Crystal structure of 2,5-di­methyl­anilinium hydrogen maleate

Abstract

The crystal structure of the title salt, C₈H₁₂N⁺·C₄H₃O₄ ⁻, consists of a 2,5-di­methyl­anilinium cation and an hydrogen maleate anion. In the anion, a strong intra­molecular O—H⋯O hydrogen bond is observed, leading to an S(7) graph-set motif. In the crystal, the cations and anions pack in alternating layers parallel to (001). The ammonium group undergoes inter­molecular N—H⋯O hydrogen-bonding inter­actions with the O atoms of three different hydrogen maleate anions. This results in the formation of ribbons extending parallel to [010] with hydrogen-bonding motifs of the types R ⁴ ₄(12) and R ⁴ ₄(18).

Related literature  

For active pharmaceutical ingredients (API), see: Kelley et al. (2013 ▶). An example of the modification of API properties through the change of one of the mol­ecular components is the substitution of the saccharinate anion in the anti-HIV active lamivudine saccharinate by maleate (Martins et al., 2009 ▶). For 2,5-di­methyl­anilinium cations in combination with other anions, see: Smirani & Rzaigui (2009a ▶,b ▶).

Experimental  

Crystal data  

• C₈H₁₂N⁺·C₄H₃O₄ ⁻

• M _r = 237.25

• Triclinic,

• a = 6.7983 (17) Å

• b = 8.515 (2) Å

• c = 11.012 (3) Å

• α = 108.784 (8)°

• β = 98.026 (7)°

• γ = 98.742 (7)°

• V = 584.3 (3) ų

• Z = 2

• Mo Kα radiation

• μ = 0.10 mm⁻¹

• T = 173 K

• 0.45 × 0.26 × 0.19 mm

Data collection  

• Rigaku XtaLAB mini diffractometer

• Absorption correction: multi-scan (REQAB; Rigaku, 1998 ▶) T _min = 0.833, T _max = 0.981

• 6136 measured reflections

• 2667 independent reflections

• 2222 reflections with F ² > 2.0σ(F ²)

• R _int = 0.021

Refinement  

• R[F ² > 2σ(F ²)] = 0.042

• wR(F ²) = 0.108

• S = 1.06

• 2667 reflections

• 172 parameters

• H atoms treated by a mixture of independent and constrained refinement

• Δρ_max = 0.25 e Å⁻³

• Δρ_min = −0.28 e Å⁻³

Data collection: CrystalClear (Rigaku, 2011 ▶); cell refinement: CrystalClear; data reduction: CrystalClear; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: CrystalStructure (Rigaku, 2011 ▶); software used to prepare material for publication: CrystalStructure.

Supplementary Material

CCDC reference: 1029719

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

Table 1. Hydrogen-bond geometry (, ).

DHA	DH	HA	D A	DHA
O1H1O3	1.02(3)	1.45(3)	2.4651(16)	175(2)
N1H1AO3	0.92(3)	1.94(3)	2.859(2)	177.2(15)
N1H1CO4i	0.92(2)	1.86(2)	2.7602(18)	168(2)
N1H1BO2ii	0.94(2)	1.88(2)	2.7920(17)	161.4(16)

Symmetry codes: (i) ; (ii) .

supplementary crystallographic information

S1. Comment

Use of salts and co-crystals of active pharmaceutical ingredients (APIs) as a method for tuning their delivery and activity is an area of growing interest. (Kelley et al. (2013)). Modifying API properties such as solubility by finding new salts that employ similar hydrogen-bonding have been successful. A recent example includes increasing the solubility of the anti-HIV drug lamivudine saccharinate by substituting with the anion maleate. (Martins et al. (2009)). In an effort to further study the hydrogen-bonding patterns of the maleate ion with other ammonium salts, we report here the synthesis and crystal structure of 2,5-dimethylanilinium maleate.

The structure consists of a protonated 2,5-dimethylanilinium cation with the hydrogen maleate anion (Fig. 1). H1 of the maleate anion undergoes intramolecular O—H···O hydrogen-bonding with O3 as the acceptor. This is common in many structures of maleic acid as the cis disposition of the alkene places hydrogen bonding donors and acceptors in close proximity. As such, the maleate anion is very flat (mean deviation from a least-squares plane composed of atoms O1–O4, C9–C12, H1 of 0.04 Å). Parallel maleate anions pack in layers in between layers of parallel 2,5-dimethylanilinium cation layers. The cation layers are parallel with the ab plane at c = 0. The anion layers are parallel with the ab plane at c = 1/2 (Fig. 2). The hydrogen atoms of the protonated amine (H1A, H1B, H1C) undergo intermolecular N—H···O hydrogen-bonding interactions with oxygen atoms of three different maleate anions. The two hydrogen-bonding motifs dominating the structure are R⁴₄(12) and R⁴₄(18). These ring motifs form ribbons of hydrogen bonding that are parallel with the b axis (Fig. 3).

