H. Wójtowicz-Rajchel, H. Koroniak, A. Katrusiak
FULL PAPER
N3–H) ppm; for E isomer: δ = 5.86 (d, J = 8 Hz, 1 H,C5–H), 6.82
H, C2–H), 8.51 (s, 1 H, C8–H) ppm. 19F NMR (282 MHz, [D6]-
DMSO, 25 °C): for Z isomer: δ = –54.38 (dd, J = 7 and 17 Hz, 3
(dq, J = 5 and 7 Hz, 1 H, Hβ), 7.90 (d, J = 8 Hz, 1 H, C6–H),
11.88, (br. s, 1 H, N3–H) ppm. 1H NMR (CDCl3, 25 °C): for Z F, CF3), –90.48 (dq, J = 17 and 32 Hz, 1 F, Fα) ppm; for E isomer:
isomer: δ = 5.90 (dq, J = 7 and 29 Hz, 1 H, Hβ), 5.94 (d, J = 8 Hz, δ = –57.18 (dd, J = 7 and 14 Hz, 3 F, CF3), –70.86 (dq, J = 6 and
1 H, C5–H), 7.41 (d, J = 8 Hz, 1 H, C6–H), 9.07 (br. s, 1 H, N3–
14 Hz, 1 F, Fα) ppm. MS (EI): m/z = 247 [M]+ (100%). C8H5F4N5
H); for E isomer: δ = 5.87 (m, 1 H, Hβ), 5.91 (d, J = 8 Hz, 1 H,C5– (247.16): calcd. C 38.88, H 2.04, N 28.34; found C 38.54, H 2.42,
H), 7.19 (d, J = 8 Hz, 1 H, C6–H), 9.07, (br. s, 1 H, N3–H) ppm. N 28.05.
19F NMR (282 MHz, [D6]DMSO, 25 °C) for Z isomer: δ = –56.75
N9-(1,3,3,3-Tetrafluoroprop-1-enyl)guanine (7b): Compound
7
(dd, J = 8 and 18 Hz, 3 F, CF3), –76.51 (dq, J = 18 and 27 Hz, 1
F, Fα) ppm; for E isomer: –57.98 (dd, J = 7 and 13 Hz, 3 F, CF3),
–72.82 (dq, J = 5 and 13 Hz, 1 F, Fα) ppm. 19F NMR (CDCl3,
25 °C): for Z isomer: δ = –58.11 (dd, J = 8 and 18 Hz, 3 F, CF3),
–86.30 (dq, J = 18 and 29 Hz, 1 F, Fα); for E isomer: –59.61 (dd,
J = 7 and 13 Hz, 3 F, CF3), –74.38 (dq, J = 5 and 13 Hz, 1 F,
(302 mg, 2 mmol) gave 7b (310 mg, 59% yield) as a yellowish solid.
M.p.; decomposition from 176 °C. 1H NMR (300 MHz, [D6]-
DMSO, 25 °C): for Z isomer: δ = 6.60 (dq, J = 8 and 32 Hz, 1 H,
Hβ), 6.95 (br. s, 2 H, NH2), 8.10 (s, 1 H, C8–H), 11.04 (br. s, 1 H,
N1–H) ppm; for E isomer: δ = 6.80 (m, 1 H, Hβ), 6.95 (br. s, 2 H,
NH2), 8.01 (s, 1 H, C8–H), 10.94 (br. s, 1 H, N1–H) ppm. 19F NMR
(282 MHz, [D6]DMSO, 25 °C): for Z isomer: δ = –54.41 (dd, J =
8 and 18 Hz, 3 F, CF3), –89.11 (dq, J = 17 and 32 Hz, 1 F, Fα) ppm;
for E isomer: δ = –57.06 (dd, J = 7 and 12 Hz, 3 F, CF3), –70.26
(dq, J = 6 and 12 Hz, 1 F, Fα) ppm. MS (EI): m/z = 263 [M]+
(100%). C8H5F4N5O (263.16): calcd. C 36.51, H 1.92, N 26.61;
found C 36.82, H 2.07; N 26.22.
Fα) ppm. MS (EI): m/z
=
224 [M]+ (18%), 181 (100%).
C7H4F4N2O2 (224.12): calcd. C 37.51, H 1.80, N 12.45; found C
37.21, H 1.98, N 12.09.
N1-(1,3,3,3-Tetrafluoroprop-1-enyl)thymine (3b): Compound
3
(252 mg, 2 mmol) gave 3b (357 mg, 75% yield) as a colourless solid.
