5,7-Dichloro-1,3-dithiolo-[4,5-d]pyrimidine-2-thione and -2-selone: Synthesis, crystal structure, solvatochromism, and reactions with nucleophiles

Article abstract of DOI:10.1023/A:1014811527518

We have obtained for the first time the halo derivatives of a novel heterocyclic system, 1,3-dithiolo-[4,5-d]pyrimidine-2-thione and -2-selone, by reaction of 5,7-dioxo(4H, 6H)-1,3-dithiolo[4,5-d]- pyrimidine-2-thione and -2-selone with POCl₃. The crystal structure of thione confirms that we had obtained the desired compound. The electronic absorption spectra reveal an interesting solvatochromism connected with the appearance of low-intensity n→π transitions from selenium and sulfur atoms in the visible region of the spectrum. The chlorine atoms in the studied compounds have significant mobility in reactions with nucleophiles (amines, thiourea, azidione), which ensures that new derivatives of 1,3-dithiolo[4,5-d]pyrimidine-2-selone are obtained, and specifically 7-N,N-dialkylamino, 7-N-alkyl-N-arylamino derivatives and 7-isothiuronium salts. The 2-selones obtained can be used in synthesis of new tetrathiafulvalenes.

Full text of DOI:10.1023/A:1014811527518

Chemistry of Heterocyclic Compounds, Vol. 38, No. 1, 2002
5,7-DICHLORO-1,3-DITHIOLO-
d
[4,5- ]PYRIMIDINE-2-THIONE AND
-2-SELONE: SYNTHESIS, CRYSTAL
STRUCTURE, SOLVATOCHROMISM,
AND REACTIONS WITH NUCLEOPHILES*
O. Neilands1, R. Valters1, and S. V. Belyakov2
We have obtained for the first time the halo derivatives of a novel heterocyclic system, 1,3-dithiolo-
[4,5-d]pyrimidine-2-thione and -2-selone, by reaction of 5,7-dioxo(4H,6H)-1,3-dithiolo[4,5-d]-
pyrimidine-2-thione and -2-selone with POCl3. The crystal structure of thione confirms that we had
obtained the desired compound. The electronic absorption spectra reveal an interesting
solvatochromism connected with the appearance of low-intensity n→π transitions from selenium and
sulfur atoms in the visible region of the spectrum. The chlorine atoms in the studied compounds have
significant mobility in reactions with nucleophiles (amines, thiourea, azidione), which ensures that new
derivatives
of
1,3-dithiolo[4,5-d]pyrimidine-2-selone
are
obtained,
and
specifically
7-N,N-dialkylamino, 7-N-alkyl-N-arylamino derivatives and 7-isothiuronium salts. The 2-selones
obtained can be used in synthesis of new tetrathiafulvalenes.
Keywords: 1,3-dithiolo[4,5-d]pyrimidines, crystal structure, nucleophilic substitution in
chloropyrimidines, solvatochromism of thiones and selones.
Tetrathiafulvalenes (TTF) are basic components for obtaining organic metals and superconductors
[1, 2]. Tetrathiafulvalenes condensed with nitrogen-containing heterocycles, especially pyrimidines, have not
been widely studied. Dioxopyrimido- and aminooxopyrimido-annelated TTFs 1-3 (Scheme 1), which can form
intermolecular complementary hydrogen bonds, are of interest [3].
The starting materials for synthesis of TTF 1 are thione 4, or more often selone 5 [3-5]. To obtain
thiones and selones substituted by different functional groups, the key compounds may be 5,7-dichloro-1,3-
dithiolo[4,5-d]pyrimidine-2-thione (6) and selone 7. Such compounds had not been described before the
research done by our group. The familiar route for conversion of dioxopyrimidines to dichloropyrimidines
proved to be successful, namely treatment of thione 4 or selone 5 with phosphorus oxychloride POCl3 in the
presence of N,N-diethylaniline at 120°C-125°C. The yield of chromatographically pure orange compound 6 and
dark green compound 7 is 55%-75%. When the reaction is carried out under harsher conditions (125°C, 3 h) in
the presence of N,N-dimethylaniline, we could chromatographically isolate two compounds: selone 7 and a red-
_______
* This paper is dedicated to Mikhail Grigorievich Voronkov on his 80th birthday.
__________________________________________________________________________________________
1
2
Riga Technical University, Riga LV-1048, Latvia; e-mail: neilands@ktf.rtu.lv. Latvian Institute of
Organic Synthesis, Riga LV-1006; e-mail: serg@osi.lv. Translated from Khimiya Geterotsiklicheskikh Soedinenii,
No. 1, pp. 87-94, January, 2002. Original article submitted June 19, 2001.
0009-3122/02/3801-0079$27.00©2002 Plenum Publishing Corporation
79

