organic papers
Acta Cryst.(2005). E61, o365±o367 doi:10.1107/S1600536805000383 Zavodniket al. C8H12N2O2
o365
Acta Crystallographica Section EStructure Reports Online
ISSN 1600-5368
5-Acetyl-4,6-dimethyl-1,2,3,4-tetrahydro-pyrimidin-2-one
Valery E. Zavodnik,a
Anatoly D. Shutalev,b
Galina V. Gurskaya,c
Adam I. Stasha* and
Vladimir G. Tsirelsond
aKarpov Institute of Physical Chemistry,
10 Vorontsovo Pole, 105064 Moscow, Russia, bLomonosov State Academy of Fine Chemical
Technology, 86 Vernadsky Prospect, 119571 Moscow, Russia,cEngelhardt Institute of Molecular Biology, Russian Academy of Sciences, 32 Vavilova Street, 119991 Moscow, Russia, anddMendeleev University of Chemical Technology, 9 Miusskaya Square, 125047 Moscow, Russia
Correspondence e-mail: adam@cc.nifhi.ac.ru
Key indicators
Single-crystal X-ray study T= 293 K
Mean(C±C) = 0.002 AÊ Rfactor = 0.029 wRfactor = 0.095
Data-to-parameter ratio = 10.5
For details of how these key indicators were automatically derived from the article, see http://journals.iucr.org/e.
#2005 International Union of Crystallography Printed in Great Britain ± all rights reserved
The title compound, C8H12N2O2, belongs to the class of
5-substituted 1,2,3,4-tetrahydropyrimidin-2-ones, which exhibit a wide spectrum of biological activities. The conformation of the tetrahydropyrimidine ring is that of a distorted boat. In the crystal structure, NÐH O hydrogen bonds form molecular dimers and also link these dimers into chains along thecaxis of the unit cell.
Comment
The title compound, (I), belongs to the class of 5-substituted 1,2,3,4-tetrahydropyrimidin-2-ones, which are known as `Biginelli compounds' (Kappe, 1993). Some representatives of this group have emerged as orally active antihypertensive agents (Atwal et al., 1991; Grover et al., 1995; Kappe, 2000; Kappe et al., 1997; Rovnyaket al., 1995), mitotic kinesin Eg5 inhibitors which can be considered as potential anticancer drugs (Haggartyet al., 2000; Kappe, 2000), and-1a adreno-ceptor-selective antagonists, useful for the treatment of benign prostatic hyperplasia (Kappe, 2000; Nagarathnamet al., 1999).
To establish a correlation between the biological activity and spatial structure of molecules in the series of 1,2,3,4-tetrahydropyrimidin-2-ones and their 2-thioxo analogues, the conformation of the pyrimidine ring is usually considered (Kappeet al., 1997; Gurskayaet al., 2003a,b). In (I) (Fig. 1), the pyrimidine ring has the conformation of a distorted boat. The deviations of atoms N1 and C4 from the C2/N3/C5/C6 plane are 0.146 and 0.412 AÊ, respectively.
Molecules of (I) are linked into dimers by pairs of inter-molecular NÐH O hydrogen bonds (Table 1 and Fig. 2) across centres of symmetry. These dimers are linked by further NÐH O hydrogen bonds to form chains along thecaxis.
Experimental
The title compound was prepared according to the general method of synthesis of 5-substituted 1,2,3,4-tetrahydropyrimidin-2-ones (or
thiones) (Shutalev et al., 1997, 1998). The synthesis of (I) was performed by the reaction ofN-(1-tosylethyl)urea with the sodium enolate of acetylacetone in dry acetonitrile, followed by a TsOH-catalyzed dehydration of the resulting 5-acetyl-4-hydroxy-4,6-dimethylhexahydropyrimidin-2-one, without isolation of the latter. Crystals of (I) suitable for X-ray structure analysis were prepared at room temperature by slow evaporation of the solvent from a satu-rated solution of (I) (19 mg) in ethanol (1 ml).
