Syntheses of functionalized pyrimidines from the products of addition of triphenylphosphoranylideneacetonitrile to acyl isothiocyanates

Article abstract of DOI:10.1023/B:RUGC.0000045875.40116.eb

The products of addition of accessible phosphorus-containing ylide Ph ₃⁺P-CHCN to acyl and alkoxycarbonyl isocyanates readily cyclize under the action of methanolic HCl. This reaction was used for preparing a broad range of new 5-pho

Full text of DOI:10.1023/B:RUGC.0000045875.40116.eb

Russian Journal of General Chemistry, Vol. 74, No. 7, 2004, pp. 1115 1121. Translated from Zhurnal Obshchei Khimii, Vol. 74, No. 7, 2004,
pp. 1206 1212.
Original Russian Text Copyright
2004 by Muzychka, Smolii, Drach.
Syntheses of Functionalized Pyrimidines from the Products
of Addition of Triphenylphosphoranylideneacetonitrile
to Acyl Isothiocyanates
L. V. Muzychka, O. B. Smolii, and B. S. Drach
Institute of Bioorganic and Petroleum Chemistry, National Academy of Sciences of Ukraine, Kiev, Ukraine
Received July 15, 2002
+
Abstract The products of addition of accessible phosphorus-containing ylide Ph3P CHCN to acyl and
alkoxycarbonyl isocyanates readily cyclize under the action of methanolic HCl. This reaction was used for
preparing a broad range of new 5-phosphonium derivatives of di- and trifunctionalized pyrimidine bases.
Among them, the corresponding tertiary phosphonium salts containing no labile hydrogen atoms are especially
important. Under mild conditions, they undergo dephosphorylation in the presence of alkalis to give 4-mer-
capto, 4,6-dimercapto-, and 2,4,6-trimercaptopyrimidine derivatives which are difficult or impossible to
prepare by traditional routes.
Recently we found that successive treatment of well
studied triphenylphosphoranylideneacetonitrile first
with acyl isothiocyanates and then with hydrogen
chloride yields phosphorus-containing derivatives of
4-hydroxy-6-mercaptopyrimidine [1, 2]. In this work
we substantially expanded the sphere of application
of this approach. Starting from accessible ylide
betaines II and III obtained from benzoyl, anisyl,
2-thiophenoyl, and methoxycarbonyl isocyanates, we
prepared a variety of new pyrimidine derivatives
IV XIX (see scheme). These compounds can be
subdivided into three groups. The first group includes
the stabilized phosphonium ylide betaines of the
pyrimidine series: IV, VII, IX, and X. The second
group consists of 5-pyrimidinylphosphonium salts V,
VI, VIII, and XI XV. The third group includes
phosphorus-free functionalized pyrimidines XVI XIX.
The majority of transformations used to prepare
these three groups of compounds are quite routine and
do not deserve detailed consideration. Nevertheless,
we must briefly describe the key reactions. The main
of them is the heterocyclization of II to IV, which
was described in detail previously [1, 2], and the
structure of one of the parent representatives of ylide
betaines, IV, in which R is CH3, was confirmed by
X-ray structural and quantum-chemical studies [2, 3].
The cyclization of III into VII, studied for the first
time in this work, resembles the above-described
betaines IV and VII, they are regioselectively me-
thylated at the sulfur atom, which was proved by the
1H NMR spectra. The SCH3 signal in the spectra of
V, VI, IX, and X is located in the range 2.1 2.5 ppm,
whereas for the isomeric N- or O-methylation products
the CH3 signal should be observed at > 3 ppm [2].
