12 Oxidation - Reduction

Date Started @January 25, 2021

Status

Unit/Module Chapter 12

Week 1

12 Oxidation & Reduction

OXIDATION
- increase in number of C—Z bonds (usually C—O Bonds) or a decrease in number of C—H bonds
- decreasing electron density of carbon when adding more electronegative atom than carbon [O]
- dehydrogenation or removal of hydrogen
REDUCTION
- decrease in number of C—Z bonds (usually C—O Bonds) or an increase in number of C—H bonds

- increasing electron density of carbon when adding less electronegative atom than carbon [H]
where Z = element more electronegative than carbon

METHYL ←→ ALCOHOL ←→ ALDEHYDE ←→ CARBOXYLIC ACID

CH4 can be oxidized by replacing C—H bond with C—O bonds, and so on. Whilst, it can be reduced by replacing C—O bond with C—H bonds.

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 📌 OXIDATION = adding [O] more electronegative atom than carbon atom / removing of hydrogen
REDUCTION = adding [H] less electronegative atom than carbon atom

Oxidation and Reduction of Hydrocarbons

📌 special case : two atoms are involve in a oxidation or reduction reaction net change in the number of C—H or C—Z bonds at
both atoms must be taken into account: in redox, one reaction cannot proceed without the other.

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 conversion of alkyne to alkene, and alkene to alkane = REDUCTION, wherein each process adds two new C—H bonds.

REDUCTION
there are three types of reduction, differing in how H2 is added.

simplest reducing agent molecular H₂

- carried out in the presence of a metal catalyst, acting as a surface where reaction occurs.
- addition is in a syn fashion

metals
Pd, Pt, Rh, or Ni are absorbed onto a finely divided inert solid, such as charcoal [C]

second way to deliver H2

- adding two protons [2H+] and two electrons [2e-] to a substrate. [H₂ = 2H + 2e]
- uses liquid ammonia (NH3) as source of protons & alkali metals as source of electrons.

third way to deliver the equivalent of two hydrogen atoms

- adding hydride [H-] and a proton [H+]

common reducing agents: contain hydrogen atom bonded to Boron or Aluminum (metal hydride reagents) — delivers hydride
to substrate & then a proton is added from H₂O or an Alcohol.

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 [NaBH4] - borohydride
[LiAlH4] - lithium aluminum hydride

Issues to be Addressed:

Chemoselectivity
- ability to distinguish a set of reagents' reactivity
- selective reduction of one group in the presence of another
- slecective reaction to one reduction state

Stereoselectivity
- ability of certain reaction to give a specific a stereoisomeric product
- element can distinguish the reactivity

💡 walden process something - S reactant is converted to its counterpart

REDUCTION OF ALKENE
its reduction forms an alkane by addition of H₂.

- two bonds broken—weak 𝜋 bond of alkene & H₂ σ bond— and C—H σ bonds are formed.
- only occurs in presence of a metal catalyst—catalytic hydrogenation.

hydrogenation catalyst are insoluble → heterogenous reaction mixture. hence, it can be filtered away from other reactants after completing the reaction.

Reduction of Alkene - Hydrogenation and Alkene Stability

Hydrogenation reaction

- exothermic— bonds in the product are stronger than bonds

in the reactants
- 𝚫Hº = heat of hydrogenation— measures relative stability of
two different alkenes that are hydrogenated to same alkane.

→ cis isomer releases more energy than trans isomer of

alkene being hydrogenated which is more stable.

more stable alkene has smaller heat of hydrogenation ( 𝚫Hº )

Reduction of Alkene - Mechanism of Catalytic Hydrogenation

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 Addition of H₂ to an Alkene—Hydrogenation:
[1] H₂ adsorbs to catalyst surface with partial or complete
cleavage of H—H bond

[2] 𝜋 bond of alkene complexes with metal

[3]-[4] two (2) H atoms are transferred sequentially to 𝜋
bond, to form alkane.
The alkane (product) has no 𝜋 bond complexing with the
metal, it will now be separated/released from the catalyst
surface

- because of fast sequential addition of H₂. this results in syn addition

- less crowded double bonds complex which are readily available to catalyst
surface. results in fast reaction.