Crystal data
C8H12N2O2 Mr= 168.20
Monoclinic,C2/c a= 14.473 (3) AÊ
b= 6.994 (1) AÊ
c= 17.200 (3) AÊ
= 103.37 (3) V= 1693.9 (6) AÊ3 Z= 8
Dx= 1.319 Mg mÿ3
MoKradiation Cell parameters from 24
re¯ections
= 11.7±12.4
= 0.10 mmÿ1 T= 293 (2) K Prism, colourless 0.460.420.12 mm
Data collection
Enraf±Nonius CAD-4 diffractometer
±2scans
Absorption correction: none 1712 measured re¯ections 1660 independent re¯ections 1187 re¯ections withI> 2(I)
Rint= 0.019
max= 26.0 h=ÿ17!15
k= 0!8
l=ÿ21!15 3 standard re¯ections
frequency: 60 min intensity decay: 0.5%
Refinement
Re®nement onF2 R[F2> 2(F2)] = 0.029 wR(F2) = 0.095 S= 1.07 1660 re¯ections 158 parameters
All H-atom parameters re®ned
w= 1/[2(Fo2) + (0.0592P)2
+ 0.1584P]
whereP= (Fo2+ 2Fc2)/3
(/)max< 0.001
max= 0.19 e AÊÿ3
min=ÿ0.12 e AÊÿ3
Extinction correction:SHELXL97
(Sheldrick, 1997)
Extinction coef®cient: 0.0043 (12)
Table 1
Hydrogen-bond geometry (AÊ,).
DÐH A DÐH H A D A DÐH A
N1ÐH1 O1i 0.858 (16) 1.991 (17) 2.8487 (15) 177.7 (14)
N3ÐH3 O2ii 0.828 (17) 2.110 (17) 2.8891 (16) 156.8 (13)
Symmetry codes: (i)ÿx1
2;ÿy32;ÿz1; (ii)ÿx12;y12;ÿz12.
All H atoms were located in difference syntheses and re®ned isotropically. The CÐH and NÐH bond lengths are in the ranges 1.00 (2)±0.92 (2) AÊ and 0.86 (2)±0.83 (2) AÊ, respectively.
Data collection:CAD-4-PC Software (Enraf±Nonius, 1993); cell re®nement: CAD-4-PC Software; data reduction: CAD-4-PC Soft-ware; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to re®ne structure:SHELXL97(Sheldrick, 1997); molecular graphics: XP in SHELXTL (Sheldrick, 1991); software used to prepare material for publication:SHELXL97and
CIFTAB(Sheldrick, 1997).
The authors are grateful to RFBR (grant No. 04±03-33053).
References
Atwal, K. S., Swanson, B. N., Unger, S. E., Floyd, D. M., Moreland, S., Hedberg, A. & O'Reilly, B. C. (1991).J. Med. Chem.34, 806±811.
Enraf±Nonius (1993).CAD-4-PC Software. Version 1.2. Enraf±Nonius, Delft, The Netherlands.
Grover, G. J., Dzwonczyk, S., McMullen, D. M., Normandin, D. E., Parham, C. S., Sleph, P. G. & Moreland, S. (1995).J. Cardiovasc. Pharmacol.26, 289± 294.
Gurskaya, G. V., Zavodnik, V. E. & Shutalev, A. D. (2003a).Crystallogr. Rep. 48, 92±97.
Gurskaya, G. V., Zavodnik, V. E. & Shutalev, A. D. (2003b).Crystallogr. Rep. 48, 416±421.
Haggarty, S. J., Mayer, T. U., Miyamoto, D. T., Fathi, R., King, R. W., Mitchison, T. J. & Schreiber, S. L. (2000).Chem. Biol.7, 275±286.
