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Acta Cryst. (2009). E65, o2073-o2074    [ doi:10.1107/S160053680902978X ]

(Z)-2-Phenyl-3-pivaloyl-1,1-dipropylguanidine

M. Said, G. Murtaza, E. Freisinger, S. Anwar and A. Rauf

Abstract top

In the title compound, C18H29N3O, a polysubstituted guanidine, the torsion angles indicate that the guanidine unit and the carbonyl group are almost perpendicular to one another [O-C-N-C= -7.40 (18), C-N-C-N= -97.21 (15) and 86.41 (13)°]. The crystal packing is stablized by intermolecular N-H...O hydrogen bonds, which link the molecules into a chain.

Comment top

The guanidinium moiety is present in diverse biologically active natural substances as well as in a number of medicinal compounds (Berlinck, 2002). Polysubstituted guanidines had received considerable interest as DNA binders (Ohara et al., 2007) and as anticancer agents (Ma et al., 2008; Brzozowski et al., 2007). In addition to their biological role, guanidine derivatives are widely utilized in synthetic organic chemistry, due to their high catalytic potential (Gomez et al., 2000; Kovacevic & Maksic, 2001). Due to their high proton affinity, guanidines can be considered as super-bases (Ishikawa & Isobe, 2002).

The title compound (Fig. 1) is a typical tetra-substituted guanidine with normal geometric parameters (Cunha et al., 2005; Murtaza et al., 2007, 2008, 2009). The C3—O1 bond shows the expected full double bond character [1.2243 (15) Å ]. The short value for the C2—N3 bond length [1.2812 (16) Å] also shows double bond character, while the values for the C2—N11, C2—N1, and C3—N1 bond lengths [1.3548 (15), 1.4348 (15) and 1.3510 (14) Å, respectively] indicate partial double bond character. The dihedral angles between the guanidine mean plane [C(2)/N(1)/N(3)/N(11)] and the phenyl ring [C31–C36] is 67.96 (10)°. The carbonyl group [C3═O1] is almost perpendicular the guanidine moiety mean plane, as reflected by torsion angles O1—C3—N1—C2= -7.40 (18)°, C3—N1—C2—N3= -97.21 (15)°, and C3—N1—C2—N11= 86.41 (13)°. This is probably due to the absence of intramolecular N—H···O hydrogen bonding forming a six-membered ring, which is commonly observed in this class of compounds (Cunha et al., 2005).

The crystal packing of the title compound shows intermolecular N—H···O hydrogen bonds, which link the molecules into a continuous chain (Fig. 2).

Related literature top

For the biological and chemical properties of guanidine derivatives, see: Ohara et al. (2007); Berlinck (2002); Ma et al. (2008); Brzozowski et al. (2007); Gomez et al. (2000); Kovacevic & Maksic (2001); Ishikawa & Isobe (2002); Rauf et al. (2009). For related structures, see: Cunha et al. (2005); Murtaza et al. (2007, 2008, 2009).

Experimental top

1-phenyl-3-(pivaloyl)thiourea (0.236 g, 1 mmol) [Rauf et al., 2009], dissolved in 10 ml of DMF, was placed in a two neck round bottom flask. Dipropylamine (0.14 g, 1 mmol) and triethylamine (0.28 ml, 2 mmol) were added and the mixture was stirred well at a temperature below 278 K. Mercuric chloride (0.272 g, 1 mmol) was then added and the mixture was stirred vigorously for 20 h. The progress of the reaction was monitored by TLC, untill the completion of reaction. When all the thiourea had been consumed, 20 ml of CH2Cl2 was added and the suspension was filtered through a cintered glass funnel to remove residual HgS, formed as a byproduct during the reaction. The solvent was then evaporated under reduced pressure and the residue dissolved in 20 ml of CH2Cl2. Other byproducts were extracted out with water (4×30 ml). The organic phase was dried over anhydrous MgSO4 and then filtered. The solvent was evaporated and the product was further purified by column chromatography. The target guanidine was recrystallized using ethanol.

Refinement top

The NH H-atom was located in a different electron-density map and freely refined: N-H = 0.837 (17) Å. The C-bound H-atoms were included in calculated positions and treated as riding atoms: C—H = 0.95 - 0.98 Å with Uiso(H) = k × Ueq(C), where k = 1.2 for H-aromatic, and 1.5 for H-methyl.

