Silicon-, germanium-, and tin-containing derivatives of barbital and methyluracil

Article abstract of DOI:10.1007/s11176-005-0337-4

1,3-Bis(trimethylsilyl)- and 1,3-bis(tributylstannyl)-5,5-diethylpyrimidine-2,4,6(1H,3H,5H)-triones were synthesized in high yields by the reactions of 5,5-diethyl-2,4,6(1H,3H,5H)-trione (barbital) with hexamethyldisilazane and bis(tributylstannyl) oxide, respectively. The products were reacted with acetyl, benzoyl, and 3-(triethylgermyl)propionyl halides to obtain the corresponding bisacylated pyrimidine derivatives. The reaction of 1-methyluracil with (Bu ₃Sn)₂O gave 1-methyl-3-(tributylstannyl)pyrimidine-2,4(1H,3H)-dione.

Full text of DOI:10.1007/s11176-005-0337-4

Russian Journal of General Chemistry, Vol. 75, No. 6, 2005, pp. 870 872. Translated from Zhurnal Obshchei Khimii, Vol. 75, No. 6, 2005,
pp. 923 926.
Original Russian Text Copyright
2005 by Gordetsov, Loginova, Zimina, Cherepenikova, Kurskii.
Silicon-, Germanium-, and Tin-containing Derivatives
of Barbital and Methyluracil
A. S. Gordetsov, L. B. Loginova, S. V. Zimina, N. F. Cherepenikova, and Yu. A. Kurskii
Nizhny Novgorod State Medical Academy, Nizhny Novgorod, Russia
Received January 9, 2004
Abstract 1,3-Bis(trimethylsilyl)- and 1,3-bis(tributylstannyl)-5,5-diethylpyrimidine-2,4,6(1H,3H,5H)-
triones were synthesized in high yields by the reactions of 5,5-diethyl-2,4,6(1H, 3H,5H)-trione (barbital) with
hexamethyldisilazane and bis(tributylstannyl) oxide, respectively. The products were reacted with acetyl,
benzoyl, and 3-(triethylgermyl)propionyl halides to obtain the corresponding bisacylated pyrimidine deriva-
tives. The reaction of 1-methyluracil with (Bu3Sn)2O gave 1-methyl-3-(tributylstannyl)pyrimidine-2,4(1H,3H)-
dione.
Aiming at extending the range of biologically
active nitrogen-containing compounds we turned to
the reactions of 5,5-diethyl-2,4,6(1H,3H,5H)-trione
(barbital), one of the most active opiates, with HMDS
and bis(tributylstannyl) oxide. Organosilicon deriva-
tives of pyrimidine and sym-triazine have received
sufficient study [1, 2], but 1,3-bis(trimethylsilyl)-5,5-
diethyl(1H, 3H,5H)-trione (Ib) has only been
mentioned in [3], where it, along with other nitrogen-
containing compounds, has been characterized by
GLC parameters. No physicochemical or spectral
characteristics, elemental analysis, or synthesis of this
compound have so far been reported.
presence of catalytic amounts of ammonium sulfate
(no solvent, heating from 124 to 164 C, 2 3 h) to
give compound Ia as an amorphous Paraffin-like
colorless material formed upon cooling to room
temperature of the yellowish thick transparent oil
remaining after evacuation of the reaction mixture
(3 4 mm Hg, 160 C, 1 h). Subsequent vacuum distilla-
tion of this material gave a colorless transparent
glycerol-like liquid that no longer solidified (com-
pound Ib). By NMR and IR spectroscopy we showed
that compounds Ia and Ib are the O Si and N Si
isomers of the organosilicon barbital derivatives that
exist in different aggregative states at room tempera-
ture.
We found that barbital reacts with HMDS in the
OSiMe3
O
C
O
Et
Et
Et
O
Et
C
C
(Me3Si)2NH
NH3
N
C
C
C
HN
C
Me3SiN
C
C
C
C
t
Et
O
Et
(1)
C
O
Me3SiO
N
N
N
H
O
O
SiMe3
Ia
Ib
Thus, undistilled compound Ia (solid) has the fol-
lowing H NMR spectrum (200 MHz; DMF), , ppm:
of isomer Ia, whereas compound Ia obtained under
more rigid conditions (heating above 164 C longer
than 3 h) contains an admixture of compound Ib. As
seen from the table, the IR spectrum of compound Ia,
unlike that of compound Ib, contains a Si N absorp-
1
0.09 s, 0.12 s (OSiMe3), 0.86 t (6H, CH3, J 7.0 Hz),
1.93 q (4H, CH2CH3). Compound Ib (liquid) formed
1
during vacuum distillation has another H NMR spec-
1
trum, , ppm: 0.42 s (NSiMe3), 0.77 t (6H, CH3, J
7.2 Hz), 1.88 q (4H, CH2CH3). The same method was
used to show that compound Ib contains an admixture
tion band (950 cm ). The IR spectrum of compound
Ib, as would be expected [3], has a Si O C absorp-
1
tion band (1110 cm ). Expected changes in the
1070-3632/05/7506-0870 2005 Pleiades Publishing, Inc.

