Chemistry Reference
In-Depth Information
theoretical PA values are 257.6 (250.2 [31]) and 250 kcal mol
1
, respectively, while
aqueous pK
a
values are estimated to be 21.0 (44) and 15.8 (43). However, deprotonation
experiments have shown that 44 is ineffective as a base, because the inside proton can be
neither inserted nor removed by conventional proton transfers [32]. A very low energy
barrier for proton transfer between the nitrogen atoms contributes to the high thermody-
namic stability of inside protonated 44 [33]. Calculations show that strain in 45 is not
effectively relieved by protonation, since the calculated PA is only a little higher than that
for 43. Diamines 46 and 47 are quite flexible, and are able to achieve relatively strain-free
conformations. The calculated PAs of 46 and 47 are 253.3 and 243.3 kcal mol
1
, presum-
ably due to the electron-withdrawing acetal groups. Diamines 48 and 49, in which each
nitrogen atom is built into a bicyclic framework, retain enough conformational freedom to
allow one of the lone pairs to interact with external hydrogen bond donors. Their calculated
PAs are 268.6 and 265.8 kcal mol
1
, respectively, making them stronger bases than 44,
since the hydrogen bond in protonated 44 (44H
þ
) is shorter than ideal. There is greater
strain relief when 48 and 49 are protonated than in the case of 44. The C
C angles in 48
average 109.8
, thus signifying perfect sp
3
hybridization. Tricyclic diamines 50 and 51 are
only slightly weaker bases than 49. For the C
2
-symmetrical bis tertiary diamine 52 [34] it
was found that the proton is buried in the core, leaving a hydrophobic surface. Tertiary
amine 52 is more basic than DBU in acetonitrile (pK
a
¼
N
24.7) (Figure 2.6).
Bell [35] has developed a series of triamines 53-55 which show enhanced basicities. The
pK
a
values in water for 53, 55 and 54 are
13.5, 13.1 and 12.8, respectively, due to the
exceptional stability of rapidly protonated 53 obtained by strain relief [36]. Cooperation
between all three nitrogen atoms of a triamine in stabilization of a single proton increases
the pK
a
, as evidenced from the crystal structure of 55H
þ
, where three nitrogen atoms are
participating almost equally in a hydrogen-bonded network. The strength of the hydrogen
bond of 6.2 kcal mol
1
was estimated from dynamic NMR for 55 (Figure 2.7).
Meyer investigated the physico-chemical properties of the tripyrollydinyl-1,4,7-triaza-
cyclononane system 56 [37]. Triamine 56 has a sterically favourable disposition of the three
nitrogen lone pairs towards an electrophilic centre, leading to the high Brønsted basicity in
aqueous solution (pK
a
¼
>
12.8). Due to an effective stabilization of the positive charge, the
PA is up to 20 kcal mol
1
, higher than the values of noncyclic tertiary aliphatic amines, as
estimated by experiment and MP2/6-31
G* calculations. The stabiliz-
ing effect is an energy-lowering interaction between the lone pairs of both the unprotonated
nitrogen atoms with the positive charge of the ammonium group via hydrogen bridges
(Figure 2.7).
Macrocyclic cryptates 57-61 behave as superbasic fast-equilibrating PS due to their
flexibility (Figure 2.8). For instance, bicyclo[6.6.2] tetraamine 57 (cross-bridged cyclam) is
capable of adopting conformations having all four nitrogen lone pairs pointing towards
the cavity centre. The acid dissociation constant for 57H
þ
is larger than 13.5 in water,
and the pK
a
¼
þ
G*//MP2/6-31
þ
24.9 in acetonitrile, which is a comparable basicity to DBU (24.32 in
acetonitrile) [38].
Cage-adamanzanes such as [3]
6
adamanzane 58 capture a proton, which in solution
rapidly shuttles between all four nitrogen atoms. All the nitrogen lone pairs in the polyaza
cage were pointed inward toward the cation, so the complex enjoys both thermodynamic
and kinetic stability [39]. As reported by Springborg, these cryptate species are so
kinetically resistant to deprotonation that it survives in the presence of strong bases and
