Crystal and molecular structure of 2H- and 2-(p-tolylamino)-5,6-dimethylthieno[2,3-d]pyrimidin-4-ones

Article abstract of DOI:10.1023/A:1015064920578

The crystal and molecular structure of 2H- and 2-(p-tolylamino)-5,6-dimethylthieno[2,3-d]pyrimidin-4-ones was investigated by X-ray diffraction. In crystals, the tautorneric form with a localized N(1)=C(2) bond is realized. A comparative analysis of the two structures using the literature data is given to examine the conjugation effect on the geometrical parameters of a pseudoaromatic pyrimidine system.

Full text of DOI:10.1023/A:1015064920578

Journal of Structural Chemistry, Vol. 42, No. 6, pp. 995-1001, 2001
Original Russian Text Copyright © 2001 by B. Tashkhodzhaev, K. K. Turgunov, B. Usmanova,
B. A. Urakov, I. I. Vorontsov, M. Yu. Antipin, and Kh. M. Shakhidoyatov
CRYSTAL AND MOLECULAR STRUCTURE
OF 2H- AND 2-(p-TOLYLAMINO)-5,6-
DIMETHYLTHIENO[2,3-d]PYRIMIDIN-4-ONES
B. Tashkhodzhaev, K. K. Turgunov, B. Usmanova,
B. A. Urakov, I. I. Vorontsov,
UDC 548.737
M. Yu. Antipin, and Kh. M. Shakhidoyatov
The crystal and molecular structure of 2H- and 2-(p-tolylamino)-5,6-dimethylthieno[2,3-d]pyrimidin-4-ones
was investigated by X-ray diffraction. In crystals, the tautomeric form with a localized N(1)=C(2) bond
is realized. A comparative analysis of the two structures using the literature data is given to examine the
conjugation effect on the geometrical parameters of a pseudoaromatic pyrimidine system.
INTRODUCTION
2
H-5,6-dimethylthieno[2,3-d]pyrimidin-4-one (1) and its substituted derivatives, especially those with a heteroatom
oxygen, sulfur, selenium, or amino group) at carbon in the 2 position, may exist in several tautomeric forms. Thus compound
exists as three tautomeric forms resulting from migration of the hydrogen atom from N(3) to N(1) or to oxygen at C(4).
(
1
For this compound, alkylations occur at either N(1) or N(3) atoms, or simultaneously at N(1) and at oxygen bonded to
C(4) [1-3]. Therefore it is interesting to determine the tautomeric form of the compound and examine the solid-state
methylation reaction.
Compound 1 was synthesized from ethyl 2-amino-4,5-dimethylthiophene-2-carboxylic ether and formamide
according to the following scheme:
2
-(p-Tolylamino)-5,6-dimethylthieno[2,3-d]pyrimidin-4-one (2) has one more arylamino group compared to 1; due
to this, the number of possible tautomeric forms increases to five. Compound 2 was prepared by nucleophilic substitution
of the methylthio group of 2-methylthio-5,6-dimethylthieno[2,3-d]pyrimidin-4-one (3) by p-toluidine according to the scheme:
2
3
Institute of Phytochemistry, Academy of Sciences, Uzbekistan Republic. Institute of Organoelement Compounds,
Russian Academy of Sciences, Moscow. Translated from Zhurnal Strukturnoi Khimii, Vol. 42, No. 6, pp. 1188-1194,
November-December, 2001. Original article submitted January 24, 2001.
0
022-4766/01/4206-0995$25.00 ©2001 Plenum Publishing Corporation
995

Compound 3, in turn, was obtained by alkylation of 2-thioxo-5,6-dimethylthieno[2,3-d]pyrimidin-4-one by methyl
iodide.
