Intramolecular photoreaction of thiobarbiturates with an alkenyl or a benzyl group in their N-alkyl side chain. Regioselective synthesis of ring-fused pyrimidine derivatives through photocyclization of mono- and dithiobarbiturates

Article abstract of DOI:10.3987/COM-02-S37

Upon irradiation, thiobarbiturates with an alkenyl (4,5) or a benzyl (14,15,21) group in their N-alkyl side chain give bi- and tri-cyclic fused pyrimidine derivatives through regioselective [2+2] photocycloaddition or Norrish type II reaction, respectively.

Full text of DOI:10.3987/COM-02-S37

HETEROCYCLES, Vol. 59, No. 1, 2003, pp. 303 – 316, Received, 31st July, 2002
INTRAMOLECULAR
BARBITURATES WITH
PHOTOREACTION
AN ALKENYL
OF
THIO-
OR A BENZYL
GROUP IN THEIR N-Alkyl SIDE CHAIN.
REGIOSELECTIVE
SYNTHESIS OF RING-FUSED PYRIMIDINE DERIVATIVES
THROUGH
PHOTOCYCLIZATION OF
MONO- AND DI-
THIOBARBITURATES1
Haruko Takechi,* Hajime Takahashi, Reijiro Mahara, and Minoru
Machida
Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido,
Ishikari-Tobetsu, Hokkaido 061-0293, Japan
E-mail: takechi@hoku-iryo-u.ac.jp
Abstract- Upon irradiation, thiobarbiturates with an alkenyl (4,5) or a benzyl
(14,15,21) group in their N-alkyl side chain give bi- and tri-cyclic fused
pyrimidine derivatives through regioselective [2+2] photocycloaddition or Norrish
type II reaction, respectively.
During the course of our systematic studies on the photochemistry of nitrogen-thiocarbonyl systems, we
found that the major photochemical processes of the cyclic thioimides2 and aromatic thioamides3 are limited
to [2+2] photocycloaddition (Paterno-Büchi reaction) with olefins, although certain thioimides having a
benzylic hydrogen in the N-alkyl side chain undergo the Norrish type II reaction to give cyclized
products.2e ,4 As an extension of this work, our finding led us to investigate the photoreaction of
thiobarbiturates,5 whose skeletons consist of a combination of a thioimide and an amide or a thioamide. In
this system it was found that the intermolecular thietane formation occurred regioselectively, i.e., in the case
of 2-monothiobarbiturate (1a), photoaddition of olefin occurred only at the 2-position to give thietane (2a),
whereas for 2,4-di- and 2,4,6-trithiobarbiturates (1b and 1c), the resulting thietanes (3b and 3c) were the
products reacting with the 4-thiocarbonyl (Scheme 1). As an application of this regioselective reaction, the
construction of various diaza-heterocycles was examined through the intramolecular photocyclization of
thiobarbiturates with an alkenyl group in their N-alkyl side chain.6 The present report is concerned with
the detailed results of intramolecular Paterno-Büchi and intramolecular Norrish type II cyclization reactions
in these thiobarbiturate systems.
A series of thiobarbiturate derivatives (4,5,14, and 15) were prepared from 2,3-dihydro-1,5,5-trimethyl-

Scheme 1
CH
X
O
CH
CH
3
3
3
S
N
N
N
CH
4
3
hν
CH
CH
3
3
3
5
2
1
N
S
S
or
CH
6
3
CH
3
CH
3
S
N
N
Y
CH
O
CH
3
Y
CH
3
3
1a: X=O, Y=O
1b: X=S, Y=O
1c: X=S, Y=S
3b: Y=O
3c: Y=S
2a
2-thioxo-4,6(1H, 5H)-pyrimidinedione or 2,3,4,5-tetrahydro-1,5,5-trimethyl-2,6-dithioxo-4(1H)-pyrimi-
dinone and the appropriate alcohols, respectively. Substrates (21a and 21b) were obtained by the
thionation of 2,3-dihydro-1,3,5-trimethyl-5-(ω-phenylalkyl)-2-thioxo-4,6(1H,5H)-pyrimidinedione which
were prepared from the corresponding methyl(ω-phenylalkyl)methane-1,1-dicarbonyl chloride and 1,3-
dimethyl-2-thiourea. The yields and analytical data of thiobarbiturates (4,5,14,15, and 21) are listed in
Table 1.
Photolyses of thiobarbiturates (4,5,14,15, and 21) were performed in acetonitrile (10 mM) using a 1 kW
high-pressure mercury lamp through a Pyrex filter under a nitrogen atmosphere at room temperature. The
results are shown in Scheme 2, Scheme 4, and Table 2.
Scheme 2
O
O
O
O
N
N
N
N
CH3
CH3
CH3
CH3
CH3
CH3
CH2
CH2
*
Ph
C
(CH2)n
N
X
C
R
R
N
N
R
4
5
S
7b
7c
8b
8c
CH3
CH3
6
hν
CH3
O
CH2
C
CH3
O
CH3
S
CH3
CH3CN
(CH2)n
N
N
H
R
O
CH3
HS
N
N
*
N
N
S
CH3
CH3
CH3
4a: X=O, n=2, R=CH3
4b: X=O, n=3, R=Ph
4c: X=O, n=3, R=H
5a: X=S, n=2, R=CH3
5b: X=S, n=3, R=Ph
5c: X=S, n=3, R=H
S
S
CH3
S
CH3
N
CH3
9
10a
10b
10c
11-i, 11-ii
O
CH3
O
CH3
O
CH3
In the photoreaction of N-(4-phenyl-4-pentenyl)monothiobarbiturate (4b), the [2+2] cycloaddition of olefin
moiety occurred at the 2-thiocarbonyl (C=S) in preference to the 4-carbonyl (C=O), giving the
corresponding tricyclic thietane (6) in 34% yield, accompanied by dethioformylated enamide compound
(7b) in 26% yield. Probably the compound (7b) arises from the initially formed 6 through photochemical
fission (cycloreversion) of the thietane ring.5 Interestingly, besides the Paterno-Büchi products (6 and 7b),

