Alcohols, Ethers, and Epoxides - Synthesis | Organic Chemistry 1

An alcohol is a compound with the general structure ROH. It contains a hydroxy group (OH group) bonded to a sp³ hybridized carbon atom

• Alcohols exhibit molecular polarity due to the electronegativity of oxygen
• Alcohols have a hydrophobic part (the carbon chain) and a hydrophilic part (the OH group):
  - alcohols with less than 6 carbons are soluble in water
  - alcohols with 6 or more carbons are insoluble in water because the non-polar alkyl part is too large to be dissolved in H₂O
  - alcohols of any size are soluble in organic solvents
• The hydroxy functional groups form hydrogen bonds with other alcohol molecules ⇒ alcohols have higher boiling and melting points than the corresponding alkanes
• Alcohols are amphoteric: they can be deprotonated by strong bases or protonated by strong acids

The -ane ending of the corresponding alkane is replaced by -anol

1. Find the longest carbon chain containing the carbon bonded to the OH group
2. Number the carbon chain starting from the end closest to the OH group (if equal, start with the end closest to the first substituent)
3. Write the number corresponding to the location of the OH group before the parent name
   Use the suffixes diol, triol ... if there is more than one OH group
   When an OH group is attached to a ring, the ring is numbered starting with the OH group (the "1" is usually omitted from the name)
4. Identify substituents and assign locators
5. Assemble the substituents alphabetically as prefixe

Alcohols can be prepared by S_N2 reactions with HO^- as nucleophile, by reduction of carbonyls (mainly aldehydes and ketones) or by reaction of carbonyls with organometallics. Alcohols can also be prepared by the hydration of alkenes, as we will see in the chapter on alkenes

Alkyl halides can be converted to alcohols by an S_N2 reactions using HO^- as strong nucleophile. As in all S_N2, the reaction works best with CH₃X and primary alkyl halides

Aldehydes and ketones can undergo a reduction process for the formation of a primary or secondary alcohol with sodium borohydride (NaBH₄) or lithium aluminium hydride (LiAlH₄). NaBH₄ and LiAlH₄ contain a polar metal-hydrogen bond that is a source of nucleophilic hydride H^-

The carbon-oxygen double bond is highly polar, and the slightly positive carbon atom is attacked by the hydride ion of sodium borohydride (NaBH₄) or lithium aluminium hydride (LiAlH₄). The second step is the protonation of the alkoxide in the presence of water

Primary alcohols can be oxidized to form aldehydes and carboxylic acids depending on the reaction conditions; secondary alcohols can be oxidized to ketones

Primary alcohols can be oxidized to aldehydes using pyridinium chlorochromate (PCC) or to carboxylic acids using sodium dichromate (Na₂Cr₂O₇) under acidic conditions. In the case of the formation of carboxylic acids, the alcohol is first oxidized to an aldehyde, which is then oxidized further to the acid

Organometallics are chemical compounds containing at least one chemical bond between a carbon and a metal

The 3 common types of organometallics R-M (with R = alkyl chain) are:

• Alkyl lithium RLi
• Organomagnesium or Grignard reagent RMgBr
• Organocuprates or Gilman reagent R₂CuLi

Organometallics are very powerful nucleophiles that attack at the carbonyl group to give alcohols, forming a new C-C bond. It is one of the most important ways to make carbon-carbon bonds. Addition to aldehydes forms a secondary alcohol, while addition to ketones forms a tertiary alcohol

One way to make ethers is to use the Williamson ether synthesis, an S_N2 reaction in which an alkoxide ion is a nucleophile that displaces a halide ion from an alkyl halide to give an ether

The Williamson ether synthesis works best with CH₃X and primary alkyl halides

Epoxides can be synthesized from a halohydrin via an intramolecular Williamson epoxide synthesis. In this two-step reaction sequence, removal of the proton from the hydroxy group with a base forms an alkoxide which then reacts as a nucleophile in an intramolecular S_N2 reaction to form the epoxide