To name alcohols:

The carbon that the hydroxyl is attached to must be in the longest chain

If an alkene is present, it must be in longest chain

When numbering, hydroxyl takes precedence

To name ethers:

Simply list both substituents and add “ether”

R-O-R’

List R and R’ in alphabetical order and add “ether”

Ethers can also be alkoxy alkanes

See 2-methoxypentane and 1,3-dimethoxypropane

When an oxygen is part of a ring, pretend it’s a carbon and add “oxa” prefix

Oxacyclobutane would be 3 carbons and an oxygen in a ring

Oxacyclopentane is also called THF and tetrahydrofuran

When oxygen is part of a ring, it is always number 1 position

When there are two, give the two oxygens the lowest numbers possible

1,4 dioxacyclohexane

4-ethyl-2,2-dimethyloxacyclopentane

4-methoxy-1,3-dioxacyclohexane

If a ring is present, and OH is a substituent, use the prefix “hydroxy” instead of “ol” suffix

Remember that an alcohol (ROH) has a higher boiling point than an ether (ROR)
Synthesis of alcohols from alkenes

First, take an alkene and add sulfuric or phosphoric acid, do not use HCl or HBr because leaving
group will attach

Then add water

First, a carbocation will form and water will attach to it, then water will remove the extra proton

Oxymercuration and demurcuration

They AVOID REARRANGEMENT

Add Hg(OAc)2, THF-H2O to alkene

Carbocation will form and water will attach to it

Then add NaBH4, OH- and a hydrogen will remove the mercury, leaving you with a secondary
alcohol

Both of these AlkeneAlcohol RXNs create a secondary alcohol

To create a primary alcohol, use hydroboronation

Add BH3, THF to alkene

BH2 will add to least substituted side, H will add to most

Then add H2O2, OH- and an OH will replace the BH2 group, leaving you with a primary alcohol

The acidity of alcohols

ROH has a pka around 16-18

Phenols have around 10 due to resonance

RXNs of alcohols

R-OH + H-X  R-X + H2O

R-OH + sulfuric or phosphoric acid yields alkene

RXNs of Alcohols with PBr3 and SOCl2 to give alkyl halides

**does not work with tertiary OHs nor phenols**

Must be primary or secondary

R-OH + PBr3  R-Br + PBr2OH

PBr2OH could be reused for a 2nd and 3rd reactions

R-OH + SOCl2  R-CL + SOClOH

Tosylates, Mesylates, Triflates

Know structures

ARE EXTREMELY GOOD LEAVING GROUPS

F < Cl < Br < I <<<mesylate, tosylate, triflate

Abbr. Ts, Tf, Ms

Tosyl group + R group = Tosylate

To make tosylate, add ROH to Tosyl Chloride, kick chloride off via SN2

These groups can be reacted with alcohols to form better leaving groups, then reacted with a
nucleophile to form a new compound via SN2 RXN

Ether by intermolecular dehydration of a primary alcohol

Ethanol + Sulfuric Acid will yield an ethanol with an extra hydrogen on the oxygen (water
group)
Water group will leave when additional ethanol attacks via backside attack, forming diethyl ether

So primary alcohol + sulfuric/phosphoric acid will produce an ether

R-O-Metal (alkoxide) + R’-LG (leaving group)  ether

Isopropyl alcohol + NaH  (CH3)2 – CH – ONa

(CH3)2 – CH – ONa + CH3-I  (CH3)2 – CH – O – CH3 (ether)

Ph – OH + NaOH  Ph – O-

Ph – O- + CH3CH2 – OMs  Ph – O – CH2CH3 (Ether)

Ethers by alkoxymercuration/demurcuration

Regular mercuration:

CH2 = CH2 + 1) Hg(OAc)2 / THF – H2O , 2) NaBH4, OH  CH3-CH2-OH

Alkoxymercuration:

CH2 = CH2 + 1) Hg(OAc)2 / THF – CH3OH 2) NaBH4, OH  CH3-CH2-OH-CH3 (ether)

NO REARRANGEMENT

Silyl ethers as protecting groups for alcohols

R-OH + tert-butyldimethylsilylchloride (TBS) with imidazole as a weak base and DMF as a

See notes for mechanism

Any alcohol: Ph-OH + TBS/Imidazole/DMF  Ph-O-TBS

To remove the protecting group (TBS), we need a Flouride ion (HF) or

(TBAF) tetrabutyl ammonium fluoride

This allows an alcohol to react without ionizing the acidic hydrogen on the OH

OH – CH2 – CH2 – CH2 – Br + 1) TBSCL  TBS - O– CH2 – CH2 – CH2 – Br

(TBS - O– CH2 – CH2 – CH2 – Br + 2) NaC(trpl bond)C-CH3 

TBS - O– CH2 – CH2 – CH2 – C(trpl bond)C-CH3)