trace amounts of diene compound (8b), which arose by elimination of hydrogen sulfide from the initially
formed intramolecular Norrish type II product (thiol), were also obtained. Similarly, in the case of N-(4-
pentenyl)monothiobarbiturate (4c), dethioformylated compound (7c) was obtained in 36% yield together
with the Norrish type II product (8c, 3%). However, N-(3-methyl-3-butenyl)monothiobarbiturate (4a),
having a shorter N-alkyl side chain than ones of 4b and 4c, yielded a complex photolysate, and isolable
products were not obtained.
Next, photolyses of dithiobarbiturates (5) having both 2-thiocarbonyl and 4-thiocarbonyl groups were
examined. Photoaddition of alkenyl group in dithiobarbiturate (5a) occurred only at the 4-position to give
tricyclic thietane (9) and dethioformylated bicyclic ene-thioamide compound (10a) in 18 and 46% yields,
respectively. Similarly, photolyses of 5b and 5c afforded the dethioformylated cyclic ene-thioamides
(10b,c) in 37 and 21% yields, respectively. In addition, in 5c, Norrish type II product, thiol compound
(11-i) was also obtained in 20% yield, together with a trace of its isomer (11-ii).
The structures of all products were determined on the basis of the spectral and analytical data (Table 2 and
Table 3). The MS spectra of thiethanes (6 and 9) and thiol compound (11-i) showed the molecular ion
peaks at m/z 330 (6), 270 (9), and 270 (11-i) corresponding to the molecular weights of 4b, 5a, and 5c,
respectively. Cyclic enamide and ene-thioamide compounds (7b,c, and 10a-c) and conjugated diene
compounds (8b,c) showed the peaks corresponding to the molecular formula which was equivalent to the
loss of thioformaldehyde or hydrogen sulfide from the initially formed thiethanes or thiols, respectively.
The formations of the thiethane ring in 6 and 9 were confirmed by the NMR spectra (Table 3). In the 1H-
NMR spectra of thiethanes (6 and 9), the signals due to methylene protons of newly formed thietane ring
appeared at δ 2.96 and 3.71 (each 1H, d, J= 9.7 Hz ), and 2.71 and 3.06 (each 1H, d, J= 9.0 Hz), instead
of signals due to olefinic protons in the N-alkyl side chains of 4b and 5a, respectively. Further, as
regarding 6, it was observed that a signal due to one of the methylene protons has shifted to downfield (δ
3.71) as compared with that of 9 (δ 3.06), owing to the anisotropic effect of the benzene ring. The
position of a thiocarbonyl group reacting with a carbon-carbon double bond moiety was confirmed by
13
comparison of C-NMR spectra. For 6, a signal due to a quaternary carbon atom (*) adjacent to two
nitrogens and a sulfur atom appeared at δ 88.4 (s), whereas the corresponding signal of 9 appeared at
upfield [δ 80.7 (s)] in comparison with that of 6. This difference in the chemical shift between 6 and 9
was also observed in those of thietane rings in the previously reported 1-thia-5,9-diazaspiro[3,5]nonane (2)
and 1-thia-5,7-diazaspiro[3.5]nonane (3) systems.4 For the cyclic enamide and ene-thioamide compounds
(7b,c, and 10a-c), each 1 3C-NMR spectrum showed the singlet peaks due to the sp2 carbon adjacent to
one or two nitrogens at δ 131.1-138.6. The 1H-NMR spectrum of 10b showed a singlet due to 5-methyl
protons at an upfield (δ 1.08), owing to an anisotropic effect of the benzene ring, however, this upfield
shift was not observed in 7b (δ 1.50). To confirm the reaction site, the products (7b and 10b) were treated
with Lawesson's reagent, respectively (Scheme 3). The thionation product (12) derived from 7b was not
identical with the dithio compound (13) from 10b. This indicated that the photocycloaddition occurred at

the 2-position in monothiobarbiturate (4), and at 4-position in dithiobarbiturate (5), respectively.
Scheme 3
S
Ph
Lawesson's
reagent
Lawesson's
reagent
Lawesson's
reagent
N
N
N
CH
3
7b
10b
CH
3
S
CH
3
Ph
CH
N
3
13
12
S
CH
3
S
CH
3
1
In regard to the diene compounds (8b and 8c), the H-NMR spectra showed characteristic signal due to
terminal vinyl protons at δ 5.25 and 5.72 (each 1H, d, J= 1.3 Hz) and 4.9-5.1 (2H, m), respectively.
Further, in the 13C-NMR spectra, the singlet peaks due to the sp2 carbons adjacent to two nitrogens and the
other sp2 carbons on pyrroline ring appeared at δ 131.2-132.0 and 103.1-103.7, respectively. The 1H-
NMR spectrum of thiol compound (11-i) showed peaks due to thiol and vinyl protons at δ 1.96 (1H, s,
SH), 5.2-5.4 (2H, m, CH2=C-) and 5.9-6.1 (1H, m, CH2 =CH-), respectively. Further, nuclear
Overhauser effect (NOE) was not observed between the methine proton (δ 3.2-3.3) and thiol proton (δ
1.96), indicating that the configuration of a vinyl and a thiol group in 11-i is cis as shown in Figure 1.
Figure 1. NOEs observed in cyclized Products
CH
2
Ph
S
H
H
C
Ph
H
H
0%
0%
19
6.6%
N
N
HS
HS
H
N
N
S
S
CH
CH
3
3
CH
3
S
CH
CH
3
3
N
N
CH
3
20
O
CH
O
CH
11-i
3
3
O
CH
3
0%
0%
Ph
4.3%
SH
H
Ph
Ph
H
H
SH
SH
CH
CH
3
3
CH
3
N
N
N
1.9%
3.8%
1.8%
S
S
S
CH
3
CH
3
CH
3
N
N
N
22a-i
22a-ii
O
CH
22b
O
CH
3
3
O
CH
3
As observed in the present work, certain thiobarbiturates (4b,c and 5c) possessing three methylene

carbons in their N-ω-alkenyl side chain underwent not only [2+2] cycloaddition but also Norrish type II
reaction to give cyclized compounds. Therefore, to investigate the scope of this Norrish type II reaction, the
photoreaction of thiobarbiturates (14 and 15) having a benzylic hydrogen in their N-alkyl side chain was
examined (Scheme 4). As expected, photolyses of monothiobarbiturates (14a,b) gave bicyclic pyrimidine
Scheme 4
O
O
(CH )
2 n-1
N
N
N
N
CH
3
CH
3
(CH ) Ph
2 n
X
CH
3
14
15
Ph
CH
3
Ph
N
S
N
CH
3
hν
16a
7b
17
O
CH
3
O
CH
3
CH
3
Ph
H
CH CN
3
(CH )
2 n-1
Ph
HS
O
CH
Ph
CH
S
3
N
N
N
N
14a: X=O, n=3
14b: X=O, n=4
15a: X=S, n=3
15b: X=S, n=4
CH
CH
3
3
3
S
S
S
CH
CH
3
CH
3
3
N
N
19
20
18a
10b
O
CH
O
CH
3
3
O
O
CH
3
Ph
SH
Ph
S
CH
3
CH
3
CH
3
CH
3
N
N
N
N
(CH )
2 n-1
hν
CH CN
Ph-(CH )
2 4
Ph-(CH2)n
S
S
S
S
CH
CH
3
3
CH
3
CH
3
N
N
3
N
N
24
O
CH
O
CH
22a-i, 22a-ii
22b
3
3
O
CH
O
CH
3
3
23
21a: n=3
21b: n=4
derivatives (16a,7b) in 78 and 40% yields, respectively. The reaction resulted in the C-C bond formation
between the 2-thiocarbonyl and the benzylic carbon in their N-alkyl side chain, followed by elimination of
hydrogen sulfide from initially formed thiol compound corresponding to Norrish type II product. In the
case of 14a, pyrrole derivative (17) was also obtained in 6% yield, apparently derived from the initially
formed 16a through photochemical and/or thermal oxidative dehydrogenation. On the other hand, 15a
(dithio analog of 14a) underwent benzylic hydrogen abstraction at the 4-thiocarbonyl group, giving a cyclic
ene-thioamide (18a) in 23% yield. Further, in the reaction of 15b, both thiol (19) and ene-thioamide
(10b) were obtained in 8 and 13% yields, respectively, accompanied by unexpected cyclic thioether (20) in
9% yield. The mechanism for formation of 20 can be reasonably explained in terms of initial formed 1,6-
biradical intermediate (25) which was generated by benzylic hydrogen abstraction of a 4-thiocarbonyl
group, followed by hydrogen transfer, and then addition of thiol group to the intramolecular olefinic carbon
leading to 20 (Scheme 5).
Further, to investigate the synthesis of a variety of ring-fused pyrimidine derivatives, photolyses of
dithiobarbiturates (21a,b) having a benzylic hydrogen in their C-5-alkyl side chain were performed. In

