New results on the photoreactivity of 5-fluoro-1,3-dimethyluracil with methoxylated naphthalenes

Article abstract of DOI:10.3987/COM-12-S(N)116

Photocycloaddition of 5-fluoro-1,3-dimethyluracil (5-FDMU) with various methoxy and dimethoxynaphthalenes was investigated. Reaction of 5-FDMU with 1,x-dimethoxynaphthalenes (x = 4-7) gave rise to the selective formation of cycloadducts, conjugated arylpropenylidene-1,3-diazin-2-ones, which were derived from an initially formed oxetane moiety via the Paterno-Buechi reaction cycloadduct. The present study shows that the presence of a methoxy substituent on the ?-position in naphthalene is essential for the formation of products through the Paterno-Buechi reaction. This unique photoreaction involving formation of an oxetane between 5-FDMU and a naphthalene ring, followed by a concomitant disruption of the initially formed oxetane moiety and an aromatic ring of naphthalene moiety, can be regarded as a novel aromatic Paterno-Buechi reaction.

Full text of DOI:10.3987/COM-12-S(N)116

HETEROCYCLES, Vol. 86, No. 2, 2012
1465
HETEROCYCLES, Vol. 86, No. 2, 2012, pp. 1465 - 1481. © 2012 The Japan Institute of Heterocyclic Chemistry
Received, 31st August, 2012, Accepted, 12th October, 2012, Published online, 18th October, 2012
DOI: 10.3987/COM-12-S(N)116
NEW RESULTS ON THE PHOTOREACTIVITY OF 5-FLUORO-1,3-
DIMETHYLURACIL WITH METHOXYLATED NAPHTHALENES
Kazue Ohkura,*1 Kazuya Aizawa,1 Rie Mukaida,1 Hiromichi Akizawa,1 and
Koh-ichi Seki*2
1School of Pharmaceutical Sciences, Health Sciences University of Hokkaido,
Ishikari-Tobetsu, Hokkaido 061-0293, Japan. 2Central Institute of Isotope Science,
Hokkaido University, Kita-15, Nishi-7, Kita-ku, Sapporo 060-0815, Japan
Abstract – Photocycloaddition of 5-fluoro-1,3-dimethyluracil (5-FDMU) with
various methoxy and dimethoxynaphthalenes was investigated. Reaction of
5-FDMU with 1,x-dimethoxynaphthalenes (x = 4-7) gave rise to the selective
formation of cycloadducts, conjugated arylpropenylidene-1,3-diazin-2-ones,
which were derived from an initially formed oxetane moiety via the
Paterno-Büchi reaction cycloadduct. The present study shows that the presence
of a methoxy substituent on the -position in naphthalene is essential for the
formation of products through the Paterno-Büchi reaction.
This unique
photoreaction involving formation of an oxetane between 5-FDMU and a
naphthalene ring, followed by a concomitant disruption of the initially formed
oxetane moiety and an aromatic ring of naphthalene moiety, can be regarded as a
novel aromatic Paterno-Büchi reaction.
INTRODUCTION
Photoreaction of nucleic bases has received much attention from both organic chemistry and biological
perspectives. The formation of thymine-adenine photoadducts1 or of pyrimidine-pyrimidine cyclobutane
dimers and bipyrimidine [6-4]-photoadducts2 between adjacent pyrimidine bases play important roles in
the direct induction of DNA damage. The former two reactions result through [2 + 2]-addition of olefinic
double bonds, while the [6-4]-photoadducts derive from oxetane or azetidine intermediates formed by
photoaddition of the C4-carbonyl of thymine or the C4-imino tautomer of cytosine3 across the C5 = C6
double bond of the adjacent base.
This paper is Dedicated to Professor Ei-ichi Negishi on the occasion of his 77th birthday.

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HETEROCYCLES, Vol. 86, No. 2, 2012
At the same time, photochemical coupling reactions involving the C = C or C = O double bonds have attracted
much attention from a synthetic view point, since the chemical modification of nucleic bases has been
recognized as one of the most promising approaches for developing bioactive substances such as
anticancer and antiviral agents.4 In this context, we have intensively studied the photochemical
modification of halogenated pyrimidines that occurs when they are irradiated in presence of aromatic
hydrocarbons such as benzene and naphthalene derivatives. We have thus successfully demonstrated that
upon UV-irradiation, 6-chloro-1,3-dimethyluracil undergoes a variety of photocycloaddition reactions
with benzene derivatives5 and naphthalenes,6 to give a structurally diverse range of photoproducts. We
recently reported that UV-irradiation of 5-FDMU with naphthalene and its derivatives substituted with
electron withdrawing groups, or an electron donating methyl group, proceeded mode-selectively by 1,2-
and 1,4-cycloaddition, to afford naphthocyclobutapyrimidines and ethenobenzoquinazolines (barrelene),
respectively, depending on the irradiation conditions.7 The cycloadditions with aromatic hydrocarbons
hitherto reported, however, are limited only to the couplings or substitutions on the C5=C6 double bond
of the pyrimidine ring. No cycloaddition involving the carbonyl group and an aromatic ring has yet been
discovered. The occurrence of a Paterno-Büchi type reaction would provide a new aspect for the
photochemical modification of pyrimidine rings with aromatic compounds.
In order to explore further the scope of this reaction, we aimed to extend our work to the photochemistry
of 5-FDMU with methoxynaphthalenes (MN). In the present paper8 we report that the photoreaction of
5-FDMU with naphthalenes with a methoxy group at the -position proceeds by way of Paterno-Büchi
cycloaddition, followed by concomitant disruption of the resulting oxetane ring to yield highly conjugated
arylpropenylidene-1,3-diazin-2-ones, while the 1,4-cycloaddition reaction occurs exclusively with
naphthalenes without a methoxy group at the -position.
RESULTS AND DISCUSSION
In contrast to the photoreaction of 5-FDMU with 2-methoxynaphthalene (2-MN), whereby 1,4-cyclo-
adducts were furnished exclusively,7b external irradiation of a degassed solution of 5-FDMU and
1-methoxynaphthalene (1-MN) in cyclohexane with a 500 W high-pressure mercury lamp in a Pyrex tube
(>300 nm) for 10 h afforded methyl 2-[(1E)-3-(5-fluoro-1,3-dimethyl-2-oxo-1,3-dihydropyrimidin-
4-ylidene)prop-1-enyl]benzoates as a mixture of the (1′E,3′E)-isomer (1aI) (24%) and the (1′E,3′Z)-
stereoisomer (1aII) (14%), together with a conventional regio-isomeric mixture of 1,4-cycloadducts (2aI,
2aII) and 1,2-cycloadducts (3aI, 3aII) as the minor components (yields are given based on 47% of
5-FDMU consumed) (Scheme 1). Compound 1aII isomerized spontaneously into the (1′E,3′E)-isomer
(1aI) when kept at room temperature in the dark (1aII; half-life time = 6.5 h at room temperature). Upon
irradiation, 1aI isomerized into 1aII, to yield a 1:1 mixture of 1aI and 1aII at the equilibrium state. The