orange product that, based on 1H NMR, electronic spectra, and elemental analysis, was assigned the structure of
the product of substitution of chlorine atom: 5-chloro-7-N-methyl-N-phenylamino-1,3-dithiolo[4,5-d]-
pyrimidine-2-selone (8). Such a product could be obtained by reaction of selone 7 with N-methylaniline.
O
O
R
R
H
O
H
S
S
S
S
S
S
S
S
N
N
H
R1
R1
N
H
N
H
N
1
2
H
N
R 2
N
O
O
R
H
O
H
O
S
S
S
S
S
S
S
N
N
S
Se
R1
S
O
N
H
N
H
N
H
3
5
4
7
C6H5
H3C
N
Cl
N
Cl
N
S
S
N
N
S
Se
S
Se
S
S
Cl
Cl
N
S
Cl
N
S
6
8
–
+
C18H37
H
C4H9
C(NH2)2 Cl
H3C
N
N
N
S
S
S
S
S
N
N
Se
Se
Se
H
S
Cl
N
N
N
Cl
N
C4H9
9
10
11
–
+
C(NH2)2 Cl
S
S
N
Se
S
S
N
+
–
(NH2)2C Cl
12
Sometimes during crystallization of selone 7, we observed formation of two types of crystals: dark green
and dark red. The latter gradually transformed to dark green ones during storage. Probably here two phases of
crystalline selone are formed, of which the dark green form is more stable. This phenomenon was not
investigated in more detail. The color of the compounds obtained proved to be nontrivial: it is not typical of the
usual 1,3-dithiol-2-thiones (yellow) and 1,3-dithiol-2-selones (orange-red). Accordingly, we took the electronic
absorption spectra of thione 6 and selone 7 in solvents of different polarities (ethanol, benzene, carbon
tetrachloride). The absorption maxima in the visible region of the spectrum and the intensities are presented in
Table 1. It is interesting to note that we observed two absorption maxima: one intense maximum, and another of
very low intensity. The compounds exhibit solvatochromism: in the polar solvent ethanol, the low-intensity
80

TABLE 1. Absorption Spectral Characteristics of 1,3-Dithiolo[4,5-d]-
pyrimidine Derivatives in the Visible Region
Com-
pound
λmax, nm
In ethanol
ε
λmax, nm
In benzene
ε
λmax, nm
In CCl4
ε
356
30900
362
447
27900
70
358
26400
6
(not
(not measured)
observed)
392
21200
240
400
551
20900
250
(not measured)
391
556
21000
260
7
8
9
546
419
523
426
532
24800
430
429
538
24500
440
426
542
25200
430
maximum is hidden under the intense absorption band. Such solvatochromism is typical of low-intensity n→π
transitions associated with transfer of an electron from the unshared electron pair of the sulfur or selenium atom
to the HOMO of the conjugated pyrimidine system. Owing to the electron-acceptor properties of the chlorine
atoms, the energy of the HOMO changes and the n→π transition occurs at lower energies compared with the
usual thiones and selones.
The structure of thione 6 was confirmed by X-ray diffraction. We were able to grow thione crystals
suitable for taking the X-ray patterns and to obtain their diffraction pattern, based on which we calculated the
crystal structure. Fig. 1 shows a three-dimensional model of molecule 6 with the designations of the atoms;
Fig. 2 illustrates the unit cell of crystals of 6. Table 2 presents the basic interatomic distances in molecule 6. We
found that molecules of thione 6 are planar within the uncertainty limits and are located practically
perpendicular to the glide reflection plane a. In the crystal structure, the molecules form stacks along the
crystallographic direction x. We observe halfway overlap between adjacent molecules in the stack, where the
five-membered ring of one molecule overlaps the six-membered ring of the other. The distance between planes
of adjacent molecules is 3.550(14) Å. All the molecules in the crystal are packed parallel to the crystallographic
_
2 0 3
). Fig. 3 shows a stereoscopic pair representing stacks of molecules in the crystal. The features of
plane (
the crystallographic structure of 6 result in the fact that during growth, the crystals form thin needles that are
_
2 0 3
] . It is difficult to obtain a high-quality diffraction pattern
elongated along the crystallographic direction [
Fig. 1. Structure of thione 6 molecule and the designation of the atoms.
81

