Synthesis and structural investigation of salts of 2-amino-3-methyl­pyridine with carb­oxy­lic acid derivatives: an experimental and theoretical study

Balasubramanian, H.; Ashraf, A.M.; Karuppannan, S.; Poomani, K.

doi:10.1107/S2053229624005473

Buy article online - an online subscription or single-article purchase is required to access this article.

Synthesis and structural investigation of salts of 2-amino-3-methylpyridine with carboxylic acid derivatives: an experimental and theoretical study

H. Balasubramanian, A. M. Ashraf, S. Karuppannan and K. Poomani

The salts bis(2-amino-3-methylpyridinium) fumarate dihydrate, 2C₆H₉N₂⁺·C₄H₂O₂²⁻·2H₂O (I), and 2-amino-3-methylpyridinium 5-chlorosalicylate, C₆H₉N₂⁺·C₇H₄ClO₃⁻ (II), were synthesized from 2-amino-3-methylpyridine with fumaric acid and 5-chlorosalicylic acid, respectively. The crystal structures of these salts were characterized by single-crystal X-ray diffraction, revealing protonation in I and II by the transfer of a H atom from the acid to the pyridine base. In the crystals of both I and II, N—H

O interactions form an R₂²(8) ring motif. Hirshfeld surface analysis distinguishes the interactions present in the crystal structures of I and II, and the two-dimensional (2D) fingerprint plot analysis shows the percentage contribution of each type of interaction in the crystal packing. The volumes of the crystal voids of I (39.65 Å³) and II (118.10 Å³) have been calculated and reveal that the crystal of I is more mechanically stable than II. Frontier molecular orbital (FMO) analysis predicts that the band gap energy of II (2.6577 eV) is lower compared to I (4.0035 eV). The Quantum Theory of Atoms In Molecules (QTAIM) analysis shows that the pyridinium–carboxylate N—H

O interaction present in I is stronger than the other interactions, whereas in II, the hydroxy–carboxylate O—H

O interaction is stronger than the pyridinium–carboxylate N—H

O interaction; the bond dissociation energies also confirm these results. The positive Laplacian [∇²ρ(r) > 0] of these interactions shows that the interactions are of the closed shell type. An in-silico ADME (Absorption, Distribution, Metabolism and Excretion) study predicts that both salts will exhibit good pharmacokinetic properties and druglikeness.

Keywords: protonation; salts; crystal structure; electron density distribution; in-silico ADME; druglikeness; fumarate; salicylate; pyridinium.

Read article Similar articles

Supporting information

	Crystallographic Information File (CIF) https://doi.org/10.1107/S2053229624005473/ef3056sup1.cif Contains datablocks global, I, II
	Structure factor file (CIF format) https://doi.org/10.1107/S2053229624005473/ef3056Isup2.hkl Contains datablock I
	Structure factor file (CIF format) https://doi.org/10.1107/S2053229624005473/ef3056IIsup3.hkl Contains datablock II
	Chemical Markup Language (CML) file https://doi.org/10.1107/S2053229624005473/ef3056Isup4.cml Supplementary material
	Chemical Markup Language (CML) file https://doi.org/10.1107/S2053229624005473/ef3056IIsup5.cml Supplementary material
	Portable Document Format (PDF) file https://doi.org/10.1107/S2053229624005473/ef3056sup6.pdf Additional tables and packing diagrams

CCDC references: 2361278; 2221382

Computing details top

Bis(2-amino-3-methylpyridin-1-ium) (2E)-but-2-enedioate dihydrate (I) top

Crystal data top

2C₆H₉N₂⁺·C₄H₂O₄²⁻·2H₂O	Z = 1
M_r = 368.39	F(000) = 196
Triclinic, P1	D_x = 1.324 Mg m⁻³
Hall symbol: -P 1	Mo Kα radiation, λ = 0.71073 Å
a = 6.8383 (2) Å	Cell parameters from 2285 reflections
b = 7.2272 (2) Å	θ = 3.1–28.3°
c = 9.7427 (2) Å	µ = 0.10 mm⁻¹
α = 82.921 (1)°	T = 293 K
β = 76.809 (1)°	Block, green
γ = 82.043 (1)°	0.64 × 0.50 × 0.28 mm
V = 462.18 (2) Å³

