Preparation of N-(alk-1-enyl) nucleobase compounds by Horner and Horner-Wadsworth-Emmons reactions

Article abstract of DOI:10.1039/b002744h

A series of new N⁹-(alk-1-enyl)adenines and N¹-(alk-1-enyl)thymines has been prepared by Homer reactions of the new phosphine oxides N⁹ -(diphenylphosphorylmethyl)adenine and N¹-(diphenylphosphorylmethyl)thymine derivatives 13a-c, or Horner-Wadsworth-Emmons reactions of the corresponding new phosphonates 14a-b, with benzaldehyde and various ketones. Yields were highest for the Homer reactions (10-79%), and were limited by steric hindrance, enolization of the ketones, and decomposition of some of the N¹-(alk-1-enyl)thymines in the presence of excess base (NaH). Butanal gave mixtures of products under Homer conditions, probably because aldol reactions intervened.

Full text of DOI:10.1039/b002744h

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Preparation of N-(alk-1-enyl) nucleobase compounds by Horner
and Horner–Wadsworth–Emmons reactions
Thomas Boesen, Christian Madsen, Ulla Henriksen and Otto Dahl*
1
Department of Chemistry, University of Copenhagen, The H. C. Ørsted Institute,
Universitetsparken 5, DK-2100 Copenhagen, Denmark
Received (in Cambridge, UK) 6th April 2000, Accepted 20th April 2000
Published on the Web 5th June 2000
A series of new N9-(alk-1-enyl)adenines and N1-(alk-1-enyl)thymines has been prepared by Horner reactions of
the new phosphine oxides N9-(diphenylphosphorylmethyl)adenine and N1-(diphenylphosphorylmethyl)thymine
derivatives 13a–c, or Horner–Wadsworth–Emmons reactions of the corresponding new phosphonates 14a–b, with
benzaldehyde and various ketones. Yields were highest for the Horner reactions (10–79%), and were limited by steric
hindrance, enolization of the ketones, and decomposition of some of the N1-(alk-1-enyl)thymines in the presence of
excess base (NaH). Butanal gave mixtures of products under Horner conditions, probably because aldol reactions
intervened.
and 711 as well as a few buta-1,3-dienyl nucleobases.12 (iv) A few
tetrasubstituted alkenyl nucleobases 8 and 11 (B = 9-adenyl)
Introduction
N9-Alkyl derivatives of the purine nucleobases adenine and
have been obtained by double SRN1 substitutions followed by
guanine, and N1-alkyl derivatives of the pyrimidine nucleobases
cytosine, thymine and uracil, are well known and have been
Grob-type eliminations.13 (v) A trisubstituted alk-1-enyl aden-
ine derivative 12 has recently been made by aldol type conden-
extensively investigated for their biological activity, e.g. as anti-
sation of a cyanomethyl adenine with benzaldehyde.14 We are
viral compounds.1 The corresponding alk-1-enyl compounds,
interested in general methods to prepare di-, tri- and tetra-
which are enamines, have, apart from Zemlicka’s allenol deriv-
substituted alkenes with a nucleobase as one of the sub-
atives,2 been much less studied, probably because general pre-
stituents, and present here our results from a study of Horner
parative methods are lacking. Known methods (Scheme 1) to
and Horner–Wadsworth–Emmons (HWE) reactions to gener-
ate the alkenes (Scheme 2). To the best of our knowledge such
Scheme 2 Horner and HWE routes to N-(alk-1-enyl) nucleobases.
reactions have not been used before for the preparation of
N-(alk-1-enyl) nucleobases. The present work has been limited
to adenine and thymine as representative examples of the
nucleobases, and to compounds with R3 = H.
Results and discussion
Preparation of Horner and HWE reagents
The necessary Horner and HWE reagents shown in Scheme 2
can be obtained by alkylation of adenine and thymine. The
nucleobases are poor nucleophiles, and nucleophilic substitu-
tion α to a phosphine oxide or a phosphonate is difficult, but
with R3 = H and 4-nitrobenzenesulfonate as the leaving group
Scheme 1 Known N-(alk-1-enyl) nucleobases.
the new phosphine oxides 13 and phosphonates 14 could be
prepare such compounds are: (i) The Michael addition of a
nucleobase to activated alkynes, which furnishes disubstituted
alkenyl nucleobases 1,3 or trisubstituted analogs 2.4 (ii) Alkyl-
ation of nucleobases with 1,2-dihaloalkanes followed by elimin-
ation, which has led to vinyl nucleobases 35 and the alk-1-enyl
nucleobases 6,5 96 and 10.7 Similar base-induced eliminations
of a 2-mesyl8 or a 1-nitro group9 have led to the alkenyl nucleo-
bases 6 and 4, respectively. (iii) Base catalysed rearrangement of
alk-2-enyl nucleobases to give the alk-1-enyl nucleobases 510
prepared in 44–70% yields, as shown (Scheme 3). The anion of
adenine, generated with sodium hydride, was mainly alkylated
at N-9 (as shown by the characteristic shifts of C-4 and C-5 in
the 13C NMR15), and the minor N-7 isomer could be removed
by column chromatography after N-6 protection with a dibutyl-
formamidine group, to give 13a and 14a. 3-Benzoylthymine
could be alkylated in DMF in the presence of excess potassium
carbonate to give 13b and 14b, although the benzoyl group
was not totally stable under these conditions. A more stable
DOI: 10.1039/b002744h
J. Chem. Soc., Perkin Trans. 1, 2000, 2015–2021
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Scheme 3 Preparation of 9-adenyl- and 1-thymidyl-methylphosphine oxides 13 and methylphosphonates 14.
protecting group such as the benzyloxymethyl (BOM) group
were formed, but the main products were derived from the aldol
was deemed unsuitable because it is removed by hydrogenation,
which would probably reduce the N-(alk-1-enyl) nucleobase
product. The unprotected thymine derivative 13c was obtained
from bis(trimethylsilyl)thymine, which was alkylated preferen-
tially at the N-1 position (as shown by strong NOE effects
between H-6 and CH2). Alkylation of underivatised thymine
under various conditions gave mostly dialkylated products.
dimer of butanal, 2-ethylhex-2-enal. In the case of 13c the low
yield of products was demonstrated by the fact that the starting
material 13c was isolated from the reaction mixture in 80%
yield. With ketones the Horner anions derived from 13a–c gave
the new trisubstituted alkenes 16 in variable yields (Scheme 5).