HETEROCYCLES, Vol. 86, No. 2, 2012
1467
(1′E,3′Z)-stereoisomer (1aII) is too unstable to isolate in sufficient amounts as a pure form, so spectral
analyses for 1aII were made on the mixture with 1aI.
OMe
O
Me
F
O
F
N
3
N
Me
7
12
1
N
O
N
h (> 300 nm)
500 W h.p. Hg-lamp
rt, cyclohexane , 1 h
O
H
10
9
OMe
Me
5-FDMU
Me
12-OMe, 8-OMe,
11-OMe, 7-OMe
OMe
h (> 300 nm)
500 W h.p. Hg-lamp
rt, cyclohexane , 10 h
MeO2C
CO2Me
2
O
F
O
R2
F
1'
3
N
Me
9
Me
7
3
3
12
N
+
3'
2'
2'
1
N
Me
+
+
3'
O
5
H
O
N
10
9
OMe
Me
F
5"
7
R1
Me
5"
6"
F
N
Me
N
3"
2"
O
1"
6"
N
O
3aI: R1=H, R2=OMe
3aII R1=OMe, R2=H
N
2aI: 9-OMe
2aII:10-OMe
Me
Me
1aII
1aI
Scheme 1
The stereochemistry of 1aI and 1aII was determined with the aid of NOE experiments (Figure 1).
Irradiation of the H-3′ proton of 1aI significantly affected the H-1′ vinyl proton, as well as N3′′-Me. Also
6
irradiation at N3′′-Me showed enhancement of
CO2Me
1
MeO2C
5
signal for the H-3′ vinyl proton. On the other
4
2
3
3
H
1'
1'
H
4
2
H
hand, the (1′E,3′Z) isomer (1aII) showed no
NOE correlation for H-3′N3′′-Me, while
significant correlation was observed between
N3′′-MeH-2′. These differences in the NOE′s
conclusively determined the stereochemistry of
1aI as (1E′,3E′) and 1aII to be (1E′,3Z′),
respectively.8
H
H
2'
2'
H
H
3'
3'
H
H
F
F
Me
Me
3" N
N
3"
1"
1"
N
O
O
N
1aII
1aI
Me
Me
Figure 1. NOE correlations for 1aI and 1aII
The formation of 4-(3-phenylprop-2-enylidene)-5-fluoropyrimidin-2-ones (1aI, 1aII) is rationally
explained in terms of [2 + 2]-addition between the uracil C4 = O carbonyl group and the C1 = C2 double
bond of the naphthalene ring (i.e., Paterno-Büchi reaction), giving rise to the corresponding oxetane

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HETEROCYCLES, Vol. 86, No. 2, 2012
intermediate (Scheme 2), which is followed by the subsequent ring opening of the highly strained oxetane
moiety, accompanied by the concomitant cleavage of the naphthalene A-ring in the manner shown in
Scheme 2.
B
B
A
MeO
B
MeO
MeO
O
O
O
H
A
h
1aI, 1aII
Me
O
Me
O
F
F
Me
N
N
F
N
1-MN
N
N
Me
N
O
Me
5-FDMU
Me
oxetane intermediate
Scheme 2
It is noted that in most cases, enones undergo [2 + 2]-photocycloaddition with olefins, leading to the
formation of cyclobutanes via -*excited states, in competition with oxetane formation from then -*
triplet state of the carbonyl moiety.9 In order to gain more insight into the mechanism underlying the
present reaction, UV-irradiation of 5-FDMU and 1-MN was conducted in varying ratios. Thus, it is
demonstrated that the ratio of Paterno-Büchi adducts vs. (1,2-adducts + 1,4-adducts) increases as the
molar ratios of 1-MN vs. 5-FDMU decreased (Table 1). These results suggested that the present
Paterno-Büchi reaction is initiated by the n-* excited 5-FDMU. Addition of triplet quencher
trans-piperylene was inefficient on the formation of Paterno-Büchi product, suggesting the participation
of an n-* singlet state or extremely short-lived n-* triplet state of 5-FDMU.
Table 1. Photoreaction of 5-FDMU with various amounts of 1-MN in benzene for 3 h
Molar Ratio
Yield based on 5-FDMU consumed (%)
Product Ratio
Paterno-Büchi
Product (1a)
1,4-Adduct 1,2-Adduct
(1a) vs.
(2a+3a)
1,4-Adduct (2a) vs.
1,2-Adduct (3a)
1MN/5-FDMU
(2aI, 2aII)
(3aI, 3aII)
10
2
52
42
62
49
29
20
15
14
7.5
3.5
14
12
8.5
5.8
5.7
7.5
1.2
1.3
1.9
2.3
2.5
4.0
4.7
4.4
1.7
1.0
1
11
0.5
0.1
5.6
2.3
4.2
1.7

HETEROCYCLES, Vol. 86, No. 2, 2012
1469
Interestingly, the ratio of 1,4-adduct vs. 1,2-adduct increases as the molar ratio of 1-MN vs. 5FDMU
increases from 0.1 to 2 (Table 1), implying that the participation of a charge-transfer complex (CT) or
exciplex formation may participate in the 1,4-addition. However, no spectroscopic evidence supporting the
presence of any intermolecular interaction was obtained.
We then carried out the photoreaction of 5-FDMU with 1-MN in various solvents. As shown in Table 2,
the Paterno-Büchi reaction proceeds preferentially in such a non- (or weakly-)-polar solvents, such as
cyclohexane, benzene or toluene. In a polar solvent, acetonitrile, the Paterno-Büchi reaction was
suppressed significantly and 1,4-cyloadducts were formed only in sparing yield, while in a protic solvent,
methanol, the substitution reaction occurs exclusively.
Presumably, in a polar solvent, acetonitrile, photo-induced electron transfer (PET) from electron donating
1-MN prevails, to disrupt the oxetane intermediate10 and probably 1,2-adducts, cyclobutane derivatives,11
to restore the starting 5-FDMU and 1-MN, resulting in the lowest consumption of the starting 5-FDMU;
only trace amounts of 1,4-cycloadducts produced were detected.
Table 2. Photoreaction of 5-FDMU with 1-MN in various solvents (3 h)
DMU
(%)
Paterno-Büchi
Product (%)
1,4-Adduct
(%)
1,2-Adduct
(%)
ArDMU
(%)
Consumed
5-FDMU(%)
Solvent
cyclohexane
benzene
toluene
MeCN
MeOH
13 (43)
13 (62)
9 (45)
---
8 (27)
5 (24)
6 (30)
3 (10)
1 (5)
---
---
---
---
---
9 (38)
30
21
20
10
24
trace (<0.5)
---
---
---
4 (17)
( ): Yields are given based on 5-FDMU consumed. DMU: 1,3-dimethyluracil.
ArDMU: aryl 1,3-dimethyluracil (Substitution product).
In a protic solvent, methanol, conventional substitution reaction and hydrogen subtraction were observed,
as has been found in the reaction with 5-FDMU and benzene or naphthalene.7a,7b,12 The substitution
reaction can be explained in terms of PET, and subsequent protonation to the resulting radical anion of
5-FDMU, followed by the radical-radical coupling between 5-FDMU and 1-MN.
Thus, the precise mechanisms participating in the present Paterno-Büchi reaction remain unclear. The
generation of the products through Paterno-Büchi reaction can be explained in terms of the electronic
effects of a methoxy group incorporated in the -position on the oxetane intermediate which serves
importantly in the disruption of the oxetane moiety in the way to produce conjugated
arylpropenylidenepyrimidines, whereas the oxetane intermediates from the -MN, if ever derived, with
no such driving force to furnish propenylidenepyrimidine derivatives, would only revert to the original
5-FDMU and -MN.

