ALDEHYDES AND KETONES I

STRUCTURE

Aldehyde
O
C
R

R = H, alkyl, aryl

Ketone

O
C
R

R'

R and R' = alkyl or aryl

R and R' cannot be hydrogen!

NOMENCLATURE

IUPAC Nomenclature of Ketones

Choose the longest continuous carbon chain that
contains the carbonyl carbon
Number from the end of the chain closest to the
carbonyl carbon
Ketone ending is -one

Do the ketones section of Organic Nomenclature

program!

EXAMPLES
O
C
CH 3

CH 2
CH 2

CH 3

2-Pentanone

O
CH 3

C
CH 2

CH 2
CH

CH 3

CH 2
CH 3
4-Ethyl-3-hexanone

CH

CH3

CH3
3-Isopropylcyclopentanone
or 3-(1-Methylethyl)cyclopentanone

KETONES

Common, or Trivial, Names

Name each group attached to the carbonyl group as
an alkyl group
Combine into a name, according to the pattern:

alkyl alkyl ketone

NOTE: This is not all one word!

Example of Common Names

O
C
CH 3

CH 2
CH 2

CH 3

Methyl propyl ketone

O
CH3

C
CH2

CH3
CH2

Diethyl ketone

SPECIAL CASES
O

CH 3

CH 3

dimethyl ketone

diphenyl ketone

acetone

benzophenone

A common laboratory
solvent and cleaning
agent

KNOW
THESE

O
C CH3
methyl phenyl ketone
acetophenone

IUPAC Nomenclature of Aldehydes

Choose the longest continuous carbon chain that
contains the carbonyl carbon
Number from the end of the chain closest to the
carbonyl carbon (carbon #1!)
Aldehyde ending is -al

Do the aldehydes section of Organic Nomenclature

program.

EXAMPLES
H 3C

CH2

CH2
CH2

aldehyde group is
always carbon 1

H
pentanal

Cl
4

CH3

CH

CH
CH3

2-chloro-3-methylbutanal

Common Names of the Aldehydes

CH3

Formaldehyde
1

H3C CH2 C

H3C CH2

Acetaldehyde
2

Propionaldehyde
3

C
H

H3C CH2 CH2 C

Butyraldehyde

Valeraldehyde

O
C
H3C CH2 CH2 CH2 CH2
Caproaldehyde
6

RECOGNIZE
THESE

SPECIAL CASES

C
H

O
C H

formaldehyde

benzaldehyde

C
H

CH3

acetaldehyde

KNOW
THESE

Forming Common Names of Aldehydes

USE OF GREEK LETTERS

C
C
C
C
C
C
C

is always the end of the chain, no matter how long

CHO

CHO
Cl
-chlorocaproaldehyde
( -chlorohexanal )

Cl
-chlorocaproaldehyde
( -chlorohexanal )

REACTIVITY OF THE C=O GROUP

NUCLEOPHILIC ADDITION

GENERALIZED CHEMISTRY

THE CARBONYL GROUP

nucleophilic
at oxygen

.. O:

H+

electrophiles
add here

or E+

.. :O :

C
+
Nu:

nucleophiles
attack here
electrophilic
at carbon

STEREOCHEMISTRY

THE CARBONYL GROUP IS PLANAR

(SP2 HYBRIDIZED)

Nu:
.

..
..

Nu:
nucleophiles can attack from either top or bottom

LUMO OF FORMALDEHYDE
s*CH
s*CO
p* (LUMO)
p

nO

sCO
sCH

..

C O:
H

Nu:

nucleophiles add
to the larger lobe
(on carbon)

NUCLEOPHILIC ADDITION TO C=O

MECHANISMS
IN ACID AND IN BASE

Nucleophilic Addition to Carbonyl

Basic or Neutral Solution
.. _
:O:

..
O:

-:Nu

slow
C

an
alkoxide
ion

Nu
.. _
:O:

..
:O H
fast

C
Nu

H 2O

or on adding acid

Good nucleophiles
and strong bases
(usually charged)

C
Nu

BASIC SOLUTION

Nucleophilic Addition to Carbonyl

Acid Catalyzed
+
:O

..
O:
C

+
H

slow
+

fast

..
:O

.. +
O H

more reactive to
addition than the unprotonated precursor

:Nu

C
Nu

Acid catalysis speeds the rate of

addition of
weak nucleophiles and
weak bases (usually uncharged).

(+)

ACIDIC SOLUTION
pH 5-6

stronger acid
protonates the
nucleophile

CYANOHYDRINS

Addition of Cyanide

:C

N:

.. _
:O :

Buffered to pH 6-8
:O :
_
R

CN

CN
.. _
:O :
R

C
CN

..
:O
R

H2O

H
R

CN

a cyanohydrin

In acid solution there would be little CNA-,cyanohydrin

and HCN (g) would be a problem (poison).

