The structures of two conformationally similar 1,4-dihydropyrimidines with a novel carbamoyl substitution,
viz. 6-methyl-5-(
N-methylcarbamoyl)-4-phenyl-1,2,3,4-tetrahydropyrimidine-2-thione monohydrate, C
13H
15N
3OS·H
2O, (I), and 4-(4-chlorophenyl)-6-methyl-5-(
N-methylcarbamoyl)-1,2,3,4-tetrahydropyrimidine-2-thione monohydrate, C
13H
14ClN
3OS·H
2O, (II), exhibit the structural features of 1,4-dihydropyridine calcium channel blockers. In both structures, the pyrimidine ring adopts a flattened boat conformation and the carbamoyl side chain is in an extended conformation with an anticlinal orientation. The phenyl ring occupies a pseudo-axial position with respect to the pyrimidine ring in these structures. Both compounds crystallize with one molecule of water, which participates in a two-dimensional hydrogen-bonding network. The molecules are linked into dimers by N-H
S hydrogen bonds in both structures.
Supporting information
CCDC references: 263060; 263061
Compounds (I) and (II) were prepared by known synthetic methods (Sadanandam et al., 1992) and recrystallized from a methanol/ water (90:10) solution.
After location of the H atoms in difference density maps, all C and N-bound H atoms were positioned using SHELXL97 HFIX instructions (Sheldrick, 1997) and treated as riding atoms, with C—H distances in the range 0.93–0.98 Å and an N—H distance of 0.86 Å, and with Uiso(H) values of 1.5Ueq(C) for methyl H atoms and 1.2Ueq(C) for other H atoms. Water H atoms (H1W and H2W) for (I) were refined with an O—H distance restraint (please specify) (Table 2). In (II), only one H atom of the water molecule was located. Since (I) and (II) are isomorphous, the positions of the water H atoms in (I)? were utilized in (II). However, attempts to refine the coordinates of these H atoms were unsuccessful, and hence the positional and displacement parameters of water H atoms in (II) were constrained (specify constraints). Examination of both the structures with PLATON (Spek, 2003) showed that there were no solvent-accessible voids in the crystal lattice.
For both compounds, data collection: SMART (Bruker, 2001); cell refinement: SAINT (Bruker, 2001). Data reduction: SAINT for (I); SAINT (Bruker, 2001) for (II). For both compounds, program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEP-3 (Farrugia, 1997) and PLATON (Spek, 2003); software used to prepare material for publication: SHELXL97 and PARST (Nardelli, 1995).
(I) 6-methyl-5-(
N-methylcarbamoyl)-4-phenyl-1,2,3,4-dihydropyrimidine-2-thione monohydrate
top
Crystal data top
C13H15N3OS·H2O | Z = 2 |
Mr = 279.36 | F(000) = 296 |
Triclinic, P1 | Dx = 1.32 Mg m−3 |
Hall symbol: -P 1 | Mo Kα radiation, λ = 0.71073 Å |
a = 5.0116 (3) Å | Cell parameters from 5613 reflections |
b = 8.9507 (6) Å | θ = 2.3–28.0° |
c = 16.0882 (11) Å | µ = 0.23 mm−1 |
α = 86.095 (1)° | T = 273 K |
β = 84.841 (1)° | Needle, colorless |
γ = 78.241 (1)° | 0.20 × 0.15 × 0.10 mm |
V = 702.75 (8) Å3 | |
Data collection top
CCD Area Detector diffractometer | 2971 reflections with I > 2σ(I) |
Radiation source: fine-focus sealed tube | Rint = 0.017 |
Graphite monochromator | θmax = 28.0°, θmin = 2.3° |
ω scan | h = −6→6 |
8102 measured reflections | k = −11→11 |
3227 independent reflections | l = −21→20 |
Refinement top
Refinement on F2 | 2 restraints |
Least-squares matrix: full | H atoms treated by a mixture of independent and constrained refinement |
R[F2 > 2σ(F2)] = 0.041 | w = 1/[σ2(Fo2) + (0.0601P)2 + 0.1834P] where P = (Fo2 + 2Fc2)/3 |
wR(F2) = 0.115 | (Δ/σ)max = 0.001 |
S = 1.05 | Δρmax = 0.24 e Å−3 |
3227 reflections | Δρmin = −0.24 e Å−3 |
182 parameters | |
Crystal data top