Data collection top

Bruker D8 QUEST ECO diffractometer	2118 reflections with I > 2σ(I)
ω and φ scans	R_int = 0.021
Absorption correction: numerical	θ_max = 28.3°, θ_min = 3.1°
T_min = 0.985, T_max = 0.993	h = −9→9
13678 measured reflections	k = −9→9
2285 independent reflections	l = −12→12

Refinement top

Refinement on F²	Primary atom site location: dual
Least-squares matrix: full	Secondary atom site location: dual
R[F² > 2σ(F²)] = 0.041	Hydrogen site location: difference Fourier map
wR(F²) = 0.127	All H-atom parameters refined
S = 1.08	w = 1/[σ²(F_o²) + (0.0831P)² + 0.0403P] where P = (F_o² + 2F_c²)/3
2285 reflections	(Δ/σ)_max < 0.001
166 parameters	Δρ_max = 0.27 e Å⁻³
0 restraints	Δρ_min = −0.21 e Å⁻³
0 constraints

Special details top

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

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
O1	0.45370 (10)	0.59625 (12)	0.74961 (7)	0.0462 (2)
O2	0.78438 (11)	0.51702 (12)	0.72217 (7)	0.0484 (2)
O3	0.04724 (15)	0.74470 (16)	0.79679 (12)	0.0659 (3)
N2	0.47857 (12)	0.76067 (12)	0.48593 (8)	0.0376 (2)
N1	0.81571 (14)	0.65419 (14)	0.42588 (10)	0.0477 (3)
C1	0.65232 (14)	0.75031 (13)	0.38781 (9)	0.0351 (2)
C7	0.60883 (13)	0.53625 (13)	0.79683 (9)	0.0337 (2)
C8	0.58517 (13)	0.48544 (14)	0.95351 (9)	0.0380 (2)
C5	0.65334 (17)	0.84300 (14)	0.25000 (10)	0.0414 (2)
C2	0.30349 (16)	0.85702 (16)	0.46070 (12)	0.0460 (3)
C4	0.4763 (2)	0.94154 (15)	0.22736 (11)	0.0503 (3)
C3	0.29758 (19)	0.94987 (17)	0.33208 (13)	0.0532 (3)
C6	0.8443 (2)	0.8279 (2)	0.13837 (13)	0.0622 (3)
H2A	0.479 (2)	0.694 (2)	0.5790 (19)	0.062 (4)*
H2	0.192 (3)	0.855 (2)	0.538 (2)	0.076 (5)*
H1B	0.804 (2)	0.603 (2)	0.5182 (18)	0.060 (4)*
H4	0.475 (3)	1.009 (3)	0.133 (2)	0.078 (5)*
H1A	0.931 (3)	0.639 (2)	0.3676 (17)	0.063 (4)*
H6A	0.826 (3)	0.893 (3)	0.053 (3)	0.096 (6)*
H3	0.174 (3)	1.019 (2)	0.3195 (19)	0.070 (4)*
H6C	0.948 (4)	0.884 (3)	0.162 (2)	0.100 (7)*
H6B	0.887 (4)	0.694 (4)	0.116 (2)	0.108 (7)*
H8	0.710 (3)	0.427 (2)	0.9823 (17)	0.067 (4)*
H3A	0.172 (3)	0.686 (3)	0.797 (2)	0.082 (5)*
H3B	−0.022 (4)	0.653 (3)	0.777 (2)	0.096 (6)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O1	0.0314 (4)	0.0726 (5)	0.0304 (4)	−0.0010 (3)	−0.0074 (3)	0.0071 (3)
O2	0.0309 (4)	0.0762 (5)	0.0308 (4)	0.0044 (3)	−0.0001 (3)	−0.0007 (3)
O3	0.0435 (5)	0.0768 (6)	0.0760 (6)	0.0055 (4)	−0.0130 (4)	−0.0160 (5)
N2	0.0350 (4)	0.0467 (4)	0.0284 (4)	0.0003 (3)	−0.0051 (3)	−0.0014 (3)
N1	0.0359 (5)	0.0675 (6)	0.0326 (4)	0.0078 (4)	−0.0028 (3)	−0.0011 (4)
C1	0.0364 (5)	0.0399 (4)	0.0276 (4)	−0.0020 (3)	−0.0050 (3)	−0.0040 (3)
C7	0.0298 (4)	0.0428 (4)	0.0264 (4)	−0.0024 (3)	−0.0039 (3)	−0.0009 (3)
C8	0.0303 (4)	0.0532 (5)	0.0277 (4)	0.0004 (4)	−0.0064 (3)	0.0010 (3)
C5	0.0504 (6)	0.0447 (5)	0.0280 (4)	−0.0071 (4)	−0.0060 (4)	−0.0014 (3)
C2	0.0359 (5)	0.0555 (6)	0.0441 (6)	0.0031 (4)	−0.0075 (4)	−0.0069 (4)
C4	0.0665 (7)	0.0492 (6)	0.0359 (5)	−0.0016 (5)	−0.0195 (5)	0.0031 (4)
C3	0.0503 (6)	0.0572 (6)	0.0525 (6)	0.0101 (5)	−0.0229 (5)	−0.0035 (5)
C6	0.0644 (8)	0.0813 (9)	0.0321 (5)	−0.0120 (7)	0.0054 (5)	0.0029 (5)

