Chapter 11. Alcohols from carbonyl compounds
(由羰基化合物制醇) .Oxidation-reduction and organometallic compounds
(氧化 -还原和有机金属化合物)11.1 IntroductionCarbonyl (羰基) compounds are a broad group of compounds that includes aldehydes, ketones, carboxylic acids, and esters.
O
The carbonyl group
R
H
O
R
R'
O
R
HO
O
R
R'O
O
An aldehyde A ketone A carboxylic acid A carboxylate ester
ôÊ»ù È© ͪ ôÈËá õ¥
11.1A Structure of the carbonyl group
O
120o
120o
120o
1. C-sp2 hybridization2. The bond angles is 120o.
3. It is a trigonal planar structure
4. The carbon-oxygen double bond
consists of sigma-a bond and a pi-bond
O
120o
120o
120oO O
O O
O-+
Polarization of the - bond Resonance structures
11.1B Reaction of carbonyl compounds with nucleophiles
O
Polarization of the - bond
+:Nu- O-Nu
O OH[ H ] Reduction
[ O ] Oxidation
O OH[ H ] Reduction
[ O ] Oxidation
NaBH4 or LiAlH4
KMnO4
R
H
O
R
H
O-
[ H ] Reduction
NaBH4 or LiAlH4+ H-
H
ROHRCH2OH
nucleophilic addition
11.2 Oxidation-Reduction reactions in organic chemistry
Reduction of an organic molecule usually corresponds to increasing its hydrogen
content or to decreasing its oxygen content.
R
O
OH[ H ]
ReductionR
O
H
Carboxylic acid Aldehyde
oxygen content decreases
R
O
H[ H ]
ReductionR CH2OH
Aldehyde Alcohol
oxygen content decreases
[ H ]
ReductionR CH3
Alcohol Alkanes
oxygen content decreases
R CH2OH
The opposite of reduction is oxidation. Thus, increasing the oxygen content of an organic molecule or decreasing its
hydrogen content is an oxidation.
oxygen content decreases
[ O ]R CH2OH
Alkanes Alcohols
oxygen content increases
R CH3
[ H ]
[ O ]
[ H ]RCHO
[ O ]
[ H ]RCOOH
[ O ]R CH2Cl
Alkanes
R CH3
[ H ]
[ O ]
[ H ]RCHCl2
[ O ]
[ H ]RCCl3
11.3 Alcohols by reduction of carbonyl compounds
R
O
OH[ H ]
ReductionR CH2OH
Carboxylic acid 1o Alcohols
R
O
OR'[ H ]
ReductionR CH2OH
1o Alcohols
+ R'OH
R
O
H[ H ]
ReductionR CH2OH
Aldehyde 1o Alcohols
R
O
R[ H ]
Reduction
RHC
Ketone2o Alcohols
OH
R
R
O
OH R CH2OH
Carboxylic acid 1o Alcohols
[ H- ]
ReductionLiAlH4+
Lithiumaluminum hydride
Et2O
H3C
O
OH H3C CH2OH
H3C
CH3
COOH
2,2-Dimethylpropanoic acid
1. LiAlH4 / Et2O
2. H2OAcetic acid Ethanol
CH3
1. LiAlH4 / Et2O
2. H2OH3C
CH3
CH2OH
CH3
Neopentyl alcohol ÐÂÎì´¼ (92%)
CH3CH2CH2CHO
Butanal 1-Butanol
[ H- ]
ReductionNaBH4
SodiumBorohydride
H2O
+ CH3CH2CH2CH2OH
CH3CH2CCH3
Butanone2-Butanol
[ H- ]
ReductionNaBH4
SodiumBorohydride
H2O
+ CH3CH2CHCH3
O
OH
The NaBH4 is also reduced reagent
The mechanism for the reduction of a ketone by sodium borohydride and Lithium aluminum hydride
OLiAlH4
NaBH4
[H-]
Hydride transfer
O-HHOH
OHH
Alcohols
nucleophile addition
Sodium borohydride (NaBH4) is a milder reducing agent than lithium aluminum hydride (LiAlH4). Lithium aluminum hydride will reduce acids. Esters, aldehydes, and ketones; but sodium borohydride will reduce only aldehydes and ketones.
11.4 Oxidation of alcohols
Primary alcohols can be oxidized to aldehydes and carboxylic acids.
