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Chapter 8 Reduction
• In inorganic chemistry
loss of electrons is oxidation
gain of electrons is reduction
• In organic chemistry
the oxidation state of a carbon atom equals the total
number of its C–O, C–N, and C–X bonds.
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2
Heterogeneous
Catalytic hydrogenation
Homogeneous
Reduction
Metal hydride reductions
Electron transfer reactions (dissolving metal reduction)
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8.1
Catalytic hydrogenation
8.1.1
Heterogeneous catalysis
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Low pressure (0-100 oC, 1-4 atm)
Catalysts: Ra-Ni 、Pt 、Palladium、Ruthenium、
Rhodium
 Deposited on the surface of an inert support
(carbon, alumina, BaSO4, CaCO3)
---------------------------------------------->
catalyst activity decreases
Solvent: EtOH, MeOH, EtOAc, H2O, Cyclohexane,
Dioxane, THF, Acetic acid
Catalyst activity increases on going to polar, acidic
solvents
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High pressure (room temperature-300 oC, 100300atm)
Catalysts: Ra-Ni, Copper chromite CuCr2O4,
Ruthenium supported on carbon or alumina
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Look at mechanism in detail
H
Hence olefins can be isomerized over hydrogenation catalysts.
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8.1.2 Homogeneous catalysis
• Isomerization may be minimized
• Wilkinson's Catalyst: tris-(triphenylphosphine)rhodium chloride
soluble in organic sovlents (EtOH, etc.)
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• Useful for the stereospecific transfers of D2 to unhindered olefins:
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第一章 导论 (Introduction)
三、均相催化和多相催化的比较
均相催化：参与反应的所有组分都处于同一相中。这里的同一相
指液相，即所有反应物，包括催化剂，都在溶液中；
其催化剂一般是一种或几种组成和结构确定的过渡金
属络合物。
多相催化：参与反应的一个或多个组分处于不同相中。其催化剂
一般为固体，反应物为液体，或气体（多数情况下），
因此，反应是在催化剂表面上进行。
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第一章 导论 (Introduction)
活性(activity)：
TON (Turnover Number): the number of product molecules
produced per molecule of the catalyst
TOF (Turnover Frequency): the turnover number per unit time
选择性(selectivity):
化学选择性(chemoselectivity)
区域选择性(regioselectivity)
Rh
CHO
+ CO + H2
OH
+
CHO
+
Ti
OOH
catalyst
OH
(1)
+
+
OH
(2)
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第一章 导论 (Introduction)
对映选择性(enantioselectivity)
OH
+
OOH
H
Chiral
Ti-catalyst
OH
+
OH
(3)
对映选择性用对映异构体过量(enantiomeric excess, ee) 表示
ee 
RS
 100%
RS
多相催化的优点在于，催化剂为固体
• 与产物易于分离
操作费用低
• 热稳定性好
• 催化剂再生容易
in situ
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第一章 导论 (Introduction)
均相催化的优点在于，催化剂为组成和结构确定的络合物
•
高活性
•
高选择性
•
容易修饰 (modification)
机理明确，催化剂的性能可以在分子水平上得到解释，并
予以预测
•
Homogeneous catalysis, owing to their high selectivity,
are becoming increasingly important for the
manufacture of tailor-made plastics, fine chemicals,
pharmaceutical intermediates, etc.
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8.1.3 Transfer hydrogenation
 Using a hydrogen donor as the source of hydrogen, such as
Cyclohexene, propan-2-ol, formic acid, hydrazine.
 Catalyst: heterogenous or homogeneous.
 Avoid attendant hazards
 Out of accord with the economy rules of atoms
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8.2 Metal hydride reductions
 LiAlH4 most reactive
 LiAlH(OC(CH3)3)3 or LiAlH4 + 3 C(CH3)3OH
 NaAlH2(OCH2CH2OCH3)2 RED-Al
 NaBH4 less reactive C=O (type) reductions.
 LiAlH2(OCH2CH2OCH3)2
 NaBH3(CN) Sodium cyanoborohydride (only imines)
 LiBH4
 AlH3 Aluminum hydride
 [(CH3)2CHCH2]2AlH Diisobutylaluminum hydride (DlBAL-H)
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Mechanism involves coordination of cation (Li+ or Na+) with C=O and Hattack.
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 Reaction Conditions
Anhydrous conditions (except NaBH4)
LAH (non-hydroxylic solvents): ether, THF, 1,2-dimethoxyethane,
(MeO-CH2CH2-O-CH2CH2-O-Me) diglyme
NaBH4 : H2O, MeOH, EtOH, most commonly i-PrOH
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Selectivity
 Partial reduction
RCOOH -----> RCHO
 Reduction of one group in the presence of another.
