Structure and Synthesis of Alcohols and Thiols: Chapter 10 Study Notes

Structure and Synthesis of Alcohols

Nomenclature of Alcohols

Alcohols are organic compounds containing a hydroxyl (-OH) group attached to a saturated carbon atom. Their nomenclature follows IUPAC rules, with the suffix -ol added to the parent hydrocarbon name.

• Find the longest carbon chain containing the OH group.

• Number the chain so the carbon holding the OH group gets the lowest possible number.

• Drop the final "e" of the parent hydrocarbon name and use the suffix "ol".

• Name substituents as for alkanes, using prefixes and alphabetical order.

Types of Alcohols:

• Primary alcohol: OH group attached to a carbon bonded to one other carbon.

• Secondary alcohol: OH group attached to a carbon bonded to two other carbons.

• Tertiary alcohol: OH group attached to a carbon bonded to three other carbons.

Examples:

• CH3OH: methanol

• CH3CH2OH: ethanol

• CH3CH2CH2OH: 1-propanol

Diols: Compounds with two hydroxyl groups (e.g., ethylene glycol).

Phenols: Compounds with an OH group directly attached to an aromatic ring.

Physical Properties of Alcohols

Alcohols exhibit unique physical properties due to their ability to form hydrogen bonds.

• Hydrogen bonding leads to higher boiling points compared to alkanes of similar molecular weight.

• Solubility: Alcohols with one to three carbon atoms are miscible with water; solubility decreases as the alkyl group size increases.

Alcohol	Boiling Point (°C)
CH3OH	65
CH3CH2OH	78.5
CH3CH2CH2OH	89
CH3CH2CH2CH2OH	42

Acid and Base Properties of Alcohols

Alcohols can act as both acids and bases, depending on the reaction conditions.

• As a base: $R-OH + H-X \rightarrow R-OH_2^+ + X^-$

• As an acid: $R-OH + Na \rightarrow R-O^-Na^+ + H_2$

• pKa values: Regular alcohols: 16–18; phenols: ~10

Phenol Acidity: Phenol is more acidic than regular alcohols due to resonance stabilization of its conjugate base.

Factors Affecting the Acidity of Alcohols

Electron-withdrawing groups increase the acidity of alcohols by stabilizing the conjugate base, while electron-donating groups decrease acidity.

Alcohol	pKa
CH3CH2OH	15.9
ClCH2CH2OH	14.3
Cl2CHCH2OH	12.2
Phenol	10.0
p-NO2-phenol	7.2
o-NO2-phenol	4.1

Alkoxides

Preparation and Properties

Alkoxides (RO-) are strong bases and nucleophiles, useful in many organic reactions.

• Preparation: Alcohol + sodium metal: $2R-OH + 2Na \rightarrow 2R-O^-Na^+ + H_2$

• Preparation: Alcohol + sodium hydride: $R-OH + NaH \rightarrow R-O^-Na^+ + H_2$

• Alkoxides are used in substitution (SN2) and elimination (E2) reactions.

Organometallic Reagents

Grignard and Organolithium Reagents

Organometallic reagents contain carbon-metal bonds and are important for forming new C–C bonds.

• Grignard reagent: $R-X + Mg \xrightarrow{Et_2O} R-MgX$

• Organolithium reagent: $R-X + 2Li \rightarrow R-Li + LiX$

• Both are strong bases and nucleophiles, reacting with carbonyl compounds to form alcohols.

Reactions with Carbonyl Compounds

• Aldehydes/Ketones: $R_2C=O + R'-MgX \xrightarrow{H_2O} R_2C(OH)R'$

• Acid chlorides/Esters: $RCOCl + 2R'-MgX \xrightarrow{H_2O} R_2C(OH)R'$

General Mechanism: Nucleophilic addition of R- to the carbonyl carbon, followed by protonation.

Reactivity and Sensitivity

• Grignard and organolithium reagents are destroyed by water and alcohols; reactions must be performed in dry conditions.

• They can be used to deprotonate amines and terminal alkynes.

An Overview of Oxidation and Reduction

Definitions and Examples

Oxidation and reduction are fundamental processes in organic chemistry, especially for alcohols.

• Oxidation: Loss of electron density (addition of O, O2, X2; loss of H2).

• Reduction: Gain of electron density (loss of O, O2, X2; addition of H2).

Alcohol Oxidation:

• Primary alcohol: $RCH_2OH \xrightarrow{oxidation} RCHO \xrightarrow{oxidation} RCOOH$

• Secondary alcohol: $R_2CHOH \xrightarrow{oxidation} R_2CO$

• Tertiary alcohol: No simple oxidation

Hydride Reagents

Lithium Aluminum Hydride (LAH) and Sodium Borohydride (NaBH4)

Hydride reagents are used to reduce carbonyl compounds to alcohols.

• LAH: Strong reducing agent; reduces aldehydes, ketones, carboxylic acids, acid halides, and esters.

• NaBH4: Milder; reduces only aldehydes and ketones.

• Both are sources of H- (hydride), which is strongly basic and nucleophilic.

• Reactions must be performed in dry conditions to avoid destruction of the reagent.

General Mechanisms:

• Ketone or aldehyde: $R_2C=O \xrightarrow{LAH/NaBH_4} R_2CHOH$

• Ester: $RCOOR' \xrightarrow{LAH} RCH_2OH$

Thiols (Mercaptans)

Nomenclature of Thiols

Thiols are sulfur analogs of alcohols, containing an SH group.

• Add the suffix -thiol to the parent alkane name (do not drop the "e").

• Number the chain to give the SH group the lowest possible number.

Examples:

• CH3SH: methanethiol

• hexane-2-thiol

• 4-methylhexane-3-thiol

Acidity and Nucleophilicity of Thiols

• Thiols are more acidic than alcohols (pKa ~10).

• Thiolate ions (RS-) are more nucleophilic than alkoxides and are good for SN2 reactions.

Reaction	Product
R-S- + R'-X	R-S-R' (sulfide)

Synthetic Applications

Designing Syntheses

Alcohols can be synthesized from alkyl halides or carbonyl compounds using the reagents and mechanisms described above.

• From alkyl halides: Use substitution reactions or Grignard/organolithium reagents.

• From carbonyl compounds: Use reduction (hydride reagents) or nucleophilic addition (Grignard/organolithium reagents).

Example: Synthesis of 1-butanol from an alkyl halide with no more than five carbons, or from a carbonyl compound.

Additional info: These notes cover the main topics from Chapter 10: Structure and Synthesis of Alcohols, including nomenclature, physical and chemical properties, acidity, synthesis, and related organometallic and hydride chemistry. Mechanisms and examples are provided for key reactions, and tables summarize important trends and comparisons.