Module 9: Alcohols & Phenols

Pharmaceutical Organic Chemistry (Lecture)

PChem 1202 | Kristine Chesley D. Dullan | BS Pharmacy 1A | Prof. Taytayon

ALCOHOLS & PHENOLS

Oxidation of Alcohol

PHYSICAL PROPERTIES
Alcohols
● organic compounds in w/c a H atom of an aliphatic carbon Dehydration of Alcohol
is replaced with a hydroxyl group
● contain an -OH group connected to a saturated, Acidity Constant (Ka)
sp3-hybridized C atom ● Expresses strength of an acid in water
● two parts:
more acidic larger Ka | smaller pKa
1. contain alkyl group
2. contain functional hydroxyl group
● sweet odor less acidic smaller Ka | larger pKa
● higher BP in comparison to other HC having equal MW
● Hydrogen bonds Effect of alkyl substitution on alcohol acidity
○ formed between water & alcohol ● primarily due to solvation of alkoxide ion formed on acid
○ makes alcohol soluble in water dissociation
● alkyl group attached to hydroxyl group
○ hydrophobic in nature
● react with active metals to form the corresponding alkoxide
(acidic)
Alkoxide
● bases used as reagents in organic chemistry

CHEMICAL PROPERTIES
Alcohols
Phenols
● Exhibit a wide range of spontaneous chemical reactions due
● more acidic than alcohols die to resonance stabilization of
to cleavage of the C-O bond & O-H bond
the phenoxide ion
presence of an oxidizing agent to produce
electron-withdrawing substituent More acidic
Oxidation aldehydes & ketones which upon further
oxidation give carboxylic acids
electron-donating substituent Less acidic
upon treatment with protic acids, alcohols
Dehydration
undergo dehydration to form alkenes

1
PRACTICE: Rank the ff. substances in order of increasing acidity: 1.

2.

NOMENCLATURE

General Classifications of Alcohols

● based on number of organic groups bonded to the
hydroxyl-bearing carbon
3.

IUPAC system names simple alcohols as derivatives of the parent

alkane with a suffix ‘-ol’.
NAMING ALCOHOL
RULE 1: Select the longest carbon chain containing the hydroxyl
group, and derive the parent name by replacing the -e ending of the
corresponding alkane with -ol
RULE 2: Number the alkane chain beginning at the end nearer the 4.
hydroxyl group
RULE 3: Number the substituents according to their position on the
chain, and write the name, listing the substituents in alphabetical order
and identifying the position to which the -OH is bonded

NAMING PHENOL
● Phenol is used as the parent name
● Not -benzene
● Name substituents on aromatic ring by their position from
-OH

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 PREPARATION OF ALCOHOLS REACTION MECHANISM

Alcohols
● Derived from many types of compounds ALCOHOLS FROM CARBONYL COMPOUNDS:
● the hydroxyl can be converted to many other functional REDUCTION
groups
Reduction of a Carbonyl Compound
● gives an alcohol
● Addition of H to a C=O bond

Aldehydes Primary alcohol

Ketones Secondary alcohol

Alcohol synthesis
● Alcohols can be prepared by hydration of alkenes. Because
the direct hydration of alkenes with aqueous acid is
generally a poor reaction in the laboratory, two indirect
methods are commonly used. Sodium borohydride (NaBH₄)
1. Hydroboration–oxidation ● reduction reagent
○ syn, non-Markovnikov hydration ● not sensitive to moisture
product ● can be used with either water or alcohol
2. Oxymercuration–demercuration
○ Markovnikov hydration product

MECHANISM OF REDUCTION
Mechanism of Reduction
● Addition of a nucleophilic hydride ion to the positively
polarized, electrophilic C atom of the carbonyl group
● Alkoxide ion
○ protonated to yield alcohol product

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 ALCOHOLS FROM CARBONYL COMPOUNDS: REACTIONS OF ALCOHOLS
GRIGNARD REAGENTS
CONVERSION OF ALCOHOLS INTO ALKYL HALIDES
react with magnesium to produce Grignard
Organohalides Alcohols to Alkyl Halides
reagents (RMgX)

react with HCl & HBr by SN1 through

Grignard react with carbonyl compounds to yield 3° alcohols
carbocation intermediate
reagents alcohols

converted into halides by treatment SOCl₂ or

1° & 2° alcohols
PBr₃ via SN2 mechanism

CONVERSION OF ALCOHOLS INTO TOSYLATES

Alcohols to Tosylates
● Alcohols react with p-toluenesulfonyl chloride in pyridine
solution to yield alkyl tosylates, ROTos
● C-O Bond remains intact & configuration at a chirality center
is maintained
● Resulting alkyl tosylates react like alkyl halides