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HETEROCYCLES, Vol. 86, No. 2, 2012
In order to explore the important role of a methoxy group on the naphthalene ring in yielding Paterno-
Büchi reaction involved products, photoreaction of 5-FDMU with naphthalenes with methoxy groups at
varying positions was examined. UV-irradiation of 5-FDMU and 1,4-dimethoxynaphthalene (1,4-MN)
under analogous conditions furnished methyl 2-[(1E)-1-methoxy-3-(5-fluoro-1,3-dimethyl-2-oxo-1,3-
dihydropyrimidin-4-ylidene)-1-propenyl]benzoate as a separable mixture of the (1′E,3′E)-isomer (1bI)
(44%) and the (1′Z,3′E)-stereoisomer (1bII) (15%), together with a novel valence isomer 1bIII, in 20%
yield (yields are given based on 82% of 5-FDMU consumed). Upon being allowed to stand in the dark at
25 °C, 4-[(3,3-dimethoxy-1-oxoindan-2-yl)methylene]-5-fluoro-1,3-dimethyl-1,3-dihydropyrimidin-2-one
(1bIII) transformed into the oxoindenyl derivative 1bIV with a half-life time of ca. 5 h.
The stereochemistry of 1bI was determined with the aid of NOE experiments. Irradiation of the H-3′
proton significantly affected the 1′-OMe proton, as well as N3′′-Me. Also irradiation at H-2′ showed
enhancement of the signal for the H-3 aromatic proton. On the other hand, the (1′Z,3′E) isomer (1bII)
showed NOE correlation for H-3′N3′′-Me and aromatic H-3. Also significant correlation was observed
between H-2′1′-OMe. These differences in the NOE′s conclusively determined the stereochemistry of
1bI as (1′E,3′E) and 1bII to be (1′Z,3′E), respectively. The structure of the novel adduct 1bIII was
deduced by means of MS (M + H+, m/z 347) and NMR spectroscopy. The 1H-NMR spectrum showed two
OMes, H-2′′ and aromatic protons in the dimethoxy-1-oxoindan-2-yl methylene moiety. Also the
13C-NMR spectrum showed peaks due to C-1′′ carbons at 201.5 ppm and C-1′ at 92.6 ppm in oxoindanyl
methylene part. Indene derivative 1bIV was easily conformed by means of MS (M + H+, m/z 315) and
NMR spectroscopy.
The formation of indene derivatives 1bIII and 1bIV is rationally explained in terms of intramolecular
ring closure of 1bIII or 1bIV produced from the Paterno-Büchi reaction, followed by the subsequent ring
opening of the resulting oxetane moiety in the manner shown in Scheme 3.
-OMe
MeO+
MeO
O
Me
MeO
MeO
- OMe-
+ OMe-
O=C
F
- MeOH
2"
2"
1"
1"
H
O
H
O
1'
1'
OMe
O
Me
O
Me
Me
N
F
Me
F
F
N
N
N
N
Me
O
N
O
N
O
N
Me
Me
Me
1bI
1bIV
1bIII
Scheme 3
Photoreaction of 1,5-MN under the conditions employed above (in cyclohexane, 10 h) furnished methyl
3-methoxy-2-[(1′E,3′E)-3-(5-fluoro-1,3-dimethyl-2-oxo-1,3-dihydropyrimidin-4-ylidene)prop-1-enyl]-

HETEROCYCLES, Vol. 86, No. 2, 2012
1471
benzoate (1cI) in high yield (59%) together with small amounts of the (1′E, 3′Z)-isomer (1cII) (16%) (at
the stage where 54% of the 5-FDMU was consumed).
Photoreaction of 1,6-MN afforded methyl 4-methoxy-2-[(1′E)-3-(5-fluoro-1,3-dimethyl-2-oxo-1,3-
dihydropyrimidin-4-ylidene)-1-propenyl]benzoate as a mixture of the (1′E,3′E)-isomer (1dI) (39%) and
the (1′E,3′Z)-stereoisomer (1dII) (9%) (yields are given based on 46% of 5-FDMU consumed).
Similarly, 1,7-MN afforded the (5-methoxy-phenylpropenylidene)-1,3-diazin-2-ones as a mixture of the
(1′E,3′E)-isomer (1eI) (44%) and the (1′E, 3′Z)-stereoisomer (1eII) (3%) together with the conventional
1,2-cycloadduct (3e) in 6% yield (yields are given based on 39% of 5-FDMU consumed).
Next, the photoreaction with naphthalenes with methoxy groups at both of α and β-positions was
examined: Irradiation of 1,2-MN (10 h) furnished 1,2-adduct, cyclobutapyrimidine (3f) (24%) as a major
product together with the conventional 1,4-cycloadduct (2f) in 7% yield (yields are given based on 38%
of 5-FDMU consumed).
In the case of 1,3-MN (10 h), the conventional 1,2-cycloadducts (3gI, 3gII) were obtained as a
stereoisomeric mixture in 24% and 18% yields, respectively (yields are given based on 40% of 5-FDMU
consumed).
Then the photoreaction with naphthalenes bearing methoxy groups at the β-position was conducted:
Photoreaction of 2,6-MN in cyclohexane (10 h) afforded the 1,4-adduct, 8,12-dimethoxyethenobenzo-
quinazoline (2h), exclusively (88% yield at the stage where 25% of 5-FDMU consumed). In the case of
2,7-MN (3 h), 1,4-adduct (2iI) (8,11-dimethoxy derivative) was also yielded as the major product (36%),
together with the regioisomer (2iII) (7,12-dimethoxy derivative) (2%) as a minor component (yields are
given based on 42% of 5-FDMU consumed). These results are summarized in Chart 1 and Table 3.
O
α
OMe
OMe
OMe
Me
F
Paterno-Buchi reaction
N
β
A
+
B
1-MN
MeO2C
O
N
1,4-MN
1,5-MN
1,6-MN
1,7-MN
CH
CH
CH
Me
2-MN
Me
O
2,6-MN
2,7-MN
1,2-MN
1,3-MN
F
1,4-additon
N
1,2-addition
N
Me
MeO
O
OMe
OMe
F
Me
arylpropenylidene-
1,3-diazin-2-ones
(1a, 1b, 1c, 1d, 1e)
N
Me
O
O
O
N
N
Me
OMe
N
Me
F
H
ethenobenzoquinazolines
naphthocyclobutapyrimidines
(2h, 2i)
(3f, 3g)
Chart 1

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HETEROCYCLES, Vol. 86, No. 2, 2012
These results demonstrate that UV- irradiation of a mixture of 5-FDMU and MNs undergoes
photocycloaddition which can be classified into three categories of cycloaddition depending on the site of
the methoxy substituents on the naphthalene ring: 1) Naphthalenes with methoxy groups at the  or ,-
position in the A ring, or at the -position in the A ring and either the α- or, β-position in the B ring,
effected Paterno-Büchi cycloaddition preferentially.
2) In the case of naphthalenes having
Table 3. The mode selectivity on the photoreaction of
methoxy groups at the ,-position in A ring,
1,2-cycloaddition proceeds favorably. 3)
Mono- and dimethoxynaphthalenes with no
methoxy group at the -position exclusively
underwent conventional 1,4-cycloaddition.
The 1,2- and 1,3-MNs, which have an
-methoxy group as well as the -methoxy
group on the A-ring of naphthalene,
underwent 1,2-cycloaddition exclusively.
Although the precise mechanisms involved
in the reaction remain unclear, we have
previously reported7c,7d that upon UV-
5-FDMU with methoxynaphthalenes
Methoxy-
naphthalene in A ring
Position Position
Reaction Mode
in B ring
1-MN
1,4-MN
1,5-MN
1,6-MN
1,7-MN
1,2-MN
1,3-MN
2-MN
α
α, α
α
α
β
β
Paterno-Büchi
Reaction
α
α
α, β
α, β
β
1,2-Addition
1,4-Addition
2,6-MN
2,7-MN
β
β
β
β
irradiation of 5-FDMU with naphthalene, 1,4-addition took place through triplet excited states while
1,2-cycloaddition proceeded via the singlet excited state. Based on these findings, it is surmised that 1,2-
and 1,3-MNs may serve as a singlet sensitizer or a singlet quencher of 5-FDMU in the n-* singlet states,
to generate excited MNs in the -* singlet states.
In the case of naphthalenes with methoxy groups only at , the conventional 1,4-cycloaddition observed
in our serial studies on the photoreaction of 5-FDMU with naphthalenes took place exclusively.7
Thus, the present work demonstrates the significant role of the presence of a methoxy group at the
-position for yielding Paterno-Büchi cycloaddition involved adducts.
CONCLUSION
Despite a large number of examples involving oxetane formation,13 only a few papers on the aromatic
Paterno-Büchi cycloaddition have appeared,14 except for the reaction with five-membered
heteroaromatics.15 It is noteworthy that our present study provides a new example of an
aromatic-Paterno-Büchi reaction which involves the synthesis of an intermediate oxetane, followed by
concomitant ring opening of the oxetane moiety and disruption of the original aromatic ring, giving rise

