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Chapter 9: Aldehydes and Ketones
© R. Spinney 2013
Aldehydes and Ketones
Both contain a carbonyl group
– Aldehydes have at least 1 H atom attached to the carbonyl C atom, i.e. R1 or R2 = H
– Ketones have two carbon groups attached to the carbonyl C atom
– R1 / R2 can be alkyl, alkenyl, alkynyl or aromatic
O
R1 R2
Nomenclature
• IUPAC names:– The parent chain is the longest chain that contains the
carbonyl group.
– For an aldehyde, change the suffix from –e to –al; for a ketone change the suffix from –e to –one
– For an unsaturated aldehyde or ketone, show the carbon-carbon double bond by changing the infix from –an– to –en–; the location of the suffix determines the numbering pattern.
– For a cyclic molecule in which –CHO is bonded to the ring, add the suffix –carbaldehyde.
Nomenclature
Nomenclature
or formyl
Nomenclature
• Common names
– For aldehydes, the common name is derived from the common name of the corresponding carboxylic acid.
– For ketones, name the alkyl or aryl groups bonded to the carbonyl carbon and add the word ketone.
Physical Properties
Boiling Points: intermediate between alcohols and alkanes, i.e.
Solubility: smaller compounds are soluble in water as they are H-bond acceptors, i.e.
O O H
- 1 ° C 4 9 ° C 9 7 ° C
O
H
OH
HO
H
Common Aldehydes or Ketones
2) acetone: used as starting material for other chemicals and as a solvent.
c) oxidation of isopropanol
OO H [ O ]
Synthesis of Aldehydes and Ketones
Aldehydes and ketones are commonly synthesized from an alcohol by oxidation, i.e.
O
H
O H
H
O
O H
[ O ] [ O ]
[ R ] [ R ]
Synthesis of Aldehydes and Ketones
The nature of the alcohol and oxidizing agent determine the product. Jones reagent oxidizes 1° to an acid, 2° alcohol to a ketone.
OHO
OH
OH O
CrO3
H+, acetone
CrO3
H+, acetone
Synthesis of Aldehydes and Ketones
PCC reagent oxidizes 1° to an aldehyde.
3° alcohols can not be oxidized.
O HO
HP C C
COH
R
R'
R"
[O]
No Rxn
Synthesis of Aldehydes and Ketones
Aromatic ketones can be prepared by Friedel-Crafts acylation reactions, i.e.
R
O
C l R
O
A l C l 3
Synthesis of Aldehydes and Ketones
Finally methyl ketones can be prepared from terminal alkynes, i.e.
RR
OH + , H 2 O
H g 2 +
The Carbonyl Group
The carbonyl group is:
– A double bond between a C and O atom \ both are sp2 hybridized \ trigonal planar geometry
– O is more electronegative \ a polar covalent bond
O-+
The Carbonyl Group
The carbonyl group is:
– Resonance is possible due to the p bond, i.e.
O O
O O
-+
- +
Nucleophilic (Acyl) Addition Reactions
The carbonyl group is subject to:
The general reaction mechanism is:
O - +
. .
. .n u c l e o p h i l e sa t t a c k h e r e
e l e c t r o p h i l e sa t t a c k h e r e
OH
RO
HR
Nu
OHH
R
NuNu:-
H2O
trigonal planarcarbonyl compound
tetrahedral alkoxideintermediate
tetrahedral alcohol product
Nucleophilic Addition Reactions
Acids can be used to catalyze the addition of weak nucleophiles, i.e.
Note: the product is the same, but the resonant structure II enhances the attack of the nucleophile as the C has a formal positive charge.
OH
ROH
HR
Nu
O+H
RH
OH
RH
Nu:-
H+++
I II
Nucleophilic Addition ReactionsAldehydes vs. Ketones:– Generally ketones are less reactive than aldehydes
due to:• Steric hindrance at the carbonyl group
• Stability of the carbocation, i.e.
The second alkyl group stabilizes the carbocation making it less reactive (i.e. + is smaller)
O
R R '
O
R H
-
+
-
+v s .
Reactions of Aldehydes & Ketones
The following pages will deal with the nucleophilic addition reactions to carbonyl groups based on the nature of the nucleophile.