R CH2OH[ O ]
R CHO R COOH
1o Alcohol Aldehyde Carboxylic acid
[ O ]
CH3CH2CH2CH2OH
1-Butanol
K2Cr2O7
H2SO4CH3CH2CH2CHO
Butanalbp, 117.7 oC bp, 75.7 oC 50%
CH3CH2OHCu
300 oCCH3CH2OH + H2
Dehydrogenation
CH3CH2CH2CH2OH
1-Butanol
CH3CH2CH2CHO
Butanal
PCC
25 oCCH2Cl2
CrO3 + HCl +
N N
CrO
O
O Cl-
H+
Pyridinium chlorochromate
ßÁà¤ÈýÑõ»¯¸õ
Pyridine
PCC Pyridinium chlorochromate ßÁà¤ÈýÑõ»¯¸õ
11.4B Oxidation of 1o Alcohols to carboxylic acids, Oxidation of 2o
alcohols to ketone.CH3CH2CH2CH2OH
1-Butanol
CH3CH2CH2COOKKMnO4, KOH HCl
CH3CH2CH2COOH
CH3CH2CHCH3
OH
2-Butanol
KMnO4, KOHCH3CH2CCH3
O
Butanone
OH
Cyclooctanol
H2CrO4
Acetone 35 oC
O
Cyclooctanone»·¹ï´¼ »·¹ïͪ
11.4D Mechanism of Chromate oxidations (铬酸氧化机理)
Step 1
RC
R
O H
H+
HO Cr
O
O
OH RC
R
O
H
Cr
O
O
OH+ H2O
Chromate ester (¸õËáõ¥£©
RC
R
O
H
Cr
O
O
OHR
R
O + HCrO3- + H3O+
Step 2
KetoneCr 6+ Cr4+
6+4+
H2O
Chromate ester (¸õËáõ¥£©
11.4E A Chemical test for primary and secondary alcohols
Primary alcohols 1o RCH2OH
Secondary alcohols 2o R2CHOH
Secondary alcohols 3o R3COH
+ CrO3 / aqueous H2SO4
Chromic oxide
greenish opaque
solution Cr3+
greenish opaque
solution Cr3+
No reaction
11.5 Organometallic compounds (有机金属化合物)
Compounds that contain carbon-metal bonds are called organometallic compounds. It include Carbon-lead, carbon-tin, carbon-thallium, carbon-mercury, carbon-lithium and carbon-magnesi
um bonds.
C:- M+
M = Na+ or K+
(Primarily ionic)
Alkylsodium and alkylpotassium compounds are highly reactive and are among the most powerful of base
C: M
M = Mg or Li
Organometallic compounds of lithiumand magnesium are of great importancein organic synthesis. They are relativly stable in ether solutions, but their carbon-metalbonds have considerable ionic character.
(Primarily covalent)
C M
M = Pb, Sn, Hg, or TI
Organomercury and organolead compounds are much less reactiv; they are often volatile and are stable in air. They are all poisonous. They are generally soluble in nonpolar solvents. Tetraethyllead, for example, has been used as an "antiknock" compound in gasoline.
11.6 Preparation of organolithium and organomagnesium compounds
11.6A Organolithium compounds (有机锂化合物)
Organolithium compounds are often prepared by the reaction of organic halides with lithium metal.
(Butyl bromide)
CH3CH2CH2CH2Br + 2 Li- 10oC
Et2OCH3CH2CH2CH2Li + LiBr
Butyllithium(80-90%)
R X
( or Ar X)
+ 2 Li RLi + LiX
(or ArLi)
The order of reactivity of halides is;
RI RBr RCl
11.6B Grignard reagents (格利雅试剂) ;
Organomagnesium halides were discovered by the French chemist Victor Grignard in 1900. Grignard received the Nobel Prize for his discovery in 1912, and organomagnesium halides are now called Grignard reagents in his honor. Grignard reagents hav
e great use in organic synthesis.