TABLE 2. Bond Lengths in the Molecule of Compound 6
Bond
Bond length, Å
Bond
Bond length, Å
C(2)–S(1)
C(8)–S(1)
S(3)–C(2)
S(2)–C(2)
C(9)–S(3)
N(5)–C(4)
C(9)–C(4)
1.755(25)
1.759(20)
1.737(25)
1.619(25)
1.731(19)
1.327(30)
1.331(26)
Cl(1)–C(4)
C(6)–N(5)
N(7)–C(6)
Cl(2)–C(6)
C(8)–N(7)
C(9)–C(8)
1.717(18)
1.324(31)
1.299(31)
1.702(23)
1.343(29)
1.384(25)
from such crystals. This explains the very high value of the R factor (11.2%) and the large standard deviations in
the geometric parameters. For this reason, detailed discussion of the geometry of the molecule is not quite
appropriate.
We studied the reaction of selone 7 with nucleophilic reagents (selone was selected with the aim of
synthesizing new derivatives which might be used to obtain new pyrimido-TTFs). The first trials with ammonia
showed that the reaction proceeded easily; the chlorine atoms were quite mobile. However, in this case, we were
unable to isolate the reaction product in pure form. Reaction of selone 7 with N-methyloctadecylamine proved
to be more successful. In fact, in this reaction a novel product is formed which, after chromatographic
purification, was assigned the structure of 5-chloro-7-N-methyl-N-octadecylamino-1,3-dithiolo[4,5-d]-
1
pyrimidine-2-selone (9) based on H NMR and electronic absorption spectra and also elemental analysis data.
Most likely, in this compound the chlorine atom in the position 7 is more mobile than in the position 5.
Quite contradictory data are given in the literature on nucleophilic substitution of
2,4-dichloropyrimidine [6]. From the experimental section of [6] follows that on reaction of
2,4-dichloropyrimidine with ammonia in ethanol, after the procedure for separation of the mixture, about 10%
of 2-amino-4-chloropyrimidine and 30% of 4-amino-2-chloropyrimidine were isolated.
In our case, the chlorine atom in the position 7 of selone 7 can be activated more than the atom in the
position 5 due to the adjacent electron-acceptor dithiolselone group. When selone 7 was treated with
N-methylaniline in the presence of triethylamine, the reaction product proved to be the mentioned red
compound 8, the spectrum of which in the visible region resembles the spectra of other selones (Table 1), but
the intense absorption maximum is shifted to longer wavelengths.
Fig. 2. Arrangement of molecules in the unit cell of crystals of thione 6.
82

Fig. 3. Stereoscopic representation of the crystal structure along the y axis.
The reaction of selone 7 with butylamine in DMF is vigorous, with heating up of the mixture, but we
could not isolate the desired product (a yellow-brown, poorly soluble product and a foul-smelling dark red oil
were formed), so the reaction was conducted with cooling in benzene solution in the presence of triethylamine.
But in this case, we could not isolate the desired 5,7-di(butylamino)-1,3-dithiolo[4,5-d]pyrimidine-2-selone (10)
in pure form.
Selone 7 reacts on heating with thiourea in acetonitrile solution; in this case, a red-orange isothiuronium
salt insoluble in acetonitrile is isolated, which based on elemental analysis data is assigned the structure of the
monosubstituted isothiureido derivative 11. Reaction with excess thiourea on boiling in acetonitrile did not lead
to the disubstituted product, probably due to the insolubility of the monosubstituted product in acetonitrile. The
reaction is easily accomplished in DMF: the solution becomes dark red, but we could not isolate the desired
disubstituted product 12 in pure form. Possibly cleavage of the isothiuronium salt occurs in DMF when heated.
In the literature [7], it is mentioned that monochloropyrimidines and 2,4-dichloropyrimidine react easily with
thiourea in ethanol on boiling. The reaction products, depending on the structure of chloropyrimidine, are
isothiuronium salts or their cleavage products, mercapto derivatives: 2,4-dichloropyrimidine is converted to
2,4-dithiouracil. In our case, the possibility is offered of converting selone 7 to 5,7-di(thioxo)-(4H,6H)-1,3-
dithiolo[4,5-d]pyrimidine-2-selone without isolating diisothiuronium salt 12 in pure form.
The result of the facile reaction of selone 7 with sodium azide in acetonitrile on heating is a poorly
soluble, brown material that does not melt up to 330°C, the structure of which is under investigation.
TABLE 3. Coordinates of Atoms and Their Equivalent Isotropic Thermal
Parameters in the Molecule of Compound 6
Atom
x
y
z
Beq, Å2*
S(1)
C(2)
S(3)
C(4)
N(5)
C(6)
N(7)
C(8)
C(9)
S(2)
Cl(1)
Cl(2)
0.7595(4)
0.8390(29)
0.7608(4)
0.5317(21)
0.4343(26)
0.4351(25)
0.5295(24)
0.6265(22)
0.6306(21)
0.9727(4)
0.5199(4)
0.3100(4)
0.4428(5)
0.2474(32)
0.0554(5)
0.0703(23)
0.1603(29)
0.3352(29)
0.4269(27)
0.3389(25)
0.1561(22)
0.2504(5)
-0.1556(5)
0.4521(5)
0.8621(4)
0.9199(22)
0.8592(4)
0.6906(17)
0.6212(23)
0.6237(21)
0.6901(20)
0.7637(19)
0.7618(17)
1.0229(4)
0.6800(4)
0.5358(4)
2.7(7)
5.2(10)
4.8(7)
4.8(10)
4.6(9)
5.5(10)
6.4(10)
3.1(10)
3.7(10)
4.0(8)
3.5(8)
4.3(8)
_______
* The values of Beq are determined as one third of the trace of the
orthogonalized tensor Bij.
83