C13H15N3OS·H2O | γ = 78.241 (1)° |
Mr = 279.36 | V = 702.75 (8) Å3 |
Triclinic, P1 | Z = 2 |
a = 5.0116 (3) Å | Mo Kα radiation |
b = 8.9507 (6) Å | µ = 0.23 mm−1 |
c = 16.0882 (11) Å | T = 273 K |
α = 86.095 (1)° | 0.20 × 0.15 × 0.10 mm |
β = 84.841 (1)° | |
Data collection top
CCD Area Detector diffractometer | 2971 reflections with I > 2σ(I) |
8102 measured reflections | Rint = 0.017 |
3227 independent reflections | |
Refinement top
R[F2 > 2σ(F2)] = 0.041 | 2 restraints |
wR(F2) = 0.115 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.05 | Δρmax = 0.24 e Å−3 |
3227 reflections | Δρmin = −0.24 e Å−3 |
182 parameters | |
Special details top
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. |
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top | x | y | z | Uiso*/Ueq | |
S1 | 0.27882 (9) | 0.80405 (4) | 0.51855 (2) | 0.04755 (14) | |
N1 | 0.3380 (2) | 0.98831 (14) | 0.38552 (7) | 0.0397 (3) | |
H1N | 0.4508 | 1.0209 | 0.4136 | 0.048* | |
C2 | 0.2771 (3) | 1.06121 (15) | 0.30772 (8) | 0.0354 (3) | |
C3 | 0.1503 (3) | 0.99441 (15) | 0.25557 (8) | 0.0342 (3) | |
C4 | 0.0663 (3) | 0.84337 (16) | 0.28020 (8) | 0.0361 (3) | |
H4 | −0.1250 | 0.8533 | 0.2682 | 0.043* | |
N5 | 0.0839 (3) | 0.80925 (14) | 0.37017 (7) | 0.0414 (3) | |
H5N | −0.0078 | 0.7443 | 0.3936 | 0.050* | |
C6 | 0.2295 (3) | 0.87017 (16) | 0.41850 (8) | 0.0370 (3) | |
C7 | 0.2370 (3) | 0.71526 (16) | 0.22954 (9) | 0.0392 (3) | |
C8 | 0.4744 (3) | 0.62708 (19) | 0.25705 (12) | 0.0524 (4) | |
H8 | 0.5327 | 0.6446 | 0.3081 | 0.063* | |
C9 | 0.6271 (4) | 0.5121 (2) | 0.20875 (15) | 0.0679 (5) | |
H9 | 0.7871 | 0.4530 | 0.2277 | 0.081* | |
C10 | 0.5432 (5) | 0.4854 (2) | 0.13347 (14) | 0.0724 (6) | |
H10 | 0.6454 | 0.4080 | 0.1015 | 0.087* | |
C11 | 0.3093 (5) | 0.5728 (2) | 0.10550 (12) | 0.0720 (6) | |
H11 | 0.2534 | 0.5552 | 0.0541 | 0.086* | |
C12 | 0.1546 (4) | 0.6872 (2) | 0.15304 (10) | 0.0554 (4) | |
H12 | −0.0053 | 0.7457 | 0.1336 | 0.067* | |
C21 | 0.3578 (4) | 1.21356 (18) | 0.29560 (10) | 0.0470 (3) | |
H21A | 0.2913 | 1.2639 | 0.2447 | 0.070* | |
H21B | 0.5534 | 1.1998 | 0.2924 | 0.070* | |
H21C | 0.2805 | 1.2748 | 0.3419 | 0.070* | |
C31 | 0.0790 (3) | 1.05908 (15) | 0.17068 (8) | 0.0353 (3) | |
O32 | −0.1512 (2) | 1.06625 (14) | 0.14737 (7) | 0.0526 (3) | |
N33 | 0.2787 (2) | 1.10168 (15) | 0.12043 (7) | 0.0415 (3) | |
H33N | 0.4381 | 1.0912 | 0.1385 | 0.050* | |
C34 | 0.2366 (3) | 1.1651 (2) | 0.03617 (9) | 0.0524 (4) | |
H34A | 0.1036 | 1.2589 | 0.0382 | 0.079* | |
H34B | 0.1724 | 1.0937 | 0.0050 | 0.079* | |
H34C | 0.4062 | 1.1848 | 0.0096 | 0.079* | |
O1W | 0.8083 (3) | 0.56801 (18) | 0.43422 (11) | 0.0712 (4) | |
H1W | 0.672 (6) | 0.611 (4) | 0.469 (2) | 0.161 (16)* | |
H2W | 0.844 (7) | 0.476 (2) | 0.452 (2) | 0.131 (12)* | |
Atomic displacement parameters (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
S1 | 0.0653 (3) | 0.0488 (2) | 0.0318 (2) | −0.01859 (18) | −0.00912 (16) | 0.00317 (14) |
N1 | 0.0474 (6) | 0.0451 (6) | 0.0313 (5) | −0.0186 (5) | −0.0093 (5) | 0.0003 (5) |
C2 | 0.0362 (6) | 0.0383 (6) | 0.0323 (6) | −0.0095 (5) | −0.0031 (5) | 0.0002 (5) |
C21 | 0.0622 (9) | 0.0428 (8) | 0.0407 (7) | −0.0203 (7) | −0.0089 (6) | 0.0002 (6) |
C3 | 0.0311 (6) | 0.0389 (6) | 0.0331 (6) | −0.0081 (5) | −0.0035 (5) | −0.0003 (5) |
C31 | 0.0308 (6) | 0.0391 (7) | 0.0360 (6) | −0.0055 (5) | −0.0069 (5) | −0.0021 (5) |
O32 | 0.0320 (5) | 0.0764 (8) | 0.0505 (6) | −0.0124 (5) | −0.0131 (4) | 0.0060 (5) |
N33 | 0.0342 (6) | 0.0582 (7) | 0.0335 (6) | −0.0126 (5) | −0.0084 (4) | 0.0055 (5) |
C34 | 0.0570 (9) | 0.0655 (10) | 0.0350 (7) | −0.0143 (8) | −0.0078 (6) | 0.0078 (7) |
