Experimental and computational probes of a self-assembled capsule

Article abstract of DOI:10.1021/ol0607600

This research was undertaken to explore the interior surface of a synthetic receptor 1.1 with arylpyridines as guests. The interior surface differentiates the guests through the recognition of their nitrogen atoms. Experimental and computational analyses revealed that there is a delicate balance of attractions and repulsions between the host and the lone pairs of guests.

Full text of DOI:10.1021/ol0607600

Supporting Information
Experimental and Computational Probes of
a Self-Assembled Capsule
Tetsuo Iwasawa, Dariush Ajami, and Julius Rebek, Jr.*
The Skaggs Institute for Chemical Biology and the Department of Chemistry, The Scripps Research Institute
MB-26, 10550 North Torrey Pines Road, La Jolla, California 92037
Contents
(
(
(
(
(
(
(
1)
2)
3)
4)
5)
6)
7)
General (page 1S)
Materials (page 1S)
Complete list of author for Guassian, Inc., Pittsburgh, PA, 2002 (page 2S)
Preparation of biaryls in Figure 1b. (page 2S – 6S)
Competitive encapsulation studies. (page 6S)
Reference (page 6S – 7S)
1
13
H and C NMR spectra of biaryls 2a-g (page 8S – 21S), 3b-g (page 22S –
1
34S) 4 (page 35S – 36S), 6d (page 37S – 38S), 7a-c (page 39S – 44S), and all H
NMR spectra of encapsulated biaryls (page 45S – 52S) and competitive
encapsulation studies (page 53S – 57S).
(
1) General
NMR spectra were recorded on a Bruker DRX-600 spectrometer. Proton
1
(
H) chemical shifts, reported in parts per million (ppm), were indirectly referenced to
external tetramethylsilane employing resonances due to trace monoprotio-solvent as an
internal reference. Deuterated NMR solvents were obtained from Cambridge Isotope
Laboratories, Inc., and used without further purification.
(
2) Materials Compounds 3a, 6a – 6c, and 5 were purchased from Aldrich Chemical
Company, and were used as received. The compound 6e was purchased from Acros
Organics, and were used as received. The starting materials for other biaryls,
3
5
-bromopyridine,
2-bromopyridine,
2-bromo-5-methylpyridine, 4-bromotoluene,
acid, 4-ethylphenylboronic acid,
-bromopyrimidine,
p-tolylboronic
1
S

4
-n-propylphenylboronic acid, and 4-n-butylphenylboronic acid, were purchased from
Aldrich Chemical Company., and were used without further purification. The
-bromo-2-methylpyridine was purchased from Apollo Scientific Ltd., and was used
without further purification. The reagents for cross-coupling reactions, Pd(OAc) , K PO
5
2
3
4
,
K CO , and tetra-n-butylammonium bromide were purchased from Aldrich Chemical
2
3
1
Company. The catalyst Pd(OAc)
2
(Cy
2
NH)
2
was prepared according to the literature. The
2
cylindrical cavitand 1 was prepared according to the literature.
(
3) Complete list of author for Guassian, Inc., Pittsburgh, PA, 2002: Frisch, M. J.;
Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.;
Montgomery, Jr., J. A.; Vreven, T.; Kudin, K. N.; Burant, J. C.; Millam, J. M.; Iyengar, S.
S.; Tomasi, J.; Barone, V.; Mennucci, B.; Cossi, M.; Scalmani, G.; Rega, N.; Petersson, G.
A.; Nakatsuji, H.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.;
Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Klene, M.; Li, X.; Knox, J. E.; Hratchian, H.
P.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.;
Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.; Morokuma,
K.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Zakrzewski, V. G.; Dapprich, S.; Daniels, A.
D.; Strain, M. C.; Farkas, O.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J.
B.; Ortiz, J. V.; Cui, Q.; Baboul, A. G.; Clifford, S.; Cioslowski, J.; Stefanov, B. B.; Liu, G.;
Liashenko, A.; Piskorz, P.; Komaromi, I.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M.
A.; Peng, C. Y.; Nanayakkara, A.; Challacombe, M.; Gill, P. M. W.; Johnson, B.; Chen, W.;
Wong, M. W.; Gonzalez, C.; and Pople, J. A.; Gaussian, Inc., Wallingford CT, 2004.
(
4) Preparation of biaryls in Figure 1b. The biaryls 2a – 2g, 3b – 3g, 6d, and 7a – 7c
1
were prepared according to the Suzuki-Miyaura cross-coupling under aerobic conditions.
3
The synthesis of biaryl 4 was referred to the literature. Typical procedures about 2f and 4
1
13
were described below, as well as data of other biaryls. The H NMR and C NMR spectra
of 2a – 2g, 3b – 3g, 4, 6d, and 7a – 7c are also attached in from page 8S – 44S.
2
f: In the air, to a 50 mL one neck flask K
mg, 0.04 mmol), 5-bromo-2-methylpyridine (344 mg, 2 mmol), 4-n-propylboronic acid
394 mg, 2.4 mmol), and EtOH (6 mL) were added. After stirring at ambient temperature
3 4 2 2 2
PO (850 mg, 4 mmol), Pd(OAc) (Cy NH) (23
(
2
S

