682
Vol. 38
J. S. Larsen, M. T. A. Aal, E. B. Pedersen and C. Nielsen
5,6-Dibenzyl-2-thiouracil (8).
acetoxymethyl ether (1.35 g, 0.0075 mole) in anhydrous methyl-
ene chloride (15 ml). After 3 hours with stirring at room tempera-
ture the clear solution was cooled to 0° and stannane (IV)
chloride (0.1 ml, 0.001 mole) was added. The mixture was then
allowed to warm to room temperature, and was stirred overnight.
The mixture was poured into a mixture of cold saturated aqueous
sodium hydrogencarbonate (50 ml). The resulting emulsion was
filtered through Celite and separated. The aqueous layer was
extracted further with ethyl acetate (3 x 25 ml) and the combined
organic phases were dried over anhydrous sodium sulfate and
evaporated under reduced pressure. The remaining oily residue
was triturated with ether to furnish the crude oily product which
was purified by silica gel column chromatography with ethyl
acetate:petroleum ether (bp. 60-80°, 1:1, v/v) as the eluent to give
Sodium (26.0 g, 1.13 moles) was dissolved in anhydrous
ethanol (570 ml) and thiourea (59.0 g, 0.78 mole) and compound
7 (15.0 g, 0.05 mole) were added to obtain a clear solution. The
mixture was refluxed for 18 hours and evaporated in vacuo at
30-40° to leave a nearly dry residue which was redissolved in the
least amount of water (200 ml). The title compound was
precipitated by addition of 4 M hydrochloric acid (300 ml). Yield
1
8.62 g (56%); mp 190-191°; H nmr (DMSO-d ): δ 3.63 (s, 2 H,
6
CH Ph), 3.84 (s, 2 H, CH Ph), 7.07-7.29 (m, 10 H, Ar), 12.43
2
2
13
(brs, 2 H, 2 x NH); C nmr (DMSO-d ): δ 29.21 (CH Ph), 34.70
6
2
(CH Ph), 114.72 (C-5), 126.03, 126.86, 128.03, 128.29, 128.69,
2
136.22, 139.29 (Ar), 150.88 (C-2, C-6), 161.91 (C=O), 174.73
+
(C=S); EI ms: m/z 308 (M ).
1
11 (429 mg, 21%); mp 71-72°; H nmr (deuteriochloroform): δ
Anal. Calcd. for C
H N OS (308): C, 70.10; H, 5.23; N,
18 16 2
1.97 (s, 3 H, CH ), 3.78 (t, 2 H, J = 2.91 Hz, CH OCH ), 3.83
3
2
2
9.08. Found: C, 70.20; H, 5.27; N, 9.09.
(s, 2 H, 2 x CH Ph), 4.15 (t, 2 H, J = 4.59 Hz, OCH CH ), 5.17
2
2
2
13
(s, 2 H, OCH ), 7.03-7.32 (m, 10 H, Ar), 10.15 (br, 1 H, NH);
C
5,6-Dibenzyluracil (9).
2
nmr (deuteriochloroform): δ 20.69 (CH ), 30.51 (CH Ph), 33.81
3
2
5,6-Dibenzyl-2-thiouracil (8) (2.0 g, 6.5 mmoles) was
suspended in 10% aqueous chloroacetic acid (200 ml) and
subsequently refluxed for 24 hours. After cooling to room
temperature the precipitate was filtered off, washed with cold
ethanol and finally dried in vacuo to afford the title compound.
(CH Ph), 63.06 (OCH ), 67.47 (OCH CH ), 73.05 (OCH N),
2
2
2
2
2
114.63 (C-5), 126.45, 127.35, 127.48, 128.01, 128.67, 129.41,
134.78, 138.59 (Ar), 150.97 (C-2, C-6), 163.78 (C-4), 170.73
(C=O); FAB ms: (DMSO+3-nitrobenzyl alcohol) m/z 409
+
(M+H ).
1
Yield 1.25 g (66%); mp 210°; H nmr (DMSO-d ): δ 3.46 (s, 2 H,
6
Anal. Calcd. for C
H N O (408): C, 66.90; H, 5.98; N,
23 24 2 5
CH Ph), 3.59 (s, 2 H, CH Ph), 6.94-7.15 (m, 10 H, Ar), 10.73
2
2
6.78. Found: C, 66.79; H, 5.89; N, 6.71.
13
(br, 1 H, NH), 10.99 (br, 1 H, NH); C nmr (DMSO-d ): δ 29.13
6
General Procedure for the Preparation of Compounds (12a-f).
(CH Ph), 35.18 (CH Ph), 108.89 (C-5), 125.73, 126.68, 127.62,
2
2
136.18, 140.01 (Ar), 150.91, 151.03 (C-2, C-6), 164.76 (C-4); EI
ms: m/z 292 (M ).