S2. Experimental

A mixture of maleic acid (1M) and 2,5-xylidine dissolved in ethanol (molar ratio 1:1:1) was stirred for 2 h and then kept at room temperature. Colourless crystals of the title compound were obtained one week later.

S3. Refinement

H atoms were treated in calculated positions and refined as riding with distances of C—H = 0.95 and 0.98 Å for the phenyl and methyl groups, respectively, and with U_iso(H) = 1.2U_eq(C). Hydrogen atoms bonded to N or O atoms were located in a difference Fourier map, and their positions and U_iso(H) values were refined freely.

Figures

Fig. 1.

View of the molecular components of 2,5-dimethylanilinium hydrogen maleate with the atom numbering scheme. Displacement ellipsoids for non-H atoms are drawn at the 50% probability level. Hydrogen bonds are shown as dashed lines.

Fig. 2.

View of the molecular arrangement of the title compound along [100]. Hydrogen bonds are shown as dashed lines.

Fig. 3.

Graph-set description of ring-type hydrogen bonding. Hydrogen bonds are shown as dashed lines.

Crystal data

C8H12N+·C4H3O4−	Z = 2
Mr = 237.25	F(000) = 252.00
Triclinic, P1	Dx = 1.348 Mg m−3
Hall symbol: -P 1	Mo Kα radiation, λ = 0.71075 Å
a = 6.7983 (17) Å	Cell parameters from 5478 reflections
b = 8.515 (2) Å	θ = 3.1–27.7°
c = 11.012 (3) Å	µ = 0.10 mm−1
α = 108.784 (8)°	T = 173 K
β = 98.026 (7)°	Prism, colorless
γ = 98.742 (7)°	0.45 × 0.26 × 0.19 mm
V = 584.3 (3) Å3

Data collection

Rigaku XtaLAB mini diffractometer	2222 reflections with F2 > 2.0σ(F2)
Detector resolution: 6.849 pixels mm-1	Rint = 0.021
ω scans	θmax = 27.5°
Absorption correction: multi-scan (REQAB; Rigaku, 1998)	h = −8→8
Tmin = 0.833, Tmax = 0.981	k = −11→11
6136 measured reflections	l = −14→14
2667 independent reflections

Refinement

Refinement on F2	Secondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.042	Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.108	H atoms treated by a mixture of independent and constrained refinement
S = 1.06	w = 1/[σ2(Fo2) + (0.0485P)2 + 0.1991P] where P = (Fo2 + 2Fc2)/3
2667 reflections	(Δ/σ)max < 0.001
172 parameters	Δρmax = 0.25 e Å−3
0 restraints	Δρmin = −0.28 e Å−3
Primary atom site location: structure-invariant direct methods

Special details

Geometry. ENTER SPECIAL DETAILS OF THE MOLECULAR GEOMETRY

Refinement. Refinement was performed using all reflections. The weighted R-factor (wR) and goodness of fit (S) are based on F2. R-factor (gt) are based on F. The threshold expression of F2 > 2.0 σ(F2) is used only for calculating R-factor (gt).

