organic compounds
Ethyl 6-methyl-4-[2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiophen-3-yl]-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate
aDepartment of Chemistry, University of New Brunswick, Fredericton, NB, Canada E3B 6E2, and bDepartment of Chemistry, Mount Allison University, 63C York Street, Sackville, NB, Canada E4L 1G8
*Correspondence e-mail: adecken@unb.ca
A new Biginelli compound, C18H25BN2O4S2, containing a boronate ester group was synthesized from a lithium bromide-catalysed reaction. The compound crystallizes with two independent molecules in the that differ mainly in the conformation of the ester functionality. The is stabilized by intermolecular N—H⋯O and N—H⋯S hydrogen bonds involving the 3,4-dihydropyrimidine-2(1H)-thione NH groups as donors and the carbonyl O and thiophene S atoms as acceptors.
Related literature
Blacquiere et al. (2005) report on previously studied boronic acid Ugi compounds. Miyaura & Suzuki (1995) give an excellent review on the Suzuki–Miyaura cross-coupling reaction of aryl halides with organoboron derivatives. Vogels et al. (2006) describe the synthesis and characterization of aryl boronate derived from aniline. Yang et al. (2003) highlight recent advances of boron chemistry in medicinal research.
Experimental
Crystal data
|
Refinement
|
Data collection: SMART (Bruker, 1999); cell SMART; data reduction: SAINT (Bruker, 2006); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL.
Supporting information
10.1107/S1600536808005965/gk2133sup1.cif
contains datablocks I, global. DOI:Structure factors: contains datablock I. DOI: 10.1107/S1600536808005965/gk2133Isup2.hkl
2-(4,4,5,5-Tetramethyl-1,3,2,-dioxaborolan-3-yl)thiophenecarboxaldehyde (548 mg, 2.30 mmol), ethyl acetoacetate (456 mg, 3.50 mmol) and thiourea (266 mg, 3.49 mmol) were added together with CH3CN (15 ml) and a catalytic amount of lithium bromide (40 mg, 0.46 mmol). The reaction was heated at reflux for 60 h. The solvent was reduced to 5 ml and allowed to stand at room temperature. The title compound precipitated as colourless crystals. Yield: 740 mg (79%); m.p. 469 – 471 K.
Hydrogen atoms were included in calculated positions at distances of 0.88 (NH), 0.95 (CH-sp2), 0.98 (CH3), 0.99 (CH2), and 1.0 Å (CH-sp3) from the parent atom and refined using a riding model. Ueq were 1.5 times of the parent atom for CH3 hydrogen atoms and 1.2 times for all remaining hydrogen atoms.
Data collection: SMART (Bruker, 1999); cell
SMART (Bruker, 1999); data reduction: SAINT (Bruker, 2006); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).Fig. 1. Molecular structure of the title compound with displacement ellipsoids drawn at the 50% probability level. H atoms have been omitted. |
C18H25BN2O4S2 | Z = 4 |
Mr = 408.33 | F(000) = 864 |
Triclinic, P1 | Dx = 1.300 Mg m−3 |
Hall symbol: -P 1 | Mo Kα radiation, λ = 0.71073 Å |
a = 11.9274 (17) Å | Cell parameters from 5490 reflections |
b = 13.5021 (19) Å | θ = 2.7–28.5° |
c = 15.225 (2) Å | µ = 0.28 mm−1 |
α = 112.172 (2)° | T = 173 K |
β = 93.531 (2)° | Irregular, colourless |
γ = 109.706 (2)° | 0.6 × 0.6 × 0.4 mm |
V = 2086.9 (5) Å3 |
Bruker SMART1000/P4 diffractometer | 9077 independent reflections |
Radiation source: fine-focus sealed tube | 7758 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.017 |
ϕ and ω scans | θmax = 27.5°, θmin = 1.8° |
