Crystal structure of 4-carbamoylpyridinium chloride.

The hydro-chloride salt of isonicotinamide, C6H7N2O(+)·Cl(-), has been synthesized from a dilute solution of hydro-chloric acid in aceto-nitrile. The compound displays monoclinic symmetry (space group C2/c) at 150 K, similar to the related hydro-chloride salt of nicotinamide. The asymmetric unit contains one protonated isonicotinamide mol-ecule and a chloride anion. An array of hydrogen-bonding inter-actions, including a peculiar bifurcated pyridinium-chloride inter-action, results in linear chains running almost perpendicularly in the [150] and [1-50] directions within the structure. A description of the hydrogen-bonding network and comparison with similar compounds are presented.

Chemical context

Often compounds which exhibit a desirable biological function may not possess the correct physical properties for practical usage. The ability to manipulate the properties of a compound in a controlled manner, while maintaining the biological activity, is one of the ultimate goals of crystal engineering (Desiraju et al., 2011 ▸). Converting a biologically active compound into its hydro­chloride salt has proven a successful technique in this regard (Byrn et al., 1999 ▸). The structural determination and analysis of neutral, co-crystalline, and salt forms of various mol­ecules is necessary in order to expand the library of reliable tools that can be used in the design of new materials.

Isonicotinamide is a useful compound in crystal engineering as it possesses amide and pyridyl groups which have the capability to form a plethora of well established and predictable hydrogen-bonding arrangements (Bhogala et al., 2004 ▸). It also displays polymorphism in the solid state on account of its flexible hydrogen-bonding capacity (Aakeröy et al., 2003 ▸; Li et al., 2011 ▸). As a result, the mol­ecule has been heavily investigated by many groups as a co-crystal former in lots of different scenarios (Vishweshwar et al., 2003 ▸; Bhogala et al., 2005 ▸; Aakeröy et al., 2007 ▸; Thompson et al., 2011 ▸; Tothadi & Desiraju, 2012 ▸; Dubey & Desiraju, 2014 ▸; Kerr et al., 2015 ▸). The compound is also of mild pharmaceutical inter­est given its similarity to nicotinamide, the amide of Vitamin B3. The hydro­chloride salt of this mol­ecule has been synthesized and the structure determined, the results of which are discussed herein.

Structural commentary

The asymmetric unit of the title compound, shown in Fig. 1 ▸, consists of one chloride anion and a protonated isonicotinamide cation, confirmed by the identification of a proton 0.9 Å from the pyridine N atom in a difference Fourier map. The isonicotinamide cation is planar: the root-mean-square deviation of the pyridinium ring is 0.0062 Å, with an angle of 1.3 (2)° between the planes of the pyridinium and amide moieties. Analysis of structures in the Cambridge Structural Database (CSD, Version 5.37, update November 2015; Groom & Allen, 2014 ▸) containing the 4-carbamoylpyridinium cation show that the angle between the amide and pyridinium planes can take any value between 0 and 50° with no distinct configurational preference.

Figure 1

The asymmetric unit of the title compound, showing the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level. The dashed line represents a hydrogen bond.

Supra­molecular features

The most inter­esting feature of the crystal structure is the inter­molecular inter­action between the pyridinium groups and chloride ions. Two pyridinium protons form bifurcated hydrogen bonds to two chloride ions, forming an (4) ring motif which is positioned on a centre of inversion, as shown in Fig. 2 ▸ (A). The inter­action is similar to those found in many tetra­halometallate [MX 4]2− compounds, though primarily when the [MX 4]2− unit is planar (Adams et al., 2006 ▸). It is also encountered in some hydro­chloride salts of mol­ecules incorporating a pyridinium group (Nattinen & Rissanen, 2003 ▸; Zhao et al., 2008 ▸). The two unique N—H⋯Cl hydrogen bonds formed by each proton in this arrangement are usually of similar length, though one is distinctly longer than the other in this compound [N⋯Cl = 3.0416 (12) Å and 3.4882 (13) Å]. The CSD (Version 5.37, update November 2015; Groom & Allen, 2014 ▸) reveals 426 structures of the hydro­chloride salts of mol­ecules incorporating a pyridinium group. 21 of these display bifurcated pyridinium–chloride hydrogen bonds, of which only 16 possess the (4) ring motif. None of these simultaneously show the same asymmetry in the hydrogen-bond lengths (ratio of two N⋯Cl lengths = 1.147; ratio of H⋯Cl lengths = 1.317), and planarity (r.m.s.d. = 0.0151 Å) of the inter­action as the title compound. Given the lack of examples of bifurcated hydrogen bonds in this type of material, it seems likely that it is a result of maximizing the other possible inter­molecular inter­actions for a given system, where the bifurcation is a compromise. In other words, one short, linear N—H⋯Cl bond is ideal, though bifurcation is energetically more favourable than a single, weaker inter­action.