Geometric parameters (Å, º) top

O1—C7	1.2535 (11)	C8—C8ⁱ	1.3112 (18)
O2—C7	1.2529 (11)	C8—H8	0.981 (18)
O3—H3A	0.90 (2)	C5—C4	1.3662 (16)
O3—H3B	0.93 (2)	C5—C6	1.4971 (16)
N2—C1	1.3438 (12)	C2—C3	1.3530 (17)
N2—C2	1.3565 (13)	C2—H2	0.94 (2)
N2—H2A	0.974 (17)	C4—C3	1.4012 (19)
N1—C1	1.3339 (12)	C4—H4	0.984 (19)
N1—H1B	0.920 (17)	C3—H3	0.942 (19)
N1—H1A	0.863 (18)	C6—H6A	0.93 (2)
C1—C5	1.4236 (13)	C6—H6C	0.95 (2)
C7—C8	1.5022 (12)	C6—H6B	1.01 (2)

H3A—O3—H3B	103.8 (18)	C4—C5—C6	123.52 (10)
C1—N2—C2	123.19 (8)	C1—C5—C6	119.32 (10)
C1—N2—H2A	118.1 (10)	C3—C2—N2	120.28 (10)
C2—N2—H2A	118.7 (10)	C3—C2—H2	124.2 (11)
C1—N1—H1B	118.3 (10)	N2—C2—H2	115.5 (11)
C1—N1—H1A	122.6 (10)	C5—C4—C3	122.70 (10)
H1B—N1—H1A	119.0 (15)	C5—C4—H4	118.4 (11)
N1—C1—N2	117.74 (8)	C3—C4—H4	118.9 (11)
N1—C1—C5	123.53 (9)	C2—C3—C4	117.91 (10)
N2—C1—C5	118.73 (9)	C2—C3—H3	117.8 (11)
O2—C7—O1	124.41 (8)	C4—C3—H3	124.2 (11)
O2—C7—C8	117.18 (8)	C5—C6—H6A	111.3 (14)
O1—C7—C8	118.41 (8)	C5—C6—H6C	112.2 (14)
C8ⁱ—C8—C7	124.23 (10)	H6A—C6—H6C	104.2 (18)
C8ⁱ—C8—H8	121.5 (9)	C5—C6—H6B	111.1 (14)
C7—C8—H8	114.2 (9)	H6A—C6—H6B	104.8 (18)
C4—C5—C1	117.16 (10)	H6C—C6—H6B	112.8 (19)

C2—N2—C1—N1	178.78 (9)	N2—C1—C5—C6	−178.18 (10)
C2—N2—C1—C5	−0.67 (14)	C1—N2—C2—C3	−0.37 (16)
O2—C7—C8—C8ⁱ	173.25 (13)	C1—C5—C4—C3	−1.54 (17)
O1—C7—C8—C8ⁱ	−6.09 (18)	C6—C5—C4—C3	178.20 (12)
N1—C1—C5—C4	−177.84 (10)	N2—C2—C3—C4	0.45 (18)
N2—C1—C5—C4	1.58 (14)	C5—C4—C3—C2	0.54 (19)
N1—C1—C5—C6	2.41 (16)

Symmetry code: (i) −x+1, −y+1, −z+2.

