PAPER
C-5 Halogenation of Nucleosides in Ionic Liquids
3961
13C NMR (101 MHz, DMSO-d6): d = 40.13, 60.79, 69.96, 84.86,
J = 2.6, 5.3 Hz, 1 H), 3.98–3.88 (m, 2 H), 4.97 (d, J = 5.5 Hz, 1 H),
5.20 (s, 1 H), 5.33 (d, J = 5.0 Hz, 1 H), 5.68 (d, J = 3.4 Hz, 1 H),
7.17 (s, 1 H), 7.79 (s, 1 H), 8.29 (s, 1 H).
1H NMR (400 MHz, DMSO-d6, 80 °C): d = 3.57 (ddd, J = 3.2, 4.9,
12.1 Hz, 1 H), 3.69 (ddd, J = 3.0, 4.8, 12.1 Hz, 1 H), 3.84 (dt,
J = 3.0, 5.0 Hz, 1 H), 4.02–3.94 (m, 2 H), 4.68 (d, J = 4.4 Hz, 1 H),
4.90 (t, J = 5.0 Hz, 1 H), 5.02 (d, J = 3.8 Hz, 1 H), 5.75–5.69 (m, 1
H), 7.19 (s, 2 H), 8.18 (s, 1 H).
13C NMR (101 MHz, DMSO-d6): d = 60.56, 69.46, 74.97, 84.68,
90.12, 140.21, 154.45, 162.00.
LC-MS (ESI-TOF): m/z [M + Na]+ calcd for C9H12ClN3O5 + Na:
300.03632; found: 300.03475.
87.57, 95.66, 140.27, 149.74, 159.17.
LC-MS (ESI-TOF): m/z [M + H]+ calcd for C9H12BrN2O5:
307.0063; found: 1306.99241.
5-Bromouridine (3b)29
White solid; mp 190–195 °C (dec.) [Lit.29 mp 190–198 °C (dec.)].
1H NMR (400 MHz, DMSO-d6): d = 3.59–3.50 (m, 1 H), 3.67 (dd,
J = 6.7, 9.8 Hz, 1 H), 3.84 (dt, J = 2.7, 4.9 Hz, 1 H), 3.96 (d, J = 4.2
Hz, 1 H), 4.01 (dd, J = 4.7, 9.4 Hz, 1 H), 5.04 (d, J = 4.6 Hz, 1 H),
5.25 (t, J = 4.7 Hz, 1 H), 5.40 (d, J = 5.2 Hz, 1 H), 5.70 (d, J = 4.5
Hz, 1 H), 8.45 (s, 1 H), 11.78 (s, 1 H).
13C NMR (101 MHz, DMSO-d6): d = 60.11, 69.25, 73.94, 84.67,
88.49, 95.69, 140.35, 149.97, 159.14.
5-Bromo-2¢-deoxycytidine (7a)22
Highly viscous transparent material, which turned into a white
semi-solid over time.
LC-MS (ESI-TOF): m/z [M + H]+ calcd for C9H12BrN2O6:
322.98733; found: 323.0019.
1H NMR (400 MHz, DMSO-d6, 25 °C): d = 2.02–1.93 (m, 1 H),
2.11 (ddd, J = 3.8, 6.1, 13.2 Hz, 1 H), 3.56–3.48 (m, 1 H), 3.60 (ddd,
J = 3.4, 5.0, 11.8 Hz, 1 H), 3.75 (q, J = 3.4 Hz, 1 H), 4.18 (td,
J = 3.9, 7.7 Hz, 1 H), 5.08 (t, J = 5.0 Hz, 1 H), 5.18 (d, J = 4.3 Hz,
1 H), 6.05 (t, J = 6.4 Hz, 1 H), 6.94 (s, 1 H), 7.80 (s, 1 H), 8.25–8.21
(m, 1 H).