TBS - O– CH2 – CH2 – CH2 – C(trpl bond)C-CH3 + 3) TBAF  HO– CH2 – CH2 – CH2 –
C(trpl bond)C-CH3

Note that the OH group would have reacted first had it not been protected

Cleavage of ethers w/hydrogen halides

Diethyl ether + HBr  CH3CH2OH + BrCH2CH3

The H adds to the oxygen, then the bromine ion backside attacks one carbon and the alkoxy
group leaves with the hydrogen, forming an alcohol

React it again with HBr and form CH3CH2Br + H2O

(CH3)2 – CH – OCH3 + HBr  (CH3)2 – CH – OH + CH3-Br

(the bromine attacks the least substituted carbon)

Another example:

Ph-O-CH2CH3 + HCl  Ph-OH + Cl-CH2-CH3

The hydrogen goes to most substituted carbon and the ion attacks the least substituted carbon

Epoxides (cyclopropane but one carbon is oxygen)

Alkene + Peroxy acid (R-C=O (- O-O-H)  Epoxide + Carboxilic acid

Alkene + MCPBA  epoxide

RXN of epoxides

Base catalyzed ring opening

Methyl-epoxide + CH3CH2ONa / CH3CH2OH  ether

(CH3CH2-O-CH2-CH-CH3-(OH)

Note that the base attacks least substituted carbon

Acid catalyzed ring opening attacks most substituted carbon

Methyl-epoxide + CH3OH  CH3-O-CH-(CH2OH)(CH3)

Anti-diols

Alkene + 1)MCPBA  protruding epoxide

Protruding epoxide + H3O+  epoxide alcohol (protonated the epoxide)

Epoxide alcohol + H2O  anti-diol

See mechanism

Syn-diol review

Alkene + 1)OsO4 , 2) H2O2  syn-diol

Cold KMnO4 works too

Carboxylic acid  reduced to primary alcohol

Ester  reduced to primary alcohol

Aldehyde  reduced to primary alcohol

Ketone  reduced to secondary alcohol

Aldehyde + H2, (Pt, Paladium, or Ni), pressure  R-CH2-OH (primary)

Ketone + H2, Pd, Pressure  R-C-(OH)-R (secondary)

ONLY ALDEHYDES AND KETONES HYDROGENATE AS CARBONYLS

Ease of reduction:

Carboxilic acid is hardest to reduce > ester>ketone>aldehyde(easiest to reduce)

Reducing agents: NaBH4 reduces aldehydes and ketones

LiAlH4 (LAH) reduces all carbonyls, extremely reactive with water

Ph-C=O(-H) + NaBH4, H2O or alcohol  Ph-CH2-OH

Ph-C=O(-OCH3) + 1)LiAlH4, Et2O  Ph – CH – O (-OCH3)

**electrons on oxygen kick back in to form double bond, expel methoxy group**

Ph – CH = O + LiAlH4  Ph – CH2 – O- (electrons on O cant reform dbl bond)

2) add H2O to protonate O  Ph – CH2 – OH

Base strength:

:CR3 (carbanion) > NH2 > :H > :C(trpl)C–R > OR > OH

*can be methyl, primary, secondary or tertiary*

**NEVER phenylic or vinylic**

(CH3)2 - C – Br (-Et) + LiAlD4  (CH3)2 – CD – Et

CH3 – CH2 – CH2 – Br + LiAlH4  CH3-CH2-CH3

**LiAlD4 is how you introduce Deuterium into molecules**

SEE NaBH4 Problems in notes

Oxidation of primary alcohols

R – CH2 – OH (oxidation) R – CH = O (aldehyde) quickly oxidized in aqueous

**if we want aldehyde, we cannot use water**, so we use PCC or (COCl)2

COCl2 is used in SWERN OXIDATION

CH3 – (CH2)5 – CH2 – OH + PCC (in dichloromethane solvent)  CH3 - (CH2)5 – CH = O

(aldehyde, 78% yield)

Swern Oxidation:

Exactly like PCC but uses (COCl)2 and in a second step, add a weak base (Et3N)
Chromic acid oxidizes primary OH to carboxylic acid