Both sequences of quite selective transformations
IV
V
IX and VII
VI
X are typical
examples of using the Umpolung methodology based
on the alternate change of the chemical nature of each
paticipant of the consecutive process. It results in
formation of ylide betaines IX and X, polycentral
nucleophilic substrates that do not enter the Wittig
reaction with aromatic aldehydes but readily react
with alkylating agents. Some of these reactions were
studied previously [1, 2], and here we studied the
reactions of ylide betaines IX and X with phosphorus
oxychloride, which proceed quite regioselectively to
give electrophilic substrates VIII and IX containing
one or two labile chlorine atoms in the pyrimidine
moiety. The substitution of these groups with the
residues of various N- and S-nucleophiles is a con-
venient route to a series of functionalized derivatives
of 5-pyrimidinylphosphonium salts XII XV contain-
ing no labile hydrogen atoms. In all of them, the C P
bond is readily cleaved with sodium hydroxide, which
was used for the preparative synthesis of many new
derivatives of 4-mercapto-, 4,6-dimercapto-, and
2,4,6-trimercaptopyrimidine (see the transformations
cyclization II
IV, but is complicated by demethyla-
1
tion. This fact was established by H NMR spec-
troscopy (Table 1).
XII
XV
XVI, XIII
XVII, XIV
XVIII, and
XIX. These reactions significantly supplement
In spite of the mesomeric character of related ylide
the traditional methods for preparing substituted
1070-3632/04/7407-1115 2004 MAIK Nauka/Interperiodica

1116
MUZYCHKA et al.
+
+
R
NCS
MeO
NCS
+
.
.
S
Ph3P
Ph3P
.
.
.
.
S
Ph3P
.
.
.
.
.
.
..
.
.
.
O
O
.
.
..
.
OMe
O
R
O
N
H
N C
N C
N
H
N C
IIa IIc
I
III
1) HCl, MeOH;
1) HCl, MeOH;
2) Et3N
+
2) H2O
+
+
+
Ph3P
.
Ph3P
Hlg
Ph3P
MeOSO3
Ph3P
.
.
.
.
.
.
.
S
.
.
.
O
.
.
.
.
.
.
.
.
S
.
.
.
.
.
O
.
SAlk
NH
O
.
O
SMe
NH
(MeO)2SO2
AlkHlg
NH
HN
N
R
NH
HN
N
O
O
R
IVa IVc
Va Vd
VI
VII
Et3N
NaOH
+
+
+
+
ClO4
Ph3P
Ph3P
Ph3P
An
N
Ph3P
.
.
.
.
.
.
.
O
.
.
.
.
.
.
.
SMe
.
.
.
.
.
.
Cl
O
.
S
SMe
.
SAlk
1) POCl3, PhNMe2;
2) NaClO4
Cl
.
.
.
.
.
.
N
.
.
.
.
.
1) POCl3, PhNMe2;
2) NaClO4
.
.
N
N
.
.
.
.
N
.
N
HN
.
N
R
.
.
.
Cl
R
O
VIIIa VIIId
IXa IXd
X
XI
1) ArSH; Et3N
2) NaClO4
1) 2R2NH;
2) NaClO4
2ArSH, 2Et3N
4R2NH
+
+
+
+
ClO4
Ph3P
ClO4
Ph3P
ClO4
Ph3P
ClO4
Ph3P
SMe
R2N
ArS
ArS
SMe
SAlk
SAlk
R2N
N
N
N
N
N
R
N
N
R
N
NR2
SAr
XIIa XIIh
XIIIa XIIIc, XIIIe