Alcohols: Hemiacetals & Acetals
The oxygen atom of the alcohol is nucleophilic.
Note: need to use an acid catalyst as ROH is a weak nucleophile.
reaction is reversible
R O
H
O
H
R '
C O RR '
O H
H
H +
Alcohols: Hemiacetals & Acetals
The mechanism is:
RO
HC O
+R'
OH
H
H
R
C ORR'
OH
H
O
R' H
O+
R' H
H
C O+
R'
OH
H
H
R
H+
-H+
hemiacetal
Alcohols: Hemiacetals & Acetals
In the presence of excess alcohol the hemiacetal can react one more time to product an acetal, i.e.
RO
H
C OHR'
OR
H
C OH2
+R'
OR
H
C+
R'
OR
H
CR'
O+
H
R
C O+
R'
OR
H
H
R
C+
R'
OR
H
C ORR'
OR
H
H+
-H+
-H2O
acetal
Alcohols: Hemiacetals & Acetals
The overall reaction is:
Note: the mechanism is an SN1
C O HR'
O R
H
C O RR'
O R
H
R O H / H +
a ce ta l
Alcohols: Hemiacetals & Acetals
The reaction can occur intramolecular if a hydroxy group is present, i.e.
Sugars do this naturally, very common for 5 or 6 membered rings
OH
O
O
OH
H+
cyclic hemiacetal
Alcohols: Hemiacetals & Acetals
Ketones react the same way, i.e.
Note: an older convention called these a hemiketal and ketal
the reaction is easily reversed
C R 'R '
O
C O RR '
O H
R '
C O RR '
O R
R '
R O H / H +
h e m ia c e ta l
R O H / H +
a c e ta l
Water: Hydrates or Gem Diols
This is a reversible reaction, i.e.
Gem diols are not stable and will lose the H2O to reform the more stable carbonyl group.
C HR
O
C O HR
O H
H
H 2 O
- H 2 O
Organometallic Reagents
Organometallic reagents are sources of carbon nucleophiles.
They are strong nucleophiles (and bases) and produce irreversible reactions.
Products are alcohols, depending on the substrate:– Formaldehyde 1° alcohol– Other aldehydes 2° alcohol– Ketones 3° alcohols
Organometallic Reagents
Grignard reagents:
or
O O
R
O H
RH 3 O +
e t h e r
R - M g - XM g X +
O O H
R1 ) R - M g - X / e t h e r
2 ) H 3 O +
Organometallic Reagents
Organolithium reagents:
or
O
H
O
R
H
O H
R
H
H 3 O +
e t h e r
R - L iL i +
O
H
O H
R
H
1 ) R - L i / e t h e r
2 ) H 3 O +
Organometallic Reagents
Acetylide reagents:
or
O
H
O
H
OH
HC H3O +Na+
Na+
O
H
OH
H
C
2) H3O +
Na+1)
Cyanide: CyanohydrinsReversible reaction, i.e.
Mechanism: O
OH
CNKOHHCN
cyanohydrin
OO
C N
O
C N
O H
C N
KO HH C N + H 2O K + CN -+K +
K +H 2O KO H+ +
Nitrogen Nucleophiles
Amines are nucleophilic due to the lone pair of electrons. The reaction is irreversible overall and produce an imine, i.e.
O
NH2
R N H
OH
R
NR
im ine
-H 2O
tetrahedra l add ition p roduct
Nitrogen Nucleophiles
Mechanism:
O
NH2
R NH2
+O
R
NR
NH
O
R
NH
O
RNH
OH
R
imine
-H2O
not stable
H+-base
H+-base
base
Nitrogen Nucleophiles
Imines are important in biology as intermediates in some biochemical reactions, i.e.
All reactions have a common feature, the loss of a water molecule, the 2 H atoms from the amino group and the O atom from the carbonyl.
Nitrogen NucleophilesA number of different “imine” type compounds are possible depending on the nature of the nitrogen group, i.e.
These derivatives have been use in the past for structure identification purposes.
