CH21 –AY 2013-2014 SEM II -- R.D. A. Bolinas By protonating –OH in acid, we get an oxonium –OH 2 + that can leave as H 2 O E1/E2 depends on the nature.

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)



Predict the major product. Remember Zaitsev’s rule!


Predict the major product. Remember Zaitsev’s rule!


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

from a carbonyl (C=O) group

Alcohols can be oxidized into carbonyls…


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

state) PRIMARY R-OH TO ALDEHYDE ONLY


We use oxidizing agents: Acidic CrO3/CrO4

2- (with Chromium in +6 oxidation state)

PRIMARY R-OH TO CARBOXYLIC ACID


Secondary alcohols will give ketones with either reagent



Periodinane

The Williamson Ether synthesis uses an alkoxide and alkyl halide…

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


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.


Practice:


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.

http://delight.spslinfotechpvtl.netdna-cdn.com/media/catalog/product/cache/1/image/650x650/9df78eab33525d08d6e5fb8d27136e95/r/e/rebonding.jpg

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


http://delight.spslinfotechpvtl.netdna-cdn.com/media/catalog/product/cache/1/image/650x650/9df78eab33525d08d6e5fb8d27136e95/r/e/rebonding.jpg

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


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

“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

CH21 –AY 2013-2014 SEM II -- R.D. A. Bolinas By protonating –OH in acid, we get an oxonium –OH 2 + that can leave as H 2 O E1/E2 depends on the nature.

Documents

periodinane slide

sn1sn1 slide

reagent slide

hydroquinones slide

bolinas slide

pd slide

o group slide

carboxylic acid slide