Unit 25: Organic Synthesis — Short Questions

In synthesis, the target molecule is built up (forward direction) starting from simple, commercially available compounds through a series of real reactions. In retrosynthesis, the process runs in the opposite direction: the target molecule is imaginatively broken down (disconnected) into simpler, more easily available starting materials, using an open-ended retrosynthetic arrow (⟹). Synthesis tells us how to actually make the molecule; retrosynthesis is the planning tool used to work out that synthetic route.

The carboxylic acid is first converted to its acid chloride using SOCl2, and the acid chloride is then treated with ammonia to give the amide.
CH3COOH + SOCl2 → CH3COCl + SO2 + HCl
CH3COCl + 2NH3 → CH3CONH2 + NH4Cl

A synthon is an imaginary fragment (often an ionic species) produced by disconnecting the target molecule; it represents the building block needed for synthesis but is usually too unstable to exist or be used as an actual reagent. A synthetic equivalent is the real, stable reagent molecule that is capable of carrying out the chemical function of that synthon in an actual reaction. So the synthetic equivalent is the practical, usable form of the synthon.

K2Cr2O7/H2SO4 (acidified potassium dichromate) is commonly used to oxidize organic compounds, e.g. oxidizing a primary alcohol to an aldehyde and then to a carboxylic acid, or toluene (with KMnO4/H2SO4) to benzoic acid.

A disconnection is the imaginary breaking of a bond in the target molecule that results in considerable structural simplification. It is the key operation of retrosynthesis, generating two synthons from the target molecule; a series of such disconnections eventually leads back to simple, easily available starting materials.

FGI is used to install a functional group that is easier to attach by a known reaction and then convert it into the functional group actually required. For example, in synthesizing aniline, the -NH2 group cannot easily be attached to benzene directly, so FGI converts it (in the retrosynthetic plan) to -NO2, since a nitro group is easily introduced by electrophilic substitution (nitration) and can then be reduced to the amino group.

A nitro group can be reduced to an amino group using tin and hydrochloric acid (Sn/HCl).
Ar-NO2 + 6[H] (Sn/HCl) → Ar-NH2 + 2H2O

A carboxylic acid is reduced directly to a primary alcohol using lithium aluminium hydride (LiAlH4), a strong reducing agent.
RCOOH --LiAlH4--> RCH2OH

Ethane is first converted to ethyl chloride (free-radical chlorination), hydrolyzed to ethanol, and then oxidized to acetic acid.
CH3-CH3 --Cl2, light--> CH3-CH2-Cl --KOH(aq)--> CH3-CH2-OH --K2Cr2O7/H2SO4 (excess)--> CH3-COOH

Ethene undergoes acid-catalyzed addition of water (hydration) to give ethanol.
CH2=CH2 + H2O --H2SO4 (catalyst)--> CH3-CH2-OH

1-Chloropropane undergoes base-induced elimination (dehydrohalogenation) using alcoholic potassium hydroxide with heating to give propene.
CH3-CH2-CH2-Cl --KOH (alcoholic), heat--> CH3-CH=CH2 + KCl + H2O

Acetic acid is reduced directly to ethanol using lithium aluminium hydride.
CH3-COOH --LiAlH4--> CH3-CH2-OH