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
O1	0.28044 (17)	1.15154 (14)	0.58091 (10)	0.0323 (3)
O2	0.37703 (18)	1.31701 (13)	0.47170 (11)	0.0355 (3)
O3	0.19359 (18)	0.84302 (14)	0.53298 (10)	0.0329 (3)
O4	0.11116 (16)	0.60871 (13)	0.35616 (11)	0.0330 (3)
N1	0.25093 (19)	0.58663 (15)	0.64194 (11)	0.0215 (3)
C1	0.34834 (19)	0.65824 (16)	0.78115 (12)	0.0196 (3)
C2	0.2577 (2)	0.77054 (16)	0.86650 (13)	0.0215 (3)
C3	0.3508 (3)	0.83054 (18)	0.99864 (13)	0.0267 (3)
C4	0.5245 (3)	0.78132 (19)	1.04275 (14)	0.0295 (4)
C5	0.6148 (2)	0.67116 (18)	0.95572 (15)	0.0264 (3)
C6	0.5240 (2)	0.60942 (17)	0.82285 (14)	0.0231 (3)
C7	0.0705 (3)	0.82651 (19)	0.81904 (14)	0.0279 (3)
C8	0.8045 (3)	0.6188 (3)	1.00350 (18)	0.0371 (4)
C9	0.3196 (2)	1.17476 (17)	0.47453 (14)	0.0240 (3)
C10	0.2959 (3)	1.02714 (18)	0.35196 (14)	0.0261 (3)
C11	0.2359 (3)	0.86040 (17)	0.32482 (13)	0.0253 (3)
C12	0.1743 (2)	0.76436 (17)	0.41028 (14)	0.0236 (3)
H1	0.240 (4)	1.025 (4)	0.564 (3)	0.070 (8)*
H1A	0.237 (3)	0.671 (3)	0.6082 (18)	0.033 (5)*
H3	0.2938	0.9073	1.0602	0.0320*
H4	0.5826	0.8235	1.1337	0.0354*
H1C	0.124 (3)	0.523 (3)	0.6319 (19)	0.041 (5)*
H6	0.5823	0.5341	0.7611	0.0277*
H7A	−0.0376	0.7266	0.7696	0.0334*
H7B	0.1026	0.8909	0.7623	0.0334*
H7C	0.0251	0.8984	0.8943	0.0334*
H8A	0.7767	0.5596	1.0642	0.0445*
H8B	0.9130	0.7198	1.0486	0.0445*
H8C	0.8472	0.5430	0.9287	0.0445*
H1B	0.321 (3)	0.511 (3)	0.5915 (19)	0.036 (5)*
H10	0.3294	1.0566	0.2801	0.0313*
H11	0.2317	0.7919	0.2369	0.0304*

Atomic displacement parameters (Ų)

	U11	U22	U33	U12	U13	U23
O1	0.0469 (7)	0.0269 (6)	0.0224 (6)	0.0110 (5)	0.0078 (5)	0.0058 (5)
O2	0.0427 (7)	0.0205 (6)	0.0417 (7)	0.0047 (5)	0.0167 (6)	0.0062 (5)
O3	0.0478 (7)	0.0312 (6)	0.0248 (6)	0.0102 (5)	0.0101 (5)	0.0148 (5)
O4	0.0339 (6)	0.0226 (6)	0.0416 (7)	0.0012 (5)	0.0088 (5)	0.0118 (5)
N1	0.0251 (6)	0.0209 (6)	0.0179 (6)	0.0041 (5)	0.0043 (5)	0.0064 (5)
C1	0.0217 (7)	0.0179 (6)	0.0191 (7)	0.0000 (5)	0.0043 (5)	0.0082 (5)
C2	0.0233 (7)	0.0208 (7)	0.0214 (7)	0.0037 (5)	0.0059 (6)	0.0088 (6)
C3	0.0329 (8)	0.0264 (7)	0.0195 (7)	0.0053 (6)	0.0071 (6)	0.0060 (6)
C4	0.0320 (8)	0.0317 (8)	0.0209 (7)	−0.0020 (6)	−0.0014 (6)	0.0108 (6)
C5	0.0214 (7)	0.0279 (7)	0.0322 (8)	−0.0001 (6)	0.0016 (6)	0.0174 (7)
C6	0.0227 (7)	0.0223 (7)	0.0268 (7)	0.0044 (5)	0.0071 (6)	0.0111 (6)
C7	0.0294 (8)	0.0313 (8)	0.0269 (8)	0.0129 (6)	0.0088 (6)	0.0112 (6)
C8	0.0251 (8)	0.0449 (10)	0.0471 (10)	0.0044 (7)	0.0004 (7)	0.0281 (8)
C9	0.0216 (7)	0.0225 (7)	0.0263 (7)	0.0069 (6)	0.0047 (6)	0.0056 (6)
C10	0.0326 (8)	0.0250 (7)	0.0217 (7)	0.0046 (6)	0.0071 (6)	0.0095 (6)
C11	0.0308 (8)	0.0229 (7)	0.0195 (7)	0.0034 (6)	0.0043 (6)	0.0051 (6)
C12	0.0210 (7)	0.0239 (7)	0.0276 (8)	0.0060 (5)	0.0042 (6)	0.0110 (6)