Absorption correction: multi-scan (SADABS; Sheldrick, 1997) | h = −15→15 |
Tmin = 0.850, Tmax = 0.896 | k = −16→17 |
14611 measured reflections | l = −19→19 |
Refinement on F2 | Primary atom site location: structure-invariant direct methods |
Least-squares matrix: full | Secondary atom site location: difference Fourier map |
R[F2 > 2σ(F2)] = 0.040 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.113 | H-atom parameters constrained |
S = 1.04 | w = 1/[σ2(Fo2) + (0.061P)2 + 0.8428P] where P = (Fo2 + 2Fc2)/3 |
9077 reflections | (Δ/σ)max = 0.001 |
499 parameters | Δρmax = 0.51 e Å−3 |
0 restraints | Δρmin = −0.41 e Å−3 |
C18H25BN2O4S2 | γ = 109.706 (2)° |
Mr = 408.33 | V = 2086.9 (5) Å3 |
Triclinic, P1 | Z = 4 |
a = 11.9274 (17) Å | Mo Kα radiation |
b = 13.5021 (19) Å | µ = 0.28 mm−1 |
c = 15.225 (2) Å | T = 173 K |
α = 112.172 (2)° | 0.6 × 0.6 × 0.4 mm |
β = 93.531 (2)° |
Bruker SMART1000/P4 diffractometer | 9077 independent reflections |
Absorption correction: multi-scan (SADABS; Sheldrick, 1997) | 7758 reflections with I > 2σ(I) |
Tmin = 0.850, Tmax = 0.896 | Rint = 0.017 |
14611 measured reflections |
R[F2 > 2σ(F2)] = 0.040 | 0 restraints |
wR(F2) = 0.113 | H-atom parameters constrained |
S = 1.04 | Δρmax = 0.51 e Å−3 |
9077 reflections | Δρmin = −0.41 e Å−3 |
499 parameters |
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. |
x | y | z | Uiso*/Ueq | ||
B1 | 0.58518 (16) | 0.09209 (15) | 0.27239 (12) | 0.0268 (3) | |
O1 | 0.61743 (12) | 0.02062 (10) | 0.30254 (8) | 0.0377 (3) | |
O2 | 0.55784 (13) | 0.05290 (10) | 0.17436 (8) | 0.0392 (3) | |
C1 | 0.57648 (13) | 0.20455 (12) | 0.34609 (10) | 0.0241 (3) | |
C2 | 0.53195 (13) | 0.27993 (12) | 0.33090 (10) | 0.0230 (3) | |
C3 | 0.52890 (16) | 0.36718 (14) | 0.41845 (11) | 0.0324 (3) | |
H3 | 0.5002 | 0.4255 | 0.4207 | 0.039* | |
C4 | 0.57164 (17) | 0.35812 (14) | 0.49885 (11) | 0.0346 (4) | |
H4 | 0.5762 | 0.4091 | 0.5635 | 0.042* | |
C5 | 0.48905 (13) | 0.27052 (12) | 0.23100 (10) | 0.0232 (3) | |
H5 | 0.5127 | 0.2116 | 0.1819 | 0.028* | |
N6 | 0.35516 (12) | 0.23074 (11) | 0.20829 (9) | 0.0274 (3) | |
H6 | 0.3125 | 0.1567 | 0.1918 | 0.033* | |
C7 | 0.29331 (14) | 0.29623 (13) | 0.21037 (10) | 0.0271 (3) | |
N8 | 0.36068 (13) | 0.40921 (12) | 0.22901 (10) | 0.0324 (3) | |
H8 | 0.3244 | 0.4585 | 0.2442 | 0.039* | |
C9 | 0.48338 (15) | 0.45081 (13) | 0.22532 (11) | 0.0296 (3) | |
C10 | 0.54748 (14) | 0.38534 (13) | 0.22401 (10) | 0.0262 (3) | |
C11 | 0.59061 (18) | −0.08779 (14) | 0.21602 (12) | 0.0366 (4) | |
C12 | 0.5912 (2) | −0.04760 (16) | 0.13318 (13) | 0.0435 (5) | |
C13 | 0.4647 (2) | −0.17160 (18) | 0.21154 (18) | 0.0577 (6) | |
H13A | 0.4638 | −0.1794 | 0.2729 | 0.086* | |
H13B | 0.4460 | −0.2477 | 0.1580 | 0.086* | |
H13C | 0.4035 | −0.1415 | 0.2008 | 0.086* | |
C14 | 0.6837 (2) | −0.13695 (18) | 0.22800 (16) | 0.0526 (5) | |
H14A | 0.7657 | −0.0798 | 0.2377 | 0.079* | |
H14B | 0.6682 | −0.2079 | 0.1696 | 0.079* | |
H14C | 0.6778 | −0.1551 | 0.2845 | 0.079* | |
C15 | 0.5030 (3) | −0.1337 (2) | 0.03940 (16) | 0.0806 (10) | |
H15A | 0.4195 | −0.1507 | 0.0496 | 0.121* | |
H15B | 0.5180 | −0.2053 | 0.0159 | 0.121* | |
H15C | 0.5136 | −0.1013 | −0.0088 | 0.121* | |
C16 | 0.7206 (3) | −0.0007 (2) | 0.1157 (2) | 0.0859 (10) | |
H16A | 0.7208 | 0.0386 | 0.0732 | 0.129* | |
H16B | 0.7460 | −0.0654 | 0.0850 | 0.129* | |
H16C | 0.7775 | 0.0545 | 0.1780 | 0.129* | |
C17 | 0.52927 (18) | 0.56795 (15) | 0.22327 (14) | 0.0409 (4) | |
