fractionation column, the sample boils the proton. Usually this corresponds to more
Rf = X and refluxes back down over a larger surface area, electron-withdrawing groups
Y
X improving the purity of the distillate. Integration of peaks: the larger the integration,
the more protons contained under the peak
1 2 3 1 2 3
Recrystallization separates solids based on
thin-layer chromatograms differential solubility in varying temperatures. Splitting: hydrogens on adjacent carbons will
split a peak into n + 1 subpeaks, where n is the
Electrophoresis is used to separate biological number of hydrogens on the adjacent carbon
solvent
macromolecules based on size and/or charge.
sand

Type of
Chromatography Mobile Phase Stationary Phase Common Use
silica or alumina Thin-layer or Paper Nonpolar solvent Polar card Identify a sample
Reverse-phase Polar solvent Nonpolar card Identify a sample
Separate a sample into
sand Column Nonpolar solvent zPolar gel or powder
glass wool or cotton components
stopcock to control flow
Ion-exchange Nonpolar solvent Charged beads in column Separate components by charge
Polar, porous beads in
Size-exclusion Nonpolar solvent Separate components by size
column
collection flask Beads coated with antibody
Purify a molecule (usually a
Affinity Nonpolar solvent or receptor for a target
protein) of interest
molecule
column chromatography
Gas (GC) Inert gas Crushed metal or polymer Separate vaporizable compounds

High-performance Small column with Similar to column, but more

Nonpolar solvent
liquid (HPLC) concentration gradient precise