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1A···O2ⁱⁱ	0.86 (19)	2.16 (19)	2.96 (13)	154.5 (14)
N1—H1B···O2	0.92 (17)	1.98 (17)	2.90 (12)	174.3 (14)
N2—H2A···O1	0.97 (17)	1.70 (18)	2.67 (10)	173.2 (14)
O3—H3A···O1	0.90 (2)	1.92 (2)	2.79 (13)	165.0 (18)
O3—H3B···O2ⁱⁱⁱ	0.93 (2)	1.95 (3)	2.85 (14)	165 (2)
C2—H2···O3	0.94 (2)	2.55 (19)	3.40 (16)	149.1 (15)
C3—H3···O3^iv	0.95 (2)	2.46 (18)	3.35 (17)	156.1 (15)

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

2-Amino-3-methylpyridin-1-ium 5-chloro-2-hydroxybenzoate (II) top

Crystal data top

C₆H₉N₂⁺·C₇H₄ClO₃⁻	F(000) = 584
M_r = 280.7	D_x = 1.448 Mg m⁻³
Monoclinic, P2₁/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 3194 reflections
a = 11.7399 (2) Å	θ = 2.9–28.3°
b = 8.3731 (1) Å	µ = 0.30 mm⁻¹
c = 13.6779 (2) Å	T = 293 K
β = 106.782 (1)°	Plate, green
V = 1287.27 (3) Å³	0.74 × 0.45 × 0.36 mm
Z = 4

Data collection top

Bruker D8 QUEST ECO diffractometer	2907 reflections with I > 2σ(I)
ω and φ scans	R_int = 0.021
Absorption correction: numerical	θ_max = 28.3°, θ_min = 2.9°
T_min = 0.606, T_max = 0.647	h = −15→15
30652 measured reflections	k = −11→10
3194 independent reflections	l = −18→18

Refinement top

Refinement on F²	Primary atom site location: dual
Least-squares matrix: full	Secondary atom site location: dual
R[F² > 2σ(F²)] = 0.035	Hydrogen site location: difference Fourier map
wR(F²) = 0.107	All H-atom parameters refined
S = 1.05	w = 1/[σ²(F_o²) + (0.0598P)² + 0.2514P] where P = (F_o² + 2F_c²)/3
3194 reflections	(Δ/σ)_max = 0.002
224 parameters	Δρ_max = 0.30 e Å⁻³
0 restraints	Δρ_min = −0.28 e Å⁻³
0 constraints

