Reactions of Ketones and Aldehydes Nucleophilic Addition

106 Pages·2014·9.65 MB·English

SCH 206
Reactions of Ketones and Aldehydes
Nucleophilic Addition
The most characteristic reaction of aldehydes and
ketones is nucleophilic addition to the carbon–
oxygen double bond.
38
Dr. Solomon Derese
SCH 206
The nucleophile can be neutral or negatively
charged.
Neutral (H-Nu:) Negatively charged (Nu:-)
Hydroxide H O
O
Water H H
Hydride
H
Carbanion
O R:
Alcohol
R H
Alkoxide R O
R
R H Acetylide
1
N
Amines
Ph H
Ylide
R
Ph
2
Ph H
39
Dr. Solomon Derese
SCH 206
Reaction of Organometallic Reagents with Aldehydes
and Ketones
Treatment of an aldehyde or ketone with a
Grignard reagent, organolithium and sodium
(lithium) acetylide followed by an acid
treatment gives an alcohol.
40
Dr. Solomon Derese
SCH 206
General reaction
41
Dr. Solomon Derese
SCH 206
I. Addition of the organometalics to
formaldehyde (CH =O) forms a 1°
2
alcohol.
II. Addition of the organometalics to all
other aldehydes forms a 2° alcohol.
III.Addition of the organometalics to
ketones forms a 3° alcohol.
42
Dr. Solomon Derese
SCH 206
Preparation of Organometalics
43
Dr. Solomon Derese
SCH 206
Organometallic Reagents
Organometallic reagents contain a carbon atom
bonded to a metal.
Most common metals
Li, Na, Mg, Cu
Because metals are more electropositive (less
electronegative) than carbon, they donate electron
density towards carbon, so that carbon bears a
partial negative charge.
44
Dr. Solomon Derese
SCH 206
The more polar the carbon–metal bond, the more
reactive the organometallic reagent.
Electronegativity values for carbon and the
common metals in R – M reagents are C (2.5), Na
(0.93), Li (1.0), Mg (1.3), and Cu (1.8).
Because Na, Li and Mg are very electropositive
metals, organomagnesium reagents (RMgX),
organolithium (RLi) and acetylide R-C≡CNa) contain
very polar carbon–metal bonds and are therefore
very reactive reagents.
45
Dr. Solomon Derese
SCH 206
Organocopper reagents (R CuLi), also called
2
organocuprates, have a less polar carbon–metal
bond and are therefore less reactive.
Regardless of the metal, organometallic reagents
are useful synthetically because they react as if
they were free carbanions; that is, carbon bears a
negative charge, so the reagents react as bases and
nucleophiles.
46
Dr. Solomon Derese
SCH 206
Examples
O
HO CH CH HO CH CH
2 3 2 3
1. CH CH MgBr, Et O
3 2 2
1. CH CH Li, THF
3 2
2.
H O
3
2.
H O
3
2.
H O
1. H C Na 3
3
CH
3
OH
Dr. Solomon Derese 47