6-Aminopyridine-3-thiol

The title compound, C₅H₆N₂S, is a simple but novel pyridinethiol of pharmacological interest. The mol­ecule is planar. The crystal packing is dominated by hydro­phobic contacts and a pair of hydrogen-bond interactions between the amino group of one pyridine mol­ecule and the ring N atom of a neighbouring base, stabilizing the structure.

S1. Comment

During research on reproduction suppressors of Schistosoma mansoni and Trypanosoma cruzi, a number of compounds containing S have been prepared (Van den Hoek et al., 1998). Enzyme assays have shown that some dithiocarbamates are capable of inhibiting superoxide dismutase activity (da Silva, 2000). Such enzymes have been found in S. mansoni and T. cruzi and may play an important role in the parasite's defence against the host's immune response (Hong et al., 1992; Temperton et al., 1996). The preparation of such dithiocarbamates, derived from amines, generates secondary products of reaction, such as thiolpyridines, which are also active against schistosomes (da Silva, 2000; Fathala et al., 2000). In the light of this work, the structure of the title compound, (I), has been determined and the results are presented here. \sch

The structure of (I) is essentially planar, with an angle of 9(2)° between the plane of the ring and that of the amino group, with atoms N2 - 0.017 (3), H2A -0.02 (3) and H2B 0.11 (3) Å from the ring plane. The three angles around atom C5 are slightly deformed by the amino group, as is seen in other aminopyridines (Chao et al., 1975; Kvick et al., 1976). This behaviour characterizes the resonance of the N2 lone pair with the aromatic ring. The effect can also be verified by the shortening of the C5—N2 bond [1.367 (3) Å] relative to a normal single C—N bond (e.g. 1.483 Å for C—N in methaneamine, such as reported by Atoji & Lipscomb, 1953).

The thiol group at the C2 position (para to the amino group) does not cause much distortion of the angles around C2 from the ideal value of 120°, as was also seen when the substituent was a chloro group (Kvick et al., 1976). However, the angles around this same carbon position in unsubstituted 2-aminopyridine (Chao et al., 1975) are significantly distorted from 120°.

The crystal packing in (I) is dominated by hydrophobic contacts and a pair of hydrogen-bond interactions between the N2 amino group of one pyridine molecule and the ring atom N1 of another molecule related by a centre of symmetry, with N2···N1ⁱ 3.028 (2) Å and N2—H···N1ⁱ 179 (3)° [Fig. 2; symmetry code: (i) -x, -y, -z]. As in other 2-aminopyridines (Chao et al., 1975; Kvick et al., 1976), base-base stacking interactions do not appear to be an additional factor stabilizing the crystal structure, such as has been reported for aminopyrimidine packing (Aoki & Yamazaki, 1989).

S2. Experimental

Dithiocarbamates were prepared as previously described by Bereman & Nalewajek (1978). The compound used in the present experiment was obtained by adding n-butyllithium (4.20 ml, 2.4 M) to 2-amino-5-chloropyridine (1.31 g, 10 mmol) dissolved in dry tetrahydrofuran (20 ml) and allowing the reaction to proceed for 1 h. Carbon disulfide (0.62 ml, 12 mmol) was added dropwise to the mixture at 195 K over 30 min. The resulting red-yellow solution was stirred for 1 h. Precipitation was achieved by adding degassed hexane at 253 K and the precipitate was collected by filtration. The crystalline powder, (I), was recrystallized from acetone at room temperature.

S3. Refinement

At room temperature, rapid intensity decay occurred after short exposure to the X-ray beam and the crystals became completely black. The sample was immersed in synthetic oil, attached to the glass fibre by surface tension and quenched under a nitrogen stream at 100 K, which also eliminated the crystal decay. Cell parameters were determined with all data. The data were corrected for polarization and Lorentz factors but not for absorption. Atoms H1, H3 and H4 were placed in calculated positions, with C—H = 0.95 Å, while atoms H2A and H2B were located in difference Fourier maps and constrained to be 0.92 Å from atom N2 (Fig. 1). Atoms H1, H3 and H4 were refined with riding model constraints, with U_iso(H) = 1.2U_eq(C), while atoms H2A and H2B were refined isotropically. The H atom bound to S was omitted from the refinement. A previous attempt to refine the thiol H atom with an S—H distance restraint was unsuccessful. Another refinement with free structural parameters resulted in an inappropriate S—H bond length.

Computing details

Data collection: COLLECT (Nonius, 1997-2000); cell refinement: COLLECT; data reduction: HKL-2000 (Otwinowski & Minor, 1997); program(s) used to solve structure: SIR92 (Altomare et al., 1994); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: PLATON (Spek, 1990); software used to prepare material for publication: SHELXL97.

Figures

	Fig. 1. The molecular structure of (I) with 50% probability displacement ellipsoids. The H atom bound to S has been omitted, and the remaining H atoms are shown as small spheres of arbitrary radii.
	Fig. 2. A stereo view of the crystal packing in (I), showing the N—H···N hydrogen bonds (broken lines) between the rings, which are related by a centre of symmetry. The b axis is normal to the page.