H17A | 0.5924 | 0.6242 | 0.2819 | 0.061* | |
H17B | 0.4616 | 0.5932 | 0.2209 | 0.061* | |
H17C | 0.5637 | 0.5629 | 0.1657 | 0.061* | |
C18 | 0.67612 (15) | 0.42200 (14) | 0.21689 (11) | 0.0305 (3) | |
O19 | 0.74306 (12) | 0.51853 (11) | 0.22815 (9) | 0.0418 (3) | |
O20 | 0.71312 (11) | 0.33367 (11) | 0.19778 (9) | 0.0371 (3) | |
C21 | 0.83969 (17) | 0.35731 (19) | 0.18969 (14) | 0.0436 (4) | |
H21A | 0.8652 | 0.3001 | 0.2015 | 0.052* | |
H21B | 0.8925 | 0.4356 | 0.2398 | 0.052* | |
C22 | 0.8558 (2) | 0.3510 (2) | 0.09137 (15) | 0.0562 (5) | |
H22A | 0.8012 | 0.2745 | 0.0415 | 0.084* | |
H22B | 0.9405 | 0.3628 | 0.0867 | 0.084* | |
H22C | 0.8362 | 0.4114 | 0.0814 | 0.084* | |
S1 | 0.61592 (4) | 0.24412 (3) | 0.46920 (3) | 0.02971 (10) | |
S2 | 0.14012 (4) | 0.24790 (4) | 0.19037 (3) | 0.03629 (11) | |
B31 | 0.02234 (17) | 0.68959 (16) | 0.39397 (12) | 0.0284 (3) | |
O31 | 0.00329 (13) | 0.61897 (11) | 0.43996 (9) | 0.0414 (3) | |
O32 | −0.01311 (12) | 0.77979 (11) | 0.43404 (9) | 0.0381 (3) | |
C31 | 0.07500 (14) | 0.66371 (13) | 0.30092 (11) | 0.0258 (3) | |
C32 | 0.06028 (13) | 0.69246 (12) | 0.22483 (10) | 0.0238 (3) | |
C33 | 0.11366 (16) | 0.64187 (15) | 0.14773 (12) | 0.0328 (3) | |
H33 | 0.1109 | 0.6525 | 0.0895 | 0.039* | |
C34 | 0.16881 (17) | 0.57679 (17) | 0.16648 (13) | 0.0391 (4) | |
H34 | 0.2099 | 0.5374 | 0.1236 | 0.047* | |
C35 | −0.00662 (13) | 0.76922 (13) | 0.22187 (10) | 0.0241 (3) | |
H35 | −0.0143 | 0.8128 | 0.2893 | 0.029* | |
N36 | −0.13008 (12) | 0.69678 (11) | 0.15964 (9) | 0.0280 (3) | |
H36 | −0.1828 | 0.6552 | 0.1828 | 0.034* | |
C37 | −0.17010 (14) | 0.68757 (13) | 0.07252 (11) | 0.0274 (3) | |
N38 | −0.09181 (13) | 0.76047 (12) | 0.04064 (9) | 0.0315 (3) | |
H38 | −0.1143 | 0.7523 | −0.0187 | 0.038* | |
C39 | 0.02087 (15) | 0.84658 (14) | 0.09561 (11) | 0.0287 (3) | |
C40 | 0.06281 (14) | 0.85601 (13) | 0.18401 (11) | 0.0263 (3) | |
C41 | −0.03602 (17) | 0.67207 (16) | 0.52899 (12) | 0.0356 (4) | |
C42 | −0.07393 (17) | 0.76491 (15) | 0.51102 (12) | 0.0355 (4) | |
C43 | −0.1385 (2) | 0.5765 (2) | 0.53879 (17) | 0.0565 (5) | |
H43A | −0.2023 | 0.5341 | 0.4791 | 0.085* | |
H43B | −0.1728 | 0.6105 | 0.5939 | 0.085* | |
H43C | −0.1068 | 0.5229 | 0.5497 | 0.085* | |
C44 | 0.0726 (2) | 0.7245 (2) | 0.61186 (15) | 0.0584 (6) | |
H44A | 0.1004 | 0.6640 | 0.6119 | 0.088* | |
H44B | 0.0492 | 0.7581 | 0.6735 | 0.088* | |
H44C | 0.1386 | 0.7854 | 0.6040 | 0.088* | |
C45 | −0.2104 (2) | 0.7200 (2) | 0.46867 (17) | 0.0579 (6) | |
H45A | −0.2260 | 0.7746 | 0.4468 | 0.087* | |
H45B | −0.2564 | 0.7127 | 0.5186 | 0.087* | |
H45C | −0.2362 | 0.6439 | 0.4134 | 0.087* | |
C46 | −0.0335 (2) | 0.88144 (19) | 0.59638 (15) | 0.0570 (6) | |
H46A | 0.0552 | 0.9131 | 0.6192 | 0.086* | |
H46B | −0.0734 | 0.8726 | 0.6489 | 0.086* | |
H46C | −0.0561 | 0.9346 | 0.5766 | 0.086* | |
C47 | 0.08465 (18) | 0.92231 (16) | 0.04776 (13) | 0.0403 (4) | |
H47A | 0.0885 | 1.0012 | 0.0839 | 0.060* | |
H47B | 0.0395 | 0.8907 | −0.0192 | 0.060* | |
H47C | 0.1676 | 0.9244 | 0.0474 | 0.060* | |
C48 | 0.18103 (15) | 0.94540 (13) | 0.24476 (11) | 0.0280 (3) | |
O49 | 0.25664 (11) | 1.01361 (11) | 0.22269 (9) | 0.0409 (3) | |
O50 | 0.19949 (10) | 0.94226 (10) | 0.33108 (8) | 0.0307 (2) | |
C51 | 0.31590 (15) | 1.02263 (15) | 0.39685 (12) | 0.0339 (3) | |
H51A | 0.3266 | 1.1037 | 0.4118 | 0.041* | |
H51B | 0.3836 | 1.0078 | 0.3673 | 0.041* | |