CYANIDE ION BONDS TO HEMOGLOBIN

..
N
CYANIDE IS
Cyanide bonds
IS A POISON
(irreversibly) to the
C
..
site (Fe II) where
CH3
H3C

oxygen usually bonds.

N
Fe
N

N
CH3

H3C

CH2CH2COOH

You die of
suffocation lack of oxygen.

CH2CH2COOH

HCN is a gas that you can easily breathe into your lungs.

SYNTHESIS OF
-HYDROXYACIDS

SYNTHESIS OF AN -HYDROXYACID
O
CH3

OH

NaCN

C CH3

pH 8

C N

acetophenone

1) NaOH/H2O/D
2) H3O+

OH
C CH3
HO
Aldehydes also work unless
they are benzaldehydes,
which give a different reaction
(benzoin condensation).

a cyanohydrin

C O

HYDROLYSIS OF THE CYANO GROUP (NITRILES)

METHOD ONE : strong base + H2O + heat
gas

..

R C N

O:

NaOH

R C ..
+
H2O/D
O : Na+

:NH3

..

H 3 O+

neutralize

..

O:
synthesis of
carboxylic acids

R C ..
O H

OVER ALL

R-CN

..

R-COOH
Nitriles are hydrolyzed to carboxylic acids.

HYDROLYSIS OF THE CYANO GROUP (NITRILES)

METHOD TWO : strong acid + H2O + heat
..

R C N

H2SO4
H2O/D

O:
R C ..
O H

..

OVER ALL

R-CN

+ (NH4)2SO4

synthesis of
carboxylic acids

no mechanism
at this time

R-COOH
Nitriles are hydrolyzed to carboxylic acids.

ORGANOMETALLICS

REVIEW FROM CHAPTER 15

Synthesis of Alcohols

Addition of Organometallic Reagents

.. _
+
:O: M

:O :
R

(R-MgBr)

ether

C
R

(R-Li)

:R -

H2O
+
H

These reagents cannot

exist in acid solution

..
:O
R

alcohol

C
R

workup
step

H
R

M (OH)x

Summary of Reactions of
Organometallics with Carbonyl
Compounds
Organometallics with ketones yield
tertiary alcohols
Organometallics with aldehydes yield
secondary alcohols
Organometallics with formaldehyde yield
primary alcohols.
Organometallics with carbon dioxide yield
carboxylic acids.

All review
to you

etc.

HYDRATES

Addition of Water
O

O H

+
H
+

H 2O

R'

aldehyde or ketone
favored

C
O H

O
R'

C
R

R'

O H
a hydrate

hydrates are unstable

and cannot be isolated
in most cases

most hydrates revert to an aldehyde

or ketone as soon as they form
O H

+
R'

H 2O

WATER ADDS TO THE CARBONYL GROUP OF

ALDEHYDES AND KETONES TO FORM HYDRATES
H

catalyzed by a
trace of acid

..

:O

O H

..

..
O
..

..

..

+ H
:O

:O H

O+
H .. H

: O..

..
O
..

a hydrate

H
H

for most compounds the equilibrium

favors the starting materials
and you cannot isolate the hydrate

:O

O+ H

..

MICROREVERSIBILITY:
In a reaction where all steps are
reversible, the steps in the reverse
reaction are the same as those in
the forward reaction, reversed!

ACID CATALYSIS
RECALL

H
+

O H
..
H
..
+ H
:O
:O

..
:O H
+

Acid catalysis enhances the reactivity

of the carbonyl group - nucleophilic
addition proceeds more easily.

:Nu
weak nucleophiles
can react

ISOTOPE EXCHANGE REVEALS THE PRESENCE

OF THE HYDRATE
O18

O
R

+ H2O

H+

18

an excess of H2O18
shifts the equilibrium
to the right

O H
+H2O18

R C R
18 O

-H2O

exchange shows the

presence of a symmetric
intermediate

ACETALS AND
HEMIACETALS

Addition of Alcohols
TWO MOLES OF ALCOHOL WILL ADD

addition of one mole

H+

R C R' + ROH

O H
R C R'

hemiacetal

O R
addition of second mole

O H
R C R'
O R

H+

ROH

O R
R C R' + H O
O R
an acetal

ACETALS AND HEMIACETALS

R
C O

ROH

H aldehyde

R
C
H

OH ROH
OR

hemiacetal

R
C O
R

ketone

ROH

R
C
R

OH ROH
OR

OR
C

OR

acetal

OR
C

OR

(hemiketal)*

(ketal)*

*older term

*older term

..
R OH

+ H 2S O4

O
H

Like a
hydronium
ion

..

H O

:O

..

R C R

ACID CATALYZED
FORMATION OF A
HEMIACETAL

..

:O H

:O

R C R

..
O
..

R C R
O+
H .. R

first
addition

..

:
R O
H
..

:O

Normally the starting

material is favored but a second molecule
of alcohol can react
if in excess (next slide)

H
H

R C R
hemiacetal

:O
..

+ R O+

..