RX + Mg RMgXEt2O
or THF
ArX + MgEt2O
or THFArMgX
Grignard reagents
Grignard reagents are usually prepared by the reaction of an organic halides and magnesium metal in an ethe
r solvent
CH3I + Mg CH3MgIEt2O
or THF
C6H5Br + MgEt2O
or THFC6H5MgBr
Methylmagnesium iodide(95%)
Phenylmagnesium bromide(95%)
Grignard reagents
A Grignard reagent forms a complex with its ether solvent; the structure of the complex can be represe
nted as follows:
R
Mg
X
H3CH2C
O
H3CH2C
O
CH2CH3
CH2CH3
ComplexStability of Grignard reagentsThe solvent is a diethyl ether
R
Mg
X
O O
ComplexStability of Grignard reagents
The solvent is tetrahydrofuran (THF)
11.7 Reactions of organolithium and organomagnesium compounds11.7A Reactions with compounds contai
ning acidic hydrogen atomsCH3MgI
C6H5MgBr
Methylmagnesium iodide
Phenylmagnesium bromide
+ H2O CH4 + Mg
OH
I
+ H2O C6H6 + Mg
OH
Br
CH3MgI
C6H5MgBr
Methylmagnesium iodide
Phenylmagnesium bromide
+ HOCH3 CH4 + Mg
OCH3
I
+ HOCH2CH3 C6H6 + Mg
OCH2CH3
Br
Grignard reagents and organolithium compounds abstract protons that are
much less acidic than those of water and alcohols. They react with the termi
nal hydrogen atoms of 1-alkynes.
R C CH + R'MgX
Terminal alkyne Grignardreagent
R' H + R C CMgX
Alkynylmagnesium halide±»¯È²»ùþ
Alkanes
pKa = 50
R C CH + R'Li R' H + R C CLi
AlkynyllithiumAlkaneȲ»ùï®
Terminal alkyne Alkyl lithium
11.7B Reaction of Grignard reagents with oxiranes
(环氧乙烷与格利雅试剂反应)+RMgX
Grignardreagent
O
R CH2CH2OMgXH+
R CH2CH2OH
A primary alcoholOxirane
Et2O
H2O
+CH3CH2MgI
Grignardreagent
O
CH3CH2CH2CH2OMgIH+
CH3CH2CH2CH2OH
Butyl alcoholOxirane
Et2O
H2O
在合成上增加两个碳原子伯醇
+C6H5MgI
Grignardreagent
O
C6H5CH2CH2OMgI
H+
C6H5CH2CH2OH
phenylethanol
Oxirane
Et2O
H2O
±½»ùÒÒ´¼
+C6H5MgI
Grignardreagent
O
C6H5CH2CHOMgI
H+
C6H5CH2CHOH
phenylpropanol
Oxirane
Et2O
H2O
±½»ù-2-±û´¼
CH3
CH3
CH3
11.7C Reactions of Grignard reagents with Carbonyl Compounds(格利
雅试剂与羰基反应)
+RMgX
Grignardreagent
RCOMgXH+
RCOHEt2O
H2OO
Aldehyde or Ketone or ester
Nucleophile addition
Alcohols
11.8 Alcohols from Grignard reagents
1. A Grignard reagent reacts with formaldehyde to give a primary alcohol (伯醇) .
+CH3MgBr
Grignardreagent
CH3CH2OMgBrH+
CH3CH2OHEt2O
H2O
H
H
O
formaldehyde
Nucleophile addition
Ethyl Alcohols
+C6H5MgBr
Grignardreagent
C6H5CH2OMgBrH+
C6H5CH2OHEt2O
H2O
H
H
O
formaldehyde
Nucleophile addition
Benzyl Alcohol±½¼×́¼ Üлù´¼
2. Grignard reagent reacts with higher aldehydes to give seconda
ry alcohol (仲醇)