1
M.p. 105–108 °C. H NMR (300 MHz, CDCl3, 25 °C): for Z iso-
mer: δ = 2.90 (s, 3 H, CH3), 5.89 (dq, J = 7 and 27 Hz, 1 H, Hβ),
7.25 (s, 1 H, C6–H), 9.80 (br. s, 1 H, N3–H) ppm; for E isomer: δ
= 2.90 (s, 3 H, CH3), 5.83 (m, 1 H, Hβ), 7.00 (s, 1 H, C6–H), 9.80
(br. s, 1 H, N3–H) ppm. 19F NMR (282 MHz, CDCl3, 25 °C): for
Z isomer: δ = –58.04 (dd, J = 7 and 18 Hz, 3 F, CF3), –86.76 (dq,
J = 17 and 29 Hz, 1 F, Fα) ppm; for E isomer: –59.77 (dd, J = 5
and 12 Hz, 3 F, CF3), –74.56 (dq, J = 4 and 12 Hz, 1 F, Fα) ppm.
MS (EI): m/z = 238 [M]+ (40%), 195 (100%). C8H6F4N2O2
(238.15): calcd. C 40.35, H 2.54, N 11.76; found C 40.50, H 2.24,
N 11.96.
N4-Benzoyl-N1-(perfluoroprop-1-enyl)cytosine (9a): Compound 9
(430 mg, 2 mmol) gave 9a (469 mg, 68% yield) as a colourless solid.
M.p. 177–184 °C. H NMR (300 MHz, CDCl3 + CD3OD, 25 °C):
1
δ = 7.52–8.02 (m, 5 H, C6H5), 7.70 (m, 1 H, C5–H), 7.81 (m, 1 H,
C6–H) ppm. 19F NMR (282 MHz, CDCl3 + CD3OD, 25 °C): for E
isomer: δ = –68.58 (dd, J = 11 and 21 Hz, 3 F, CF3), –117.97 (dq,
J = 21 and 132 Hz, 1 F, Fα), –164.04 (dq, J = 11 and 132 Hz, 1 F,
Fβ) ppm; for Z isomer: δ = –68.52 (m, 3 F, CF3), –98.75 (m, 1 F,
Fα), –152.91 (m,1 F, Fβ) ppm. MS (EI): m/z = 345 [M]+ (12%), 105
(100%). C14H8F5N3O2 (345.24): calcd. C 48.71, H 2.34, N 12.17;
found C 48.33, H 2.18, N 12.29.
N1-(1,3,3,3-Tetrafluoroprop-1-enyl)-5-fluorouracil (4b): Compound
4 (260 mg, 2 mmol) gave 4b (368 mg, 76% yield) as a colourless
solid. M.p. 144–151 °C. 1H NMR (300 MHz, CDCl3, 25 °C): for Z
isomer: δ = 5.79 (dq, J = 7 and 30 Hz, 1 H, Hβ), 7.54 (d, J = 6 Hz,
1 H, C6–H), 10.34 (br. s, 1 H, N3–H) ppm; for E isomer: 5.88 (m,
1 H, Hβ), 7.29 (d, J = 6 Hz, 1 H, C6–H), 10.34 (br. s, 1 H, N3–
H) ppm. 19F NMR (282 MHz, CDCl3, 25 °C): for Z isomer: δ =
–58.05 (dd, J = 7 and 18 Hz, 3 F, CF3), –88.05 (dq, J = 18 and
30 Hz, 1 F, Fα), –161.30 (d, J = 6 Hz, 1 F, C5-F) ppm; for E isomer:
δ = –59.88 (dd, J = 7 and 13 Hz, 3 F, CF3), –75.47 (dq, J = 4 and
13 Hz, 1 F, Fα), –162.52 (d, J = 6 Hz, 1 F, C5-F) ppm. MS (EI):
m/z = 242 [M]+ (44%), 199 (100%). C7H3F5N2O2 (242.12): calcd.
C 34.73, H 1.25, N 11.57; found C 34.40, H 1.20, N 11.19.
N6-Benzoyl-N9-(perfluoroprop-1-enyl)adenine (10a): Compound 10
(478 mg, 2 mmol) gave unstable 10a (89 mg, 12% yield) as a colour-
less solid. Unfortunately, 10a undergoes a pretty fast decomposi-
tion. We were not able to get the absolutely pure compound for
melting point determination and for elemental analysis even after a
fine workup and a separation on preparative TLC plates. 1H NMR
(300 MHz, CDCl3, 25 °C): δ = 7.54–8.03 (m, 5 H,C6H5), 8.19 (s, 1
H, C2–H), 8.86 (s, 1 H, C8–H), 9.15 (br. s, 1 H,N6–H) ppm. 19F
NMR (282 MHz, CDCl3, 25 °C): for E isomer: δ = –68.20 (dd, J
= 11 and 21 Hz, 3 F, CF3), –118.58 (dq, J = 21 and 132 Hz, 1 F,
Fα), –164.84 (dq, J = 11 and 132 Hz, 1 F, Fβ) ppm; for Z isomer:
δ = –68.28 (dd, J = 10 and 12 Hz, 3 F, CF3), –94.99 (m, 1 F, Fα),
–148.70 (m, 1 F, Fβ) ppm. MS (EI): m/z = 369 [M]+ (11%), 105
(100%).