XIVa, XIVb
XIVa XIVc
NaOH
N
R N =
O
NaOH
2
NaOH
NaOH
O
N
SMe
ArS
ArS
SAlk
SMe
SAlk
R2N
N
N
N
N
N
N
N
N
N
O
R
SAr
R
XVIa XVIh
XVIIa XVIIc, XVIIe
XVIIa, XVIIb
XIX
R = C6H5 (IIa, IVa, Va, Vd, VIIIa, VIIId, IXa, IXd, XIIa, XIId, XIIe, XIIIa, XIIIe, XVIa, XVId, XVIe, XVIIa,
XVIIe), 4-CH3OC6H4 (IIb, IVb, Vb, VIIIb, IXb, XIIb, XIIf, XIIIb, XVIb, XVIf, XVIIb), (IIc, IVc,
S
Vc, VIIIc, IXc, XIIc, XIIg, XIIh, XIIIc, XVIc, XVIg, XVIh, XVIIc); Alk = CH3 (Va Vc, VIIIa VIIIc, IXa IXc,
XIIa XIIc, XIIe XIIh, XIIIa XIIIc, XIIIe, XVIa XVIc, XVIe XVIh, XVIIa XVIIc, XVIIe), C6H5CH2 (Vd, VIIId,
IXd, XIId, XVId); Hlg = Cl (Vd), I (Va Vc); An = Cl (VIIIa, VIIIb), ClO4 (VIIIc, VIIId); Ar = 4-CH3C6H4 (XIIIa,
XIIIb, XVIIa, XVIIb, XVIIIa), 4-ClC H (XIIIc, XIIIe, XVIIc, XVIIe, XVIIIb); R N =
(XIIa XIId,
O
N
6
4
2
XVa, XVIa XVId),
(XIIe, XIIf, XVb, XVIe, XVIf),
(XIIg, XVc, XVIg),
(XIIh, XVh).
N
N
N
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 74 No. 7 2004

SYNTHESES OF FUNCTIONALIZED PYRIMIDINES
Table 1. 1H NMR spectra of compounds obtained
1117
Comp.
no.
, ppm [(CD3)2SO]
IIb
III
IVb
Vc
VII
3.83 s (3H, OCH3), 7.01 7.98 m (19Harom), 10.43 s (1H, NH)
3.66 s (3H, OCH3), 7.61 7.77 m (15Harom), 10.04 s (1H, NH)
3.84 s (3H, OCH3), 7.04 8.09 m (19Harom), 11.83 br.s (1H, NH)
2.44 s (3H, SCH3), 7.37 8.37 m (18Harom.), 13.6 br.s (1H, NH)
7.51 7.74 m (15Harom), 10.50 s (1H, NH), 11.04 s (1H, NH)
VIIId
IXb
X
4.52 s (2H, CH2), 7.25 8.27 m (25Harom)
2.35 s (3H, SCH3), 3.82 s (3H, OCH3), 7.03 8.31 m (19Harom
2.12 s (3H, SCH3), 7.60 7.74 m (15Harom), 10.28 s (1H, NH)
)
XIId
XIIIb
XVIb
3.09 3.24 m (8H, 4CH2), 4.34 s (2H, CH2), 6.90 8.51 m (25Harom
2.38 s (3H, CH3), 2.41 s (3H, SCH3), 3.84 s (3H, OCH3), 7.02 8.16 m (23Harom
2.56 s (3H, SCH3), 3.68 s (8H, 4CH2), 3.82 s (3H, OCH3), 6.52 s (1H, C5H), 7.01 d (2Harom, JHH 8.0 Hz),
8.28 d (2Harom
3JHH 8.0 Hz)
2.54 s (3H, SCH3), 3.67 s (8H, 4CH2), 6.51 s (1H, C5H), 7.14 7.86 m (3H, C4H3S)
)
)
3
,
XVIc
XVIIb 2.41 s (3H, CH3), 2.53 s (3H, SCH3), 3.83 s (3H, OCH3), 6.56 s (1H, C5H), 7.03 d (2Harom, JHH 9.0 Hz),
3
7.38 d (2Harom
XVIIIa 2.25 s (3H, CH3), 2.37 s (3H, CH3), 3.38 s (3H, CH3), 6.02 s (1H, C5H), 7.29 7.43 m (8Harom
XIX
2.41 s (3H, SCH3), 3.49 m (4H, 2CH2), 3.61 m (12H, 6CH2), 5.97 s (1H, C5H)
, , ,
3JHH 7 Hz), 7.56 d (2Harom 3JHH 7 Hz), 8.21 d (2Harom 3JHH 9 Hz)
)
mercaptopyrimidines (see reviews [4 6] and original
papers [7 10]).
