118 1,2-Azoles and 1,3-Azoles
As a fi nal example in this category we show the synthesis of 2-formylimidazole. An imino-ether (normally formed by
treating a nitrile with HCl gas and an alcohol) is, in this case, prepared from dichloroacetonitrile under basic condi-
tions. The methoxyl group is displaced by reaction with aminoethanal dimethyl acetal giving an amidine; so in the con-
text of this section, one of the ‘carbonyl’ groups is an imine and one is, at this stage, masked as an acetal. Ring closure
is effi cient, the dichloromethyl group being concurrently hydrolysed to reveal the aldehyde group.
Synthesis of 1,3-azoles using tosylmethyl isocyanide
(1,2- and 4,5-bonds made)
All three types of 1,3-azole can be constructed using tosylmethyl isocyanide (TosMIC; TsCH 2 NC). Illustrated below
are imidazole and oxazole examples. The anion of TosMIC can be generated using mild base, though often a stronger
base is employed. Addition of this anion to a carbonyl or imine unit, then ring closure of the heteroatom onto the
isonitrile carbon and fi nally loss of p-toluenesulfi nic acid produces the aromatic azole (compare with the use of
TosMIC for the synthesis of pyrroles, on page 84).
Synthesis of 1,3-azoles via dehydrogenation
The ring synthesis of tetrahydro-1,3-azoles is simply the formation of N,N-, N,O- or N,S-analogues of aldehyde ethyl-
ene glycol cyclic acetals, that is, the reaction of an aldehyde with HXCHR^1 CHR^2 NH 2 with removal of water. They can be
dehydrogenated to produce the aromatic azoles using various oxidants – manganese(IV) oxide in the example below.
Note that the mildness of the conditions allows retention of the integrity of the asymmetric centre.
The construction of 1,3-diaryl 4,5-dihydroimidazolium cations can be achieved by the reaction of 1,2-diamines with
triethyl orthoformate (HC(OEt) 3 ). 1,3-Diarylimidazolium salts, as precursors for N-heterocyclic carbenes such as
1,3-di(2,6-diisopropylphenyl)imidazol-2-ylidene, can be made from a glyoxal bis-imine, the remaining carbon being
provided by ethyl chloromethyl ether.