C4 | 0.0353 (6) | 0.0443 (7) | 0.0320 (6) | −0.0146 (5) | −0.0051 (5) | −0.0007 (5) |
N5 | 0.0490 (7) | 0.0484 (7) | 0.0318 (6) | −0.0231 (5) | −0.0021 (5) | 0.0010 (5) |
C6 | 0.0396 (7) | 0.0402 (7) | 0.0315 (6) | −0.0088 (5) | −0.0021 (5) | −0.0027 (5) |
C7 | 0.0448 (7) | 0.0394 (7) | 0.0367 (7) | −0.0173 (6) | −0.0010 (5) | 0.0003 (5) |
C8 | 0.0492 (8) | 0.0493 (9) | 0.0601 (10) | −0.0120 (7) | −0.0075 (7) | −0.0030 (7) |
C9 | 0.0564 (10) | 0.0506 (10) | 0.0914 (15) | −0.0049 (8) | 0.0065 (10) | 0.0007 (9) |
C10 | 0.0948 (15) | 0.0521 (10) | 0.0652 (12) | −0.0142 (10) | 0.0271 (11) | −0.0117 (9) |
C11 | 0.1112 (17) | 0.0625 (11) | 0.0417 (9) | −0.0176 (11) | 0.0057 (10) | −0.0116 (8) |
C12 | 0.0748 (11) | 0.0556 (9) | 0.0368 (8) | −0.0129 (8) | −0.0079 (7) | −0.0041 (7) |
O1W | 0.0640 (8) | 0.0603 (8) | 0.0913 (11) | −0.0215 (7) | −0.0097 (8) | 0.0136 (8) |
Geometric parameters (Å, º) top
S1—C6 | 1.6982 (14) | C4—N5 | 1.4657 (16) |
N1—C6 | 1.3422 (18) | C4—C7 | 1.5209 (19) |
N1—C2 | 1.4008 (16) | C4—H4 | 0.9800 |
N1—H1N | 0.8600 | N5—C6 | 1.3252 (18) |
C2—C3 | 1.3358 (18) | N5—H5N | 0.8600 |
C2—C21 | 1.4952 (19) | C7—C8 | 1.378 (2) |
C21—H21A | 0.9600 | C7—C12 | 1.387 (2) |
C21—H21B | 0.9600 | C8—C9 | 1.389 (3) |
C21—H21C | 0.9600 | C8—H8 | 0.9300 |
C3—C31 | 1.4912 (17) | C9—C10 | 1.368 (3) |
C3—C4 | 1.5137 (18) | C9—H9 | 0.9300 |
C31—O32 | 1.2326 (16) | C10—C11 | 1.364 (3) |
C31—N33 | 1.3299 (18) | C10—H10 | 0.9300 |
N33—C34 | 1.4499 (18) | C11—C12 | 1.383 (3) |
N33—H33N | 0.8600 | C11—H11 | 0.9300 |
C34—H34A | 0.9600 | C12—H12 | 0.9300 |
C34—H34B | 0.9600 | O1W—H1W | 0.886 (18) |
C34—H34C | 0.9600 | O1W—H2W | 0.844 (18) |
| | | |
C6—N1—C2 | 123.37 (11) | C3—C4—C7 | 111.27 (11) |
C6—N1—H1N | 118.3 | N5—C4—H4 | 108.0 |
C2—N1—H1N | 118.3 | C3—C4—H4 | 108.0 |
C3—C2—N1 | 119.28 (12) | C7—C4—H4 | 108.0 |
C3—C2—C21 | 127.80 (13) | C6—N5—C4 | 125.46 (11) |
N1—C2—C21 | 112.87 (11) | C6—N5—H5N | 117.3 |
C2—C21—H21A | 109.5 | C4—N5—H5N | 117.3 |
C2—C21—H21B | 109.5 | N5—C6—N1 | 117.38 (12) |
H21A—C21—H21B | 109.5 | N5—C6—S1 | 122.21 (11) |
C2—C21—H21C | 109.5 | N1—C6—S1 | 120.41 (10) |
H21A—C21—H21C | 109.5 | C8—C7—C12 | 118.84 (15) |
H21B—C21—H21C | 109.5 | C8—C7—C4 | 121.74 (13) |
C2—C3—C31 | 124.31 (12) | C12—C7—C4 | 119.41 (14) |
C2—C3—C4 | 120.96 (12) | C7—C8—C9 | 120.24 (18) |
C31—C3—C4 | 114.73 (11) | C7—C8—H8 | 119.9 |
O32—C31—N33 | 121.91 (13) | C9—C8—H8 | 119.9 |
O32—C31—C3 | 121.25 (12) | C10—C9—C8 | 120.34 (19) |
N33—C31—C3 | 116.77 (11) | C10—C9—H9 | 119.8 |
C31—N33—C34 | 122.21 (12) | C8—C9—H9 | 119.8 |
C31—N33—H33N | 118.9 | C11—C10—C9 | 119.83 (18) |
C34—N33—H33N | 118.9 | C11—C10—H10 | 120.1 |
N33—C34—H34A | 109.5 | C9—C10—H10 | 120.1 |
N33—C34—H34B | 109.5 | C10—C11—C12 | 120.50 (19) |
H34A—C34—H34B | 109.5 | C10—C11—H11 | 119.8 |
N33—C34—H34C | 109.5 | C12—C11—H11 | 119.8 |
H34A—C34—H34C | 109.5 | C11—C12—C7 | 120.25 (18) |
H34B—C34—H34C | 109.5 | C11—C12—H12 | 119.9 |
N5—C4—C3 | 109.98 (10) | C7—C12—H12 | 119.9 |
N5—C4—C7 | 111.55 (11) | H1W—O1W—H2W | 104 (3) |
| | | |
C6—N1—C2—C3 | −13.9 (2) | C7—C4—N5—C6 | 103.84 (16) |
C6—N1—C2—C21 | 163.75 (14) | C4—N5—C6—N1 | 10.2 (2) |
N1—C2—C3—C31 | −178.88 (12) | C4—N5—C6—S1 | −170.10 (11) |
C21—C2—C3—C31 | 3.9 (2) | C2—N1—C6—N5 | 8.3 (2) |
N1—C2—C3—C4 | 1.41 (19) | C2—N1—C6—S1 | −171.46 (10) |
C21—C2—C3—C4 | −175.86 (14) | N5—C4—C7—C8 | −31.61 (18) |
C2—C3—C31—O32 | −132.12 (15) | C3—C4—C7—C8 | 91.62 (16) |
C4—C3—C31—O32 | 47.60 (18) | N5—C4—C7—C12 | 149.30 (13) |
C2—C3—C31—N33 | 50.90 (19) | C3—C4—C7—C12 | −87.48 (16) |
C4—C3—C31—N33 | −129.37 (13) | C12—C7—C8—C9 | −0.2 (2) |
O32—C31—N33—C34 | 2.6 (2) | C4—C7—C8—C9 | −179.25 (14) |