EXPERIMENTAL
The IR spectra were taken on a Specord M-80 apparatus in paraffin oil or hexachlorobutadiene. The
1H NMR spectra were recorded on a Bruker WH-90/DS (90 MHz) spectrometer in CDCl3 or DMSO-d6, with
TMS as the internal standard. The UV and visible spectra were taken on Specord M-40 in the appropriate
solvents.
The starting thione 4 and selone 5 were obtained as in [4, 5].
d
Mixture of freshly distilled phosphorus
5,7-Dichloro-1,3-dithiolo[4,5- ]pyrimidine-2-thione (6).
oxychloride (18 ml) and N,N-diethylaniline (2 ml) was added to thione 4 (0.65 g). With stirring, the temperature
was slowly raised up to 90°C and then was raised rapidly up to 120°C. At this temperature, the mixture was
stirred for 1 h, cooled, and poured over 50 g of ice. After 15 h, the residue was filtered off, washed with water,
dried, and crystallized from hexane. The yield of orange crystals of compound 6 was 0.43 g (55%); mp 134°C.
IR spectrum, ν, cm-1: 1512, 1480, 1305, 1280, 1080, 1060, 884, 850, 815. Found, %: Cl 28.50. C5Cl2N2S3.
Calculated, %: Cl 27.78.
d
Mixture of freshly distilled phosphorus
5,7-Dichloro-1,3-dithiolo[4,5- ]pyrimidine-2-selone (7).
oxychloride (36 ml) and N,N-diethylaniline (3.6 ml) was added to selone 5 (2.12 g, 8 mmol). With stirring, the
temperature was raised up to 90°C over the course of 1 h, and then was raised rapidly up to 120°C. The mixture
was stirred for 3 h at temperature of 120-125°C, then it was cooled and poured over ice (250 g). Green oil was
separated which solidified under stirring. The green residue was filtered off, washed with water until it tested
neutral, and dried in air. The dry product was dissolved with boiling in benzene (200 ml). The red solution was
passed through a column with silica gel; the red eluate was completely evaporated down in a rotary evaporator.
The oily residue was crystallized. The yield of dark green, shiny crystals of compound 7 was 1.85 g (76%);
mp 118-120°C. On crystallization from a moderate amount of benzene, along with the green crystals sometimes
orange-red crystals formed, which on storage transformed to dark green crystals. The material can be
recrystallized from absolute ethanol. Crystallization is not needed for further nucleophilic substitution reactions.
IR spectrum, ν, cm-1: 1512, 1490, 1306, 1274, 1212, 982, 956, 892, 860, 826. Found, %: Cl 23.05; S 20.80.
C5Cl2N2S2Se. Calculated, %: Cl 23.47; S 21.23.
d
A. Phosphorus
5-Chloro-7-(N-methyl-N-phenyl)amino-1,3-dithiolo[4,5- ]pyrimidine-2-selone (8).
oxychloride (10 ml) and dimethylaniline (1 ml) were added to selone 5 (0.53 g, 2 mmol). The temperature was
raised to 125°C and the mixture was stirred at this temperature for 3 h. After cooling, the reaction mixture was
poured into water (200 ml). The precipitate was filtered off, washed with water, dried, and dissolved in benzene,
then chromatographed on silica gel (1:1 benzene–hexane as the eluent) and two fractions were collected. After
evaporating down the first fraction, 0.18 g (30% yield) of selone 7 were obtained; after evaporating down the
second fraction, 0.23 g of red-orange crystals of selone 8 were obtained (31% yield).
B. Dichloroselone 7 (0.15 g, 0.5 mmol) was added to acetonitrile (15 ml) and heated until dissolved.
Then mixture of N-methylaniline (0.06 g, 0.56 mmol) and triethylamine (0.06 g, 0.59 mmol) in acetonitrile
(5 ml) was added. This was stirred at 50-60°C until the starting selone disappeared. The reaction mixture was
evaporated down to dryness, and the residue was dissolved in benzene and chromatographed on silica gel (1:1
benzene–hexane as the eluent). The eluate was evaporated down and the residue was mixed with a moderate
amount of hexane. Selone 8 was filtered off; yield 0.1 g (54%). 1H NMR spectrum (CDCl3), δ, ppm: 3.55 (3H, s,
CH3); 7.28 and 7.55 (5H, m, C6H5). Found, %: C 38.35; H 2.03; Cl 9.92; N 10.91; S 17.45. C12H8ClN3S2Se.
Calculated, %: C 38.67; H 2.16; Cl 9.51; N 11.27; S 17.20.
d
Methylocta-
5-Chloro-7-(N-methyl-N-octadecyl)amino-1,3-dithiolo[4,5- ]pyrimidine-2-selone (9).
decylamine (0.375 g, 1.32 mmol) was added to solution of selone 7 (0.2 g, 0.65 mmol) in benzene (10 ml) and
stirred at room temperature until the starting compound disappeared. The reaction was followed using TLC
(silica gel, 1:1 benzene–hexane as the eluent). The reaction took several days. The mixture was separated
1
chromatographically on silica gel. Obtained a red substance, yield 0.2 g (55%). H NMR spectrum (CDCl3),
84