Horner reactions
The Horner reagents 13a–c were treated with 1 equiv. of NaH
(2 equiv. in the case of 13c) in DMF for 1–2 h at 0 ЊC to give
yellow or green anions. Addition of benzaldehyde as an
example of a non-enolizable oxo compound and stirring at rt
gave slowly the new alkenes 15a–c as a mixture of E and Z
isomers (Scheme 4). For the adenine derivative 13a the product
Scheme 5 Horner reactions with ketones.
The reactions were run at rt until TLC indicated that 13a–c
were absent or the amount did not decrease further (3 h to 5
days). The adenine derivative 13a gave the highest yield (79%)
with acetone and 34–74% with higher substituted ketones. No
reaction was observed with the crowded di-tert-butyl ketone, or
with the easily enolizable dibenzyl ketone; however the fairly
easily enolizable cyclopentanone gave 66% of the Horner prod-
uct 16ac. The benzoyl protected thymine derivative 13b with
acetone and 1 equiv. of NaH gave 34% of 16ba, but with excess
of NaH the product was unstable. We were able to isolate a
ring-opened product 17 from a reaction with excess NaH
(Scheme 6). The formation of 17 may be explained by a
Michael addition of HϪ, or more probably OHϪ from adventi-
tious water, at C-6 of the thymine ring, followed by elimination
of N-1 and hydrolysis at C-4; the alk-1-enyl substituent is
expected to facilitate elimination of the N-1 group by resonance
stabilisation, and the benzoyl group should facilitate hydrolysis
at C-4. A similar reaction could explain the decomposition of
the Z-15b isomer described above. With the more hindered
heptan-4-one, 13b gave a lower yield (10%) of the alkene
Scheme 4 Horner reactions with benzaldehyde.
15a could be isolated after 1 day at rt in 65% yield as a 2:7
mixture of E- and Z-15a. The benzoyl protected thymine
derivative 13b gave a 55% isolated yield of 15b (E:Z 1:5) after
1 day, but the yield decreased and the E:Z ratio increased when
the reaction time was prolonged in the presence of excess of
NaH. Since the yield of the E isomer stayed approximately
constant this indicates that the Z isomer is unstable under the
reaction conditions. The unprotected thymine derivative 13c,
transformed to the dianion with NaH, was converted to the
alkene product 15c (E:Z 1:2) in a yield similar to 15b after
1 day. Reactions between the anions of 13a–c and enolizable
aliphatic aldehydes gave low yields of mixtures of N-(alk-1-
enyl) nucleobases, probably because aldol condensations of the
aldehydes competed effectively with the Horner reaction. Thus
butanal and 13a–c gave mixtures of products from which no
pure N-(pent-1-enyl) nucleobases could be isolated. According
to 1H NMR on purified fractions some of the desired products
2016
J. Chem. Soc., Perkin Trans. 1, 2000, 2015–2021

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and 14 are strong bases. Despite these limitations the routes
described here are complementary to previous known methods
to prepare N-(alk-1-enyl) nucleobases, and open up a general
route to trisubstituted alkenyl nucleobases.
Experimental
N,N-Dibutylformamide dimethyl acetal,17 3-benzoylthymine,18
Scheme 6 Ring-opened product 17 from the decomposition of 16ba.
and
(4-nitrophenylsulfonyloxymethyl)diphenylphosphine
oxide19 were prepared according to the literature. NaH was 55–
60% in mineral oil from Aldrich. Diethyl phosphite was purum
from Fluka. Aldehydes and ketones were 97–99% pure from
Aldrich, Fluka, or Merck. Solvents were HPLC grade from
LABSCAN, of which DMF and pyridine were dried over
molecular sieves (Grace 4 Å) to a water content below 30 ppm,
measured on a Metrom 652 KF-Coulometer. TLC was run on
Merck 5554 silica 60 aluminium sheets, column chromato-
graphy on Merck 9385 silica 60 (0.040–0.063 mm). NMR spec-
tra (reference tetramethylsilane for δH and δC, external 85%
H3PO4 for δP, J values are given in Hz) were run on a Varian
Mercury 300 MHz spectrometer, and FAB MS data obtained
on a JEOL HX 110/110 Mass Spectrometer.
product 16bb. The unprotected thymine derivative 13c gave 40%
of the alkene derivative 16ca with acetone. No ring-opened
product seemed to form in this case, but the reaction mixture
turned brown, and a mixture of unidentified polar by-products
was formed. With heptan-4-one, 13c gave 44% of the alkene
16cb, and with cyclohexanone 68% of the alkene 16cc. The
yields were higher than those obtained from the benzoyl pro-
tected 13b, probably because 13b suffered partial loss of the
benzoyl protecting group during the reactions, and because of
ring-opening reactions.
HWE reactions
Horner–Wadsworth–Emmons anions without resonance stabil-
izing substituents are generally not stable at ambient tem-
perature,16 but alkenes can be prepared from a mixture of
unstablized phosphonates and oxo compounds upon addition
of a strong base, and these reactions are usually faster than the
corresponding Horner reactions. This was also the case for the
phosphonates 14a and 14b (Scheme 7). The adenine derivative
Diethyl (4-nitrophenylsulfonyloxymethyl)phosphonate
This compound was prepared in the same way as the published
4-chloro analogue.20 The crude product from evaporation of the
diethyl ether phase was recrystallized from EtOAc–hexane 1:1
v/v to give pure diethyl (4-nitrophenylsulfonyloxymethyl)-
phosphonate (21.2 g, 60%) as light yellow crystals, mp 65.5–
67 ЊC. NMR (CDCl3): δP 14.7. δH 8.44 (2H, m, Ar), 8.15 (2H, m,
Ar), 4.32 (2H, d, J 9.6, CH2P), 4.17 (4H, dq, J 7.1 and 7.1, Et),
1.34 (6H, t, J 7.1, Et). δC 150.78, 140.53, 129.32, 124.37, 63.44
(d, J 6), 62.15 (d, J 169), 16.36 (d, J 6). FABϩ MS: 354.0
(M ϩ Hϩ calc. 354.0) (Found: C, 37.5; H, 4.4; N, 3.95. Calc. for
C11H16NO8PS: C, 37.4; H, 4.6; N, 4.0%).
Scheme 7 HWE reactions with benzaldehyde.
N6-(Dibutylaminomethylene)-9-(diphenylphosphorylmethyl)-
adenine (13a)
14a and benzaldehyde in DMF with NaH gave after 2 h at 0 ЊC
15a in 39% isolated yield as a 1:4 mixture of E and Z isomers.