C3—C31—N33—C34 | 179.52 (13) | C7—C8—C9—C10 | 0.0 (3) |
C2—C3—C4—N5 | 13.51 (18) | C8—C9—C10—C11 | 0.4 (3) |
C31—C3—C4—N5 | −166.23 (11) | C9—C10—C11—C12 | −0.6 (3) |
C2—C3—C4—C7 | −110.62 (14) | C10—C11—C12—C7 | 0.5 (3) |
C31—C3—C4—C7 | 69.64 (14) | C8—C7—C12—C11 | −0.1 (3) |
C3—C4—N5—C6 | −20.12 (19) | C4—C7—C12—C11 | 179.03 (16) |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
O1W—H1W···S1 | 0.88 (3) | 2.45 (3) | 3.2868 (18) | 157 (3) |
O1W—H2W···O1Wi | 0.84 (2) | 2.60 (3) | 3.014 (3) | 112 (3) |
O1W—H2W···S1ii | 0.84 (2) | 2.70 (2) | 3.4708 (15) | 153 (3) |
N1—H1N···S1iii | 0.86 | 2.62 | 3.4499 (12) | 164 |
N5—H5N···O1Wiv | 0.86 | 2.03 | 2.8791 (19) | 171 |
N33—H33N···O32v | 0.86 | 2.04 | 2.8788 (15) | 164 |
C8—H8···O1W | 0.93 | 2.53 | 3.391 (2) | 153 |
C21—H21A···N33 | 0.96 | 2.56 | 3.138 (2) | 119 |
Symmetry codes: (i) −x+2, −y+1, −z+1; (ii) −x+1, −y+1, −z+1; (iii) −x+1, −y+2, −z+1; (iv) x−1, y, z; (v) x+1, y, z. |
(II) 4-(4-chlorophenyl)-6-methyl-5-(
N-methylcarbamoyl)-1,2,3,4-dihydropyrimidine- 2-thione monohydrate
top
Crystal data top
C13H14ClN3OS·H2O | Z = 2 |
Mr = 313.8 | F(000) = 328 |
Triclinic, P1 | Dx = 1.408 Mg m−3 |
Hall symbol: -P 1 | Mo Kα radiation, λ = 0.71073 Å |
a = 4.8853 (3) Å | Cell parameters from 4058 reflections |
b = 9.7093 (7) Å | θ = 2.3–29.4° |
c = 16.0343 (11) Å | µ = 0.40 mm−1 |
α = 79.506 (1)° | T = 273 K |
β = 84.792 (1)° | Plate, colorless |
γ = 82.834 (1)° | 0.18 × 0.15 × 0.08 mm |
V = 740.18 (9) Å3 | |
Data collection top
CCD Area Detector diffractometer | 2988 reflections with I > 2σ(I) |
Radiation source: fine-focus sealed tube | Rint = 0.023 |
Graphite monochromator | θmax = 28.0°, θmin = 2.2° |
ω scan | h = −6→6 |
8550 measured reflections | k = −12→12 |
3391 independent reflections | l = −21→20 |
Refinement top
Refinement on F2 | 2 restraints |
Least-squares matrix: full | H-atom parameters constrained |
R[F2 > 2σ(F2)] = 0.055 | w = 1/[σ2(Fo2) + (0.0789P)2 + 0.438P] where P = (Fo2 + 2Fc2)/3 |
wR(F2) = 0.150 | (Δ/σ)max < 0.001 |
S = 1.09 | Δρmax = 0.68 e Å−3 |
3391 reflections | Δρmin = −0.46 e Å−3 |
183 parameters | |
Crystal data top
C13H14ClN3OS·H2O | γ = 82.834 (1)° |
Mr = 313.8 | V = 740.18 (9) Å3 |
Triclinic, P1 | Z = 2 |
a = 4.8853 (3) Å | Mo Kα radiation |
b = 9.7093 (7) Å | µ = 0.40 mm−1 |
c = 16.0343 (11) Å | T = 273 K |
α = 79.506 (1)° | 0.18 × 0.15 × 0.08 mm |
β = 84.792 (1)° | |
Data collection top
CCD Area Detector diffractometer | 2988 reflections with I > 2σ(I) |
8550 measured reflections | Rint = 0.023 |
3391 independent reflections | |
Refinement top
R[F2 > 2σ(F2)] = 0.055 | 2 restraints |
wR(F2) = 0.150 | H-atom parameters constrained |
S = 1.09 | Δρmax = 0.68 e Å−3 |
3391 reflections | Δρmin = −0.46 e Å−3 |
183 parameters | |
Special details top
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. |
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top | x | y | z | Uiso*/Ueq | |
Cl1 | 0.75794 (19) | 0.41129 (8) | 0.11627 (6) | 0.0814 (3) | |
S1 | 0.25270 (16) | 0.81350 (8) | 0.53336 (4) | 0.0596 (2) | |
N1 | 0.3387 (4) | 0.9822 (2) | 0.38652 (11) | 0.0434 (4) | |
H1 | 0.4623 | 1.0126 | 0.4112 | 0.052* | |
C2 | 0.2788 (4) | 1.0501 (2) | 0.30423 (12) | 0.0366 (4) | |
C3 | 0.1422 (4) | 0.9851 (2) | 0.25714 (12) | 0.0341 (4) | |
C4 | 0.0499 (4) | 0.8417 (2) | 0.29214 (12) | 0.0381 (4) | |
H4 | −0.1418 | 0.8435 | 0.2782 | 0.046* | |
N5 | 0.0548 (4) | 0.8141 (2) | 0.38475 (11) | 0.0436 (4) | |
H5 | −0.0528 | 0.7557 | 0.4130 | 0.052* | |
C6 | 0.2132 (4) | 0.8724 (2) | 0.42864 (13) | 0.0416 (5) | |
C7 | 0.2244 (4) | 0.7272 (2) | 0.25137 (13) | 0.0381 (4) | |
C8 | 0.4407 (5) | 0.6419 (2) | 0.29067 (15) | 0.0469 (5) | |
