Chemistry Reference
In-Depth Information
3
Amidines in Organic Synthesis
Tsutomu Ishikawa and Takuya Kumamoto
Graduate School of Pharmaceutical Sciences, Chiba University,
1-33 Yayoi, Inage, Chiba 263-8522, Japan
3.1
Introduction
Amidines are the nitrogen analogues of carboxylic acids and contain two nitrogen atoms in
amino and imino groups. Amidines are widely used for the constructions of nitrogen-
containing heterocycles because of the functional units of biologically and medicinally
important compounds[1].Then
conjugatedheteroallylicsystems, isoconjugatable tothe
allyl ions resulting in cross-conjugated (or Y-conjugated) hetero
p
-systems [2], control the
total functionality of amidine as bases and/or nucleophiles in organic reactions (Figure 3.1).
Benzamidine reacts with p-nitrophenyl acetate in chlorobenzene at least 15 000 times
faster than n-butylamine, which has a basicity similar to that of benzamidine. This reactivity
is attributable to bifunctional nature of the nucleophile, which can concertedly attack the
carbonyl carbon of the ester and deliver a proton to the carbonyl oxygen (Scheme 3.1) [3].
The bifunctional character allows for amidines to catalyse the transfer of two hydrogen
atoms in allylic rearrangement and enolization (epimerization) through formal intermo-
lecular 1,3-sigmatropic shifts (Scheme 3.2a). However, monofunctional 1,3-rearrangement
is possible, too, and thus amidines can also operate as monofunctional catalysts
(Scheme 3.2b). These modes of reaction are dependent upon the conditions and/or the
amidine substrates used [1a].
On the other hand, in the 1960s sterically hindered bicyclic amidines, 1,8-diazabicylo
[5.4.0]undec-7-ene (DBU) (1) and 1,5-diazabicylo[4.3.0]non-5-ene (DBN) (2), were
introduced as useful dehydrohalogenation reagents in the synthesis of vitaminA. Treatment
p
