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micrOTOF TOF mass spectrometer. Molecular modeling calculations were carried out with
HyperChem software (Release 8.0, trial version from http://www.hypercube.com, USA) [29] using
Austin Model 1 (AM1) method. A Polak-Ribiere algorithm was employed until the root-mean
square (RMS) gradient was 0.01 kcal.mol –1 . All calculations were carried out in vacuo and no
influence of solvents was taken into account. [30]
(2R,3R)-Ethyl 2,3-di(hydrazinecarbonyl)1,4-dioxa-8-azaspiro[4.5]decane-8-carboxylate 26
To a stirred solution of (+)-diethyl L-tartrate 24 (5.7 mL, 33.29 mmol) in ethyl acetate (20 mL)
were added ethyl 4-oxopiperidine-1-carboxylate 25 (5 mL, 33.19 mmol) and boron trifluoride
etherate (17 mL, 82.97 mmol). The mixture was refluxed for 7 h, cooled to room temperature,
carefully quenched with saturated sodium bicarbonate solution (100 mL), extracted with water,
dried with sodium sulfate, filtered off and evaporated in vacuum. The crude oil (10.29 g) was
dissolved without further purification in absolute ethanol (40 mL) and hydrazine monohydrate
was added (3 mL). The mixture was refluxed for 7 h. The solvent was evaporated in vacuum; the
residue was dissolved in water (10 mL) and extracted with ethyl acetate (3×100 mL). The water
extract was dissolved in ethanol (200 mL), dried and evaporated in vacuum to give compound 26
as a yellow gummy material (4.36 g, 13.17 mmol) in 46 % yield. 1 H NMR (400 MHz,
[D 6 ]DMSO, 300 K): δ = 1.3 (t, J = 7.3, CH 3 , 3H), 1.5-1.7 (m, CH 2 , 4H), 3.3-3.4 (m, CH 2 , 4H),
3.9-4.0 (q, J = 7.3, CH 2 , 2H), 3.4 (brs, NH 2 , 4H), 4.4 (brs, CH, 2H), 9.3 (brs, NH, 2H) ppm. 13 C
NMR (100 MHz, [D 6 ]DMSO, 300 K): δ = 15.0, 35.4, 41.8, 61.3, 77.2, 110.9, 155.0, 167.6 ppm;
FT-IR: ṽ = 3309 (NH and NH 2 ), 1668 cm –1 (C[dbond]O); HRMS (ESI, negative ion mode):
Calcd. for [C 12 H 21 N 5 O 6 –H + ]: 330.1436; found 330.1419, (Error, ˗5.0 ppm ).
Dynamic reversibility of tetra-carbohydrazide cyclophane macrocycles
(a) Refluxing compounds 1, 2, 3 and 4 in DMF/MeOH
(2R,3R)-1,4-Dioxaspiro[4.5]decane-2,3-dicarbohydrazide 1 (100 mg, 0.39 mmol), (4R,5R)-1,3-
dioxolane-4,5-dicarbohydrazide 4 (147.3 mg, 0.78 mmol), 4-(4-formylphenoxy)benzaldehyde 2
(175.2 mg, 0.78 mmol) and 4,4'-diformyltriphenylamine 3 (116.67 mg, 0.39 mmol) were mixed
in 5 mL MeOH and 5 mL DMF, 50 µL of catalytic AcOH were added and the mixture was
refluxed for 192 h. Aliquot was taken and 5 µL of DMF was added. Sample was well sonicated,
diluted with ACN and infused into the ESI-TOF mass spectrometer in the positive ion mode.
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