Longer reaction times at rt did not increase the yield. The
thymine derivative 14b with benzaldehyde and excess NaH in
DMF gave after 1 h at rt 15b (E:Z 1:3) in an isolated yield
of 55%. The yield decreased and the E:Z ratio increased at
longer reaction times, as was the case for the Horner reaction.
With ketones the yields were lower for the HWE reactions than
for the Horner reactions, most likely because the anions could
not be preformed and the more strongly basic conditions
favoured aldol condensations. Thus 14a with acetone gave 18%
of 16aa, and with heptan-4-one only 2% of 16ab. From 14b and
acetone only a 7% yield of 16ba could be isolated.
To a suspension of NaH (5.67 g, 55–60% in mineral oil, 0.13–
0.14 mol) in dry DMF (1100 ml) was added adenine (13.5 g,
0.10 mol), and the mixture was stirred at rt under nitrogen for
3 h. A solution of (4-nitrophenylsulfonyloxymethyl)diphenyl-
phosphine oxide (41.3 g, 0.10 mol) dissolved in DMF (250 ml)
was added dropwise, and the mixture stirred at rt under nitro-
gen for 4 days. Ethanol (980 ml) was added and the solvents
removed in vacuo. The residue was refluxed with water (600 ml),
kept at 10 ЊC overnight and filtered. The residue (27.9 g), a
1:3 mixture of 7- and 9-(diphenylphosphorylmethyl)adenine
(judged by NMR), was suspended under nitrogen in DMF (275
ml). N,N-Dibutylformamide dimethyl acetal (31.5 ml, 0.16 mol)
was added in one portion and the solution was stirred for 3 days
followed by evaporation in vacuo. The residue was purified by
column chromatography on silica, eluted with EtOAc–Et3N–
MeOH 92:5:3 v/v/v, to give pure 13a (27.4 g, 56%), Rf = 0.33,
mp 130–131.5 ЊC. NMR (DMSO-d6): δP 25.8. δH 8.89 (1H, s,
Conclusion
A series of new N9-(alk-1-enyl)adenines and N1-(alk-1-enyl)-
thymines has been prepared by Horner reactions of the phos-
phine oxides 13a–c or Horner–Wadsworth–Emmons reactions
of the phosphonates 14a–b with benzaldehyde and various
ketones. Yields were highest for the Horner reactions, where the
adenine derivative 13a gave 65–79% with benzaldehyde and
unhindered ketones. Lower yields were obtained with sterically
hindered ketones, although tert-butyl methyl ketone still gave a
34% yield of 16ae, and yields were generally lower for the thy-
mine derivatives than for the adenine derivatives, in part due to
the N1-(alk-1-enyl)thymines being unstable in the presence of
strong base. Aliphatic aldehydes containing α-hydrogen atoms
gave mixtures of products under Horner conditions, probably
because competitive aldol reactions were faster, and enolate
anion formation seems also a limiting factor for obtaining high
yields from enolizable ketones, since the anions derived from 13
CH᎐N), 8.32 (1H, s, adenine), 8.05 (1H, s, adenine), 7.87 (4H,
᎐
m, phenyl), 7.57 (6H, m, phenyl), 5.41 (2H, d, J 5.8, CH2P), 3.56
(2H, t, J 7.4, Bu), 3.42 (2H, t, J 7.0, Bu), 1.58 (4H, m, Bu), 1.31
(4H, m, Bu), 0.91 (6H, m, Bu). δC 158.8, 157.4, 151.4, 151.1,
142.0, 132.1, 130.9, 130.7, 130.6, 129.5, 128.6, 128.4, 124.0,
50.7, 44.2, 42.0 (d, J 72), 30.3, 28.5, 19.5, 19.0, 13.6, 13.5. FABϩ
MS: 489.0 (M ϩ Hϩ calc. 489.3) (Found: C, 66.3; H, 6.8; N,
17.1. Calc. for C27H33N6OP: C, 66.4; H, 6.8; N, 17.2%).
3-Benzoyl-1-(diphenylphosphorylmethyl)thymine (13b)
To a solution of 3-benzoylthymine (1.98 g, 8.6 mmol) and
(4-nitrophenylsulfonyloxymethyl)diphenylphosphine
(3.94 g, 9.4 mmol) in dry DMF (30 ml) was added solid K2CO3
oxide
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(2.4 g, 17 mmol), and the mixture stirred at 55 ЊC under nitro-
gen for 2 days. The solvent was removed in vacuo, and the resi-
due was partitioned between CH2Cl2 (200 ml) and sat. aq.
NH4Cl (100 ml). The organic phase was extracted with water
(100 ml), brine (50 ml), dried over Na2SO4, and the solvent
removed in vacuo to give the crude product (4.06 g). Flash
chromatography on silica, with CH2Cl2–MeOH 98:2 v/v fol-
lowed by CH2Cl2–MeOH 95:5 v/v as eluent, gave a nearly pure
product (2.60 g), which was recrystallized from ethanol–water
to give pure 13b (1.68 g, 44%) as colourless crystals, mp 228–
230 ЊC. NMR (DMSO-d6): δP 26.7. δH 7.88–7.52 (16H, m,
Ar ϩ H6), 4.92 (2H, d, J 4.4, CH2P), 1.82 (3H, s, CH3). δC
168.9, 162.3, 148.8, 142.2, 135.3, 132.4, 131.2, 130.9, 130.8,
130.7, 129.9, 129.3, 128.8, 128.6, 108.4, 45.5 (d, J 73), 11.8.
FABϩ MS: 445.1 (M ϩ Hϩ calc. 445.1) (Found: C, 67.4; H, 4.5;
N, 6.2. Calc. for C25H21N2O4P: C, 67.6; H, 4.8; N, 6.3%).
425.2 (M ϩ Hϩ calc. 425.2) (Found: C, 53.6; H, 8.1; N, 19.6.
Calc. for C19H33N6O3P: C, 53.8; H, 7.8; N, 19.8%).