CH3 – CH2 – CH2 – OH + H2CrO4 (Chromic acid)  CH3-CH2-COOH

To get chromic acid… use jones reagent

CrO3 + H2SO4 (in H2O) H2CrO4 OR

K2CrO7 + H2SO4(in H2O) H2CrO4

Propanol + 1)KMnO4, OH, H2O, Heat; 2) H3O+  CH3-CH2-COOH

Simply put, to oxidize primary OH to Aldehyde,

use PCC/nonpolar solvent or (COCl)2/ weak base

to oxidize primary OH to COOH, use Chromic acid in water, or KMnO4 in OH, H2O, and heat
then acidify with H3O+

Secondary alcohol oxidation

USE ANY OXIDIZING REAGENT

Since it cannot form an aldehyde, it wont form a carboxylic acid, and will always be a ketone no
matter what oxidizing agent you use

Tertiary alcohols and Phenols

CANNOT BE OXIDIZED
Organometallic compounds

(R – X)  X is more electronegative and R is more electropositive

(R – Metal)  R is more electronegative and the metal is electropositive

When carbon bonds to Sn, Hg, Cu etc, it is a covalent bond

When carbon bonds to Mg or Li, it is ionic and partial charges form

Organometallic nomenclature

-named as substituents of the metals

-metal is the parent name

- group is the substituent

CH3CH2Li  ethyl lithium

/_\ - Li  cyclopropyl lithium

NaCH3  methyl sodium

(CH3CH2)2Mg  diethyl magnesium

Ph-Li  phenyl lithium

______________________________________________________________________

When the metal bears a substituent other than carbon, the substituent is treated as an anion and
named separately

NaCl  sodium chloride

CH3MgI  methyl magnesium iodide

Ph-MgBr  phenyl magnesium bromide

___________________________________________________________________

Preparation of organolithium compounds

R – X + 2Metal in diethyl ether R-M + X-M

Ph-Br + 2Li SET Ph-Br]. degrades Ph* + Br- Li Ph-Li + LiBr

____________________________________________________________

Preparation of organomagnesium compounds

GRIGNARD REACTION

R – X + Mg  R-MgX(Grignard reagent) (done in Et2O)

Mechanism is same as Li but only 1 equivalent of Mg is needed since it gets rid of 2 radicals

See example reactions

_________________________________________________________________

RXN of organolithium and grignards (they are interchangeable)

AVOID RXNS WITH ACIDIC PROTONS

Avoid water, alcohols, terminal alkynes

Reactions with epoxides

Ph-MgBr + 2-methyloxacyclopropane  Ph-CH2-CH-O(-CH3)+H3O+

Ph-CH2-CH-OH(-CH3) **base attacks least substituted carbon**

RXNs with carbonyls

Formaldehyde carbonyl gives primary alcohol

See Mechanism
Regular aldehydes give secondary alcohol

See mechanism

RXNs with ketones gives tertiary alcohols

See mechanism

RXNs with esters gives tertiary alcohols

See mechanism

RXNs with CYCLIC esters give diols, one primary, one tertiary

See mechanism
Grignard + Carboxilic acid

Ph-COOH + CH3MgBr  CH4 + Ph-COO- H3O+ Ph-COOH (useless reaction)

CARBOXILIC ACID WILL NOT REACT WITH GRIGNARD

Retrosynthesis

Cleave one substituent off and add it to MgBr,

Use central carbon and make it carbonyl, and the R-MgBr and carbonyl compound are the
reagents

CH3-CH2-C-(CH3)2(-OH) =>

CH3MgBr + EtC(C)=O OR

CH3CH2MgBr + C-C=O(-C)

OR if you have two identical groups, cleave them both off and use 2 equiv. + ester

2 CH3MgBr + Et-C=O(-OCH3)

See examples

If two alcohols are present in the product, to synthesize, cleave off two identical substituents
from both carbonyls and use them in 2 equiv. of reagents

See example
Restrictions on use of grignards

R-X + Mg  RMgX (standard)

Must avoid all acidic hydrogens on R group

NO ROH, ROOH, NH2, RNH, SH, :C(trpl)CH, aldehyde, any carbonyl, epoxide, nitrile, or nitro

CAN use Ph, alkyl, vinylic, alkyne halide, tertiary amine, ether

Ways to get around acidic hydrogens

USE 2 equiv. (excess) Grignard, then acidify

See example

Use protecting groups

1-hydroxyl-3-bromo-cyclopentane + 1)TBSCL, imidazole, DMF turns OH to OTBS

2)Mg turns bromo group to MgBr

3)react protected Grignard with carbonyl

4)remove TBS with Flouride and acidify [HF] or [H3O + NaBH4F]

See mechanism
Use of lithium reagent

Propyl lithium + ketone in Et2O  -O-C-(CH3)2(Et)acidify with H3O tertiary OH

See mechanism (can also use propyl magnesium bromide)

Can also use sodium CH3-C(trpl)C:-Na+