8.4 Reactions of AlcoholsCH21 –AY 2013-2014 SEM II -- R.D. A. Bolinas

Alcohols can undergo E1/E1cB/E2 reactions to form alkenes

By protonating –OH in acid, we get an oxonium –OH2+ that can leave as H2O

E1/E2 depends on the nature of ROH, but usually E1 prevails, except for 1° alcohols (E2)

Alcohols can undergo E1/E1cB/E2 reactions to form alkenes

Alcohols can undergo E1/E1cB/E2 reactions to form alkenes

Predict the major product. Remember Zaitsev’s rule!

Alcohols can undergo E1/E1cB/E2 reactions to form alkenes

Predict the major product. Remember Zaitsev’s rule!

Alcohols can undergo E1/E1cB/E2 reactions to form alkenes

E1cB occurs in biological systems: the -OH group is two carbons away

from a carbonyl (C=O) group

Alcohols can be oxidized into carbonyls…

Alcohols can be oxidized into carbonyls…

We use oxidizing agents: periodinane (with Iodine in +5 oxidation

state) PRIMARY R-OH TO ALDEHYDE ONLY

Alcohols can be oxidized into carbonyls…

We use oxidizing agents: Acidic CrO3/CrO4

2- (with Chromium in +6 oxidation state)

PRIMARY R-OH TO CARBOXYLIC ACID

Alcohols can be oxidized into carbonyls…

Secondary alcohols will give ketones with either reagent

Alcohols can be oxidized into carbonyls…

Alcohols can be oxidized into carbonyls…

Periodinane

The Williamson Ether synthesis uses an alkoxide and alkyl halide…

Ethers (R-O-R) SN2 reaction between R-X and R-O-

The Williamson Ether synthesis uses an alkoxide and alkyl halide…

SN2 reaction between R-X and R-O- WE NEED TO CONSIDER STERIC

HINDERANCE. This might lead to E2!

Backside attack is not favorable!

Methoxide is also a very strong base.

The Williamson Ether synthesis uses an alkoxide and alkyl halide…

Practice:

The Williamson Ether synthesis uses an alkoxide and alkyl halide…

Practice:

Phenols can sometimes react like alcohols in forming ethers.

CANNOT: be dehydrated with acid, convert into halides with HX

CAN: convert to ether via Williamson ether synthesis, react via EArS (review)The aromatic ring allows the

H+ to leave easily, making phenols ACIDIC.

Oxidation of phenols gives us QUINONES

Because they don’t have a hydrogen on the C-OH carbon, phenols become quinones

Oxidation of phenols gives us QUINONES

Quinones easily change form into hydroquinones

Quinones are biologically significant redox facilitators

Ethers generally undergo only acidic cleavages.

Ethers are unreactive to most common reagents

Only strong acids can usually react with them: HI/HBr via SN1 or SN2

Ethers generally undergo only acidic cleavages.

Ethers are unreactive to most common reagents

Only strong acids can usually react with them: HI/HBr via SN1 or SN2

SN1

Cyclic ethers are also generally as unreactive, except for EPOXIDES.

Epoxides come from alkenes + peroxy acids

High angular strain induces reactivity.

SN2 attacks with H3O+ or HX lead to trans-diol or trans-halohydrins, other nucleophiles work too.

Cyclic ethers are also generally as unreactive, except for EPOXIDES.

SN2 attacks with H3O+ or HX lead to trans-diol or trans-halohydrins, other nucleophiles work too.

beta-blocker that is used for treatment of cardiac arrhythmias, hypertension, and heart attacks

Sulfur analogs of alcohols and ethers are called thiols and sulfides.

Thiols can be made via SH- and RX, and can react via Williamson mechanismSN2 Synthesis:

Williamson thioether synthesis

Disulfides are formed via oxidation. Reduction to thiols can occur as well.

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http://b.vimeocdn.com/ts/147/230/147230470_640.jpg

Disulfides are formed via oxidation. Reduction to thiols can occur as well.

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For rebonding:

(1)Thioglycolate (acid-like) to convert disulfide bonds in hair protein to thiolates

(2)Hydrogen peroxide to oxidize the thiolates back to disulfides.

(3)Reforming the disulfides helps re-align amino acids and make hair straight

Disulfides are formed via oxidation. Reduction to thiols can occur as well.

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“antioxidant” because it protects your cells from oxidative degradation.

Propose a synthetic route from 2-phenylethanol to make:

AB C

D

E

Propose a synthetic route from 2-phenylethanol to make:

H2SO4 P

eri

od

inan

e

CrO3

KMnO4

1. H2SO4 2. H2/Pd

Problems

Problems

More synthetic routes

More synthetic routes

More synthetic routes: propose reagents for each step!

More synthetic routes: propose reagents for each step!

NaBH4, H3O+

PBr3

1. Convert to Grignard (Mg/ether)

2. add CH2=O then acid

1. Ph-CH2-MgBr 2. 2. H3O+

Periodinane

conc’d H2SO4