Computing details top

Data collection: CrysAlis CCD (Oxford Diffraction, 2006); cell refinement: CrysAlis RED (Oxford Diffraction, 2006); data reduction: CrysAlis RED (Oxford Diffraction, 2006); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 (Farrugia, 1997); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008).

Figures top
[Figure 1] Fig. 1. Molecular structure of of the title compound, showing the atom numbering scheme and displacement ellipsoids drawn at the 50% probability level.
[Figure 2] Fig. 2. A view of the formation of the N—H···O intermolecular hydrogen bonded chain of molecules of the title compound (see Table 1 for details).
(Z)-2-Phenyl-3-pivaloyl-1,1-dipropylguanidine top
Crystal data top
C18H29N3OF(000) = 664
Mr = 303.44Dx = 1.064 Mg m−3
Orthorhombic, P212121Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2abCell parameters from 31051 reflections
a = 9.898 (5) Åθ = 2.5–33.1°
b = 12.648 (5) ŵ = 0.07 mm−1
c = 15.126 (5) ÅT = 183 K
V = 1893.6 (14) Å3Block, colourless
Z = 40.42 × 0.42 × 0.32 mm
Data collection top
Oxford diffraction Xcalibur R
diffractometer		7202 independent reflections
Radiation source: Enhance (Mo) X-ray Source5107 reflections with I > 2σ(I)
graphiteRint = 0.029
Detector resolution: 10.4498 pixels mm-1θmax = 33.1°, θmin = 2.5°
Profile data from ω scansh = −14→15
Absorption correction: multi-scan
(CrysAlis RED; Oxford Diffraction, 2006)		k = −19→19
Tmin = 0.973, Tmax = 0.979l = −23→23
31051 measured reflections
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.056H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.134 w = 1/[σ2(Fo2) + (0.0786P)2]
where P = (Fo2 + 2Fc2)/3
S = 0.97(Δ/σ)max < 0.001
7202 reflectionsΔρmax = 0.30 e Å−3
211 parametersΔρmin = −0.18 e Å−3
0 restraintsAbsolute structure: Flack (1983), 3174 Friedel pairs
Primary atom site location: structure-invariant direct methodsFlack parameter: 0.20 (12)
Crystal data top
C18H29N3OV = 1893.6 (14) Å3
Mr = 303.44Z = 4
Orthorhombic, P212121Mo Kα radiation
a = 9.898 (5) ŵ = 0.07 mm−1
b = 12.648 (5) ÅT = 183 K
c = 15.126 (5) Å0.42 × 0.42 × 0.32 mm
Data collection top
Oxford diffraction Xcalibur R
diffractometer		7202 independent reflections
Absorption correction: multi-scan
(CrysAlis RED; Oxford Diffraction, 2006)		5107 reflections with I > 2σ(I)
Tmin = 0.973, Tmax = 0.979Rint = 0.029
31051 measured reflectionsθmax = 33.1°
Refinement top
R[F2 > 2σ(F2)] = 0.056H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.134Δρmax = 0.30 e Å−3
S = 0.97Δρmin = −0.18 e Å−3
7202 reflectionsAbsolute structure: Flack (1983), 3174 Friedel pairs
211 parametersFlack parameter: 0.20 (12)
0 restraints
Special details top

Experimental. Empirical absorption correction using spherical harmonics, implemented in SCALE3 ABSPACK scaling algorithm CrysAlis RED (Oxford Diffraction, 2006)