FORMATION OF THE ACETAL ( from the hemiacetal )

remove

R
H O

..

..

:O H

..

R C R

H
O
+
R C R

: O..

:O..

..
O
..

:O
..

second
addition

R C R

R C R

:O +

:O

SN1

hemiacetal

..

..

R O:
H

:O R
R C R

:O
..

R O:
H

..

O R

R C R

: O..
acetal

Resonance
stabilized
carbocation

WATER SEPARATOR
AZEOTROPE
Two miscible liquids that distill
as a single substance with a
boiling point that is lower than
either of the original liquids.
when cooled,
the azeotrope
separates

benzene 80o C
water 100o C
benzene-water
azeotrope
69.4o C
benzene and water do not mix,
but in the azeotrope the vapors
(gases) mix and distill together
benzene
+ water

benzene
water

Az

REMOVAL OF WATER SHIFTS THE EQUILIBRIUM

( Le Chatelier Principle )

O H

R C R

R C R

+
O
R
2

O R

O H

starting materials
are favored

Removal of water
shifts equilibrium

STABILITY OF ACETALS AND HEMIACETALS

Most hemiacetals are not stable, except for those of sugars
(see later).
Acetals are not stable in aqueous acid, but they are stable to
aqueous base.

AQUEOUS
ACID

AQUEOUS
BASE

OR H2SO4
OR

H2O

OR NaOH
C
OR H2O

ROH
C O +
ROH

no reaction

CYCLIC ACETALS
Cyclic acetals can be formed if a bifunctional alcohol is used.
1,2-ethanediol
H2C CH2
H2C

HO OH
O
C

CH2

H+ /benzene

O
C

CH3

H2 O

acetophenone

1,3-propanedithiol
O

HS

SH

H+ /benzene

H2 O

CH3

PROTECTING GROUP STRATEGY

Functional Group 1
TARGET

Functional Group 2
NON-TARGET

Add
Protecting
Group
TARGET

NON-TARGET

React
Unprotected
Group
NEW
GROUP

NEW
GROUP

Changed

NON-TARGET

Remove
Protecting
Group
NON-TARGET

Unchanged

USE OF A CYCLIC ACETAL AS A PROTECTING GROUP

O

Br

MgBr

Br

The Grignard
Reaction Takes
Place in Basic
Solution - The
Acetal is Stable

H3O+

COOH

Acetals Hydrolyze
in Acidic Solution

COOMgBr

SUMMARY

ADDITION OF WATER AND ALCOHOLS

WATER

H 2O

HO

OH

hydrate

ALCOHOLS
R-O-H

R-O-H
HO

RO

OR

OR

H2 O
hemiacetal

RO

OR

H+
H 2O
H 2O

NaOH

O
+2 ROH
no reaction

acetal

acetals are
stable to base
but not to
aqueous acid

CYCLIZATIONS
O

H2C CH2
H O OH

cyclic
acetal

OFTEN USED
AS A PROTECTIVE
GROUP

H 2O

OH

OR

C
OH

R-O-H

H 2O
cyclic hemiacetal
STABLE IF
FORMED FROM A
CARBOHYDRATE

cyclic acetal
A STARCH OR
POLYSACCHARIDE
IF FORMED FROM
CARBOHYDRATES

ADDITIONS OF AMINES
TO CARBONYL GROUPS
Aldehydes and Ketones

MANTRA

(Memorization Jingle)

Reactions with C=O :

Primary amines yield imines

Secondary amines yield enamines
Tertiary amines do not react

we will come back to this again and again

AMINES:

R N H

R N H

..

R N R

primary

secondary

tertiary

..

..

PRIMARY AMINES
IMINES

Addition-Elimination:
The Formation of Imines
R

ketone or
aldehyde

O
C

..
NH2

R
+

..

C
R

..

N
H

HA

O+

a carbinolamine
intermediate

H 2O

primary
amine
G is a primary
alkyl group

R
C

OH

an imine

Addition of the amine

is followed by a loss
of water (elimination).

Imines are compounds

with a C=N bond

Mechanism of Imine Formation

weak base addition - acid catalyzed

H
H-O
2

..
NH2 +

..
O
.. 1

C
R

R
G

loss of water
(elimination)

R
G

..
N

R
G

+
N
H

H-O
H

an imine
G

deprotonation

..
OH
..