for overnight, EtOAc (50 mL) was added, and the mixture was washed with water and
brine, and dried over Na SO . Evaporation of the solvent provided the crude product, which
2
4
was purified by column chromatography to afford the desired products in 50% yield (210
1
mg) as pale yellow crystals. H NMR (600 MHz, C D ) δ 8.91 (d, J = 2.4 Hz, 1H), 7.40
6
6
(
7
dd, J = 2.4 Hz, 7.8 Hz, 1H), 7.30 (d, J = 8.4 Hz, 2H), 7.04 (d, J = 8.4 Hz, 2H), 6.74 (d, J =
.8 Hz, 1H), 2.47 (s, 3H), 2.43 (t, J = 7.2 Hz, 2H), 1.52 (dt, J = 7.2 Hz, 7.2 Hz, 2H), 0.849
1
3
(
t, J = 7.2 Hz, 3H). C NMR (150 MHz, C
6
D
6
) δ 157.3, 148.0, 142.2, 136.0, 134.1, 133.8,
+
1
29.4, 127.1, 122.9, 37.9, 24.8, 24.2, 13.9. HRMS (ESI, MH ): Calcd. For C15
H18N:
212.1434. Found: 212.1440.
3
4
0
5
: Under a nitrogen atmosphere, a mixture of K
2
CO
3
(1.10 g, 8 mmol), Pd(OAc)
(1.29 g, mmol)
-bromo-2-methylpyridine (1.37 g, 8 mmol) in a mix of DMF (0.9 mL) / H O (0.35 mL)
2
(90 mg,
.4
mmol),
tetra-n-butylammonium
bromide
4
and
2
was stirred for 2 minutes at 115 °C. Isopropanol (480 mg, 8 mmol) was added. After
stirring for 48 h, the reaction mixture was allowed to cool to ambient temperature. To the
mixture was water and ether, and the organic phase was washed with water and brine, and
2 4
dried over Na SO . Evaporation of the solvent provided the crude product, which was
purified by column chromatography to afford the desired products in 51% yield (377 mg)
1
as white crystals. H NMR (600 MHz, C
6
D
6
) δ 8.70 (d, J = 2.4 Hz, 2H), 7.18 (dd, J = 2.4
1
3
Hz, 7.8 Hz, 2H), 6.66 (d, J = 7.8 Hz, 2H), 2.44 (s, 6H).
C NMR (150 MHz, C D )
6
6
+
δ 157.9, 147.9, 134.0, 130.8, 123.0, 24.2. HRMS (ESI, MH ): Calcd. For C12
H
13
N
2
:
185.1073. Found: 185.1067.
5
1
2
a : H NMR (600 MHz, C D ) δ 8.97 (d, J = 1.2 Hz, 1H), 8.52 (d, J = 3.6 Hz, 1H), 7.39 –
6
6
7
.37 (m, 1H), 7.21 (d, J = 8.4 Hz, 2H), 6.96 (d, J = 8.4 Hz, 2H), 6.78 – 6.77 (m, 1H), 2.10
1
3
(
s, 3H). C NMR (150 MHz, C
6
D
6
) δ 148.8, 148.7, 137.7, 136.6, 135.5, 133.6, 129.9, 127.2,
11N: 170.0964. Found: 170.0970.
+
123.4, 21.0. HRMS (ESI, MH ): Calcd. For C12
H
1
2
7
2
1
1
b: H NMR (600 MHz, C D ) δ 8.89 (d, J = 2.4 Hz, 1H), 7.39 (dd, J = 2.4 Hz, 7.8 Hz, 1H),
6
6
.25 (d, J = 8.4 Hz, 2H), 6.99 (d, J = 8.4 Hz, 2H), 6.73 (d, J = 7.8 Hz, 1H), 2.48 (s, 3H),
1
3
.11 (s, 3H).
C NMR (150 MHz, C
6
D
6
) δ 157.3, 148.0, 137.4, 135.7, 134.1, 133.8,
+
29.9, 127.1, 122.9, 24.2, 21.0. HRMS (ESI, MH ): Calcd. For C13
H
13N: 184.1121. Found:
84.1123.
3
S