SILICON-, GERMANIUM-, AND TIN-CONTAINING DERIVATIVES
871
1
Absorption bands, , cm , in the IR spectra of pyrimidine derivatives
Comp.
no.
C H
C=O
CN ring
1400, 800
CH in C2H5
Other vibrations
Ia 2980, 2920
Ib 2980, 2920
II 2960, 2910, 2870, 2845 1690, 1640, 1610 1450, 1425, 760
1700, 1670
1280, 890
1270, 870
1245, 845 (CHMe3Si),
1110 (SiOC)
1240, 840 (CHMe3Si),
950 (SiN)
1730, 1690, 1680 1410, 780
1240, 860
III 1745, 1690
IV 1740, 1690, 1650
1460, 755
1420, 740
1220, 830
1220, 850
3100, 805 (Ph)
V
2960, 2920, 2860
1750, 1705, 1670 1430, 755
1230, 860
605, 505 (GeC)
VI 2980, 2940, 2870, 2840 1770, 1700
1460, 1450, 1415, 760 1240, 870
carbonyl absorption region are also observed. Thus,
unlike related sym-triazine derivatives [3], organo-
silicon derivatives of barbital prefer the oxo form.
In a similar way, from compounds I and II we pre-
pared
1,3-diacetyl-5,5-diethylpyrimidine-2,4,6(1H,-
3H,5H)-trione (IV) and 1,3-bis[3-(triethylgermyl)-
propionyl]-5,5-diethyldiethylpyrimidine-2,4,6(1H,3H,-
5H)-trione (V) in yields of up to 71 and 60%, respec-
tively. The IR spectra show that acylated barbital
derivatives III V, as would be expected, prefer the
lactam form. The same isomeric form of compounds
I and II also follows from the calculated molecular
refractions (MRD).
The reaction of barbital with bis(tributylstannyl)
oxide (no solvent, gradual heating from 100 to 208 C,
slow evacuation from 760 to 3 mm Hg, 2 h) gave
92% of 1,3-bis(tributylstannyl)-5,5-diethylpyrimidine-
2,4,62,4,6(1H,3H,5H)-trione (II) as a yellowish trans-
parent glycerol-like liquid.
O
O
C
Unlike barbital, 1-methyluracil, another pyrimidine
derivative, is much less reactive toward HMDS. Upon
prolonged heating of the reagents under reflux in the
presence of catalytic amounts of ammonium sulfate
(48 h, 124 C), slight ammonia evolution was ob-
served, and the starting compounds were isolated
almost unchanged. At the same time, when the same
pyrimidine derivative was heated with bis(tributyl-
stannyl) oxide under conditions of synthesis of com-
pounds II [reaction (2)], 1-methyl-3-(tributylstannyl)-
pyrimidine-2,4(1H,3H)-dione (VI) was formed in a
yield of up 90%.
Et
Et
O
C
Et
Et
O
C
C
(Bu3Sn)2O Bu3SnN
HN
C
C
C
(2)
H2O
C
N
N
H
O
O
SnBu3
II
In the IR spectra of compound II (see table), like
in those of organotin sym-triazines, the carbonyl ab-
sorption frequencies are decreased, probably, because
of weakening of the C=O bonds due to metal coordina-
tion with neighboring ring nitrogen atoms [3].
Compounds I and II, like sym-triazines, can give
acyl derivatives with carboxylic acid chlorides. Thus,
compound I reacts with benzoyl chloride (gradual
heating to 120 C with simultaneous distillation of
chlorotrimethylsilane, 2 h) to give 88% of 1,3-di-
benzoyl-5,5-diethylpyrimidine-2,4,6(1H,3H,5H)-trione
(III) as fine colorless crystals.
O
C
O
C
Bu3SnN
CH
CH
1/2(Bu3Sn)2O
1/2H2O
CH
CH
HN
C
(4)
C
O
N
N
O
CH3
CH3
VI
O
O
C
Et
Et
O
C
Et
Et
O
The IR spectrum gave evidence in favor of the
R C(O)N
C
C
2R C(O)X
2R3MX
C
C
R3MN
lactam structure of compound VI.
(3)
C
O
C
O
N
N
Compounds I and II are readily hydrolyzed with
atmospheric moisture, whereas compounds III VI are
fairly stable and fast react with water on heating only.
The major hydrolysis product is the corresponding
starting pyrimidine, which implies preservation of the
RC(O)
III IV
R3M
R3M = Me3Si, Bu3Sn; R = Ph (III), Me (IV), Et3Ge
(CH2)2 (V); X = Cl, Br.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 75 No. 6 2005