Kappe, C. O. (1993).Tetrahedron,49, 6937±6963. Kappe, C. O. (2000).Acc. Chem. Res.33, 879±888.
Kappe, C. O., Fabian, W. M. F. & Semones, M. A. (1997).Tetrahedron,53, 2803±2816.
Nagarathnam, D., Miao, S. W., Lagu, B., Chiu, G., Fang, J., Dhar, T. G. M., Zhang, J., Tyagarajan, S., Marzabadi, M. R., Zhang, F. Q., Wong, W. C., Sun, W. Y., Tian, D., Wetzel, J. M., Forray, C.et al. (1999).J. Med. Chem.42, 4764± 4777.
organic papers
o366
Zavodniket al. C8H12N2O2 Acta Cryst.(2005). E61, o365±o367Figure 1
The molecular structure of (I), showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 50% probability level.
Figure 2
Rovnyak, G. C., Kimball, S. D., Beyer, B., Cucinotta, G., DiMarco, J. D., Gougoutas, J., Hedberg, A., Malley, M., McCarthy, J. P., Zhang, R. A. & Moreland, S. (1995).J. Med. Chem.38, 119±129.
Sheldrick, G. M. (1991).SHELXTL. Siemens Analytical X-ray Instruments Inc., Madison, Wisconsin, USA.
Sheldrick, G. M. (1997).SHELXS97,SHELXL97andCIFTAB. Release 97-2. University of GoÈttingen, Germany.
Shutalev, A. D., Kishko, E. A., Sivova, N. V. & Kuznetsov, A. Yu. (1998).
Molecules, 3, 100±106.
Shutalev, A. D. & Kuksa, V. A. (1997).Khim. Geterotsikl. Soedin.pp. 105±109.
organic papers
supporting information
sup-1 Acta Cryst. (2005). E61, o365–o367
supporting information
Acta Cryst. (2005). E61, o365–o367 [https://doi.org/10.1107/S1600536805000383]
5-Acetyl-4,6-dimethyl-1,2,3,4-tetrahydropyrimidin-2-one
Valery E. Zavodnik, Anatoly D. Shutalev, Galina V. Gurskaya, Adam I. Stash and Vladimir G.
Tsirelson
5-acetyl-4,6-dimethyl-1,2,3,4-tetrahydropyrimidin-2-one
Crystal data
C8H12N2O2
Mr = 168.20
Monoclinic, C2/c
Hall symbol: -C 2yc
a = 14.473 (3) Å
b = 6.994 (1) Å
c = 17.200 (3) Å
β = 103.37 (3)°
V = 1693.9 (6) Å3
Z = 8
F(000) = 720
Dx = 1.319 Mg m−3
Mo Kα radiation, λ = 0.71073 Å
Cell parameters from 24 reflections
θ = 11.7–12.4°
µ = 0.10 mm−1
T = 293 K
Prism, colourless 0.46 × 0.42 × 0.12 mm
Data collection
Enraf–Nonius CAD-4 diffractometer
Radiation source: fine-focus sealed tube Beta-filter monochromator
θ–2θ scans
1712 measured reflections 1660 independent reflections 1187 reflections with I > 2σ(I)
Rint = 0.019
θmax = 26.0°, θmin = 2.4°
h = −17→15
k = 0→8
l = −21→15
3 standard reflections every 60 min intensity decay: 0.5%
Refinement
Refinement on F2
Least-squares matrix: full R[F2 > 2σ(F2)] = 0.029
wR(F2) = 0.095
S = 1.07
1660 reflections 158 parameters 0 restraints
Primary atom site location: structure-invariant direct methods
Secondary atom site location: difference Fourier map
Hydrogen site location: difference Fourier map All H-atom parameters refined
w = 1/[σ2(F
o2) + (0.0592P)2 + 0.1584P]
where P = (Fo2 + 2Fc2)/3
(Δ/σ)max < 0.001
Δρmax = 0.19 e Å−3
Δρmin = −0.12 e Å−3
Extinction correction: SHELXL97 (Sheldrick, 1997), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
supporting information
sup-2 Acta Cryst. (2005). E61, o365–o367
Special details
Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.
Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2,
conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > σ(F2) is used
only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2
are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2)
x y z Uiso*/Ueq
O1 0.31811 (7) 0.72513 (15) 0.42729 (5) 0.0529 (3)
O2 0.11886 (8) −0.00279 (14) 0.27906 (6) 0.0581 (3)
N1 0.19369 (8) 0.53897 (15) 0.44034 (6) 0.0407 (3)
N3 0.27067 (7) 0.48107 (15) 0.34084 (6) 0.0387 (3)
C2 0.26391 (9) 0.59101 (17) 0.40215 (7) 0.0375 (3)
C4 0.19446 (8) 0.35429 (17) 0.30044 (7) 0.0376 (3)
C5 0.14675 (8) 0.26497 (17) 0.36127 (7) 0.0356 (3)
C5′ 0.10586 (9) 0.07488 (18) 0.33966 (7) 0.0396 (3)
C5′′ 0.04751 (11) −0.0303 (2) 0.38736 (9) 0.0506 (4)
C6 0.14486 (8) 0.36756 (17) 0.42763 (7) 0.0358 (3)
C4′ 0.12405 (11) 0.4592 (2) 0.23516 (8) 0.0519 (4)
C6′ 0.09575 (11) 0.3223 (2) 0.49339 (8) 0.0473 (3)
H1 0.1901 (11) 0.607 (2) 0.4810 (9) 0.049 (4)*
H3 0.3106 (11) 0.510 (2) 0.3153 (9) 0.042 (4)*
H4 0.2235 (9) 0.255 (2) 0.2758 (8) 0.039 (3)*
H41′ 0.1562 (13) 0.509 (2) 0.1965 (11) 0.069 (5)*
H42′ 0.0723 (13) 0.378 (3) 0.2094 (10) 0.067 (5)*
H43′ 0.0966 (12) 0.569 (2) 0.2588 (10) 0.057 (4)*
H51′′ 0.0255 (13) −0.147 (3) 0.3555 (11) 0.075 (5)*
H52′′ 0.0840 (14) −0.061 (3) 0.4421 (12) 0.080 (6)*
H53′′ −0.0068 (13) 0.047 (3) 0.3957 (10) 0.071 (5)*
H61′ 0.1204 (16) 0.213 (3) 0.5214 (13) 0.095 (7)*
H62′ 0.0987 (13) 0.435 (3) 0.5288 (11) 0.076 (5)*
H63′ 0.0284 (16) 0.309 (3) 0.4739 (12) 0.089 (6)*
Atomic displacement parameters (Å2)
U11 U22 U33 U12 U13 U23
O1 0.0623 (6) 0.0563 (6) 0.0438 (5) −0.0194 (5) 0.0197 (4) −0.0117 (4)
O2 0.0692 (7) 0.0551 (6) 0.0602 (7) −0.0178 (5) 0.0360 (5) −0.0197 (5)
N1 0.0500 (6) 0.0413 (5) 0.0353 (5) −0.0029 (5) 0.0189 (4) −0.0063 (4)
N3 0.0398 (5) 0.0449 (6) 0.0351 (5) −0.0054 (4) 0.0164 (4) −0.0017 (4)
C2 0.0418 (6) 0.0402 (6) 0.0307 (5) −0.0008 (5) 0.0088 (5) 0.0007 (5)
C4 0.0432 (6) 0.0392 (6) 0.0343 (6) −0.0034 (5) 0.0171 (5) −0.0060 (5)
C5 0.0364 (6) 0.0392 (6) 0.0339 (6) 0.0022 (5) 0.0140 (4) 0.0015 (5)
