Post on 17-Jan-2023
Chapter 12
Alcohols from Carbonyl CompoundsOxidation-Reduction & Organometallic Compounds
Ch. 12 - 1
Ch. 12 - 2
O
1. Structure of the Carbonyl Group
Carbonyl compounds
O
R HAldehyde Ketone
O
R R'
Carboxylic acid
O
R OH
Ester
O
R OR'
Amide
O
R NR'
R"
Ch. 12 - 5
1A. Reactions of Carbonyl Compoundswith Nucleophiles
One of the most important reactions of carbonyl compounds is nucleophilic addition to the carbonyl group
Nu
O
C
δ−
δ+ nucleophilic
addition
O
CNu
Ch. 12 - 6
Two important nucleophiles:● Hydride ions (from NaBH4 and
LiAlH4)● Carbanions (from RLi and RMgX)
Another important reactions:
O
CR H
OH
R HH
oxidation
reduction
1o alcohol aldehyde
Ch. 12 - 7
2. Oxidation-Reduction Reactions inOrganic Chemistry
Reduction of an organic molecule usually corresponds to increasing its hydrogen content or decreasing its oxygen content
carboxylicacid
reduction
[H] O
R H
O
R OH
aldehyde
oxygen contentdecreases
reduction
[H] OH
R H
O
R HH
hydrogen contentdecreases
Ch. 12 - 8
The opposite reaction of reduction is oxidation. Increasing the oxygen content of on organic molecule or decreasing its hydrogen content is oxidation
OH
R HH
O
R OH
O
R H
[O]RCH3
[H]
[O]
[H]
[O]
[H]
lowestoxidation
state
highestoxidation
state
Ch. 12 - 9
Oxidation of an organic compound may be more broadly defined as a reaction that increases its content of any element more electronegative than carbon
[O]
[H]
[O]
[H]
[O]
[H]Ar CH3 Ar CH2Cl Ar CHCl2 Ar CCl3
Ch. 12 - 10
2A. Oxidation States in Organic Chemistry Rules
● For each C–H (or C–M) bond -1● For each C–C bond 0● For each C–Z bond +1
(where M = electropositive element and is equivalent to H, e.g. Li, K, etc.; Z = electronegative heteroatom, e.g. OR, SR, PR2, halogen, etc.)
Calculate the oxidation state of each carbon based on the number of bonds it is forming to atoms more (or less) electronegative than carbon
Ch. 12 - 11
Examples
H
C
H
H H(1)Bonds to C:4 to H = (- 1) x 4 = - 4
Total = - 4
Oxidation state of C = - 4
Ch. 12 - 12
Examples
H
C
H
H OH(2)Bonds to C:
3 to H = - 3
Total = - 2
Oxidation state of C = - 2
1 to O = +1
Ch. 12 - 13
Examples
O
CH H
(3)Bonds to C:
2 to H = - 2
Total = 0
Oxidation state of C = 0
2 to O = +2
Ch. 12 - 14
Examples
O
CH OH
(4)Bonds to C:
1 to H = - 1
Total = +2
Oxidation state of C = +2
3 to O = +3
Ch. 12 - 15
Overall order
O
C
O
H
C
H
H H
H
C
H
H OH
O
CH OH
O
CH H
< < < <
- 4 - 2 0 +2 +4
lowest oxidationstate of carbon
highest oxidationstate of carbon
oxidationstate
Ch. 12 - 16
3. Alcohols by Reduction of Carbonyl Compounds
R OH
H H(1o alcohol)
[H]
R R'
O
R R'
HO H
H
R O
[H]
[H]OH
R O
[H]OR'
R O
Ch. 12 - 17
3A. Lithium Aluminum Hydride
LiAlH4 (LAH)● Not only nucleophilic, but also very
basic● React violently with H2O or acidic
protons (e.g. ROH)● Usually reactions run in ethereal
solvents (e.g. Et2O, THF)● Reduces all carbonyl groups
Ch. 12 - 18
ExamplesO
R OH
OH
R HH
1. LiAlH4, Et2O
2. H+, H2O(1)
O
R OR'
1. LiAlH4, Et2O
2. H+, H2O(2)
OH
R HH
+ HOR'
O
R H
OH
R HH
1. LiAlH4, Et2O
2. H+, H2O(3)
Ch. 12 - 19
MechanismO
R OR'
H
Al HH
H
+
O
OR'R
HO
R HR'O +
H
Al HH
HO
RH
H
OH H
OH
RH
H
Esters are reduced to 1o alcohols
Ch. 12 - 20
3B. Sodium Borohydride
NaBH4● less reactive and less basic than
LiAlH4● can use protic solvent (e.g. ROH)● reduces only more reactive carbonyl