Reduction of Alkene - Hydrogenation Data and Degrees of Unsaturation

Degrees of Unsaturation
- total number of rings and 𝜋 bonds in a molecule.
- H₂ adds to 𝜋 bond only, not to C—C σbonds of rings

Hydrogenation Data
- lets us determine how many degrees of unsaturated are dure to 𝜋 bonds and how many are due to rings
- comparing degrees of unsaturation before and after treatment of H₂.

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 💡 eg.
how many rings and 𝜋 bonds are contained in a compound of molecular formula C₈H₁₂ that is hydrogenated to a compound
of molecular formula C₈H₁₄?

Solution:
Before addition of H₂:
→ 2n + 2, max number of H possible
2(8) + 2 = 18
→ 18 H's max versus 12 H's actual
18 - 12 = 6 H's fewer than max number
→ number of fewer H than max ÷ 2 H's removed for each degree of unsaturation, degree of unsaturation
6 ÷ 2 = 3 degrees of unsaturation

After addition of H₂:

→ 2n + 2, max number of H possible
2(8) + 2 = 18
→ 18 H's max versus 14 H's actual
18 - 14 = 4 H's fewer than max number
→ number of fewer H than max ÷ 2 H's removed for each degree of unsaturation, degree of unsaturation
4 ÷ 2 = 2 degrees of unsaturation

degrees of unsaturation AFTER addition of H₂ = number of rings

degrees of unsaturation BEFORE - AFTER addition of H₂ = number of 𝜋 bonds

two rings & one 𝜋 bonds

Reduction of Alkene - Hydrogenation of Other Double Bonds

Compounds with Carbonyl Group
- also react with H₂ and a metal catalyst.

example:

aldehydes and ketones -reduced→ 1º and 2º alcohols respectively.

Application: Hydrogenation of Oils

Reduction of Alkynes
Reduction of an alkyne

- adds H₂ to one or both of the 𝜋 bonds

- three deferent ways by which H₂ can be added to a tripple
bond

adding two equivalents (2 eq) of H₂ → alkane

adding one equivalent (1 eq) of H₂ in syn fashion →

cis alkene

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 adding one equivalent (2 eq) of H₂ in anti fashion →
trans alkene

Reduction of Alkynes - an Alkyne → an Alkane

when treated to two or more equivalents of H₂ and Pd catalyst, alkyne's two 𝜋 bonds are reduced.

four new C—H bonds are formed; and with Pd catalyst reaction cannot be stopped from proceeding to the addition of second equivalent
of H₂
Syn addition of one equivalent of H₂ → cis alkene → addition of second equivalent of H₂ → alkane,

Reduction of Alkynes - an Alkyne → a Cis Alkene

since, Pd metal is too active to allow hydrogenation of alkyne to stop from proceeding to the addition of second equivalent of H₂.
to have a cis alkene, from alkyne and H₂, a less active Pd catalyst is used— Pd is adsorbed onto a CaCO₃ with added lead (II)
acetate and quinoline or the Lindar Catalyst;

H2/Ni2B

Pt or pd

reduction of alkyne to a cis alkene is a stereoselective reaction— only one stereoisomer is formed.

Reduction of Alkynes - an Alkyne → a Trans Alkene

dissolving Metal Reduction

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 using a (Na in NH₃), H₂ are added in an anti-fashion to alkyne → trans alkene.

Dissolving Metal Reduction of an Alkyne to Tans Alkene

[1] addition of an electron from Na to alkyne → radiral anion— a species with both negative charge& an unpaired electron
[2] protonation pf anion with solven H-NH₂ → radical; net result of [1] & [2] is addition of H atom to alkyne
[3] addition of second electron from Na → vinyl carbanion
[4] protonation of carbanion → trans alkene; net result of [3] & [4] is addition of secon H atom to alkyne

in step [3], two different arrangement is possible, though trans alkene is formed which is more stable vinyl carbanion—with larger R
groups farther away from each other avoiding steric interactions

dissolving metal reductions always form more stable trans product preferentially; and is a stereoselectrive reaction because its
formation of trans product exclusively.