supporting information
sup-3 Acta Cryst. (2005). E61, o365–o367
C5′′ 0.0597 (9) 0.0486 (8) 0.0472 (8) −0.0113 (7) 0.0198 (7) 0.0013 (6)
C6 0.0366 (6) 0.0383 (6) 0.0346 (6) 0.0047 (5) 0.0124 (4) 0.0027 (5)
C4′ 0.0551 (8) 0.0644 (9) 0.0351 (6) −0.0096 (7) 0.0081 (6) 0.0031 (6)
C6′ 0.0558 (8) 0.0506 (8) 0.0429 (7) 0.0000 (7) 0.0265 (6) −0.0004 (6)
Geometric parameters (Å, º)
O1—C2 1.2350 (15) C5—C5′ 1.4677 (17)
O2—C5′ 1.2279 (15) C5′—C5′′ 1.4993 (18)
N1—C2 1.3803 (16) C5′′—H51′′ 0.991 (19)
N1—C6 1.3831 (16) C5′′—H52′′ 0.99 (2)
N1—H1 0.858 (16) C5′′—H53′′ 0.991 (19)
N3—C2 1.3270 (15) C6—C6′ 1.5021 (16)
N3—C4 1.4598 (16) C4′—H41′ 0.960 (19)
N3—H3 0.828 (17) C4′—H42′ 0.963 (19)
C4—C5 1.5152 (15) C4′—H43′ 0.997 (18)
C4—C4′ 1.5192 (19) C6′—H61′ 0.93 (2)
C4—H4 0.959 (14) C6′—H62′ 0.99 (2)
C5—C6 1.3538 (16) C6′—H63′ 0.96 (2)
C2—N1—C6 123.98 (10) C5′—C5′′—H51′′ 104.5 (11)
C2—N1—H1 115.5 (10) C5′—C5′′—H52′′ 112.4 (11)
C6—N1—H1 119.1 (10) H51′′—C5′′—H52′′ 112.5 (15)
C2—N3—C4 122.94 (10) C5′—C5′′—H53′′ 112.2 (11)
C2—N3—H3 117.9 (10) H51′′—C5′′—H53′′ 111.3 (15)
C4—N3—H3 116.1 (10) H52′′—C5′′—H53′′ 104.2 (15)
O1—C2—N3 124.11 (11) C5—C6—N1 118.90 (10)
O1—C2—N1 120.77 (11) C5—C6—C6′ 128.93 (12)
N3—C2—N1 115.03 (11) N1—C6—C6′ 112.16 (10)
N3—C4—C5 109.67 (9) C4—C4′—H41′ 109.6 (10)
N3—C4—C4′ 111.24 (11) C4—C4′—H42′ 111.8 (10)
C5—C4—C4′ 111.99 (11) H41′—C4′—H42′ 110.2 (14)
N3—C4—H4 106.8 (8) C4—C4′—H43′ 109.5 (9)
C5—C4—H4 108.9 (8) H41′—C4′—H43′ 107.9 (14)
C4′—C4—H4 108.0 (8) H42′—C4′—H43′ 107.7 (15)
C6—C5—C5′ 127.45 (10) C6—C6′—H61′ 111.8 (15)
C6—C5—C4 117.71 (10) C6—C6′—H62′ 109.5 (11)
C5′—C5—C4 114.83 (10) H61′—C6′—H62′ 112.3 (16)
O2—C5′—C5 118.93 (11) C6—C6′—H63′ 112.1 (13)
O2—C5′—C5′′ 117.63 (12) H61′—C6′—H63′ 109.8 (18)
C5—C5′—C5′′ 123.43 (11) H62′—C6′—H63′ 100.8 (16)
Hydrogen-bond geometry (Å, º)
D—H···A D—H H···A D···A D—H···A
supporting information
sup-4 Acta Cryst. (2005). E61, o365–o367
N3—H3···O2ii 0.828 (17) 2.110 (17) 2.8891 (16) 156.8 (13)