C52 | 0.3146 (2) | 1.0030 (2) | 0.48767 (15) | 0.0570 (6) | |
H52A | 0.2462 | 1.0165 | 0.5153 | 0.085* | |
H52B | 0.3914 | 1.0568 | 0.5350 | 0.085* | |
H52C | 0.3054 | 0.9229 | 0.4719 | 0.085* | |
S3 | 0.15505 (4) | 0.57455 (4) | 0.27683 (3) | 0.03606 (11) | |
S4 | −0.31028 (4) | 0.59544 (4) | 0.00464 (3) | 0.03619 (11) |
U11 | U22 | U33 | U12 | U13 | U23 | |
B1 | 0.0314 (9) | 0.0225 (8) | 0.0266 (8) | 0.0111 (7) | 0.0046 (7) | 0.0102 (7) |
O1 | 0.0608 (8) | 0.0294 (6) | 0.0272 (6) | 0.0273 (6) | 0.0044 (5) | 0.0087 (5) |
O2 | 0.0701 (9) | 0.0296 (6) | 0.0245 (5) | 0.0290 (6) | 0.0087 (5) | 0.0101 (5) |
C1 | 0.0282 (7) | 0.0220 (7) | 0.0214 (6) | 0.0092 (6) | 0.0049 (5) | 0.0093 (5) |
C2 | 0.0270 (7) | 0.0199 (6) | 0.0228 (6) | 0.0093 (6) | 0.0060 (5) | 0.0096 (5) |
C3 | 0.0467 (10) | 0.0283 (8) | 0.0271 (7) | 0.0214 (7) | 0.0099 (7) | 0.0103 (6) |
C4 | 0.0493 (10) | 0.0309 (8) | 0.0242 (7) | 0.0202 (8) | 0.0089 (7) | 0.0081 (6) |
C5 | 0.0275 (7) | 0.0197 (7) | 0.0233 (6) | 0.0089 (6) | 0.0055 (5) | 0.0101 (5) |
N6 | 0.0289 (7) | 0.0222 (6) | 0.0308 (6) | 0.0072 (5) | 0.0038 (5) | 0.0140 (5) |
C7 | 0.0319 (8) | 0.0298 (8) | 0.0201 (6) | 0.0125 (6) | 0.0045 (6) | 0.0106 (6) |
N8 | 0.0352 (7) | 0.0268 (7) | 0.0376 (7) | 0.0163 (6) | 0.0044 (6) | 0.0129 (6) |
C9 | 0.0371 (8) | 0.0226 (7) | 0.0262 (7) | 0.0084 (6) | 0.0005 (6) | 0.0112 (6) |
C10 | 0.0330 (8) | 0.0219 (7) | 0.0232 (7) | 0.0081 (6) | 0.0055 (6) | 0.0115 (6) |
C11 | 0.0522 (11) | 0.0266 (8) | 0.0310 (8) | 0.0208 (8) | 0.0056 (7) | 0.0078 (7) |
C12 | 0.0767 (14) | 0.0308 (9) | 0.0301 (8) | 0.0310 (9) | 0.0170 (9) | 0.0105 (7) |
C13 | 0.0665 (14) | 0.0335 (10) | 0.0689 (14) | 0.0158 (10) | 0.0229 (12) | 0.0195 (10) |
C14 | 0.0705 (14) | 0.0420 (11) | 0.0486 (11) | 0.0375 (11) | 0.0057 (10) | 0.0101 (9) |
C15 | 0.151 (3) | 0.0480 (13) | 0.0311 (10) | 0.0518 (16) | −0.0135 (13) | −0.0019 (9) |
C16 | 0.119 (3) | 0.0636 (16) | 0.101 (2) | 0.0466 (17) | 0.083 (2) | 0.0432 (16) |
C17 | 0.0500 (11) | 0.0251 (8) | 0.0476 (10) | 0.0113 (8) | −0.0009 (8) | 0.0201 (8) |
C18 | 0.0352 (8) | 0.0289 (8) | 0.0247 (7) | 0.0077 (7) | 0.0063 (6) | 0.0130 (6) |
O19 | 0.0404 (7) | 0.0334 (6) | 0.0465 (7) | 0.0030 (5) | 0.0085 (6) | 0.0219 (6) |
O20 | 0.0338 (6) | 0.0349 (6) | 0.0438 (7) | 0.0133 (5) | 0.0150 (5) | 0.0170 (5) |
C21 | 0.0352 (9) | 0.0517 (11) | 0.0443 (10) | 0.0170 (8) | 0.0140 (8) | 0.0198 (9) |
C22 | 0.0513 (12) | 0.0645 (14) | 0.0458 (11) | 0.0183 (11) | 0.0217 (9) | 0.0184 (10) |
S1 | 0.0382 (2) | 0.0288 (2) | 0.02272 (18) | 0.01457 (17) | 0.00229 (15) | 0.01086 (15) |
S2 | 0.0301 (2) | 0.0475 (3) | 0.0326 (2) | 0.01577 (18) | 0.00692 (16) | 0.01790 (19) |
B31 | 0.0318 (9) | 0.0316 (9) | 0.0264 (8) | 0.0150 (7) | 0.0083 (7) | 0.0144 (7) |
O31 | 0.0678 (9) | 0.0464 (7) | 0.0334 (6) | 0.0363 (7) | 0.0252 (6) | 0.0262 (6) |
O32 | 0.0580 (8) | 0.0422 (7) | 0.0335 (6) | 0.0314 (6) | 0.0248 (6) | 0.0231 (5) |
C31 | 0.0286 (7) | 0.0256 (7) | 0.0268 (7) | 0.0135 (6) | 0.0075 (6) | 0.0120 (6) |
C32 | 0.0241 (7) | 0.0231 (7) | 0.0255 (7) | 0.0089 (6) | 0.0084 (5) | 0.0113 (6) |
C33 | 0.0382 (9) | 0.0375 (9) | 0.0287 (7) | 0.0191 (7) | 0.0146 (7) | 0.0153 (7) |
C34 | 0.0428 (10) | 0.0458 (10) | 0.0356 (9) | 0.0274 (8) | 0.0172 (7) | 0.0141 (8) |
C35 | 0.0249 (7) | 0.0250 (7) | 0.0252 (7) | 0.0097 (6) | 0.0075 (5) | 0.0132 (6) |
N36 | 0.0244 (6) | 0.0313 (7) | 0.0314 (6) | 0.0087 (5) | 0.0084 (5) | 0.0178 (6) |