H
H-O-H
+

proton exchanges

fast

..
C

slow

H
H-O-H
+

acid-catalyzed
addition

..
N

H R
+
N C O H

..
N

R
C
R

+
H-O-H

Formation of Simple Imines

overall result
remove
R
C
R

..
O + H2N

R
C

R + H 2O

R
an imine

These reactions do not favor the formation of the

imine unless:
- the product is insoluble
(crystallizes or precipitates) or
- water is removed to drive the equilibrium

shown
below

CRYSTALLINE IMINES
There are some special amines that
yield insoluble products (imines)
that are easy to crystallize ..
O

:NH2OH

H2 N C

hydroxylamine

..
R-NH-NH2 various
hydrazine
compounds

..
NHNH2

semicarbazine

..
NHNH2

O2N
NO2

2,4-dinitrophenylhydrazine

Formation of Oximes

R
C

..
H2 N

R
N

OH

hydroxylamine
aldehyde
or ketone

OH

an oxime

(usually crystallizes)

H 2O

Formation of Hydrazones

R
C

aldehyde
or ketone

..
+ H 2N

R
NH

a hydrazine

NH

R
a hydrazone

H 2O

2,4-Dinitrophenylhydrazones
NO2
R
C

..
H2 N

2,4-dinitrophenylhydrazine

NO2

NH

2,4-dinitrophenylhydrazine

aldehyde
or ketone

NO2
R
C

NO2

NH

insoluble
red, orange or yellow
precipitate forms

2,4-dinitrophenylhydrazone
a 2,4-DNP

(precipitates)

H 2O

Formation of Semicarbazones
semicarbazine

R
C
R
aldehyde
or ketone

..
+ H2N

NH C

NH2

semicarbazide

R
C

NH C

NH2

H2O

R
a semicarbazone
(usually crystallizes)

DERIVATIVES
CRYSTALLINE IMINES CAN BE USED AS DERIVATIVES
A derivative is a solid compound (formed from the
original compound) whose melting point can help
to identify the original compound.
What you will see in the tables of unknowns:

ketones
2-undecanone
4-chloroacetophenone
4-phenyl-2-butanone

bp

semicarbazone
2,4-dinitrophenylmp
hydrazone

231
232
235

12
12
-

122
204
142

63
236
127

BIOLOGICAL REACTIONS

Pyridoxyl-5-phosphate (P-5-P)
Converts amino acids to -ketoacids, and vice versa.
Biologically important in transamination reactions.

O
O

C H

HO P O CH2

..

OH

H2N C
R

O
N

CH3

H
pyridoxyl-5-phosphate

O
OH

an amino acid
H

- H 2O

( P-5-P )

N C
C

OH

OH

formation of
the imine

CH3

continued

first imine

:Enz

Enz-H
H

O O

R CH C

R C C

NH2

N C
C

OH
N
H

converts

OH

OH

OH

tautomerism

H-Enz
O

CH3

H N C
R
H C

Enz:

first imine

OH

-ketoacid

OH

O O

H 2O
N

new imine

NH2 R C C

CH3

CH2
OH

Removing the
amino group

hydrolysis of
the new imine

OH

N
H

CH3

pyridoxamine

TRANSFERRING THE AMINO GROUP

a different-ketoacid
O O
NH2 R C C
CH2

OH

OH

R
N

H N C
R
H C

CH3

OH

OH

R
N

CH3

pyridoxamine

tautomerism

hydrolysis of the imine

These steps are the
reverse of those on
the previous slides.

H
H2N C
R

O
OH

a different
amino acid

SUMMARY

Amino Acid-1 + pyridoxyl-5-phosphate

( takes NH2 group )

-Ketoacid-2 + pyridoxamine
( gives NH2 back )

a different
one reacts
here

-Ketoacid-1 +
pyridoxamine
( has NH2 )

Amino Acid-2 +
pyridoxyl- 5-phosphate

SECONDARY AMINES
ENAMINES

Formation of Enamines
-hydrogen

secondary
amine
H

is required

+
H

..

R2NH

benzene

OH

NR2

carbinolamine

NR2

H2O

an enamine

generally removed
by azeotropic
distillation

COMPARISON
carbinolamine intermediates

PRIMARY AMINES

SECONDARY AMINES
hydrogen on the
adjacent carbon

O
C

hydrogen
on the
nitrogen

..

N
H

H OH

R C C R
R NR2

..

-H2O

imine

-H2O

no hydrogen
on nitrogen

enamine
When there is no hydrogen on
nitrogen, one is lost from carbon.

piperidine

N
H

pyrrolidine

N
H

Water must be removed

morpholine

N
H

SOME SECONDARY
AMINES FREQUENTLY
USED TO FORM
ENAMINES

Enamine Formation
MECHANISM
1)

H
R

H
H-O-H
+

:O :
C

..
+O

H
H-O-H
+
H

..
:O

+N

..
:O

2)

..
+O

C
+

H
R

..
+OH2

N:

slow
R

..
N
R

H
R

O-H
H

continued .

Enamine Formation (cont)

MECHANISM
3)

..
+OH2

H
R

N:

+
C

N:
R

H
C

+
C

:
N+
R

N+
R

+ H 2O

H 2O

H
O-H

4)

N:
R

enamine

HH

3O

water must
be removed
to force the
equilibrium

Nucleophilic Character of Enamines

R

R
:N

R
C
R

..
C

C
R

+N

C
R

nucleophilic
at carbon

X
SN2
2)

Reactions of Enamines as Nucleophiles

R
:N

R
C

R
R

R
R

SN2

+N

:N

C
+

an iminium salt
R

_
+

hydrolysis

alkylation

ALKYLATION OF A KETONE
pyrrolidine

..

