Chemistry Reference
In-Depth Information
cryptand structure developed by the Ciampolini and Micheloni groups, such as 60 and 61,
are kinetically much more active [43]. Their respective pK
a
values in water are
>
14, while
pK
a
ð
60
Þ
H
2
O
=
DMSO
¼
8. Protonation of 60 at the secondary nitrogen atom gives IMHB,
which is stabilized by interactions with bridgehead atoms. The specially pre-organized
structural array of six hydrogen bonds makes the structure particularly stable from a
thermodynamic point of view, albeit no single hydrogen bond is particularly strong,
accounting for its fast protonation/deprotonation kinetics (Figure 2.8).
The substitution of nitrogen for oxygen greatly increases the proton affinity of aza-18-
crown-6 ether (62) relative to 18-crown-6; it was detected to be 250 kcal mol
1
by the
kinetic method. This unusually high basicity is rationalized by a highly symmetrical
structure for protonated 62 in which the three most distant oxygen atoms are able to fold
back and simultaneously hydrogen bond with the protonated nitrogen [44] (Figure 2.8).
14
:
2.3 Amidines
Formamidines are iminoamines built from two nitrogen-containing functionalities, one
imine and one amine. Until recently, amidines and guanidines were generally considered
the strongest synthetically useful auxiliary bases. Their high basicity is the effect of
resonance-stabilized cations. A number of amidine bases are well established reagents in
organic synthesis, the strongest of them that are commercially available are 1,5-diazabi-
cyclo[4.3.0]non-5-ene (DBN) and DBU.
Basicity measurements of a great number of amidines have been conducted, both in
solution and more recently in the gas phase. It was established that the basicity of amidines
depends on the extent and type of substitution at three sites: at the amino and imino nitrogen
atoms and at the functional carbon atom. Since the protonation occurs at the imino nitrogen
atom, substitution at this site has the largest influence on the pK
a
value of amidines,
followed by the substitution at the functional carbon [45]. The pK
a
values of alkyl-N-
substituted amidines measured in ethanol are presented in Table 2.3. Since these sub-
stituents show identical electronic effects, pK
a
s are quite uniform along the series, and the
values indicate a modest superbasicity at the lower part of the superbasicity scale.
As shown by Koppel, solution basicity of amidines could be increased to some extent by
OCH
3
and NCH
3
groups positioned at the end of an alkyl chain [47] (Table 2.4). Here, the
Table 2.3
pK
a
values of amidines (in 98.5% EtOH) [46]
R
R
R
R
N
N
N
N
R
sssssssssssssssssssssssss
Me
2
N
H
Me
2
N
Me
Me
2
N
Et
Me
2
N
i-
Pr
i
Pr
12.56
12.20
12.26
cyclohexyl
12.55
12.20
12.26
n
Pr
12.22
12.46
12.20
12.26
n
hexyl
12.37
12.11
11.95
n
Bu
12.34
12.13
12.22
i
Bu
12.30
11.96
11.93
