Furans and Thiophenes 105Ring synthesis – disconnections
Various routes for the ring synthesis of furans and thiophenes have been devised; interest in furan construction has
been particularly popular. Here we deal only with the most straightforward strategy, which involves 1,4-di-functional-
ised four-carbon precursors; the new bonds made are shown.
Synthesis of furans and thiophenes from 1,4-dicarbonyl
compounds(1,2-bond made)
The conversion of a 1,4-diketone into a furan is simply a dehydration (it is the converse of the hydrolytic ring opening
discussed on page 100) and is known as the Paal–Knorr synthesis. The most likely sequence has intramolecular addition
of enolic oxygen to the other carbonyl group requiring then, simply loss of water.
1,4-Diketones can be obtained in several ways: the alkylation of a 1,3-keto-ester with an -halo-ketone is one such and
is illustrated below.
Variants on this route require only a C 4 -unit with an oxygen at a terminus, and two degrees of unsaturation located
somewhere in the fi ve-atom sequence. For example, -hydroxy-enones are isomeric and at the same oxidation level
as 1,4-diketones. There are various ways in which to produce such compounds, one of which is the acid (Lewis acid)
promoted eliminative opening of an epoxide. The acid then catalyses the ring closure and conversion into the aromatic
furan via the 1,4-elimination of water (for simplicity, the scheme shows a proton in lieu of the Lewis acid).
To change this strategy into a thiophene synthesis, all that is necessary is to expose a 1,4-dicarbonyl precursor to condi-
tions that convert carbonyl into thiocarbonyl. It is generally not known whether both carbonyl groups are converted,
but exactly comparable sequences lead to the aromatic thiophene, with loss of H 2 S (if both have been thionated) or
H 2 O (if only one has been thionated). Traditionally, the thionation reagent was P 4 S 10 , but Lawesson’s reagent is more
soluble in organic solvents and is now the reagent of choice.