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Reduction
RCHO
RCH2OH
RCOR
RCHOHR
RCOCl
RCH2OH
RCOOR`
RCH2OH+R`OH
RCOOH
RCH2OH
RCONR2
RCH2NR2
RC= N
RCH2NH2
RX
RH
Reducing agent
LiAlH4 NaBH4
+
+
+
+
+
+
+
+
+
+
+
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DIBAL-H allows the addition of one equivalent of hydride
to an ester
Replacing some of hydrogens of LiAlH4 with OR groups
decreases the reactivity of the metal hydride
Partial reduction
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NaBH4 can be used to selectively reduce an aldehyde or
a keto group in a compound
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8.3 Electron transfer reactions (dissolving metal reduction)
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Reaction Conditions
Metals commonly used: lithium, sodium, potassium, zinc, magnesium, tin, iron
Solvents
NH3 (b.p. - 33˚) for alkali metals (and Calcium); "Birch Reduction"
low molecular wt. amines
hexamethylphosphoramide (HMPA)
ether, THF, dimethoxyethane (DME) -- dilute solns.
crown ether complexes
ether, toluene, xylene -- suspensions
Proton Source
ethanol -- Present in reaction medium
isopropanol -- added with compound to be reduced
t-BuOH -- added during isolation.
H2O
Amalgams with Hg (Free metal and HgCl2): Magnesium, Aluminum, Zinc, Tin
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8.4 Reduction of functional groups
8.4.1 Reduction of alkenes
Cat
alkene
H2
alkane
– Catalytic hydrogenation (Pt or Pd)
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Isomerization.
H2
Catalyst
Catalyst
H2
Catalyst
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In hindered alkenes, syn addition to less hindered sides
H
H
COOH
H2 PtO2
COOH
H
H
COOH
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Selective reduction in the presence of esters and ketones.
O
O
H2
Ph
Pt
CHO
Ph
CHO
H2
Pd/C
H2
(Ph3P)3RhCl
O
O
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8.4.2 Reduction of alkynes
Alkyne
Cat
H2
alkene
Cat
H2
alkane
• Using lindar’s catalyst (palladium on calcium carbonate
treated with lead acetate and poisoned with quinoline), the
Z-alkenes can be obtained for non-terminal alkynes
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The dissolving metal procedure using lithium or sodium in
liquid ammonia gives E-alkenes.
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8.4.3 Reduction of aldehydes and ketones
8.4.3.1 Reduction to alcohols
 MPV (Meerwein-Ponndorf-Verley reaction) reduction
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O
OH
Br
Br
MPV
MPV
O
OH
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Dehydrated alumina
CHO
CH2OH
(CH3)2CHOH
Al2 O3 CCl4
NO2
NO2
O
(CH3)2CHOH
OH
Al2O3 CCl4
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8.4.3.2
Bimolecular Reduction
Competing with
Clemmensen reaction
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8.4.3.3 Reduction of ketones to methylene group
 Clemmensen reduction (strong acidic condition)
OH+
R
Zn
R
Zn
OH2+
OH
R
Zn
R
Zn
Zn
H+
Zn
R
R
Zn
Zn
Zn
-Zn2+
-H2O
R
H2
C
Zn
R
2H+
R
R
-Zn2+
Zn
Zn
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Wolff-Kishner –Minglon (strong basic condition)
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N2H4
KOH, digol
S
S
O
O
OH
O
O
p-CH3C6H4SO2N2H4
O
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NaBH3CN
O
9
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Indirect method (mild conditon, hydrogenolysis of ketone dithioketals)
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8.4.4 Reduction of carboxylic acids and their
derivatives
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no cooling
OH
DIBAL-H
O
OEt
DIBAL-H
O
-70 ° C
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8.4.5 Reduction of nitriles
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8.4.6 Reduction of imines and oximes, including
reductive alkylation
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CH3 NH2
H2/Pt
O
N
H
H
N
NO2
HCHO
H2 /Ni
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8.5 Reductive cleavage of carbon-heteroatom bonds
Rosemund Reduction
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COOC2H 5
COOC2H 5
CN
CN
H2, Pd/BaCO3
Rt 1atm
H3 C
N
Cl
H3 C
NO2
N
Cl
NH2
H2, Ni
Rt 1atm
Cl
Cl
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Exercise
 Complete the following synthesis.
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