Mol­ecular cocrystals of 5-(4-bromo­phenyl)-1,3,4-thia­diazol-2-amine: hydrogen bonding in the structures of the 1:1 adduct with 2-(naphthalen-2-yl­oxy)acetic acid and the salt with 3,5-di­nitro­benzoic acid

The crystal structures of the anhydrous products from the inter­action of 5-(4-bromo­phenyl)-1,3,4-thia­diazol-2-amine with 2-(naphthalen-2-yl­oxy)acetic acid, viz. the 1:1 adduct C₈H₆BrN₃S·C₁₂H₁₀O₃, (I), and with 3,5-di­nitro­benzoic acid, viz. the salt 2-amino-5-(4-bromo­phenyl)-1,2,4-thia­diazol-3-ium 3,5-di­nitro­benzoate, C₈H₇BrN₃S⁺·C₇H₃N₂O₆⁻, (II), have been determined. In adduct (I), a heterodimer is formed through a cyclic hydrogen-bonding motif [graph set R₂²(8)], involving carb­oxy­lic acid–heteroatom O—H...N and amine–carb­oxy­lic acid N—H...O inter­actions. The heterodimers are essentially planar, with a thia­diazole-to-naphthalene ring dihedral angle of 15.9 (2)° and an intra­molecular thia­diazole-to-benzene ring angle of 4.7 (2)°. An amine–heteroatom N—H...N hydrogen bond between the heterodimers generates a one-dimensional chain structure extending down [001]. Also present are weak benzene–benzene and naphthalene–naphthalene π–π stacking inter­actions down the b axis [minimum ring-centroid separation = 3.936 (3) Å]. With salt (II), the cation–anion association is also through a cyclic R₂²(8) motif but involving duplex N—H...O_carboxylate hydrogen bonds, giving a heterodimer that is close to planar [dihedral angles between the thia­diazole ring and the two benzene rings = 5.00 (16) (intra) and 7.23 (15)° (inter)]. A secondary centrosymmetric cyclic (8) N—H...O_{carbox­ylate} hydrogen-bonding association involving the second amino H atom generates a hetero­tetra­mer. Also present in the crystal structure are weak π–π inter­actions between thia­diazo­lium rings [minimum ring-centroid separation = 3.9466 (18) Å], as well as a short Br...O_nitro inter­action [3.314 (4) Å]. The two structures reported here now provide a total of three crystallographically characterized examples of cocrystalline products from the inter­action of 5-(4-bromo­phen­yl)-1,3,4-thia­diazol-2-amine with carb­oxy­lic acids, of which only one involves proton transfer.

S1. Introduction

1,3,4-Thia­diazo­les exhibit a broad range of biological activities (Jain et al., 2013) and numerous crystal structures of these compounds have been reported. The structure count of 1,3,4-thia­dizol-2-amine derivatives alone is currently well over 100. These compounds, like many other 2-amino-N(1)-heterocyclic compounds, inter­associate in the solid state through a centrosymmetric cyclic hydrogen-bonding motif [graph set R₂²(8); Etter et al., 1990] involving duplex N—H···N hydrogen bonds. In many cases, the second H atom of the 2-amino group forms an inter­molecular hydrogen bond with an N4 heteroatom, giving a polymer extension. This secondary association is still observed in some of the structures of 5-phenyl-1,3,4-thia­diazol-2-amine analogues. Currently, there are 12 known structures of these having variously substituted 5-phenyl rings (Wan et al., 2006, 2009; Guan et al., 2009; Wang, Kong et al., 2009; Wang et al., 2009a,b,c,d; Yin et al., 2008; Lynch, 2009a,b; Zhang et al., 2011). However, there is only one reported structure of a cocrystal of a 5-phenyl-substituted analogue of the parent compound, that being the 1:1 adduct of 5-(4-meth­oxy­phenyl)-1,3,4-thia­diazol-2-amine with 4-nitro­benzoic acid (Lynch, 2009c). In this structure, the carb­oxy­lic acid group forms a cyclic R₂²(8) association across the N3/N21 site through carb­oxy­lic acid O—H···N and amine N—H···O hydrogen bonds. This association is analogous with the common carb­oxy­lic acid–pyrimidin-2-amine homodimeric motif (Etter & Adsmond, 1990). In the 4-nitro­benzoic acid adduct, the second amino H atom inter­associates with atom N4 of an adjacent molecule, giving a one-dimensional chain structure.

We report here the structures of the 1:1 adduct of 5-(4-bromo­phenyl)-1,3,4-thia­diazol-2-amine with 2-(naphthalen-2-yl­oxy)acetic acid, (I) (Fig. 1), and the salt with 3,5-di­nitro­benzoic acid, 2-amino-5-(4-bromo­phenyl)-1,2,4-thia­diazol-3-ium 3,5-di­nitro­benzoate, (II) (Fig. 2). 3,5-Di­nitro­benzoic acid has been employed extensively for the formation of cocrystalline adducts with Lewis bases and some carb­oxy­lic acids (Etter & Frankenbach, 1989; Lynch et al., 1991; Krishnamohan Sharma et al., 1993), and many structures have been reported. In a minority are the structures of proton-transfer salts of this acid, e.g. with organic di­amines (Burchell et al., 2001) or with isonipecotamide (Smith & Wermuth, 2010).

S2. Experimental

S2.1. Synthesis and crystallization

Compounds (I) and (II) were prepared by the reaction of 5-(4-bromo­phenyl)-1,3,4-thia­diazol-2-amine (1 mmol, 260 mg) with, respectively, 2-(naphthalen-2-yl­oxy)acetic acid (1 mmol, 200 mg) or 3,5-di­nitro­benzoic acid (1 mmol 210 mg) in ethanol (30 ml), with 10 min of reflux. Partial evaporation of the solvent gave colourless plates of (I) and pale-yellow prisms of (II), from which specimens were cleaved for the X-ray analyses.