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) top
xyzUiso*/Ueq
N10.64742 (9)0.28579 (7)0.00092 (7)0.02445 (18)
H10.5657 (17)0.2689 (11)0.0027 (9)0.031 (3)*
N30.67372 (13)0.43416 (8)0.09671 (7)0.0375 (3)
N110.71989 (11)0.45147 (7)−0.05199 (7)0.0299 (2)
C11A0.74991 (15)0.56368 (9)−0.03790 (10)0.0386 (3)
H11A0.81000.5889−0.08580.080*
H11B0.79880.57190.01880.080*
C12A0.62283 (18)0.63189 (11)−0.03603 (12)0.0520 (4)
H12A0.57970.6314−0.09510.080*
H12B0.55780.60230.00700.080*
C13A0.6579 (2)0.74502 (11)−0.01020 (13)0.0614 (5)
H13A0.70480.74500.04690.0803 (17)*
H13B0.57480.7867−0.00550.0803 (17)*
H13C0.71660.7761−0.05540.0803 (17)*
C11B0.72858 (13)0.40828 (10)−0.14124 (8)0.0331 (3)
H11C0.76490.3355−0.13760.080*
H11D0.79380.4511−0.17550.080*
C12B0.59584 (17)0.40521 (13)−0.19124 (10)0.0459 (3)
H12C0.56100.4780−0.19860.080*
H12D0.52860.3644−0.15690.080*
C13B0.6147 (2)0.35420 (16)−0.28203 (11)0.0632 (5)
H13D0.68100.3948−0.31610.0803 (17)*
H13E0.52820.3536−0.31360.0803 (17)*
H13F0.64710.2815−0.27460.0803 (17)*
O10.86233 (8)0.23044 (7)0.00147 (7)0.0390 (2)
C20.68297 (11)0.39354 (8)0.01936 (8)0.0265 (2)
C30.74191 (11)0.20881 (8)−0.00239 (8)0.0271 (2)
C210.68941 (12)0.09564 (9)−0.01267 (10)0.0366 (3)
C220.6283 (2)0.08507 (15)−0.10465 (14)0.0698 (6)
H22A0.55250.1344−0.11070.0803 (17)*
H22B0.59600.0126−0.11330.0803 (17)*
H22C0.69710.1015−0.14910.0803 (17)*
C230.80917 (14)0.02055 (10)−0.00221 (14)0.0550 (4)
H23A0.87820.0377−0.04640.0803 (17)*
H23B0.7787−0.0525−0.01070.0803 (17)*
H23C0.84750.02830.05720.0803 (17)*
C240.58315 (17)0.07004 (12)0.05771 (15)0.0597 (5)
H24A0.62070.08380.11660.0803 (17)*
H24B0.5574−0.00460.05320.0803 (17)*
H24C0.50330.11450.04840.0803 (17)*
C310.64035 (15)0.36809 (11)0.16887 (8)0.0377 (3)
C320.51984 (17)0.38671 (15)0.21422 (10)0.0513 (4)
H320.46400.44480.19830.070 (3)*
C330.4819 (2)0.31964 (17)0.28296 (11)0.0613 (5)
H330.39850.33100.31240.070 (3)*
C340.5638 (2)0.23707 (16)0.30876 (11)0.0648 (5)
H340.53630.19060.35470.070 (3)*
C350.6853 (2)0.22300 (16)0.26725 (10)0.0650 (5)
H350.74390.16790.28600.070 (3)*
C360.72416 (19)0.28850 (15)0.19788 (11)0.0530 (4)
H360.80930.27820.17030.070 (3)*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
N10.0163 (4)0.0234 (4)0.0336 (5)−0.0025 (3)0.0004 (4)0.0011 (4)
N30.0474 (7)0.0315 (5)0.0335 (5)−0.0081 (5)0.0063 (5)−0.0019 (4)
N110.0322 (5)0.0245 (4)0.0329 (5)−0.0028 (4)0.0041 (4)0.0026 (4)
C11A0.0450 (8)0.0240 (5)0.0469 (7)−0.0079 (5)0.0106 (6)0.0021 (5)
C12A0.0585 (10)0.0288 (6)0.0687 (10)0.0005 (6)0.0091 (8)−0.0044 (6)