Method A: Compound 8 (1.0 mmole) was mixed with the
appropriate halogen compound (1.0 mmole) and anhydrous
potassium carbonate (1.0 mmole) in anhydrous N,N-dimethyl-
formamide (3 ml). Method B: Compound 8 was mixed with
(2.2 mmoles) of the appropriate halo compound and sodium
(1.1 mmoles) in methanol (3 ml). The mixture was stirred
overnight at room temperature. After treatment with water
(60 ml), the solution was extracted with ethyl acetate (3 x 50 ml),
dried over anhydrous sodium sulfate and evaporated in vacuo to
afford the corresponding crude 2-alkylthio derivatives. The
compounds 12a-f were purified by the procedures describes for
each compound.
+
Anal. Calcd. for C
H N O (292): C, 73.96; H, 5.52; N,
18 16 2 2
9.58. Found: C, 73.74; H, 5.54; N, 9.57.
1-(Ethoxymethyl)-5,6-dibenzyluracil (10).
Compound 9 (0.29 g, 1 mmole) was suspended in anhydrous
chloroform (15 ml), and N,O-bis(trimethylsilyl)acetamide (BSA)
(0.6 ml, 2.5 mmoles) was added dropwise under nitrogen After
stirring 10 minutes, chloromethyl ethyl ether (0.14 ml,
1.5 mmoles) was added to the clear solution and the mixture was
stirred at room temperature overnight. The mixture was
quenched, and neutralised by addition of saturated aqueous
sodium hydrogencarbonate (7 ml) and ethanol (20 ml), and was
evaporated in vacuo to afford the title compound which was
purified by silica gel column chromatography with ethyl
acetate:petroleum ether (bp. 60-80°, 3:10, v/v) as the eluent to
5,6-Dibenzyl-2-(methylthio)pyrimidine-4(3H)-one (12a).
The compound was recrystallised from ethanol. Yield 70 mg
1
(53%); mp 195-196°; H nmr (DMSO-d ): δ 2.45 (s, 3 H, CH ),
6
3
3.89 (s, 2 H, CH Ph), 3.94 (s, 2 H, CH Ph), 7.13-7.25 (m, 10 H,
Ar), 12.55 (brs, 1 H, NH); C nmr (DMSO-d ): δ 13.24 (CH ),
30.39 (CH Ph), 40.76 (CH Ph), 119.39 (C-5), 126.06, 126.39,
2
2
1
13
give 10 (183 mg, 52%); mp133-134°; H nmr (deuterio-
6
3
chloroform): δ 1.16 (t, 3 H, J = 7.11 Hz, CH ), 3.60 (q, 2 H, J =
3
2
2
7.07 Hz, CH O), 3.82 (s, 2 H, CH Ph), 4.15 (s, 2 H, CH Ph),
128.27, 128.39, 128.45, 129.09, 137.72, 139.78 (Ar), 158.03
2
2
2
+
5.12 (s, 2 H, OCH ), 7.03-7.33 (m, 10 H, Ar), 8.77 (brs, 1 H,
(C-6), 163.22 (C-2), 165.26 (C-4); EI ms: m/z 322 (M ).
2
13
NH); C nmr (deuteriochloroform): δ 15.01 (CH CH ), 30.64
(CH Ph), 33.98 (CH Ph), 65.80 (OCH ), 72.88 (OCH N),
Anal. Calcd. for C
H N OS (322): C, 70.78; H, 5.63; N,
3
2
19 18 2
8.68. Found: C, 70.60; H, 5.59; N, 8.69.
2
2
2
2
114.35 (C-5), 126.37, 127.27, 127.33, 128.11, 128.54, 129.21,
134.56, 138.98 (Ar), 151.35, 151.56 (C-2, C-6), 163.26 (C-4);
FAB ms: (DMSO+3-nitrobenzyl alcohol) m/z 351 (M+H ).
5,6-Dibenzyl-2-(ethylthio)pyrimidine-4(3H)-one (12b).
The compound was recrystallised from ethanol. Yield 178 mg
+
1
Anal. Calcd. for C
H N O (350): C, 71.98; H, 6.33; N,
(53%); mp 134°; H nmr (deuteriochloroform): δ 1.22 (t, 3 H, J =
21 22 2 3
7.99. Found: C, 72.00; H, 6.34; N, 7.99.
7.20 Hz, CH ), 3.05 (q, 2 H, J = 7.50 Hz, CH ), 3.88 (s, 2 H,
3
2
13
CH Ph), 3.95 (s, 2 H, CH Ph), 7.11-7.27 (m, 10 H, Ar); C nmr
2
2
1-[(2-Acetoxyethoxy)methyl]-5,6-dibenzyluracil (11).
(deuteriochloroform): δ 14.48 (CH CH ), 25.05 (CH CH ),
3
2
2
3
N,O-Bis(trimethylsilyl)acetamide (3 ml, 0.012 mole) was
added dropwise under nitrogen to a stirred mixture of 5,6-
dibenzyluracil (9) (1.46 g, 0.005 mole) and 2-acetoxyethyl
30.37 (CH Ph), 40.71 (CH Ph), 119.36 (C-5), 126.34, 126.61,
2 2
128.22, 128.39, 128.89, 129.55, 137.65, 139.20 (Ar), 157.55
+
(C-6), 163.26 (C-2), 165.39 (C-4); EI ms: m/z 336 (M ).