+CH3CH2MgBr
CH3CH2CHOMgBrH+
CH3CH2CHOHEt2O
H2O
H3C
H
O
AcetaldehydeÒÒÈ©
Nucleophile addition
2-Butanol
2o ´¼
CH3 CH3
Ethylmagnesium bromide ä廯ÒÒ»ùþ
+C6H5MgBr
Grignardreagent
C6H5CHOMgBrH+
C6H5CHOHEt2O
H2O
H3C
H
O
Acetaldehyde
Nucleophile addition
Phenyl ethanol±½»ùÒÒ´¼CH3
CH3
3. Grignard reagent reacts with ketones to give tertiary alcohol (叔醇)
+CH3CH2MgBr
CH3CH2COMgBrH+
CH3CH2COHEt2O
H2O
H3C
H3C
O
Acetone±ûͪ
Nucleophile addition
2-Methyl-2-butanol
3o ´¼ £¨Êå´¼£©
CH3 CH3
Ethylmagnesium bromide ä廯ÒÒ»ùþ
CH3 CH3
+C6H5MgBr
Grignardreagent
H+Et2O
H2O
cyclohexanone»·¼ºÍª
Nucleophile addition
O
OMgBrOH
4. A Grignard reagent also adds to the carbonyl group of an ester (酯) .
+RMgBr
Grignardreagent
RCEt2OR
R'O
O
esters
Nucleophile addition
OR'
R
Initial product(Unstable)
O MgBr
Br
Mg
OR'
R
R
O
-Ketones
H+
H2O
Tertiary alcohols
3o ´¼ £¨Êå´¼£©
RMgBrR C
R
R
OMgBr R C
R
R
OH
+CH3CH2MgBr
Grignardreagent
CH3CH3CEt2OH3C
H3CH2CO
O
Ethyl acetateÒÒËáÒÒõ¥
Nucleophile addition
OCH2CH3
CH3
Initial product(Unstable)
Br
Mg
OCH2CH3
H3C
H3CH2C
O
-2-Butone
O MgBr
H+
H2O
3-Methyl-3-pentanol
3o ´¼ £¨Êå´¼£©
CH3CH2MgBrH3CH2C C
CH2CH3
CH3
OMgBr H3CH2C C
CH2CH3
CH3
OH
12
345
11.8 Planning a Grignard synthesis
CH3CH2 C
C6H5
OH
CH2CH3
a
b
3-Phenly-3-pentanol
(3-±½»ù-3-Îì´¼£©
C6H5MgBr + CH3CH2CCH2CH3
O
a
CH3CH2MgBr + C6H5CCH2CH3
O
b
CH3CH2MgBr + C6H5COCH2CH3
O
2
Synthesis of 3-phenyl-3-pentanol
CH3CH2CCH2CH3
O
1.
Br
Mg
Et2O
1.
2. H3O+
CH3CH2 C
C6H5
OH
CH2CH3
3-Phenly-3-pentanol
(3-±½»ù-3-Îì´¼£©
MgBr
2. CH3CH2Br CH3CH2MgBrMg
Et2O
C6H5CCH2CH3
O
1.
2. H3O+CH3CH2 C
C6H5
OH
CH2CH3
3. 2 CH3CH2MgBrC6H5COCH2CH3
O
1.
2. H3O+CH3CH2 C
C6H5
OH
CH2CH3CH3CH2BrMg
Et2O
Illustrating a Multistep Synthesis (举例说明多步合成)
O
2,5-Dimethyl-3-hexanone2,5-¶þ¼×»ù-3-¼ºÍª
OH
2,5-Dimethyl-3-hexanol2,5-¶þ¼×»ù-3-¼º´¼
O
H
MgBr
O
H
Br MgBrMg
Et2O
OMgBr
2,5-Dimethyl-3-hexanone2,5-¶þ¼×»ù-3-¼ºÍª
H3O+
OH
H2CrO4
acetone
O
phenyl-acetaldehyde±½ÒÒÈ©
O
H
OH
H
2-Phenyl-ethanol
MgBr +O
Phenylmagnesium bromide Oxirane
Synthesis of phenyl-acetaldehyde
MgBrO
Phenylmagnesium bromide
BrMg
Et2O CH2CH2OMgBr
H3O+
CH2CH2OHPCC
CH2Cl2CH2CHO
11.8B Restrictions on the use of Grignard reactions
CH3MgBr + HOCH2CH2CCH3
O
HOCH2CH2C
OMgBr
CH3
CH3
OH, -NH2, -NHR, COOH, SO3H, SH, C CH
CHO, COR, COOR, CONH2, NO2, CN,O
Grignard reagents containing these groups cannot be prepared
CH3MgBr + HOCH2CH2CCH3
O
CH4 + BrMgOCH2CH2CCH3
O
11.8C The use of lithium reagents
Organolithium reagents (RLi) react with carbonyl compounds in the same way as Grignard reagents.
RLi + O
R C OLiH3O+
R C OH
Organolithiumreagent
aldehyde or ketones Lithium alkoxide Alcohol
CH3Li +H3C
H3C
O
H3C C
CH3
CH3
OLiH3O+
H3C C
CH3
CH3
OH
Organolithiumreagent
acetone Lithium alkoxide 2-Methyl-2-propanol
11.8D The use of sodium alkynides (炔化钠的使用)
Sodium alkynides also react with aldehydes and ketones to yield alcohols.
H3C C CH +NaNH2
H3C C CNa NH3
H3C C CNa +H3C
H3C
O H3C C C C
CH3
CH3
ONa
H3O+
H3C C C C
CH3
CH3
OH
HO
CH3
H3C C CNa
HO
CH3O
NaO
CH3
H3O+
nucleophile addition