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The title compound, C
10H
16N
·Cl
−·C
2H
6O, is an important intermediate in the convergent synthesis of amidine-substituted polycyclic heterocycles, a class of compounds that shows significant anticancer activity. The molecule of (I) is not planar, having a dihedral angle of 25.00 (7)° between the aniline and amidine (–C—NH=C=NH
2) groups. The protonation of the amidine molecular fragment is accompanied by delocalized C—N bond distances of 1.320 (2) and 1.317 (2) Å. The cations and chloride anions are involved in a network of hydrogen bonds, resulting in the formation of infinite chains propagating along the
b direction. The chains are further grouped within the
ab plane, in such a way that the structure is segregated into layers dominated by hydrophobic interactions involving
N-isopropyl residues and layers dominated by N—H
Cl [N
Cl = 3.275 (2)–3.596 (2) Å], O—H
Cl [O
Cl = 3.229 (3) Å] and N—H
O [N
O = 2.965 (3) Å] hydrogen bonds.
Supporting information
CCDC reference: 264806
Compound (I) was prepared from 4-aminobenzonitrile by a modified Pinner reaction (Ferroni et al., 1995) (see scheme). A suspension of 4-aminobenzonitrile (9 g, 0.076 mmol) in absolute ethanol (130 ml) was cooled to 273 K and saturated with dry HCl gas. The suspension was stirred until IR spectra indicated the absence of the cyano peak (8 d). The imine ester hydrochloride intermediate was precipitated from the solution by addition of dry diethyl ether, filtered off, washed with dry ether and dried over KOH. Isopropyl amine (19.5 ml, 0.23 mmol) was added to the suspension of the crude imine ester hydrochloride in absolute ethanol (130 ml). The mixture was stirred at room temperature for 5 d. The crude product (9.35 g, yield 69%, m.p. 517–521 K) was filtered off, washed with acetone and recrystallized from ethanol. IR (KBr, cm−1): 3480, 3300, 3080, 2950, 1650, 1590; 1H NMR (300 MHz, DMSO-d6): 8.98–9.03 (m, 2 H, Hamidine), 8.65 (s, 1 H, Hamidine), 7.48 (d, 2 H, Harom., J = 8.72 Hz), 6.64 (d, 2 H, Harom, J = 8.71 Hz), 6.17 (s, 2 H, Hamine), 4.02–4.04 (m, 1 H, HCH), 1.24 (d, 6 H, HCH3, J = 6.46 Hz); 13C (300 MHz, DMSO-d6): 161.1 (s), 153.9 (s), 129.9 (s, 2 C), 113.9 (s), 112.7.
Methyl atom C12 of the ethanol solvent molecule is disordered; the relative occupancies of the two positions, C12A (major component) and C12B, were refined to a final ratio of 73 (1):27 (1). The C12A—C11 [1.419 (5) Å] and C12B—C11 [1.472 (9) Å] bond distances were loosely restrained to a Csp3—Csp3 value (DFIX in SHELXL97; Sheldrick, 1997). H atoms bonded to C atoms were introduced at calculated positions and refined as riding [Uiso(H) = 1.2 or 1.5Ueq(C), and C—H = 0.93 (Car—H), 0.96 (Cmethyl—H), 0.97 (Cmethylene—H) and 0.98 Å (Ctertiary—H)]. The H atoms of the NH2 group (N1) were also refined as riding [N—H = 0.86 Å and Uiso(H) = 1.2Ueq(N)]. The H atoms bonded to atoms N2, N3 and O1 were found in difference Fourier maps and refined freely.
Data collection: CrysAlis (Oxford Diffraction, 2004); cell refinement: CrysAlis; data reduction: CrysAlis; program(s) used to solve structure: SHELXS97 (Sheldrick, 1990); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: PLATON98 (Spek, 1998); software used to prepare material for publication: SHELXL97 (Sheldrick, 1997).