3-Benzoyl-1-(diethoxyphosphorylmethyl)thymine (14b)
To a solution of 3-benzoylthymine (2.00 g, 8.7 mmol) and
diethyl (4-nitrophenylsulfonyloxymethyl)phosphonate (3.40 g,
9.6 mmol) in dry DMF (20 ml) was added solid K2CO3 (2.4 g,
17 mmol), and the mixture stirred at 60 ЊC under nitrogen
for 7 h. The solvent was removed in vacuo, and the residue
was partitioned between CH2Cl2 (200 ml) and sat. aq. NH4Cl
(100 ml). The organic phase was extracted with water (100 ml),
brine (50 ml), dried over Na2SO4, and the solvent removed
in vacuo to give the crude product (3.12 g) as an oil. Flash
chromatography on silica, with CH2Cl2–MeOH 98:2 v/v as
eluent, gave pure 14b (2.19 g, 66%) as a colourless oil. NMR
(CDCl3): δP 19.3. δH 7.87–7.39 (5H, m, phenyl), 7.18 (1H,
q, J 1, thymine), 4.05–4.15 (6H, m, CH2P and Et), 1.91 (3H,
d, J 1, thymine), 1.25 (6H, t, J 7, Et). δC 168.8, 163.0, 149.7,
140.0, 135.3, 131.6, 130.6, 129.3, 111.5, 63.5 (J 6), 42.1 (J 156),
16.6 (J 6), 12.6. FABϩ MS: 381.1 (M ϩ Hϩ calc. 381.1) (Found:
C, 53.5; H, 5.6; N, 7.4. Calc. for C17H21N2O6P: C, 53.7; H, 5.6;
N, 7.4%).
1-(Diphenylphosphorylmethyl)thymine (13c)
Bis(trimethylsilyl)acetamide (35 ml, 140 mmol) was added
under nitrogen to a suspension of thymine (7.57 g, 60 mmol)
in acetonitrile (40 ml), to give a clear solution after 5 min.
(4-Nitrophenylsulfonyloxymethyl)diphenylphosphine
oxide
(8.35 g, 20 mmol) was then added, and the mixture heated at
reflux under nitrogen for 4 days. The suspension was cooled to
0 ЊC and water (100 ml) and 2 M aq. NH3 (10 ml) were added,
followed by 4 M aq. acetic acid to pH ca. 5 (2 ml). After stand-
ing overnight the resulting precipitate was filtered off, washed
with water and dissolved in 1 M aq. NaOH (100 ml). Small
amounts of non-acidic impurities were extracted with dichloro-
methane (2 × 30 ml), and the aqueous phase filtered and diluted
with water (600 ml). The product was precipitated by decreas-
ing the pH to ca. 9.6 by slow addition of 1 M aq. NH4Cl (100
ml). The nearly pure product (5.50 g, 81%) was recrystallised
once from pyridine (220 ml) to give pure 13c as colourless crys-
tals (4.75 g, 70%), mp > 250 ЊC. NMR (DMSO-d6): δP 26.8.
δH 11.25 (1H, s, NH), 7.85–7.55 (10H, m, Ar), 7.45 (1H, s, H6),
4.83 (2H, d, J 4.7, CH2), 1.71 (3H, s, CH3). The compound had
too low a solubility for 13C NMR. FABϩ MS: 341.3 (M ϩ Hϩ
calc. 341.1) (Found: C, 63.4; H, 5.0; N, 8.4. Calc. for C18H17-
N2O3P: C, 63.5; H, 5.0, N, 8.2%).
Horner reactions with benzaldehyde
N6-(Dibutylaminomethylene)-9-(2-phenylethenyl)adenine
(15a). Compound 13a (0.49 g, 1 mmol) was evaporated in vacuo
from pyridine (10 ml), dissolved under N2 in dry DMF (10 ml),
and cooled to 0 ЊC. Sodium hydride (55% suspension in mineral
oil, 0.045 g, 1 mmol) was added in one portion and the mixture
stirred for 2 h at 0 ЊC. Benzaldehyde (0.14 ml, 1.4 mmol) was
added, and the mixture was allowed to warm up slowly to room
temperature and stirred for 1 day at rt. Water (10 ml) was added
at 5 ЊC, and the solution extracted with diethyl ether (7 × 10
ml). The combined organic layers were dried over Na2SO4 and
evaporated in vacuo. The residue was purified by column
chromatography on silica, eluted with heptane–EtOAc–Et3N,
58:38:4 v/v/v, to give 15a (0.25 g, 65%) as an oily mixture of E
1
and Z isomers (E:Z 2:7 according to H NMR). The isomers
were not separated. The E isomer: NMR (CDCl3): δH 8.93 (1H,
s, CH᎐N), 8.54 (1H, s, adenine), 8.13 (1H, s, adenine), 7.61 (1H,
᎐
d, J 14.7, HC᎐C), 7.22 (6H, m, phenyl ϩ C᎐CH), 3.62 (2H, m,
᎐
᎐
Bu), 3.30 (2H, m, Bu), 1.54 (4H, m, Bu), 1.30 (4H, m, Bu), 0.85
(6H, m, Bu). The Z isomer: NMR (CDCl3): δ 8.91 (1H, s,
N6-(Dibutylaminomethylene)-9-(diethoxyphosphorylmethyl)-
adenine (14a)
CH᎐N), 8.51 (1H, s, adenine), 7.60 (1H, s, adenine), 7.22 (5H,
᎐
To a suspension of NaH (0.96 g, 55–60% in mineral oil, 22–24
mmol) in dry DMF (60 ml) was added adenine (2.70 g, 20
mmol), and the mixture was stirred at rt under nitrogen for
3 h. A solution of diethyl (4-nitrophenylsulfonyloxymethyl)-
phosphonate (7.07 g, 20 mmol) in dry DMF (20 ml) was added,
and the mixture stirred at rt under nitrogen for 3 days. After
removal of DMF in vacuo the solid residue (11.2 g) was
Soxhlet-extracted with ethyl acetate (400 ml) overnight, and
crude 9-(diethoxyphosphorylmethyl)adenine (6.7 g, contains
ca. 1.3 g of sodium 4-nitrobenzenesulfonate, and ca. 85% of
the 9-isomer and 6% of the 7-isomer according to 31P NMR)
isolated by evaporation of the ethyl acetate suspension. To a
suspension of crude 9-(diethoxyphosphorylmethyl)adenine
(6.35 g) in dry DMF (50 ml) was added N,N-dibutylformamide
dimethyl acetal (6.9 g, 33 mmol), and the mixture stirred under
nitrogen at rt for 2 days. Evaporation in vacuo gave a red–brown
oil which was purified by column chromatography on silica,
eluted with EtOAc–MeOH–Et3N 90:5:5 v/v/v, to give pure 14a
(4.40 g, 55%) as a yellow oil. NMR (CDCl3): δP 18.8. δH 9.02
m, phenyl), 6.95 (1H, d, J 9.2, HC᎐C), 6.49 (1H, d, J 9.2,
᎐
HC᎐C), 3.62 (2H, m, Bu), 3.30 (2H, m, Bu), 1.54 (4H, m, Bu),
᎐
1.30 (4H, m, Bu), 0.85 (6H, m, Bu). FABϩ MS: 377.2 (M ϩ Hϩ
calc. 377.2) (Found: C, 69.6; H, 7.7; N, 21.7. Calc. for C22H28N6:
C, 70.2; H, 7.5; N, 22.3%).