HETEROCYCLES, Vol. 86, No. 2, 2012
1473
to highly conjugated methyl 2-[-3-(5-fluoro-1,3-dimethyl-2-oxo-1,3-dihydropyrimidin-4-ylidene)-1-
propenyl]benzoates.
EXPERIMENTAL
NMR spectra were measured with a JEOL JNM-ECA500 (500 MHz) spectrometer. Chemical shifts are
given on the  (ppm) scale based onthe residual deuterated solvent signals as reference. MS spectra and
high-resolution EIMS and FABMS (HRMS) spectra were recorded with a JEOL FABmate and a JEOL
JMS-HX110, respectively. HPLC was conducted on a Shim-pac PREP-Sil (H) (25 cm x 20 mm i. d.)
(silica gel), using a LC-6A apparatus (Shimadzu, Kyoto) with monitoring at 254 nm. UV-Irradiation was
carried out externally with a 500 W high-pressure mercury lamp (Eiko-sha, Osaka) in a degassed Pyrex
1
tube (> 300 nm) on a merry-go-round apparatus. Yields are determined by means of H-NMR
spectroscopy with p-dinitrobenzene as an internal standard.
Photoreaction of 5-FDMU with methoxynaphthalenes. ____ Typically, an equivalent molar solution (1.5
mM) of 5-FDMU and methoxynaphthalene in cyclohexane (160 mL) was introduced portionwise (5 mL
each) into 32 degassed Pyrex tubes, and irradiated externally at rt (10 h unless cited therein). The reaction
mixture was concentrated in vacuo, and the residual oil was submitted to HPLC with appropriate solvent
systems as follows: 5% AcOEt in CH2Cl2 for adducts 1a, 1b, 1e, 3f, and 2h 20-30% AcOEt in hexane for
adducts 1c, 1d, 3g and 2i.
Methyl 2-[(1E,3E)-3-(5-fluoro-1,3-dimethyl-2-oxo-1,3-dihydropyrimidin-4-ylidene)-1-propenyl]-
benzoate (1aI): Yellow oil. 1H-NMR (C6D6) δ: 2.43 (3H, s, N1′′-Me), 2.76 (3H, s, N3′′-Me), 3.50 (3H, s,
C1-CO2Me), 5.25 (1H, d, J = 8.6 Hz, H-6′′), 5.54 (1H, d, J = 11.0 Hz, H-3′), 6.90 (1H, dd, J = 7.4, 8.0 Hz,
H-5), 7.07 (1H, dd, J = 7.4, 8.0 Hz, H-4), 7.73 (1H, d, J = 8.0 Hz, H-3), 7.82 (1H, dd, J = 11.0, 15.0 Hz,
H-2′), 7.90 (1H, d, J = 8.0 Hz, H-6), 7.92 (1H, dd, J = 4.4, 15.0 Hz, H-1′). NOE: H-3′ with N3′′-Me
(14.1%), H-1′ (6.4%); H-6′′ with N1′′-Me (7.1%); H-2′ with H-3 (2.0%); H-3 with H-2′ (3.2%), H-4
(5.8%). FAB-MS m/z: 317 [M+H]+. HRFAB-MS: Calcd for C17H18N2O3F: 317.1301. Found: 317.1316.
UV λmax (CHCl3) nm (ε): 376 (21290).
Methyl 2-[(1E,3Z)-3-(5-fluoro-1,3-dimethyl-2-oxo-1,3-dihydropyrimidin-4-ylidene)-1-propenyl]-
1
benzoate (1aII): H-NMR (C6D6) δ: 2.44 (3H, s, N1′′-Me), 3.20 (3H, s, N3′′-Me), 3.46(3H, s,
C1-CO2Me), 5.25 (1H, d, J = 6.9 Hz, H-6′), 5.86 (1H, d, J = 12.0 Hz, H-3′), 6.94 (1H, dd, J = 7.4, 8.0 Hz,
H-5), 7.12 (1H, dd, J = 7.4, 8.0 Hz, H-4), 7.12 (1H, dd, J = 12.0, 15.0 Hz, H-2′), 7.43 (1H, d, J = 8.0 Hz,
H-3), 7.71 (1H, d, J = 15.0 Hz, H-1′), 7.90 (1H, d, J = 8.0 Hz, H-6). NOE: H-3′ with H-1′ (20.4%), H-2′
(5.4%); H-6′′ with N1′′-Me (7.1%); H-2′ with N3′′-Me (3.2%), H-3 (4.0%). HRFAB-MS: Calcd for
C17H18N2O3F: 317.1301. Found: 317.1296.
4a-Fluoro-4a,5,10,10a-tetrahydro-10-methoxy-1,3-dimethyl-cis-5,10-ethenobenzo[f]quinazoline-2,4-

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HETEROCYCLES, Vol. 86, No. 2, 2012
dione (2aI): Colorless crystals, mp 134-135 °C (hexane). 1H-NMR (CDCl3) δ: 2.59 (3H, s, N3-Me), 3.20
(3H, s, N1-Me), 3.66 (1H, d, J = 31.7 Hz, H-10a), 3.71 (3H, s, C10-OMe), 4.51 (1H, dt, J = 1.7, 6.0 Hz,
H-5), 6.68 (1H, dd, J = 6.0, 8.2 Hz, H-12), 6.88 (1H, dd, J = 1.7, 8.2 Hz, H-11), 7.15-7.17 (3H, H-6, H-7,
H-8), 7.42 (1H, d, J = 7.7 Hz, H-9). HRFAB-MS: Calcd for C17H18N2O3F: 317.1301. Found: 317.1324.
4a-Fluoro-4a,5,10,10a-tetrahydro-9-methoxy-1,3-dimethyl-cis-5,10-ethenobenzo[f]quinazoline-2,4-
dione (2aII): Colorless crystals, mp 149-151 °C (hexane). 1H-NMR (C6D6) δ: 2.69 (3H, s, N1-Me), 2.77
(3H, s, N3-Me), 3.13 (1H, dd, J = 2.9, 31.0 Hz, H-10a), 3.18 (3H, s, C9-OMe), 4.46 (1H, ddd, J = 1.2, 2.9,
6.3 Hz, H-10), 4.66 (1H, ddd, J = 1.7, 4.6, 6.3 Hz, H-5), 6.19 (1H, ddd, J = 1.7, 6.3, 7.5 Hz, H-11), 6.22
(1H, d, J = 8.0 Hz, H-8), 6.32 (1H, ddd, J = 1.2, 5.8, 7.5 Hz, H-12), 6.79 (1H, dd, J = 7.5, 8.0 Hz, H-7),
6.92 (1H, d, J = 7.5 Hz, H-6). HRFAB-MS: Calcd for C17H18N2O3F: 317.1301. Found: 317.1328.
10a-Fluoro-6a,6b,10a,10b-tetrahydro-5-methoxy-7,9-dimethylnaphtho[1′,2′:3,4]cyclobuta[1,2-d]-
1
pyrimidine-8,10-dione (3aI): Colorless oil. H-NMR (CDCl3) δ: 2.94 (3H, d, J = 1.1 Hz, N9-Me), 3.11
(3H, s, N7-Me), 3.67 (3H, s, C5-OMe), 3.83 (1H, ddd, J = 3.7, 7.3, 10.8 Hz, H-6a), 3.96 (1H, dd, J = 10.8,
18.1 Hz, H-10b), 4.34 (1H, dd, J = 7.3, 20.7 Hz, H-6b), 4.44 (1H, d, J = 3.7 Hz, H-6), 7.11-7.15 (4H, m,
H1-H4). NOE: H-6 with H-6a, N7-Me, C5-Me; H-6b with N1-Me; H-10b with H-6a, H-1. FAB-MS m/z:
317 [M+H]+. HRFAB-MS: Calcd for C17H17N2O3F: 317.1301. Found: 317.1284.
10a-Fluoro-6a,6b,10a,10b-tetrahydro-10b-methoxy-7,9-dimethylnaphtho[1′,2′:3,4]cyclobuta[1,2-d]-
pyrimidine-8,10-dione (3aII): Colorless oil.1H-NMR (CDCl3) δ: 2.75 (3H, d, J = 1.1Hz, N9-Me), 3.03
(3H, s, N7-Me), 3.16 (3H, s, C10b-OMe), 3.80 (1H, ddd, J = 1.1, 5.0, 9.7 Hz, H-6a), 4.47 (1H, dd, J = 9.7,
22.9 Hz, H-5), 5.74 (1H, dd, J = 5.0, 9.7 Hz, H-6), 7.05-7.44 (4H, m, H1-H4). NOE: H-6b with H-6a,
N7-Me; H-6a with H-6b, H-6, C10b-OMe; H-6 with H-5, H-6a; N7-Me with H-6b, H-6. FAB-MS m/z:
317 [M+H]+. HRFAB-MS: Calcd for C17H17N2O3F:317.1301. Found: 317.1306.
Methyl 2-[(1E,3E)-1-methoxy-3-(5-fluoro-2,4-dimethyl-2-oxo-1,3-dihydropyrimidin-4-ylidene)prop-
1-enyl]benzoate (1bI): Yellow oil. 1H-NMR (acetone-d6) δ: 2.86 (3H, s, N3′′-Me), 3.12 (3H, s, N1′′-Me),
3.44 (3H, s, C1′-OMe), 3.79 (3H, s, C1-CO2Me), 5.70 (1H, d, J = 12.0 Hz, H-3′), 6.23 (1H,d, J = 12.0 Hz,
H-2′), 6.75 (1H, d, J = 9.7 Hz, H-6”), 7.39 (1H, dt, J = 1.2, 7.5 Hz, H-4), 7.49 (1H, dd, J = 1.2, 7.5 Hz,
H-5), 7.51 (1H, dt, J = 1.2, 7.5 Hz, H-3), 7.60 (1H, dd, J = 1.2, 7.5 Hz, H-6). NOE: H-3′ with C1′-OMe
(4.4%), N3′′-Me (19%), H-2′ (11%); H-6′′ with N1′′-Me (9.2%); H-2′ with H-3′ (8.8%), H-3 (5.2%);
13
N1′′-Me with H-5′′ (16%). C-NMR (acetone-d6) δ: 31.1 (N3′′-Me), 35.5 (N1′′-Me), 51.0 (OMe), 58.0
(OMe), 95.2 (3′), 110.7 (2′), 117.3 (6′′), 127.9 (4), 128.4 (5), 128.7 (3), 130.3 (4′′), 130.8 (2), 135.2 (6),
142.3 (5′′), 151.8 (2′′), 151.8 (1′), 170.0 (1). HMBC：H-1 with C1-CO, C-2; H-3 with C-1′, C-4; H-4 with
C-2, C-5; H-5 with C-1, C-5; H-6 with C-1, C-4; H-2′ with C-2, C-1′, C-4′′; H-3′with C-6”, C-2′, C-4′′;
N1′′-Me with C-2′′; N1′′-Me with C-2′′,C-6′′; H-6′′ with C-5′′, C-2′′, C-4′′. FAB-MS m/z: 347 [M+H]+.
HRFAB-MS: Calcd for C18H20N2O4F: 347.1409. Found: 347.1409.