Geometric parameters (Å, º)

O1—C9	1.305 (2)	C4—C5	1.391 (3)
O1—H1	1.02 (3)	C4—H4	0.9500
O2—C9	1.227 (2)	C5—C6	1.397 (2)
O3—C12	1.2777 (18)	C5—C8	1.509 (3)
O4—C12	1.2422 (17)	C6—H6	0.9500
N1—C1	1.4671 (17)	C7—H7A	0.9800
N1—H1A	0.922 (19)	C7—H7B	0.9800
N1—H1C	0.92 (2)	C7—H7C	0.9800
N1—H1B	0.941 (19)	C8—H8A	0.9800
C1—C2	1.3926 (19)	C8—H8B	0.9800
C1—C6	1.389 (2)	C8—H8C	0.9800
C2—C3	1.3946 (19)	C9—C10	1.4876 (19)
C2—C7	1.510 (3)	C10—C11	1.337 (2)
C3—C4	1.388 (3)	C11—C12	1.494 (3)
C3—H3	0.9500
C9—O1—H1	109.8 (14)	C5—C6—H6	120.0
C12—O3—H1	111.1 (9)	C2—C7—H7A	109.5
C1—N1—H1A	111.0 (11)	C2—C7—H7B	109.5
C1—N1—H1C	109.7 (12)	H7A—C7—H7B	109.5
H1A—N1—H1C	108.3 (16)	C2—C7—H7C	109.5
C1—N1—H1B	112.6 (11)	H7A—C7—H7C	109.5
H1A—N1—H1B	109.7 (15)	H7B—C7—H7C	109.5
H1C—N1—H1B	105.3 (16)	C5—C8—H8A	109.5
C6—C1—C2	122.76 (12)	C5—C8—H8B	109.5
C6—C1—N1	119.04 (12)	H8A—C8—H8B	109.5
C2—C1—N1	118.19 (12)	C5—C8—H8C	109.5
C1—C2—C3	116.33 (12)	H8A—C8—H8C	109.5
C1—C2—C7	122.09 (12)	H8B—C8—H8C	109.5
C3—C2—C7	121.57 (12)	O2—C9—O1	121.78 (13)
C4—C3—C2	121.87 (13)	O2—C9—C10	117.86 (13)
C4—C3—H3	119.1	O1—C9—C10	120.36 (12)
C2—C3—H3	119.1	C11—C10—C9	131.55 (13)
C3—C4—C5	120.95 (13)	C11—C10—H10	114.2
C3—C4—H4	119.5	C9—C10—H10	114.2
C5—C4—H4	119.5	C10—C11—C12	130.50 (13)
C4—C5—C6	118.13 (13)	C10—C11—H11	114.8
C4—C5—C8	120.96 (14)	C12—C11—H11	114.8
C6—C5—C8	120.91 (14)	O4—C12—O3	123.77 (13)
C1—C6—C5	119.94 (13)	O4—C12—C11	116.61 (13)
C1—C6—H6	120.0	O3—C12—C11	119.59 (12)
C6—C1—C2—C3	−1.19 (19)	C2—C1—C6—C5	1.2 (2)
N1—C1—C2—C3	177.61 (12)	N1—C1—C6—C5	−177.58 (12)
C6—C1—C2—C7	178.07 (12)	C4—C5—C6—C1	−0.11 (19)
N1—C1—C2—C7	−3.14 (18)	C8—C5—C6—C1	179.49 (12)
C1—C2—C3—C4	0.1 (2)	O2—C9—C10—C11	−179.46 (15)
C7—C2—C3—C4	−179.14 (13)	O1—C9—C10—C11	0.7 (2)
C2—C3—C4—C5	0.9 (2)	C9—C10—C11—C12	−1.0 (3)
C3—C4—C5—C6	−0.9 (2)	C10—C11—C12—O4	175.04 (15)
C3—C4—C5—C8	179.48 (13)	C10—C11—C12—O3	−6.8 (2)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O1—H1···O3	1.02 (3)	1.45 (3)	2.4651 (16)	175 (2)
N1—H1A···O3	0.92 (3)	1.94 (3)	2.859 (2)	177.2 (15)
N1—H1C···O4i	0.92 (2)	1.86 (2)	2.7602 (18)	168 (2)
N1—H1B···O2ii	0.94 (2)	1.88 (2)	2.7920 (17)	161.4 (16)

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