S2.2. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 1. H atoms potentially involved in hydrogen-bonding inter­actions were located by difference methods and their positional and isotropic displacement parameters were refined. Other H atoms were included at calculated positions (aromatic C—H = 0.95 Å) and treated as riding, with U_iso(H) = 1.2U_eq(C). Although not of particular relevance in the achiral structure of (I), the absolute structure Flack parameter (Flack, 1983) was determined as 0.001 (13) (1386 Friedel pairs).

S3. Results and discussion

The 1:1 adduct of 5-(4-bromo­phenyl)-1,3,4-thia­diazol-2-amine with (naphthalen-2-yl­oxy)acetic acid (I) (Fig. 1) is similar in many respects to the 1:1 adduct of the 5-meth­oxy analogue with 4-nitro­benzoic acid (Lynch, 2009c). The presence of the adduct rather than a salt structure is confirmed both on the basis of the located and refined H atom on atom N3B, and by features of the carb­oxy­lic acid group [C—O = 1.313 (7) Å and C═O = 1.205 (7) Å]. The dihedral angle between the 4-bromo­phenyl ring and the thia­diazole ring is 4.7 (2)°, while the dihedral angle between the thia­diazole ring and the plane of the naphthalene ring is 15.9 (2)°. These values compare with 25.6 (2) and 32.2 (2)°, respectively, for the corresponding angle in the 5-(4-meth­oxy­phenyl)-1,3,4-thia­diazol-2-amine adduct with 4-nitro­benzoic acid (Lynch, 2009c). In (I), the dihedral angle between the oxyacetic acid group and the naphthalene ring system is 5.7 (2)°, similar to that in the parent acid [3.59 (5)°; Pattabhi et al., 1978; Howie et al., 2001]. Previous cocrystals incorporating 2-(naphthalen-2-yl­oxy)acetic acid include the 1:1 organic salt with 2-thia­zolin-2-amine (Lynch, 2004a) and the 1:1:1 organic salt adduct 2-amino­pyrimidinium 2-(naphthalen-2-yl­oxy)acetate 2-(naphthalen-2-yl­oxy)acetic acid (Lynch, 2004b). The primary inter­molecular association in (I) is also the expected thia­diazole N3/N21···O,O'_carboxyl hydrogen-bonded R₂²(8) motif, giving the heterodimer (Table 2). A secondary association between the second amino H atom and atom N4ⁱ of an adjacent molecule (details and symmetry code in Table 2) gives a one-dimensional chain structure which extends along [001] (Fig. 3). Also present in the structure are weak benzene–benzene and naphthalene–naphthalene π–π ring-stacking inter­actions down the short b-axis direction of the cell [minimum ring-centroid separation = 3.936 (3) Å].

The 3,5-di­nitro­benzoate salt, (II) (Fig. 2), is confirmed as such also on the basis of the located and refined H atom on N3B and the carboxyl C—O bond lengths [1.257 (4) and 1.240 (4) Å]. The primary association in this structure is the expected cyclic R₂²(8) N3/N21···O,O'_{carboxyl­ate} heterodimer motif (Table 3). The difference compared with the adduct motif is in the location of the transferred carb­oxy­lic acid H atom on the hetero N atom, giving duplex N—H···O hydrogen bonds. The dihedral angle between the benzene and thia­diazole rings is 5.00 (16)°, while the angle between the benzoate and thia­diazole rings is 7.23 (15)°. A secondary centrosymmetric cyclic R₂²(8) N21B—H···O_{carboxyl­ate} hydrogen-bonding association involving the second amino H atom generates a hetero­tetra­mer (Fig. 4). Present also are weak π–π inter­actions between thia­diazo­lium rings [minimum ring-centroid separation = 3.936 (3) Å], and a short contact between atom Br1B and nitro atom O31Aⁱⁱ [3.314 (4) Å; symmetry code: (ii) -x, -y, -z + 1]. No associations involving hetero atom N4B are present.

A comparison of the dihedral angles between the two ring systems in the structures of the known 5-phenyl-substituted thia­diazo­les with those of the three known cocrystals [(I) and (II), and including the 4-nitro­benzoic acid adduct (III) (Lynch, 2009c)] (Table 4), indicates that the thia­diazole molecule is generally more planar when it crystallizes with another molecule. This holds true for the 4-meth­oxy derivative (Lynch, 2004a), which is an ethanol solvate with the ethanol O atom associating with atom N4 of the thia­diazole ring through an O—H···N hydrogen bond. Understandably, some of the derivatives listed in Table 4 have large dihedral angles and one, the 4-phen­oxy-substituted analogue (Wan et al., 2009), has a very small angle, because of the influence of their phenyl substitutents (stereochemical as well as associative), but it is inter­esting that all examples having simple unassociative substituent groups have dihedral angles of ca 30° or greater, whereas those which have crystallized with another molecule have dihedral angles of ca 25° or less.

The structures presented here now give a small total of three crystallographically characterized examples of cocrystalline products from the inter­action of 5-(4-bromo­phenyl)-1,3,4-diatriazol-2-amine with carb­oxy­lic acids, of which one, with 3,5-di­nitro­benzoic acid, involves proton transfer. A notable feature is the overall close-to-planar conformational features of the heterodimeric units in these structures compared with the usual conformation of the 5-phenyl-substituted thia­diazo­les themselves.

Related literature

For related literature, see: Burchell et al. (2001); Etter & Adsmond (1990); Etter & Frankenbach (1989); Etter, MacDonald & Bernstein (1990); Flack (1983); Guan et al. (2009); Howie et al. (2001); Jain et al. (2013); Krishnamohan Sharma, Panneerselvam, Pilati & Desiraju (1993); Lynch (2004a, 2004b, 2009a, 2009b, 2009c); Lynch et al. (1991); Pattabhi et al. (1978); Smith & Wermuth (2010); Wan et al. (2006, 2009); Wang et al. (2009, 2009a, 2009b, 2009c, 2009d); Yin et al. (2008); Zhang et al. (2011).

Computing details

For both compounds, data collection: CrysAlis PRO (Agilent, 2012); cell refinement: CrysAlis PRO (Agilent, 2012); data reduction: CrysAlis PRO (Agilent, 2012); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008) within WinGX (Farrugia, 2012); molecular graphics: PLATON (Spek, 2009); software used to prepare material for publication: PLATON (Spek, 2009).