1
2
7
8
c: H NMR (600 MHz, C
6 6
D ) δ 8.98 (d, J = 1.8 Hz, 1H), 8.52 (dd, J = 1.8 Hz, 4.8 Hz, 1H),
.41 – 7.39 (m, 1H), 7.25 (d, J = 7.8 Hz, 2H), 7.02 (d, J = 7.8 Hz, 2H), 6.78 (dd, J = 4.8 Hz,
1
3
.4 Hz, 1H), 2.44 (q, J = 7.8 Hz, 2H), 1.08 (t, J = 7.8 Hz, 3H).
C NMR (150 MHz,
C
6
D
6
) δ 148.8, 148.7, 144.1, 136.6, 135.8, 133.7, 128.8, 127.4, 123.4, 28.8, 15.7. HRMS
+
(
ESI, MH ): Calcd. For C13
H
14N: 184.1121. Found: 184.1128.
1
2
d: H NMR (600 MHz, C D ) δ 8.91 (s, 1H), 7.40 (dd, J = 2.4 Hz, 7.8 Hz, 1H), 7.29 (d, J
6
6
=
8.4 Hz, 2H), 7.03 (d, J = 8.4 Hz, 2H), 6.74 (d, J = 7.8 Hz, 1H), 2.47 (s, 3H), 2.45 (q, J =
1
3
7
1
.8 Hz, 2H), 1.09 (t, J = 7.8 Hz, 3H). C NMR (150 MHz, C
6
D
6
) δ 157.3, 148.0, 143.8,
+
35.9, 134.1, 133.8, 128.7, 127.2, 122.9, 28.8, 24.2, 15.8. HRMS (ESI, MH ): Calcd. For
C
14
H
16N: 198.1277. Found: 198.1280.
1
2
7
2
e: H NMR (600 MHz, C
6
D
6
) δ 8.99 (d, J = 2.4 Hz, 1H), 8.52 (dd, J = 2.4 Hz, 4.8 Hz, 1H),
.41 – 7.39 (m, 1H), 7.25 (d, J = 8.4 Hz, 2H), 7.01 (d, J = 8.4 Hz, 2H), 2.42 (t, J = 7.8 Hz,
1
3
H), 1.52 (dt, J = 7.8 Hz, 7.8 Hz, 2H), 0.84 (t, J = 7.8 Hz, 3H).
C NMR (150 MHz,
C
6
D
6
) δ 148.8, 148.7, 142.5, 136.6, 135.8, 133.7, 129.7, 127.3, 123.4, 37.9, 24.8, 13.9.
+
HRMS (ESI, MH ): Calcd. For C14
H
16N: 198.1277. Found: 198.1284.
6
1
2
g : H NMR (600 MHz, C D ) δ 9.00 (d, J = 2.4 Hz, 1H), 8.53 – 8.52 (m, 1H), 7.42 – 7.40
6
6
(
m, 1H), 7.26 (d, J = 8.4 Hz, 2H), 7.03 (d, J = 8.4 Hz, 2H), 6.79 – 6.77 (m, 1H), 2.46 (t, J =
7
7
1
.8 Hz, 2H), 1.49 (dd, J = 7.8 Hz, 7.8 Hz, 2H), 1.24 (dt, J = 7.2 Hz, 7.8 Hz, 2H), 0.86 (t, J =
1
3
.2 Hz, 3H). C NMR (150 MHz, C
6
D
6
) δ 148.8, 148.7, 142.8, 136.6, 135.8, 133.7, 129.4,
+
27.3, 123.4, 35.6, 33.9, 22.6, 14.1. HRMS (ESI, MH ): Calcd. For C15
H
18N: 212.1434.
Found: 212.1434.
7
1
3
b : H NMR (600 MHz, C
6 6
D ) δ 8.49 (d, J = 2.4 Hz, 1H), 8.15 (d, J = 7.8 Hz, 2H), 7.35 (d,
J = 8.4 Hz, 1H), 7.11 (d, J = 7.8 Hz, 2H), 6.99 (dd, J = 2.4 Hz, 8.4 Hz, 1H), 2.13 (s, 3H),
1
3
1
1
.85 (s, 3H).
C NMR (150 MHz, C D ) δ 155.0, 150.5, 138.5, 137.3, 136.8, 131.0,
6
6
+
29.7, 127.0, 119.2, 21.2, 17.8. MS (EI, m/z): 183 (M ).
1
3
c: H NMR (600 MHz, C D ) δ 8.55 − 8.53 (m, 1H), 8.02 (d, J = 7.8 Hz, 2H), 7.36 (d, J =
6
6
7
.8 Hz, 1H), 7.24 – 7.21 (m, 1H), 7.12 (d, J = 7.8 Hz, 2H), 6.75 – 6.73 (m, 1H), 2.55 (q, J =
4
S