3-Benzoyl-1-(2-phenylethenyl)thymine (15b). Compound 13b
(0.44 g, 1 mmol) was evaporated from dry pyridine (10 ml),
dissolved in dry DMF (15 ml), and NaH (55% suspension in
mineral oil, 0.045 g, 1 mmol) added under N2. After 2 h benzal-
dehyde (0.106 g, 0.102 ml, 1 mmol) was added, and the mixture
stirred at rt for 20 h. Then additional benzaldehyde (0.050 ml,
0.5 mmol) and NaH (0.020 g, 0.5 mmol) were added, and the
mixture stirred for 3 h at rt. Water (60 ml) was added, and the
suspension extracted with ethyl acetate (3 × 40 ml), the ethyl
acetate solution dried (MgSO4) and evaporated in vacuo, and
the residue purified by column chromatography on silica, eluted
with hexane–ethyl acetate 2:1 v/v, to give 15b (0.185 g, 55%) as
a semisolid mixture of E and Z isomers (E:Z 1:5 according to
1H NMR). The isomers were not separated. NMR (CDCl3):
(1H, s, CH᎐N), 8.57 (1H, s, adenine), 8.07 (1H, s, adenine), 4.62
᎐
(2H, d, J 12.0, CH2P), 4.11 (4H, dq, J 7.0 and 8.2, Et), 3.72 (2H,
t, J 7.6, Bu), 3.40 (2H, t, J 7.2, Bu), 1.66 (4H, m, Bu), 1.39 (4H,
m, Bu), 1.24 (6H, t, J 7.0, Et), 0.95 (6H, m, Bu). δC 160.1, 158.3,
152.9, 151.7, 141.5, 125.2, 63.2 (d, J 6), 5.19, 45.2, 38.4 (d,
J 157), 31.0, 29.3, 20.2, 19.8, 16.3 (d, J 6), 13.9, 13.7. FABϩ MS:
E isomer: δH 7.25–8.00 (12H, m, phenyl ϩ H-6 ϩ NCH᎐C),
᎐
6.62 (1H, d, J 14.7, C᎐CHPh), 2.07 (3H, d, J 1.2, Me).
᎐
Z isomer: δH 7.25–8.00 (10H, m, phenyl), 6.91 (1H, q, J 1.2,
H-6), 6.72 (1H, d, J 9.0, NCH᎐C), 6.49 (1H, d, J 9.0, C᎐CHPh),
᎐
᎐
1.77 (3H, d, J 12, Me). FABϩ MS: 333.1 (M ϩ Hϩ calc. 333.1)
2018
J. Chem. Soc., Perkin Trans. 1, 2000, 2015–2021

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(Found: C, 71.6; H, 4.8; N, 8.5. Calc. for C20H16N2O3: C, 72.3;
H, 4.85; N, 8.4%).
(4H, m, Bu), 0.85 (6H, m, Bu). δC 159.4, 157.5, 152.2, 150.5,
142.0, 139.9, 124.4, 111.1, 51.2, 44.5, 31.6, 30.3, 29.4, 28.6, 25.6,
25.3, 19.6, 19.1, 13.3, 13.1. FABϩ MS: 355.0 (M ϩ Hϩ calc.
355.3) (Found: C, 67.4; H, 8.8; N, 23.1. Calc. for C20H30N6: C,
67.8; H, 8.5; N, 23.7%).
1-(2-Phenylethenyl)thymine (15c). Compound 13c (0.34 g,
1 mmol) was evaporated from dry pyridine (10 ml), suspended
in dry DMF (20 ml), and NaH (55% suspension in mineral
oil, 0.100 g, 2.2 mmol) added under N2. After 2 h benzaldehyde
(0.106 g, 0.102 ml, 1 mmol) was added, and the mixture stirred
at rt for 20 h. Water (30 ml) was added, and the suspension
extracted with ethyl acetate (3 × 50 ml), the ethyl acetate solu-
tion dried (Na2SO4) and evaporated in vacuo, and the residue
purified by column chromatography on silica, eluted with
heptane–EtOAc–MeOH–Et3N 50:49:0.5:0.5 v/v/v/v, to give
15c (0.120 g, 53%) as a solid mixture of E and Z isomers (E:Z
N6-(Dibutylaminomethylene)-9-(cyclohexylidenemethyl)-
adenine (16ad). Prepared in the same way as 16aa from
cyclohexanone (0.15 ml), stirred for 4 days. Yield: 0.27 g (74%,
oil), Rf = 0.20 (heptane–EtOAC–Et3N 58:38:4 v/v/v). NMR
(CDCl ): δ 8.77 (1H, s, CH᎐N), 8.32 (1H, s, adenine), 7.58 (1H,
᎐
3
H
s, adenine), 6.29 (1H, s, C᎐CH), 3.46 (2H, t, J 7.6, Bu), 3.14
᎐
(2H, t, J 7.3, Bu), 2.06 (2H, t, J 5.8, cyclohexyl), 1.88 (2H, t,
J 5.5, cyclohexyl), 1.38 (10H, m, cyclohexyl ϩ Bu), 1.14 (4H,
m, Bu), 0.68 (6H, m, Bu). δC 159.1, 157.3, 152.1, 151.2, 142.8,
141.0, 124.5, 111.3, 51.1, 44.5, 32.8, 30.4, 28.6, 27.8, 27.2, 26.6,
25.5, 19.6, 19.1, 13.3, 13.1. FABϩ MS: 368.5 (M ϩ Hϩ calc.
369.3) (Found: C, 68.05; H, 8.9; N, 22.55. Calc. for C21H32N6:
C, 68.4; H, 8.75; N, 22.8%).
1
1:2 according to H NMR). The isomers were not separated.
NMR (DMSO-d6): E isomer: δH 11.5 (1H, br s, NH), 8.05 (1H,
s, H-6), 7.58 (1H, d, J 14.8, NCH᎐C), 7.26–7.49 (5H, m,
᎐
phenyl), 6.86 (1H, d, J 14.8, C᎐CHPh), 1.87 (3H, s, Me). Z
᎐
isomer: δH 11.5 (1H, br s, NH), 7.26–7.49 (5H, m, phenyl), 7.03
(1H, s, H-6), 6.59 (1H, d, J 9.1, NCH᎐C), 6.49 (1H, d, J 9.1,
᎐
C᎐CHPh), 1.63 (3H, s, Me). FABϩ MS: 229.2 (M ϩ Hϩ calc.