872
GORDETSOV et al.
ring structure in the course of all the above inter-
conversions.
washed with absolute ether and dried in a vacuum to
obtain 0.80 g (88%) of compound III as colorless fine
crystals, mp 214 C. Found, %: C 67.00; H 5.54.
C22H20N2O5. Calculated, %: C 67.34; H 5.14.
EXPERIMENTAL
Compound IV was obtained in a similar way from
compound II and acetyl bromide, yield 71%. Found,
%: C 53.36; H 6.26. C12H16N2O5. Calculated, %:
C 53.72; H 6.02.
The IR spectra were obtained on Specord IR-75
and Specord M-80 spectrophotometers in thin films
(neat or with mineral oil) between KBr or ZnSe plates.
The 1H NMR spectra were measured on a Bruker
DPX-200 spectrometer (200 MHz, DMF). The reac-
tions were performed under dry argon or in a vacuum.
The starting Et3Ge(CH2)2C(O)Cl was prepared by the
procedure in [4].
Reaction of 1,3-bis(trimethylsilyl)-5,5-diethyl-
pyrimidine-2,4,6(1H,3H,5H)trione with 3-(triethyl-
germyl)propionyl chloride. A solution of 3.15 g of
Et3Ge(CH2)2C(O)Cl in 10 ml of dry toluene was
added dropwise with stirring to a solution of 1.97 g
of compound Ib in 30 ml of the same solvent (reagent
ratio 1:2). The mixture was stirred for 12 h, the sol-
vent was removed, and the viscous residue was dis-
solved in chloroform. Compound IV, 2.22 g (60%),
was precipitated as yellowish crystals from the chloro-
form solution with hexane, mp 184 189 C. Found, %:
C 50.55; H 7.99; Ge 23.59. C26H48Ge2N2O5. Cal-
culated, %: C 50.87; H 7.88; Ge 23.65.
Reaction of barbital with hexamethyldisilazane.
A mixture of 10.0 g of barbital and 8.75 g of HMDS
(reagent ratio 1:1) was refluxed in the presence of
catalytic amounts of (NH4)2SO4 until ammonia no
longer evolved (3 h). The final temperature of the re-
action mixture was 130 C. During reaction the start-
ing pyrimidine dissolved completely. After cooling,
17.0 g (95%) of compound Ia was obtained as a
Paraffin-like material, mp > 50 C. Vacuum distilla-
tion of the product gave 14.3 g (80%) of compound
Ib as a colorless glycerol-like liquid, bp 137 138 C
(5 mm Hg), d240 1.0320, nD20 1.4720. MRD 89.145,
calc. 89.184 (ring increment 1.20 [5]). Found, %: C
51.28; H 8.61; Si 16.61. C14H28N2O3Si2. Calculated,
%: C 51.18; H 8.59; Si 17.10.
Reaction of 1-methyluracil with bis(tributyl-
stannyl) oxide. A mixture of 0.28 g of 1-methyluracil
and 0.67 g of bis(tributylstannyl)oxide (reagent ratio
2:1) was heated in a distillation flask for 1 h at
atmospheric pressure and then for 1 h with gradual
evacuation to 5 mm Hg [3]. The maximal temperature
was 200 C. Compound VI, 0.84 g (90%), was ob-
tained as a yellowish salvelike material. Found, %: C
49.00; H 7.71; Sn 28.89. C17H32N2O2Sn. Calculated,
%: C 49.18; H 7.77; Sn 28.59. Water separation was
observed during reaction.
Reaction of barbital with bis(tributylstannyl)
oxide. A mixture of 0.22 g of barbital and 0.71 g of
bis(tributylstannyl) oxide (reagent ratio 1:1) was
heated in a distillation flask for 1 h at atmospheric
pressure and then for 1 h with gradual evacuation to
5 mm Hg. The maximal temperature was 208 C. Com-
pound II, 0.84 g (92%), was obtained as a yellowish
transparent glycerol-like liquid, d240 1.2240, nD20 1.5081.
MRD 185.676, calc. 185,168. Found, %: C 50.30; H
8.82; Sn 31.55. C32H64N2O3Sn2. Calculated, %: C
50.42; H 8.46; Sn 31.14. Water separation was ob-
served during reaction.
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RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 75 No. 6 2005