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Methyl 2-[(1Z,3E)-1-methoxy-3-(5-fluoro-1,3-dimethyl-2-oxo-1,3-dihydropyrimidin-4-ylidene)-
1
prop-1-enyl]benzoate (1bII): Yellow oil. H-NMR (acetone-d6) δ: 2.90 (3H, s, N3′′-Me), 3.09 (3H, s,
N1′′-Me), 3.64 (3H, s, C1′-OMe), 3.77 (3H, s, C1-CO2Me), 5.15 (1H, d, J = 12.0 Hz, H-3′), 6.15 (1H,d, J
= 12.0 Hz, H-2′), 6.79 (1H, d, J = 9.7 Hz, H-5′′), 7.50 (1H, dd, J = 7.5, 8.0 Hz, H-5), 7.56 (1H, d, J = 8.0
Hz, H-3), 7.60 (1H, dd, J = 1.0, 7.7 Hz, H-4), 7.78 (1H, d, J = 7.5 Hz, H-6). NOE: H-3′ with N3′′-Me
(14.0%), H-3 (6.4%), H-6′′ with N1′′-Me (7.1%), H-2′ with H-3′ (2.0%), C1′-OMe (10.0%), N1′′-Me with
13
H-6′′ (4.6%). C-NMR (acetone-d6) δ: 30.7 (N3′′-Me), 35.3 (N1′′-Me), 52.0 (OMe), 55.0 (OMe), 97.4
(3′), 98.2 (2′), 116.0 (6′′), 127.2 (1′′), 128.2 (4), 129.9 (5), 131.3 (4), 132.2 (2), 143,0 (5′′), 150.3 (3′),
155.2 (1′), 168.0 (1). HMBC：H-1 with C1-CO, C-2; H-3 with C-1′, C-4; H-4 with C-2, C-5; H-5 with
C-1, C-5; H-2 with C-1, C-4; H-2′ with C-2, C-1′, C-1′′; H-3′ with C-5′′, C-2′, C-1′′; N1′′-Me with C-2′′;
N3′′-Me with C-2′′, C-6′′; H-6′′ with C-5′′, C-2′′, C-4′′. FAB-MS m/z: 347 [M+H]+. HRFAB-MS: Calcd
for C18H20N２O4F: 347.1409. Found: 347.1390.
4-[(3,3-dimethoxy-1-oxoindan-2-yl)methylene]-5-fluoro-1,3-dimethyl-1,3-dihydroprymidine-2-one
1
(1bIII): Light yellow oil. H-NMR (CDCl3) δ: 3.15 (3H, s, N1-Me), 3.18 (3H, s, N3-Me), 3.28 (3H, s,
C3′-OMe), 3.40 (3H, s, C3′′-OMe), 4.29 (1H, dd, J = 3.5, 9.8 Hz, H-2′′), 4.69 (1H, d, J = 9.8 Hz, H-1′),
6.31 (1H, d, J = 9.2 Hz, H-6), 7.51 (1H, dd, J = 7.5, 8.0 Hz, H-5′′), 7.65 (1H, dd, J = 7.5, 8.0 Hz, H-6′′),
7.70 (1H, d, J = 8.0 Hz, H-4′′), 7.78 (1H, d, J = 7.5 Hz, H-7′′). NOE: H-1′ with N3-Me (12.6%); H-6 with
13
N3-Me (21.3%); H-1′′ with C3′′-OMe (7.1%). C-NMR (CDCl3) δ: 32.2 ( N3-Me), 36.5 (N1-Me), 50.2
(OMe), 51.5 (OMe), 57.4 (1′′), 92.6 (1′), 104.1 (3′′), 116.6 (6), 124.2 (4′′), 125.2 (7′′), 130.4 (5′′), 132.9
(4), 134.2 (6′′), 135.2 (3′′a), 142.0 (5), 149.0 (7′′a), 150.9 (2), 201.5 (1′′). HMBC: H-1′ with C-1′′, C-4,
C-5, C-3′′; H-2′′ with C-1′′, C-1′, C-3′′, C-4; H-6 with C-5, C-2, C-4; H-5′′ with C-7′′, C-3′′a; H-6′′ with
C-4′′, C-7′′a; H-4′′ with C-3′′, C-3′′a; H-7′′ with C-7′′a, C-1′′ C-6′′; N3-Me with C-2, C-4; N1-Me with
C-6, C-2; OMe with C-3′′. FAB-MS m/z: 347 [M+H]+. HRFAB-MS: Calcd for C18H20N2O4F: 347.1396.
Found: 347.1439.
5-Fluoro-4-[(3-methoxy-1-oxoinden-2-yl)methylene]-1,3-dimethyl-1,3-dihydroprymidine-2-one
1
(1bIV): Light red oil. H-NMR (CDCl3) δ: 3.16 (3H, s, N1-Me), 3.28 (3H, s, N3-Me), 4.22 (3H, s,
C3′′-OMe), 4.98 (1H, s, H-1'), 6.28 (1H, d, J = 9.2 Hz, H-6), 7.15 (1H, d, J = 7.4 Hz, H-4′′), 7.22 (1H, dd,
J = 0.9, 7.5 Hz, H-6′′), 7.31(1H, dd, J = 1.2, 7.4 Hz, H-5′′), 7.38 (1H, d, J = 7.5 Hz, H-7′′). NOE:
H-1’with N3-Me (17.5%), C3′′-OMe (5.3%); H-6 with N3-Me (13.0%); C3′′-OMe with H-1' (3.4%),
H-4′′ (1.2%). 13C-NMR (CDCl3) δ: 31.7 (N3-Me), 36.5 (N1-Me), 59.2 (OMe), 86.4 (1'), 107.2 (1′′), 116.5
(6), 118.3 (4′′), 121.1 (7′′), 129.2 (6′′), 132.0 (7′′a), 132.4 (5′′), 140.9 (3′′a), 142.0 (5), 150.5 (2), 170.5
(3′′), 194.6 (1′′). HMBC: H-1' with C-1′′, C-4, C-5, C-3′′; H-6 with C-5, C-2, C-6; H-5′′ with C-4′′, C-7′′,
C-3′′a; H-6′′ with C-4′′, C-7′′a; H-4′′ with C-3′′, C-3′′a; H-7′′ with C-7′′a, C-1′′ C-6′′; N1-Me with C-2,