Figures

Fig. 1. The molecular conformation and atom-numbering scheme for adduct (I), with inter-species hydrogen bonds shown as dashed lines. Displacement ellipsoids are drawn at the 50% probability level.

Fig. 2. The molecular conformation and atom-numbering scheme for salt (II), with cation–anion hydrogen bonds shown as dashed lines. Displacement ellipsoids are drawn at the 50% probability level.

Fig. 3. The one-dimensional hydrogen-bonded chain structure in (I), extending down b. Hydrogen-bonding associations are shown as dashed lines and non-associative H atoms have been omitted. [Symmetry code: (i) -x + 1/2, y, z + 1/2.]

Fig. 4. A perspective view of the centrosymmetric hydrogen-bonded heterotetramer units in the structure of (II), showing conjoined cyclic R₂²(8) structural motifs. [Symmetry code: (ii) -x + 2, -y + 1, -z + 1.]

(I) 5-(4-Bromophenyl)-1,3,4-thiadiazol-2-amine–2-(naphthalen-2-yloxy)acetic acid (1/1)

Crystal data

C8H6BrN3S·C12H10O3	F(000) = 928
Mr = 458.33	Dx = 1.629 Mg m^−3
Orthorhombic, Pca21	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2c -2ac	Cell parameters from 1229 reflections
a = 41.357 (2) Å	θ = 3.4–28.8°
b = 3.9369 (3) Å	µ = 2.34 mm^−1
c = 11.4761 (5) Å	T = 200 K
V = 1868.53 (19) Å^3	Plate, colourless
Z = 4	0.30 × 0.22 × 0.05 mm

Data collection

Oxford Gemini-S CCD area-detector diffractometer	3309 independent reflections
Radiation source: fine-focus sealed tube	2842 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.046
Detector resolution: 16.077 pixels mm^-1	θmax = 26.0°, θmin = 3.5°
ω scans	h = −25→51
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2012)	k = −4→4
Tmin = 0.900, Tmax = 0.980	l = −14→11
5208 measured reflections

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)] = 0.056	H atoms treated by a mixture of independent and constrained refinement
wR(F^2) = 0.088	w = 1/[σ^2(Fo^2) + (0.0169P)^2] where P = (Fo^2 + 2Fc^2)/3
S = 1.10	(Δ/σ)max = 0.001
3309 reflections	Δρmax = 0.55 e Å^−3
262 parameters	Δρmin = −0.40 e Å^−3
1 restraint	Absolute structure: Flack (1983), with 1386 Friedel pairs
Primary atom site location: structure-invariant direct methods	Absolute structure parameter: 0.001 (13)

Special details

Geometry. Bond distances, angles etc. have been calculated using the rounded fractional coordinates. All su's are estimated from the variances of the (full) variance-covariance matrix. The cell e.s.d.'s are taken into account in the estimation of distances, angles and torsion angles

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 (Ų)