Reduction of Polar C—X σ Bonds

C—X σ Bonds

- react with strong nucleophiles

- reduced with metal hydride reagents(LiAlH₄)

alkyl halides → alkane

epoxides → alcohol

- reduction of these is an example of nulceophilic substitution

Reduction of RX with LiAlH₄ (Sᴺ2 Mechanism)

[1] nucleophile H⁻ replaces the leaving group X⁻ in a single step

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 unhindered CH₃ and 1º alkyl halides are more easily reduced & in unsymmetrical epoxides, nucleophilic attach of H⁻ occurs at less substitued atom.

OXIDIZING AGENT
reagents with O—O bond: O₂, O₃, H₂O₂, (CH₃)₃COOH (tert-butylhydro peroxide) and peroxyacids.

Peroxyacids' general structure: RCO₃H.

- have more than one more oxygen atom than carboxylic acids (RCO₂H)
- maybe prepared commercialy or syntehsixed.

peroxyacetic acid

meta-chloroperoxybenzoic acid (mCPBA)

reagents with metal—O bonds: contains either Cr in +6 oxidatation state (six Cr—O bonds) or seven Mg—O bonds.

common Cr⁶⁺
- strong oxidants used with a strong aqueous acid like H₂SO₄

CrO₃

K₂Cr₂O₇ or Na₂Cr₂O₇

Pyridium chlorochromate (PCC): can be used with strong acid present, making it a more selective oxidant

common Mn⁷⁺

KMn₄: strong water-soluble oxidant

OsO₄

Ag₂O

Oxidation Reaction of Alkenes, Alkynes & Alcohols

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 Oxidation
- replacing C—H bonds on the carbon bearing the OH groyp by C—O bonds

EPOXIDATION
- addition of single oxygen atom to an alkene → epoxide
- weak 𝜋 bond of alkene is broken → C—O σ bonds
- carried out by peroxyacid → cleavage of weak O—O bond of reagent
- occurs via concerted addition of one oxygen atom of peroxyacid to 𝜋 bond
- resembles formation of bridged halonium ion → two bonds in three membered ring in one step

Epoxidation of an Alkene with Peroxyacid

[1] all bonds are broken and formed in single step. Two epoxide C—O bonsa are formed from one electron pair of 𝜋 bond and one
lone pair of peroxyacid. Weak O—O bond is broken.

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 Epoxidation: Sterochemistry
- occurs via syn addition of an oxugen atom from either side of planar double bond → C—O bonds formed in same side.
- relative position of substituents in alkene are retained

cis alkene → epoxide with cis substituents

trans alkene → epoxide with trans substituents

- a stereospecific reaction, because cis and trans alkenes yield different stereoisomers as products

📌 an achiral starting material gives achiral or racemic products (enantiomers)

Epoxidation: Synthesis of Dispalure

- sex pheromone of female gypsy moth
[1] formation of two C—C Bonds using acetylide anion (NaNH₄)

[2] reduction of alkyne B → cis alkene

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 [3] epoxidation of A → dispalure

DIHYDROXYLATION
- addition of two hydroxy groups to a double bond → diol or glycol,
- depending on the reagent two OH may be added in two ways

anti-addition (opposite sides)

syn-addition (same sides)

Anti Dihydroxylation
- treatment with RCO₃H or mCPBA & H₂O (H⁺ or ⁻OH)
- achieved in two steps:

[1] epoxidation of alkene by treatment of RCO₃H or mCPBA

[2] hydrolysis— H₂O (H⁺ or ⁻OH)

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 addition O atom of alkene (epoxidation) → epoxide → single achiral epoxide

epoxide above the plane → Nu:⁻ attack below the plane

anti-addition of two OG groups to an alkene

Syn Dihydroxylation
- alkene is treated with KMnO₄ or OsO₄ (with NaHSO₃ in hydrolysis)
- reagent adds two Oxygen atoms to same side of double bonds
- hydration of cyclic intermediate cleaves metal-oxygen bonds → cis-1,2-diol
[1] treatment with KMnO₄ or OsO₄
[2] hydrolysis — NaHSO₃ and/or H₂O

KMnO₄

- inexpensive & readily available but has limited uses because of its organic insolbulity
- OH⁻ is added in the reaction mixture to keep it basic

OsO₄
- selective oxidant and organic soluble, but it is toxic and expensive
- use fo catalytic amount of it should be carried out, if oxidant NMO is added.