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HETEROCYCLES, Vol. 86, No. 2, 2012
C-6; N3-Me with C-4, C-2; OMe with C-3′′. FAB-MS m/z: 315 [M+H]+. HRFAB-MS: Calcd for
C17H16N2O3F: 315.1145. Found: 315.1168.
Methyl 3-methoxy-2-[(1E,3E)-3-(5-fluoro-1,3-dimethyl-2-oxo-1,3-dihydropyrimidin-4-ylidene)-
1
1-propenyl]benzoate (1cI): Yellow oil. H-NMR (CDCl3) δ: 3.17 (3H, s, N1′′-Me), 3.27 (3H, s,
N3′′-Me), 5.46 (1H, d, J = 12.0 Hz, H-3'), 6.30 (1H, dd, J = 0.9, 8.4 Hz, H-6′′), 6.77 (1H, dd, J = 4.4, 15.4
Hz, H-1'), 6.96 (1H, dd, J = 1.0, 7.9 Hz, H-4), 7.15 (1H, dd, J = 7.7, 7.9 Hz, H-5), 7.22 (1H, dd, J = 1.0,
7.7 Hz, H-6), 7.49 (1H, dd, J = 12.0, 15.4 Hz, H-2'). NOE: H-3′ with H-1′ (20.8%), N3”-CH3 (15.3%);
H-6′′ with N1′′-Me (11.5%); H-1' with H-3' (13.9%); N1′′-Me with H-6′′ (4.3%); N3′′-Me with H-3′
(6.1%); C5-OMe with H-4 (2.2%), H-2′ (0.8%). FAB-MS m/z: 347 [M+H]+. HRFAB-MS: Calcd for
C18H20N2O4F: 347.1407. Found: 347.1390.
Methyl 3-methoxy-2-[(1E,3Z)-3-(5-fluoro-1,3-dimethyl-2-oxo-1,3-dihydropyrimidin-4-ylidene)-
1-propenyl]benzoate (1cII): 1H-NMR (C6D6) δ: 2.42 (3H, s, N1′′-Me), 2.78 (3H, s, N3′′-Me), 3.15 (3H,
s, C3-OMe), 3.46 (3H, s, C1-CO2Me), 5.24 (1H, d, J = 12.0 Hz, H-2′′), 5.88 (1H, dd, J = 0.9, 8.4 Hz,
H-6′′), 6.46 (1H, d, J = 8.0 Hz, H-4), 6.86 (1H, t, J = 8.0 Hz, H-5), 7.26 (1H, d, J = 15 Hz, H-5), 7.40 (1H,
d, J = 8.0 Hz, H-6), 7.71 (1H, dd, J = 12.0, 15.0 Hz, H-2′). NOE: N3′′-Me with H-4 (9.8%); H-2′ with
N3′′-Me (10.4%), H-1′ (3.8%), H-3’ (1.4%); H-1′ with H-2′ (9.7%), H-3′ (10.5%); N1′′-Me with H-6′′
(4.4%), N3′′-Me with H-2′ (6.1%); H-3′ with H-1′ (10.6%); C3-OMe with H-4 (11.6%). FAB-MS m/z:
347 [M+H]+. HRFAB-MS: Calcd for C18H20N2O4F: 347.1407. Found: 347.1394.
Methyl 4-methoxy-2-[(1E,3E)-3-(5-fluoro-1,3-dimethyl-2-oxo-1,3-dihydropyrimidin-4-ylidene)-
1-propenyl]benzoate (1dI): Yellow oil.1H-NMR (C6D6) δ: 2.42 (3H, s, N1′′-Me), 2.78 (3H, s, N3′′-Me),
3.23(3H, s, C4-OMe), 3.54 (3H, s, C1-CO2Me), 5.27 (1H, dd, J = 1.2, 8.6 Hz, H-6′′), 5.41 (1H, d, J =
12.0 Hz, H-3′), 6.57 (1H, dd, J = 2.6, 8.7 Hz, H-5), 7.38 (1H, d, J = 2.6 Hz, H-3), 7.81 (1H, dd, J = 12.0,
15.0 Hz, H-2′), 8.02 (1H, d, J = 8.7 Hz, H-6), 8.09 (1H, dd, J = 4.4, 15.0 Hz, H-1′). NOE: H-3′ with H-1′
(20.8%), N3′′-Me (15.3%); H-6′′ with N1′′-Me (11.5%); H-1′ with H-3′ (13.9%); C4-OMe with H-4
(2.2%), H-2′ (0.8%). 13C-NMR (C6D6) δ: 31.3 (N3′′-Me), 35.5 (N1′′-Me), 51.3 (OMe), 54.6 (OMe), 103.3
(3′), 110.9 (3), 112.4 (5), 116.5 (6′′), 120.7 (1), 128 (1′-2′), 133.5 (6), 132.0 (4′′), 143.0 (5′′), 144.9 (2′′),
162.8 (4), 167.37 (C1-CO). HMBC: H-1 with CO; H-3 with C-5, C-1, C-4; H-4 with C-4; H-5 with C-1,
C-3; H-6 with C-2, C-4, CO; H-1′ with C-3, C-3′; H-2′ with C-2; H-3′ with C-5′′, C-6′′, C-4′′; N3′′-Me
with C-2′′, C-4′′; N1′′-Me with C-3′′, C-6′′; H-6′′ with C-5′′, C-2′′, C-4′′. FAB-MS m/z: 347 [M+H]+.
HRFAB-MS: Calcd forC18H20N2O4F: 347.1407. Found: 347.1390. UV λmax(CHCl3) nm (ε): 376 (19400).
Methyl 4-methoxy-2-[(1E,3Z)-3-(5-fluoro-1,3-dimethyl-2-oxo-1,3-dihydropyrimidin-4-ylidene)-
1- propenyl]benzoate (1dII): 1H-NMR (C6D6) δ: 2.43 (3H, s, N1′′-Me), 3.15 (3H, s, N3′′-Me), 3.24 (3H,
s, C4-OCH3), 3.51 (3H, s, C1-CO2Me), 5.24 (1H, d, J = 6.9 Hz, H-6′′), 5.90 (1H, d, J = 12.0 Hz, H-3′),
6.53 (1H, dd, J = 2.3, 8.6 Hz, H-5), 7.12 (1H, dd, J = 12.0, 15.0 Hz, H-2′), 7.40 (1H, d, J =2.3 Hz, H-3),