1H NMR (400 MHz, DMSO-d6, 80 °C): d = 2.01 (dd, J = 6.6, 13.3
Hz, 1 H), 2.16 (ddd, J = 3.8, 6.1, 13.3 Hz, 1 H), 3.55 (ddd, J = 3.8,
5.0, 11.8 Hz, 1 H), 3.62 (ddd, J = 3.5, 5.0, 11.8 Hz, 1 H), 3.79 (q,
J = 3.6 Hz, 1 H), 4.21 (td, J = 3.9, 7.8 Hz, 1 H), 4.81 (t, J = 6.5 Hz,
1 H), 4.95 (d, J = 4.4 Hz, 1 H), 7.07 (s, 2 H), 8.17 (s, 1 H).
5-Iodo-2¢-deoxyuridine (4a)29
White solid; mp 172–180 °C (dec.) [Lit.29 mp 170–180 °C (dec.)].
1H NMR (400 MHz, DMSO-d6): d = 2.12 (dd, J = 4.6, 8.5 Hz, 2 H),
3.67–3.51 (m, 2 H), 3.79 (q, J = 3.2 Hz, 1 H), 4.24 (dt, J = 4.3, 8.6
Hz, 1 H), 5.14 (t, J = 4.8 Hz, 1 H), 5.24 (d, J = 4.2 Hz, 1 H), 6.10 (t,
J = 6.5 Hz, 1 H), 8.40 (s, 1 H), 11.66 (s, 1 H).
13C NMR (101 MHz, DMSO-d6): d = 40.18, 60.80, 69.25, 69.99,
84.63, 87.50, 145.03, 150.09, 160.48.
LC-MS (ESI-TOF): m/z [M + H]+ calcd for C9H12IN2O5:
354.97854; found: 354.995241.
13C NMR (101 MHz, DMSO-d6): d = 40.79, 48.60, 60.82, 69.91,
85.40, 86.18, 87.40, 141.93, 153.64, 161.82.
LC-MS (ESI-TOF): m/z [M + Na]+ calcd for C9H12BrN3O4 + Na:
5-Iodouridine (4b)29
White solid; mp 205–210 °C (dec.) [Lit.29 mp 207–209 °C (dec.)].
327.99089; found: 327.98891.
1H NMR (400 MHz, DMSO-d6): d = 3.62–3.53 (m, 1 H), 3.73–3.64
(m, 1 H), 3.87 (dt, J = 2.6, 4.9 Hz, 1 H), 4.01 (dq, J = 4.6, 21.6 Hz,
2 H), 5.07 (d, J = 5.0 Hz, 1 H), 5.26 (t, J = 4.5 Hz, 1 H), 5.41 (d,
J = 5.0 Hz, 1 H), 5.72 (d, J = 4.6 Hz, 1 H), 8.48 (s, 1 H), 11.68 (s, 1
H).
13C NMR (101 MHz, DMSO-d6): d = 60.18, 69.31, 73.95, 84.73,
88.27, 96.17, 145.11, 150.35, 160.48.
5-Bromocytidine (7b)36
White solid; mp 182–185 °C [Lit.36 mp 183–185 °C (dec.)].
1H NMR (400 MHz, DMSO-d6, 25 °C): d = 3.54 (ddd, J = 2.6, 4.8,
12.1 Hz, 1 H), 3.67 (ddd, J = 2.8, 4.8, 12.1 Hz, 1 H), 3.85–3.78 (m,
1 H), 3.98–3.88 (m, 1 H), 4.98 (d, J = 5.4 Hz, 1 H), 5.20 (t, J = 4.8
Hz, 1 H), 5.34 (d, J = 5.0 Hz, 1 H), 5.68 (d, J = 3.4 Hz, 1 H), 6.96
(s, 1 H), 7.79 (s, 1 H), 8.36 (s, 1 H).
1H NMR (400 MHz, DMSO-d6, 80 °C): d = 3.57 (ddd, J = 3.2, 4.6,
12.1 Hz, 1 H), 3.69 (ddd, J = 3.1, 4.4, 12.0 Hz, 1 H), 3.89–3.82 (m,
1 H), 3.98 (s, 1 H), 4.69 (d, J = 2.8 Hz, 1 H), 4.91 (t, J = 4.6 Hz, 1
H), 5.02 (d, J = 1.9 Hz, 1 H), 5.72 (d, J = 3.5 Hz, 1 H), 7.10 (s, 2 H),
8.25 (s, 1 H).
13C NMR (101 MHz, DMSO-d6): d = 60.52, 69.45, 74.98, 84.70,
86.88, 90.11, 142.92, 154.56, 162.49.