EXPERIMENTAL
Syntheses of parent compounds. 5,6-Dimethylthieno[2,3-d]pyrimidin-4-one. A suspension of ethyl 2-amino-4,5-
dimethylthiophene-3-carboxylic ether (1.0 g, 5 mmol) and formamide (2 ml, 20 mmol) was heated on an oil bath at
20-130°C for 2 h. Then the mixture was cooled and the precipitate was washed with water and dried. Recrystallization
1
form alcohol gave 0.6 g (60%) of a substance with Tm = 267-268°C, R = 0.3 (Silufol, acetone:benzene = 1:3).
f
An analogous procedure with formamide replaced by ammonium rhodanide gave 2-thioxo-5,6-dimethylthieno[2,3-
d]pyrimidinone-4 with Tm = 313-315°C, R = 0.45 (Silufol, acetone:benzene = 1:3).
f
Methylation of 2-thioxo-5,6-dimethylthieno[2,3-d]pyrimidin-4-one in the presence of methyl iodide afforded
2
-methylthio-5,6-dimethylthieno[2,3-d]pyrimidinone-4 (yield 40%).
-(p-Tolylamino)-5,6-dimethylthieno[2,3-d]pyrimidin-4-one. A suspension of 2-methylthio-5,6-dimethylthieno[2,3-
2
d]pyrimidin-4-one (1.0 g, 5 mmol) and p-toluidine (1.0 g, 10 mmol) was heated on an oil bath at 200-220 °C for 4 h. The
reaction mixture was treated with hot water, filtered, and dried. The precipitate was dissolved in a 2% solution of alkali.
The residue was filtered off, washed with water, and dried. This gave 0.6 g (60%) of a substance with Tm = 298-300°C
(
acetone), R = 0.61 (Silufol, acetone:benzene = 1:3).
f
X-ray diffraction analysis. The cell parameters and the space group of crystals 1 and 2 were determined and
refined on a Siemens P3 diffractometer. Table 1 lists the main experimental and calculated data. The intensity data were
collected on the same diffractometer (θ/2θ scan mode, MoK radiation, graphite monochromator).
α
The structures were solved by direct methods (SHELX-86 [4], on-line mode). The structure refinement was
performed by the least-squares method in sequential isotropic-anisotropic approximation using SHELXL-93 [5] for
TABLE 1. Selected Crystal Data and Characteristics of X-Ray Diffraction Experiment for Molecules 1 and 2
Parameter
1
2
a, Å
b, Å
c, Å
V, Å3
dcalc, g/cm3
α, deg
11.090(2)
6.863(1)
11.419(2)
821.2(3)
1.458
19.624(5)
26.621(7)
14.146(5)
5759(3)
1.316
90.0
90.0
β, deg
γ, deg
109.11(3)
90.0
128.80(2)
90.0
Space group
P2 /n, Z = 4
C2/c, Z = 16
1
No. of reflections
R[I > 2σ (I)] index
R (all data)
1446 (I > 0), 1344 (I > 2σ)
3641 (I > 0), 2510 (I > 2σ)
R = 0.0336, wR = 0.0902
1 2
R = 0.0679, wR = 0.0964
1 2
R = 0.0430, wR = 0.1235
1
2
R = 0.0458, wR = 0.1442
1
2
4
2
3
TABLE 2. Coordinates (×10 ) and Equivalent Isotropic Thermal Parameters U = 1/3(U11 + U22 + U ) (Å ×10 )
33
of Nonhydrogen Atoms in 1
Atom
1
x/a
y/b
z/c
U
2
3
4
5
O(1)
N(1)
C(2)