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7.90 (1H, d, J =15.0 Hz, H-1′), 8.04 (1H, d, J = 8.6 Hz, H-6). NOE: N3′′-Me with H-2′; H-1′ with H-3′,
H-2′; H-3′ with H-1′; C4-OMe with H-3, H-5.
Methyl 5-methoxy-2-[(1E,3E)-3-(5-fluoro-1,3-dimethyl-2-oxo-1,3-dihydropyrimidin-4-ylidene)-
1
1-propenyl]benzoate (1eI): Yellow oil. H-NMR (CDCl3) δ: 3.16 (3H, s, N1′′-Me), 3.24 (3H, s,
N3′′-Me), 3.38 (3H, s, C5-OMe), 3.89 (3H, s, C1-CO2Me), 5.50 (1H, d, J = 10.4 Hz, H-3′), 6.30 (1H, dd,
J = 1.0, 8.3 Hz, H-6”), 6.98 (1H, dd, J = 2.8, 9.0 Hz, H-4), 7.17 (1H, dd, J = 4.2, 15.4 Hz, H-1′), 7.27 (1H,
dd, J = 10.4, 15.4 Hz, H-2′), 7.32 (1H, d, J = 2.8 Hz, H-6), 7.54 (1H, d, J = 9.0 Hz, H-5). NOE: H-3′ with
13
N3′′-Me (20.0%), H-1′(23%); H-6′′ with N1′′-Me (8.5%); H-2′ with H-3 (8.8%). C-NMR (CDCl3) δ:
31.9 (N3′′-Me), 36.3 (N1′′-Me), 52.1 (OMe), 55.5 (OMe), 103.4 (3′), 114.0 (6), 116.0 (6′′), 118.9 (4),
126.0 (2′), 127.2 (1′), 127.5 (3), 128.4 (1), 130.7 (4′′), 132.5 (2) ,143.0 (5′′), 150.7 (2′′), 169.7 (C1-CO).
HMBC: H-1 with CO; H-3 with C-5, C-1; H-4 with C-3, C-2, C-5; C5-OMe with C-5; H-6 with C-1, C-3;
H-2′ with C-2, C-1′, C-3′; H-3′ with C-6′′, C-2′, C-1′′; N3′′-Me with C-2′′, C-4′′, N1′′-Me with C-2′′, C-6′′,
C-5′′, H-6′′ with C-5′′, C-2′′, C-4′′. FAB-MS m/z: 347 [M+H]+. HRFAB-MS: Calcd for C18H20N2O4F:
347.1407. Found: 347.1386. UV λmax (CHCl3) nm (ε): 376 (21070).
Methyl 5-methoxy-2-[(1E,3Z)-3-(5-fluoro-1,3-dimethyl-2-oxo-1,3-dihydropyrimidin-4-ylidene)-
1-propenyl]benzoate (1eII): 1H-NMR (C6D6) δ: 2.55 (3H, s, N1′′-Me), 3.25 (3H, s, N3′′-Me), 3.25 (3H,
s, C5-OMe), 3.46 (3H, s, C1-CO2Me), 5.27 (1H, d, J = 6.9 Hz, H-6′′), 5.90 (1H, d, J = 12.0 Hz, H-3′),
6.89 (1H, dd, J = 2.9, 8.6 Hz, H-4), 7.09 (1H, dd, J = 12.0, 15.0 Hz, H-2′), 7 .41 (1H, d, J = 8.6 Hz, H-3),
7.53 (1H, d, J = 2.9 Hz, H-6), 7.68 (1H, d, J = 15.0 Hz, H-1′). NOE: H-2′ with H-3 (15.5%), N3′′-Me
(11.3%).
6b-Fluoro-6a,6b,10a,10b-tetrahydro-1,6a-dimethoxy-8,10-dimethylnaphtho[1′,2′:3,4]cyclobuta-
1
[1,2-d]pyrimidine-7,9-dione (3e): Colorless crystals, mp 156-158 °C. H-NMR (C6D6) δ: 2.18 (3H, s,
N10-Me), 3.11 (3H, s, N8-Me), 3.12 (3H, s, C1-OMe), 3.25 (3H, s, C6a-OMe), 3.87 (1H, dd, J = 9.2,
25.2 Hz, H-10a), 4.43 (1H, d, J = 9.2 Hz, H-10b), 5.69 (1H, dd, J = 1.1, 10.3 Hz, H-6), 6.24 (1H, d, J =
8.1 Hz, H-2), 6.26 (1H, d, J = 10.3 Hz, H-5), 6.44 (1H, d, J = 7.5 Hz, H-4), 6.88 (1H, dd, J = 7.5, 8.1 Hz,
H-3). NOE: H-10a with H-10b, N10-CH3; H-6 with H-5 (14.9%), C6a-OMe (7.7%); C6a-OMe with H-6
(5.3%).
6b-Fluoro-6a,6b,10a,10b-tetrahydro-6a,10b-dimethoxy-cis-8,10-dimethylnaphtho[1′,2′:3,4]cyclobuta-
[1,2-d]pyrimidine-7,9-dione (3f): Colorless crystals, mp 161-162 °C (hexane). 1H-NMR (CDCl3) δ: 2.60
(3H, s, N8-Me), 3.05 (3H, s, C10b-OMe), 3.17 (3H, s,N10-Me), 3.78 (3H, s, C6a-OMe), 4.64 (1H, dd, J =
0.8, 24.6 Hz, H-10a), 6.35 (1H, d, J = 10.1 Hz, H-6), 6.53 (1H, d, J = 10.1 Hz, H-5), 7.13 (1H, m, H-4),
7.25 (1H, m, H-1), 7.30-7.34 (2H, H-2, H-3). NOE: H-10a with N10-Me (7.1%); H-6 with H-5 (15.7%),
C6a-OMe (9.1%); H-5 with H-6 (8.9%), H-4 (8.7%), C6a-OMe with H-6 (4.0%), N10-Me with H-10a
(4.1%), H-1 (2.7%). FAB-MS m/z: 347 [M+H]+. HRFAB-MS: Calcd for C18H20N2O4F: 347.1402. Found:

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HETEROCYCLES, Vol. 86, No. 2, 2012
347.1395. UV λmax (cyclohexane) nm (ε): 267 (2020).
4a-Fluoro-4a,5,10,10a-tetrahydro-8,9-dimethoxy-1,3-dimethyl-cis-5,10-ethenobenzo[f]quinazoline-
2,4-dione (2f): Colorless crystals, mp 115-117 °C. 1H-NMR (CDCl3) δ: 2.57 (3H, s, N3-Me), 3.21 (3H, s,
N1-Me), 3.72 (3H, s, C8-OMe), 3.83 (3H, s, C9-OMe), 3.71 (1H, d, J = 30.0 Hz, H-10a), 4.34 (1H, dd, J
= 6.4, 6.9 Hz, H-5), 5.30 (1H, d, J = 6.9 Hz, H-12), 7.12-7.26 (3H, H-6, H-7, H-8), 7.43 (1H, d, J = 7.1
Hz, H-9). NOE: H-10a with N1-Me (7.8%), H-11 (2.7%), H-10 (7.2%); H-5 with H-6 (7.2%), H-12
(7.9%); H-12 with H-5 (11.2%), C11-OMe (7.1%); C10-OMe with H-9 (2.2%); C11-OMe with H-12
(3.2%), H-7 (1.2%); N1-Me with H-10a (3.5%), C10-OMe (0.5%). FAB-MS m/z: 347 [M+H]+.
HRFAB-MS: Calcd for C18H20N2O4F: 347.1402. Found: 347.1393. UV λmax (cyclohexane) nm (ε): 240
(3300), 283 (720).
6a-Fluoro-6a,6b,10a,10b-tetrahydro-5,6a-dimethoxy-cis-8,10-dimethylnaphtho[1’,2’:3,4]cyclobuta-
[1,2-d]pyrimidine-7,9-dione (3gI): Colorless oil. 1H-NMR (C6D6) δ: 1.96 (3H, s, N10-Me), 3.09 (3H, s,
N8-CH3), 3.12 (3H, s, C5-OMe), 3.26 (3H, s, C6a-OMe), 3.50 (1H, dd, J = 8.7, 24.6 Hz, H-10a), 3.81
(1H, d, J = 10.1 Hz, H-10b), 4.61 (1H, s, H-6), 6.65 (1H, d, J = 7.5 Hz, H-1), 6.92 (1H, t, J = 7.5 Hz, H-2),
7.01 (1H, t, J = 7.5 Hz, H-3), 7.71 (1H, d, J = 7.5 Hz, H-4). NOE: H-10a with N10-Me (7.2%), H-10b
(9.6%); H-10b with H-10a (14.7%), H-1 (10.0%), C6a-OMe (9.1%); H-6 with C5-OMe (8.4%),
C6a-OMe (6.3%); C6a-OMe with H-6 (3.3%), H-10b (2%); N10-Me with H-10a (3.4%), H-1 (1.5%).
FAB-MS m/z: 347 [M+H]+. HRFAB-MS: Calcd for C18H20N2O4F: 347.1407. Found: 347.1382. UV λmax
(cyclohexane) nm (ε): 223 (7960), 270 (2080).
6a-Fluoro-6a,6b,10a,10b-tetrahydro-5,6a-dimethoxy-trans-8,10-dimethylnaphtho[1′,2′:3,4]cyclobuta-
1
[1,2-d]pyrimidine-7,9-dione (3gII): Light yellow oil. H-NMR (C6D6) δ:1.95 (3H, s, N10-CH3), 3.09
(3H, s, N8-CH3), 3.12 (3H, s, C5-OCH3), 3.26 (3H, s, C6a-OCH3), 2.89 (1H, d, J = 7.9 Hz, H-10b), 3.17
(1H, dd, J = 17.5 Hz, 10.1 Hz, H-10a), 4.86 (1H, s, H-6), 6.57 (1H, d, J = 7.5 Hz, H-1), 6.94 (1H, dd, J =
7.5, 7.7 Hz, H-2), 7.05 (1H, dd, J = 7.2, 7.7 Hz, H-3), 7.78 (1H, d, J = 7.2 Hz, H-4). NOE: H-10a with
N10-CH3 (1.2%); H-10b with H-1 (9.0%), N10-CH3 (1.2%), C6a-OCH3 (2.1%); H-6 with C5-OCH3
(3.4%), C6a-OCH3 (9.3%), C5-OCH3 with H-6 (6.7%), H-4 (0.1%), H-1 with H-10b (10.2%), N10-CH3
(2.6%). FAB-MS m/z: 347 [M+H]+. HRFAB-MS: Calcd for C18H20N2O4F: 347.1407. Found: 347.1398.
UV λmax (cyclohexane) nm (ε): 235 (5020) 280 (1040).
4a-Fluoro-4a,5,10,10a-tetrahydro-8,12-dimethoxy-1,3-dimethyl-cis-5,10-ethenobenzo[f]quinazoline-
1
2,4-dione (2h): Degradative colorless crystals. H-NMR (C6D6) δ: 2.59 (3H, s, N3-CH3), 2.77 (3H, s,
N1-Me), 3.17 (3H, s, C12-OMe), 3.21 (3H, s, C8-OMe), 3.31(1H, dd, J = 2.5, 31.7 Hz, H-10a), 3.49 (1H,
dd, J = 2.5, 6.9 Hz, H-10), 4.64 (1H, dd, J = 2.4, 4.8 Hz, H-5), 4.73 (1H, dd, J = 2.4, 6.9 Hz, H-11), 6.30
(H, dd, J = 2.7, 8.3 Hz, H-7), 6.65 (1H, d, J = 2.7 Hz, H-9), 6.81 (1H, d, J = 8.3 Hz, H-6). NOE: H-10a
with N1-Me (7.3%), H-10 (5.2%), H-11 (2.0%); H-5 with H-6(8.8%); H-10 with H-9 (9.7%), H-11