C13A0.0930 (13)0.0275 (6)0.0637 (10)−0.0057 (7)0.0275 (10)−0.0062 (6)
C11B0.0347 (6)0.0330 (5)0.0316 (6)−0.0006 (5)0.0067 (5)0.0056 (5)
C12B0.0480 (8)0.0471 (8)0.0427 (7)0.0090 (6)−0.0081 (7)0.0005 (7)
C13B0.0798 (13)0.0689 (11)0.0409 (9)0.0042 (10)−0.0133 (9)−0.0021 (8)
O10.0181 (4)0.0343 (4)0.0647 (6)−0.0013 (3)0.0010 (4)0.0017 (5)
C20.0207 (5)0.0247 (5)0.0340 (6)−0.0016 (4)0.0005 (4)0.0011 (4)
C30.0194 (5)0.0260 (4)0.0358 (6)−0.0018 (4)0.0006 (5)0.0030 (5)
C210.0234 (5)0.0243 (5)0.0621 (8)−0.0007 (4)−0.0032 (6)0.0000 (5)
C220.0741 (13)0.0471 (9)0.0882 (14)−0.0103 (8)−0.0347 (11)−0.0170 (9)
C230.0337 (7)0.0287 (6)0.1028 (14)0.0057 (5)−0.0018 (9)−0.0006 (8)
C240.0383 (8)0.0322 (7)0.1086 (15)−0.0060 (6)0.0181 (9)0.0162 (8)
C310.0472 (8)0.0387 (7)0.0271 (6)−0.0112 (6)0.0022 (5)−0.0056 (5)
C320.0471 (9)0.0683 (11)0.0384 (8)−0.0075 (8)0.0036 (7)0.0031 (7)
C330.0550 (10)0.0903 (14)0.0387 (8)−0.0193 (10)0.0083 (8)0.0046 (8)
C340.0904 (14)0.0744 (12)0.0296 (7)−0.0249 (11)0.0002 (9)0.0103 (8)
C350.0958 (15)0.0657 (11)0.0334 (7)0.0116 (11)−0.0007 (9)0.0094 (7)
C360.0615 (10)0.0613 (9)0.0364 (7)0.0057 (8)0.0063 (7)0.0039 (7)
Geometric parameters (Å, °) top
N1—C31.3510 (14)O1—C31.2243 (15)
N1—C21.4348 (15)C3—C211.5307 (16)
N1—H10.837 (17)C21—C221.522 (2)
N3—C21.2812 (16)C21—C231.5270 (18)
N3—C311.4140 (17)C21—C241.532 (2)
N11—C21.3548 (15)C22—H22A0.9800
N11—C11B1.4590 (17)C22—H22B0.9800
N11—C11A1.4656 (16)C22—H22C0.9800
C11A—C12A1.526 (2)C23—H23A0.9800
C11A—H11A0.9900C23—H23B0.9800
C11A—H11B0.9900C23—H23C0.9800
C12A—C13A1.523 (2)C24—H24A0.9800
C12A—H12A0.9900C24—H24B0.9800
C12A—H12B0.9900C24—H24C0.9800
C13A—H13A0.9800C31—C361.376 (2)
C13A—H13B0.9800C31—C321.396 (2)
C13A—H13C0.9800C32—C331.394 (2)
C11B—C12B1.516 (2)C32—H320.9500
C11B—H11C0.9900C33—C341.378 (3)
C11B—H11D0.9900C33—H330.9500
C12B—C13B1.529 (2)C34—C351.369 (3)
C12B—H12C0.9900C34—H340.9500
C12B—H12D0.9900C35—C361.391 (3)
C13B—H13D0.9800C35—H350.9500
C13B—H13E0.9800C36—H360.9500
C13B—H13F0.9800
C3—N1—C2121.47 (9)O1—C3—N1120.74 (10)
C3—N1—H1119.1 (9)O1—C3—C21122.97 (10)
C2—N1—H1118.2 (9)N1—C3—C21116.28 (10)
C2—N3—C31119.01 (10)C22—C21—C23110.35 (15)
C2—N11—C11B123.42 (10)C22—C21—C24110.14 (15)
C2—N11—C11A117.56 (10)C23—C21—C24109.27 (13)
C11B—N11—C11A119.01 (10)C22—C21—C3108.02 (12)
N11—C11A—C12A112.54 (12)C23—C21—C3107.92 (10)
N11—C11A—H11A109.1C24—C21—C3111.11 (12)
C12A—C11A—H11A109.1C21—C22—H22A109.5
N11—C11A—H11B109.1C21—C22—H22B109.5
C12A—C11A—H11B109.1H22A—C22—H22B109.5
H11A—C11A—H11B107.8C21—C22—H22C109.5
C13A—C12A—C11A110.38 (15)H22A—C22—H22C109.5
C13A—C12A—H12A109.6H22B—C22—H22C109.5
