Chemistry Reference
In-Depth Information
solution. The pK
a
values in acetonitrile obtained for biguanides (27-32) were larger than for
the corresponding guanidines (23-26) [69].
By combining the proton sponge skeleton, with highly basic guanidine, a superbasic
TMGN was obtained by Raab [70]. It represents the one of most basic guanidines
experimentally determined, with pK
a
(MeCN)
25.1. This value is comparable with
basicities of MTBD (7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene) and PMG in acetoni-
trile and it is by 5.2 pK
a
units higher than DMAN (1). In a subsequent paper, Kova
¼
c
and Maksic report theoretical PA and pK
a
values for TMGN and related proton sponges
(Table 2.8), as well as giving an insight into the origin of the high basicity of TMGN [71].
The basicity of these bisguanidines is the combined result of the unfavourable nonbonded
repulsions in the initial base, the large PA of guanidine group and strong IMHB present in
the protonated species.
The computational results suggest that the origin of high PA and basicity in guanidine
proton sponges arises from the inherent basicity of the tetramethyl substituted guanidine
fragment and from strong IMHB in the corresponding conjugate acid. The structural and
electronic motif given by guanidine fragments undergoes a very strong cationic resonance
stabilization that is caused by protonation. Resonance stabilization is found not only in the
directly bonded guanidine moiety, but also in the other guanidine fragment, which is more
distant from proton (partial protonation). The strength of IMHB is enhanced by this effect
and contributes to the IMHB stabilization. Furthermore, angular strain effect and steric
repulsion are practically nonexistent in TMGN, contributing to its high basicity. The
nonbonded repulsions in the fluorene proton sponge counterpart [4,5-bis(tetramethylgua-
nidino)fluorene (TMGF)] are higher than in TMGN, which in conjunction with a slightly
stronger IMHB in the corresponding conjugate acids makes TMGF more basic (PA
(MP2)
cevi
263.7 kcal mol
1
).
When the guanidine moiety of proton sponge is incorporated in a five-membered ring,
such as in bis(dimethylethyleneguanidino)naphthalene (DMEGN), it has been shown by
experiment and calculations to be less basic than its TMGN counterpart [72]. The decrease
of DMEGN basicity is the consequence of constraints imposed by the geometry of the five-
membered imidazoline ring. It leads to considerable pyramidalization of ring nitrogen
atoms, thus preventing a perfect
¼
-conjugation of both amino groups with the CN
3
unit. In
TMGN, N(CH
3
)
2
groups are conformationally less constrained, thus being in better
conjugation with the CN3 unit. Basicity could be increased by involving the peripheral
nitrogen atoms in an aromatic planar 1,3-dimethylimidazole system (e.g. by introduction of
C
p
¼
p
-conjugation in imidazoline ring by protonation
indicates that the IMHB is a complex phenomenon, affecting the whole conjugate acid.
IMHB in guanidine and its proton sponge derivatives plays an important role in the basicity
increase [73] (Table 2.8). The strength of IMHB could be deduced from the molecular
structures of protonated species: 80 and 81 have the shortest H
þ
...
C bond in 84). Induction of some
N distance, the highest
hydrogen bond stabilization and largest APAs. At the same time, the N
H
þ
...
N angle
assumes maximal value for 80 and 81 (138
and 137
). On the contrary, N
N distance in a
protonated base (BH
þ
) is not a good indicator of the strength of IMHB. The
...
partial
of other N imino atoms in BH
þ
is a general feature for all molecules.
Good choice of molecular backbone for attachment of bis(tetramethylguanidine) frag-
ments leads to a strong superbase. The substitution of the aromatic backbone could also
affect the basicity, as shown for 1,2-bis(dimethylethyleneguanidino)benzene (86)by
protonation