C37 | 0.0276 (7) | 0.0283 (7) | 0.0275 (7) | 0.0140 (6) | 0.0091 (6) | 0.0099 (6) |
N38 | 0.0335 (7) | 0.0358 (7) | 0.0234 (6) | 0.0089 (6) | 0.0046 (5) | 0.0149 (6) |
C39 | 0.0328 (8) | 0.0278 (8) | 0.0283 (7) | 0.0112 (6) | 0.0084 (6) | 0.0149 (6) |
C40 | 0.0291 (8) | 0.0245 (7) | 0.0282 (7) | 0.0098 (6) | 0.0080 (6) | 0.0145 (6) |
C41 | 0.0440 (10) | 0.0445 (10) | 0.0257 (7) | 0.0211 (8) | 0.0138 (7) | 0.0182 (7) |
C42 | 0.0457 (10) | 0.0397 (9) | 0.0286 (8) | 0.0225 (8) | 0.0172 (7) | 0.0157 (7) |
C43 | 0.0691 (15) | 0.0523 (12) | 0.0567 (12) | 0.0208 (11) | 0.0256 (11) | 0.0325 (11) |
C44 | 0.0548 (13) | 0.0888 (17) | 0.0381 (10) | 0.0383 (13) | 0.0068 (9) | 0.0250 (11) |
C45 | 0.0492 (12) | 0.0742 (16) | 0.0594 (13) | 0.0369 (12) | 0.0166 (10) | 0.0256 (12) |
C46 | 0.0811 (16) | 0.0480 (12) | 0.0403 (10) | 0.0300 (12) | 0.0205 (10) | 0.0116 (9) |
C47 | 0.0455 (10) | 0.0405 (10) | 0.0341 (8) | 0.0059 (8) | 0.0041 (7) | 0.0252 (8) |
C48 | 0.0320 (8) | 0.0249 (7) | 0.0308 (7) | 0.0112 (6) | 0.0062 (6) | 0.0156 (6) |
O49 | 0.0372 (7) | 0.0382 (7) | 0.0454 (7) | 0.0009 (5) | 0.0016 (5) | 0.0290 (6) |
O50 | 0.0304 (6) | 0.0308 (6) | 0.0272 (5) | 0.0060 (5) | 0.0029 (4) | 0.0143 (5) |
C51 | 0.0315 (8) | 0.0316 (8) | 0.0325 (8) | 0.0084 (7) | 0.0003 (6) | 0.0117 (7) |
C52 | 0.0549 (13) | 0.0628 (14) | 0.0447 (11) | 0.0078 (11) | −0.0086 (9) | 0.0302 (10) |
S3 | 0.0420 (2) | 0.0420 (2) | 0.0362 (2) | 0.0287 (2) | 0.01057 (18) | 0.01775 (18) |
S4 | 0.0273 (2) | 0.0421 (2) | 0.0285 (2) | 0.00897 (17) | 0.00539 (15) | 0.00812 (17) |
B1—O2 | 1.357 (2) | B31—O31 | 1.352 (2) |
B1—O1 | 1.361 (2) | B31—O32 | 1.361 (2) |
B1—C1 | 1.553 (2) | B31—C31 | 1.552 (2) |
O1—C11 | 1.4688 (19) | O31—C41 | 1.4639 (19) |
O2—C12 | 1.465 (2) | O32—C42 | 1.4575 (19) |
C1—C2 | 1.378 (2) | C31—C32 | 1.373 (2) |
C1—S1 | 1.7280 (14) | C31—S3 | 1.7265 (15) |
C2—C3 | 1.420 (2) | C32—C33 | 1.425 (2) |
C2—C5 | 1.5185 (19) | C32—C35 | 1.517 (2) |
C3—C4 | 1.361 (2) | C33—C34 | 1.357 (2) |
C3—H3 | 0.9500 | C33—H33 | 0.9500 |
C4—S1 | 1.7045 (17) | C34—S3 | 1.7088 (18) |
C4—H4 | 0.9500 | C34—H34 | 0.9500 |
C5—N6 | 1.4737 (19) | C35—N36 | 1.4766 (19) |
C5—C10 | 1.5184 (19) | C35—C40 | 1.5184 (19) |
C5—H5 | 1.0000 | C35—H35 | 1.0000 |
N6—C7 | 1.322 (2) | N36—C37 | 1.327 (2) |
N6—H6 | 0.8800 | N36—H36 | 0.8800 |
C7—N8 | 1.368 (2) | C37—N38 | 1.369 (2) |
C7—S2 | 1.6836 (16) | C37—S4 | 1.6808 (16) |
N8—C9 | 1.393 (2) | N38—C39 | 1.390 (2) |
N8—H8 | 0.8800 | N38—H38 | 0.8800 |
C9—C10 | 1.346 (2) | C39—C40 | 1.350 (2) |
C9—C17 | 1.503 (2) | C39—C47 | 1.504 (2) |
C10—C18 | 1.470 (2) | C40—C48 | 1.466 (2) |
C11—C14 | 1.507 (3) | C41—C44 | 1.509 (3) |
C11—C13 | 1.524 (3) | C41—C43 | 1.512 (3) |
C11—C12 | 1.549 (2) | C41—C42 | 1.574 (2) |
C12—C15 | 1.495 (3) | C42—C46 | 1.505 (3) |
C12—C16 | 1.540 (3) | C42—C45 | 1.531 (3) |
C13—H13A | 0.9800 | C43—H43A | 0.9800 |
C13—H13B | 0.9800 | C43—H43B | 0.9800 |
C13—H13C | 0.9800 | C43—H43C | 0.9800 |
C14—H14A | 0.9800 | C44—H44A | 0.9800 |
C14—H14B | 0.9800 | C44—H44B | 0.9800 |
C14—H14C | 0.9800 | C44—H44C | 0.9800 |
C15—H15A | 0.9800 | C45—H45A | 0.9800 |
C15—H15B | 0.9800 | C45—H45B | 0.9800 |
C15—H15C | 0.9800 | C45—H45C | 0.9800 |
C16—H16A | 0.9800 | C46—H46A | 0.9800 |
C16—H16B | 0.9800 | C46—H46B | 0.9800 |
C16—H16C | 0.9800 | C46—H46C | 0.9800 |
C17—H17A | 0.9800 | C47—H47A | 0.9800 |