EXPERIMENTAL
1
The H NMR spectra were obtained on a Varian
VXR-300 spectrometer in DMSO-d6 relative to TMS.
The spectral data are listed in Table 1. The constants,
yields, and elemental analyses of the new compounds
are presented in Table 2.
One of the characteristic features of the above-
described phosphonium syntheses of pyrimidine bases
is that the final dephosphorylation products contain
no substituents in position 5 of pyrimidine ring, and
in this respect they resemble many natural and syn-
thetic pyrimidine derivatives exhibiting high biolog-
ical activity (cf. [11]). Furthermore, by consecutive
3-Acylamino-3-thioxo-2-triphenylphosphoranyl-
idenepropionitriles IIa IIc.1 A solution of 0.01 mol
of appropriate acyl isocyanate in 20 ml of aceto-
nitrile was added to a suspension of 0.01 mol of
triphenylphosphoranylideneacetonitrile I in 30 ml
of acetonitrile. The mixture was kept for 1 h at 50
70 C and then for 1 h at 20 25 C. The precipitate was
filtered off and recrystallized.
transformations IV
V
IX
VIII
XIII
XVII, we prepared the 4,6-dimercaptopyrimidine
derivatives containing different residues at sulfur
atoms, hardly accessible by the previously developed
routes. At the same time, it is quite evident that the
field of application of phosphonium syntheses of
functionalized pyrimidines can be considerably
expanded, because the scheme presents only the most
important examples illustrating the transformations of
accessible ylide betaines IV and VII. The electron
density distribution in them follows not only from the
consideration of the generalized mesomeric structures
shown in the scheme, but also from the evaluation of
increment of specific mesomeric structures. As shown
previously [1 3], the most significant among them
are betaines with the anionic charge on sulfur.
Nonpolar phosphinomethylene structures are useful
for classification and construction of the most con-
venient names of compounds IV, VII, IX, and X (see
Experimental), but they do not make the major
contribution.
3-Methoxycarbonylamino-3-thioxo-2-triphenyl-
phosphoranylidenepropionitrile III. A solution of
0.01 mol of methoxycarbonyl isothiocyanate [12] in
20 ml of acetonitrile was added to a suspension of
0.01 mol of ylide I in 30 ml of acetonitrile. The
mixture was kept for 2 h at 20 26 C, the solvent was
removed at reduced pressure, and the residue was
recrystallized.
2-Aryl(2-thienyl)-4-oxo-6-thioxo-5-triphenyl-
phosphoranylidene-1,4,5,6-tetrahydropyrimidines
IVa IVc. To a suspension of 0.01 mol of IIa IIc in
1
Here and hereinafter, the names of mesomeric compounds are
given as for the nonpolar mesomeric structure.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 74 No. 7 2004

1118
MUZYCHKA et al.
Table 2. Constants, yields, and elemental analyses of compounds obtained
Found, %
Calculated, %
Comp. Yield, mp, C (solvent for
Formula
no.
