Alcohols, Phenols, Ethers, And Their Sulfur Analog

most commonly occurring functional groups in organic chemistry

are those that contains oxygen atom (C-O and C=O)

Alcohols (R-OH)

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 (R-SH), Thiophenols (Ar-SH), and Sulfides (R-S-R’)

are all analogs of the O-containing organic compounds.

Alcohols, Phenols, and Ethers

are seen as derivatives of water (H-O-H).

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

As bases, they form

oxonium ions

• As acids, they form

alkoxide / phenoxide ions.

Phenols

are more acidic than alcohols

Despite the similarities, R-OH and Ar-OH

undergoes different reactions.

Ethers and Epoxides

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

R-SH and R-S-R’

are commonly found in living organisms.

R-SH

possess distinct appalling odor — skunk-like.

Alcohols can be synthesized from:

• alkenes via electrophilic addition (hydration)

• haloalkanes via nucleophilic substitution with H2O

• carbonyl group (RC=O) via reduction and RMgX reaction.

Reduction of carbonyl group

uses compounds like aldehydes, ketones, carboxylic acids, and esters

Aldehydes and Ketones

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

Aldehydes are reduced to

1° ROH

Ketones reduced to

2° ROH

Carboxylic acid and Esters

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

Carboxylic acids and Esters are reduced to

1° ROH

Reduction of Carbonyl Group

NaBH4 and LiAlH4 adds

a hydride ion to the carbonyl carbon, resulting to an alkoxide intermediate

Reduction of Carbonyl Group

NaBH4 and LiAlH4 adds a hydride ion to the carbonyl carbon, resulting to?

an alkoxide intermediate

alkoxide intermediate is protonated by the

acidic condition finally resulting to the alcohol product

Grignard reaction employs a reaction

between Grignard reagent (RMgX) and carbonyl compounds like aldehydes, ketones, and esters.

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 with RMgX

results to 2° ROH.

Ketones and Esters with RMgX

results to 3° ROH.

Reactions of Alcohols

• Acid-catalyzed dehydration via E1 mechanism

• Oxidation of 1° and 2° ROH

• Ether synthesis via SN2 mechanism

Acid-catalyzed Dehydration of ROH

removes H2O from the ROH and forms an alkene product

Acid-catalyzed Dehydration

follows an E1 mechanism with a carbocation intermediate and follows Zaitsev’s rule to determine the major product

2° and 3° ROH are dehydrated effectively in

strong acid solution (eg. H2SO4/H2O

Oxidation of alcohols

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

ROH carrying alpha / benzylic hydrogens

can undergo oxidation

1° ROH oxidizes into

aldehyde then into a carboxylic acid.

2° ROH oxidizes into

a ketone.

3° ROH

do not undergo oxidation.

Oxidation reagents:

chromium trioxide (CrO3), Na dichromate (Na2Cr2O7), KMnO4 in acidic solution.

most common and current oxidation reagents

periodinane in DCM.

3° ROH do not react and cannot be oxidized.

The non-reactivity of the 3° ROH to oxidizing agents is due the absence of alpha/benzylic hydrogens.

Ether synthesis

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

Ether synthesis is called

Williamson ether synthesis

Ether Synthesis

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

The RO- reacts with 1° RX via

SN2 mechanism

Williamson ether synthesis follows SN2 mechanism.

NaH aids the -OH to be a good leaving group and simultaneously the alkoxide (RO) ion substitutes the halogen from a 1° RX

NaH

aids the -OH to be a good leaving group and simultaneously the alkoxide (RO) ion substitutes the halogen from a 1° RX

In order to avoid E2 from happening in ether synthesis

a bulkier alkoxide is used to react with a simpler (1°) RX.

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

Dow Process

Dow Process

can use substrates like a chlorobenzene or benzene sulfonic acid to react with NaOH to form a Na phenoxide which in turn will be set for pyrolysis

Dow Process can use substrates like a chlorobenzene or benzene sulfonic acid to react with

NaOH to form a Na phenoxide which in turn will be set for pyrolysis.

Reactions of Phenols

• Electrophilic substitution (SE)

• Williamson ether synthesis (via SN2)

• Oxidation-Reduction

Synthesis of ethers and epoxides

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

Synthesis of Ether

• Addition of ROH to Alkenes

• Williamson ether synthesis

Synthesis of Epoxides

• Addition of Peracid to Alkenes

Reactions of Ethers

Acidic ether cleavage

Acidic ether cleavage

is the only reaction that ethers undergo forming ROH and RX.

Acidic ether cleavage

uses HI or HBr & occurs via SN1 and SN2

SN2

— if the alkyl (R) groups in the ether are 1° or 2°

SN2

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

SN1

— if the alkyl (R) groups in the ether is 3°

SN1

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.

Epoxides reactions are similar to ether reactions and in addition to ______ can be used to open the epoxides

strong acids (e.g. HX) even dilute acids (i.e H3O+)

Due to the angle strain, epoxides can also undergo ring-opening reactions with

bases and other Nü reagents via SN2 mechanism

When epoxides undergo ring-opening reaction via SN2, the products are in a

trans stereochemistry

via SN2 mechanism, Nü (like HO-, RO-, RNH2 /R2NH, RMgX) can attack the

less hindered ether carbon and simultaneously the dilute acid solution cleaves the cyclic form to yield a hydroxyl (-OH) substituent

Thiols

are alcohol analogs but carries the mercapto group (-SH).

Thiols

It is synthesized via SN2 reaction of RX and a sulfur Nü (e.g. H2S).

Sulfides

are ether analogs but carries one sulfur atom in between two R-groups.

Sulfides

It is synthesized via SN2 reaction of 1° or 2° RX and thiolate ion (RS-).