N(3)
5195(1)
2708(1)
3090(2)
3898(1)
–3670(2)
40(2)
–1629(2)
–2858(2)
1334(1)
–1130(1)
–1421(2)
–609(1)
43(1)
40(1)
39(1)
35(1)
9
96

TABLE 2 (Continued)
1
2
3
4
5
C(4)
C(4a)
C(5)
C(6)
S(7)
C(7a)
C(8)
C(9)
4441(2)
4033(1)
4395(1)
3849(2)
2876(1)
3209(1)
5261(2)
4019(2)
–2498(2)
–674(2)
195(2)
1988(2)
2618(1)
458(2)
654(1)
1022(1)
2233(1)
2196(2)
716(1)
107(1)
3389(2)
3240(2)
32(1)
31(1)
34(1)
38(1)
42(1)
34(1)
47(1)
56(1)
–734(3)
3405(3)
4
2
3
TABLE 3. Coordinates (×10 ) and Equivalent Isotropic Thermal Parameters U = 1/3(U + U22 + U ) (Å ×10 ) of
11
33
Nonhydrogen Atoms in 2
Molecule 2B
y/b z/c
Molecule 2A
Atom
x/a
U
x/a
y/b
z/c
U
O(1)
N(1)
C(2)
N(3)
C(4)
C(4a)
C(5)
C(6)
S(7)
C(7a)
C(8)
C(9)
C(1′)
C(2′)
C(3′)
C(4′)
C(5′)
C(6′)
N(7′)
C(8′)
5589(1)
3697(1)
3538(2)
4190(1)
5075(2)
5270(1)
6097(2)
6004(2)
4911(1)
4559(2)
6964(2)
6701(2)
1918(2)
1780(2)
943(2)
–3926(1)
–5030(1)
–4549(1)
–4192(1)
–4288(1)
–4815(1)
–5066(1)
–5573(1)
–5756(1)
–5141(1)
–4805(1)
–5970(1)
–4580(1)
–5092(1)
–5271(1)
–4963(2)
–4452(2)
–4263(1)
–4353(1)
–5171(2)
9219(2)
7553(2)
7381(2)
7976(2)
8783(2)
8994(2)
9757(2)
9687(2)
8709(1)
8355(2)
10557(2)
10315(3)
5779(2)
5602(2)
4722(3)
3995(3)
4185(3)
5047(3)
6615(2)
3040(3)
55(1)
42(1)
42(1)
45(1)
42(1)
37(1)
43(1)
50(1)
51(1)
39(1)
62(1)
80(1)
49(1)
59(1)
72(1)
73(1)
76(1)
65(1)
55(1)
106(1)
6787(1)
6045(1)
5890(2)
6158(1)
6607(2)
6808(1)
7274(2)
7305(2)
6774(1)
6497(2)
7663(2)
7709(2)
5058(2)
4919(2)
4503(2)
4212(2)
4365(2)
4780(2)
5449(1)
3739(3)
–3315(1)
–2163(1)
–2637(1)
–3018(1)
–2947(1)
–2435(1)
–2226(1)
–1716(1)
–1482(1)
–2081(1)
–2536(1)
–1356(1)
–2537(1)
–2024(1)
–1800(1)
–2067(1)
–2573(1)
–2809(1)
–2806(1)
–1812(2)
7961(2)
9074(2)
9111(2)
8755(2)
8312(2)
8283(2)
7898(2)
7977(2)
8515(1)
8648(2)
7462(2)
7640(3)
9902(2)
9779(3)
10174(3)
10696(3)
10827(3)
10435(3)
9507(2)
11108(4)
60(1)
46(1)
43(1)
49(1)
46(1)
41(1)
46(1)
52(1)
56(1)
42(1)
63(1)
75(1)
49(1)
61(1)
75(1)
74(1)
80(1)
68(1)
52(1)
115(1)
228(2)
379(2)
1199(2)
2725(1)
–678(2)
nonhydrogen atoms. The H atoms at the heteroatoms N(2) and N(3) were located on difference Fourier maps. The H atoms
bonded to the carbon atoms were placed geometrically using the riding model and refined isotropically. The coordinates
of the basic atoms obtained in the last cycle of the least-squares refinement are listed in Tables 2 and 3.
DISCUSSION OF RESULTS
The spatial structure of molecules 1 and 2 obtained by X-ray diffraction analysis is shown in Figs. 1 and 2. The
independent part of the unit cell of crystal 2 has two molecules. The geometrical parameters of the molecules (bond lengths
and angles) are given in Tables 4 and 5.