N
H
O

H+

..

CH3I

iminium
salt

+
N

CH3
H2O
remove
water

enamine

H 3 O+

workup

O
CH3
+

Az

N
H

Enamine Reactions -- Summary

O

secondary
amine

R
+N
R

R2NH
H

alkyl or
acyl
halide

H2O
H+
O
R

TERTIARY AMINES
DO NOT REACT

COMPARISON

PRIMARY AMINE

You need to lose two Hs,

one to form the intermediate,
one to eliminate water.

loses H from N
R

N R

O
C

..

N
H

SECONDARY AMINE

H is lost to form intermediate

loses H from C

H OH

N R

R C C R

TERTIARY AMINE
H is lost
.. H

: N-R
R

H :O

R N R
R
no H to lose

R C C R
R

N-R
+
R

unstable
reverses

The tertiary amine cant

form the carbinolamine
intermediate because
it lacks an H on N.

WITTIG REACTION

Ylide
A compound or intermediate
with both a positive and a
negative charge on adjacent
atoms.

- ..

Y
BOND

Betaine or Zwitterion
A compound or intermediate
with both a positive and a
negative charge, not on
adjacent atoms, but in different
parts of the molecule.

MOLECULE

-:

Preparation of a Phosphorous Ylide

( WITTIG REAGENT )
precipitates
R2
R1

benzene

(C6H5)3P :

R1

+
(C6 H5)3P

heat

R2

- ..

: O-CH
3
..

..
ether

strong base

Ph

Triphenylphosphine
( Ph = C6H5 )

Ph P Ph

+
(C6 H5)3P

- ..

R1

C
R2

an ylide

Resonance in Ylides
+
(C6H5)3P

..
C

R
(C6H5)3P

R
dp-pp BACKBONDING

..

Remember that Phosphorous

is a Period III element (d orbitals).

P C
3d

2p

Backbonding to phosphorous
reduces the formal charges
and stabilizes the negative
charge on carbon.

The Wittig Reaction

MECHANISM
R1
C

O +

-..

+
(C6H5)3P

R3

R2
R4

R2

ylide

R1

R3
C

R2

betaine

C
R4

synthesis of
an alkene

P(C6H5)3

INSOLUBLE
very thermodynamically
stable molecule

R2

R1

R3

: O:
.. _

P(C6H5)3
+

R1

R3

:O
..

R4

R4

P(C6H5)3

oxaphosphetane
(UNSTABLE)

SYNTHESIS OF AN ALKENE - WITTIG REACTION

H3C

CH2CH3

H3C

Br

CH2CH3

H3C

H3C

H3C
:P(C 6H 5)3

O
H3C
+

+
(C6H5)3P CH2CH3
ylide

(C6H5)3P
CH3ONa

CH2CH3
H

ANOTHER WITTIG ALKENE SYNTHESIS

H

+
Br
C P(C6H5)3

CH2Br

H
:P(C6H5)3

PhLi

H
C
H

C P(C6H5)3

..

+
ylide

..
O P(C 6 H 5)3
: ..
+

Br
C

triphenylphosphine
oxide (insoluble)

H H

Muscalure
H

CH3(CH2)6CH2

Sex pheromone of the

common house fly.
Musca Domestica

CH2(CH2)11CH3
(Z)-9-tricosene

Wittig

The reaction can be made to give the

cis alkene (Z) by correct choice of
solvent and temperature, or by the
separation of a mixture of cis and trans.

O
CH3(CH2)6

Cl
H

CH2(CH2)12CH3

ALDEHYDES AND KETONES II.

Oxidation and Reduction;
and Synthesis

CATALYTIC REDUCTION

OXIDATION AND REDUCTION

REDUCTION OF ALDEHYDES AND KETONES

C O

+ 2H+ + 2e-

C O
H H

OXIDATION OF ALCOHOLS

C O

- 2H+ - 2e-

C O

H H
These two reactions are the inverse of each other!

MANTRA
REDUCTION OF ALDEHYDES AND KETONES

Aldehydes react with one mole of reducing

agent to give a
Primary Alcohol
Ketones react with one mole of reducing
agent to give a
Secondary Alcohol
R

C O
H R
C O
R

CH OH
H R
CH OH
R

CATALYTIC REDUCTION
CH2

H2, 40 o C

C O Ni, 2 atm
H

. H. H.
H.

CH2
H

C O
H H
syn
addition

Reduction of a C=O group

is more difficult than the
reduction of a C=C double
bond.

A specially prepared
catalyst called
Raney Nickel
is often used for C=O.

. and reduction of a
benzene ring is more
difficult yet.

Often heat and pressure

are required.