C17—H17B | 0.9800 | C47—H47B | 0.9800 |
C17—H17C | 0.9800 | C47—H47C | 0.9800 |
C18—O19 | 1.216 (2) | C48—O49 | 1.2187 (19) |
C18—O20 | 1.346 (2) | C48—O50 | 1.3379 (18) |
O20—C21 | 1.457 (2) | O50—C51 | 1.4494 (19) |
C21—C22 | 1.495 (3) | C51—C52 | 1.503 (3) |
C21—H21A | 0.9900 | C51—H51A | 0.9900 |
C21—H21B | 0.9900 | C51—H51B | 0.9900 |
C22—H22A | 0.9800 | C52—H52A | 0.9800 |
C22—H22B | 0.9800 | C52—H52B | 0.9800 |
C22—H22C | 0.9800 | C52—H52C | 0.9800 |
O2—B1—O1 | 113.78 (14) | O31—B31—O32 | 114.26 (14) |
O2—B1—C1 | 124.84 (14) | O31—B31—C31 | 121.32 (15) |
O1—B1—C1 | 121.33 (14) | O32—B31—C31 | 124.37 (14) |
B1—O1—C11 | 107.00 (12) | B31—O31—C41 | 108.06 (13) |
B1—O2—C12 | 106.97 (12) | B31—O32—C42 | 107.96 (12) |
C2—C1—B1 | 130.36 (13) | C32—C31—B31 | 130.28 (14) |
C2—C1—S1 | 109.91 (11) | C32—C31—S3 | 110.11 (11) |
B1—C1—S1 | 119.54 (11) | B31—C31—S3 | 119.35 (11) |
C1—C2—C3 | 113.10 (13) | C31—C32—C33 | 113.05 (14) |
C1—C2—C5 | 123.78 (12) | C31—C32—C35 | 123.94 (13) |
C3—C2—C5 | 123.12 (13) | C33—C32—C35 | 123.01 (13) |
C4—C3—C2 | 112.63 (14) | C34—C33—C32 | 112.64 (14) |
C4—C3—H3 | 123.7 | C34—C33—H33 | 123.7 |
C2—C3—H3 | 123.7 | C32—C33—H33 | 123.7 |
C3—C4—S1 | 111.65 (12) | C33—C34—S3 | 111.55 (12) |
C3—C4—H4 | 124.2 | C33—C34—H34 | 124.2 |
S1—C4—H4 | 124.2 | S3—C34—H34 | 124.2 |
N6—C5—C10 | 109.92 (12) | N36—C35—C32 | 109.80 (12) |
N6—C5—C2 | 109.99 (11) | N36—C35—C40 | 109.87 (12) |
C10—C5—C2 | 111.69 (12) | C32—C35—C40 | 110.98 (12) |
N6—C5—H5 | 108.4 | N36—C35—H35 | 108.7 |
C10—C5—H5 | 108.4 | C32—C35—H35 | 108.7 |
C2—C5—H5 | 108.4 | C40—C35—H35 | 108.7 |
C7—N6—C5 | 125.95 (13) | C37—N36—C35 | 127.04 (13) |
C7—N6—H6 | 117.0 | C37—N36—H36 | 116.5 |
C5—N6—H6 | 117.0 | C35—N36—H36 | 116.5 |
N6—C7—N8 | 116.36 (14) | N36—C37—N38 | 116.33 (14) |
N6—C7—S2 | 123.93 (12) | N36—C37—S4 | 123.02 (12) |
N8—C7—S2 | 119.70 (12) | N38—C37—S4 | 120.63 (12) |
C7—N8—C9 | 123.85 (14) | C37—N38—C39 | 124.42 (13) |
C7—N8—H8 | 118.1 | C37—N38—H38 | 117.8 |
C9—N8—H8 | 118.1 | C39—N38—H38 | 117.8 |
C10—C9—N8 | 118.87 (14) | C40—C39—N38 | 119.54 (14) |
C10—C9—C17 | 127.11 (16) | C40—C39—C47 | 126.23 (15) |
N8—C9—C17 | 114.02 (15) | N38—C39—C47 | 114.23 (14) |
C9—C10—C18 | 121.80 (14) | C39—C40—C48 | 121.59 (14) |
C9—C10—C5 | 120.77 (14) | C39—C40—C35 | 121.27 (14) |
C18—C10—C5 | 117.42 (13) | C48—C40—C35 | 117.01 (13) |
O1—C11—C14 | 108.90 (14) | O31—C41—C44 | 106.68 (15) |
O1—C11—C13 | 106.61 (15) | O31—C41—C43 | 107.56 (16) |
C14—C11—C13 | 109.29 (17) | C44—C41—C43 | 110.40 (17) |
O1—C11—C12 | 102.07 (13) | O31—C41—C42 | 102.79 (12) |
C14—C11—C12 | 116.75 (17) | C44—C41—C42 | 113.58 (17) |
C13—C11—C12 | 112.48 (17) | C43—C41—C42 | 115.03 (16) |
O2—C12—C15 | 109.08 (17) | O32—C42—C46 | 108.64 (16) |
O2—C12—C16 | 106.04 (17) | O32—C42—C45 | 105.51 (15) |
C15—C12—C16 | 110.6 (2) | C46—C42—C45 | 109.92 (17) |
O2—C12—C11 | 102.69 (13) | O32—C42—C41 | 103.19 (12) |
C15—C12—C11 | 116.02 (18) | C46—C42—C41 | 115.69 (16) |
C16—C12—C11 | 111.7 (2) | C45—C42—C41 | 113.09 (17) |
C11—C13—H13A | 109.5 | C41—C43—H43A | 109.5 |
C11—C13—H13B | 109.5 | C41—C43—H43B | 109.5 |
H13A—C13—H13B | 109.5 | H43A—C43—H43B | 109.5 |
C11—C13—H13C | 109.5 | C41—C43—H43C | 109.5 |
H13A—C13—H13C | 109.5 | H43A—C43—H43C | 109.5 |
H13B—C13—H13C | 109.5 | H43B—C43—H43C | 109.5 |
C11—C14—H14A | 109.5 | C41—C44—H44A | 109.5 |
C11—C14—H14B | 109.5 | C41—C44—H44B | 109.5 |
