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(4R,5R)- and (4S,5S)-dimethyl-2,2-dimethyl-1,3-dioxolane-4,5-dicarboxylate
1 and 3 reacted with hydrazine hydrate in absolute
ethanol to afford the corresponding dicarbohydrazides 2 and 4 in
good yields (Scheme 1).
The reaction conditions were tuned in terms of stoichiometries and
concentration of the reactants to form selectively the [2+2]-macrocycles.
32
Figure 1. Bird's-eye view for the computed structure of chiral dicarbohydrazides 2 and 4
using MM+ method and a Polak-Ribiere conjugate gradient with rms ˂ 0.01 Kcal.mol –1 .
Scheme 1. Synthetic route to chiral dicarbohydrazides 2 and 4.
Similarly, chiral dihydrazides 7 and 9 were prepared from (+)-
diethyl L-tartrate 6 and (–)-diethyl D-tartrate 8, respectively by
reacting with 1,1-dimethoxycyclohexane 5 as shown in Scheme 2.
Structures of dicarbohydrazides 2, 4, 7 and 9, which constitute the
building blocks of the novel macrocycles, were fully elucidated
using various spectroscopic techniques.
The novel hydrazides showed fascinating molecular self-assembly
in the gas phase as confirmed by ESI-TOF MS (See supporting
information and table 1). Dicarbohydrazides 2, 4, 7 and 9 assembled
to hydrogen-bonded dimeric, sodium adduct of dimeric and trimeric
macrocycles. Protonated molecular ions [M+H] + for tetrameric
macrocycles were observed only with dicarbohydrazides 7 and 9.
Molecular modeling studies at the MM+ and AMBER force fields
were conducted to simulate such interesting interactions. Energyminimised
structures are shown in Figure 2. To the best of our
knowledge self-assembly of four molecules in the gas phase has not
been reported yet.
Scheme 2. Synthetic route to chiral dicarbohydrazides 7 and 9.
1 H-NMR spectrum for (i.e., dicarbohydrazide 2) showed broad
signals at δ 9.3, 4.4, 4.2 and 1.3 ppm corresponding to (NH), (CH),
(NH 2 ) and (CH 3 ), respectively. 13 C-NMR spectrum showed four
signals at δ 167.8, 112.2, 77.2 and 26.6 ppm corresponding to
(C=O), quaternary C-atom, (CH) and (CH 3 ), respectively. FT-IR
spectrum showed a strong absorption band at ṽ 1660 cm -1
corresponding to the stretching vibration of the carbonyl group. It
showed also weak absorption bands at ṽ 3316 cm -1 corresponding to
the primary and secondary amino moieties. ESI-TOF MS showed
the expected pseudo-molecular ion peak at 241.0900 Da (M+Na + ).
Molecular modeling at the MM+ level showed that the novel
dicarbohydrazides adopt conformations in which the carbonyl
groups are anti-oriented to each other. These conformations are
stabilised by strong n → π* interaction and intramolecular hydrogen
bonding (C=O…HN) (Figure 1). 31
We next examined the behaviour of the novel dicarbohydrazides
towards the cyclocondensation reaction with aromatic dialdehydes.
Figure 2. Molecular modeling simulation for self-assembly of chiral dicarbohydrazides
7 and 9 using MM+, AMBER force field methods and a Polak-Ribiere conjugate
gradient with rms ˂ 0.01 Kcal.mol –1 . (a) Self-assembled two molecules of 7 or 9 and (b)
macrocycle (a) hosting Na + ion.
(4R,5R)- and (4S,5S)-2,2-dimethyl-1,3-dioxolane-4,5-dicarbohydrazide
2 and 4 reacted with 4-(4-formylphenoxy)-benzaldehyde and
4,4ʹ-diformyltriphenylamine to yield macrocycles 10-13 in quantitative
yields 94-99%. Spiro-macrocycles 14-17 were synthesized
as similar way as previously described from (2R,3R)- and (2S,3S)-
1,4-dioxaspiro[4.5]decane-2,3-dicarbohydrazide 7 and 9 (Scheme 3).
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