N6-(Dibutylaminomethylene)-9-(2,3,3-trimethylbut-1-enyl)-
adenine (16ae). Prepared in the same way as 16aa from 2,2-
dimethylbutan-3-one (0.17 ml), stirred for 4 days. Yield: 0.13 g
(34%, E:Z 3:7) consisting of pure E isomer (0.02 g), a mixed
fraction (0.07 g), and pure Z isomer (0.04 g). The E isomer:
oil, Rf = 0.21 (heptane–EtOAc–Et3N 58:38:4 v/v/v). NMR
᎐
229.3) (Found: C, 67.8; H, 5.3; N, 12.0. Calc. for C13H12N2O2:
C, 68.4; H, 5.3; N, 12.3%).
Horner reactions with ketones
N6-(Dibutylaminomethylene)-9-(2-methylprop-1-enyl)adenine
(16aa). Compound 13a (0.49 g, 1 mmol) was evaporated in
vacuo from pyridine (10 ml), dissolved under N2 in dry DMF
(10 ml), and cooled to 0 ЊC. NaH (55% suspension in mineral
oil, 0.045 g, 1 mmol) was added in one portion and the mixture
stirred for 2 h at 0 ЊC. Acetone (0.10 ml, 1.4 mmol) was dis-
solved in dry DMF (4 ml) and added dropwise. The mixture
was allowed to warm up slowly to room temperature and stirred
for 2 days. Water (10 ml) was added at 5 ЊC, and the solution
extracted with diethyl ether (7 × 10 ml). The combined extracts
were dried over Na2SO4 and the solvent removed in vacuo. The
residue was purified by column chromatography on silica,
eluted with heptane–EtOAc–Et3N 58:38:4 v/v/v. Yield: 0.26 g
(79%, oil), Rf = 0.11 (heptane–EtOAc–Et3N 58:38:4 v/v/v).
(CDCl3): δH 9.00 (1H, s, CH᎐N), 8.59 (1H, s, adenine), 7.86
᎐
(1H, s, adenine), 6.66 (1H, d, J 1.4, C᎐CH), 3.73 (2H, t, J 7.7,
᎐
Bu), 3.41 (2H, t, J 7.3, Bu), 1.72 (3H, d, J 1.4, CH3), 1.67 (4H,
m, Bu), 1.39 (4H, m, Bu), 1.25 (9H, s, But), 0.96 (6H, m, Bu).
δC 159.6, 157.7, 152.6, 151.7, 147.7, 141.7, 125.1, 113.9, 51.8,
45.1, 35.8, 31.0, 29.2, 28.8, 20.2, 19.8, 13.9, 13.7, 13.3. The
Z isomer: mp 90–92 ЊC, Rf = 0.16 (heptane–EtOAc–Et3N
58:38:4 v/v/v). NMR (CDCl3): δH 9.01 (1H, s, CH᎐N), 8.59
᎐
(1H, s, adenine), 7.78 (1H, s, adenine), 6.38 (1H, d, J 1.4,
C᎐CH), 3.73 (2H, t, J 7.7, Bu), 3.40 (2H, t, J 7.3, Bu), 1.97 (3H,
᎐
d, J 1.1, CH3), 1.67 (4H, m, Bu), 1.36 (4H, m, Bu), 0.96 (6H, t,
J 6.7, Bu), 0.96 (9H, s, But). δC 159.7, 157.8, 152.8, 152.5, 152.0,
142.2, 125.1, 113.9, 51.8, 45.1, 36.0, 31.0, 29.4, 29.2, 20.4, 20.2,
19.7, 13.9, 13.7. FABϩ MS: 370.5 (M ϩ Hϩ calc. 371.3) (Found:
C, 67.8; H, 9.3; N, 22.25. Calc. for C21H34N6ؒ0.1H2O: C, 67.7;
H, 9.3; N, 22.6%).
NMR (CDCl3): δH 9.03 (1H, s, CH᎐N), 8.58 (1H, s, adenine),
᎐
7.88 (1H, s, adenine), 6.60 (1H, d, J 1.4, C᎐CH), 3.74 (2H, t,
᎐
J 7.6, Bu), 3.42 (2H, t, J 7.3, Bu), 1.97 (3H, s, CH3), 1.73 (3H, d,
J 1.1, CH3), 1.68 (4H, m, Bu), 1.40 (4H, m, Bu), 0.96 (6H, t,
J 7.3, Bu). δC 159.4, 157.5, 152.5, 151.3, 141.1, 136.1, 124.7,
114.8, 51.5, 44.8, 30.7, 28.9, 22.4, 19.9, 19.5, 17.8, 13.6, 13.4.
FABϩ MS: 328.5 (M ϩ Hϩ calc. 329.2) (Found: C, 65.7; H, 8.7;
N, 25.4. Calc. for C18H28N6: C, 65.8; H, 8.6; N, 25.6%).
N6-(Dibutylaminomethylene)-9-(2-methyl-3-phenoxyprop-1-
enyl)adenine (16af). Prepared in the same way as 16aa from
phenoxyacetone (0.19 ml), stirred for 4 days. Yield: 0.20 g (48%,
semi-solid mixture of the two isomers, E:Z 2:5), Rf = 0.15
(heptane–EtOAc–Et3N 58:38:4 v/v/v). The isomers were not
separated. The E isomer: NMR (CDCl3): δH 8.92 (1H, s,
N6-(Dibutylaminomethylene)-9-(2-propylpent-1-enyl)adenine
(16ab). Prepared in the same way as 16aa from heptan-4-one
(0.20 ml), stirred for 2 days. Yield: 0.18 g (49%, oil), Rf = 0.26
(heptane–EtOAc–Et3N 58:38:4 v/v/v). NMR (CDCl3): δH 8.88
CH᎐N), 8.49 (1H, s, adenine), 7.89 (1H, s, adenine), 7.83 (1H, s,
᎐
C᎐CH), 7.18 (2H, m, phenyl), 6.79 (3H, m, phenyl), 4.38 (2H, s,
᎐
OCH2), 3.62 (2H, m, Bu), 3.29 (2H, m, Bu), 2.00 (3H, s, CH3),
1.54 (4H, m, Bu), 1.28 (4H, m, Bu), 0.84 (6H, m, Bu). The
(1H, s, CH᎐N), 8.40 (1H, s, adenine), 7.67 (1H, s, adenine), 6.39
᎐
Z isomer: NMR (CDCl3): δH 8.92 (1H, s, CH᎐N), 8.49 (1H, s,
(1H, s, C᎐CH), 3.55 (2H, t, J 7.6, Bu), 3.24 (2H, t, J 7.3, Bu),
᎐
᎐
adenine), 7.90 (1H, s, adenine), 7.18 (2H, m, phenyl), 7.00 (1H,
2.06 (2H, t, J 7.3, Pr), 1.85 (2H, t, J 7.8, Pr), 1.48 (6H, m,
Pr ϩ Bu), 1.23 (6H, m, Pr ϩ Bu), 0.80 (9H, m, Pr ϩ Bu), 0.62
(3H, t, J 7.4, Pr). δC 158.9, 157.6, 152.0, 151.3, 144.1, 141.3,
124.6, 114.6, 51.5, 44.8, 35.5, 31.2, 30.6, 28.8, 20.5, 20.4, 19.8,
13.6, 13.5, 13.3. FABϩ MS: 384.6 (M ϩ Hϩ calc. 385.3)
(Found: C, 68.7; H, 9.8; N, 21.3. Calc. for C22H36N6: C, 68.7;
H, 9.4; N, 21.85%).
