PHA615 LEC: Alcohols, Phenols, Ethers, Sulfur Analogs

Alcohols

are characterized by the presence of a hydroxyl (-OH) group bonded to a carbon chain

Phenols

• (Ar-OH) have the -OH group attached to an aromatic ring.

Ethers

(R-O-R’) has an oxygen bonded to 2 carbons

Epoxides

• are ethers in a cyclic arrangement where the organic parts are also bonded to each other.

Thiols, Thiophenols, Sulfides

• are all analogs of the O-containing organic compounds.

ROH and Ar-OH

exhibit H-bonding similar to H2O resulting to a higher boiling point than R-O-R’.

ROH and Ar-OH

are also weakly basic and weakly acidic like H2O.

oxonium ions.

As bases, they form

alkoxide/phenoxide ions

As acids, they form

Ethers and Epoxides

 are both practically unreactive to most reagents which makes them good reaction solvents.

R-SH and R-S-R’

• re commonly found in living organisms. R-SH possess distinct appalling odor — skunk-like.

Synthesis of Alcohol

Hydration, SN Haloalkene with H2O, Reduction and RMgX

Aldehydes and Ketones

uses weak reducing agent — NaBH₄ in water or alcohol solution in a weakly acidic condition (H₃O+).

Carboxylic acid and Esters

uses strong reducing agent — LiAlH₄ in ether solution in a weakly acidic condition (H3O+).

1° ROH

Aldehydes are reduced to _

2° ROH

Ketones to .

RMgX

adds a carbanion to the carbonyl carbon, similar to reduction adding a hydride, to produce various ROH products

Formaldehyde

with RMgX results to 1° ROH.

Aldehydes

Ketones and Esters

with RMgX results to 3° ROH.

DEHYDRATION

removes H₂O from the ROH and forms an alkene product.

E1 mechanism

What Mechanism is ACID-CATALYZED DEHYDRATION

strong acid solution

2° and 3° ROH are dehydrated effectively in _

OXIDATION OF ALCOHOLS

is the most valuable reaction of ROH which produces carbonyl compounds (e.g aldehydes, ketones, carboxylic acids)

alpha / benzylic hydrogens

ROH carrying_ can undergo oxidation

Oxidation Reagents

chromium trioxide (CrO3), Na dichromate (Na2Cr2O7), KMnO4 in acidic solution. The most common and current choice is periodinane in DCM

ETHER SYNTHESIS

• is a reaction that converts R-OH to R-OR’ by reacting ROH with RX via SN2 mechanism.

SN2

Mechanism for WIlliamson ether synthesis

NaH

An alkali metal or a strong base like _reacts with ROH to form an alkoxide (RO-).

Phenols

are aromatic alcohols that are synthesized via a special process

Dow Process

Phenols are aromatic alcohols that are synthesized via a special process called as the

Phenols

_despite being alcoholic, do not react similarly to regular ROH.

Electrophilic substitution (SE)

since phenols are benzene derivatives. Reaction with phenols substitutes an E+ at the ortho/para position.

Williamson ether synthesis (via SN2)

since phenols are still alcoholic and bulky as well, it acts as good substrates for ether synthesis.

Oxidation-Reduction

is different from regular C=C oxidation.

quinones

Phenol oxidation proceeds using Na₂Cr₂O₇/H₃O which produces _

reduced

Quinones can be easily reacting with SnCl₂ in H₂O or NaBH₄.

SYNTHESIS OF ETHER AND EPOXIDES

are performed via A_E reactions with alkenes. Ethers are also synthesized using ROH.

Synthesis of ether and epoxides

Addition of ROH to Alkenes

Addition of Peracid to Allkenes

Williamson ether synthesis

Acidic ether cleavage

is the only reaction that ethers undergo forming ROH and RX. This reaction uses HI or HBr and occurs via two mechanisms:

HI or HBr

Reagent for Acidic ether cleavage

S_N2

the ether oxygen stays with the bulkier R group, and the halogen attaches to the less bulky R group of the ether.

S_N1

the ether oxygen stays with the less bulky R group, and the halogen attaches to the bulkier R group of the ether.

Epoxides

are cyclic ethers forming 3-membered heterocyclic ring that exhibits angle strain — making them more reactive than ethers in milder conditions.

dilute acids

Epoxides reactions are similar to ether reactions and in addition to strong acids (e.g. HX) even _ (i.e H3O+) can be used to open the epoxides.

angle strain

Due to the _, epoxides can also undergo ring-opening reactions with bases and other Nü reagents via S_N2 mechanism.

Thiols

It is synthesized via S_N2 reaction of RX and a sulfur Nü (e.g. H2S).

It is synthesized via S_N2 reaction of 1° or 2° RX and thiolate ion (RS-)

sulfur Nu

reagents to produce thiol

thiolate ion (RS-)

reagents to produce sulfides