	x	y	z	Uiso*/Ueq
O21A	0.37092 (9)	0.2424 (9)	0.4263 (3)	0.0300 (12)
O24A	0.30244 (10)	0.7191 (10)	0.3469 (3)	0.0320 (12)
O25A	0.31844 (10)	0.5208 (10)	0.5203 (3)	0.0353 (16)
C1A	0.40911 (13)	0.1450 (11)	0.2690 (5)	0.0193 (16)
C2A	0.40009 (14)	0.1199 (13)	0.3833 (5)	0.0243 (17)
C3A	0.41916 (13)	−0.0339 (14)	0.4674 (5)	0.0273 (19)
C4A	0.44860 (16)	−0.1617 (14)	0.4355 (5)	0.0337 (19)
C5A	0.49032 (12)	−0.2669 (11)	0.2838 (8)	0.0310 (17)
C6A	0.50039 (15)	−0.2460 (13)	0.1718 (6)	0.0357 (19)
C7A	0.47987 (14)	−0.0992 (13)	0.0878 (5)	0.0313 (17)
C8A	0.45075 (13)	0.0257 (13)	0.1191 (5)	0.0247 (17)
C9A	0.43975 (14)	0.0112 (13)	0.2360 (5)	0.0247 (17)
C10A	0.45997 (14)	−0.1417 (12)	0.3197 (5)	0.0263 (18)
C22A	0.35023 (12)	0.4127 (13)	0.3493 (5)	0.0220 (17)
C23A	0.32210 (14)	0.5544 (13)	0.4168 (5)	0.0230 (17)
Br1B	0.07257 (1)	1.78772 (12)	0.29602 (7)	0.0349 (2)
S1B	0.21410 (4)	1.2310 (4)	0.60715 (11)	0.0273 (4)
N3B	0.25182 (12)	0.9844 (12)	0.4541 (3)	0.0227 (16)
N4B	0.22574 (11)	1.1083 (11)	0.3930 (4)	0.0250 (17)
N21B	0.27152 (13)	0.9194 (13)	0.6446 (4)	0.0293 (17)
C2B	0.24955 (17)	1.0268 (12)	0.5671 (5)	0.0233 (19)
C5B	0.20433 (13)	1.2442 (13)	0.4602 (4)	0.0233 (17)
C51B	0.17331 (13)	1.3862 (12)	0.4192 (5)	0.0197 (17)
C52B	0.16513 (12)	1.3892 (11)	0.3010 (6)	0.0273 (17)
C53B	0.13540 (13)	1.5098 (13)	0.2642 (5)	0.0287 (17)
C54B	0.11357 (13)	1.6278 (12)	0.3446 (5)	0.0230 (17)
C55B	0.12100 (15)	1.6299 (13)	0.4620 (5)	0.0290 (17)
C56B	0.15084 (15)	1.5124 (13)	0.4977 (5)	0.0290 (19)
H1A	0.39530	0.24870	0.21320	0.0232*
H3A	0.41190	−0.05030	0.54580	0.0328*
H4A	0.46180	−0.26700	0.49290	0.0404*
H5A	0.50410	−0.36900	0.34000	0.0372*
H6A	0.52110	−0.32950	0.15010	0.0428*
H7A	0.48660	−0.08800	0.00870	0.0376*
H8A	0.43730	0.12580	0.06150	0.0296*
H21A	0.34230	0.25360	0.28880	0.0264*
H22A	0.36200	0.59930	0.31010	0.0264*
H24A	0.2859 (14)	0.823 (13)	0.386 (5)	0.0384*
H21B	0.2885 (14)	0.827 (13)	0.619 (6)	0.0352*
H22B	0.2676 (15)	1.004 (15)	0.719 (5)	0.0352*
H52B	0.18020	1.30740	0.24510	0.0328*
H53B	0.13010	1.51100	0.18360	0.0344*
H55B	0.10580	1.71120	0.51740	0.0348*
H56B	0.15610	1.51810	0.57820	0.0348*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O21A	0.023 (2)	0.044 (2)	0.023 (2)	0.003 (2)	0.0010 (17)	0.0074 (19)
O24A	0.029 (2)	0.046 (2)	0.021 (2)	0.011 (2)	0.0013 (18)	−0.0001 (19)
O25A	0.031 (3)	0.058 (3)	0.017 (2)	0.016 (2)	0.001 (2)	0.004 (2)
C1A	0.021 (3)	0.019 (2)	0.018 (3)	0.001 (2)	−0.003 (2)	−0.001 (2)
C2A	0.023 (3)	0.028 (3)	0.022 (3)	−0.005 (3)	−0.003 (3)	−0.003 (3)
C3A	0.026 (4)	0.037 (3)	0.019 (3)	0.000 (3)	−0.005 (3)	0.005 (3)
C4A	0.038 (4)	0.035 (3)	0.028 (3)	0.001 (3)	−0.009 (3)	0.006 (3)
C5A	0.026 (3)	0.026 (3)	0.041 (3)	0.006 (2)	−0.009 (4)	0.006 (4)
C6A	0.026 (3)	0.033 (3)	0.048 (4)	0.003 (3)	0.004 (3)	−0.019 (3)
C7A	0.029 (3)	0.037 (3)	0.028 (3)	−0.006 (3)	0.006 (3)	−0.012 (3)
C8A	0.019 (3)	0.027 (3)	0.028 (3)	−0.003 (3)	−0.004 (3)	−0.005 (3)
C9A	0.022 (3)	0.021 (3)	0.031 (3)	−0.007 (3)	−0.003 (3)	−0.001 (2)
C10A	0.031 (3)	0.021 (2)	0.027 (4)	−0.003 (2)	−0.005 (3)	−0.002 (2)
C22A	0.017 (3)	0.032 (3)	0.017 (3)	0.003 (3)	−0.002 (2)	0.003 (2)
C23A	0.023 (3)	0.023 (3)	0.023 (3)	0.001 (3)	−0.004 (3)	−0.001 (3)
Br1B	0.0267 (3)	0.0408 (3)	0.0371 (3)	0.0059 (3)	−0.0002 (4)	0.0052 (5)
S1B	0.0295 (8)	0.0364 (8)	0.0161 (6)	0.0046 (7)	0.0032 (6)	−0.0022 (7)
N3B	0.021 (3)	0.038 (3)	0.009 (2)	0.003 (2)	−0.001 (2)	−0.004 (2)
N4B	0.020 (3)	0.037 (3)	0.018 (3)	−0.001 (2)	−0.003 (2)	0.000 (2)
N21B	0.025 (3)	0.052 (3)	0.011 (3)	0.012 (3)	0.000 (2)	−0.005 (2)
C2B	0.019 (3)	0.029 (3)	0.022 (4)	−0.004 (3)	0.006 (3)	−0.002 (3)
C5B	0.024 (3)	0.024 (3)	0.022 (3)	−0.002 (3)	0.003 (2)	−0.006 (3)
C51B	0.017 (3)	0.023 (3)	0.019 (3)	−0.003 (2)	0.005 (2)	−0.001 (2)
C52B	0.031 (3)	0.030 (3)	0.021 (3)	0.002 (2)	0.014 (4)	0.003 (3)
C53B	0.029 (3)	0.037 (3)	0.020 (3)	0.001 (3)	−0.001 (3)	0.001 (3)
C54B	0.016 (3)	0.024 (3)	0.029 (3)	0.005 (2)	−0.002 (3)	0.005 (2)
C55B	0.029 (3)	0.035 (3)	0.023 (3)	0.009 (3)	0.005 (3)	−0.004 (3)
C56B	0.038 (4)	0.037 (3)	0.012 (3)	0.006 (3)	−0.001 (3)	−0.001 (3)

Geometric parameters (Å, º)

