Beilstein J. Org. Chem. 2013, 9, 1111–1118.
was obtained. This solution was stored overnight at rt to Kinetics studies
promote gel formation, which was confirmed by the complete Reaction conversions were unambiguously calculated by
absence of gravitational flow upon turning the vial upside 1H NMR analysis of the reaction mixtures according to the inte-
down. Then, a solution consisting of 4-nitrobenzaldehyde gration of the characteristic signals of the species in the reac-
(15.1 mg, 0.1 mmol) and nitromethane (27 μL, 0.5 mmol,) in tion mixture in the presence of an appropriate internal standard.
DMSO (0.5 mL) was added on top of the gel. The vial was Each experimental point represents the average of at least two
stored without shaking for 24 h at rt to allow diffusion. independent experiments. Among various kinetics models, lines
After this time, EtOAc (1 mL) and EtOH (1 mL) were presented in the kinetics plots show best-fits of the first-order
added to quench the reaction and remove the supernatant model for each case (i.e., [NO2R] ≥ [aldehyde]). Nevertheless,
organic layer. Next, the gel was gently heated to obtain a solu- the possibility of more complex kinetics was also suggested in
tion, which was further diluted with H2O (2 mL) and EtOAc some cases where the fits were not ideal (e.g., TMEDA: pres-
(2 mL), and finally extracted with EtOAc (2 × 2 mL). The ence of a fast introductory phase and subsequent stagnation of
combined organic layers were dried over anhydrous Na2SO4, the reaction rate: t = 30 s, yield 52%; t = 60 s, yield 60%; t =
filtered and evaporated under reduced pressure to obtain the 90 s, yield 66%; t = 120 s, yield 67%; t = 180 s, yield 63%; t =
crude product. The 1H NMR yield was determined as described 240 s, yield 67% (Figure S3) [8]). Due to the fact that not all
above.
reactions reached 100% yield, data fitting was made according
to the variation of ln[(Ct − C∞)/(C∞ − C0)] with time, where Ct
is the concentration at a given time t; C∞ the final concentration
Notes
a) A control experiment to quantify any possible effect of the (at infinite time) and C0 the initial concentration (at t = zero
hydrogel on the reaction was carried out as follows: PSTA time). For reaction conversions close to 100%, plots of ln(Ct/
(6 mg), 4-nitrobenzaldehyde (15.1 mg, 0.1 mmol), nitromethane C0) versus time provided consistent results (C∞ = 0). Under
(27 mL, 0.5 mmol,) H2O (0.3 mL) and DMSO (0.5 mL) were these considerations, minor differences were observed between
mixed in a screw cap vial (4 mL) and the mixture was stirred the exponential and linear fits. All errors reported for the rate
for 24 h at rt. After this time, EtOAc (1 mL) and EtOH (1 mL) constants k were calculated by graphical analysis. Solubility of
were added to quench the reaction. The mixture was diluted gelatin during the reaction was found to play no role in the pro-
with H2O (2 mL) and EtOAc (2 mL), and finally extracted with duct yield.
EtOAc (2 × 2 mL). The combined organic layers were dried
over anhydrous Na2SO4, filtered and evaporated under reduced
Supporting Information
pressure to obtain the crude product. The 1H NMR yield was
determined as described above.
Supporting Information File 1
Optimization studies, additional experiments, figures and
b) For the reaction with cooked gelatin purchased from the
supermarket, 10 g of gelatin sheets were dissolved in 100 mL
water by heating it on a heating plate, and the mixture was
stored overnight in the fridge. The reactions were carried out
with 20 mg of the formed hydrogel.
tables.
Acknowledgements
c) All condensation products are known and the spectroscopic
data obtained from the NMR analysis of the reaction mixtures
were in agreement with those reported in the literature (see
This work was supported by the Universität Regensburg
(Förderlinie C des Finanziellen Anreizsystems für Drittmit-
teleinwerbung), Ministerio de Ciencia e Innovación – FEDER
(CTQ2010-17436), Gobierno de Aragón-FSE (research group
E40). B.B.D. thanks CSIR for appointment as a Sr Research As-
sociate (Scientist’s Pool Scheme). We are also indebted to Prof.
M.G. Finn for valuable discussions.
Recycling experiments
In general, acetone or ethanol (1 mL per 2 mg of catalyst) could
be used to precipitate all of the gelatin catalyst, which could be
further separated by centrifugation (10 min, 3800 rpm), washing
with EtOAc (2 mL), centrifugation cycles, and finally drying of
the residue under vacuum before the next catalytic cycle. Addi-
tionally, direct extraction of aqueous solutions with EtOAc may
allow reuse of the aqueous solution of the catalyst in subse-
quent cycles.
References
1. Imeson, A. Food stabilisers, thickeners and gelling agents;
Wiley-Blackwell Pub.: Chichester, U.K., 2010.
2. Kang, S.-Z.; Wu, T.; Li, X.; Mu, J. Colloids Surf., A 2010, 369, 268–271.
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