Formula Name Derivative Name
RNH2 or ArNH2 1° amine C=NR or C=Nar Imine
NH2OH Hydroxylamine C=NOH Oxime
NH2NH2 Hydrazine C=NNH2 Hydrazone
NH2NHC6H5 phenylhydrazine C=NNHPh phenylhydrazone
Reduction of Carbonyls
Aldehydes and ketones can be reduced to 1° and 2° alcohols respectively.
Common reducing agents are:
– Lithium aluminium hydride: LiAlH4
– Sodium borohydride: NaBH4
Reduction of Carbonyls
In both cases the metal – hydrogen bond is polarized so that the electron density is on the H atom, i.e.
Both reagents act as hydride (H:-) donors, which is a nucleophile (and very strong base).
Note: NaBH4 is a “milder” reagent and can be used in alcohol solvents while LiAlH4 cannot.
A l H
- +
Reduction of Carbonyls
The reaction mechanism is:
Or more commonly:
O
H A l H3
O
H
A l H3 O
H
H
L i +
L i +
H 3 O +
O OH1) LiAlH4
2) H3O+
Reduction of Carbonyls
Neither of these reducing agents will affect a C=C p bond, so you can selectively reduce a carbonyl group without affecting the alkene or alkyne, but the reverse is not true, catalytic hydrogenation will affect carbonyl groups.
O OH1) NaBH4
2) H3O+
Oxidation of Carbonyls
Aldehydes are more easily oxidized than ketones.
Common oxidizing reagent include:
– CrO3, H+ (Jones’ reagent), KMnO4, Ag2O and peracids
– KMnO4 and peracids can reacts with C=C p bonds
Oxidation of Carbonyls
i.e.
Note: Ag2O is good if C=C p bonds are present as it will not oxidize them, i.e.
O
O H
O
C rO 3 , H +
O
O H
O
A g 2O
Oxidation of Carbonyls
Tollen’s Test: relies on the easy oxidization of aldehydes as a test.
The silver deposits on the glass
surface of a clean test-tube.
O H
OO A g (N H 3 ) 2
3 O H -
2 A g ( s ) 4 N H 3 2 H 2 O
Enols
Keto-enol tautomerism: these are structural isomers not resonance structures.
The keto form is much more stable as the C=O bond is stronger.
To have a tautomer possible there needs to be an a-hydrogen atom.
O O H
O H
H
H
H
a-carbon atoms
a-hydrogen atoms
Enols
Keto-enol tautomerism: some compounds only exist in the keto form as they have no a-hydrogen atoms. i.e.
H
O
HH
O O
Enols
Acidity of the a-hydrogen atoms: much more acidic than a normal alkane type H atom, i.e.
CH3
O
CH3
CH3
CH3
CH3
CH2
CH3
O
CH2
+ H + pK a = 50
+ H + pK a = 19
Enols
The increased acidity is a results of:1. Inductive electron withdrawal by the carbonyl group
2. Resonance stabilization of the anion
O
H
+
-
CH3
O
C H2
CH3
O
C H2
C H2
O
CH3
H
B : -
e n o l a t e a n i o n
Aldol Condensation
The Aldol condensation makes use of the acidity of an a-H in aldehydes and ketones to combine two molecules together.
Enolates act as a C nucleophile (carbanion).
Product is a b-hydroxyaldehyde or ketone, i.e.
R
O O
R
OH
RKOH
2
Aldol Condensation
The mechanism is: O
H
O O
O O O O
O O OH O
OH-
step 1: generate the enolate
..
step 2: nucleophilic attack by the enolate
..
step 3: protonate the oxide
H2OOH-
Aldol Condensation
The previous example is the condensation of two aldehydes (or ketones). A similar process can be done between to different aldehydes, but now we have to make sure only one can form an enolate or there will be a mixture of products, i.e.
OO O H OO H -
+
Aldol Condensation
Note: ketones need to be symmetric or you could form two different enolates, i.e.
This reaction is used to synthesis a number of compounds commercially from acetaldehyde: crotonal, butanal, butanol…
O O OO H -
Aldol Condensation
Heating the b-hydroxyaldehyde or ketone product, or the use of an acid catalyst, will cause the loss of a water molecule (an elimination reaction) to form a conjugated C=C bond, i.e.
OO H O H 3 O +
o rh e a t
H 2 O