%
recrystallization)
Cl (I)
N
P
S
Cl (I)
N
P
S
IIa
IIb
IIc
96 167 169 (ethanol)
89 238 240 (acetonitrile)
90 210 212 (ethanol
acetonitrile, 1: 1)
86 175 177 (ethanol)
90 268 270 (ethanol)
82 238 240 (ethanol)
97 253 255 (ethanol
acetonitrile, 1: 1)
6.15 6.71 6.87 C28H21N2OPS
5.92 6.21 6.53 C29H23N2O2PS
5.89 5.63 13.61 C26H29N2OPS2
6.03 6.67
5.66 6.26
5.95 6.58 13.63
6.90
6.48
IIIa
IVa
IVb
IVc
6.74 7.56 7.70 C23H19N2O2PS
6.11 6.59 6.43 C28H21N2OPS
5.87 6.34 6.42 C29H23N2O2PS
6.03 6.61 13.64 C26H19N2OPS2
6.69 7.40
6.03 6.67
5.66 6.26
7.66
6.90
6.48
5.95 6.58 13.68
Va
Vb
Vc
Vd
VI
94 235 237 (ethanol)
98 198 201 (ethanol)
93 189 192 (ethanol)
85 210 212 (ethanol)
83 238 240 (ethanol
acetonitrile, 1: 1)
(20.89) 4.83 5.24 5.00 C29H24IN2OPS
(19.97) 4.35 4.91 5.08 C30H26IN2O2PS
(20.94) 4.63 4.93 10.51 C27H22IN2OPS2
(20.93) 4.62 5.11
(19.94) 4.40 4.87
(20.72) 4.57 5.06 10.47
5.28
5.04
6.17
4.82 5.31 12.12 C35H28ClN2OPS
5.33 5.80 12.04 C24H23N2O6PS2
6.00
4.74 5.24
5.28 5.84 12.09
5.42
VII
52 290 293 (aceto-
nitrile dimethyl-
6.87 7.89 7.92 C22H17N2O2PS
6.93 7.66
7.93
formamide, 2: 1)
64 167 169 (ethanol
diethyl ether, 1: 1)
72 191 193 (ethanol
diethyl ether, 1: 1)
VIIIa
VIIIb
13.32
12.43
5.57 5.74 6.07 C29H23Cl2N2PS
4.84 5.65 5.71 C30H25Cl2N2OPS
13.29
12.58
5.25 5.81
4.97 5.50
6.01
5.69
VIIIc
VIIId
95 201 203 (ethanol)
82 138 140 (ethanol
acetonitrile, 2: 1)
11.83
10.61
4.69 5.20 10.70 C27H21Cl2N2O4PS2
4.18 4.53 4.71 C35H27Cl2N2O4PS
11.75
10.53
4.64 5.13 10.63
4.16 4.60
4.76
IXa
78 290 292 (acetonitrile)
93 266 268 (ethanol
acetonitrile, 1: 1)
5.91 6.41 6.73 C29H23N2OPS
5.60 6.11 6.27 C30H25N2O2PS
5.85 6.47
5.51 6.09
6.70
6.30
IXbb
IXc
86 310 312 (ethanol
acetonitrile, 1: 1)
5.91 6.42 13.20 C27H21N2OPS2
5.78 6.39 13.23
IXd
X
97 223 225 (acetonitrile)
72 315 318 (ethanol
acetonitrile, 1: 1)
5.10 5.61 5.80 C35H27N2OPS
6.73 7.43 7.65 C23H19N2O2PS
5.05 5.58
6.69 7.40
5.78
7.66
XI
78 139 141 (ethanol
acetonitrile, 1: 1)
19.19
5.09 5.61 5.80 C23H18Cl3N2O4PS
19.14
5.04 5.57
5.77
XIIa
XIIb
XIIc
XIId
58 208 210 (ethanol)
54 298 300 (ethanol)
92 186 189 (ethanol)
75 279 281 (ethanol
acetonitrile, 1: 1)
5.51
5.30
5.45
4.86
6.52 4.83 4.99 C33H31ClN3O5PS
6.27 4.61 4.70 C34H33ClN3O6PS
6.34 4.68 9.78 C31H29ClN3O5PS2
5.74 4.31 4.43 C39H35ClN3O5PS
5.47
5.23
5.42
4.89
6.48 4.78
6.20 4.57