4-Amino-
N-isopropylbenzamidinium chloride ethanol solvate
top
Crystal data top
C10H16N3+·Cl−·C2H6O | Z = 2 |
Mr = 259.78 | F(000) = 280 |
Triclinic, P1 | Dx = 1.168 Mg m−3 |
Hall symbol: -P 1 | Melting point = 517–521 K |
a = 8.7458 (15) Å | Mo Kα radiation, λ = 0.71073 Å |
b = 9.2177 (14) Å | Cell parameters from 2250 reflections |
c = 9.7938 (15) Å | θ = 6–20° |
α = 96.339 (12)° | µ = 0.25 mm−1 |
β = 105.022 (14)° | T = 296 K |
γ = 100.649 (13)° | Prism, colourless |
V = 738.9 (2) Å3 | 0.48 × 0.19 × 0.18 mm |
Data collection top
Oxford Diffraction Xcalibur2 diffractometer with Sapphire 3 CCD detector | 2461 reflections with I > 2σ(I) |
Radiation source: fine-focus sealed tube | Rint = 0.022 |
Graphite monochromator | θmax = 27.0°, θmin = 4.4° |
ϕ and ω scans | h = −11→11 |
9188 measured reflections | k = −11→11 |
3183 independent reflections | l = −12→12 |
Refinement top
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)] = 0.047 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.145 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.11 | w = 1/[σ2(Fo2) + (0.0883P)2 + 0.0256P] where P = (Fo2 + 2Fc2)/3 |
3183 reflections | (Δ/σ)max < 0.001 |
184 parameters | Δρmax = 0.30 e Å−3 |
2 restraints | Δρmin = −0.27 e Å−3 |
Crystal data top
C10H16N3+·Cl−·C2H6O | γ = 100.649 (13)° |
Mr = 259.78 | V = 738.9 (2) Å3 |
Triclinic, P1 | Z = 2 |
a = 8.7458 (15) Å | Mo Kα radiation |
b = 9.2177 (14) Å | µ = 0.25 mm−1 |
c = 9.7938 (15) Å | T = 296 K |
α = 96.339 (12)° | 0.48 × 0.19 × 0.18 mm |
β = 105.022 (14)° | |
Data collection top
Oxford Diffraction Xcalibur2 diffractometer with Sapphire 3 CCD detector | 2461 reflections with I > 2σ(I) |
9188 measured reflections | Rint = 0.022 |
3183 independent reflections | |
Refinement top
R[F2 > 2σ(F2)] = 0.047 | 2 restraints |
wR(F2) = 0.145 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.11 | Δρmax = 0.30 e Å−3 |
3183 reflections | Δρmin = −0.27 e Å−3 |
184 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 | Occ. (<1) |
Cl1 | 0.39400 (5) | 0.78069 (5) | 0.08104 (6) | 0.0596 (2) | |
O1 | 0.2560 (2) | 0.8158 (3) | 0.3556 (3) | 0.1024 (8) | |
H1O | 0.272 (4) | 0.786 (3) | 0.290 (3) | 0.078 (10)* | |
N1 | −0.24967 (17) | 0.02685 (16) | 0.16455 (17) | 0.0498 (4) | |
H1A | −0.3283 | −0.0379 | 0.1752 | 0.060* | |
H1B | −0.2681 | 0.1061 | 0.1305 | 0.060* | |
N2 | −0.06852 (19) | −0.11549 (16) | 0.25277 (17) | 0.0478 (4) | |
H2N | 0.023 (3) | −0.113 (3) | 0.285 (3) | 0.069 (7)* | |
N3 | 0.4164 (2) | 0.4300 (2) | 0.1313 (2) | 0.0626 (5) | |