C11A—C12A—H12A109.6C21—C23—H23A109.5
C13A—C12A—H12B109.6C21—C23—H23B109.5
C11A—C12A—H12B109.6H23A—C23—H23B109.5
H12A—C12A—H12B108.1C21—C23—H23C109.5
C12A—C13A—H13A109.5H23A—C23—H23C109.5
C12A—C13A—H13B109.5H23B—C23—H23C109.5
H13A—C13A—H13B109.5C21—C24—H24A109.5
C12A—C13A—H13C109.5C21—C24—H24B109.5
H13A—C13A—H13C109.5H24A—C24—H24B109.5
H13B—C13A—H13C109.5C21—C24—H24C109.5
N11—C11B—C12B114.80 (11)H24A—C24—H24C109.5
N11—C11B—H11C108.6H24B—C24—H24C109.5
C12B—C11B—H11C108.6C36—C31—C32118.80 (14)
N11—C11B—H11D108.6C36—C31—N3122.50 (14)
C12B—C11B—H11D108.6C32—C31—N3118.67 (14)
H11C—C11B—H11D107.5C33—C32—C31119.64 (17)
C11B—C12B—C13B110.64 (14)C33—C32—H32120.2
C11B—C12B—H12C109.5C31—C32—H32120.2
C13B—C12B—H12C109.5C34—C33—C32120.91 (18)
C11B—C12B—H12D109.5C34—C33—H33119.5
C13B—C12B—H12D109.5C32—C33—H33119.5
H12C—C12B—H12D108.1C35—C34—C33119.04 (17)
C12B—C13B—H13D109.5C35—C34—H34120.5
C12B—C13B—H13E109.5C33—C34—H34120.5
H13D—C13B—H13E109.5C34—C35—C36120.78 (19)
C12B—C13B—H13F109.5C34—C35—H35119.6
H13D—C13B—H13F109.5C36—C35—H35119.6
H13E—C13B—H13F109.5C31—C36—C35120.62 (17)
N3—C2—N11122.01 (10)C31—C36—H36119.7
N3—C2—N1122.72 (10)C35—C36—H36119.7
N11—C2—N1115.16 (10)
C2—N11—C11A—C12A−82.33 (15)O1—C3—C21—C22−110.60 (16)
C11B—N11—C11A—C12A96.56 (14)N1—C3—C21—C2268.37 (16)
N11—C11A—C12A—C13A173.14 (13)O1—C3—C21—C238.71 (19)
C2—N11—C11B—C12B83.80 (15)N1—C3—C21—C23−172.32 (13)
C11A—N11—C11B—C12B−95.02 (14)O1—C3—C21—C24128.49 (15)
N11—C11B—C12B—C13B−177.43 (13)N1—C3—C21—C24−52.54 (16)
C31—N3—C2—N11−177.27 (12)C2—N3—C31—C3665.47 (19)
C31—N3—C2—N16.59 (19)C2—N3—C31—C32−116.74 (15)
C11B—N11—C2—N3−178.62 (12)C36—C31—C32—C33−5.0 (2)
C11A—N11—C2—N30.21 (18)N3—C31—C32—C33177.09 (14)
C11B—N11—C2—N1−2.21 (16)C31—C32—C33—C342.1 (3)
C11A—N11—C2—N1176.62 (10)C32—C33—C34—C351.6 (3)
C3—N1—C2—N3−97.25 (15)C33—C34—C35—C36−2.3 (3)
C3—N1—C2—N1186.36 (13)C32—C31—C36—C354.4 (2)
C2—N1—C3—O1−7.40 (18)N3—C31—C36—C35−177.80 (15)
C2—N1—C3—C21173.61 (12)C34—C35—C36—C31−0.8 (3)
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
N1—H1···O1i0.837 (17)2.01 (2)2.830 (2)165 (1)
Symmetry codes: (i) x−1/2, −y+1/2, −z.
Table 1
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
N1—H1···O1i0.837 (17)2.01 (2)2.830 (2)165 (1)
Symmetry codes: (i) x−1/2, −y+1/2, −z.
Acknowledgements top

The authors are grateful to the HEC-Pakistan for financial support for this research project and to the Swiss National Science Foundation (SNF-Förderungsprofessor PP002–119106/1 to EF).

references
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