Br1B—C54B	1.893 (5)	C8A—C9A	1.418 (8)
S1B—C5B	1.735 (5)	C9A—C10A	1.409 (8)
S1B—C2B	1.734 (7)	C22A—C23A	1.505 (8)
O21A—C2A	1.390 (7)	C1A—H1A	0.9500
O21A—C22A	1.401 (6)	C3A—H3A	0.9500
O24A—C23A	1.313 (7)	C4A—H4A	0.9500
O25A—C23A	1.205 (7)	C5A—H5A	0.9500
O24A—H24A	0.92 (6)	C6A—H6A	0.9500
N3B—N4B	1.376 (6)	C7A—H7A	0.9500
N3B—C2B	1.311 (7)	C8A—H8A	0.9500
N4B—C5B	1.290 (7)	C22A—H22A	0.9900
N21B—C2B	1.340 (8)	C22A—H21A	0.9900
N21B—H22B	0.93 (6)	C5B—C51B	1.476 (7)
N21B—H21B	0.84 (6)	C51B—C56B	1.386 (8)
C1A—C2A	1.367 (8)	C51B—C52B	1.398 (9)
C1A—C9A	1.424 (8)	C52B—C53B	1.384 (7)
C2A—C3A	1.386 (8)	C53B—C54B	1.372 (8)
C3A—C4A	1.367 (8)	C54B—C55B	1.382 (8)
C4A—C10A	1.412 (8)	C55B—C56B	1.380 (9)
C5A—C10A	1.410 (8)	C52B—H52B	0.9500
C5A—C6A	1.354 (11)	C53B—H53B	0.9500
C6A—C7A	1.408 (9)	C55B—H55B	0.9500
C7A—C8A	1.350 (8)	C56B—H56B	0.9500
C2B—S1B—C5B	87.3 (3)	C5A—C6A—H6A	120.00
C2A—O21A—C22A	118.2 (4)	C7A—C6A—H6A	120.00
C23A—O24A—H24A	113 (4)	C6A—C7A—H7A	120.00
N4B—N3B—C2B	113.8 (5)	C8A—C7A—H7A	120.00
N3B—N4B—C5B	112.4 (4)	C7A—C8A—H8A	119.00
H21B—N21B—H22B	128 (6)	C9A—C8A—H8A	119.00
C2B—N21B—H22B	112 (4)	O21A—C22A—H22A	110.00
C2B—N21B—H21B	118 (5)	O21A—C22A—H21A	110.00
C2A—C1A—C9A	118.1 (5)	H21A—C22A—H22A	108.00
O21A—C2A—C1A	123.5 (5)	C23A—C22A—H21A	110.00
O21A—C2A—C3A	113.5 (5)	C23A—C22A—H22A	110.00
C1A—C2A—C3A	123.0 (5)	S1B—C2B—N3B	112.4 (5)
C2A—C3A—C4A	118.8 (5)	N3B—C2B—N21B	124.6 (6)
C3A—C4A—C10A	121.9 (5)	S1B—C2B—N21B	122.9 (4)
C6A—C5A—C10A	122.0 (6)	N4B—C5B—C51B	124.3 (5)
C5A—C6A—C7A	119.3 (5)	S1B—C5B—C51B	121.6 (4)
C6A—C7A—C8A	120.3 (5)	S1B—C5B—N4B	114.1 (4)
C7A—C8A—C9A	121.6 (5)	C5B—C51B—C52B	121.5 (5)
C1A—C9A—C8A	121.5 (5)	C5B—C51B—C56B	120.7 (5)
C8A—C9A—C10A	118.2 (5)	C52B—C51B—C56B	117.7 (5)
C1A—C9A—C10A	120.3 (5)	C51B—C52B—C53B	120.9 (5)
C5A—C10A—C9A	118.6 (6)	C52B—C53B—C54B	119.7 (5)
C4A—C10A—C9A	117.9 (5)	Br1B—C54B—C55B	119.0 (4)
C4A—C10A—C5A	123.5 (6)	Br1B—C54B—C53B	120.3 (4)
O21A—C22A—C23A	109.0 (5)	C53B—C54B—C55B	120.8 (5)
O24A—C23A—O25A	125.4 (5)	C54B—C55B—C56B	119.1 (5)
O24A—C23A—C22A	110.3 (5)	C51B—C56B—C55B	121.8 (5)
O25A—C23A—C22A	124.3 (5)	C51B—C52B—H52B	120.00
C2A—C1A—H1A	121.00	C53B—C52B—H52B	120.00
C9A—C1A—H1A	121.00	C52B—C53B—H53B	120.00
C4A—C3A—H3A	121.00	C54B—C53B—H53B	120.00
C2A—C3A—H3A	121.00	C54B—C55B—H55B	121.00
C10A—C4A—H4A	119.00	C56B—C55B—H55B	120.00
C3A—C4A—H4A	119.00	C51B—C56B—H56B	119.00
C6A—C5A—H5A	119.00	C55B—C56B—H56B	119.00
C10A—C5A—H5A	119.00
C2B—S1B—C5B—C51B	177.5 (4)	C5A—C6A—C7A—C8A	1.4 (8)
C2B—S1B—C5B—N4B	0.1 (4)	C6A—C7A—C8A—C9A	−0.6 (8)
C5B—S1B—C2B—N21B	−178.5 (5)	C7A—C8A—C9A—C10A	−0.7 (8)
C5B—S1B—C2B—N3B	0.1 (4)	C7A—C8A—C9A—C1A	179.6 (5)
C22A—O21A—C2A—C1A	−2.6 (7)	C1A—C9A—C10A—C5A	−179.1 (5)
C2A—O21A—C22A—C23A	−174.0 (4)	C8A—C9A—C10A—C4A	−178.7 (5)
C22A—O21A—C2A—C3A	177.9 (4)	C1A—C9A—C10A—C4A	1.0 (7)
C2B—N3B—N4B—C5B	0.5 (6)	C8A—C9A—C10A—C5A	1.2 (7)
N4B—N3B—C2B—N21B	178.2 (5)	O21A—C22A—C23A—O25A	−0.5 (7)
N4B—N3B—C2B—S1B	−0.4 (6)	O21A—C22A—C23A—O24A	179.3 (4)
N3B—N4B—C5B—C51B	−177.6 (5)	S1B—C5B—C51B—C52B	−178.4 (4)
N3B—N4B—C5B—S1B	−0.4 (6)	S1B—C5B—C51B—C56B	−0.4 (7)
C2A—C1A—C9A—C8A	179.6 (5)	N4B—C5B—C51B—C52B	−1.4 (8)
C2A—C1A—C9A—C10A	−0.1 (7)	N4B—C5B—C51B—C56B	176.7 (5)
C9A—C1A—C2A—C3A	−1.0 (8)	C5B—C51B—C52B—C53B	177.2 (5)
C9A—C1A—C2A—O21A	179.6 (5)	C56B—C51B—C52B—C53B	−0.9 (7)
O21A—C2A—C3A—C4A	−179.4 (5)	C5B—C51B—C56B—C55B	−176.5 (5)
C1A—C2A—C3A—C4A	1.1 (8)	C52B—C51B—C56B—C55B	1.6 (8)
C2A—C3A—C4A—C10A	−0.1 (8)	C51B—C52B—C53B—C54B	−0.1 (7)
C3A—C4A—C10A—C9A	−0.9 (8)	C52B—C53B—C54B—Br1B	−179.1 (4)
C3A—C4A—C10A—C5A	179.2 (5)	C52B—C53B—C54B—C55B	0.5 (8)
C10A—C5A—C6A—C7A	−0.9 (8)	Br1B—C54B—C55B—C56B	179.8 (4)
C6A—C5A—C10A—C4A	179.5 (5)	C53B—C54B—C55B—C56B	0.2 (8)
C6A—C5A—C10A—C9A	−0.4 (8)	C54B—C55B—C56B—C51B	−1.3 (8)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N21B—H21B···O25A	0.84 (6)	2.07 (6)	2.875 (6)	160 (6)
N21B—H22B···N4B^i	0.93 (6)	2.06 (6)	2.948 (7)	160 (5)
O24A—H24A···N3B	0.92 (6)	1.73 (6)	2.643 (6)	174 (6)
C56B—H56B···S1B	0.95	2.67	3.106 (6)	108

Symmetry code: (i) −x+1/2, y, z+1/2.