H13N | 0.406 (3) | 0.522 (3) | 0.125 (2) | 0.069 (7)* | |
H23N | 0.491 (3) | 0.397 (2) | 0.101 (2) | 0.052 (5)* | |
C1 | 0.1721 (2) | 0.07569 (18) | 0.16374 (18) | 0.0443 (4) | |
H1 | 0.1801 | −0.0236 | 0.1626 | 0.053* | |
C2 | 0.2983 (2) | 0.17866 (19) | 0.14698 (19) | 0.0469 (4) | |
H2 | 0.3906 | 0.1484 | 0.1357 | 0.056* | |
C3 | 0.2894 (2) | 0.32857 (19) | 0.14663 (18) | 0.0464 (4) | |
C4 | 0.1493 (2) | 0.3699 (2) | 0.1640 (2) | 0.0532 (5) | |
H4 | 0.1408 | 0.4690 | 0.1638 | 0.064* | |
C5 | 0.0233 (2) | 0.26660 (19) | 0.1814 (2) | 0.0490 (4) | |
H5 | −0.0693 | 0.2966 | 0.1925 | 0.059* | |
C6 | 0.03322 (19) | 0.11669 (17) | 0.18236 (16) | 0.0407 (4) | |
C7 | −0.1006 (2) | 0.00468 (18) | 0.20043 (17) | 0.0415 (4) | |
C8 | −0.1875 (2) | −0.2401 (2) | 0.2734 (2) | 0.0525 (5) | |
H8 | −0.2931 | −0.2449 | 0.2051 | 0.063* | |
C9 | −0.1362 (3) | −0.3857 (2) | 0.2419 (3) | 0.0676 (6) | |
H9A | −0.1246 | −0.3974 | 0.1468 | 0.101* | |
H9B | −0.2172 | −0.4680 | 0.2492 | 0.101* | |
H9C | −0.0344 | −0.3840 | 0.3099 | 0.101* | |
C10 | −0.2031 (4) | −0.2119 (3) | 0.4230 (3) | 0.0982 (9) | |
H10A | −0.1001 | −0.2057 | 0.4912 | 0.147* | |
H10B | −0.2823 | −0.2925 | 0.4357 | 0.147* | |
H10C | −0.2369 | −0.1195 | 0.4375 | 0.147* | |
C11 | 0.3546 (4) | 0.7966 (4) | 0.4878 (4) | 0.1129 (11) | |
H11A | 0.3166 | 0.8401 | 0.5641 | 0.135* | 0.728 (14) |
H11B | 0.4647 | 0.8516 | 0.5009 | 0.135* | 0.728 (14) |
H11C | 0.3896 | 0.8916 | 0.5526 | 0.135* | 0.272 (14) |
H11D | 0.4508 | 0.7672 | 0.4731 | 0.135* | 0.272 (14) |
C12A | 0.3576 (9) | 0.6454 (5) | 0.5014 (7) | 0.115 (3) | 0.728 (14) |
H12D | 0.4314 | 0.6420 | 0.5920 | 0.172* | 0.728 (14) |
H12E | 0.3928 | 0.6004 | 0.4252 | 0.172* | 0.728 (14) |
H12F | 0.2507 | 0.5916 | 0.4962 | 0.172* | 0.728 (14) |
C12B | 0.2716 (19) | 0.6835 (19) | 0.5549 (15) | 0.118 (6) | 0.272 (14) |
H12A | 0.1903 | 0.7215 | 0.5883 | 0.177* | 0.272 (14) |
H12B | 0.3492 | 0.6614 | 0.6345 | 0.177* | 0.272 (14) |
H12C | 0.2211 | 0.5939 | 0.4859 | 0.177* | 0.272 (14) |
Atomic displacement parameters (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
Cl1 | 0.0469 (3) | 0.0539 (3) | 0.0862 (4) | 0.0182 (2) | 0.0204 (2) | 0.0309 (2) |
O1 | 0.0802 (12) | 0.158 (2) | 0.1109 (17) | 0.0646 (13) | 0.0459 (12) | 0.0880 (16) |
N1 | 0.0435 (8) | 0.0449 (8) | 0.0675 (10) | 0.0140 (6) | 0.0197 (7) | 0.0200 (7) |
N2 | 0.0380 (8) | 0.0474 (8) | 0.0598 (9) | 0.0101 (6) | 0.0113 (7) | 0.0217 (7) |
N3 | 0.0548 (10) | 0.0492 (10) | 0.0901 (13) | 0.0079 (8) | 0.0296 (9) | 0.0231 (9) |