H14A—C14—H14B | 109.5 | H44A—C44—H44B | 109.5 |
C11—C14—H14C | 109.5 | C41—C44—H44C | 109.5 |
H14A—C14—H14C | 109.5 | H44A—C44—H44C | 109.5 |
H14B—C14—H14C | 109.5 | H44B—C44—H44C | 109.5 |
C12—C15—H15A | 109.5 | C42—C45—H45A | 109.5 |
C12—C15—H15B | 109.5 | C42—C45—H45B | 109.5 |
H15A—C15—H15B | 109.5 | H45A—C45—H45B | 109.5 |
C12—C15—H15C | 109.5 | C42—C45—H45C | 109.5 |
H15A—C15—H15C | 109.5 | H45A—C45—H45C | 109.5 |
H15B—C15—H15C | 109.5 | H45B—C45—H45C | 109.5 |
C12—C16—H16A | 109.5 | C42—C46—H46A | 109.5 |
C12—C16—H16B | 109.5 | C42—C46—H46B | 109.5 |
H16A—C16—H16B | 109.5 | H46A—C46—H46B | 109.5 |
C12—C16—H16C | 109.5 | C42—C46—H46C | 109.5 |
H16A—C16—H16C | 109.5 | H46A—C46—H46C | 109.5 |
H16B—C16—H16C | 109.5 | H46B—C46—H46C | 109.5 |
C9—C17—H17A | 109.5 | C39—C47—H47A | 109.5 |
C9—C17—H17B | 109.5 | C39—C47—H47B | 109.5 |
H17A—C17—H17B | 109.5 | H47A—C47—H47B | 109.5 |
C9—C17—H17C | 109.5 | C39—C47—H47C | 109.5 |
H17A—C17—H17C | 109.5 | H47A—C47—H47C | 109.5 |
H17B—C17—H17C | 109.5 | H47B—C47—H47C | 109.5 |
O19—C18—O20 | 123.16 (16) | O49—C48—O50 | 122.17 (14) |
O19—C18—C10 | 126.16 (16) | O49—C48—C40 | 127.06 (14) |
O20—C18—C10 | 110.66 (13) | O50—C48—C40 | 110.75 (13) |
C18—O20—C21 | 117.03 (14) | C48—O50—C51 | 116.55 (12) |
O20—C21—C22 | 111.17 (16) | O50—C51—C52 | 106.59 (14) |
O20—C21—H21A | 109.4 | O50—C51—H51A | 110.4 |
C22—C21—H21A | 109.4 | C52—C51—H51A | 110.4 |
O20—C21—H21B | 109.4 | O50—C51—H51B | 110.4 |
C22—C21—H21B | 109.4 | C52—C51—H51B | 110.4 |
H21A—C21—H21B | 108.0 | H51A—C51—H51B | 108.6 |
C21—C22—H22A | 109.5 | C51—C52—H52A | 109.5 |
C21—C22—H22B | 109.5 | C51—C52—H52B | 109.5 |
H22A—C22—H22B | 109.5 | H52A—C52—H52B | 109.5 |
C21—C22—H22C | 109.5 | C51—C52—H52C | 109.5 |
H22A—C22—H22C | 109.5 | H52A—C52—H52C | 109.5 |
H22B—C22—H22C | 109.5 | H52B—C52—H52C | 109.5 |
C4—S1—C1 | 92.71 (7) | C34—S3—C31 | 92.65 (8) |
C2—C1—B1—O2 | 6.2 (3) | C18—O20—C21—C22 | −81.2 (2) |
S1—C1—B1—O1 | 3.4 (2) | C48—O50—C51—C52 | 179.83 (16) |
C32—C31—B31—O32 | −24.7 (3) | C10—C18—O20—C21 | −179.33 (13) |
S3—C31—B31—O31 | −20.9 (2) | C40—C48—O50—C51 | 177.11 (13) |
D—H···A | D—H | H···A | D···A | D—H···A |
N8—H8···S3 | 0.88 | 2.91 | 3.7702 (15) | 167 |
N6—H6···O49i | 0.88 | 2.06 | 2.8666 (17) | 152 |
N36—H36···O19ii | 0.88 | 2.14 | 2.9670 (17) | 155 |
N38—H38···S2iii | 0.88 | 2.61 | 3.4817 (14) | 170 |
Symmetry codes: (i) x, y−1, z; (ii) x−1, y, z; (iii) −x, −y+1, −z. |
Experimental details
Crystal data | |
Chemical formula | C18H25BN2O4S2 |
Mr | 408.33 |
Crystal system, space group | Triclinic, P1 |
Temperature (K) | 173 |
a, b, c (Å) | 11.9274 (17), 13.5021 (19), 15.225 (2) |
α, β, γ (°) | 112.172 (2), 93.531 (2), 109.706 (2) |
V (Å3) | 2086.9 (5) |
Z | 4 |
Radiation type | Mo Kα |
µ (mm−1) | 0.28 |
Crystal size (mm) | 0.6 × 0.6 × 0.4 |
Data collection | |
Diffractometer | Bruker SMART1000/P4 diffractometer |
Absorption correction | Multi-scan (SADABS; Sheldrick, 1997) |
Tmin, Tmax | 0.850, 0.896 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 14611, 9077, 7758 |
Rint | 0.017 |
(sin θ/λ)max (Å−1) | 0.650 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.040, 0.113, 1.04 |
No. of reflections | 9077 |
No. of parameters | 499 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.51, −0.41 |
Computer programs: SMART (Bruker, 1999), SAINT (Bruker, 2006), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELXTL (Sheldrick, 2008).