groups (i.e. aldehydes and ketones) but not reactive towards esters or carboxylic acids
Ch. 12 - 22
Mechanism
O
R R'
H
B HH
H
+
δ−
δ+
O
R'R
H
OH HOH
RH
R'
Aldehydes are reduced to 1° alcohols & ketones are reduced to 2° alcohols
Ch. 12 - 23
3C. Overall Summary of LiAlH4 and NaBH4 Reactivity
O
R O<
O
R OR'
O
R R'<
O
R H<
ease of reduction
reduced by NaBH4
reduced by LiAlH4
Ch. 12 - 24
4. Oxidation of Alcohols
[O]R OH
O
R OH
O
R H
[O]
1o alcohol aldehyde carboxylicacid
4A. Oxidation of Primary Alcohols to Aldehydes
The oxidation of aldehydes to carboxylic acids in aqueous solutions is easier than oxidation of 1o alcohols to aldehydes
It is, therefore, difficult to stop the oxidation of a 1o alcohol to the aldehyde stage unless specialized reagents are used
Ch. 12 - 25
PCC oxidation● Reagent
(Pyridinium chlorochromate)
N
H
[CrO3Cl]PCC =
CrO3 + HCl N+
Pyridine(C5H5N)
Pyridiniumchlorochromate
(PCC)
N H [CrO3Cl]
Ch. 12 - 26
PCC oxidation
R OHPCC
CH2Cl2
O
R H
R R'
O
R R'
OH PCC
CH2Cl2
R R'
OH
R
No ReactionPCC
CH2Cl2
Ch. 12 - 27
4B. Oxidation of Primary Alcohols toCarboxylic Acids
R OHR OH
O
R O
O
K
H3O+KMnO4, OH-
H2O, heat
Chromic acid (H2CrO4) usually prepared by[CrO3 or Na2Cr2O7] + aqueous H2SO4
Jones reagent
H2CrO4(chromic acid)
Ch. 12 - 28
Jones oxidation● Reagent: CrO3 + H2SO4● A Cr(VI) oxidant
R OH
O
R OH
CrO3
H2SO4(orange solution)
+ Cr(III)
(green)
R R'
O
R R'
CrO3
H2SO4(orange solution)
+ Cr(III)
(green)
OH
RR'
CrO3
H2SO4
OH
R"No Reaction
Ch. 12 - 29
4D. Mechanism of Chromate Oxidations
CH3C
HH3C
O
H
Cr
O
O
+ HO O
H O H
H
Formation of the Chromate Ester
Cr
O
O OO
H
O
H
H
CH3C H
H3C
H
OH
H O H
H
Cr
O
O OO
H
O
H
CH3C H
H3CH
Cr
O
OC
H3C H
H3C
OH
O
H
OH
+
Ch. 12 - 31
4E. A Chemical Test for Primary andSecondary Alcohols
R OH
O
R OH
CrO3
H2SO4(orange solution)
+ Cr(III)
(green)
R R'
O
R R'
CrO3
H2SO4(orange solution)
+ Cr(III)
(green)
OH
RR'
CrO3
H2SO4
OH
R"No Reaction
Ch. 12 - 32
4F. Spectroscopic Evidence for Alcohols
Alcohols give rise to broad O-H stretching absorptions from 3200 to 3600 cm-1 in IR spectra
The alcohol hydroxyl hydrogen typically produces a broad 1H NMR signal of variable chemical shift which can be eliminated by exchange with deuterium from D2O
Hydrogen atoms on the carbon of a 1o or 2o
alcohol produce a signal in the 1H NMR spectrumbetween δ 3.3 and δ 4.0 ppm that integrates for 2 and 1 hydrogens, respectively
The 13C NMR spectrum of an alcohol shows a signal between δ 50 and δ 90 ppm for the alcohol carbon
Ch. 12 - 33
5. Organometallic Compounds
Compounds that contain carbon-metal bonds are called organometallic compounds
C M
primarily ionic(M = Na or K)
δ− δ+C : M
(M = Mg or Li)
C M
primarily covalent(M = Pb, Sn, Hg or Tl)
Ch. 12 - 34
6. Preparation of Organolithium &Organomagnesium Compounds
R 2 Li RLi LiXEt2O
(or THF)++X
6A. Organolithium Compounds
Order of reactivity of RX● RI > RBr > RCl
Preparation of organolithium compounds
Ch. 12 - 36
R RMgXEt2O
+X Mg
Ar ArMgXEt2O
+X Mg
6B. Grignard Reagents
Order of reactivity of RX● RI > RBr > RCl
Preparation of organomagnesium compounds (Grignard reagents)
Ch. 12 - 38
7. Reactions of Organolithium andOrganomagnesium Compounds
7A. Reactions with Compounds Con-taining Acidic Hydrogen Atoms
Grignard reagents and organolithium compounds are very strong bases
RMgX ~ R:MgX RLi ~ R:Liδ− δ+ δ− δ+
δ− δ+R MgX H Y+