C1 | 0.0472 (9) | 0.0376 (8) | 0.0505 (9) | 0.0126 (7) | 0.0141 (7) | 0.0116 (7) |
C2 | 0.0433 (9) | 0.0466 (9) | 0.0549 (10) | 0.0149 (7) | 0.0155 (7) | 0.0138 (8) |
C3 | 0.0480 (9) | 0.0438 (9) | 0.0466 (9) | 0.0061 (7) | 0.0133 (7) | 0.0117 (7) |
C4 | 0.0558 (11) | 0.0361 (9) | 0.0707 (12) | 0.0117 (7) | 0.0208 (9) | 0.0127 (8) |
C5 | 0.0496 (10) | 0.0431 (9) | 0.0615 (11) | 0.0163 (7) | 0.0222 (8) | 0.0129 (8) |
C6 | 0.0442 (9) | 0.0376 (8) | 0.0408 (8) | 0.0093 (7) | 0.0121 (7) | 0.0089 (7) |
C7 | 0.0439 (9) | 0.0410 (8) | 0.0417 (8) | 0.0113 (7) | 0.0137 (7) | 0.0090 (7) |
C8 | 0.0421 (9) | 0.0479 (10) | 0.0696 (12) | 0.0073 (7) | 0.0143 (8) | 0.0265 (9) |
C9 | 0.0640 (12) | 0.0485 (11) | 0.0881 (15) | 0.0105 (9) | 0.0172 (11) | 0.0173 (10) |
C10 | 0.133 (3) | 0.0783 (17) | 0.111 (2) | 0.0178 (16) | 0.082 (2) | 0.0302 (15) |
C11 | 0.094 (2) | 0.118 (3) | 0.122 (3) | 0.0215 (18) | 0.0116 (18) | 0.048 (2) |
C12A | 0.123 (5) | 0.089 (3) | 0.103 (4) | 0.005 (3) | −0.016 (3) | 0.041 (3) |
C12B | 0.142 (13) | 0.169 (14) | 0.078 (8) | 0.078 (11) | 0.043 (8) | 0.059 (8) |
Geometric parameters (Å, º) top
O1—C11 | 1.407 (4) | C8—C10 | 1.506 (3) |
O1—H1O | 0.73 (3) | C8—C9 | 1.517 (3) |
N1—C7 | 1.320 (2) | C8—H8 | 0.9800 |
N1—H1A | 0.8600 | C9—H9A | 0.9600 |
N1—H1B | 0.8600 | C9—H9B | 0.9600 |
N2—C7 | 1.317 (2) | C9—H9C | 0.9600 |
N2—C8 | 1.470 (2) | C10—H10A | 0.9600 |
N2—H2N | 0.77 (3) | C10—H10B | 0.9600 |
N3—C3 | 1.365 (2) | C10—H10C | 0.9600 |
N3—H13N | 0.87 (3) | C11—C12A | 1.419 (5) |
N3—H23N | 0.87 (2) | C11—C12B | 1.472 (9) |
C1—C2 | 1.374 (2) | C11—H11A | 0.9700 |
C1—C6 | 1.386 (2) | C11—H11B | 0.9700 |
C1—H1 | 0.9300 | C11—H11C | 0.9700 |
C2—C3 | 1.399 (2) | C11—H11D | 0.9700 |
C2—H2 | 0.9300 | C12A—H12D | 0.9600 |
C3—C4 | 1.393 (3) | C12A—H12E | 0.9600 |
C4—C5 | 1.377 (2) | C12A—H12F | 0.9600 |
C4—H4 | 0.9300 | C12B—H12A | 0.9600 |
C5—C6 | 1.401 (2) | C12B—H12B | 0.9600 |
C5—H5 | 0.9300 | C12B—H12C | 0.9600 |
C6—C7 | 1.473 (2) | | |
| | | |
C11—O1—H1O | 119 (2) | C10—C8—H8 | 108.5 |
C7—N1—H1A | 120.0 | C9—C8—H8 | 108.5 |
C7—N1—H1B | 120.0 | C8—C9—H9A | 109.5 |
H1A—N1—H1B | 120.0 | C8—C9—H9B | 109.5 |
C7—N2—C8 | 126.21 (15) | H9A—C9—H9B | 109.5 |
C7—N2—H2N | 115.2 (18) | C8—C9—H9C | 109.5 |
C8—N2—H2N | 118.0 (18) | H9A—C9—H9C | 109.5 |
C3—N3—H13N | 118.6 (16) | H9B—C9—H9C | 109.5 |
C3—N3—H23N | 118.5 (13) | C8—C10—H10A | 109.5 |
H13N—N3—H23N | 120 (2) | C8—C10—H10B | 109.5 |
C2—C1—C6 | 121.39 (15) | H10A—C10—H10B | 109.5 |