1
3
7
.2 Hz, 1H), 1.20 (t, J = 7.2 Hz, 3H).
C NMR (150 MHz, C D ) δ 157.6, 149.9, 145.3,
6
6
+
1
37.5, 136.2, 128.5, 127.3, 121.7, 119.8, 28.9, 15.6. HRMS (ESI, MH ): Calcd. For
C
13
H
14N: 184.1121. Found: 184.1128.
1
3
7
2
1
d: H NMR (600 MHz, C D ) δ 8.49 – 8.48 (m, 1H), 8.17 (d, J = 7.8 Hz, 2H), 7.36 (d, J =
6
6
.8 Hz, 2H), 7.16 – 7.14 (m, 1H), 6.99 (dd, J = 2.4 Hz, 7.8 Hz, 1H), 2.47 (q, J = 7.8 Hz,
1
3
H), 1.85 (s, 3H), 1.09 (t, J = 7.8 Hz, 3H). C NMR (150 MHz, C
44.9, 137.5, 136.9, 131.1, 128.5, 127.1, 119.4, 28.9, 17.8, 15.7. HRMS (ESI, MH ): Calcd.
6
D
6
) δ 155.0, 150.4,
+
For C H N: 198.1277. Found: 198.1283.
1
4
16
1
3
e: H NMR (600 MHz, C
6 6
D ) δ 8.60 – 8.58 (m, 1H), 8.14 (d, J = 8.4 Hz, 2H), 7.38 (d, J =
7
.8 Hz, 1H), 7.14 – 7.11 (m, 3H), 6.65 (m, 1H), 2.44 (t, J = 7.2 Hz, 2H), 1.51 (dt, J = 7.2
1
3
Hz, 7.8 Hz, 2H), 0.83 (t, J = 7.8 Hz, 3H).
C NMR (150 MHz, C D ) δ 157.6, 150.0,
6
6
+
143.7, 137.5, 136.3, 129.1, 127.2, 121.7, 119.8, 38.0, 24.7, 13.9. HRMS (ESI, MH ): Calcd.
For C14H16N: 198.1277. Found: 198.1279.
1
3
8
1
f: H NMR (600 MHz, C D ) δ 8.51 – 8.49 (m, 1H), 8.19 (d, J = 8.4 Hz, 2H), 7.37 (d, J =
6
6
.4 Hz, 1H), 7.16 – 7.14 (m, 3H), 7.00 – 6.97 (m, 1H), 2.45 (t, J = 7.8 Hz, 2H), 1.85 (s, 3H),
1
3
6 6
.53 (dt, J = 7.8 Hz, 7.2 Hz, 2H), 0.85 (t, J = 7.2 Hz, 3H). C NMR (150 MHz, C D )
δ 155.1, 150.5, 143.3, 137.6, 136.9, 131.1, 129.1, 127.0, 119.3, 38.0, 24.8, 17.8, 13.9.
+
HRMS (ESI, MH ): Calcd. For C H N: 212.1434. Found: 212.1436.
1
5
18
8
1
3
g : H NMR (600 MHz, C
6 6
D ) δ 8.60 – 8.59 (m, 1H), 8.15 (d, J = 7.8 Hz, 2H), 7.38 – 7.37
(
m, 1H), 7.13 (d, J = 7.8 Hz, 2H), 7.12 – 7.10 (m, 1H), 6.64 (dd, J = 4.8 Hz, 7.2 Hz, 1H),
2
0
2
.48 (t, J = 7.8 Hz, 2H), 1.49 (dd, J = 7.8 Hz, 7.2 Hz, 2H), 1.23 (dt, J = 7.8 Hz, 7.2 Hz, 2H),
+
.85 (t, J = 7.8 Hz, 3H). HRMS (ESI, MH ): Calcd. For C15
H18N: 212.1434. Found:
12.1439.
9
1
6
d : H NMR (600 MHz, CDCl ) δ 7.49 (d, J = 8.4 Hz, 2H), 7.47 (d, J = 7.8 Hz, 2H), 7.10
3
(
d, J = 7.8 Hz, 2H), 7.07 (d, J = 8.4 Hz, 2H), 2.49 (q, J = 7.8 Hz, 2H), 2.16 (s, 3H), 1.12 (t,
13
J = 7.8 Hz, 3H). C NMR (150 MHz, C
6
D
6
) δ 143.1, 139.1, 138.9, 136.6, 129.8, 128.6,
+
1
27.3, 127.2, 28.8, 21.1, 15.9. MS (EI, m/z): 196 (M ).
5
S