LC-MS (ESI-TOF): m/z [M + H]+ calcd for C9H13BrN3O5:
322.003859; found: 322.00262.
LC-MS (ESI-TOF): m/z [M + H]+ calcd for C9H12IN2O6:
370.97346; found: 370.99221.
5-Chloro-2¢-deoxycytidine (6a)21
Highly viscous transparent material, which turned into a white
semi-solid over time.
1H NMR (400 MHz, DMSO-d6, 25 °C): d = 2.03–1.92 (m, 1 H),
2.11 (ddd, J = 3.8, 6.1, 13.2 Hz, 1 H), 3.56–3.50 (m, 1 H), 8.16 (s,
1 H), 3.63–3.57 (m, 1 H), 3.76 (q, J = 3.4 Hz, 1 H), 4.18 (td, J = 3.8,
7.6 Hz, 1 H), 5.08 (t, J = 5.0 Hz, 1 H), 5.18 (d, J = 4.3 Hz, 1 H), 6.06
(t, J = 6.4 Hz, 1 H), 7.16 (s, 1 H), 7.79 (s, 1 H).
1H NMR (400 MHz, DMSO-d6, 80 °C): d = 2.05–1.95 (m, 1 H),
2.20–2.11 (m, 1 H), 3.59–3.52 (m, 1 H), 3.65–3.59 (m, 1 H), 3.79
(q, J = 3.6 Hz, 1 H), 4.21 (td, J = 3.9, 7.7 Hz, 1 H), 4.81 (t, J = 5.1
Hz, 1 H), 4.95 (d, J = 4.4 Hz, 1 H), 6.06 (t, J = 6.5 Hz, 1 H), 7.33–
6.97 (m, 2 H), 8.10 (s, 1 H).
13C NMR (101 MHz, DMSO-d6): d = 41.41, 61.54, 70.62, 86.05,
88.06, 99.52, 139.87, 154.22, 162.01.
5-Iodo-2¢-deoxycytidine (8a)37
White solid; mp 185–188 °C.
1H NMR (400 MHz, DMSO-d6, 25 °C): d = 2.02–1.91 (m, 1 H),
2.10 (ddd, J = 3.8, 6.1, 13.2 Hz, 1 H), 3.51 (ddd, J = 3.5, 4.9, 11.8
Hz, 1 H), 3.59 (ddd, J = 3.4, 5.0, 11.8 Hz, 1 H), 3.75 (q, J = 3.4 Hz,
1 H), 4.20–4.14 (m, 1 H), 5.07 (t, J = 5.0 Hz, 1 H), 5.17 (d, J = 4.3
Hz, 1 H), 6.04 (t, J = 6.4 Hz, 1 H), 6.56 (s, 1 H), 7.76 (s, 1 H), 8.25
(s, 1 H).
1H NMR (400 MHz, DMSO-d6, 80 °C): d = 1.99 (dt, J = 6.5, 13.2
Hz, 1 H), 2.20–2.11 (m, 1 H), 3.58–3.50 (m, 1 H), 3.61 (ddd,
J = 3.7, 4.7, 11.7 Hz, 1 H), 3.78 (q, J = 3.6 Hz, 1 H), 4.20 (td,
J = 3.8, 7.6 Hz, 1 H), 4.80 (t, J = 5.0 Hz, 1 H), 4.94 (d, J = 4.4 Hz,
1 H), 6.05 (t, J = 6.5 Hz, 1 H), 6.88 (s, 2 H), 8.21 (s, 1 H).
LC-MS (ESI-TOF): m/z [M + Na]+ calcd for C9H12ClN3O4 + Na:
284.04140; found: 284.04074
5-Chlorocytidine (6b)35
White solid; mp 212–215 °C (Lit.35 mp 211–214 °C (dec.)].
1H NMR (400 MHz, DMSO-d6, 25 °C): d = 3.54 (ddd, J = 2.7, 4.9,
12.1 Hz, 1 H), 3.67 (ddd, J = 2.8, 4.8, 12.1 Hz, 1 H), 3.81 (dt,
Synthesis 2009, No. 23, 3957–3962 © Thieme Stuttgart · New York