D—H···A | D—H | H···A | D···A | D—H···A |
N8—H8···S3 | 0.88 | 2.91 | 3.7702 (15) | 167 |
N6—H6···O49i | 0.88 | 2.06 | 2.8666 (17) | 152 |
N36—H36···O19ii | 0.88 | 2.14 | 2.9670 (17) | 155 |
N38—H38···S2iii | 0.88 | 2.61 | 3.4817 (14) | 170 |
Symmetry codes: (i) x, y−1, z; (ii) x−1, y, z; (iii) −x, −y+1, −z. |
Acknowledgements
This work was funded by the Natural Science and Engineering Research Council and AIF/ACOA (Canada).
References
Blacquiere, J. M., Sicora, O., Vogels, C. M., Čuperlović-Culf, M., Decken, A., Ouellette, R. J. & Westcott, S. A. (2005). Can. J. Chem. 83, 2052–2059. Web of Science CSD CrossRef CAS Google Scholar
Bruker (1999). SMART. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Bruker (2006). SAINT. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Miyaura, N. & Suzuki, A. (1995). Chem. Rev. 95, 2457–2483. Web of Science CrossRef CAS Google Scholar
Sheldrick, G. M. (1997). SADABS. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar
Vogels, C. M., Decken, A. & Westcott, S. A. (2006). Tetrahedron Lett. 47, 2419–2422. Web of Science CSD CrossRef CAS Google Scholar
Yang, W., Gao, X. & Wang, B. (2003). Med. Res. Rev. 23, 346–368. Web of Science CrossRef PubMed CAS Google Scholar
This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.
Compounds containing boronic acids [RB(OH)2] or boronate esters [RB(OR')2] have found remarkable synthetic utility in Suzuki-Miyaura cross coupling reactions (Miyaura and Suzuki, 1995) over the past decade. Interest in these compounds also arises from their diverse and potent biological activities (Yang et al., 2003). Indeed, we have recently shown that dihydropyrimidinones (Biginelli products) containing boronic acids show significant promise for their ability to inhibit the MCF7 breast cancer cell line (Blacquiere et al., 2005). Biginelli compounds containing thiophenes showed the most promise in this study. Some of the biological properties of boron compounds have been attributed to the ability of the three-coordinate boron atom to form bonds with biomolecules, as well as form hydrogen bonds with the adjacent O atoms of the boronic acid or boronate ester group. We are preparing a family of boron-containing Biginelli products in order to understand the mechanism of action of these compounds in an effort to design more potent candidates.
The title compound crystallizes with two independent molecules per asymmetric unit. In one of the independent molecules the ester group is coplanar with the pyrimidine ring [torsion angles: C40—C48—O50—C51 = 177.11 (13)° and C48—O50—C51—C52 = 179.83 (16)°], the second independent molecule shows rotation of the ethyl group of the ester moiety that displaces the methyl group from the pyrimidine ring plane [torsion angles: C10—C18—O20—C21 = -179.33 (13)° and C18—O20—C21—C22 = -81.2 (2)°]. Conversely, the latter molecule displays coplanar dioxaborolane and thiophene rings [torsion angles: C2—C1—B1—O2 = 6.2 (3)° and S1—C1—B1—O1 = 3.4 (2)°], while the former shows rotation about the inter-ring linkage [torsion angles: C32—C31—B31—O32 = 20.9 (2)° and S3—C31—B31—O31 = 24.7 (3)°]. However, these torsion angles allow for orbital overlap between the boron pz orbital and the aryl π-electron system. The Bpin skeleton displays similar bond lengths and angles as found in related aniline derivatives (Vogels et al., 2006). Although steric crowding at the boron center is not present, the title compound shows no appreciable intra- or intermolecular Lewis acid-base interactions. However, hydrogen bonding is observed for all N—H groups of the 3,4-dihydropyrimidine-2(1H)-thione fragment. Two NH···O bonds are present for H6 and H36 (H6···O49i = 2.06 Å, (i): x, y - 1, z and H36···O19ii = 2.14 Å. (ii): x - 1, y, z) while two very long NH···S bonds are found for H8 and H38 (H8···S3 = 2.91 Å and H38···S2iii = 2.61 Å, (iii): -x, -y + 1, -z).