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R. Quevedo et al. / Journal of Molecular Structure 1041 (2013) 68–72
for 12 h. After this time, the solution was cooled to 0 °C and
neutralized with concentrated NH4OH. The ammonium sulfate
formed was filtered and washed with isopropanol (3 Â 5 mL). The
filtrate was concentrated under reduced pressure (50 mm Hg,
50 °C) to a third of its volume. The ester was extracted with
chloroform (3 Â 5 mL), the organic phase was dried with anhy-
drous sodium sulfate, and chloroform was removed under reduced
pressure (50 mm Hg, room temperature).
3. Results and discussion
3.1. Formation of macrocyclic amino acid aggregates
To explore the possible formation of aggregates by macrocyclic
amino acid 3 in aqueous solution, 1H NMR spectra in D2O at 25 °C
and 50 °C were recorded. The spectra showed that all signals
shifted approximately 0.4 ppm downfield with increasing temper-
ature. No changes were observed in the number and multiplicity of
the signals; these data show that the aggregates break down with
increasing temperature, thereby exposing the different nuclei.
However, this does not provide information about the type of
interaction present.
L-Alanine isopropyl ester (C6H13NO2ÁHOC3H7) b.p.125–127 °C ,
yield 69%. 1H NMR (CDCl3) d: 1.27 (d,6H, J = 6.8 Hz), 1.29 (d,6H,
J = 6.4 Hz), 1.61 (d,3H, J = 7.2 Hz), 4.11 (q,1H, J = 7.2 Hz), 4.62 (hep-
tet,1H, J = 6.4 Hz), 5.10 (heptet,1H, J = 6.4 Hz), ESI-MS: m/z 131.90
[M + H]+.
L
-phenylalanine isopropyl ester (C12H17NO2ÁHOC3H7) m.p. 81–
To increase the amphiphilic character of compound 3 and gain
information about the formation of aggregates, the synthesis of
the corresponding sodium dicarboxylate 4 was performed. This
product was obtained by dissolving compound 3 in NaOH solution
(10%); the dicarboxylate was precipitated by addition of ethanol.
Azacyclophane dicarboxylate 4 was soluble in water and insol-
uble in organic solvents. The ESI-MS of 4 gave a molecular ion [M]+
at 430.3 (m/z), consistent with a molecular formula of C20H20N2-
Na2O6. The structure was determined by 1H NMR; the spectro-
scopic data were also compared with the data reported for 2 and
3. The 1H NMR spectra presented the characteristic signals of
1,2,4-trisubstituted rings in the aromatic region. Diastereotopic
hydrogens from both tyrosine units were observed as a multiplet
at 2.75 ppm, which overlapped with two methylene groups in
the molecule. The signals corresponding to the chiral methine were
observed at 3.33 ppm. The signals of the N–CH2–Ph groups were
observed as overlapping doublets at 3.70 and 3.52 ppm because
of the presence of two methylenes in the molecule.
84 °C, yield 53%. 1H NMR (CDCl3) d: 1.08 (d,3H, J = 6.4 Hz),
1.16(d,3H, J = 6.0 Hz), 1.28 (d,6H, J = 6.0 Hz), 3.22 (dd,1H,J1,2 =
14 Hz, J1,3 = 8 Hz), 3.39 (dd,1H, J1,2 = 14 Hz, J1,3 = 5,2 Hz), 4.30
(dd,1H, J = 7.6 Hz and J = 5.6 Hz), 4.61 (heptet,1H, J = 6.4 Hz), 4.96
(heptet,1H, J = 6.4 Hz), 7.27 (br s,5H), ESI-MS: m/z 207.95 [M + H]+.
Glycine isopropyl ester (C5H11NO2ÁHOC3H7) b.p. 118–120 °C,
yield 71%. 1H NMR (CDCl3) d: 1.26 (d,6H, J = 6 Hz), 1.27
(d,6H, J = 6 Hz), 3.87 (s,2H), 4.59 (heptet,1H, J = 6.4 Hz), 5.09
(heptet,1H, J = 6.4 Hz), ESI-MS: m/z 235.16 [2 M + H]+.
⁄⁄⁄ -Valine isopropyl ester (C8H17NO2ÁHOC3H7) b.p. undeter-
L
mined by decomposition, yield 43%. 1H NMR (CDCl3) d: 1.09
(d,6H, J = 7.2 Hz), 1.30 (d,12H, J = 6.4 Hz), 2.37 (m,1H), 3.93 (d,1H,
J = 4 Hz), 4.64 (heptet,1H, J = 6.4 Hz), 5.13 (heptet,1H, J = 6.4 Hz),
ESI-MS: m/z 159.90 [M + H]+.
L
-isoleucine isopropyl ester (C9H18NO2ÁHOC3H7) b.p. 122–
124 °C , yield 57%. 1H NMR (CDCl3) d: 0.96 (t,3H, J = 7.2 Hz), 1.03
(d,3H, J = 6.8 Hz), 1.31 (d,12H, J = 6.4 Hz), 1.40 (m,1H), 1.53
(m,1H), 2.08 (m,1H), 4.00 (d,1H, J = 2.8 Hz), 4.63 (heptet,1H,
J = 6.4 Hz), 5.12 (heptet,1H, J = 6 Hz), ESI-MS: m/z 173.96 [M + H]+.
In addition to the signals expected for compound 4, two signals
were observed in the aliphatic region, a triplet at 1.11 ppm and a
quartet at 3.58 ppm. These two signals corresponded to ethanol
molecules used in the synthesis and retained by interactions with
azacyclophane, a behavior observed previously in benzoxazine-
phane-type molecules [6]. The integral ratio between the chiral
carbon hydrogen and alcohol methyl was 1:0.7. Other synthetic
L
-Serine isopropyl ester (C6H13NO3ÁHOC3H7) b.p. 134–135 °C,
yield 35%. 1H NMR (CDCl3) d: 1.29 (d,12H, J = 6.4 Hz), 4.01
(dd,1H,2 J = 12.4 Hz, 3 J = 5.2 Hz), 4.14 (d,1H, J = 12 Hz), 4.18 (br
s,1H), 4.62 (heptet,1H, J = 6 Hz), 5,12 (heptet,1H, J = 6.4 Hz), ESI-
MS: m/z 147.96 [M + H]+.
Fig. 3. 1H NMR data for
L-alanine isopropyl ester-isopropyl alcohol and L-phenylalanine isopropyl ester-isopropyl alcohol.