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 OXIDATIVE CLEAVAGE OF ALKENES
- breaks both σ and 𝜋 bonds of double bonds to form two carbonyl groups
→ yields ketones or aldehyde, depending on the number of R-Groups

- two-step procedure with O₃ (ozone) as oxidant in first step— Ozonolysis

[1] Ozonolysis: treatment of alkene with ozone → molozonide → ozonide

[2] treatment of Zn (in H₂O) or dimethyl sulfide (CH₃SCH₃) → carbonyl compound

OXIDATIVE CLEAVAGE OF ALKYNES

- breaks σ and both 𝜋 bond of triple bonds

internal alkynes oxidized → carboxylic acid (RCOOH)

terminal alkyne → carboxylic acids and CO₂ from sp hybrized C—H bond

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 [1] treatment of alkyne with ozone

[2] cleavage of ozonide with H₂O → carboxylix acids (or with CO₂)

OXIDATION OF ALCOHOLS
- oxidized to a variety of carbonyl compounds, depends on the type of alcohol and reagent

1° OH → aldehyde or carboxylic acids

- replacement of either one or two C—H binds by C—O bonds

- aldehydes formed with PCC in dichloromethane (mild reaction)
- carboxylic acids formed with CrO₃, NaCr₂O₇ and K₂Cr₂O₇ in presence H₂O
and H₂SO₄ (harsh reaction)

2° OH → ketones
- replacement of the one C—H bon by C—O bond
- effectively oxidized by Cr⁶⁺

3° OH → NOT OXIDIZED

- because it does not have H atom on the carbon with OH group

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 - occur by involving bonding in leaving group Z to oxygen. Elimination with a base → C=O and a metal in a lower oxidation state than Z.
- typically carried out with the Cr⁶⁺ oxidant reduced → Cr³⁺ product

CrO₃, NaCr₂O₇ and K₂Cr₂O₇

- strong, nonselective oxidants used in aqueous acid (sulfuric acid + water)

PCC

- more selective & milder oxidant, soluble in dichloromethane and can be used with out strong acid present

Oxidation of Alcohols: 1°
aldehydes formed with PCC in dichloromethane (mild reaction)

carboxylic acids formed with CrO₃, NaCr₂O₇ and K₂Cr₂O₇ in presence H₂O and H₂SO₄ (harsh reaction)

Oxidation of Primary Alcohol to a Carboxylic Acid

[1] primary alcohol is oxidized → aldehyde by three-step sequence

[2] hydration oof C=O in aldehyde → hydrate— compound with two OH groups bonded to same carbon
[3] oxidation of C—H bond of hydrate → chromate ester and loss of proton

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 Oxidation of Alcohols: 2°
- effectively oxidized by Cr⁶⁺ → ketone

Oxidation of An Alcohol with CrO₃

[1] - [2] Nu:⁻ attack of alcohol on elctrophilic metal → proton transfer → chromate ester
[3] base (water) protonate the ester group → new 𝜋 bond of C=O. Carbon is oxidized

GREEN CHEMISTRY
- use of environmentally benign methods to sysnthesize compounds
- purpose: use safer reagent and less solvent, and develop reactions → fewer by-products and generate less wate

SHARPLESS EPOXIDATION
- achiral reactant + achiral reagent → achiral product or a racemic mixture of two enantiomers

if a chiral product is desired → half of the product mixture is the desired enantiomer and the other is not.

- enantioselective reaction affords predominantly of exlusively one enantiomer

- reaction convers an achiral starting material → predominantly onen enantiomer —asymmetric reaction
- an asymmetric epoxidation is an enantioselective reaction oxidizes alkenes → epoxides

Sharpless reagent

tert-butyl hyperperoxide (CH₃)₃COOH

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 titanium catalyst: titanium (IV) isoperoxide Ti[OCH(OCH₃)₂]₄

diethyl tartrate (+ or - DET)

+ DET adds oxygen from above the plane

- DET adds oxygen from below the plane

- identity if the DET isomer determines which enantiomer is the major product

- degree of enantioselectivity of a reaction is measured by its enantiomeric excess (ee)

🧮 enantiomeric excess (ee) = % of one enantiomer - % of the other enantiomer

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