Tertiary Amide Rotation in a Nanoscale Host
FULL PAPER
added p-tolylacylchloride (1.6 mL, 12 mmol) and triethylamine
(3.4 mL, 24 mmol). The mixture was stirred overnight at room (76%). H NMR (300 MHz, CDCl3): δ = 7.15 (m, 4 H), 3.71 (s, 2
1-(Piperidin-1-yl)-2-p-tolylethanone (6): Colorless oil. Yield: 2.143 g
1
temp. and then diluted with CH2Cl2 (50 mL), washed with NaOH
(1 ; 20 mL), HCl (1 ; 20 mL), saturated NaHCO3 (20 mL), and
brine (20 mL). The organic phase was then dried with Na2SO4,
filtered, and concentrated in vacuo. The crude residue was purified
on silica gel.
H), 3.59 (m, 2 H), 3.38 (m, 2 H), 2.34 (m, 3 H), 1.56 (m, 4 H), 1.37
(m, 2 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 169.0, 135.6,
131.9, 128.9, 128.0, 46.8, 42.4, 40.3, 25.8, 25.1, 24.0, 20.6 ppm.
HRMS (ESI-TOF): calcd. for C14H19NO [M + H]+ 218.1539;
found 218.1539.
1-(4-Methylpiperidin-1-yl)-2-p-tolylethanone (7): Colorless oil.
Yield: 2.538 g (85%). H NMR (300 MHz, CDCl3): δ = 7.11 (m, 4
Piperidin-1-yl(p-tolyl)methanone (3): Colorless oil. Yield: 1.851 g
(76%). 1H NMR (300 MHz, CDCl3): δ = 7.28 (d, J = 8.0 Hz, 2 H),
7.19 (d, J = 7.9 Hz, 2 H), 3.69 (m, 2 H), 3.36 (m, 2 H), 2.37 (s, 3
H), 1.67 (m, 2 H), 1.63 (m, 2 H), 1.53 (m, 2 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 170.5, 139.3, 133.5, 128.9, 126.9, 48.7, 43.1,
26.4, 25.7, 24.6, 21.3 ppm. HRMS (ESI-TOF): calcd. for
C13H17NO [M + H]+ 204.1383; found 204.1382.
1
H), 4.58 (m, 1 H), 3.81 (m, 1 H), 3.67 (s, 2 H), 2.90 (m, 1 H), 2.53
(m, 1 H), 2.31 (s, 3 H), 1.68–1.50 (m, 3 H), 1.15–0.75 (m, 2 H),
0.88 (d, J = 6.2 Hz, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ =
169.4, 136.0, 132.2, 129.2, 128.3, 46.4, 42.1, 40.7, 34.3, 33.6, 30.9,
21.6, 20.9 ppm. HRMS (ESI-TOF): calcd. for C15H21NO [M +
H]+ 232.1696; found 232.1696.
N,N-Diethyl-2-naphthamide (4): Colorless oil. Yield: 2.043 g (75%).
1H NMR (300 MHz, CDCl3): δ = 7.89–7.80 (m, 4 H), 7.55–7.43
(m, 3 H), 3.43 (m, 4 H), 1.14 (m, 6 H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 171.1, 134.4, 133.2, 132.6, 128.1, 127.6, 126.6, 126.4,
125.5, 123.7, 43.2, 39.2, 14.1, 12.8 ppm. HRMS (ESI-TOF): calcd.
for C15H17NO [M + H]+ 228.1383; found 228.1382.
1-(4,4-Dimethylpiperidin-1-yl)-2-p-tolylethanone (8): Colorless oil.
Yield: 2.229 g (70%). H NMR (300 MHz, CDCl3): δ = 7.11 (m, 4
1
H), 3.67 (s, 2 H), 3.56 (m, 2 H), 3.34 (m, 2 H), 2.31 (m, 3 H), 1.31
(m, 2 H), 1.16 (m, 2 H), 0.91 (s, 6 H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 169.4, 136.0, 132.2, 129.2, 128.3, 42.8, 40.6, 38.7, 38.3,
37.9, 28.9, 27.6, 20.9 ppm. HRMS (ESI-TOF): calcd. for
C16H23NO [M + H]+ 246.1852; found 246.1855.
Pyrrolidin-1-yl(p-tolyl)methanone (5): White solid. Yield: 2.086 g
(92%). 1H NMR (300 MHz, CDCl3): δ = 7.39 (d, J = 8.1 Hz, 2 H),
7.16 (d, J = 7.8 Hz, 2 H), 3.61 (m, 2 H), 3.41 (m, 2 H), 2.34 (s, 3
H), 2.00–1.76 (m, 4 H) ppm. 13C NMR (75 MHz, CDCl3): δ =
169.7, 139.7, 134.2, 128.7, 127.1, 49.5, 46.1, 26.3, 24.3, 21.3 ppm.