H8 | 0.4764 | 0.6505 | 0.3454 | 0.056* | |
C9 | 0.6045 (6) | 0.5440 (3) | 0.25009 (18) | 0.0561 (6) | |
H9 | 0.7493 | 0.4870 | 0.2771 | 0.067* | |
C10 | 0.5499 (6) | 0.5322 (2) | 0.16902 (16) | 0.0530 (6) | |
C11 | 0.3337 (6) | 0.6135 (3) | 0.12904 (15) | 0.0552 (6) | |
H11 | 0.2972 | 0.6034 | 0.0747 | 0.066* | |
C12 | 0.1715 (5) | 0.7100 (3) | 0.17028 (14) | 0.0494 (5) | |
H12 | 0.0238 | 0.7648 | 0.1435 | 0.059* | |
C21 | 0.3697 (5) | 1.1941 (2) | 0.28217 (14) | 0.0482 (5) | |
H21A | 0.2982 | 1.2410 | 0.2293 | 0.072* | |
H21B | 0.5681 | 1.1870 | 0.2768 | 0.072* | |
H21C | 0.3014 | 1.2471 | 0.3262 | 0.072* | |
C31 | 0.0694 (4) | 1.0440 (2) | 0.16846 (12) | 0.0347 (4) | |
O32 | −0.1642 (3) | 1.03907 (19) | 0.14632 (10) | 0.0500 (4) | |
N33 | 0.2700 (3) | 1.0941 (2) | 0.11453 (10) | 0.0406 (4) | |
H33 | 0.4316 | 1.0905 | 0.1326 | 0.049* | |
C34 | 0.2285 (5) | 1.1544 (3) | 0.02662 (14) | 0.0537 (6) | |
H34A | 0.0875 | 1.1101 | 0.0070 | 0.081* | |
H34B | 0.3982 | 1.1395 | −0.0074 | 0.081* | |
H34C | 0.1724 | 1.2537 | 0.0219 | 0.081* | |
O1W | 0.7517 (6) | 0.5760 (3) | 0.4771 (2) | 0.1086 (9) | |
H1W | 0.6269 | 0.6372 | 0.4936 | 0.080* | |
H2W | 0.8231 | 0.5560 | 0.5254 | 0.080* | |
Atomic displacement parameters (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
Cl1 | 0.0999 (6) | 0.0593 (4) | 0.0844 (6) | −0.0026 (4) | 0.0235 (4) | −0.0298 (4) |
S1 | 0.0812 (5) | 0.0698 (4) | 0.0302 (3) | −0.0246 (3) | −0.0066 (3) | −0.0026 (3) |
N1 | 0.0492 (10) | 0.0541 (11) | 0.0311 (8) | −0.0182 (8) | −0.0069 (7) | −0.0082 (7) |
C2 | 0.0361 (10) | 0.0436 (11) | 0.0312 (9) | −0.0061 (8) | −0.0010 (7) | −0.0084 (8) |
C21 | 0.0615 (14) | 0.0475 (12) | 0.0396 (11) | −0.0174 (11) | −0.0039 (10) | −0.0106 (9) |
C3 | 0.0287 (9) | 0.0421 (10) | 0.0327 (9) | −0.0047 (7) | −0.0013 (7) | −0.0089 (8) |
C31 | 0.0288 (9) | 0.0406 (10) | 0.0358 (10) | 0.0007 (7) | −0.0062 (7) | −0.0106 (8) |
O32 | 0.0291 (7) | 0.0704 (11) | 0.0519 (9) | −0.0047 (7) | −0.0112 (6) | −0.0104 (8) |
N33 | 0.0304 (8) | 0.0590 (11) | 0.0318 (8) | −0.0046 (7) | −0.0066 (6) | −0.0048 (7) |
C34 | 0.0542 (14) | 0.0693 (16) | 0.0349 (11) | −0.0045 (12) | −0.0057 (10) | −0.0022 (10) |
C4 | 0.0351 (10) | 0.0494 (12) | 0.0327 (10) | −0.0128 (8) | −0.0032 (7) | −0.0084 (8) |
N5 | 0.0491 (10) | 0.0528 (11) | 0.0320 (9) | −0.0206 (8) | 0.0034 (7) | −0.0082 (7) |
C6 | 0.0447 (11) | 0.0488 (12) | 0.0322 (10) | −0.0072 (9) | 0.0000 (8) | −0.0090 (8) |
C7 | 0.0436 (11) | 0.0378 (10) | 0.0348 (10) | −0.0140 (8) | −0.0014 (8) | −0.0057 (8) |
C8 | 0.0530 (13) | 0.0487 (12) | 0.0417 (11) | −0.0096 (10) | −0.0086 (9) | −0.0098 (9) |
C9 | 0.0604 (15) | 0.0463 (13) | 0.0613 (15) | −0.0025 (11) | −0.0077 (12) | −0.0091 (11) |
C10 | 0.0678 (15) | 0.0386 (11) | 0.0539 (14) | −0.0149 (11) | 0.0129 (12) | −0.0136 (10) |
C11 | 0.0780 (17) | 0.0532 (14) | 0.0380 (11) | −0.0148 (12) | 0.0003 (11) | −0.0143 (10) |
C12 | 0.0606 (14) | 0.0516 (13) | 0.0380 (11) | −0.0058 (11) | −0.0101 (10) | −0.0100 (9) |
O1W | 0.0989 (19) | 0.0979 (19) | 0.120 (2) | −0.0142 (15) | −0.0207 (17) | 0.0125 (17) |
Geometric parameters (Å, º) top
Cl1—C10 | 1.742 (2) | C34—H34C | 0.9600 |
S1—C6 | 1.693 (2) | C4—N5 | 1.462 (2) |
N1—C6 | 1.340 (3) | C4—C7 | 1.522 (3) |
N1—C2 | 1.402 (3) | C4—H4 | 0.9800 |
N1—H1 | 0.8600 | N5—C6 | 1.329 (3) |
C2—C3 | 1.336 (3) | N5—H5 | 0.8600 |
C2—C21 | 1.491 (3) | C7—C8 | 1.383 (3) |
C21—H21A | 0.9600 | C7—C12 | 1.392 (3) |
C21—H21B | 0.9600 | C8—C9 | 1.381 (3) |
C21—H21C | 0.9600 | C8—H8 | 0.9300 |
C3—C31 | 1.490 (3) | C9—C10 | 1.378 (4) |
C3—C4 | 1.510 (3) | C9—H9 | 0.9300 |
C31—O32 | 1.235 (2) | C10—C11 | 1.371 (4) |
C31—N33 | 1.325 (3) | C11—C12 | 1.375 (3) |