these systems, each abstraction from benzylic hydrogen occurred only at the 4-thiocarbonyl group, giving
Scheme 5
Ph
S
(CH ) Ph
2 4
Ph
HS
Ph
HS
CH
N
S
H-transfer
Cyclization
CH
hν
3
S
N
N
H
N
CH
3
3
CH
3
CH
3
S
N
S
S
H-abstraction
CH
CH
3
3
CH
3
N
N
N
O
CH
3
O
CH
O
CH
O
CH
3
3
20
25
3
15b
Cyclization
Ph
Ph
HS
N
N
N
S
N
- H S
2
CH
CH
3
3
S
CH
CH
3
3
O
CH
O
CH
3
3
19
10b
the corresponding thiols [22a-i: 25%, 22a-ii: 23%, and 22b: 12% ] and cyclic ene-thioamide (23: 6%).
Further, 21b also gave the oxidative desulfurization product (24) in 9% yield (Scheme 4).
The structures of these products were determined on the basis of the spectral and analytical data (Table 2
and Table 3). Spectral data of 7b (from 14b) and 10b (from 15b) were in agreement with those of the
products obtained from 4b and 5b, respectively.
The MS spectra of 16-20 and 22-24 showed the peaks corresponding to the molecular formula of each
compound. The structures of the thiols (19, 22a-i, 22a-ii, and 22b) were confirmed by the NMR
1
spectra (Table 3). Their H-NMR spectra showed peaks due to thiol and benzylic protons at δ 2.17-2.54
(SH) and 3.2-3.6 (PhCH-), respectively. In addition, the 1 3C-NMR spectra showed peaks due to a
benzylic carbon and a quaternary carbon adjacent to a nitrogen and a sulfur atom at δ 47.3-58.8 (d) and
77.5-83.9 (s), respectively. The stereochemistries of thiol compounds were assigned from the NOE
experiments (Figure 1). In the spectrum of 22a-i , irradiation at the signal of the methine proton [δ 3.56
(1H, t)] enhanced hardly the signal intensity of the thiol proton [δ 2.17 (1H, s)]. In 22a-ii, on irradiation
at the methine proton [δ 3.5-3.6 (1H, m)] a 4.3% increment of the thiol signal [δ 2.54 (1H, s)] was
observed. Further, the NOE enhancement was observed between the signals of the methyl proton and
thiol proton in each isomer (i and ii). This NMR spectroscopy supported the structures of 22a-i and 22a-
ii as shown in Figure 1. Similarly, the stereochemistries of other thiols (19 and 22b) were determined by
the NOE experiments (Figure 1).
The 13C-NMR spectra of cyclic enamide and ene-thioamides (16a,18a, and 23) were analogous to those of
7b,c and 10a-c, that is, the singlet peaks due to the sp2 carbon adjacent to one or two nitrogens and its

adjacent sp2 carbons appeared at δ 130.6-135.8 and 104.0-130.5 respectively. Further, the spectrum of
pyrrole derivative (17) showed two doublet signals at δ 111.8 and 116.6, besides two singlet signals of sp2
carbons (each δ =130.1 and 112.2) as mentioned above, indicated the presence of pyrrole moiety. The
structural assignment of cyclic thioether (20) was based on the following data. The HRMS gave analytical
1
value corresponding to the molecular formula of 20. The H-NMR spectrum of 20 showed peaks due to a
benzylic proton, and a methine proton adjacent to a nitrogen and a sulfur atom at δ 4.11 (1H, dd, J= 10.3,
1.5 Hz) and 4.76 (1H, s), respectively. In addition, the 13C-NMR spectrum showed two doublet peaks
due to two methine carbons adjacent to a sulfur atom at δ 51.4 (d) and 71.4 (d), and two singlet peaks
due to carbony and thiocarbonyl carbons at δ 170.8 (s) and 179.8 (s), respectively. IR spectrum showed
the presence of monothioimide (-N-C=O) at 1694 cm-1, and the absence of thiol group. Further, a 6.6%
NOE enhancement was observed between the two methine protons (δ 4.11 and 4.76), supporting the
stereostructure of 2 0 as shown in Figure 1.
In conclusion, this regioselective photocyclization could provide a useful method for the construction of a
variety of ring-fused pyrimidine derivatives, i.e., pyridino[1,2-a]pyrimidine, pyrrolino[1,2-a]pyrimidine,
pyridino[1,2-c]pyrimidine, pyrrolino[1,2-c]pyrimidine, pyridino[1,2-d]pyrimidine, pyrrolino[1,2-d]-
pyrimidine, otherwise inaccessible by conventional thermal reaction.
Table 1. Physical Properties and Spectral Data for Thiobarbiturates (4,5,1 4,1 5, and 2 1)
Substrate Yield
(%)
mp
(° C)
MS (m/z) Formula
HRMS
Calcd (Found)
1H-NMR (90 MHz, CDCl3) δ
M+
4a
4b
4 c
77 Yellow oil
254
330
254
C12H18N2O2S
C18H22N2O2 S
C12H18N2O2S
254.1089
(254.1094)
1.55 (6H, s, CH3x2), 1.81 (3H, s, C=CCH3),2.3-
2.4 (2H, m, C=C-CH2-), 3.67 (3H, s, NCH3), 4.4-
4.5 (2H, m, NCH2-), 4.72 (1H, s, C=CH2), 4.79
(1H, s, C=CH2)
1.52 (6H, s, CH3x2), 1.6-2.0 (2H, m, NCH2CH2-),
2.56 (2H, t, J= 7.5 Hz, C=C- CH2-), 3.64 (3H, s,
NCH3), 4.3-4.5 (2H, m, NCH2-), 5.1 and 5.3 (2H,)
br s, C=CH2), 7.2-7.5 (5H, m, ArH)
74 Yellow oil
330.1402
(330.1379)
81
Yellow oil
25 4.1089
(254.1086)
1.55 (6H, s, CH3x2), 1.7-1.8 (2H, m,
NCH2CH2-), 2.1-2.2 (2H, m, C=C-CH2-), 3.67
(3H, s, NCH3), 4.3-4.4 (2H, m, NCH2-), 4.9-5.1
(2H, m, C=CH2), 5.8-5.9 (1H, m, CH2=CH-)
1.64 (6H, s, CH3x2), 1.81 (3H, s, CH3), 2.3-
2.6 (2H, m, C=C-CH2-), 3.66 (3H, s, NCH3),
5a
5b
33 Orange oil
270
C12H18N2OS2
270.0860
(270.0846)
4.7-4.9 (2H, m, C=CH ), 4.9-5.1(2H, m,
NCH 2-)
2
51 Orange oil
346
C18H22N2OS2
346.1174
1.60 (6H, s, CH3x2), 1.7-2.1 (2H, m, NCH2CH2-),
2.58 (2H, t, J= 7.5 Hz, C=C-CH2-), 3.62 (3H, s,
NCH3), 4.8-5.1 (2H, m, NCH2-), 5.11 (1H, d,
J= 1.3 Hz, C=CH2), 5.30 (1H, br s, C=CH2),
(346.1248)