s, C᎐CH), 6.79 (3H, m, phenyl), 4.53 (2H, s, OCH ), 3.62 (2H,
᎐
2
m, Bu), 3.29 (2H, m, Bu), 1.82 (3H, s, CH3), 1.54 (4H, m, Bu),
1.28 (4H, m, Bu), 0.84 (6H, m, Bu). FABϩ MS: 420.6 (M ϩ Hϩ
calc. 421.3) (Found: C, 68.2; H, 7.5; N, 19.8. Calc. for C24H32-
N6O: C, 68.5; H, 7.7; N, 20.0%).
3-Benzoyl-1-(2-methylprop-1-enyl)thymine (16ba). Com-
pound 13b (0.44 g, 1 mmol) was evaporated from dry pyridine
(10 ml), dissolved in dry DMF (10 ml), and NaH (55% suspen-
sion in mineral oil, 0.045 g, 1 mmol) added under N2. After 2 h
at rt acetone (0.15 ml, 2 mmol) was added, and the mixture
stirred at rt for 4 days. Diethyl ether (60 ml) followed by water
(60 ml) were added, the phases were separated, and the water
phase (pH adjusted to 7–8) was extracted with diethyl ether
(2 × 40 ml). The combined organic phases were washed with
N6-(Dibutylaminomethylene)-9-(cyclopentylidenemethyl)-
adenine (16ac). Prepared in the same way as 16aa from
cyclopentanone (0.12 ml), stirred for 3 hours. Yield: 0.23 g
(66%, oil), Rf = 0.17 (heptane–EtOAc–Et3N 58:38:4 v/v/v).
NMR (CDCl3): δH 8.80 (1H, s, CH᎐N), 8.34 (1H, s, adenine),
᎐
7.80 (1H, s, adenine), 6.64 (1H, quintet, J 2.3, C᎐CH), 3.49 (2H,
᎐
t, J 7.6, Bu), 3.17 (2H, t, J 7.3, Bu), 2.30 (2H, m, cyclopentyl),
2.19 (2H, m, cyclopentyl), 1.44 (8H, m, cyclopentyl ϩ Bu), 1.18
J. Chem. Soc., Perkin Trans. 1, 2000, 2015–2021
2019

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brine, dried (MgSO4) and evaporated in vacuo, and the residue
purified by column chromatography on silica, eluted with
hexane–ethyl acetate 3:2 v/v, to give 16ba (0.096 g, 34%) as
colourless crystals, mp 135–136 ЊC, Rf = 0.44 (hexane–ethyl
acetate 2:3 v/v). NMR (CDCl3): δH 7.92 (2H, dd, J 8 and 1, Ph),
7.62 (1H, tt, J 8 and 1, Ph), 7.49 (2H, t, J 8, Ph), 7.02 (1H, q,
benzaldehyde (0.20 ml, 2 mmol) was added, and the mixture
was cooled to 0 ЊC. Sodium hydride (55% suspension in mineral
oil, 0.045 g, 1 mmol) was added in one portion and the mixture
stirred for 2 hours at 0 ЊC. Water (10 ml) was added, and the
solution extracted with diethyl ether (7 × 10 ml). The combined
organic layers were dried over Na2SO4 and evaporated in vacuo.
The residue was purified by column chromatography on silica,
eluted with heptane–EtOAc–Et3N, 58:38:4 v/v/v, to give 15a
(0.15 g, 39%) as an oily mixture of E and Z isomers (E:Z 1:3
J 1.2, H-6), 6.15 (1H, septet, J 1.5, NCH᎐C), 1.97 (3H, d, J 1.2,
᎐
T-Me), 1.84 (3H, d, J 1.5, E-Me), 1.74 (3H, d, J 1.5, Z-Me).
FABϩ MS: 285.2 (M ϩ Hϩ calc. 285.1) (Found: C, 67.1; H, 5.6;
N, 9.9. Calc. for C16H16N2O3: C, 67.6; H, 5.7; N, 9.85%).
1
according to H NMR). The isomers were not separated. The
product had identical data to the same compound prepared by
the Horner reaction.
1-Benzoyl-2-(2-methylprop-1-enyl)urea (17). When 13b (0.44
g, 1 mmol) was reacted with acetone (0.15 ml, 2 mmol) as
described above but with excess of NaH (2 mmol), compound
17 (0.060 g, 28%) was isolated after column chromatography
as colourless crystals, mp 174–175 ЊC, Rf = 0.57 (hexane–ethyl
acetate 2:3 v/v). NMR (DMSO-d6): δH 10.99 (1H, s, NH), 10.34
(1H, d, J 10.2, NH), 7.98 (2H, d, J 8, Ph), 7.64 (1H, t, J 8, Ph),
3-Benzoyl-1-(2-phenylethenyl)thymine (15b). Compound 14b
(0.38 g, 1 mmol) was evaporated from dry pyridine (10 ml),
dissolved in dry DMF (10 ml), and NaH (55% suspension in
mineral oil, 0.090 g, 2 mmol) was added under N2 at rt. After
5 min benzaldehyde (0.15 ml, 1.5 mmol) was added, and the
mixture stirred for 1 h at rt. Diethyl ether (60 ml) followed by
water (60 ml) were added. The phases were separated, and the
water phase extracted with diethyl ether (2 × 40 ml). The com-
bined organic phases were washed with brine, dried (MgSO4)
and evaporated in vacuo, and the residue purified by column
chromatography on silica, eluted with hexane–ethyl acetate 3:2
v/v, to give 15b (0.18 g, 55%) as a semisolid mixture of E and Z
7.51 (2H, t, J 8, Ph), 6.46 (1H, d, J 10.2, NCH᎐C), 1.71 (3H, s,
᎐
E-Me), 1.66 (3H, s, Z-Me). FABϩ MS: 219.1 (M ϩ Hϩ calc.