(II) 2-Amino-5-(4-bromophenyl)-1,2,4-thiadiazol-3-ium 3,5-dinitrobenzoate

Crystal data

C8H7BrN3S^+·C7H3N2O6^−	F(000) = 936
Mr = 468.25	Dx = 1.805 Mg m^−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 1748 reflections
a = 7.5815 (6) Å	θ = 3.4–27.9°
b = 7.6164 (7) Å	µ = 2.56 mm^−1
c = 29.846 (2) Å	T = 200 K
β = 91.444 (7)°	Prism, pale yellow
V = 1722.9 (2) Å^3	0.28 × 0.12 × 0.05 mm
Z = 4

Data collection

Oxford Gemini-S CCD area-detector diffractometer	3381 independent reflections
Radiation source: Enhance(Mo) X-ray source	2601 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.036
Detector resolution: 16.077 pixels mm^-1	θmax = 26.0°, θmin = 3.4°
ω scans	h = −9→9
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2012)	k = −5→9
Tmin = 0.535, Tmax = 0.883	l = −35→36
7135 measured reflections

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.046	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.097	H atoms treated by a mixture of independent and constrained refinement
S = 1.07	w = 1/[σ^2(Fo^2) + (0.0326P)^2 + 0.6885P] where P = (Fo^2 + 2Fc^2)/3
3381 reflections	(Δ/σ)max = 0.001
265 parameters	Δρmax = 0.37 e Å^−3
0 restraints	Δρmin = −0.69 e Å^−3

Special details

Geometry. Bond distances, angles etc. have been calculated using the rounded fractional coordinates. All su's are estimated from the variances of the (full) variance-covariance matrix. The cell e.s.d.'s are taken into account in the estimation of distances, angles and torsion angles

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 (Ų)