(or RLi) (Y = O, N or S)
δ−δ+++ XR H Y Mg2+ +
Ch. 12 - 39
Examples● As base
CH3OH+
MgBr
+ Mg2+ + Br−
+ CH3O−(2)
CH3MgBr + H2O + OH−H3C H(1)
+ Mg2+ + Br−
Ch. 12 - 40
Examples● As base
(3) H + H3C MgBr
MgBr H CH3+
A good method for the preparationof alkynylmagnesium halides
Ch. 12 - 41
7B. Reactions of Grignard Reagentswith Epoxides (Oxiranes)
Grignard reagents react as nucleophiles with epoxides (oxiranes), providing convenient synthesis of alcohols
then H2OOR
OH+RMgBr
Ch. 12 - 43
Also work for substituted epoxides
then H2OO+RMgBr
R'
H
R OH
R'
H
(2o alcohol)
then H2OO+RMgBr
R'
R"
R OH
R'
R"
(3o alcohol)
Ch. 12 - 44
7C. Reactions of Grignard Reagentswith Carbonyl Compounds
O
R R'
1. Et2O
2. H3O++ R"MgX
OH
RR"
R'
R' = H (aldehyde)R' = alkyl (ketone)
Ch. 12 - 46
8. Alcohols from Grignard Reagents
O
R R'
1. Et2O
2. H3O++ R"MgX
OH
RR"
R'
R' = H (aldehyde)R' = alkyl (ketone)
Ch. 12 - 47
R, R’ = H (formaldehyde)● 1o alcohol
O
H HMgXR +δ+δ−
formaldehyde
O MgX
RH
H
OH
RH
H
H3O+
1o alcohol
Ch. 12 - 48
R = alkyl, R’ = H (higher aldehydes)● 2o alcohol
O
R' HMgXR +
δ− δ+
higheraldehyde
O MgX
RH
R'
OH
RH
R'
H3O+
2o alcohol
Ch. 12 - 49
R, R’ = alkyl (ketone)● 3o alcohol
O
R' R"MgXR +δ+δ−
ketone
O MgX
RR"
R'
OH
RR"
R'
NH3ClH2O
3o alcohol
Ch. 12 - 51
O
R R"+R'O
O
RR"
OR'
MgX
O
RR"
R"
MgX
Mechanism
O
R OR'MgXR"+δ+δ−
H O H
HOH
RR"
R"
MgXR"δ+δ−
Ch. 12 - 57
OH
MeMe
disconnection
MgBr
+O
Me Me
Method 1● Retrosynthetic analysis
● Synthesis OH
MeMeMgBr
+O
Me Me
1. Et2O
2. H3O+
Ch. 12 - 58
OH
MeMe
disconnection
+MeMgBrMe
O
Method 2● Retrosynthetic analysis
● SynthesisOH
MeMe
+MeMgBrMe
O
1. Et2O
2. H3O+
Ch. 12 - 59
OH
MeMe
disconnection
+ 2 MeMgBrOEt
Odisconnection
Method 3● Retrosynthetic analysis
● SynthesisOH
MeMe1. Et2O
2. H3O+
+ 2 MeMgBr
OEt
O
Ch. 12 - 60
8B. Restrictions on the Use ofGrignard Reagents
Grignard reagents are useful nucleophiles but they are also very strong bases
It is not possible to prepare a Grignard reagent from a compound that contains any hydrogen more acidic than the hydrogen atoms of an alkane or alkene
Ch. 12 - 61
A Grignard reagent cannot be prepared from a compound containing an –OHgroup, an –NH– group, an –SH group, a –CO2H group, or an –SO3H group
Since Grignard reagents are powerful nucleophiles, we cannot prepare a Grignard reagent from any organic halide that contains a carbonyl, epoxy, nitro, or cyano (–CN) group
Ch. 12 - 62
Grignard reagents cannot be prepared in the presence of the following groups because they will react with them:
OH, NH2, NHR, CO2H,
SO3H, SH, C C H,
O
H,
O
R,
O
OR,
O
NH2,
NO2, C N, O
Ch. 12 - 63
8C. The Use of Lithium Reagents
Organolithium reagents have the advantage of being somewhat more reactive than Grignard reagents although they are more difficult to prepare and handle
OLiR +δ+δ−
organo-lithiumreagent
aldehydeor
ketone
OH
R
OLi
R
lithiumalkoxide
alcohol
H3O+
Ch. 12 - 64
8D. The Use of Sodium Alkynides
Preparation of sodium alkynides
R H RNaNH2
-NH3Na
Reaction via ketones (or aldehydes)O
+OHONa H3O
+
R Na
RR
Ch. 12 - 66
Retrosynthetic analysis
HO
OH O
HOMgBr +
disconnection
HOBr
However
HOBr
Mg
Et2O OMgBr
H
δ+
δ−
BrMg OHacidic proton powerful
base
Ch. 12 - 67
Need to “protect” the –OH group first
HOBr (protection)
"P"OBr
"P"OMgBr
Mg, Et2O
(no acidic OH group)
O
"P"O
OH
2. H3O+
1.
HO
OH
(deprotection)