N4-Benzoyl-N1,N9-bis(perfluoroprop-1-enyl)adenine (12): Com-
pound 10 (239 mg, 1 mmol and 4 molar excess of NaH) gave 12
(324 mg, 65% yield) as an oil. Compound 12 after certain period
of time turns brown and undergoes a very slow decomposition. 1H
NMR (300 MHz, CDCl3, 25 °C): δ = 7.42–7.59 and 8.03–8.08 (m,
5 H, C6H5), 7.81 and 7.92 (m, 2 H, C2–H and C8–H) ppm. 19F
NMR (282 MHz, CDCl3, 25 °C): δ = –67.93 [dd, J = 9 and 11 Hz,
3 F, (Z)-CF3], –68.01 [dd, J = 8 and 11 Hz, 3 F, (Z)-CF3], –68.23
to –68.56 [m, 6 F, (E)-CF3], –94.94 [m, 1 F, (Z)-Fα], –98.35 [m, 1
F, (Z)-Fα], –117.04 [dm, J = 133 Hz, 1 F, (E)-Fα], –117.85 [dm, J
= 133 Hz, 1 F, (E)-Fα], –148.11 [m, 1 F, (Z)-Fβ], –149.66 [m, 1 F,
(Z)-Fβ], –161.70 [dm, J = 133 Hz, 1 F, (E)-Fβ], –163.81 [dm, J =
133 Hz, 1 F, (E)-Fβ] ppm. MS (EI): m/z = 499 [M]+ (11%), 352
(43%), 105 (100%). C18H7F10N5O (327.25): calcd. C 43.30, H 1.41,
N 14.03; found C 42.94, H 1.79, N 13.79
N1-(1,3,3,3-Tetrafluoroprop-1-enyl)cytosine (5b): Compound
5
(222 mg, 2 mmol) gave 5b (299 mg, 67% yield) as a yellowish solid.
1
M.p. 168–173 °C. H NMR (300 MHz, [D6]DMSO, 25 °C): for Z
isomer: δ = 5.87 (d, J = 7 Hz, 1 H, C5–H), 6.31 (dq, J = 8 and
27 Hz, Hβ), 7.72 (d, J = 7 Hz, 1 H, C6–H), 7.86 (br. s, 2 H,
NH2) ppm; for E isomer: δ = 5.87 (d, J = 7 Hz, 1 H, C5–H), 6.56
(m, 1 H, Hβ), 7.71 (d, J = 7 Hz, 1 H, C6–H), 7.86 (br. s, 2 H,
NH2) ppm. 19F NMR (282 MHz, [D6]DMSO, 25 °C): for Z isomer:
δ = –56.19 (dd, J = 8 and 18 Hz, 3 F, CF3), –76.26 (dq, J = 18 and
28 Hz, 1 F, Fα) ppm; for E isomer: δ = –57.23 (dd, J = 7 and 14 Hz,
3 F, CF3), –70.48 (dq, J = 5 and 14 Hz, 1 F, Fα) ppm. MS (EI):
m/z = 223 [M]+ (100%). C7H5F4N3O (223.14): calcd. C 37.68, H
2.26, N 18.83; found C 37.36, H 2.42, N 18.48.
N9-(1,3,3,3-Tetrafluoroprop-1-enyl)adenine (6b): Compound
6
(270 mg, 2 mmol) gave 6b (257 mg, 52% yield) as a colourless solid.
1
M.p. 150–155 °C. H NMR (300 MHz, [D6]DMSO, 25 °C): for Z
isomer: δ = 6.68 (dq, J = 7 and 32 Hz, 1 H, Hβ), 7.72 (s, 2 H,
NH2), 8.32 (s, 1 H, C2–H), 8.58 (s, 1 H, C8–H) ppm; for E isomer:
N4-Benzoyl-N1-(1,3,3,3-tetrafluoroprop-1-enyl)cytosine (9b): Com-
7.02 (dq, J = 6 and 7 Hz, 1 H, Hβ), 7.61 (s, 2 H, NH2), 8.24 (s, 1 pound 9 (430 mg, 2 mmol) gave 9b (582 mg, 89% yield) as a colour-
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Eur. J. Org. Chem. 2008, 368–376