	x	y	z	Uiso*/Ueq
O21A	0.5835 (3)	0.4153 (3)	0.42266 (8)	0.0404 (8)
O22A	0.8555 (3)	0.5095 (3)	0.43875 (8)	0.0394 (8)
O31A	0.3469 (4)	0.4800 (4)	0.27142 (10)	0.0567 (10)
O32A	0.4984 (4)	0.5996 (5)	0.22060 (10)	0.0790 (13)
O51A	1.0917 (4)	0.7889 (4)	0.25291 (10)	0.0612 (11)
O52A	1.1928 (4)	0.7825 (4)	0.32083 (10)	0.0622 (11)
N3A	0.4804 (4)	0.5487 (4)	0.25863 (10)	0.0412 (11)
N5A	1.0781 (4)	0.7549 (4)	0.29270 (11)	0.0446 (11)
C1A	0.7448 (4)	0.5450 (4)	0.36485 (11)	0.0299 (10)
C2A	0.6071 (4)	0.5221 (4)	0.33442 (11)	0.0318 (11)
C3A	0.6267 (4)	0.5750 (4)	0.29078 (11)	0.0327 (11)
C4A	0.7799 (4)	0.6494 (4)	0.27589 (12)	0.0343 (11)
C5A	0.9129 (4)	0.6726 (4)	0.30725 (11)	0.0321 (10)
C6A	0.8997 (4)	0.6222 (4)	0.35105 (11)	0.0324 (11)
C11A	0.7278 (4)	0.4850 (4)	0.41273 (11)	0.0320 (11)
Br1B	−0.17691 (5)	−0.24730 (5)	0.64638 (1)	0.0501 (2)
S1B	0.62338 (11)	0.18741 (12)	0.58022 (3)	0.0366 (3)
N3B	0.5522 (4)	0.2764 (4)	0.50067 (10)	0.0327 (9)
N4B	0.4070 (3)	0.1864 (4)	0.51313 (9)	0.0314 (9)
N21B	0.8267 (5)	0.3754 (5)	0.52422 (13)	0.0531 (14)
C2B	0.6792 (5)	0.2922 (4)	0.53166 (12)	0.0358 (11)
C5B	0.4237 (4)	0.1323 (4)	0.55396 (11)	0.0277 (10)
C51B	0.2849 (4)	0.0360 (4)	0.57688 (10)	0.0258 (10)
C52B	0.1319 (4)	−0.0074 (5)	0.55314 (12)	0.0371 (11)
C53B	−0.0046 (4)	−0.0928 (5)	0.57363 (12)	0.0384 (11)
C54B	0.0127 (4)	−0.1340 (4)	0.61832 (11)	0.0319 (11)
C55B	0.1645 (4)	−0.0949 (4)	0.64249 (11)	0.0341 (11)
C56B	0.2997 (4)	−0.0109 (4)	0.62159 (11)	0.0332 (11)
H2A	0.49970	0.47030	0.34350	0.0380*
H4A	0.79270	0.68300	0.24550	0.0410*
H6A	0.99540	0.64000	0.37170	0.0390*
H3B	0.553 (5)	0.326 (5)	0.4731 (14)	0.057 (12)*
H21B	0.845 (6)	0.421 (6)	0.4980 (17)	0.085 (17)*
H22B	0.900 (6)	0.395 (6)	0.5443 (16)	0.080 (17)*
H52B	0.12080	0.02220	0.52230	0.0450*
H53B	−0.10900	−0.12280	0.55710	0.0460*
H55B	0.17550	−0.12570	0.67330	0.0410*
H56B	0.40520	0.01540	0.63810	0.0400*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O21A	0.0348 (13)	0.0569 (15)	0.0295 (14)	−0.0106 (12)	0.0001 (11)	0.0092 (11)
O22A	0.0360 (14)	0.0536 (15)	0.0284 (14)	−0.0137 (12)	−0.0028 (11)	0.0034 (11)
O31A	0.0470 (17)	0.0678 (19)	0.0544 (18)	−0.0223 (14)	−0.0136 (14)	0.0138 (15)
O32A	0.0526 (19)	0.152 (3)	0.0318 (17)	−0.024 (2)	−0.0123 (14)	0.0145 (19)
O51A	0.0521 (17)	0.090 (2)	0.0419 (18)	−0.0126 (15)	0.0095 (14)	0.0248 (15)
O52A	0.0453 (17)	0.097 (2)	0.0442 (18)	−0.0301 (15)	0.0017 (14)	−0.0007 (15)
N3A	0.0429 (19)	0.0496 (19)	0.0309 (18)	−0.0032 (15)	−0.0044 (15)	0.0003 (14)
N5A	0.0366 (18)	0.0527 (19)	0.045 (2)	−0.0076 (15)	0.0094 (15)	0.0052 (16)
C1A	0.0330 (18)	0.0295 (18)	0.0272 (18)	−0.0018 (15)	0.0026 (15)	0.0008 (14)
C2A	0.0318 (18)	0.0316 (19)	0.0322 (19)	−0.0029 (14)	0.0034 (16)	0.0005 (14)
C3A	0.0323 (18)	0.0359 (19)	0.0295 (19)	0.0013 (15)	−0.0041 (15)	−0.0019 (15)
C4A	0.0375 (19)	0.037 (2)	0.0285 (19)	0.0033 (16)	0.0049 (15)	0.0025 (15)
C5A	0.0296 (17)	0.0346 (18)	0.0321 (19)	−0.0017 (15)	0.0026 (15)	0.0023 (15)
C6A	0.0344 (18)	0.0346 (19)	0.0281 (18)	−0.0010 (15)	0.0003 (15)	−0.0004 (15)
C11A	0.0334 (19)	0.0316 (19)	0.0312 (19)	−0.0029 (15)	0.0056 (16)	−0.0013 (15)
Br1B	0.0394 (2)	0.0639 (3)	0.0475 (3)	−0.0126 (2)	0.0129 (2)	0.0095 (2)
S1B	0.0286 (4)	0.0535 (5)	0.0276 (5)	−0.0079 (4)	−0.0031 (4)	0.0071 (4)
N3B	0.0296 (15)	0.0425 (18)	0.0260 (15)	−0.0070 (13)	0.0003 (12)	0.0080 (13)
N4B	0.0263 (14)	0.0393 (15)	0.0286 (16)	−0.0044 (12)	0.0017 (12)	0.0063 (12)
N21B	0.040 (2)	0.084 (3)	0.035 (2)	−0.0301 (18)	−0.0021 (16)	0.0129 (19)
C2B	0.0330 (19)	0.044 (2)	0.0303 (19)	−0.0067 (16)	−0.0008 (15)	0.0031 (15)
C5B	0.0236 (16)	0.0313 (18)	0.0281 (18)	−0.0015 (14)	0.0009 (14)	0.0036 (14)
C51B	0.0250 (16)	0.0276 (17)	0.0248 (17)	0.0016 (13)	0.0018 (14)	0.0022 (13)
C52B	0.0308 (18)	0.054 (2)	0.0265 (18)	−0.0029 (16)	−0.0004 (15)	0.0056 (16)
C53B	0.0282 (18)	0.057 (2)	0.030 (2)	−0.0067 (16)	−0.0004 (15)	0.0052 (16)
C54B	0.0294 (17)	0.0326 (19)	0.034 (2)	−0.0003 (15)	0.0096 (15)	0.0041 (15)
C55B	0.0376 (19)	0.041 (2)	0.0238 (18)	0.0001 (16)	0.0049 (15)	0.0053 (15)
C56B	0.0323 (19)	0.0379 (19)	0.0292 (19)	0.0003 (15)	−0.0035 (15)	0.0039 (15)

Geometric parameters (Å, º)