Figure 2

A view of the hydrogen bonding arrangements within 4-carbamoylpyridinium chloride, showing the pyridinium–chloride (A) amide–amide (B) and amine–chloride (C) inter­actions. Hydrogen bonds are drawn as light-blue dashed lines. Possible C—H⋯X inter­actions have been omitted.

The amine group of the amide moiety is directed toward the carboxyl group of an adjacent mol­ecule related by a centre of inversion; this shows the existence of a classic (8) amide-amide inter­action, seen in Fig. 2 ▸ (B). The combination of the two ring inter­actions form (16) chains running in the [150] and [10] directions, and are related by a 21 screw axis. The two chain directions are almost perpendicular to each other (82°) and are held in this respective orientation by a (10) inter­action which incorporates the (8) and (4) motifs, and hydrogen bonds between the protons not involved in the amide–amide inter­actions and the chloride ions of neighbouring chains, as shown in Fig. 2 ▸ (C). For the overall packing arrangement, see Fig. 3 ▸. There is some evidence of C—H⋯X hydrogen bonds (Table 1 ▸); however, these only seem to reinforce the stronger inter­actions discussed above and their role in determining the crystal packing in this compound is unclear.

Figure 3

Crystal packing diagram of 4-carbamoylpyridinium chloride viewed along the b axis. Hydrogen bonds are drawn as light-blue dashed lines.

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C1—H1⋯O1i	0.95	2.74	3.295 (2)	118
C2—H2⋯O1i	0.92	2.61	3.2205 (18)	124
C4—H4⋯Cl1ii	0.95	2.59	3.5377 (15)	172
C5—H5⋯Cl1iii	0.93	2.62	3.3284 (15)	133
N1—H1A⋯Cl1	0.89	2.24	3.0416 (12)	149
N1—H1A⋯Cl1iii	0.89	2.95	3.4882 (13)	121
N2—H2A⋯O1iv	0.88 (2)	2.02 (2)	2.8892 (15)	174 (2)
N2—H2B⋯Cl1ii	0.87 (2)	2.33 (2)	3.1907 (13)	169 (2)

Symmetry codes: (i) ; (ii) ; (iii) ; (iv) .

The related salt of nicotinamide contains the same amide–amide inter­actions as in the title compound, though neither 3- or 4-carb­oxy­pyridinium chloride show the equivalent di­carb­oxy­lic acid inter­action. (Gubin et al., 1989 ▸; Slouf, 2001 ▸; Adams et al., 2006 ▸). The chloride ions in these structures act only as hydrogen-bond acceptor atoms between donor atoms of mol­ecules in the same chain, with no further inter­actions between the chains. It would be inter­esting to see how these almost classic co-crystal formers would behave when crystallized with the hydro­chloride salts of other mol­ecules, and whether the same hydrogen-bonding arrangements persist.

Related structures

For the crystal structure of 4-carbamoylpyridinium di­hydro­gen phosphate, see Gholivand et al. (2007 ▸); for 4-carbamoyl­pyridinium perchlorate, see Chen (2009 ▸); for nicotinamide hydro­chloride, see Gubin et al. (1989 ▸); for nicotinic acid hydro­chloride, see Slouf (2001 ▸); and for isonicotinic acid hydro­chloride and a comprehensive study on the tetra­chloro­platinate and palladate salts of similar pyridinium compounds, see Adams et al. (2006 ▸).

Synthesis and crystallization

Hydro­chloric acid (0.08 ml, 12 M) in aceto­nitrile (3 ml) was added to isonicotinamide (0.244 g, 2 mmol) dissolved in aceto­nitrile (25 ml). The resultant white mixture was heated until the precipitate dissolved and the solution left to evaporate slowly over several days, resulting in the formation of large colourless block-shaped crystals of the title compound.

Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2 ▸. Hydrogen atoms were readily identified in difference Fourier maps. The pyridinium hydrogen atom was positioned in a geometrically optimized position; N1—H1A was constrained to a value of 0.88 Å with an su of 0.03 Å. C-bound H atoms were sited with a riding model and the C—H distance refined subject to the restraint that all C—H distances should be the same with an su of 0.03 Å. The amide hydrogen atoms were refined freely subject to restraint that the two N—H bond lengths were equal with an su of 0.03 Å and the H⋯H distance was 3 × lN–H (su 0.03 Å) to set the H—N—H angle to 120°.

