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H. F. Nour, A. M. Lopez-Periago and N. Kuhnert
(b) Mixing equimolar quantities of dialdehydes 19 and 33 with
(1R,2R)-1,2-diaminocyclohexane 1 in DCM
To a stirred solution of (1R,2R)-1,2-diaminocyclohexane 1
(15.62 mg, 0.137 mmol) in DCM (182 mL) were added 3-
phenoxybiphenyl-4,4′-dicarbaldehyde 19 (18.12 mg, 0.06 mmol)
in DCM (182 mL) and ethyl 4-[4,4′-diformyl-(1,1′-biphenyl)-3-yl]-
piperazine-1-carboxylate 33 (23.3 mg, 0.06 mmol) in DCM
(182 mL). The mixture was stirred at room temperature for 46 h.
Aliquots were taken at defined time intervals and a few drops
of MeOH were added to the sample before it was infused into
the ESI-TOF mass spectrometer.
RESULTS AND DISCUSSION
The formation of trianglimines constitutes a complex multistep
reaction, in which six imine bonds are formed in a single
one-pot reaction at relatively high concentrations of all reactants.
Gawroński et al. reported that the reactions of (1R,2R)-
1,2-diaminocyclohexane 1 with terephthaldehyde 2 and
isophthaldehyde 3 resulted in clean formation of the corresponding
trianglimines 4 and 5 after 2–3 h of stirring at room temperature
(Fig. 1). [9] We decided to study the mechanism of this reaction
in detail taking advantage of the capability of ESI-MS in the positive
ion mode to potentially detect all possible reaction intermediates.
The reactions were conducted between 1 and 2 or 3 at a
concentration of 0.1 M in DCM at room temperature. For MS
analysis, aliquots of the reaction mixture were taken at different
time intervals, diluted to a concentration of 0.1 mM and directly
infused into the ESI-TOF mass spectrometer.
Cyclocondensation mechanism of trans-(1R,2R)-1,2-
diaminocyclohexane with terephthaldehyde and
isophthaldehyde
By monitoring the reaction between (1R,2R)-1,2-diaminocyclohexane
1 and dialdehyde 2 and 3 in real time with ESI-TOF
MS, a total of eleven different reaction intermediates could be detected
by the appearance of their protonated pseudomolecular
ions and their structures were assigned based on their highresolution
m/z values (Figs. 2 and 3). The reaction intermediates
include a series of mono- topenta-imines 7–17 along with some
long-chain higher polyimine oligomers (not shown in figures;
for structures and ESI-TOF data, see Supplementary Information).
In the course of the reaction the higher oligomers disappear
at the expense of the final macrocyclization products.
Interestingly, the relative intensity of the ions corresponding
to the intermediates of the reaction with isophthaldehyde and
terephthaldehyde are very different, suggesting that the
mechanism of formation of the two geometrically distinct
macrocycles is different. For terephthaldehyde 2 the intermediates
with the two most intense signals correspond to monoimine
7 and bis-imine 8 bearing two terminal amino moieties.
In contrast, for isophthaldehyde 3 the bis-imine 14 with two
Figure 2. ESI-TOF mass spectrum in the positive ion mode recorded after 10 min from
the start of the reaction of (1R,2R)-1,2-diaminocyclohexane 1 with terephthaldehyde 2;
the products were detected as [M+H] + ions.
1072
Figure 3. ESI-TOF mass spectrum in the positive ion mode recorded after 10 min from
the start of the reaction of (1R,2R)-1,2-diaminocyclohexane 1 with isophthaldehyde 3;
the products were detected as [M+H] + ions.
wileyonlinelibrary.com/journal/rcm Copyright © 2012 John Wiley & Sons, Ltd. Rapid Commun. Mass Spectrom. 2012, 26, 1070–1080