Br1B—C54B	1.890 (3)	C1A—C11A	1.509 (5)
S1B—C2B	1.717 (4)	C2A—C3A	1.375 (5)
S1B—C5B	1.739 (3)	C3A—C4A	1.376 (4)
O21A—C11A	1.258 (4)	C4A—C5A	1.370 (5)
O22A—C11A	1.240 (4)	C5A—C6A	1.369 (5)
O31A—N3A	1.210 (4)	C2A—H2A	0.9500
O32A—N3A	1.210 (4)	C4A—H4A	0.9500
O51A—N5A	1.222 (4)	C6A—H6A	0.9500
O52A—N5A	1.212 (4)	C5B—C51B	1.466 (4)
N3A—C3A	1.462 (4)	C51B—C56B	1.383 (4)
N5A—C5A	1.476 (4)	C51B—C52B	1.384 (4)
N3B—C2B	1.324 (5)	C52B—C53B	1.378 (5)
N3B—N4B	1.357 (4)	C53B—C54B	1.373 (5)
N4B—C5B	1.290 (4)	C54B—C55B	1.375 (4)
N21B—C2B	1.309 (5)	C55B—C56B	1.372 (4)
N3B—H3B	0.91 (4)	C52B—H52B	0.9500
N21B—H21B	0.87 (5)	C53B—H53B	0.9500
N21B—H22B	0.82 (5)	C55B—H55B	0.9500
C1A—C6A	1.385 (4)	C56B—H56B	0.9500
C1A—C2A	1.377 (4)
C2B—S1B—C5B	87.83 (17)	C1A—C2A—H2A	120.00
O31A—N3A—O32A	123.3 (3)	C3A—C4A—H4A	122.00
O31A—N3A—C3A	118.6 (3)	C5A—C4A—H4A	122.00
O32A—N3A—C3A	118.0 (3)	C5A—C6A—H6A	120.00
O51A—N5A—O52A	124.0 (3)	C1A—C6A—H6A	120.00
O51A—N5A—C5A	118.0 (3)	S1B—C2B—N3B	110.9 (3)
O52A—N5A—C5A	118.0 (3)	S1B—C2B—N21B	126.7 (3)
N4B—N3B—C2B	115.8 (3)	N3B—C2B—N21B	122.3 (3)
N3B—N4B—C5B	111.1 (3)	S1B—C5B—N4B	114.4 (2)
N4B—N3B—H3B	119 (2)	N4B—C5B—C51B	123.1 (3)
C2B—N3B—H3B	125 (2)	S1B—C5B—C51B	122.5 (2)
C2B—N21B—H21B	120 (3)	C5B—C51B—C56B	122.5 (3)
C2B—N21B—H22B	122 (3)	C52B—C51B—C56B	118.6 (3)
H21B—N21B—H22B	118 (4)	C5B—C51B—C52B	118.9 (3)
C2A—C1A—C11A	120.3 (3)	C51B—C52B—C53B	121.0 (3)
C6A—C1A—C11A	120.2 (3)	C52B—C53B—C54B	119.0 (3)
C2A—C1A—C6A	119.5 (3)	Br1B—C54B—C53B	118.7 (2)
C1A—C2A—C3A	119.3 (3)	C53B—C54B—C55B	121.2 (3)
N3A—C3A—C2A	118.9 (3)	Br1B—C54B—C55B	120.1 (2)
N3A—C3A—C4A	118.5 (3)	C54B—C55B—C56B	119.2 (3)
C2A—C3A—C4A	122.6 (3)	C51B—C56B—C55B	121.1 (3)
C3A—C4A—C5A	116.4 (3)	C51B—C52B—H52B	119.00
N5A—C5A—C4A	118.0 (3)	C53B—C52B—H52B	120.00
N5A—C5A—C6A	118.9 (3)	C52B—C53B—H53B	121.00
C4A—C5A—C6A	123.1 (3)	C54B—C53B—H53B	120.00
C1A—C6A—C5A	119.1 (3)	C54B—C55B—H55B	120.00
O22A—C11A—C1A	117.6 (3)	C56B—C55B—H55B	120.00
O21A—C11A—C1A	116.5 (3)	C51B—C56B—H56B	120.00
O21A—C11A—O22A	125.9 (3)	C55B—C56B—H56B	119.00
C3A—C2A—H2A	120.00
C5B—S1B—C2B—N21B	−179.9 (4)	C11A—C1A—C2A—C3A	−178.9 (3)
C2B—S1B—C5B—N4B	1.0 (3)	C1A—C2A—C3A—C4A	0.5 (5)
C5B—S1B—C2B—N3B	−1.1 (3)	C1A—C2A—C3A—N3A	179.5 (3)
C2B—S1B—C5B—C51B	−177.7 (3)	C2A—C3A—C4A—C5A	−1.5 (5)
O31A—N3A—C3A—C2A	−0.5 (5)	N3A—C3A—C4A—C5A	179.6 (3)
O31A—N3A—C3A—C4A	178.5 (3)	C3A—C4A—C5A—N5A	−178.9 (3)
O32A—N3A—C3A—C2A	178.4 (3)	C3A—C4A—C5A—C6A	1.5 (5)
O32A—N3A—C3A—C4A	−2.7 (5)	C4A—C5A—C6A—C1A	−0.5 (5)
O51A—N5A—C5A—C4A	−4.1 (5)	N5A—C5A—C6A—C1A	180.0 (3)
O52A—N5A—C5A—C4A	176.8 (3)	S1B—C5B—C51B—C52B	−178.1 (3)
O52A—N5A—C5A—C6A	−3.6 (5)	S1B—C5B—C51B—C56B	3.0 (4)
O51A—N5A—C5A—C6A	175.5 (3)	N4B—C5B—C51B—C52B	3.5 (5)
N4B—N3B—C2B—N21B	179.9 (3)	N4B—C5B—C51B—C56B	−175.5 (3)
C2B—N3B—N4B—C5B	−0.3 (4)	C5B—C51B—C52B—C53B	−177.9 (3)
N4B—N3B—C2B—S1B	1.0 (4)	C56B—C51B—C52B—C53B	1.1 (5)
N3B—N4B—C5B—S1B	−0.6 (4)	C5B—C51B—C56B—C55B	177.4 (3)
N3B—N4B—C5B—C51B	178.0 (3)	C52B—C51B—C56B—C55B	−1.6 (5)
C6A—C1A—C2A—C3A	0.6 (5)	C51B—C52B—C53B—C54B	0.3 (5)
C2A—C1A—C6A—C5A	−0.6 (5)	C52B—C53B—C54B—Br1B	178.9 (3)
C11A—C1A—C6A—C5A	178.8 (3)	C52B—C53B—C54B—C55B	−1.4 (5)
C2A—C1A—C11A—O21A	−0.2 (4)	Br1B—C54B—C55B—C56B	−179.3 (2)
C2A—C1A—C11A—O22A	−179.7 (3)	C53B—C54B—C55B—C56B	1.0 (5)
C6A—C1A—C11A—O21A	−179.6 (3)	C54B—C55B—C56B—C51B	0.5 (5)
C6A—C1A—C11A—O22A	0.9 (4)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N3B—H3B···O21A	0.91 (4)	1.67 (4)	2.574 (4)	172 (4)
N21B—H21B···O22A	0.87 (5)	1.90 (5)	2.762 (5)	173 (5)
N21B—H22B···O22A^i	0.82 (5)	2.04 (5)	2.768 (4)	147 (4)
C4A—H4A···O31A^ii	0.95	2.54	3.031 (4)	112
C52B—H52B···N4B	0.95	2.53	2.843 (4)	100
C56B—H56B···S1B	0.95	2.75	3.159 (3)	107

Symmetry codes: (i) −x+2, −y+1, −z+1; (ii) −x+1, y+1/2, −z+1/2.