δ, ppm: 0.85 t, 1.23 m, 2.5 m (C17H35); 3.25 (3H, s, CH3N); 3.57 (2H, t, CH2N). Found, %: C 51.95; H 7.21;
N 7.56; S 12.05. C24H40ClN3S2Se. Calculated, %: C 52.49; H 7.34; N 7.65; S 11.68.
d
Thiourea (0.05 g,
5-Chloro-7-isothiuronio-1,3-dithiolo[4,5- ]pyrimidine-2-selone Chloride (11).
0.66 mmol) was added to acetonitrile (5 ml) and heated until it dissolved. Selone 7 (0.15 g, 0.5 mmol) was
dissolved in acetonitrile (5 ml) with heating; both solutions were combined and boiled for 30 min until the
starting selone disappeared. The reaction was followed using TLC (silica gel, 1:1 benzene–hexane as the
eluent). An orange-brown residue was formed, which was filtered off and washed with acetonitrile. Yield 0.15 g
(80%). The sample did not melt up to 220°C. IR spectrum, ν, cm-1: 3200, 2980, 1690, 1670, 1660, 1640.
Found, %: Cl 18.2; S 26.1. C6H4Cl2N4S3Se. Calculated, %: Cl 18.75; S 25.44.
X-ray Diffraction Analysis. 1363 Diffraction reflections were measured on a Syntex-P21 automatic
four-circle diffractometer using molybdenum radiation (λ 0.71069 Å). Single crystals of compound 6 are
assigned to monoclinic syngony, crystal lattice parameters: a = 9.642(3), b = 7.570(3), c = 12.016(4) Å;
β = 100.36(3)°; V = 862.7 Å3; Dx = 1.96 g·cm-3; µ = 1.38 cm-1; F(000) = 504; space group P 21/a; Z = 4. The
structure was solved by the direct method and refined by the least squares method in the full-matrix anisotropic
approximation. We used 964 independent reflections with |F| > 2σF and 109 refined parameters in the
calculations. The final value of the R factor was 0.112. The coordinates of the atoms and their equivalent
isotropic thermal parameters are given in Table 3. The calculations were performed using the AREN software
package [8].
I. Sudmale, I. Lielbriedis, and I. Gudele participated in the experimental work.
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4.
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85