Table 1. Continued
Substrate Yield
(%)
mp
(° C)
MS (m/z) Formula
HRMS
Calcd (Found)
1H-NMR (90 MHz, CDCl3) δ
M+
7.2-7.5(5H, m, ArH)
5 c
14a
14b
15a
55 Orange oil
270
304
318
C12H18N2OS2
C16H20N2O2S
270.0861
(270.0860)
1.64 (6H, s, CH3x2), 1.8-1.9 (2H, m,
NCH2CH2-), 2.1-2.2 (2H, m, C=C-CH2-), 3.65
(3H, s, NCH3), 4.9-5.0 (2H, m, NCH2-), 4.9-5.1
(2H, m, C=CH2), 5.8-5.9 (1H, m, CH2=CH-)
1.52 (6H, s, CH3x2), 1.9-2.1 (2H, m, NCH2CH2-),
2.68 (2H, t, J= 7.8 Hz, PhCH2-), 3.64 (3H, s,
NCH3), 4.3-4.5 (2H, m, NCH2-), 7.1-7.4 (5H, m,
ArH)
1.5-1.9 (4H, m, NCH2CH2CH2-), 1.53 (6H, s,
CH3x2), 2.5-2.8 (2H, m, PhCH2-), 3.65 (3H, s,
NCH3), 4.2-4.5 (2H, m, NCH2-), 7.0-7.4
(5H, m, ArH)
80 Pale yellow
prisms
304.1246
(304.1245)
125-127
82 Pale yellow
prisms
C17H22N2O2S 318.1402
(318.1340)
73-74
48
C16H20N2OS2 320.1017
(320.0989)
1.62 (6H, s, CH3x2), 2.0-2.2 (2H, m,
NCH2CH2-), 2.68 (2H, t, J= 7.8 Hz, PhCH2-),
3.63 (3H, s, NCH3), 4.9-5.0 (2H, m, NCH2-),
7.1-7.4 (5H, m, ArH)
15b
21a
21b
49 Orange
prisms
334
320
334
C17H22N2OS2
334.1174
(334.1164 )
1.5-1.9 (4H, m, NCH2CH2CH2-), 1.63 (6H, s,
CH3x2), 2.6-2.7 (2H, m, PhCH2-), 3.65 (3H, s,
NCH3), 4.9-5.0 (2H, m, NCH2-), 7.1-7.4 (5H,
m, ArH)
1.2-1.8 (2H, m, PhCH2CH2-), 1.68 (3H, s, CH3),
2.0-2.3 (2H, m, PhCH2CH2CH2-), 2.55 (2H, t,
J= 7.5 Hz, PhCH2-), 3.64 (3H, s, NCH3), 4.19
(3H, s, NCH3), 7.0-7.4 (5H, m, ArH)
0.9-1.7 (4H, m, PhCH2CH2CH2-), 1.70 (3H, s,
CH3), 2.0-2.2 (2H, m, CH3C-CH2-), 2.55 (2H, t,
J= 7.5 Hz, PhCH2-), 3.64 (3H, s, NCH3), 4.19
(3H, s, NCH3), 7.0-7.4 (5H, m, ArH)
56-57
43 Orange
prisms
C16H20N2OS2
320.1017
(320.1001)
66-67.5
48 Orange oil
C17H22N2OS2 334.1173
(334.1196)
Table 2. Physical Properties and Spectral Data for Products (6-11, 16-20, and 22-24)
Substrate Time Product Yield
(h) (%)
mp (°C) IR (Nujol)
(cm-1)
M(m/z) Formula
Analysis
Calcd (Found)
M+
C
H
N
S
4b
4c
1.17
6
34
26
125-127
112-114
1670
1640
1695
1655
330
284
C 18H22N2O2S
65.43 6.72 8.48 9.68
(65.42 6.74 8.34 9.83)
71.80 7.09 9.85
7b
C17H20N2O2
(71.85 7.10 9.98)
8b
7c
trace
36
oil
oil
296
208
a)
0.67
1698
1650
C11H16N2O2
208.1212
(208.1208)