6.42 4.74
5.80 4.28
4.95
4.73
9.80
4.43
XIIe
XIIf
90 214 217 (ethanol)
68 305 307 (ethanol
acetonitrile, 1: 1)
5.80
5.37
6.64 4.92 5.10 C33H31ClN3O4PS
6.41 4.71 4.83 C34H33ClN3O5PS
5.61
5.35
6.65 4.90
6.35 4.68
5.08
4.84
XIIg
86 256 258 (ethanol)
82 273 275 (ethanol)
76 193 195 (ethanol)
58 230 233 (ethanol)
85 254 256 (ethanol)
84 165 167 (ethanol)
55 225 227 (ethanol
acetonitrile, 1: 1)
5.28
5.52
5.10
6.29 4.67 9.66 C33H33ClN3O4PS2
6.42 4.80 9.85 C32H31ClN3O4PS2
4.00 4.57 9.37 C36H30ClN2O4PS2
3.95 4.29 8.94 C37H32ClN2O5PS2
3.99 4.37 13.53 C33H25Cl2N2O4PS3
5.32
5.44
5.17
4.96
9.96
6.31 4.65
6.44 4.75
4.09 4.52
3.92 4.33
3.94 4.35 13.51
3.97 4.39
8.53 4.71
9.63
9.83
9.36
8.97
XIIh
XIIIa
XIIIb
XIIIc
XIIIe
XVa
4.89
10.00
10.11
5.41
4.03 4.35 9.10 C35H27Cl2N2O4PS2 10.05
9.08
4.88
8.49 4.75 4.86 C31H34ClN4O6PS
5.39
XVb
XVc
88 159 162 (ethanol)
80 267 269 (ethanol)
5.72
5.47
9.01 4.98 5.16 C31H34ClN4O4PS
8.63 4.70 4.90 C33H38ClN4O4PS
5.67
5.43
8.96 4.95
8.58 4.74
5.13
4.91
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 74 No. 7 2004

SYNTHESES OF FUNCTIONALIZED PYRIMIDINES
Found, %
1119
Table 2. (Contd.)
Calculated, %
Comp. Yield, mp, C (solvent for
Formula
no.
%
recrystallization)
Cl (I)
N
S
Cl (I)
N
S
XVIa
XVIb
XVIc
XVId
XVIe
75 140 142 (ethanol)
60 149 151 (ethanol)
62 138 141 (ethanol)
48 111 113 (ethanol)
45 121 123 (ethanol)
55 118 120 (ethanol)
14.65
13.30
14.28
11.58
15.53
14.00
14.50
13.82
8.71
8.03
8.03
8.15
7.53
11.12
10.12
21.86
8.87
C15H17N3OS
C16H19N3O2S
C13H15N3OS2
C21H21N3OS
C15H17N3S
C16H19N3OS
C14H17N3S2
C15H19N3S2
C18H16N2S2
C19H18N2OS2
C15H11ClN2S3
C17H13ClN2S2
C19H18N2S3
C17H12Cl2N2S3
C13H20N4O2S
14.62
13.24
14.32
11.56
15.48
13.94
14.42
13.76
8.63
7.90
7.98
8.12
7.56
11.16
10.10
21.86
8.82
11.90
10.62
21.98
21.01
19.79
18.11
27.37
18.58
26.00
23.41
10.82
11.82
10.64
22.00
20.99
19.76
18.09
27.41
18.59
25.96
23.38
10.82
XVIf
XVIg
XVIh
XVIIa
XVIIb
XVIIc
XVIIec
XVIIIa
XVIIIb
XIX
50
44
67
75
73 75 (ethanol)
67 69 (ethanol)
95 97 (ethanol)
87 89 (ethanol)
60 100 102 (ethanol)
10.15
10.32
10.10
10.28
82
45
40
99 101 (ethanol)
97 99 (acetonitrile)
68 70 (ethanol)
17.14
6.90
19.01
17.24
6.81
18.90
45 134 137 (ethanol)
a
b
Found, %: C 65.96: H 4.53. Calculated, %: C 66.02; H 4.58. Found, %: C 70.90: H 5.01. Calculated, %: C 70.85; H 4.95.
