6
H. Saeidian and M. Abdoli
4. Spectral data of the N-monoalkyl and N,Nꢀ-dialkyl Topiramate derivatives
OSO2NHR
1
O
O
O
11
6
5
2
3
8
12
4
O
O
7
9
10
1
Topiramate: H NMR (500 MHz, CDCl3): δ 1.38, 1.46, 1.52, 1.59 (4 × s, 12H, –C(CH3)2),
3.81–3.83 (m, 1H, H-6), 3.94 (dd, 1H, J 13.0, 1.8 Hz, H-6), 4.26–4.29 (m, 2H, H-1 and H-5),
4.33–4.38 (m, 2H, H-1 and H-3), 4.65 (dd, 1H, J 7.9, 2.6 Hz, H-4), 4.91 (br s, 2H, NH2). 13C
NMR (125 MHz, CDCl3): δ = 24.0, 25.4, 26.2, 26.8, 61.7, 70.4, 70.9, 71.0, 71.5, 101.4, 109.7,
109.8.
N-methyl Topiramate (4a): 1H NMR (400 MHz, CDC13): δ 1.37, 1.45, 1.50, 1.57 (4 × s, 12H,
–C(CH3)2), 2.85 (s, 3H, N-CH3), 3.78 (ABdd, 1H, J 12.8, 0.4 Hz, H-6), 3.93 (ABdd, 1H, J 12.8,
2.0 Hz, H-6), 4.14 (ABd, 1H, J 10.8 Hz, H-1), 4.20 (ABd, 1H, J 10.4 Hz, H-1), 4.27 (dd, 1H, J
7.6, 1.2 Hz, H-5), 4.36 (d, 1H, J 2.8 Hz, H-3), 4.64 (dd, 1H, J 7.6, 2.8 Hz, H-4), 4.78 (br s, 1H,
NH). 13C NMR (100 MHz, CDCl3): δ 24.0, 25.2, 25.8, 26.5, 29.8, 61.3, 69.9, 70.0, 70.2, 70.6,
100.8, 109.2, 109.3. Anal. Calcd for C13H23NO8S: C, 44.18; H, 6.56; N, 3.96. Found: C, 44.27;
H, 6.62; N, 3.89.
N-ethyl Topiramate (4b): 1H NMR (400 MHz, CDCl3): δ 1.25 (t, 3H, J 7.2 Hz, N-CH2CH3),
1.36, 1.44, 1.49, 1.57 (4 × s, 12H, –C(CH3)2), 3.23 (m, 2H, N-CH2CH3), 3.78 (ABd, 1H, J 12.8,
0.4 Hz, H-6), 3.93 (ABdd, 1H, J 12.8, 1.6 Hz, H-6), 4.13 (ABd, 1H, J 10.4 Hz, H-1), 4.20 (ABd,
1H, J 10.4 Hz, H-1), 4.27 (dd, 1H, J 8.0, 1.2 Hz, H-5), 4.36 (d, 1H, J 2.4 Hz, H-3), 4.63 (dd,
1H, J 8.0, 2.4 Hz, H-4), 4,68 (t, 1H, J 6.0 Hz, NH). 13C NMR (100 MHz, CDCl3): δ = 15.0,
24.0, 25.2, 25.8, 26.5, 38.9, 61.3, 69.7, 69.9, 70.1, 70.6, 100.9, 109.15, 109.22. Anal. Calcd for
C14H25NO8S: C, 45.77; H, 6.86; N, 3.81. Found: C, 45.71; H, 6.91; N, 3.75.
N-propyl Topiramate (4c): 1H NMR (400 MHz, CDCl3): δ 0.95 (t, 3H, J 14.8 Hz, N-
CH2CH2CH3), 1.35, 1.42, 1.48, 1.55 (4 × s, 12H, –C(CH3)2), 1.60 (m, 2H, N-CH2CH2CH3),
3.12 (m, 2H, N-CH2CH2CH3), 3.76 (ABd, 1H, J 13.2 Hz, H-6), 3.91 (ABdd, 1H, J 12.8, 0.8 Hz,
H-6), 4.11 (ABd, 1H, J 10.4 Hz, H-1), 4.18 (ABd, 1H, J 10.4 Hz, H-1), 4.25 (d, 1H, J 7.6 Hz,
H-5), 4.35 (d, 1H, J 2.4 Hz, H-3), 4.62 (dd, 1H, J 8.0, 2.4 Hz, H-4), 4.93 (br s, 1H, NH). 13C
NMR (100 MHz, CDCl3): δ 11.0, 22.7, 23.9, 25.1, 25.7, 26.4, 45.3, 61.2, 69.4, 69.8, 70.0, 70.6,
100.8, 109.0, 109.1.
N-benzyl Topiramate (4d): 1H NMR (400 MHz, CDCl3): δ 1.36, 1.42, 1.47, 1.55 (4 × s, 12H,
–C(CH3)2), 3.73 (ABd, 1H, J 13.2 Hz, H-6), 3.89 (ABd, 1H, J 13.2 Hz, H-6), 4.13 (ABd, 1H, J
10.4 Hz, H-1), 4.21 (ABd, 1H, J 9.6 Hz, H-1), 4.23 (d, 1H, J 7.6 Hz, H-5), 4.31–4.32 (m, 3H,
N-CH2 and H-3), 4.60–4.65 (m, 1H, H-4), 5.33 (br s, 1H, NH), 7.31–7.38 (m, 5H, Ar). 13C NMR
(100 MHz, CDCl3): δ 24.0, 25.2, 25.6, 26.5, 47.7, 61.3, 69.86, 69.95, 70.2, 71.6, 109.2, 109.3,
128.15, 128.20, 128.8, 136.2. Anal. Calcd for C19H27NO8S: C, 53.13; H, 6.34; N, 3.26. Found:
C, 53.23; H, 6.27; N, 3.34.
N,Nꢀ-dibenzyl Topiramate (5d): 1H NMR (400 MHz, CDCl3): δ 1.32, 1.40, 1.51, 1.56 (4 × s,
12H, -C(CH3)2), 3.78 (ABd, 1H, J 12.4 Hz, H-6), 3.94 (ABd, 1H, J 12.4 Hz, H-6), 4.18 (ABd,
1H, J 10.4 Hz, H-1), 4.22 (ABd, 1H, J 10.0 Hz, H-1), 4.26–4.33 (m, 2H, H-5, H-3), 4.31 (ABd,
2H, J 14.8 Hz, N-CH2), 4.44 (ABd, 2H, J 14.8 Hz, N-CH2), 4.64 (dd, 1H, J 7.6, 2.4 Hz, H-4),
7.29–7.4 (m, 10H, Ar). 13C NMR (100 MHz, CDCl3): δ 24.1, 25.2, 26.0, 26.6, 50.9, 61.4, 69.2,
70.0, 70.7, 100.9, 109, 128.2, 128.7, 129.0, 135.0.