C2—C1—H1 | 119.3 | C8—C10—H10C | 109.5 |
C6—C1—H1 | 119.3 | H10A—C10—H10C | 109.5 |
C1—C2—C3 | 120.72 (16) | H10B—C10—H10C | 109.5 |
C1—C2—H2 | 119.6 | O1—C11—C12A | 114.5 (3) |
C3—C2—H2 | 119.6 | O1—C11—C12B | 113.0 (6) |
N3—C3—C4 | 121.87 (17) | O1—C11—H11A | 108.6 |
N3—C3—C2 | 120.09 (17) | C12A—C11—H11A | 108.6 |
C4—C3—C2 | 118.04 (15) | O1—C11—H11B | 108.6 |
C5—C4—C3 | 121.14 (16) | C12A—C11—H11B | 108.6 |
C5—C4—H4 | 119.4 | H11A—C11—H11B | 107.6 |
C3—C4—H4 | 119.4 | O1—C11—H11C | 109.0 |
C4—C5—C6 | 120.56 (16) | C12B—C11—H11C | 109.0 |
C4—C5—H5 | 119.7 | O1—C11—H11D | 109.0 |
C6—C5—H5 | 119.7 | C12B—C11—H11D | 109.0 |
C1—C6—C5 | 118.14 (15) | C11—C12A—H12D | 109.5 |
C1—C6—C7 | 120.58 (14) | C11—C12A—H12E | 109.5 |
C5—C6—C7 | 121.27 (15) | C11—C12A—H12F | 109.5 |
N2—C7—N1 | 121.42 (15) | C11—C12B—H12A | 109.5 |
N2—C7—C6 | 119.07 (15) | C11—C12B—H12B | 109.5 |
N1—C7—C6 | 119.51 (14) | H12A—C12B—H12B | 109.5 |
N2—C8—C10 | 109.60 (17) | C11—C12B—H12C | 109.5 |
N2—C8—C9 | 109.25 (16) | H12A—C12B—H12C | 109.5 |
C10—C8—C9 | 112.46 (19) | H12B—C12B—H12C | 109.5 |
N2—C8—H8 | 108.5 | | |
| | | |
C6—C1—C2—C3 | −0.7 (3) | C4—C5—C6—C7 | −179.83 (16) |
C1—C2—C3—N3 | 179.34 (17) | C8—N2—C7—N1 | 2.4 (3) |
C1—C2—C3—C4 | 0.1 (3) | C8—N2—C7—C6 | −177.88 (16) |
N3—C3—C4—C5 | −179.06 (18) | C1—C6—C7—N2 | 25.8 (2) |
C2—C3—C4—C5 | 0.2 (3) | C5—C6—C7—N2 | −155.16 (17) |
C3—C4—C5—C6 | 0.2 (3) | C1—C6—C7—N1 | −154.49 (16) |
C2—C1—C6—C5 | 1.0 (2) | C5—C6—C7—N1 | 24.6 (2) |
C2—C1—C6—C7 | −179.89 (15) | C7—N2—C8—C10 | −92.5 (2) |
C4—C5—C6—C1 | −0.8 (3) | C7—N2—C8—C9 | 143.84 (19) |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
N1—H1A···Cl1i | 0.86 | 2.56 | 3.344 (2) | 153 |
N1—H1B···Cl1ii | 0.86 | 2.51 | 3.275 (2) | 148 |
O1—H1O···Cl1 | 0.73 (3) | 2.54 (3) | 3.229 (3) | 158 (3) |
N2—H2N···O1iii | 0.78 (3) | 2.22 (3) | 2.965 (3) | 162 (3) |
N3—H13N···Cl1 | 0.88 (3) | 2.49 (3) | 3.356 (2) | 172 (2) |
N3—H23N···Cl1iv | 0.87 (3) | 2.79 (2) | 3.596 (2) | 155 (2) |
C1—H1···O1iii | 0.93 | 2.56 | 3.277 (3) | 135 |
C8—H8···Cl1i | 0.98 | 2.76 | 3.708 (2) | 164 |
Symmetry codes: (i) x−1, y−1, z; (ii) −x, −y+1, −z; (iii) x, y−1, z; (iv) −x+1, −y+1, −z. |
Experimental details
Crystal data |
Chemical formula | C10H16N3+·Cl−·C2H6O |
Mr | 259.78 |
Crystal system, space group | Triclinic, P1 |
Temperature (K) | 296 |
a, b, c (Å) | 8.7458 (15), 9.2177 (14), 9.7938 (15) |
α, β, γ (°) | 96.339 (12), 105.022 (14), 100.649 (13) |
V (Å3) | 738.9 (2) |
Z | 2 |
Radiation type | Mo Kα |