Table 2. Continued
Substrate Time Product Yield
mp (°C) IR (Nujol)
M(m/z) Formula
Analysis
Calcd (Found)
1
(h)
(%)
(cm- )
M+
C
H
N
S
a)
8c
9
3
87-90
174-176
68-69.5
126-127
89-90.5
1686, 1646 220
C 12H16N2O2
220.1212
1626
1695
(220.1208)
5a
0.25
18
46
270
C12H18N2OS2
C11H16N2OS
C17H20N2OS
C11H16N2OS
53.32 6.72 10.37 23.68
(53.22 6.65 10.17 23.61)
58.90 7.20 12.50 14.27
(58.96 7.26 12.35 14.06)
67.97 6.72 9.33 10.65
(67.86 6.85 9.29 10.65)
58.90 7.19 12.49 14.29
(58.86 7.19 12.45 14.65)
10a
10b
10c
1695,1680 224
1655
5b
5 c
0.67
0.25
37
21
1700
300
224
270
1701
1660
a)
11-i
20
semisolid
1705
C12H18N2OS2
270.0861
(270.0858)
11-ii
16a
trace
78
14a
0.28
124-126
102-104
1696
1655, 1640
270
268
C16H18N2O2
C16H16N2O2
71.09 6.71 10.36
(71.16 6.93 10.28)
a)
1 7
6
1735
1670
268.1212
(268.1216)
14b
15a
0.7
1.5
7b
18a
40
23
121-123
159-161
1690
1660
286
C16H18N2OS
C17H22N2OS2
67.11 6.34 9.79 11.18
(67.23 6.48 9.91 11.04)
15b
0.5
10b
1 9
13
8
a)
2527
1691
1694
334
334
334.1174
(334.1165)
a)
2 0
9
97-99
C17H22N2OS2
C16H20N2OS2
C16H20N2OS2
C17H22N2OS2
334.1174
(334.1175)
21a
0.83
22a-i
25
99-100
130-132
187-188
2580
1690
2560
1695
2560
1695
320
59.98 6.30 8.75 19.98
(60.04 6.33 8.63 19.80)
59.98 6.30 8.75 19.98
(59.96 6.29 8.70 19.97)
22a-ii 23
320
334
21b 18.5
22b
2 3
12
6
61.06 6.64 8.38
9.14
(61.05 6.63 8.24 19.27)
a)
oil
oil
1701
300
318
C17H20N2OS
C17H22N2O2S
300.1296
(300.1302)
24
9
1725
a
Determined by HRMS spectrometry. Upper figure, calcd for M+; lower figure, found.
Table 3. NMR Spectral Data for the Componds (6-11, 16-20, and 22-24)
Compd
1H-NMR (CDCl3, 400 MHz) δ
13C-NMR (CDCl3, 400 MHz) δ
6
1.39 (3H, s, CH3), 1.58 (3H, s, CH3), 1.9-2.2 (2H, m, NCH2CH2-), 17.9(t), 24.3(q), 25.9(q), 30.2(t), 32.2(q), 41.3 (t),

Table 3. Continued
Compd
1H-NMR (CDCl3, 400 MHz) δ
13C-NMR (CDCl3, 400 MHz) δ
2.75 (3H, s, NCH3), 2.96 (1H, d, J= 9.7 Hz, S-CH2-), 3.4-3.7 (2H,
42.2 (t), 44.4(s), 64.4(s), 88.4(s), 123.7(d) x2,
m, NCH2CH2CH2-), 3.71 (1H, d, J= 9.7 Hz, SCH2-), 4.5-4.9 (2H,
127.0(d), 128.8(d)x2, 145.3(s), 172.0(s), 172.3(s)
m, NCH2-), 6.9-7.2 (2H, m, ArH), 7.2-7.5 (3H, m, ArH)
1.50 (6H, s, CH3x2), 1.8-2.1 (2H, m, NCH2CH2-), 2.61 (2H, t,
J= 6.2 Hz, C=C-CH2-), 2.64 (3H, s, NCH3), 3.8-4.0 (2H, m,
NCH2-), 7.1-7.5 (5H, m, ArH)
7b
8b
21.2(q)x2, 22.0(t), 29.6(t), 36.3(q), 42.0(t),
47.5(s), 112.3(s), 127.6(d), 128.1(d)x2,
128.9(d)x2, 131.1 (s), 139.3(s), 169.6(s), 171.5(s)
1.48 (6H, s, CH3x2), 2.75-2.85 (2H, br t, C=C-CH2-), 3.03
(3H, s, NCH3), 3.9-4.0 (2H, br t, NCH2-), 5.25(1H, d, J= 1.3 Hz,
C=CH2), 5.72 (1H, d, J= 1.3 Hz, C=CH2), 7.2-7.5 (5H, m, ArH)
23.8(q)x2, 31.3(t), 32.6(q), 42.7(t), 46.2(s),
103.1 (s), 116.8(t), 126.5(d)x2, 127.8(d),
128.1(d)x2, 132.0(s), 139.4(s), 142.7(s),
168.0(s), 171.8(s)
7 c
8 c
9
1.43 (6H, s, CH3x2), 1.8-1.9 (2H, m, NCH2CH2-), 2.3-2.4
(2H, m, C=CH-CH2-), 3.23 (3H, s, NCH3), 3.8-3.9 (2H, m,
NCH2-), 4.69 (1H, t, J= 4 Hz, C=CH-CH2-)
1.46 (6H, s, CH3x2), 2.8-2.9 (2H, m, C=C-CH2-), 3.51 (3H,
s, NCH3), 3.90 (2H, t, J= 8.8 Hz, NCH2-), 4.9-5.1 (2H, m,
C=CH2), 6.9-7.0 (1H, m, CH2=CH-)
1.17 (3H, s, CH3), 1.55 (3H, s, CH3), 1.71 (3H, s, CH3), 1.8-
2.0 (1H, m, NCH2CH2-), 2.0-2.1 (1H, m, NCH2CH2-), 2.71
(1H, d, J= 9 Hz, SCH2-), 3.06 (1H, d, J= 9 Hz, SCH2-), 3.50 (3H,
s, NCH3), 4.2-4.3 (1H, m, NCH2-), 4.3-4.5 (1H, m, NCH2-)
1.57 (6H, s, CH3x2), 1.89 (3H, t, J= 1.5 Hz, C=C-CH3), 2.5-2.6
(2H, br t, C=C-CH2-), 3.59 (3H, s, NCH3), 4.20 (2H, t,
J= 8.3 Hz, NCH2-)
24.1(t), 22.1(t), 23.2(q)x2, 30.4(q), 41.1(t),
46.4 (s), 91.6(d), 133.9(s), 169.0(s), 169.6(s)
24.1(q)x2, 26.7(t), 33.1(q), 42.6(t), 45.9(s),
103.7 (s), 113.3(t), 128.9(d), 131.2(s), 167.9(s),
171.7(s)
20.2(q), 20.6(q), 23.9(q), 30.7(t), 34.2(q), 37.8(t),
47.2(s), 51.1(t), 58.3(s), 80.7(s), 171.0 (s),
177.7(s)
10a
14.4(q), 26.2(q)x2, 33.0(t), 34.2(q), 40.9(s),
52.0 (t), 121.8(s), 134.6(s), 170.7(s), 171.3(s)
10b 1.08 (6H, s, CH3x2), 1.8-2.2 (2H, m, NCH2CH2-), 2.37 (2H, t,
J= 6 Hz, C=C-CH2-), 3.59 (3H, s, NCH3), 4.49 (2H, br t, J= 5 Hz,
NCH2-), 7.0-7.5 (5H, m, ArH)
22.5(t), 25.4(q)x2, 35.0(t), 35.2(q), 44.7(s),
50.2(t), 127.2(d), 128.1(d)x2, 128.3(d)x2,
128.5 (s), 133.7 (s), 141.3(s), 171.4(s), 177.1(s)
22.2(t), 23.2(t), 23.9(q)x2, 35.0(q), 42.3(s),
49.9(t), 110.2(d), 138.6(s), 171.2(s), 177.1(s)
10c
1.35 (6H, s, CH3x2), 1.9-2.0 (2H, m, NCH2CH2-), 2.2-2.3 (2H,
m, C=CH-CH2-), 3.60 (3H, s, NCH3), 4.3-4.4 (2H, m, NCH2-),
5.27 (1H, t, J= 4 Hz, C=CH-CH2-)
11-i
1.19 (3H, s, CH3), 1.39 (3H, s, CH3), 1.96 (1H, s, SH), 2.0-2.3
(2H, m, NCH2CH2-), 3.2-3.3 (1H, m, C=C-CH-), 3.56 (3H,
s, NCH3), 3.7-3.8 (1H, m, NCH2-), 4.1-4.2 (1H, m, NCH2-),
5.2-5.4 (2H, m, C=CH2), 5.9-6.1 (1H, m, CH2=CH-)
19.7(q), 20.6(q), 27.5(t), 34.1(q), 48.3(s),
49.7 (d), 51.9(t), 77.6(s), 119.4(t), 135.6(d),
171.5(s), 176.8(s)
11-ii 1.04 (3H, s, CH3), 1.26 (3H, s,CH3), 1.7-1.9 (1H, m,
NCH2CH2-), 2.1-2.2 (1H, m, NCH2CH2-), 2.9-3.0 (1H,
m, C=C-CH-), 3.50 (3H, s, NCH3), 3.6-3.8 (1H, m, NCH2-),
4.1-4.3 (1H, m, NCH2-), 5.1-5.3 (2H, m, C=CH2), 5.6-5.8
(1H, m, CH2=CH-)
16a
1.50 (6H, s, CH3x2), 2.97 (3H, s, NCH3), 2.9-3.1 (2H, m,
C=C-CH2-), 3.97 (2H, br t, J= 8.5 Hz, NCH2-), 7.2-7.4 (5H,
m, ArH)
1.60 (6H, s, CH3x2), 3.04 (3H, s, NCH3), 6.30 (1H, d,
J= 3.5 Hz, C=CH-), 7.15 (1H, d, J= 3.5 Hz, C=CH-), 7.2-7.4
(5H, m, ArH)
23.6(q)x2, 31.7(t), 33.6(q), 42.5(t), 46.4(s),
104.0(s), 127.4(d), 128.3(d)x2, 129.0(d)x2,
130.6(s), 134.9(s), 168.2(s), 172.2(s)
24.3(q)x2, 33.2(q), 48.0(s), 111.8(d),
112.2(s), 116.6(d), 127.5(d), 128.3(d)x2,
129.9(d)x2, 130.1(s), 134.5(s), 169.4(s),
170.5(s)
17
18a
1.33 (6H, s, CH3x2), 2.8-2.9 (2H, m, C=C-CH2-), 3.62 (3H,
s, NCH3), 4.3-4.5 (2H, m, NCH2-), 7.1-7.2 (2H, m,
ArH), 7.3-7.5 (3H, m, ArH)
26.7(q)x2, 34.3(q), 34.7(t), 41.6(s), 52.6(t),
126.3(s), 127.9(d), 128.5(d)x4, 135.8(s),
136.2(s), 171.1(s), 172.4(s)