HRMS (ESI-TOF): calcd. for C12H15NO [M + H]+ 190.1226;
found 190.1225.
Study of the Rotational Barriers: To prepare the sample for the
study of the encapsulated amides, a deuterated mesitylene solution
(450 µL) of 1 (4 m) and the guest (30 m) was prepared and soni-
cated overnight. To obtain a good signal-to-noise ratio, 250 scans
1
were acquired for each H NMR spectrum. For the measurement
of the rotational barriers outside the capsule, a sample (450 µL) of
a deuterated mesitylene solution of the guest (30 m) was used. In
(4-Methylpiperidin-1-yl)(p-tolyl)methanone (9): Colorless oil. Yield:
1.770 g (68%). 1H NMR (600 MHz, CDCl3): δ = 7.29 (d, J = the competition experiment between 7 and 8, the two guests were
7.9 Hz, 2 H), 7.19 (d, J = 7.9 Hz, 2 H), 4.66 (m, 1 H), 3.75 (m, 1
dissolved in mesitylene in the same concentration (30 m) and then
4 m of 1 was added. The sample was used after sonication over-
H), 2.96 (m, 1 H), 2.76 (m, 1 H), 2.37 (s, 3 H), 1.74 (m, 1 H), 1.64
(m, 2 H), 1.17 (m, 2 H), 0.97 (d, J = 6.4 Hz, 3 H) ppm. 13C NMR night.
(150 MHz, CDCl3): δ = 170.4, 139.3, 133.5, 128.9, 126.9, 48.1, 42.5,
Supporting Information (see footnote on the first page of this arti-
cle): Various spectral data for compound 2–9 and 11 and the com-
puter structures of 8 and 10 encapsulated in 1·1.
34.6, 33.8, 31.1, 21.7, 21.3 ppm. HRMS (ESI-TOF): calcd. for
C14H19NO [M + H]+ 218.1539; found 218.1539.
(3-Methylpiperidin-1-yl)(p-tolyl)methanone (10): Colorless oil.
1
Yield: 2.109 g (81%). H NMR (600 MHz, CDCl3): δ = 7.30 (d, J
Acknowledgments
= 7.9 Hz, 2 H), 7.21 (d, J = 8.2 Hz, 2 H), 4.54 (m, 1 H), 3.72 (m,
1 H), 2.89 (m, 1 H), 2.54 (m, 1 H), 2.39 (s, 3 H), 1.87 (m, 1 H),
1.68 (m, 2 H), 1.53 (m, 1 H), 1.18 (m, 1 H), 0.91 (m, 3 H) ppm.
13C NMR (150 MHz, CDCl3): δ = 170.4, 139.3, 133.5, 128.9, 126.9,
55.1 (br.), 48.3 (br.), 42.7 (br.), 33.1, 31.3 (br.), 25.2 (br.), 21.3,
18.9 ppm. HRMS (ESI-TOF): calcd. for C14H19NO [M + H]+
218.1539; found 218.1540.
We are grateful to the Skaggs Foundation and the National Insti-
tutes of Health (GM 50174) for support. We thank Prof. C. L. Per-
rin for advice and fruitful discussion, and acknowledge Dr. D.-H.
Huang and Dr. L. Pasternack for NMR assistance.
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Azepan-1-yl(p-tolyl)methanone (11): Colorless oil. Yield: 2.0 g
(77%). 1H NMR (600 MHz, CDCl3): δ = 7.26 (d, J = 8.0 Hz, 2 H),
7.18 (d, J = 7.7 Hz, 2 H), 3.66 (m, 2 H), 3.37 (m, 2 H), 2.36 (s, 3
H), 1.83 (m, 2 H), 1.66–1.55 (m, 6 H) ppm. 13C NMR (150 MHz,
CDCl3): δ = 171.6, 138.9, 134.4, 128.9, 126.5, 49.7, 46.3, 29.5, 27.8,
27.2, 26.4, 21.3 ppm. HRMS (ESI-TOF): calcd. for C14H19NO [M
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General Procedure for the Synthesis of Amides 6–8: To a solution
of p-tolylacetic acid (2 g, 13 mmol) in CH2Cl2 (50 mL) was added
the secondary amine (14 mmol), triethylamine (3.7 mL, 26 mmol),
and PyBroP (6.5 g, 14 mmol). The mixture was stirred overnight at
room temp. and then diluted with CH2Cl2 (50 mL), washed with
NaOH (1 ; 20 mL), HCl (1 ; 20 mL), satd. NaHCO3 (20 mL),
and brine (20 mL). The organic phase was then dried with Na2SO4,
filtered, and concentrated in vacuo. The crude residue was purified
on silica gel.
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© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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