N33—C34 | 1.447 (3) | C11—H11 | 0.9300 |
N33—H33 | 0.8600 | C12—H12 | 0.9300 |
C34—H34A | 0.9600 | O1W—H1W | 0.86 |
C34—H34B | 0.9600 | O1W—H2W | 0.86 |
| | | |
C6—N1—C2 | 123.36 (18) | C3—C4—C7 | 111.22 (16) |
C6—N1—H1 | 118.3 | N5—C4—H4 | 107.9 |
C2—N1—H1 | 118.3 | C3—C4—H4 | 107.9 |
C3—C2—N1 | 118.88 (19) | C7—C4—H4 | 107.9 |
C3—C2—C21 | 127.93 (19) | C6—N5—C4 | 124.90 (18) |
N1—C2—C21 | 113.13 (17) | C6—N5—H5 | 117.5 |
C2—C21—H21A | 109.5 | C4—N5—H5 | 117.5 |
C2—C21—H21B | 109.5 | N5—C6—N1 | 116.97 (18) |
H21A—C21—H21B | 109.5 | N5—C6—S1 | 122.10 (17) |
C2—C21—H21C | 109.5 | N1—C6—S1 | 120.92 (16) |
H21A—C21—H21C | 109.5 | C8—C7—C12 | 118.3 (2) |
H21B—C21—H21C | 109.5 | C8—C7—C4 | 122.56 (18) |
C2—C3—C31 | 124.41 (18) | C12—C7—C4 | 119.13 (19) |
C2—C3—C4 | 120.74 (18) | C9—C8—C7 | 121.1 (2) |
C31—C3—C4 | 114.85 (16) | C9—C8—H8 | 119.4 |
O32—C31—N33 | 122.35 (19) | C7—C8—H8 | 119.4 |
O32—C31—C3 | 120.64 (18) | C10—C9—C8 | 119.0 (2) |
N33—C31—C3 | 116.91 (16) | C10—C9—H9 | 120.5 |
C31—N33—C34 | 122.80 (17) | C8—C9—H9 | 120.5 |
C31—N33—H33 | 118.6 | C11—C10—C9 | 121.2 (2) |
C34—N33—H33 | 118.6 | C11—C10—Cl1 | 119.2 (2) |
N33—C34—H34A | 109.5 | C9—C10—Cl1 | 119.6 (2) |
N33—C34—H34B | 109.5 | C10—C11—C12 | 119.2 (2) |
H34A—C34—H34B | 109.5 | C10—C11—H11 | 120.4 |
N33—C34—H34C | 109.5 | C12—C11—H11 | 120.4 |
H34A—C34—H34C | 109.5 | C11—C12—C7 | 121.2 (2) |
H34B—C34—H34C | 109.5 | C11—C12—H12 | 119.4 |
N5—C4—C3 | 109.68 (16) | C7—C12—H12 | 119.4 |
N5—C4—C7 | 112.14 (17) | H1W—O1W—H2W | 93.4 |
| | | |
C6—N1—C2—C3 | −16.4 (3) | C4—N5—C6—N1 | 12.6 (3) |
C6—N1—C2—C21 | 160.8 (2) | C4—N5—C6—S1 | −168.37 (17) |
N1—C2—C3—C31 | −178.96 (18) | C2—N1—C6—N5 | 9.9 (3) |
C21—C2—C3—C31 | 4.2 (3) | C2—N1—C6—S1 | −169.13 (16) |
N1—C2—C3—C4 | 0.8 (3) | N5—C4—C7—C8 | −23.7 (3) |
C21—C2—C3—C4 | −176.0 (2) | C3—C4—C7—C8 | 99.5 (2) |
C2—C3—C31—O32 | −134.9 (2) | N5—C4—C7—C12 | 158.35 (19) |
C4—C3—C31—O32 | 45.3 (3) | C3—C4—C7—C12 | −78.4 (2) |
C2—C3—C31—N33 | 48.6 (3) | C12—C7—C8—C9 | 1.4 (3) |
C4—C3—C31—N33 | −131.18 (19) | C4—C7—C8—C9 | −176.5 (2) |
O32—C31—N33—C34 | 3.6 (3) | C7—C8—C9—C10 | 0.1 (4) |
C3—C31—N33—C34 | −179.9 (2) | C8—C9—C10—C11 | −1.4 (4) |
C2—C3—C4—N5 | 17.3 (3) | C8—C9—C10—Cl1 | 178.97 (19) |
C31—C3—C4—N5 | −162.85 (16) | C9—C10—C11—C12 | 1.1 (4) |
C2—C3—C4—C7 | −107.3 (2) | Cl1—C10—C11—C12 | −179.26 (19) |
C31—C3—C4—C7 | 72.5 (2) | C10—C11—C12—C7 | 0.5 (4) |
C3—C4—N5—C6 | −25.1 (3) | C8—C7—C12—C11 | −1.7 (4) |
C7—C4—N5—C6 | 99.0 (2) | C4—C7—C12—C11 | 176.3 (2) |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
O1W—H1W···S1 | 0.86 | 2.47 | 3.321 (3) | 177 |
O1W—H2W···O1Wi | 0.86 | 2.30 | 2.764 (4) | 114 |
N1—H1···S1ii | 0.86 | 2.63 | 3.457 (2) | 161 |
N5—H5···O1Wiii | 0.86 | 2.14 | 2.990 (4) | 167 |
N33—H33···O32iv | 0.86 | 2.00 | 2.824 (2) | 161 |
C8—H8···O1W | 0.93 | 2.55 | 3.397 (4) | 151 |
C21—H21A···N(33) | 0.96 | 2.55 | 3.116 (3) | 118 |
Symmetry codes: (i) −x+2, −y+1, −z+1; (ii) −x+1, −y+2, −z+1; (iii) x−1, y, z; (iv) x+1, y, z. |
Experimental details
| (I) | (II) |
Crystal data |
Chemical formula | C13H15N3OS·H2O | C13H14ClN3OS·H2O |
Mr | 279.36 | 313.8 |
Crystal system, space group | Triclinic, P1 | Triclinic, P1 |
Temperature (K) | 273 | 273 |
a, b, c (Å) | 5.0116 (3), 8.9507 (6), 16.0882 (11) | 4.8853 (3), 9.7093 (7), 16.0343 (11) |
α, β, γ (°) | 86.095 (1), 84.841 (1), 78.241 (1) | 79.506 (1), 84.792 (1), 82.834 (1) |
V (Å3) | 702.75 (8) | 740.18 (9) |
Z | 2 | 2 |
Radiation type | Mo Kα | Mo Kα |
µ (mm−1) | 0.23 | 0.40 |
Crystal size (mm) | 0.20 × 0.15 × 0.10 | 0.18 × 0.15 × 0.08 |
|
Data collection |
Diffractometer | CCD Area Detector diffractometer | CCD Area Detector diffractometer |