2-amino-5-thiolpyridine

Crystal data

C5H6N2S	F(000) = 264
Mr = 126.18	Dx = 1.539 Mg m^−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
a = 13.3430 (3) Å	Cell parameters from 2311 reflections
b = 5.7560 (3) Å	θ = 3.2–27.5°
c = 7.2730 (6) Å	µ = 0.47 mm^−1
β = 104.753 (3)°	T = 100 K
V = 540.17 (5) Å^3	Prismatic, light orange
Z = 4	0.07 × 0.05 × 0.03 mm

Data collection

Nonius KappaCCD area-detector diffractometer	1001 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.036
Graphite monochromator	θmax = 27.5°, θmin = 3.2°
oscillation scans	h = 0→17
2311 measured reflections	k = −7→7
1240 independent reflections	l = −9→9

Refinement

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F^2 > 2σ(F^2)] = 0.036	H atoms treated by a mixture of independent and constrained refinement
wR(F^2) = 0.100	w = 1/[σ^2(Fo^2) + (0.0563P)^2 + 0.08P] where P = (Fo^2 + 2Fc^2)/3
S = 1.05	(Δ/σ)max < 0.001
1240 reflections	Δρmax = 0.32 e Å^−3
86 parameters	Δρmin = −0.23 e Å^−3
2 restraints	Extinction correction: SHELXL97 (Sheldrick, 1997), Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.031 (6)

Special details

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Refinement. Refinement of F^{2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F}2, conventional R-factors R are based on F, with F set to zero for negative F^{2. The threshold expression of F}2 > σ(F^{2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F}2 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 (Ų)

	x	y	z	Uiso*/Ueq
C1	0.22172 (14)	0.2029 (3)	0.0894 (3)	0.0224 (4)
H1	0.2148	0.3508	0.1430	0.027*
C2	0.31823 (14)	0.1363 (3)	0.0713 (3)	0.0221 (4)
C3	0.32983 (14)	−0.0804 (3)	−0.0062 (2)	0.0232 (4)
H3	0.3956	−0.1312	−0.0181	0.028*
C4	0.24367 (15)	−0.2184 (3)	−0.0650 (3)	0.0239 (4)
H4	0.2490	−0.3664	−0.1196	0.029*
C5	0.14730 (14)	−0.1396 (3)	−0.0438 (3)	0.0236 (4)
N1	0.13713 (12)	0.0681 (3)	0.0346 (2)	0.0239 (4)
N2	0.06043 (13)	−0.2746 (3)	−0.0966 (3)	0.0320 (4)
H2A	0.0000 (11)	−0.214 (5)	−0.078 (3)	0.045 (7)*
H2B	0.062 (2)	−0.408 (3)	−0.166 (3)	0.054 (8)*
S1	0.42348 (3)	0.32395 (8)	0.13957 (6)	0.0230 (2)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C1	0.0223 (9)	0.0205 (9)	0.0239 (9)	0.0012 (7)	0.0053 (7)	0.0020 (7)
C2	0.0212 (9)	0.0233 (9)	0.0215 (9)	−0.0025 (7)	0.0050 (7)	0.0017 (7)
C3	0.0239 (9)	0.0223 (9)	0.0245 (9)	0.0033 (7)	0.0084 (7)	0.0033 (7)
C4	0.0281 (9)	0.0209 (9)	0.0231 (9)	0.0026 (8)	0.0074 (7)	0.0003 (8)
C5	0.0234 (9)	0.0248 (10)	0.0221 (8)	−0.0011 (7)	0.0050 (7)	0.0013 (7)
N1	0.0222 (8)	0.0225 (8)	0.0272 (8)	−0.0002 (6)	0.0067 (6)	−0.0010 (6)
N2	0.0263 (9)	0.0289 (10)	0.0421 (10)	−0.0051 (7)	0.0111 (8)	−0.0093 (8)
S1	0.0189 (3)	0.0222 (3)	0.0276 (3)	−0.00251 (16)	0.00561 (18)	−0.00215 (17)

Geometric parameters (Å, º)

C1—N1	1.344 (2)	C5—N2	1.367 (3)
C1—C2	1.382 (2)	C1—H1	0.9500
C2—C3	1.394 (3)	C3—H3	0.9500
C2—S1	1.7406 (18)	C4—H4	0.9500
C3—C4	1.373 (3)	N2—H2A	0.920 (5)
C4—C5	1.408 (3)	N2—H2B	0.921 (5)
C5—N1	1.346 (3)
C1—C2—C3	119.28 (17)	N1—C1—H1	118.5
C1—C2—S1	120.31 (15)	C2—C1—H1	118.5
C3—C2—S1	120.39 (14)	C4—C3—C2	118.25 (17)
N1—C5—N2	117.01 (17)	C4—C3—H3	120.9
N1—C5—C4	121.72 (17)	C2—C3—H3	120.9
N2—C5—C4	121.23 (18)	C3—C4—C5	119.66 (17)
C5—N2—H2A	117.0 (17)	C3—C4—H4	120.2
C5—N2—H2B	119.5 (17)	C5—C4—H4	120.2
H2A—N2—H2B	123 (2)	C1—N1—C5	118.09 (16)
N1—C1—C2	122.97 (18)
N1—C1—C2—C3	−0.3 (3)	C3—C4—C5—N1	−0.6 (3)
N1—C1—C2—S1	178.24 (14)	C3—C4—C5—N2	−178.46 (18)
C1—C2—C3—C4	1.1 (3)	C2—C1—N1—C5	−1.0 (3)
S1—C2—C3—C4	−177.42 (14)	N2—C5—N1—C1	179.37 (18)
C2—C3—C4—C5	−0.6 (3)	C4—C5—N1—C1	1.5 (3)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2A···N1^i	0.92 (1)	2.11 (1)	3.028 (2)	179 (3)

Symmetry code: (i) −x, −y, −z.