Amato et al.
JOCArticle
Experimental Section
a stirred solution of (S)-2-anilinomethyl-1-ethylpyrrolidine (600
mg, 3 mmol) in CH2Cl2. The reaction was monitored by TLC
(CH3OH/CHCl3, 9:1). During the reaction a white precipitated
formed. After the disapperance of the substrate (48 h) the pre-
cipitate was filtered and washed with CH2Cl2 (420 mg, 1.21
Materials. Trimethylphenylammonium chloride, benzyltri-
methylammonium chloride, tetrabutylammonium chloride,
tetrabutylammonium bromide, tetrabutylammonium iodide,
acetylcholine chloride, tetraethylammonium chloride, tetra-
methylammonium chloride, (R)-(þ)-1-phenylethylamine, (S)-
(-)-1-phenylethylamine, (R)-proline, and (S)-proline were
commercially available reagent-grade materials and were used
without further purification. NMR experiments were carried
1
mmol, 40% yield). H NMR and ESI-MS measurements in-
dicated that the precipitate was the (S)-2-anilinomethyl-(S)-1-
ethylmethylpyrrolidinium iodide (S,S-2) (see the Supporting
1
Information). H NMR (500 MHz, CDCl3) δ 1.40 (t, J=7.3
Hz, 3H), 2.01 (m, 1H), 2.18 (m, 1H), 2.29 (m, 1H), 2.57 (m, 1H),
3.20 (s, 3H), 3.59 (m, 3H), 3.75 (m, 1H), 3.84 (m, 1H), 4.23 (m,
1H), 4.48 (m, 1H), 5.38 (br s, 1H), 6.74 (d, J = 7.5 Hz, 2H), 6.77
(dd, J=7.5 Hz, 1H), 7.20 (dd, J=7.5 Hz, 2H). Anal. Calcd for
C14H23IN2: C, 48.54; H, 6.70; N, 8.09. Found: C, 48.43; H, 6.64;
N, 8.01.
out at 27 ꢀC on a 500 MHz spectrometer (1H at 499.88 MHz, 13
C
NMR at 125.7 MHz) equipped with a pulse field gradient
module (Z axis) and a tunable 5 mm Varian inverse detection
probe (ID-PFG). Unless otherwise stated, NMR spectra were
obtained in CDCl3 solutions. The chemical shifts (ppm) were
referenced to TMS. A UV/vis spectrophotometer equipped with
a 1 cm path-length cell was used for the determination of Job
plots. ESI-MS spectra were obtained by employing an ES-MS
spectrometer equipped with an ion trap analyzer. The (R)-(þ)-
and (S)-(-)-trimethyl-1-phenylethylammonium iodides were
prepared according to a literature procedure.9
The solution obtained after filtration was dried (MgSO4) and
evaporated under vacuum to give a white solid (400 mg, 1.16
mmol, 39% yield). The solid obtained is a mixture of the two
diastereomers S,S-2 and R,S-2. The separation of the two
diastereomers was based on their different solubilities in water
and in CH2Cl2. Therefore the solid was washed several times
with water until NMR measurements indicated that it was a
pure sample of (S)-2-anilinomethyl-(R)-1-ethylmethylpyrrolidi-
nium iodide (R,S-2). 1H NMR (500 MHz, CDCl3) δ 1.37 (t, J =
7.3 Hz, 3H), 2.03 (m, 1H), 2.24 (m, 2H), 2.53 (m, 1H), 3.19 (s,
3H), 3.60 (m, 3H), 3.67 (m, 1H), 3.81 (m, 1H), 4.16 (m, 1H), 4.34
(m, 1H), 5.37 (br s, 1H), 6.75 (d, J = 7.5 Hz, 2H), 6.77 (dd, J =
7.5 Hz, 1H), 7.18 (dd, J=7.5 Hz, 2H). Anal. Calcd for C14-
H23IN2: C, 48.54; H, 6.70; N, 8.09. Found: C, 48.75;, H, 6.67; N,
8.08. ESI-MS shows the molecular ion peak of the expected
compound.