LIMITATIONS OF GRIGNARD REAGENTS

Limitation of Grignard Reagents
● if other reactive functional groups are present in the same
molecule, grignard reagent cannot be prepared from an
organohalide DEHYDRATION OF ALCOHOLS TO YIELD ALKENES
Tertiary alcohols
● dehydrated using acid-catalyzed reactions
Acid-catalyzed dehydrations
● usually follow Zaitsev’s rule
● yield the more stable alkene as the major product
Reactivity
● Result of the nature of the carbocation intermediate

MECHANISM OF THE ADDITION OF A GRIGNARD REAGENT

Mechanism of the Addition of a Grignard Reagent
● Grignard reagents act as nucleophilic carbon anions
● Intermediate alkoxide
○ protonated to produce alcohol

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 Practice:
CONVERSION OF ALCOHOLS INTO ESTERS What products would you expect from oxidation of the following
compounds with CrO3 in aqueous acid? With the Dess–Martin
Alcohols to Esters
periodinane?
● rxn can be carried out in a single step
(a) 1-Hexanol
● with the use of a strong acid as catalyst
(b) 2-Hexanol
Reactivity of Carboxylic Acid
● increased by converting it into carboxylic acid chloride
○ which then reacts with alcohol

PROTECTION OF ALCOHOLS

Protection of Alcohols
● done to overcome incompatibility that might arise by
protecting the interfering FG

OXIDATION OF ALCOHOLS

Reagents that Accomplish Oxidation of Alcohols Steps in Protection

1. KMnO₄ 1. Introducing a protecting group to block the interfering
2. CrO₃ function
3. Na₂Cr₂O₇ 2. Carrying out the desired reaction
3. Removing the protecting group

USES OF PHENOLS

Isopropylbenzene
● used to synthesize phenol
● commonly called cumene

REACTIONS OF PHENOLS

oxidized to either aldehydes/carboxylic ELECTROPHILIC AROMATIC SUBSTITUTION REACTIONS

acids Hydroxyl group
● a strongly activating, ortho- and para-directing substituent
primary alcohols
To prepare aldehyde from a primary alcohol in electrophilic aromatic substitution reactions
is to use the I(V)-containing Dess–Martin ● makes phenols substrates for:
periodinane in DCM solvent 1. Electrophilic halogenation
2. Nitration
oxidize easily to give ketones 3. Sulfonation
4. Friedel–Crafts reactions
secondary
effective w/ inexpensive reagents such as OXIDATION OF PHENOLS
Na₂Cr₂O₇ in acetic acid Oxidation of Phenols
● yields a 2,5-cyclohexadiene-1,4-dione, or quinone
Fremy’s Salt
● used in more complex cases
● [(KSO₃)₂NO]

Quinone
● can be easily reduced to hydroquinones
● by reagents such as NaBH₄ & SnCl₂

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 SPECTROSCOPY OF ALCOHOLS PHENOLS EFFECTS OF ALCOHOL

Infrared Spectroscopy Alcohol interferes with the brain's communication

pathways, and can affect the way the brain looks
and works.
Alcohol C-O stretching Near 1050 cm⁻¹ BRAIN
These disruptions can change mood and
absorption
behavior, and make it harder to think clearly and
move with coordination.
Characteristic O-H 3300-3600 cm⁻¹
stretching absorption
Drinking a lot over a long time or too much on a
single occasion can damage the heart, causing
depends on the extent of
exact position of the O]H problems including:
hydrogen-bonding in the
stretch ● Cardiomyopathy
molecule
○ Stretching and drooping of
HEART
heart muscle
● Arrhythmias
PHARMACEUTICAL USES
○ Irregular heart beat
● Stroke
Alcohols & important solvents & synthesis ● High blood pressure
Phenols intermediates
Heavy drinking takes a toll on the liver, and can
Ethanol lead to a variety of problems and liver
solvent, fuel, beverage
(ethyl alcohol) inflammations including:
LIVER ● Steatosis/fatty liver
has diverse uses & gives name to the ● Alcoholic hepatitis
Phenol
general class of compounds ● Cirrhosis
● Fibrosis
are protected because Grignard reagents
Functional Groups can’t be prepared from alkyl halides that Alcohol causes the pancreas to produce toxic
contain reactive FG in the same molecule substances that can eventually lead to
PANCREAS pancreatitis, a dangerous inflammation and
swelling of the blood vessels in the pancreas that
Alcohol Phenols
prevents proper digestion

Mainly used in pharmaceutical

Used in alcoholic
products as antiseptic
beverage - hangover
substances
- alcohol poisoning
Among the most Potential - falls & accidents
Aromatic counterparts of alcohol Short-term Effects - conflict
versatile of all organic
& are more acidic - lowered inhibitions
compounds
- risky behaviors
Can be oxidized to quinones &
Occur widely in nature & alc. consumption contributes to more than
quinones reduced back to Long-term Effects
important industrially 200 different types of diseases & injury
hydroquinones