SELECTIVE HYDROGENATIONS
H

OH

?
O

Hydride
reagents

20O C
1 atm
Pd/C

+ H2

easy
H

OH

Ni 40O C
2 atm
O

PtO2

100o C
5 atm
Conditions will vary
with the specific
compound.

OH

more
difficult
most
difficult

CATALYTIC HYDROGENATION AT 1 ATM

Hydrogen gas is just bubbled through
the solution

H2
solvent +
compound

magnetic
stir bar

suspended
catalyst

ROCKING BOTTLE HYDROGENATION

NOT SHOWN
perforated screen
surrounds the bottle

Good for pressures

up to about 2 atm.

H2

HYDROGENATION BOMB
pressure
gauge

stirrer

H2

inlet

head bolts
heavy steel
shield
threaded

heater

thick steel
walls

Good to pressures
of 5-10 atm.

HYDRIDE REDUCING REAGENTS

Another Method of Reduction

HYDRIDE REAGENTS

.. _
: O:

..
O:
R C R
H:

H3O+

R C R

R C R
H

OH

simplified mechanism

H
Na+ H B - H
H

sodium borohydride

Li

+ H Al -H
H

lithium aluminum hydride

THERE IS A DIFFERENCE IN REACTIVITY

more overlap

period 2
element

B
period 3
element

Al

2sp3 - 1s

NaBH4

H
more
diffuse

shorter, stronger bond

LESS REACTIVE
less overlap

3sp3 - 1s

LiAlH4
longer, weaker bond
MORE REACTIVE

COVALENT / IONIC CHARACTER

+

The Al-H bond has

more ionic character
and is a stronger base.
MORE REACTIVE

The B-H bond has more

covalent character.
LESS REACTIVE

Al

:H

SODIUM BOROHYDRIDE
REDUCTIONS

SODIUM BOROHYDRIDE IS SELECTIVE

NaBH4 only reduces aldehydes and ketones
aldehyde

ketone

C O
H R
C O
R

CH OH or R-CH2-OH
H R
CH OH
secondary
R
alcohol

OH

The double bond

and the ester are
not touched.

1 NaBH4
2 H 3 O+
O

primary alcohol

OMe

OMe

SELECTIVE HYDROGENATIONS
H

OH

1) NaBH4
2) H3O+
O

20O C
1 atm
Pd/C

+ H2

OH

Ni 40O C
2 atm
PtO2

?
Protective
group!

100o C
5 atm

OH

C
A, B, and C
progressive

Sodium Borohydride Reduction of

Aldehydes and Ketones
aldehyde
and ketones

O
R

NaBH4
R

+ Na
BH3
O

R C R
H

BH3

H3O+
workup
step

OH
R

H
alcohol

ADDITION IS CONCERTED
AND SYN STEREOSPECIFIC
..

..

C O:

C O:

H BH3

H BH3

reacts three
more times

Sodium Borohydride Reduction

of Norcamphor
exo attack

1 NaBH4

2 H 3 O+

O
bicyclo[2.2.1]heptan-2-one
(norcamphor)

OH
endo alcohol
(86%)

+
OH
H
exo alcohol
(14%)

Sodium Borohydride
Reduction of Camphor
hindered

CH3

H3C

CH3

H3C

H3C

CH3

1 NaBH4

CH3

2 H 3 O+

O
camphor

endo attack

H
CH3

OH

(exo)

OH
CH3

(endo)

borneol
(15%)

isoborneol
(85%)

LITHIUM ALUMINUM HYDRIDE

REDUCTIONS

LiAlH4 (LAH) IS NOT SELECTIVE

LiAlH4 reduces anything with a polar multiple bond!
+

or

C=Y:
..

C Y:

As with NaBH4 these compounds give alcohols:

CH OH

C O

aldehyde

CH OH

C O

ketone

LiAlH4 IS NOT SELECTIVE (cont)

These acid derivatives also give alcohols
R

CH OH

C O

ester

CH OH

C O

acid chloride

Cl

CH OH

C O
HO

ROH

RO

carboxylic
acid

LiAlH4 IS NOT SELECTIVE (cont)

These compounds give amines:

R
amide

nitrile

nitro
compound

R CH2 NH2

C O
NH2

N O
O

R CH2 NH2

R NH2

SIMPLE ALKENES DO NOT REACT

alkenes

or

alkynes

they are
not polar !

.. unless they are conjugated with a polar group.

.. which polarizes them.

Lithium Aluminum Hydride

Reduction of Aldehydes and Ketones
O
LiAlH4

4
R

ether
R

R
H C O
R

Al Li
4

O H

H C O
R

Al Li
4

4 H 2O

R + Al(OH)3

H
+ LiOH

REACTION OF HYDRIDES WITH WATER

LiAlH4 Reacts Explosively With H2O, Causing Fire
LiAlH4 + 4 H2O
LiOH + Al(OH)3 + 4 H2 + heat
Ether solvents are used: diethyl ether, THF, etc.