Table 2

Experimental details

Crystal data
Chemical formula	C6H7N2O+·Cl−
M r	158.59
Crystal system, space group	Monoclinic, C2/c
Temperature (K)	150
a, b, c (Å)	24.960 (2), 5.1055 (4), 12.4664 (9)
β (°)	117.545 (5)
V (Å3)	1408.6 (2)
Z	8
Radiation type	Mo Kα
μ (mm−1)	0.47
Crystal size (mm)	0.34 × 0.28 × 0.26
Data collection
Diffractometer	Stoe IPDS 2
Absorption correction	Analytical (X-RED and X-SHAPE; Stoe & Cie, 2012 ▸)
T min, T max	0.861, 0.913
No. of measured, independent and observed [I > 2σ(I)] reflections	4768, 1865, 1520
R int	0.047
(sin θ/λ)max (Å−1)	0.685
Refinement
R[F 2 > 2σ(F 2)], wR(F 2), S	0.034, 0.093, 1.01
No. of reflections	1865
No. of parameters	104
No. of restraints	8
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å−3)	0.45, −0.48

Computer programs: X-AREA (Stoe & Cie, 2012 ▸), X-RED (Stoe & Cie, 2012 ▸), SHELXT (Sheldrick, 2015a ▸), SHELXL2014 (Sheldrick, 2015b ▸), SHELXTL (Sheldrick, 2008 ▸) and Mercury (Macrae et al., 2008 ▸).

Crystal structure: contains datablock(s) I. DOI: 10.1107/S2056989016003340/zl2658sup1.cif

Structure factors: contains datablock(s) I. DOI: 10.1107/S2056989016003340/zl2658Isup2.hkl

Click here for additional data file.

Supporting information file. DOI: 10.1107/S2056989016003340/zl2658Isup3.mol

Web address for enhanced figure. DOI: 10.1107/S2056989016003340/zl2658sup4.txt

Click here for additional data file.

Supporting information file. DOI: 10.1107/S2056989016003340/zl2658Isup5.cml

CCDC reference: 1455942

Additional supporting information: crystallographic information; 3D view; checkCIF report

C6H7N2O+·Cl−	F(000) = 656
Mr = 158.59	Dx = 1.496 Mg m−3
Monoclinic, C2/c	Mo Kα radiation, λ = 0.71073 Å
a = 24.960 (2) Å	Cell parameters from 5016 reflections
b = 5.1055 (4) Å	θ = 3.7–59.1°
c = 12.4664 (9) Å	µ = 0.47 mm−1
β = 117.545 (5)°	T = 150 K
V = 1408.6 (2) Å3	Block, colourless
Z = 8	0.34 × 0.28 × 0.26 mm

Stoe IPDS 2 diffractometer	1865 independent reflections
Radiation source: fine-focus sealed X-ray tube	1520 reflections with I > 2σ(I)
Detector resolution: 6.67 pixels mm-1	Rint = 0.047
ω scans	θmax = 29.2°, θmin = 1.8°
Absorption correction: analytical (X-RED and X-SHAPE; Stoe & Cie, 2012)	h = −34→34
Tmin = 0.861, Tmax = 0.913	k = −6→6
4768 measured reflections	l = −17→17

Refinement on F2	8 restraints
Least-squares matrix: full	Hydrogen site location: mixed
R[F2 > 2σ(F2)] = 0.034	H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.093	w = 1/[σ2(Fo2) + (0.0636P)2] where P = (Fo2 + 2Fc2)/3
S = 1.01	(Δ/σ)max = 0.001
1865 reflections	Δρmax = 0.45 e Å−3
104 parameters	Δρmin = −0.48 e Å−3

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
Cl1	0.05337 (2)	1.08640 (7)	0.66004 (3)	0.02094 (12)
C1	0.14210 (7)	0.6050 (3)	0.62858 (14)	0.0235 (3)
H1	0.1565 (2)	0.7082 (17)	0.7004 (12)	0.028*
C2	0.17821 (6)	0.4124 (3)	0.61830 (13)	0.0206 (3)
H2	0.2164 (7)	0.3837 (6)	0.6800 (11)	0.025*
C3	0.15607 (5)	0.2616 (3)	0.51318 (11)	0.0175 (3)
C4	0.09760 (6)	0.3065 (3)	0.42116 (13)	0.0236 (3)
H4	0.0814 (3)	0.2027 (17)	0.3497 (12)	0.028*
C5	0.06356 (7)	0.5048 (3)	0.43560 (14)	0.0270 (3)
H5	0.0247 (7)	0.5390 (7)	0.3747 (12)	0.032*
C6	0.19697 (6)	0.0497 (3)	0.50687 (12)	0.0173 (3)
N1	0.08665 (6)	0.6468 (2)	0.53714 (12)	0.0228 (3)
H1A	0.0642 (4)	0.775 (2)	0.54449 (16)	0.027*
N2	0.17626 (5)	−0.0961 (2)	0.40762 (11)	0.0209 (3)
O1	0.24768 (4)	0.0199 (2)	0.59516 (9)	0.0228 (2)
H2A	0.2004 (8)	−0.216 (4)	0.4039 (16)	0.027*
H2B	0.1426 (8)	−0.069 (4)	0.3420 (17)	0.027*