Analysis of the valence heterobond lengths (Tables 4 and 5) and the experimental positions of H atoms shows that
molecules 1 and 2 in crystal exist in tautomeric forms corresponding to the above structural formulas.
9
97

Fig. 1. Spatial structure and H-bonding in the packing of molecule 1
the numbering is given for some atoms of the basic molecule).
(
Fig. 2. Spatial structure and the fragment of packing demonstrating the
island character of H-bonds in the crystal structure of 2 (basic
molecules A and B).
The pyrimidothiophene nucleus of both molecules and the benzene ring of the toluidine residue in 2 are planar
within ±0.015 Å. The minor (up to ±0.08 Å) deviations of the methyl groups at C5 and C6 from the plane of the
pyrimidothiophene nucleus seems to be the result of steric hindrances, the anisotropy of the thermal vibrations of atoms,
and molecular packing.
In the structure of 2, the arrangement of the aromatic ring relative to the bicyclic system is of interest from
stereochemical viewpoint. The crystallographically independent molecules 2A and 2B (Fig. 2) do not differ essentially by
appearance, and the benzene ring bonded via the N(7′) atom is virtually coplanar with the pyrimidothiophene nucleus.
This is indicated by the values of the torsion angles N(3)–C(2)–N(7′)–C(1′) [–172.9° (2A), –177.9° (2B)] and
C(2)–N(7′)–C(1′)–C(2′) [3.5° (2A), 11.3° (2B)] defining the arrangement of the aromatic ring.
9
98

TABLE 4. Bond Lengths (d) and Angles (ω) in 1
Bond
d, Å
Angle
ω, deg
Angle
ω, deg
O(1)–C(4)
N(1)–C(2)
N(1)–C(7a)
C(2)–N(3)
N(3)–C(4)
C(4)–C(4a)
C(4a)–C(7a)
C(4a)–C(5)
C(5)–C(6)
C(5)–C(8)
C(6)–C(9)
C(6)–S(7)
S(7)–C(7a)
1.235(2)
1.302(2)
1.368(2)
1.353(2)
1.391(2)
1.440(2)
1.381(2)
1.437(2)
1.366(2)
1.497(2)
1.502(2)
1.736(2)
1.728(2)
C(2)–N(1)–C(7a)
N(1)–C(2)–N(3)
C(2)–N(3)–C(4)
O(1)–C(4)–N(3)
O(1)–C(4)–C(4a)
N(3)–C(4)–C(4a)
C(7a)–C(4a)–C(5)
C(7a)–C(4a)–C(4)
C(5)–C(4a)–C(4)
C(6)–C(5)–C(4a)
113.10(13)
124.85(14)
124.37(13)
120.74(14)
126.49(14)
112.76(13)
113.67(14)
117.48(14)
128.83(14)
111.30(14)
C(6)–C(5)–C(8)
C(4a)–C(5)–C(8)
C(5)–C(6)–C(9)
C(5)–C(6)–S(7)
C(9)–C(6)–S(7)
C(7a)–S(7)–C(6)
N(1)–C(7a)–C(4a)
N(1)–C(7a)–S(7)
C(4a)–C(7a)–S(7)
124.1(2)
124.6(2)
128.3(2)
112.48(12)
119.21(13)
91.78(7)
127.4(2)
121.81(12)
110.75(12)
TABLE 5. Bond Lengths (d) and Angles (ω) in 2
d, Å
Bond
2B
d, Å
Bond
2
A
2A
2B
O(1)–C(4)
N(1)–C(2)
N(1)–C(7a)
C(2)–N(7′)
C(2)–N(3)
N(3)–C(4)
C(4)–C(4a)
C(4a)–C(7a)
C(4a)–C(5)
C(5)–C(6)
C(5)–C(8)
1.242(3)
1.305(3)
1.353(3)
1.352(3)
1.378(3)
1.379(3)
1.436(3)
1.392(3)
1.432(3)
1.358(3)
1.497(3)
1.245(3)
1.307(3)
1.366(3)
1.369(3)
1.375(3)
1.378(3)
1.426(3)
1.387(3)
1.438(3)
1.360(3)
1.494(3)
C(6)–C(9)
C(6)–S(7)