Absorption correction | – | – |
No. of measured, independent and observed [I > 2σ(I)] reflections | 8102, 3227, 2971 | 8550, 3391, 2988 |
Rint | 0.017 | 0.023 |
(sin θ/λ)max (Å−1) | 0.661 | 0.660 |
|
Refinement |
R[F2 > 2σ(F2)], wR(F2), S | 0.041, 0.115, 1.05 | 0.055, 0.150, 1.09 |
No. of reflections | 3227 | 3391 |
No. of parameters | 182 | 183 |
No. of restraints | 2 | 2 |
H-atom treatment | H atoms treated by a mixture of independent and constrained refinement | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.24, −0.24 | 0.68, −0.46 |
Selected geometric parameters (Å, º) for (I) topN1—C6 | 1.3422 (18) | C31—O32 | 1.2326 (16) |
N1—C2 | 1.4008 (16) | C31—N33 | 1.3299 (18) |
C2—C3 | 1.3358 (18) | C4—N5 | 1.4657 (16) |
C3—C4 | 1.5137 (18) | N5—C6 | 1.3252 (18) |
| | | |
C6—N1—C2—C3 | −13.9 (2) | C3—C4—N5—C6 | −20.12 (19) |
C2—C3—C4—N5 | 13.51 (18) | C2—N1—C6—N5 | 8.3 (2) |
Hydrogen-bond geometry (Å, º) for (I) top
D—H···A | D—H | H···A | D···A | D—H···A |
O1W—H1W···S1 | 0.88 (3) | 2.45 (3) | 3.2868 (18) | 157 (3) |
O1W—H2W···O1Wi | 0.84 (2) | 2.60 (3) | 3.014 (3) | 112 (3) |
O1W—H2W···S1ii | 0.84 (2) | 2.70 (2) | 3.4708 (15) | 153 (3) |
N1—H1N···S1iii | 0.86 | 2.62 | 3.4499 (12) | 164 |
N5—H5N···O1Wiv | 0.86 | 2.03 | 2.8791 (19) | 171 |
N33—H33N···O32v | 0.86 | 2.04 | 2.8788 (15) | 164 |
C8—H8···O1W | 0.93 | 2.53 | 3.391 (2) | 153 |
C21—H21A···N33 | 0.96 | 2.56 | 3.138 (2) | 119 |
Symmetry codes: (i) −x+2, −y+1, −z+1; (ii) −x+1, −y+1, −z+1; (iii) −x+1, −y+2, −z+1; (iv) x−1, y, z; (v) x+1, y, z. |
Selected geometric parameters (Å, º) for (II) topCl1—C10 | 1.742 (2) | C3—C4 | 1.510 (3) |
N1—C6 | 1.340 (3) | C31—O32 | 1.235 (2) |
N1—C2 | 1.402 (3) | C31—N33 | 1.325 (3) |
C2—C3 | 1.336 (3) | C4—N5 | 1.462 (2) |
| | | |
C6—N1—C2—C3 | −16.4 (3) | C3—C4—N5—C6 | −25.1 (3) |
C2—C3—C4—N5 | 17.3 (3) | C2—N1—C6—N5 | 9.9 (3) |
Hydrogen-bond geometry (Å, º) for (II) top
D—H···A | D—H | H···A | D···A | D—H···A |
O1W—H1W···S1 | 0.86 | 2.47 | 3.321 (3) | 177 |
O1W—H2W···O1Wi | 0.86 | 2.30 | 2.764 (4) | 114 |
N1—H1···S1ii | 0.86 | 2.63 | 3.457 (2) | 161 |
N5—H5···O1Wiii | 0.86 | 2.14 | 2.990 (4) | 167 |
N33—H33···O32iv | 0.86 | 2.00 | 2.824 (2) | 161 |
C8—H8···O1W | 0.93 | 2.55 | 3.397 (4) | 151 |
C21—H21A···N(33) | 0.96 | 2.55 | 3.116 (3) | 118 |
Symmetry codes: (i) −x+2, −y+1, −z+1; (ii) −x+1, −y+2, −z+1; (iii) x−1, y, z; (iv) x+1, y, z. |
Pyrimidines, being critical components of naturally occurring nucleic acid, are an integral part of medically important compounds including antiviral, antitumour and cardiovascular agents (Atwal et al., 1989). Owing to their biological importance, these compounds have been the focus of synthetic activity during the past few years (Weis & van der Plas, 1986). The structural relation and potential mimicking of the clinically important dihydropyridine (DHP) calcium channel blockers led us to studies of substituted 1,4-dihydropyrimidines (DHPMs). Furthermore, being inherently asymmetric, dihydropyrimidines provide an opportunity to study the effect of chirality on biological activity. To gain insight into the conformational aspect of various substitutions at the phenyl ring as well as to obtain the possible relationship between structure and activity, an X-ray study of a series of phenyl substituted 1,4-dihydropyrimidines – having a novel carbamoyl group at C3 and a thione group at C6 of the dihydropyrimidine ring – has been undertaken. We report here the crystal and molecular structures of 1,4-dihydro-6-methyl-5-N-methyl carbamoyl-4-phenyl-2(3H)- pyrimidinethione, (I), and 1,4-dihydro-6-methyl-5-N– methyl carbamoyl-4-(4'-chlorophenyl-2(3H)-pyrimidinethione), (II).