	U11	U22	U33	U12	U13	U23
Cl1	0.01780 (17)	0.0231 (2)	0.01907 (18)	0.00607 (12)	0.00610 (13)	−0.00009 (13)
C1	0.0261 (7)	0.0220 (7)	0.0249 (7)	−0.0003 (5)	0.0138 (6)	−0.0034 (6)
C2	0.0179 (6)	0.0215 (7)	0.0208 (6)	0.0012 (5)	0.0075 (5)	−0.0015 (5)
C3	0.0171 (6)	0.0167 (6)	0.0190 (6)	0.0021 (5)	0.0087 (5)	0.0014 (5)
C4	0.0195 (6)	0.0255 (8)	0.0212 (6)	0.0065 (5)	0.0056 (5)	−0.0034 (6)
C5	0.0207 (7)	0.0294 (8)	0.0277 (7)	0.0091 (6)	0.0086 (6)	0.0003 (6)
C6	0.0155 (6)	0.0170 (7)	0.0190 (6)	0.0022 (5)	0.0075 (5)	0.0013 (5)
N1	0.0236 (6)	0.0195 (6)	0.0303 (7)	0.0055 (5)	0.0166 (5)	0.0003 (5)
N2	0.0173 (5)	0.0217 (6)	0.0198 (6)	0.0061 (4)	0.0052 (5)	−0.0024 (5)
O1	0.0170 (4)	0.0250 (6)	0.0202 (5)	0.0067 (4)	0.0034 (4)	−0.0015 (4)

C1—N1	1.342 (2)	C4—H4	0.951 (16)
C1—C2	1.3795 (19)	C5—N1	1.336 (2)
C1—H1	0.955 (16)	C5—H5	0.931 (18)
C2—C3	1.3948 (19)	C6—O1	1.2443 (17)
C2—H2	0.918 (16)	C6—N2	1.3271 (18)
C3—C4	1.3964 (18)	N1—H1A	0.894 (14)
C3—C6	1.5141 (18)	N2—H2A	0.876 (16)
C4—C5	1.3858 (19)	N2—H2B	0.871 (18)
N1—C1—C2	119.73 (14)	N1—C5—C4	119.84 (14)
N1—C1—H1	120.1	N1—C5—H5	120.1
C2—C1—H1	120.1	C4—C5—H5	120.1
C1—C2—C3	119.26 (13)	O1—C6—N2	123.66 (12)
C1—C2—H2	120.4	O1—C6—C3	118.43 (12)
C3—C2—H2	120.4	N2—C6—C3	117.91 (12)
C2—C3—C4	119.39 (12)	C5—N1—C1	122.81 (12)
C2—C3—C6	117.34 (11)	C5—N1—H1A	118.6
C4—C3—C6	123.25 (12)	C1—N1—H1A	118.6
C5—C4—C3	118.94 (14)	C6—N2—H2A	117.5 (12)
C5—C4—H4	120.5	C6—N2—H2B	125.3 (12)
C3—C4—H4	120.5	H2A—N2—H2B	116.7 (16)

D—H···A	D—H	H···A	D···A	D—H···A
C1—H1···O1i	0.95	2.74	3.295 (2)	118
C2—H2···O1i	0.92	2.61	3.2205 (18)	124
C4—H4···Cl1ii	0.95	2.59	3.5377 (15)	172
C5—H5···Cl1iii	0.93	2.62	3.3284 (15)	133
N1—H1A···Cl1	0.89	2.24	3.0416 (12)	149
N1—H1A···Cl1iii	0.89	2.95	3.4882 (13)	121
N2—H2A···O1iv	0.88 (2)	2.02 (2)	2.8892 (15)	174 (2)
N2—H2B···Cl1ii	0.87 (2)	2.33 (2)	3.1907 (13)	169 (2)