µ (mm−1) | 0.25 |
Crystal size (mm) | 0.48 × 0.19 × 0.18 |
|
Data collection |
Diffractometer | Oxford Diffraction Xcalibur2 diffractometer with Sapphire 3 CCD detector |
Absorption correction | – |
No. of measured, independent and observed [I > 2σ(I)] reflections | 9188, 3183, 2461 |
Rint | 0.022 |
(sin θ/λ)max (Å−1) | 0.639 |
|
Refinement |
R[F2 > 2σ(F2)], wR(F2), S | 0.047, 0.145, 1.11 |
No. of reflections | 3183 |
No. of parameters | 184 |
No. of restraints | 2 |
H-atom treatment | H atoms treated by a mixture of independent and constrained refinement |
Δρmax, Δρmin (e Å−3) | 0.30, −0.27 |
Selected geometric parameters (Å, º) topN1—C7 | 1.320 (2) | N3—C3 | 1.365 (2) |
N2—C7 | 1.317 (2) | C6—C7 | 1.473 (2) |
N2—C8 | 1.470 (2) | | |
| | | |
C7—N2—C8 | 126.21 (15) | N2—C7—C6 | 119.07 (15) |
N2—C7—N1 | 121.42 (15) | N1—C7—C6 | 119.51 (14) |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
N1—H1A···Cl1i | 0.86 | 2.56 | 3.344 (2) | 153 |
N1—H1B···Cl1ii | 0.86 | 2.51 | 3.275 (2) | 148 |
O1—H1O···Cl1 | 0.73 (3) | 2.54 (3) | 3.229 (3) | 158 (3) |
N2—H2N···O1iii | 0.78 (3) | 2.22 (3) | 2.965 (3) | 162 (3) |
N3—H13N···Cl1 | 0.88 (3) | 2.49 (3) | 3.356 (2) | 172 (2) |
N3—H23N···Cl1iv | 0.87 (3) | 2.79 (2) | 3.596 (2) | 155 (2) |
C1—H1···O1iii | 0.93 | 2.56 | 3.277 (3) | 135 |
C8—H8···Cl1i | 0.98 | 2.76 | 3.708 (2) | 164 |
Symmetry codes: (i) x−1, y−1, z; (ii) −x, −y+1, −z; (iii) x, y−1, z; (iv) −x+1, −y+1, −z. |
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Amidine compounds have been widely investigated because of their biological activity. One of the first groups of amidine-substituted organic compounds included pentamidine and its analogs, which were prepared for screening against a rat model of Pneumocystis carinii pneumonia (PCP) (Tidwell et al., 1990; Patric et al., 1997). In addition to their activity against PCP, these compounds were also evaluated for DNA affinity, and showed modest anti-HIV-1 activity and selectivity in primary lymphocytes (Kumar et al., 1996). Amidine compounds show antiparasitic activity (Danan et al., 1997) and antifungal activity (Del Poeta, Schell, Dykstra, Jones, Tidwell, Czarny et al., 1998), as well as activity against a wide range of eucaryotic pathogens for Candida albicans and Cryptococus neoformans. Selected compounds were also found to be active against Aspergillus fumigantus, Fusarium solani and Candida species other than C. albicans (Del Poeta, Schell, Dykstra, Jones, Tidwell, Kumar et al., 1998).