Table 3. Continued
Compd
1H-NMR (CDCl3, 400 MHz) δ
13C-NMR (CDCl3, 400 MHz) δ
19
0.76 (3H, s, CH3), 1.35 (3H, s, CH3), 1.8-2.0 (2H, m,
NCH2CH2-), 2.0-2.2 (1H, m, NCH2CH2CH2-), 2.22 (1H, s, SH),
2.2-2.4 (1H, m, NCH2CH2CH2-), 3.3-3.5 (1H, m, PhCH-), 3.65
(3H, s, NCH3), 4.3-4.5 (1H, m, NCH2-), 4.7-4.9 (1H, m, NCH2-),
7.2-7.4 (5H, m, ArH)
20.5(q), 20.7(q), 22.8(t), 29.8(t), 36.2(q),
47.3(d), 49.1(t), 50.1(s), 77.5(s), 127.9(d)x2,
128.8(d)x3, 141.6(s), 170.9(s), 181.4(s)
2 0
1.30 (3H, s, CH3), 1.32 (3H, s, CH3), 1.7-1.9 (1H, m,
NCH2CH2-), 2.1-2.2 (1H, m, NCH2CH2CH2-), 2.3-2.4 (1H, m,
NCH2CH2-), 2.4-2.6 (1H, m, NCH2CH2CH2-), 3.5-3.7 (1H,
m, NCH2-), 3.62 (3H, s, NCH3), 4.11 (1H, dd, J= 10.3, 1.5 Hz,
PhCH-), 4.76 (1H, s, SCH-), 5.1-5.2 (1H, m, NCH2-), 7.2-
7.4 (5H, m, ArH)
21.6(q), 24.2(q), 25.3(t), 34.7(q), 36.9(t),
42.2(s), 51.4(d), 53.6(t), 71.4(d), 127.3(d)x2,
127.8 (d), 128.8(d)x2, 141.4(s), 170.8(s),
179.8(s)
22a-i 1.34 (3H, s, CH3), 1.9-2.1 (2H, m, PhCHCH2CH2-), 2.1-2.3
(1H, m, PhCHCH2-), 2.17 (1H, s, SH), 2.9-3.0 (1H, m,
PhCHCH2-), 3.28 (3H, s, NCH3), 3.56 (1H, t, J= 10 Hz, PhCH-),
3.73 (3H, s, NCH3), 7.2-7.3 (2H, m, ArH), 7.3-7.4 (3H, m, ArH)
22a-ii 1.42 (3H, s, CH3), 2.0-2.2 (2H, m, PhCHCH2CH2-), 2.2-2.4
(1H, m, PhCHCH2-), 2.54 (1H, s, SH), 3.0-3.1 (1H, m,
PhCHCH2-), 3.25 (3H, s, NCH3), 3.51 (3H, s, NCH3),
3.5-3.6 (1H, m, PhCH-), 7.02 (2H, d, J=7.8 Hz, ArH),
7.2-7.3 (3H, m, ArH)
20.3(q), 23.6(t), 31.7(t), 36.0(q), 44.1(q),
54.0(s), 54.9(d), 82.8(s), 128.5(d), 128.7(d)x2,
129.6(d)x2, 136.4(s), 171.2(s), 178.8(s)
23.5(q), 27.0(t), 33.5(t), 35.3(q), 44.1(q),
52.6(s), 58.8(d), 83.9(s), 128.3(d)x2,
128.4(d) x3, 138.3(s), 170.7(s), 179.7(s)
22b 1.23 (3H, s, CH3), 1.5-1.7 (1H, m, CH3C-CH2-), 1.7-1.9 (2H,
m, PhCHCH2CH2-), 1.9-2.0 (1H, m, CH3C-CH2-), 2.3-2.4 (1H,
m, PhCHCH2-), 2.35 (1H, s, SH), 2.4-2.5 (1H, m, PhCHCH2-),
3.02 (3H, s, NCH3), 3.2-3.4 (1H, m, PhCH-), 3.72 (3H, s,
NCH3), 7.1-7.2 (2H, m, ArH), 7.3-7.4 (3H, m, ArH)
22.3(q), 22.3(t), 28.3(t), 32.0(t), 35.4(q),
44.2(q), 49.3(s), 50.1(d), 81.0(s), 128.1(d),
128.6(d)x2, 129.5(d)x2, 138.8(s), 170.5(s),
179.2(s)
2 3
1.28 (3H, s, CH3), 1.6-1.8 (1H, m, CH3C-CH2-), 1.8-1.9 (1H, m,
CH3C-CH2-), 2.0-2.1 (2H, m, C=C-CH2CH2-), 2.2-2.4 (1H, m,
C=C-CH2-), 2.6-2.8 (1H, m, C=C-CH2-), 2.96 (3H, s, NCH3),
3.57 (3H, s, NCH3), 7.1-7.2 (2H, m, ArH), 7.2-7.4 (3H, m, ArH)
0.9-1.9 (4H, m, PhCH2CH2CH2- ), 1.54 (3H, s, CH3), 1.9-2.1 (2H,
m, CH3C-CH2-), 2.5-2.6 (2H, m, PhCH2-), 3.65 (6H, s, NCH3x2),
7.0-7.4 (5H, m, ArH)
18.8(t), 22.4(q), 31.4(t), 31.6(t), 34.5(q),
42.8(s), 45.0(q), 128.0(d)x2, 128.1(d),
128.9(d)x2, 130.5(s), 134.5(s), 139.3(s),
172.5(s), 179.6(s)
2 4
EXPERIMENTAL
All melting points were determined on a Yamato melting point apparatus (model MP-21) and are
uncorrected. IR spectra were recorded on a JASCO A-102 spectrophotometer. NMR spectra were taken
on JEOL-FX-90Q and JEOL JNM-EX 400 spectrometers. Chemical shifts are reported in ppm (δ) with
tetramethylsilane as an internal standard. MS spectra were determined with a JEOL JMS-QH-100 gas
chromatograph-mass spectrometer with a direct inlet system and HRMS spectra were recorded using a
Micromass Auto Spec 3000 mass spectrometer.
Irradiations of substrates were conducted using a 1 kW high-pressure mercury lamp and a water-cooled
quartz immersion well (Eikosha EHB-W-1000). Stirring of the reaction mixture was effected by the