(R)-2-Anilinomethyl-(R)-1-ethylmethylpyrrolidinium Iodide
(R,R-2). The previous experimental procedure was followed
for the reaction of (R)-2-anilinomethyl-1-ethylpyrrolidine with
CH3I. Unfortunately in this case only the isomer (R)-2-
anilinomethyl-(R)-1-ethylmethylpyrrolidinium iodide was ob-
tained as a pure compound. The product was characterized by
NMR, ESI-MS, and 2-D NMR NOESY measurements (see the
Supporting Information). 1H NMR (500 MHz, CDCl3) δ 1.40
(t, J = 7.3 Hz, 3H), 2.01 (m, 1H), 2.18 (m, 1H), 2.29 (m, 1H),
2.57 (m, 1H), 3.20 (s, 3H), 3.59 (m, 3H), 3.75 (m, 1H), 3.84 (m,
1H), 4.23 (m, 1H), 4.48 (m, 1H), 5.38 (br s, 1H), 6.74 (d, J = 7.5
Hz, 2H), 6.77 (dd, J = 7.5 Hz, 1H), 7.20 (dd, J = 7.5 Hz, 2H).
Anal. Calcd for C14H23IN2: C, 48.54; H, 6.70; N, 8.09. Found:
C, 48.80; H, 6.63; N, 8.06.
The syntheses of the macrocycles and their uranyl complexes
are reported elsewhere.4
(R)- or (S)-Acetylproline. (R)- or (S)- acetylproline was pre-
pared by a slight modification of a literature procedure.10
A
mixture of (R)- or (S)-proline (2.53 g, 22 mmol) and acetic
anhydride (4.2 mL, 44 mmol) in ethyl acetate (44 mL) was
sonicated for 10 min at room temperature. At the end of the
reaction, the solvent was evaporated and the residue dried under
1
vacuum (3.34 g, 21.2 mmol, 96% yield, mp 111-113 ꢀC). H
NMR (500 MHz, CDCl3) δ 1.95 (m, 1H), 2.04 (m, 2H), 2.18 (s,
3H), 2.56 (m, 1H), 3.47(m, 1H), 3.58 (m, 1H), 4.61-4.63 (dd, J=
8.0, 1.7 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ 22.1, 24.7, 27.9,
48.4, 59.6, 172.3, 172.8.
(R)- and (S)-Acetylprolinanilide. (R)- and (S)-acetylprolina-
nilide were prepared as reported in the literature.11 1H NMR
(500 MHz, CDCl3) δ 1.82 (m, 1H), 2.05 (m, 1H), 2.15 (s, 3H),
2.19 (m, 1H), 2.62 (m, 1H), 3.46 (m, 1H), 3.56 (m, 1H), 4.78 (d,
J = 7.6 Hz, 1H), 7.06 (t, J = 7.6 Hz, 1H), 7.29 (t, J=8.05 Hz,
2H), 7.53 (d, J = 8.05 Hz, 1H), 9.66 (br s, 1H).
(R)- and (S)-Anilinomethyl-1-ethylpyrrolidine. (R)- and (S)-
anilinomethyl-1-ethylpyrrolidine were prepared as reported in the
literature.11 1H NMR (500 MHz, CDCl3) δ1.11 (t, J=7.3 Hz, 3H),
1.77 (m, 3H), 1.91 (m, 1H), 2.22 (m, 2H), 2.68 (m, 1H), 2.85 (m,
1H), 3.10 (m, 1H), 3.23 (m, 2H), 4.26 (br s, 1H), 6.62 (d, J = 7.6
Hz, 1H), 6.67 (t, J=7.32 Hz, 2H), 7.17 (t, J=7.32 Hz, 2H).
(S)-2-Anilinomethyl-(S)-1-ethylmethylpyrrolidinium Iodide
(S,S-2) and (S)-2-Anilinomethyl-(R)-1-ethylmethylpyrrolidinium
Iodide (R,S-2). CH3I (1.25 mL, 20 mmol) was added under N2 to
Acknowledgment. We thank the University of Catania for
financial support.
Supporting Information Available: 1H NMR titrations and
Job plots, 1D and 2D-NMR spectra, 2D-NMR NOESY, and
synthesis of proline isomers. This material is available free of
(9) Guijarro, D.; Martinez, P. J.; Najera, C.; Yus, M. Arkivoc 2004, iv, 5.
(10) Anuradha, M. V.; Ravindranath, B. Tetrahedron 1997, 53, 1123.
(11) Suzuki, K.; Igekawa, A.; Mukajyama, T. Bull. Chem. Soc. Jpn. 1982,
55, 3277.
J. Org. Chem. Vol. 75, No. 5, 2010 1443