Found, %: C 59.15: H 3.74. Calculated, %: C 59.20; H 3.80.
c
100 ml of methanol, 2 ml of concentrated sulfuric acid
90 C until the precipitate dissolved completely. The
resulting mixture was poured into 150 ml of absolute
diethyl ether, and the precipitate was filtered off and
recrystallized.
was added, and the mixture was heated for 3 4 h at
45 50 C until the precipitate fully dissolved. The
solvent was removed in a vacuum, and the residue
was dissolved in 30 ml of methanol. A solution of
0.011 mol of triethylamine in 10 ml of ethanol was
added, and the mixture was heated to 50 60 C until a
precipitate formed. After that, it was left for 1 h at
20 25 C, and the precipitate was filtered off and
recrystallized.
2,4-Dioxo-6-thioxo-5-triphenylphosphoranyl-
idene-1,2,3,4,5,6-hexahydropyrimidine VII. A
suspension of 0.01 mol of III in 25 ml of methanol
was saturated with hydrogen chloride for 5 h, the
solvent and excess hydrogen chloride were removed
in a vacuum, and the residue was washed with water
ethanol mixture and recrystallized.
Aryl(2-thienyl)-6-methylthio-4-oxo-1,4-dihydro-
pyrimidin-5-yltriphenylphosphonium iodides
Va Vc. To a suspension of 0.01 mol of IVa IVc in
50 ml of acetonitrile, 0.011 mol of methyl iodide was
added. The mixture was left at 20 25 C for 5 8 h
until the precipitate fully dissolved, the solvent was
removed in a vacuum, and the residue was recrystal-
lized.
6-Alkylthio-2-aryl-4-chloropyrimidin-5-yltriphe-
nylphosphonium chlorides VIIIa and VIIIb. To a
mixture of 0.055 mol of phosphorus oxychloride and
0.0155 mol of N,N-dimethylaniline, 0.01 mol of IXa
or IXb (see below) was added under cooling with ice-
cold water; the resulting mixture was kept for 3 h at
80 90 C, cooled to 20 25 C, and poured onto crushed
ice. The oily residue was separated by decanting and
triturated for crystallization with 30 ml of ethanol; the
crystals were filtered off and recrystallized.
5-Benzylthio-4-oxo-2-phenyl-1,4-dihydropyrimi-
din-5-yltriphenylphosphonium chloride Vd. To a
suspension of 0.01 mol of IVa in 25 ml of acetonitrile,
0.011 mol of benzyl chloride was added, the mixture
was refluxed for 3 h, and the precipitate was filtered
off and recrystallized.
6-Alkylthio-2-phenyl(2-thienyl)-4-chloropyr-
imidin-5-yltriphenylphosphonium perchlorates
VIIIc and VIIId were prepared similarly to VIIIa
and VIIIb, but the residue after decanting was dis-
solved in 30 ml of ethanol, and 15 ml of saturated
aqueous solution of sodium perchlorate was added.
The precipitate was filtered off, washed with water,
and recrystallized.
6-Methylthio-2,4-dioxo-1,2,3,4-tetrahydropyr-
imidin-5-yltriphenylphosphonium methyl sulfate
VI. A suspension of 0.01 mol of VII (see below) in
6 ml of dimethyl sulfate was heated for 1 h at 80
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1120
MUZYCHKA et al.
6-Alkylthio-2-aryl(2-thienyl)-4-oxo-5-triphenyl-
6-Methylthio-2-(2-thienyl)-4-p-chlorophenylthio-
pyrimidin-5-yltriphenylphosphonium perchlorate
XIIIc was prepared as described above, starting from
VIIIc.
phosphoranylidene-4,5-dihydropyrimidines
IXa IXd. To a suspension of 0.01 mol of phospho-
nium salts Va Vd in 40 ml of ethanol, a solution of
0.01 mol of sodium hydroxide in 10 ml of ethanol
was added; the mixture was heated for 1 3 h at 50
60 C until a new precipitate formed, which was
filtered off and recrystallized.