1.502(4)
1.742(3)
1.725(2)
1.381(3)
1.387(3)
1.394(3)
1.383(4)
1.376(4)
1.382(5)
1.511(4)
1.368(4)
1.500(3)
1.747(3)
1.733(2)
1.380(3)
1.383(4)
1.395(3)
1.381(4)
1.381(4)
1.367(4)
1.528(4)
1.388(4)
S(7)–C(7a)
C(1′)–C(2′)
C(1′)–N(7′)
C(1′)–C(6′)
C(2′)–C(3′)
C(3′)–C(4′)
C(4′)–C(5′)
C(4′)–C(8′)
C(5′)–C(6′)
ω, deg
ω, deg
Angle
Angle
2
A
2B
2A
2B
C(2)–N(1)–C(7a)
N(1)–C(2)–N(7′)
N(1)–C(2)–N(3)
N(7′)–C(2)–N(3)
C(2)–N(3)–C(4)
O(1)–C(4)–N(3)
O(1)–C(4)–C(4a)
N(3)–C(4)–C(4a)
C(7a)–C(4a)–C(5)
C(7a)–C(4a)–C(4)
C(5)–C(4a)–C(4)
C(6)–C(5)–C(4a)
C(6)–C(5)–C(8)
C(4a)–C(5)–C(8)
C(5)–C(6)–C(9)
C(5)–C(6)–S(7)
113.4(2)
123.6(2)
122.8(2)
113.6(2)
125.7(2)
118.6(2)
128.7(2)
112.7(2)
113.6(2)
116.6(2)
129.8(2)
111.8(2)
123.6(2)
124.6(2)
128.8(2)
112.3(2)
113.8(2)
123.8(2)
123.1(2)
113.1(2)
124.4(2)
119.7(2)
126.0(2)
114.3(2)
114.2(2)
116.4(2)
129.3(2)
111.2(2)
125.2(2)
123.6(2)
128.1(2)
112.6(2)
C(9)–C(6)–S(7)
118.9(2)
91.9(1)
119.3(2)
91.8(1)
C(7a)–S(7)–C(6)
N(1)–C(7a)–C(4a)
N(1)–C(7a)–S(7)
C(4a)–C(7a)–S(7)
C(2′)–C(1′)–N(7′)
C(2′)–C(1′)–C(6′)
N(7′)–C(1′)–C(6′)
C(1′)–C(2′)–C(3′)
C(4′)–C(3′)–C(2′)
C(3′)–C(4′)–C(5′)
C(3′)–C(4′)–C(8′)
C(5′)–C(4′)–C(8′)
C(6′)–C(5′)–C(4′)
C(5′)–C(6′)–C(1′)
C(2)–N(7′)–C(1′)
128.7(2)
120.9(2)
110.4(2)
125.1(2)
118.0(2)
116.9(2)
119.4(3)
123.1(3)
116.5(3)
121.9(4)
121.6(3)
121.7(3)
121.2(3)
131.1(2)
127.9(2)
121.9(2)
110.2(2)
125.0(2)
118.1(3)
116.9(2)
119.9(3)
122.7(3)
116.8(3)
121.8(3)
121.4(3)
121.8(3)
120.8(3)
129.9(2)
9
99

Analysis of data in Tables 4 and 5 indicates that the S(7)–C(7a) and C(5)–C(6) bonds are slightly shorter than the
analogous bonds S(7)–C(6) and C(4a)–C(7a) arranged symmetrically in the thiophene ring. The S(7)–C(7a) and C(5)–C(6)
bond lengths averaged over the three X-ray structures (1, 2A, and 2B) are 1.729 and 1.361 Å, respectively. The S(7)–C(6)
and C(4a)–C(7a) bonds arranged symmetrically relative to the above bonds are 1.742 and 1.387 Å, although for “ideal”
thiophene, spectroscopic studies [6] showed that S–C is 1.714 Å and C=C is 1.370 Å. The loss of symmetry found for the
bond lengths of the thiophene ring may be explained by the effect of the π-electrons of the N(1)=C(2) bond on the
heteroaromatic system. The analogous tendency of bond length variation in the thiophene ring with a loss of symmetry in
the thiophene ring is also observed in related pyrimidothiophene-containing compounds [7, 8] (Cambridge Structural Database,
March, 2000). Another evidence in support of this assumption is lengthening (to 1.307 Å) of the formal double bond
N(1)=C(2) with respect to the N=C bonds of 1.265 Å [9], which is observed, for example, in quinazolone alkaloids containing
an analogous pyrimidine heterocycle [10, 11].