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(10.6%), H-10a (6.6%), N1-CH3 (7.1%), H-11 with H-10a (7.2%), H-10 (9.2%). FAB-MS m/z: 347
[M+H]+. HRFAB-MS: Calcd for C18H20N2O4F: 347.1407. Found: 347.1431.
4a-Fluoro-4a,5,10,10a-tetrahydro-8,11-dimethoxy-1,3-dimethyl-cis-5,10-ethenobenzo[f]quinazoline-
1
2,4-dione (2iI): Colorless crystals, mp 61-62 °C. H-NMR (CDCl3) δ: 2.77 (3H, d, J = 0.8 Hz, N3-Me),
3.10 (3H, s, N1- Me), 3.61 (3H, s, C11-OMe), 3.74 (3H, s, C8-OMe), 3.75 (1H, dd, J = 2.7, 30.4 Hz,
H-10a), 3.95 (1H, dd, J = 2.2, 2.7 Hz, H-10), 4.44 (1H, dd, J = 5.3, 6.4 Hz, H-5), 5.23 (1H, dd, J = 2.2,
6.4 Hz, H-12), 6.62 (1H, dd, J = 2.4, 8.2 Hz, H-7), 6.77 (1H, d, J = 2.4 Hz, H-9), 7.04 (1H, d, J = 8.2 Hz,
H-6). NOE: H-10a with N1-Me, H-10, H-11, H-5 with H-6, H-12, H-10 with C11-OMe, H-9, C11-OMe
with H-10, H-12. FAB-MS m/z: 347 [M+H]+. HRFAB-MS: Calcd for C18H20N2O4F: 347.1407. Found:
347.1387.
4a-Fluoro-4a,5,10,10a-tetrahydro-7,12-dimethoxy-1,3-dimethyl-cis-5,10-ethenobenzo[f]quinazoline-
2,4-dione (2iII): Colorless crystals. 1H-NMR (acetone-d6) δ: 2.65 (3H, d, J = 0.8 Hz, N3-Me), 3.08 (3H, s,
N1-Me), 3.59 (3H, s, C12-OMe), 3.73 (3H, s, C7-OMe), 3.76 (1H, dd, J = 2.7, 32.4 Hz, H-10a), 4.20 (1H,
dd, J = 2.4, 5.1 Hz, H-10), 4.31 (1H, dd, J = 2.7, 7.0 Hz, H-5), 5.37 (1H, dd, J = 2.4, 7.0 Hz, H-11), 6.68
(1H, dd, J = 2.6, 8.1 Hz, H-8), 6.79 (1H, d, J = 2.6 Hz, H-6), 7.21 (1H, d, J = 8.1 Hz, H-9). FAB-MS m/z:
347 [M+H]+. HRFAB-MS: Calcd for C18H20N2O4F: 347.1407. Found: 347.1494.
Photoreaction of 5-FDMU with1-methoxynaphthalene in the presence of piperylene. An equivalent
molar solution (1.5 mM) of 5FDMU and 1-methoxynaphthalene in cyclohexane containing
trans-piperylene (1.5 mM) was irradiated.
Photoreaction of 5-FDMUwith 1-methoxynaphthalene in various solvents. Equivalent molar solutions
(1.5 mM) of 5FDMU and 1-methoxynaphthalene in cyclohexane, benzene, toluene, MeCN, and MeOH,
respectively, were irradiated.
Substitution products: 1,3-dimethyl-5-(4-methoxy-1-naphtyl)uracil (4aI): Colorless crystals, mp
217-218 °C (hexane). 1H-NMR (acetone-d6) δ: 3.31 (3H, s, N3-Me), 3.48 (3H, s, N1-Me), 4.03 (3H, C4′-
OMe), 6.94 (1H, d, J = 8.0 Hz, H-3′), 7.30 (1H, d, J = 8.0 Hz, H-2′), 7.45 (1H, dt, J = 1.7, 6.9 Hz, H-7′),
7.47 (1H, dt, J = 2.3, 6.9 Hz, H-6′), 7.62 (1H, s, H-6), 7.73 (1H, dd, J = 2.3, 6.9 Hz, H-8′), 8.24 (1H, dd, J
= 1.7, 6.9 Hz, H-5′). NOE: H-6 with H-2′ (22.0%), N1-Me (16.8%), C4′-Me with H-3′, H-5′. FAB-MS
m/z: 297 [M+H]+. HRFAB-MS: Calcd for C17H17N2O3: 297.1239. Found: 297.1248.
1
1,3-Dimethyl-5-(5-methoxy-1-naphthyl)uracil (4aII): Colorless oil. H-NMR (acetone-d6) δ: 3.31 (3H,
s, N3-Me), 3.49 (3H, s, N1-Me), 4.02 (3H, C4′-OMe), 6.94 (1H, dd, J = 1.2, 6.9 Hz, H-6′), 7.32-7.37 (2H,
H-7′, H-8′), 7.39 (1H, dd, J = 1.7, 6.9 Hz, H-2′), 7.47 (1H, dd, J = 6.9, 8.6 Hz, H-3′), 7.65 (1H, s, H-6),
8.25 (1H, d, J = 8.6 Hz, H-4′). NOE: H-6 with H-2′ (3.7%), N1-Me (30.0%), C5′-Me with H-6' (19.0%);
H-4′ with H-3′ (4.3%); H-3′ with H-2′ (5.9%), H-4′ (4.7%); H-6′ with H-7′ (20.0%). FAB-MS m/z: 297
[M+H]+. HRFAB-MS: Calcd for C17H17N2O3: 297.1239. Found: 297.1260.

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