Download Reactions at Benzylic Carbons Carboxylic Acids and Reduction

Reactions at Benzylic Carbons
Oxidation: KMnO4 will convert any benzylic carbon to –COOH.
KMnO4, -OH
100 °C
Reduction: Benzylic functional groups readily reduced all the
way to hydrocarbon.
(X = halogen,
-OH, -OR)
H2, Pd-C
or
LiAlH4
Carboxylic Acids and Reduction/Oxidation
• Addition of H2 (or “H-”)
• Loss of O2 or O
Reduction
carboxylic
acid
aldehyde
(or ketone)
• Loss of H2
• Addition of O2 or O
Neither oxidation nor reduction:
alcohol
alkane
Oxidation
Addition or loss of H+, H2O, or HX
Review: Carboxylic Acids by Oxidation
Chromate oxidation of primary alcohols:
Na2Cr2O7
unavoidably
H2SO4
aldehyde
Oxidative cleavage of alkynes:
1. KMnO4
KOH, 
2. H3O+
internal alkyne
(or O3, H2O)
Purifying Carboxylic Acids by Acid-Base Extraction
+ unreacted
Na2Cr2O7
Let’s say
we run
a reaction.
Na+
H2SO4
Cr(H2O)63+
+ organic
side products
How do we isolate our product from the other reaction contents?
a separatory
(sept) funnel
H2O
CHCl3
densities:
(H2O) = 1 g/mL
(CHCl3) = 1.48 g/mL
HSO4-
Na+
Cr(H2O)63+
+ organic
side products
HSO4-
HSO4-
Na+
Cr(H2O)63+
discard
H2O layer
+ organic
side products
+ organic
side products
add NaOH
add acidic
H2O (HCl)
pure!!
discard
CHCl3 layer
+ organic
side products
Nucleophilic Addition to Carbonyls
Heteroatom electron donors add reversibly to C=O groups.
Equilibrium driven
to the left by:
+
• strength of C=O
double bond
true for Cl , HS , NH3…
• entropy
Carbon anions add irreversibly to C=O groups.
Reaction driven
to the right by:
+
• instability of
charge on
RCH2-
true for all carbon anions.
Relative Stabilities of Carbanions
least stable,
most reactive
most stable,
least reactive
<
sp3
<
<
<
Increasing substitution pushes
electron density onto carbon,
destabilizes anion (and makes it
more basic, and more reactive).
sp2
<
sp
<
<
All of these anions add
irreversibly to carbonyls,
+
Organometallic Reagents are
Synthetically Equivalent to Carbanions
alkyllithium
(organolithium)
Grignard reagent
(organomagnesium halide)
alkynylsodium
Computed electronic
structure of CH3Li
All of these react as “R - ”
Generating Organometallic Reagents
1. Deprotonation.
Not common. Works for alkynyl, some sp2 anions, but not for sp3
(because alkanes are not acidic enough).
Examples:
+
+
NaNH2
hexane
+
or
(BuLi)
(Et2O)
+
NH3
Generating Organometallic Reagents
2. Metalation of an alkyl halide.
Common for Grignard reagents, sp3 alkyllithiums.
Examples:
+
Mg (s)
+
2 Li (s)
Et2O
hexane
+
LiBr
solid
metals
Generating Organometallic Reagents
3. Lithium-halogen exchange.
Common for sp2 alkyllithiums. Not useful for sp3 alkyllithiums.
Example:
+
+
2
commercially
available
Reaction is driven by
formation of more
stable carbanion:
not
commercially
available
more stable
than
+
+
LiBr