2,4-Dimorpholino(pyrrolidino, piperidino)-6-
methylthiopyrimidin-5-yltriphenylphosphonium
perchlorates XVa XVc. To a solution of phospho-
nium salt XI in 15 ml of acetonitrile, 0.008 mol of
appropriate nitrogen base was added. The resulting
mixture was heated for 3 h at 50 60 C, the solvent
was removed in a vacuum, and the residue was re-
crystallized.
2,4-Dioxo-6-methylthio-5-triphenylphosphor-
anylidene-2,3,4,5-dihydropyrimidine X. A solution
of 0.011 mol of triethylamine in 10 ml of ethanol was
added to a suspension of 0.01 mol of VI in 30 ml of
acetonitrile. The mixture was left for 1 h at 20 25 C;
the precipitate was filtered off and recrystallized.
6-Alkylthio-2-aryl(2-thienyl)-4-morpholino-
(pyrrolidino, piperidino, hexamethylenimino)-
pyrimidines XVIa XVIh. To a solution of 0.001 mol
of XIIa XIIh in 15 ml of ethanol, 0.001 mol of
sodium hydroxide was added. The resulting mixture
was kept for 12 h at 20 25 C, the solvent was re-
moved in a vacuum, and the residue was crystallized.
4-Methylthio-2,6-dichloropyrimidin-5-yltriphe-
nylphosphonium perchlorate XI. To a solution of
0.11 mol of phosphorus oxychloride and 0.03 mol of
N,N-dimethylaniline, 0.01 mol of compound X was
added. The mixture was heated for 2 h at 80 90 C,
cooled to 20 25 C, and poured onto finely crushed ice.
The precipitate was separated by decanting and dis-
solved in 30 ml of ethanol, and 20 ml of saturated
aqueous solution of sodium perchlorate was added.
The precipitate that formed was filtered off, washed
with water, and recrystallized.
2-Aryl(2-thienyl)-4-arylthio-6-methylthiopyrimi-
dines XVIIa XVIIc and XVIIe were prepared
similarly to XVIa XVIh.
2,4-Di(arylthio)-6-methylthiopyrimidines
XVIIIa and XVIIIb. To a solution of 0.002 mol of
appropriate phosphonium salt XI in 10 ml of aceto-
nitrile, 0.004 mol of appropriate thiophenol and a
solution of 0.004 mol of triethylamine in 10 ml of
acetonitrile were added. The mixture was heated for
3 h at 50 60 C, the solvent was removed in a vacuum,
and the residue was dissolved in 15 ml of ethanol.
After that, 0.002 mol of sodium hydroxide was added,
the mixture was kept for 12 h at 20 25 C, the solvent
was removed in a vacuum, and the residue was re-
crystallized.
2-Aryl-6-methylthio-4-morpholino(pyrrolidino)-
pyrimidin-5-yltriphenylphosphonium perchlorates
XIIa, XIIb, XIIe, and XIIf. To a solution of VIIIa
or VIIIb in 20 ml of acetonitrile, 0.004 mol of mor-
pholine or pyrrolidine was added. The resulting mix-
ture was heated for 3 h at 50 60 C, the solvent was
removed in a vacuum, the residue was dissolved in
20 ml of ethanol, and 15 ml of saturated aqueous
solution of sodium perchlorate was added. The pre-
cipitate was filtered off and recrystallized.
6-Methylthio-2,4-dimorpholinopyrimidine XIX
was prepared similarly to XVIa XVIh.
6-Alkylthio-2-aryl(2-thienyl)-4-morpholino-
(piperidino, hexamethylenimino)pyrimidin-5-yltri-
phenylphosphonium perchlorates XIIc, XIId, XIIg,
and XIIh were prepared similarly to XIIa, XIIb,
XIIe, and XIIf using morpholine, piperidine, and
hexamethylenimine. After removing acetonitrile, the
residue was treated with ethanol and recrystallized.
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