introduction of a stream of nitrogen at the bottom of the outer jacket. All column chromatography was
conducted using silica gel (Wakogel C-300, 200-300 mesh).
2,3-Dihydro-1,5,5-trimethyl-2-thioxo-4,6(1H,5H) -pyrimidinedione
Triethylamine (11.1
mL, 80 mmol) was added to a mixture of dimethylmalonyl dichloride (5.2 mL, 40 mmol) and 1-methyl-2-
thiourea (3.6 g, 40 mmol) in THF (250 mL) at rt. The reaction mixture was refluxed for 8 h, then poured
into ice-water, acidified with 10% HCl, and extracted with AcOEt. The organic layer was washed with
brine and dried over MgSO4 . After removal of the solvent in vacuo, the residue was recrystallized from
AcOEt-hexane to give pale yellow prisms of 2,3-dihydro-1,5,5-trimethyl-2-thioxo-4,6(1H,5H)-
pyrimidinedione (6.6 g, 89%), mp 151-152.5 °C. Anal. Calcd for C7 H10 N2O2S: C, 45.15; H, 5.41; N,
15.04; S, 17.22. Found: C, 45.21; H, 5.42; N, 15.11; S, 17.17.
2,3,4,5-Tetrahydro-1,5,5-trimethyl-2,6-dithioxo-4( 1H) -pyrimidinone A solution of 2,3-
dihydro-1,5,5-trimethyl-2-thioxo-4,6(1H,5H)-pyrimidinedione (6.0 g, 32 mmol) and Lawesson's reagent
(7.5 g, 18 mmol) in xylene (55 mL) was reflux for 3 h. The solution was directly subjected to column
chromatography on silica gel with CHCl3 - hexane (1:2, v/v) to give 2,3,4,5-tetrahydro-1,5,5-trimethyl-2,6-
dithioxo-4(1H)-pyrimidinone (4.23 g, 66%). Orange needles (from AcOEt-hexane), mp 159-160 °C.
Anal. Calcd for C7H10N2OS2: C, 41.56; H, 4.98; N, 13.85; S, 31.70. Found: C, 41.62; H, 5.07; N,
14.04; S, 31.72.
2,3-Dihydro-1-( 3-methyl-3-butenyl) -3,5,5-trimethyl-2-thioxo-4,6( 1H,5H) -pyrimidine-
dione (4a) : Typical Procedure A solution of diethyl azodicarboxylate (2.09 g, 12 mmol) in THF
(5 mL) was added dropwise under an N2 atmosphere to a stirred mixture of 2,3-dihydro-1,5,5-trimethyl-2-
thioxo-4,6(1H,5H)-pyrimidinedione (1.86 g, 10 mmol), 3-methyl-3-butene-1-ol (1.03 g , 12 mmol), and
triphenylphosphine (3.12 g, 12 mmol) in THF (50 mL) at 0 °C. The reaction mixture was stirred at the
same temperature for 4 h, then the solvent was evaporated in vacuo. The residue was chromatographed on
silica gel with AcOEt-hexane (1:20, v/v) to give 4a (1.94 g, 76%). Compounds (4, 5, 14, and 15) were
prepared from 2,3-dihydro-1,5,5-trimethyl-2-thioxo-4,6(1H,5H)-pyrimidinedione or 2,3,4,5-tetrahydro-
1,5,5-trimethyl-2,6-dithioxo-4(1H)-pyrimidinone and the corresponding alcohols respectively, according to
the procedure described above. The solvent systems used were as follows: 4b, AcOEt-hexane (1:10, v/v);
14b, 4c, 5a, 14a, AcOEt-hexane (1:20, v/v); 5b, 5c, 15a, 15b, AcOEt-hexane (1:30, v/v). Yields and
analytical data of thiobarbiturates (4,5,14, and 15) are listed in Table 1.
2,3,4,5-Tetrahydro-1,3,5-trimethyl-5-( 3-phenylpropyl) -2,6-dithioxo-4( 1H) -pyrimidi-
none (21a) i) Diethyl methylmalonate (4.35 g, 25 mmol) was added dropwise at 0 °C to a suspension of
LiH (360 mg, 45 mmol) in DMF (30 mL) under an argon atmosphere, and the reaction mixture was stirred
at the same temperature for 30 min. Then 3-phenylpropyl bromide (5.5 g, 28 mmol) was added dropwise
to the above mixture at rt, and the mixture was stirred for an additional 3 h at 80 °C. The reaction mixture
was poured into ice-water, acidified with 10% HCl, and extracted with Et2O. The organic layer was washed
with brine and dried over MgSO4 . After removal of the solvent in vacuo, the residue was