219.1) (Found: C, 65.95; H, 6.3; N, 12.7. Calc. for C12H14N2O2:
C, 66.0; H, 6.5; N, 12.8%).
3-Benzoyl-1-(2-propylpent-1-enyl)thymine (16bb). Prepared in
the same way as 16ba from 13b and heptan-4-one, reaction time
5 days. Yield: 0.035 g (10%), mp 104–105 ЊC, Rf = 0.64 (hexane–
ethyl acetate 2:3 v/v). NMR (CDCl3): δH 7.93 (2H, d, J 8, Ph),
7.64 (1H, t, J 8, Ph), 7.48 (2H, t, J 8, Ph), 6.99 (1H, q, J 1.2,
H-6), 6.13 (1H, s, NCH᎐C), 2.11 (2H, t, 7.6, E C᎐C-CH ), 2.05
1
isomers (E:Z 1:3 according to H NMR). Rf = 0.52 for the E
isomer and Rf = 0.47 for the Z isomer (ethyl acetate–hexane,
3:2 v/v). The isomers were not separated. The product had
identical data to the same compound prepared by the Horner
reaction.
᎐
᎐
2
(2H, t, J 7.7, Z C᎐C-CH ), 1.98 (3H, d, J 1.2, T-Me), 1.49 (4H,
᎐
2
m, 2 × C-CH2-Me), 0.93 (3H, t, J 7.3, Me), 0.92 (3H, t, J 7.6,
Me). FABϩ MS: 340.9 (M ϩ Hϩ calc. 341.2) (Found: C, 70.0;
H, 7.1; N, 8.2. Calc. for C20H24N2O3: C, 70.6; H, 7.1; N, 8.2%).
N6-(Dibutylaminomethylene)-9-(2-methylprop-1-enyl)adenine
(16aa). Prepared in the same way as 15a from 14a and acetone,
yield 0.060 g (18%). The product had identical data to the same
compound prepared by the Horner reaction.
1-(2-Methylprop-1-enyl)thymine (16ca). Prepared in the same
way as 16ba from 13c, 2 mmol of NaH, and acetone, reaction
time 4 days. Yield: 0.071 g (40%) as colourless crystals, mp 130–
131 ЊC, Rf = 0.21 (hexane–ethyl acetate 2:3 v/v). NMR (CDCl3):
δH 9.04 (1H, s, NH), 6.91 (1H, q, J 1.2, H-6), 6.13 (1H, septet,
N6-(Dibutylaminomethylene)-9-(2-propylpent-1-enyl)adenine
(16ab). Prepared in the same way as 15a from 14a and heptan-4-
one, yield 0.008 g (2%). The product had identical data to the
same compound prepared by the Horner reaction.
J 1.5, NCH᎐C), 1.92 (3H, d, J 1.2, T-Me), 1.83 (3H, d, J 1.5,
᎐
E-Me), 1.68 (3H, d, J 1.5, Z-Me). FABϩ MS: 181.0 (M ϩ Hϩ
calc. 181.1) (Found: C, 59.4; H, 6.8; N, 15.2. Calc. for
C9H12N2O2: C, 60.0; H, 6.7; N, 15.55%).
3-Benzoyl-1-(2-methylprop-1-enyl)thymine (16ba). Prepared
in the same way as 15b from 14b and acetone, yield 0.020 g
(7%). The product had identical data to the same compound
prepared by the Horner reaction.
1-(2-Propylpent-1-enyl)thymine (16cb). Prepared in the same
way as 16ba from 13c, 2 mmol of NaH, and heptan-4-one,
reaction time 5 days. Yield: 0.104 g (44%), mp 86–87 ЊC,
Rf = 0.38 (hexane–ethyl acetate 2:3 v/v). NMR (CDCl3): δH
References
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8.64 (1H, s, NH), 6.82 (1H, q, J 1.2, H-6), 6.55 (1H, s, NCH᎐C),
᎐
2.05 (2H, t, J 7.5, E C᎐C-CH ), 1.93 (2H, t, J 7.7, Z C᎐C-CH ),
᎐
᎐
2
2
1.86 (3H, d, J 1.2, T-Me), 1.41 (4H, m, 2 × C-CH2-Me), 0.88
(3H, t, J 7.3, Me), 0.82 (3H, t, J 7.3, Me). FABϩ MS: 237.0
(M ϩ Hϩ calc. 237.2) (Found: C, 65.8; H, 8.5; N, 11.9. Calc. for
C13H20N2O2: C, 66.1; H, 8.5; N, 11.85%)
1-(Cyclohexylidenemethyl)thymine (16cc). Prepared in the
same way as 16ba from 13c, 2 mmol of NaH, and cyclohex-
anone, reaction time 3 days. Yield: 0.150 g (68%), mp 159–
160 ЊC, Rf = 0.32 (ethyl acetate–hexane 3:2 v/v). NMR (CDCl3):
δH 8.91 (1H, s, NH), 6.88 (1H, q, J 1.2, H-6), 6.12 (1H, s,
NCH᎐C), 2.21 (2H, t, J 5.5, E C᎐CCH ), 2.11 (2H, t, J 5.5, Z
᎐
᎐
2
C᎐CCH ), 1.92 (3H, d,
J 1.2, T-Me), 1.60 (6H, m,
᎐
2
CH2CH2CH2). FABϩ MS: 221.0 (M ϩ Hϩ calc. 220.1) (Found:
C, 64.9; H, 7.35; N, 12.7. Calc. for C12H16N2O2: C, 65.4; H, 7.3;
N, 12.7%).
HWE reactions
N6-(Dibutylaminomethylene)-9-(2-phenylethenyl)adenine
(15a). Compound 14a (0.42 g, 1 mmol) was evaporated in vacuo
from pyridine (10 ml), dissolved under N2 in dry DMF (10 ml),
2020
J. Chem. Soc., Perkin Trans. 1, 2000, 2015–2021

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