1
0 1
7
7
1
a : H NMR (600 MHz, CDCl ) δ 9.18 (s, 1H), 8.93 (s, 2H), 7.48 (d, J = 8.4 Hz, 2H),
3
13
.31 (d, J = 8.4 Hz, 2H), 2.42 (s, 3H). C NMR (150 MHz, C
6
D
6
) δ 157.1, 154.7, 139.1,
+
34.2, 131.3, 130.1, 126.8, 21.2. MS (EI, m/z): 170 (M ).
1
7
b: H NMR (600 MHz, CDCl ) δ 9.27 (s, 1H), 8.69 (s, 2H), 7.02 (d, J = 8.4 Hz, 2H), 6.94
3
1
3
(
d, J = 8.4 Hz, 2H), 2.40 (q, J = 7.2 Hz, 2H), 1.06 (t, J = 7.2 Hz, 3H). C NMR (150 MHz,
+
C
6
D
6
) δ 157.9, 154.7, 144.9, 134.2, 132.2, 128.9, 127.1, 28.8, 15.6. HRMS (ESI, MH ):
13 2
Calcd. For C12H N : 185.1073. Found: 185.1079.
1
7
c: H NMR (600 MHz, C
6
D
6
) δ 9.27 (s, 1H), 8.69 (s, 2H), 7.03 (d, J = 7.8 Hz, 2H), 6.95 (d,
J = 7.8 Hz, 2H), 2.38 (t, J = 7.2 Hz, 2H), 1.48 (dd, J = 7.8 Hz, 7.2 Hz, 2H), 0.83 (t, J = 7.8
1
3
Hz, 3H). C NMR (150 MHz, C D ) δ 158.0, 154.7, 143.4, 134.1, 132.2, 129.5, 127.0,
3
6
6
+
15 2
7.8, 24.7, 13.8. HRMS (ESI, MH ): Calcd. For C13H N : 199.1230. Found: 199.1226.
(
5) Competitive encapsulation studies
In the competitive encapsulations in Table 1 and Table 2, the concentration of 1 was 4 mM,
and that of each guest was performed in 50 mM. The mixture of the host and guests was
warmed and sonicated to dissolve the host-guest complexes, and placed at ambient
temperature for at least 30 min. The ratios were based on the peaks of alkyl side-chains
1
located at the upfield of H NMR spectra, and determined on the integral values and/or
1
weighing papers of the magnified peaks. All the H NMR spectra of encapsulated guests
and the pairwise competition of Table 1 and Table 2 are shown in from page 45S to 57S.
(
6) Reference
1
2
3
1
4
2
5
6
) Tao, B.; Boykin, D. W. J. Org. Chem. 2004, 69, 4330 – 4335.
) Hayashida, O.; Sebo, L.; Rebek, J., Jr. J. Org. Chem. 2002, 67, 8291 – 8298.
) Hassan, J.; Penalva, V.; Lavenot, L.; Gozzi, C.; Lemaire, M. Tetrahedron 1998, 54,
3793 – 13804.
) Cherioux, F.; Attias, A.-J.; Maillotte, H. Advanced Functional Materials 2002, 12, 203 –
08.
) Inada, K.; Miyaura, N. Tetrahedron 2000, 56, 8661 – 8664.
) Barder, T. E.; Walker, S. D.; Martinelli, J. R.; Buchwald, S. L. J. Am. Chem. Soc. 2005,
6
S