We have synthesized and characterized a number of heterocyclic amidines and trisamidines of benzodithiophene, benzothienofuran, naphtho[2,1-b]furan and benzothiazole, which have potential as anticancer agents (Starčević et al., 2002, 2003; Hranjec et al., 2003; Ćaleta et al., 2003; Matković-Čalogović et al., 2003).
The molecule of (I) (Fig. 1) is not planar. The carboxamidinium moiety has a synperiplanar disposition with respect to the aniline group [C1—C6—C7—N2 = 25.8 (2)°]. This twist may serve to accommodate the formation of intermolecular hydrogen bonds. Deviation from coplanarity is observed, however, in other N-isopropylamidine derivatives, such as 6-(N-isopropyl)amidino-2-methylbenzothiazole and 2-amino-6-(N-isopropyl)amidinobenzothiazole, synthesized in the form of their hydrocloride salts (Ćaleta et al., 2003), in 2-amino-6-[N-(2-morpholine-4-yl-ethyl)]-1,3-benzothiazolecarboxamidinium chloride (Ćaleta et al., 2004) and in 1,3-benzothiazole-6-carboxamidinium chloride dihydrate (Matković-Čalogović et al., 2003).
The isopropyl substituent at atom N2 has an anticlinal disposition relative to atom N1 [C7—N2—C8—C9 = 143.84 (19)° and C7—N2—C8—C10 = −92.5 (2)°]. The bond distance values of C7—N1, 1.320 (2) Å, and C7—N2, 1.317 (2) Å, are equal to within 3σ, reflecting the protonation of the amidine group, while the N2—C8 bond [1.470 (2) Å] is σ in character. The N3—C3 and C6—C7 bond distances are shortened [1.365 (2) and 1.473 (2) Å, respectively] and exhibit partial π character, indicating some degree of π-electron delocalization through both the phenyl and the amidine moiety. Other bond distances are within expected values (Allen et al., 1987).
The cations and chloride ions are involved in a network of intermolecular hydrogen bonds, resulting in the formation of infinite chains propagating in the b direction (Fig. 2). The different moieties present are grouped into an AB pattern of layers parallel to the crystallographic ab plane, and composed alternately of amidinium cations and chloride ions. The layer formed principally by the N-isopropyl group of the cation and the ethyl residues of EtOH solvent molecules is characterized by hydrophobic interactions, while the layer containing the chloride ions is dominated by intermolecular hydrogen bonds. The chloride ion participates in N—H···Cl hydrogen-bond formation as a multiple proton acceptor, interacting with both the amine and amidine NH groups, [N···Cl range 3.275 (2)–3.597 (2) Å; Table 2]. The chloride ion is also involved in an O—H···Cl hydrogen bond with the ethanol O atom [O···Cl = 3.229 (3) Å]. The NH amidine group acts as a donor to the ethanol O atom, with an N···O distance of 2.966 (3) Å.