NaBH4 Reacts With H2O (or methanol) Very Slowly

NaBH4 + 4 H2O
NaOH + B(OH)3

+ H2

Water and alcohols can be used as solvents.

no fire

REMOVAL OF C=O
O

THREE METHODS
1) Clemmensen Reduction

Zn(Hg) + conc. HCl

strong acid conditions

2) Wolff-Kishner Reduction

NH2NH2 + KOH

strong base conditions

3) Desulfurization

Thioacetal + H2 + Ni

somewhat milder, but also reduces C=C

HOW WOULD YOU DO THESE ?

O
Wolf-Kishner (base)
Clemmensen (acid)

Cl

Cl

Desulfurization

O
Wolf-Kishner (base)

Clemmensen (acid)

CH2 OH

CH2 OH

Desulfurization

REDUCTIONS TO
ALDEHYDE/KETONE

LiAlH4 with Acid Chlorides

ACID CHLORIDES REACT TWICE
two hydrides react

Acid Chloride
O
R C
X
cleaves

O
R C

O H
LiAlH4

R C H
H

O H
R C H

O R'

+ LiCl + AlCl3

R'

O H

COLLAPSE OF THE INTERMEDIATE

bond is highly polar
- not strong

O
R C
Cl

AlH3
FIRST
ADDITION

O
R C H
SECOND
ADDITION

reacts again

- ..

:O:

AlH3
Cl- is lost

R C
H
Cl
The tetrahedral intermediate
collapses easily, because the
bond to Al is not strong.

LiAlH4 Reduction of an Acid Chloride

Li +
O

LiAlH4

R C

Li

Cl

.. - AlH3
: O:

R C
Cl
H

tetrahedral
intermediate
collapses

- AlH3

R C
H
H
H3O+
workup
OH
R C
H
H

LiAlH4

O
R C
aldehyde

+ Li+ ClH

leaving
group

reaction doesnt
stop here

TWO HYDRIDES REACT

REDUCTIONS OF ESTERS

.. ESTERS ALSO REACT TWICE

LiAlH4 with Esters

O H

O
R C

R C H

ESTERS REACT TWICE

Htwo hydrides react

Ester
O
R C
O R'
cleaves

O H
LiAlH4

R C H + R'
H

O H

two alcohols

LiAlH4 Reduction of an Ester

Li +
O
R C

Li

LiAlH4
OR'

.. - AlH3
: O:

R C
H
H
H3O+
workup
OH
two
alcohols

R C
H
H

LiAlH4

.. - AlH3
:O :

O
R C
aldehyde

+
R-OH

tetrahedral
intermediate
collapses

R C
OR'
H

RO

leaving
group

H
reaction doesnt
stop here

TWO HYDRIDES REACT

workup

Rosenmund Reduction
O
R C Cl + H2

Pd/BaSO4
sulfur
quinoline

SOCl2

Rosenmund catalyst

O
R C H
Ordinary catalysts
would continue and
reduce the aldehyde.

O
R C OH

R C Cl

R C Cl

. H. H.
H.

H H

Reduction of Esters to Aldehydes

DIBALH is soluble in hydrocarbon solvents because of the isobutyl groups;
ethers must be used for LAH.

O
R C
O R'
esters

DIBAL-H

toluene
- 70o C

H2O
HCl

some carboxylic
acids may be
RCOOH
reduced

R C
+
R'

H
OH

At 20o C,
LiAlH4 will
reduce the
aldehyde,
DIBAL-H

stops at the
aldehyde at
the lower
temperature.

NOTE

Sometimes LiAlH4 will also stop at the aldehyde if the temperature

is below -60o C. DIBAL-H is more consistent.

DIBAL-H ALSO REDUCES

ACID CHLORIDES TO ALDEHYDES
O
R C Cl + H2

DIBAL-H
Pd/BaSO4

R C H

o ether
-70sulfur

quinoline

This method gives better yields than the

Rosenmund reduction.
Apparently the tetrahedral
intermediate does not collapse
at -70o C (expel the leaving
group). This doesnt happen
until you warm the solution
and add aqueous acid which
destroys the DIBAL-H.

Li

stable
at -70o

+
O

- Al
H

R C
Cl
H

does not
react again

HYDROLYSIS OF THE INTERMEDIATE

Aqueous acid breaks the
complex apart.

Li

+
O

- Al

H3O+

.. H
:O

R C
Cl
H

R C
Cl
H

O
R C

+ LiCl

DIBALH ALSO REDUCES ALDEHYDES AND KETONES

The main feature of DIBALH is that it reacts only

ONCE to form a stable tetrahedral complex.
Since the complex doesnt fall apart until workup,
a second reduction is avoided.

Aldehydes and ketones only need one hydride to be

fully reduced ...
therefore, DIBAL-H reduces aldehydes and ketones.
With esters, acid chlorides and acids, more than one
hydride is required. Since DIBAL-H reacts only once,
they are not fully reduced, stopping at the aldehyde.