2
In 1 and 2, the N(3) atom is sp -hybridized and hence its lone electron pair is simultaneously involved in conjugation
with the π-electrons of the C(4)=O and N(1)=C(2) bonds. A consequence of this is pronounced lengthening of the C=O
bond to 1.245 Å, which is less pronounced in pyrimidothiophene-containing compounds (1.225 Å) [7, 8] and polymethylene
quinazolones (1.211 Å) [10]. In crystals 1 and 2, the lengthening of the ketone bond may be the result of the action of the
intermolecular H-bond involving the C=O group and having an island structure (see below); this was not noted for the
packing of the compounds compared above [7, 8, 10].
2
As opposed to 1, structure 2 has a p-toluidine fragment in the C(2) position. The N(7′) atom is sp -hybridized and
has a lone electron pair available for conjugation. The participation of the N(7′) atom in conjugation in 2 provides a
competing direction for point C(2), due to which C(2)–N(3) is lengthened (to 1.377 Å) compared to the values observed
for 1 (1.353 Å). The conjugation between the C=O bond and the lone electron pair of N(3) is strengthened, shortening the
N(3)–C(4) bond to 1.379 Å (vs 1.391 Å in 1).
Analysis of intermolecular contacts (Fig. 1) shows that in crystal 1 the molecules related by the symmetry center
due to the N–H...O type H-bond form islands with the distances N(3)...O(1) 2.81 and N(3)H...O(1) 1.99 Å and the angle
N(3)–H...O 177°. In crystal, the islands are separated by the distances typical of van der Waals interactions. Molecules 2
also form islands due to N–H...O type H-bonds in crystal (Fig. 2). Island formation, however, involves four molecules: two
molecules in the initial position and two molecules transformed by the twofold symmetry axis and approaching the basic
molecules (Fig. 2). The geometrical parameters of these intermolecular H-bonds are as follows: the distances O(1)A...N(3)B
2
.90 and O(1)A...H(3) 2.08 Å and the angle O–H–N 161°; the distances O(1)A...N(7′)B 3.05 and O(1)A...H(7′) 2.24 Å and
the angle O–H–N 156°; the distances O(1)B...N(3)A 2.77 and O(1)B...H(3) 1.96 Å and the angle O–H–N 157°; the distances
O(1)B...N(7′)A 2.90 and O(1)A...H(7′) 2.06 Å and the angle O–H–N 155°.
CONCLUSIONS
X-ray diffraction analysis of 2H- and 2-(p-tolylamino)-5,6-dimethylthieno[2,3-d]pyrimidin-4-ones indicated that a
tautomeric form with an N(1)=C(2) bond is realized in their structures. In 1 and 2, associates of two (1) and four (2)
molecules are formed by means of intermolecular H-bonds.
We are grateful to RFFR for providing financial support to obtain a permission to use the Cambridge Structural
Database (grant 99-07-90133).
REFERENCES
1
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