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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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Reduction

Catalytic hydrogenation

Metal hydride reductions

Electron transfer reactions (dissolving metal reduction)

Heterogeneous

Homogeneous

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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, 100-30

0atm)

Catalysts: Ra-Ni, Copper chromite CuCr2O4, Rutheniu

m supported on carbon or alumina

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Look at mechanism in detail

Hence olefins can be isomerized over hydrogenation catalysts.

H

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8.1.2 Homogeneous catalysis• Isomerization may be minimized

• Wilkinson's Catalyst: tris-(triphenylphosphine)rhodium chloride so

luble 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 pro

duced 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

CHO+ CO + H2+ + (1)

OH OOHTi

OH OH+ + (2)catalyst

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第一章 导论 (Introduction)

对映选择性 (enantioselectivity)

OH OOH OH

HOH+ + (3)

Ti-catalyst

Chiral

多相催化的优点在于，催化剂为固体

• 与产物易于分离

• 热稳定性好

• 催化剂再生容易 in situ

操作费用低

对映选择性用对映异构体过量 (enantiomeric excess, ee) 表示

%100

SR

SRee

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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 H- att

ack.

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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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ReductionReducing agent

LiAlH4 NaBH4

RCHO RCH2OH + +

RCOR RCHOHR + +

RCOCl RCH2OH + +

RCOOR` RCH2OH+R`OH + -

RCOOH RCH2OH + -

RCONR2 RCH2NR2 + -

RC= N RCH2NH2 + -

RX RH + -

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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 ora 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

alkene alkane

– Catalytic hydrogenation (Pt or Pd)

Cat

H2

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Isomerization.

H2

Catalyst

Catalyst

H2

Catalyst

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In hindered alkenes, syn addition to less hindered sides

COOH

H2 PtO2

COOH

H

H

COOH

H

H

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Selective reduction in the presence of esters and ketones.

Ph

O

H2 PtPh

O

H2 Pd/CCHO CHO

H2

O

(Ph3P)3RhCl

O

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8.4.2 Reduction of alkynes

Alkyne alkene alkane• Using lindar’s catalyst (palladium on calcium carbonate tre

ated with lead acetate and poisoned with quinoline), the Z-a

lkenes can be obtained for non-terminal alkynes

Cat

H2

Cat

H2

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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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Br

O

MPVBr

OH

MPV

O OH

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Dehydrated alumina

CHO

NO2

(CH3)2CHOH

Al2O3 CCl4

CH2OH

NO2

(CH3)2CHOH

Al2O3 CCl4

OOH

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8.4.3.2 Bimolecular Reduction

Competing with Clemmensen reaction

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Clemmensen reduction (strong acidic condition)

8.4.3.3 Reduction of ketones to methylene group

R

OH+

R

Zn ZnZn

R

OH

R

Zn ZnZn

H+R

OH2+

R

Zn ZnZn

-Zn2+

-H2O

R R

Zn Zn

2H+

-Zn2+

RH2C R

Zn

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Wolff-Kishner –Minglon (strong basic condition)

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S

O

N2H4

KOH, digolS

OH

O

O

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p-CH3C6H4SO2N2H4

NaBH3CNO

O O

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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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OEt

O DIBAL-H

DIBAL-H

no cooling

-70 C°

OH

O

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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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O

CH3NH2

H2/Pt

NH

NO2

HCHO

H2/Ni

HN

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8.5 Reductive cleavage of carbon-heteroatom bonds

Rosemund Reduction

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N

COOC2H5

CN

ClH3C

H2, Pd/BaCO3

Rt 1atmN

COOC2H5

CN

ClH3C

NO2

Cl

H2, Ni

Rt 1atm

NH2

Cl

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Exercise

Complete the following synthesis.