Ketone Synthesis
Lithium Dialkylcuprates
O

R C Cl + R2CuLi

0
ether

Less active than

RLi or RMgX

ketone

R C R

R Cu

LiCl

SUMMARY

MANTRA
Aldehydes react with one mole of reducing
agent to give a
Primary Alcohol
Ketones react with one mole of reducing
agent to give a
Secondary Alcohol
Acid Chlorides react with two moles of reducing
agent to give a
Primary Alcohol
Esters react with two moles of reducing
agent to give a
Primary Alcohol
+ a second alcohol

BIOLOGICAL
REDUCING REAGENTS

Nicotinamide Adenine Dinucleotide

NADH
adenine ..

..
N

NH2

H H

N:
O

:N

..
N

N
.. H C O P O P O CH
2 O
O 2
O_
H
H
H
H
_O
H
H
H
H
HO
OH
HO
OH
diphosphate
ribose

ribose

..
C NH2

nicotinamide

biological
COENZYME
works with
an enzyme

Reduction of Acetaldehyde
in Fermentation

RED

+
H

H3C C H
acetaldehyde

H H

OH
H3C C H
H

hydride
transfer

ethanol

O
C NH2

C NH2

..
N
R
NADH

OX

REVERSIBLE
This coenzyme
can also oxidize
depending on the
associated enzyme.

+
N
R
NAD

Reduction of Pyruvic Acid

in Muscle Tissue
O O
CH3 C C OH

+
H

pyruvic acid

H H

formed when
muscles contract

HO O

CH3 C C OH
H

lactic acid

O
C NH2

C NH2

..

+
N

NADH

+
NAD

OXIDATIONS OF ALCOHOLS

OXIDATION OF AN ALCOHOL
( LOSS OF 2H+ and 2e- )

carbon

C
H

- 2H
OXIDATION

REDUCTION

H
hydrogen

+ 2H

LOSS OF TWO
HYDROGENS
one an -H

Oxidations
The alcohol must
have -hydrogens.

H
R C OH
R

H
H

R C OH
R

R'

R'

R''

R C OH
R'

OH

no reaction

Remember: A dehydrogenation (loss of hydrogen)

is also a form of oxidation!

MANTRA
Primary alcohols oxidize to give
Carboxylic acids (via aldehyde)*
Seconday alcohols oxidize to give
Ketones

Tertiary alcohols do not oxidize

no oxidation
Aldehydes oxidize easily to give
Carboxylic acids
* With special reagents, the oxidation of a primary alcohol
can be stopped at the aldehyde.

Oxidation of Primary Alcohols

with KMnO4
R CH2 OH

KMnO4
heat

REQUIRES
HEAT

O
R C H
KMnO4
heat

two -hydrogens

O
R C OH

+ MnO2
precipitate

C=C Double bonds are also oxidized by this reagent.

Oxidation of Primary Alcohols

with K2Cr2O7
CHROMIC ACID
TEST

K2Cr2O7
R CH2 OH

H2SO4

O
R C H
K2Cr2O7
H2SO4
O
R C OH

3+
+ Cr

Oxidation of Secondary Alcohols

CHROMIC ACID
TEST

OH
R C R
H

K2Cr2O7
H2SO4

O
R C R

Jones Oxidation

3+
Cr

CHROMIC ACID
EQUILIBRIA

H 2SO4
CrO3 + H 2O

H 2SO4
H 2CrO4

x2

H 2Cr2O7 + H 2O

O
H O

Cr O H
O

Chromic acid

O
H O

Cr O Cr O H
O

Dichromic acid

ALL OF THESE ARE CHROMIC ACID SPECIES

CrO3

H2CrO4

NaCr2O7

H2SO4

H2SO4

H2SO4

oxidizing
agents

Oxidation with
Chromic Oxide and Pyridine
OH

CrO3 .
N

R C R
H

O
R C R

CH2Cl2
aldehydes do not
oxidize further

Sarett Oxidation

Oxidation with
Pyridinium Chlorochromate
CrO3Cl .
OH

R C R
H

O
R C R

CH2Cl2
aldehydes do not
oxidize further

PCC Oxidation

except in DMF
which enhances
reactivity

The Tollens Test

O
R

2 Ag(NH3)2OH
H

aldehyde

Ketones do
not react.

Remember that aldehydes

are easily oxidized.

metallic
silver

O
R

O NH4 +

2 Ag

+ H2O + NH3

silver mirror

PHARMACEUTICALS
Mexican Yams

HO

OH

the pill

C CH

Norethisterone

must be
injected

CH3

better absorbed through

the stomach and intestines
than progesterone

STEROID
O

progesterone

A B

C D

Mexican Yams
OH

OH

CrO3
pyridine

HOCH2CH2 OH

H+ (-H2O)
O

O
O

acetal

Na C CH
NH3(liq)
O Na

protecting group
HO

C CH

H3

C CH

O+
O

norethisterone