127, 4685 – 4696.
7
) Jung, S.; Kang, Y.; Kim, H.-S.; Kim, Y.-H.; Lee, C.-L., Kim, J.-J.; Lee, S.-K.; Kwon,
S.-K. Eur. J. Inorg. Chem. 2004, 3415 – 3423.
8
9
1
) Chia, W.-L.; Shen, S. –W.; Lin, H.-C. Tetrahedron Lett. 2001, 42, 2177 – 2179.
) Cho, C.-H.; Yun, H.-S.; Park, K. J. Org. Chem. 2003, 68, 3017 -3025.
0) Kano, S.; Yuasa, Y.; Shibuya, S.; Hibino, S. Heterocycles 1982, 19, 1079 – 1082.
1
13
(
(
7) H and C NMR spectra of biaryls 2a-g (page 8S – 21S), 3b-g (page 22S – 34S) 4
1
page 35S – 36S), 6d (page 37S – 38S), 7a-c (page 39S – 44S), and all H NMR spectra
of encapsulated biaryls (page 45S – 52S) and competitive encapsulation studies (page
3S – 57S).
5
7
S

2
a
CH3
N
9
.0
8.0
7.0
6.0
5.0
4.0
3.0
2.0
1.0
ppm (t1)
8S

2a
CH3
N
1
50
100
50
ppm (t1)
9S

2b
CH3
N
CH3
9
.0
8.0
7.0
6.0
5.0
4.0
3.0
2.0
1.0
ppm (t1)
10S

2b
CH3
N
CH3
1
50
100
50
ppm (t1)
11S

2
c
H C
3
N
5
.0
ppm (t1)
12S

2c
H C
3
N
1
50
100
50
ppm (t1)
13S

2
d
H C
3
N
CH3
9
.0
8.0
7.0
6.0
5.0
4.0
3.0
2.0
1.0
ppm (t1)
14S

2
d
H C
3
N
CH3
1
50
100
50
ppm (t1)
15S

2
e
CH3
N
9
.0
8.0
7.0
6.0
5.0
4.0
3.0
2.0
1.0
ppm (t1)
16S

2
e
CH3
N
1
50
100
50
ppm (t1)
17S

2f
CH3
N
CH3
5
.0
ppm (t1)
18S

2
f
CH3
N
CH3
1
50
100
50
ppm (t1)
19S

2
g
H C
3
N
5
.0
ppm (t1)
20S

2g
H C
3
N
1
50
100
50
ppm (t1)
21S

3b
CH3
N
CH3
9
.0
8.0
7.0
6.0
5.0
4.0
3.0
2.0
1.0
ppm (t1)
22S

3b
CH3
N
CH3
1
50
100
50
ppm (t1)
23S

3c
H C
3
CH2
N
9
.0
8.0
7.0
6.0
5.0
4.0
3.0
2.0
1.0
ppm (t1)
24S

3c
H C
3
N
1
50
100
50
ppm (t1)
25S

3d
H C
3
N
CH3
9
.0
8.0
7.0
6.0
5.0
4.0
3.0
2.0
1.0
ppm (t1)
26S

3d
H C
3
N
CH3
1
50
100
50
ppm (t1)
27S

3e
CH3
N
9
.0
8.0
7.0
6.0
5.0
4.0
3.0
2.0
1.0
ppm (t1)
28S

3e
N
1
50
100
50
ppm (t1)
29S

3e
N
1
50
100
50
ppm (t1)
30S