chro mato grap hed on s ilica g el with AcOEt-h exan e (1 :20, v/v) to give d ieth yl methy l(3 -
1
phenylpropyl)malonate (7.18 g, 98%), colorless oil. H-NMR (CDCl3, 90 MHz) δ: 1.22 (6H, t, J= 7 Hz,
CH3CH2 x 2), 1.39 (3H, s, CH3), 1.4-2.0 (4H, m, PhCH2 CH2CH2 -), 2.63 (2H, t, J= 7 Hz, PhCH2-),
4.16 (4H, q, J= 7 Hz, CH3CH2O-x2), 7.0-7.5 (5H, m, ArH).
ii)
A solution of KOH (4.17 g, 74 mmol) in H2O (4.5 mL) was added at rt to a solution of diethyl
methyl(3-phenylpropyl)malonate (7.18 g, 24.6 mmol) in EtOH (18 mL), and the reaction mixture was
refluxed overnight. After removing the solvent, the residue was dissolved in H2O, acidified with 10%
HCl, and extracted with Et2O. The organic layer was washed with brine and dried over MgSO4, and
evaporated to dryness. The residue was purified by recrystallization from AcOH-hexane to give methyl(3-
phenylpropyl)methane-1,1-dicarboxylic acid (4.62 g, 80%), colorless needles, mp 131-133 °C. IR (Nujol):
2640, 1700 cm- 1.
iii)
A mixture of the resulting dicarboxylic acid (3.54 g, 15 mmol) and phosphorus pentachloride (6.9 g,
33 mmol) in dry benzene (15 mL) was refluxed for 6 h. The reaction mixture was concentrated to yield
the methyl (3-phenylpropyl)methane-1,1-dicarbonyl chloride, which was used for the next reaction without
purification. Triethylamine (4.2 mL, 30 mmol) was added to a mixture of resulting dichloride (3.4 g, 12
mmol) and 1,3-dimethyl-2-thiourea (1.25 g, 12 mmol) in dry toluene (250 mL) at 50 °C. The reaction
mixture was refluxed for 1 h, then poured into ice-water, acidified with 10% HCl, and extracted with
AcOEt. The organic layer was washed with brine and dried over MgSO4. After removal of the solvent in
vacuo, the residue was chromatographed on silica gel with AcOEt-hexane (1:10, v/v) to give 2,3-dihydro-
1,3,5-trimethyl-5-(3-phenylpropyl)-2-thioxo-4,6(1H, 5H)-pyrimidinedione (2.80 g, 77%). Pale yellow
prisms, mp 73-74 °C (from diisopropyl ether-hexane). IR (Nujol): 1720, 1685 cm-1. 1H-NMR (CDCl3,
90 MHz) δ: 1.1-1.7 (2H, m, PhCH2CH2-), 1.53 (3H, s, CH3), 1.9-2.2 (2H, m, PhCH2-CH2CH2-), 2.57
(2H, t, J= 7.5 Hz, PhCH2-), 3.66 (6H, s, NCH3 x 2), 7.0-7.4 (5H, m, ArH). MS (m/z): 304 (M+).
iv)
A
solution of resulting 2,3-dihydro-1,3,5-trimethyl-5-(3-phenylpropyl)-2-thioxo-4,6(1H, 5H)-
pyrimidinedione (1.3 g, 4.28 mmol) and Lawesson's reagent (2.0 g, 4.95 mmol) in xylene (10 mL) was
refluxed for 2 days. The solution was directly subjected to column chromatography on silica gel with
AcOEt-hexane (1:30, v/v) to give dithiobarbiturate (21a , 538 mg , 43%) along with corresponding
trithiobarbiturate (134 mg, 9%) and unchanged monothiobarbiturate (452 mg, 35%).
2,3,4,5-Tetrahydro-1,3,5-trimethyl-5-( 4-phenylbutyl)-2,6-dithioxo-4(1H)-pyrimidinone
(21b)
Compound (21b) was obtained by the same method as described for the preparation of 21a,
but with 4-phenylbutyl bromide in place of 3-phenylpropyl bromide.
Irradiation of Thiobarbiturate Derivatives ( 4,5,14,15, and 21) : General Procedure
A
solution of thiobarbiturate (10 mM) in MeCN was irradiated with a 1 kW high-pressure mercury lamp
through a Pyrex filter with water cooling. Progress of the reaction was monitored by TLC until the
substrate disappeared. After removal of the solvent in vacuo, the residue was subjected to silica gel
column chromatography. The solvent systems used were as follows: 4a, AcOEt-hexane (3:2, v/v);
4b,21a, AcOEt-hexane (1:6, v/v); 4c, AcOEt-hexane (1:2, v/v); 5a,5b,5c,15a, AcOEt-hexane (1:10,

v/v); 14a,14b, AcOEt-hexane (1:1, v/v); 15b, AcOEt-hexane (1:15, v/v); 21b, AcOEt-hexane (1:20, v/v).
Yields and analytical data of photoproducts of 4,5,14,15, and 21 are listed in Table 2 and Table 3.
Thionation of 7b and 10b
A solution of 7b (40 mg, 0.14 mmol) and Lawesson's reagent (113 mg,
0.28 mmol) in xylene (2 mL) was reflux for 6 h. The solution was directly subjected to column
chromatography on silica gel with AcOEt-hexane (1:10, v/v) to give 12 (44 mg, 100%). Yellow prisms,
mp 146.5-147 °C (from diisopropyl ether-hexane). 1H-NMR (CDCl3, 90 MHz) δ: 1.77 (6H, s, CH3x2),
1.9-2.3 (2H, m, NCH 2CH2-), 2.68 (2H, t, J= 6 Hz, C=C-CH2 -), 3.06 (3H, s, NCH3 ), 4.3-4.5 (2H, m,
NCH2-), 7.2-7.5 (5H, m, ArH). MS (m/z): 316 (M+).
Compound (13) was obtained by the same method as described for the preparation of 12.
Yield, 95%,
yellow oil. 1H-NMR (CDCl3, 90 MHz) δ: 1.19 (6H, s, CH3 x 2), 1.8-2.2 (2H, m, NCH2CH2-), 2.2- 2.5
(2H, m, C=C-CH2-), 4.10 (3H, s, NCH3), 4.4-4.5 (2H, m, NCH2 -), 7.0-7.4 (5H, m, ArH). MS (m/z):
316 (M+).
ACKNOWLEDGMENTS
This work was supported in part by Grant-in-Aid for High Technology Research Programs from the
Ministry of Education, Culture, Sports, Science and Technology in Japan. We grateful to Center for
Instrumental Analysis, Hokkaido University for measurement of elemental analysis .
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