In all essential details, the geometry of the molecules (Figs. 1 and 2) in terms of interatomic distances and angles are in good agreement with those in similar structures (Kojic-Prodic et al., 1976; Sulmon et al., 1989; Chandra Mohan et al., 2003). The two compounds are isomorphous, both crystallizing as a monohydrate in the centrosymmetrical space group P1. An r.m.s overlay (pyrimidine plane; r.m.s deviation 0.019 Å) of the two compounds shows significant similarities (Fig. 3), differing only at the periphery of the phenyl ring. The DPHM in both the structures exist more or less in a flattened boat-like conformation [DS(C4)=0.041 (1) for (I) and DS(C4)= 0.048 (1) for (II) (Nardelli, 1983)] with atom N1 and C4 defining the stern and bow positions. Atoms N1 and C4 lie 0.113 (1) and 0.204 (1) Å in (I), and 0.137 (2) and 0.255 (2) Å in (II), respectively, from the least-squares plane defined by the remaining four atoms (C2, C3, N5 and C6) of the DPHM ring. A similar type of conformation was observed in another DPHM (Atwal et al., 1990; Kappe et al., 1997). In both the structures, the torsion angles about the C4-atom ring bonds are greater than those for the N1-atom bonds, indicating that the puckering is more influenced at atom C4. The DPHM ring exists in the thione form; the C6—S1 distance [1.698 (1) in (I) and 1.693 (2) Å in (II)] essentially has double-bond character (Trinajstic, 1968). In addition, this C—S distance in both the structures is longer than 1.61 Å, the distance expected for a C=S double bond (Pauling, 1960). A similar lengthening has been reported and discussed as due to the substantial hydrogen bonding involving the S atom (Tiekink, 1989). It can been seen in both the structures that the S atom participates in a network of hydrogen bonds.
The carbamoyl side chain in both the structures is in a fully extended conformation with C3—C31—N33—-C34 torsion angles of 179.5 (1) [for (I)] and −179.9 (2)° [for (II)]. The spatial arrangement of the carbonyl group at atom C3 adopts an anticlinal (ac) orientation about the C3—C31 bond in both structures [C2—C3—C31—O32 = −132.1 (2)° in (I) and −134.9 (2)° in (II)]. This orientation may probably be attributed to intermolecular N—H···O hydrogen bonding involving the above-mentioned carbonyl oxygen O32 atom.
The phenyl ring in both structures is significantly planar within experimental limits. It is oriented perpendicular to the DHPM ring system [C3—C4—C7—C8 = 91.6 (2)° in (I) and 99.5 (2)° in (II)]. Furthermore, the phenyl ring is positioned pseudoaxially [107.2 (1) in (I) and 103.2 (2)° in (II), as defined by the average magnitude of the C2—C3—C4—C7 and C6—N5—C4—C7 torsion angles], with respect to the C4 position of the DPHM ring.
Triggle et al. (1989), on the basis of three-dimensional structural characteristics important for calcium channel antagonist activity in DPH, proposed that a flattened boat conformation of DHP with the phenyl ring in a pseudoaxial position and a near perpendicular orientation of the phenyl ring with respect to the DHP ring corresponds to high activity. Viewing the DHPM structures of (I) and (II), a striking similarity in conformational features is observed, suggesting that these compounds may be potential mimics of prototypical DHP calcium channel blockers. Owing to a lack of pharmacological data, such a conclusion is speculation? at this stage.
A packing diagram of (I) only is shown in Fig. 4, since the compounds are isostructural. The molecules exist as dimers utilizing N—H···S hydrogen bonds (Tables 2 and 4) between centrosymmetrically related molecules described by an R22(8) ring motif. The most striking feature in the crystal packing is the hydrogen-bonding network formed by the water molecule, which is present in both the structures. The water molecule links the dimers into infinite chains along the a axis via OW—H···S and N—H···OW hydrogen bonds, thereby acting as a donor and an acceptor. Furthermore, the water molecule interlinks the dimer chain along the b axis via OW—H···S hydrogen bonds. Interestingly, the water molecule also forms a dimer with its centrosymmetric counterpart via an OW—H···OW hydrogen bond running parallel to the a axis. The carbamoyl side chains are self-linked with the N—H···O hydrogen bond. In addition, a possible bifurcated hydrogen bond is observed in (I), between the water mlecule and the S atom, while in (II) the distance between the S atom and the water molecule is 3.818 (3) Å. The hydrogen-bond networks thus formed facilitate alternate hydrophobic and hydrophilic environments in the crystal packing. Possible weak C—H···O and C—H···N interactions are also seen in both structures.