Special details top

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
Cl	1.05112 (3)	0.27065 (6)	0.57782 (3)	0.06891 (15)
O3	0.64726 (8)	0.60188 (11)	0.49608 (6)	0.0494 (2)
O1	0.70973 (9)	0.46216 (12)	0.79510 (7)	0.0506 (2)
O2	0.59619 (8)	0.61202 (12)	0.64034 (7)	0.0513 (2)
N2	0.46431 (9)	0.79911 (11)	0.40726 (7)	0.0359 (2)
N1	0.40130 (10)	0.81870 (13)	0.55084 (7)	0.0415 (2)
C8	0.38904 (9)	0.86283 (12)	0.45482 (7)	0.0329 (2)
C2	0.76984 (9)	0.46817 (12)	0.64153 (8)	0.0333 (2)
C7	0.66395 (10)	0.56791 (12)	0.58751 (8)	0.0366 (2)
C3	0.85209 (10)	0.42167 (14)	0.59101 (8)	0.0386 (2)
C9	0.30097 (10)	0.97273 (13)	0.40035 (8)	0.0372 (2)
C1	0.78668 (10)	0.41900 (14)	0.74288 (8)	0.0383 (2)
C12	0.46073 (11)	0.83664 (15)	0.31002 (9)	0.0423 (3)
C4	0.94755 (10)	0.32745 (16)	0.64037 (9)	0.0438 (3)
C11	0.37977 (12)	0.94218 (16)	0.25540 (9)	0.0472 (3)
C6	0.88328 (12)	0.32154 (17)	0.79078 (9)	0.0492 (3)
C10	0.29943 (12)	1.00941 (15)	0.30240 (9)	0.0457 (3)
C5	0.96310 (11)	0.27580 (17)	0.73958 (10)	0.0499 (3)
C13	0.21525 (12)	1.04167 (18)	0.45147 (11)	0.0499 (3)
H1A	0.3562 (15)	0.859 (2)	0.5827 (12)	0.059 (4)*
H12	0.5156 (15)	0.784 (2)	0.2873 (13)	0.056 (4)*
H3	0.8388 (13)	0.4560 (18)	0.5223 (12)	0.048 (4)*
H1B	0.4565 (15)	0.7444 (19)	0.5780 (12)	0.053 (4)*
H11	0.3748 (15)	0.969 (2)	0.1868 (12)	0.058 (4)*
H10	0.2410 (15)	1.085 (2)	0.2641 (12)	0.060 (4)*
H1	0.6558 (19)	0.517 (3)	0.7472 (16)	0.086 (6)*
H6	0.8933 (15)	0.283 (2)	0.8605 (14)	0.064 (5)*
H2	0.5216 (18)	0.725 (2)	0.4376 (15)	0.073 (5)*
H13A	0.1607 (19)	1.111 (3)	0.4046 (15)	0.088 (6)*
H13B	0.2567 (17)	1.100 (2)	0.5144 (15)	0.075 (5)*
H5	1.0313 (17)	0.199 (2)	0.7694 (15)	0.075 (5)*
H13C	0.1699 (19)	0.957 (3)	0.4738 (16)	0.086 (6)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
Cl	0.0479 (2)	0.0929 (3)	0.0708 (3)	0.01654 (17)	0.02496 (18)	−0.0117 (2)
O3	0.0525 (5)	0.0564 (5)	0.0393 (4)	0.0140 (4)	0.0131 (4)	0.0070 (4)
O1	0.0533 (5)	0.0649 (6)	0.0398 (4)	0.0047 (4)	0.0233 (4)	0.0057 (4)
O2	0.0510 (5)	0.0582 (5)	0.0502 (5)	0.0176 (4)	0.0233 (4)	0.0074 (4)
N2	0.0385 (5)	0.0380 (4)	0.0336 (4)	0.0007 (4)	0.0139 (4)	−0.0013 (3)
N1	0.0468 (5)	0.0477 (5)	0.0332 (5)	0.0080 (4)	0.0165 (4)	0.0019 (4)
C8	0.0344 (5)	0.0327 (5)	0.0324 (5)	−0.0041 (4)	0.0107 (4)	−0.0038 (4)
C2	0.0325 (5)	0.0332 (5)	0.0337 (5)	−0.0038 (4)	0.0088 (4)	−0.0025 (4)
C7	0.0378 (5)	0.0336 (5)	0.0389 (5)	−0.0007 (4)	0.0117 (4)	−0.0006 (4)
C3	0.0366 (5)	0.0440 (6)	0.0355 (5)	−0.0020 (4)	0.0110 (4)	−0.0032 (4)
C9	0.0362 (5)	0.0379 (5)	0.0367 (5)	−0.0005 (4)	0.0091 (4)	−0.0024 (4)
C1	0.0376 (5)	0.0432 (5)	0.0345 (5)	−0.0044 (4)	0.0110 (4)	−0.0010 (4)
C12	0.0487 (6)	0.0461 (6)	0.0372 (5)	−0.0043 (5)	0.0205 (5)	−0.0043 (4)
C4	0.0333 (5)	0.0512 (6)	0.0465 (6)	0.0009 (5)	0.0111 (4)	−0.0087 (5)
C11	0.0584 (7)	0.0522 (7)	0.0325 (5)	−0.0043 (5)	0.0155 (5)	0.0023 (5)
C6	0.0466 (6)	0.0602 (7)	0.0364 (6)	0.0028 (5)	0.0050 (5)	0.0070 (5)
C10	0.0475 (6)	0.0470 (6)	0.0391 (6)	0.0031 (5)	0.0070 (5)	0.0045 (5)
C5	0.0377 (6)	0.0557 (7)	0.0493 (7)	0.0063 (5)	0.0016 (5)	0.0012 (5)
C13	0.0441 (6)	0.0554 (7)	0.0511 (7)	0.0116 (6)	0.0153 (5)	−0.0012 (6)

Geometric parameters (Å, º) top

Cl—C4	1.7428 (12)	C3—H3	0.952 (15)
O3—C7	1.2417 (13)	C9—C10	1.3694 (17)
O1—C1	1.3525 (14)	C9—C13	1.4971 (16)
O1—H1	0.90 (2)	C1—C6	1.3972 (17)
O2—C7	1.2741 (13)	C12—C11	1.3538 (19)
N2—C8	1.3494 (13)	C12—H12	0.907 (17)
N2—C12	1.3554 (14)	C4—C5	1.3851 (19)
N2—H2	0.92 (2)	C11—C10	1.4036 (19)
N1—C8	1.3315 (14)	C11—H11	0.951 (16)
N1—H1A	0.849 (18)	C6—C5	1.376 (2)
N1—H1B	0.897 (17)	C6—H6	0.982 (18)
C8—C9	1.4233 (15)	C10—H10	0.967 (17)
C2—C3	1.3953 (15)	C5—H5	1.01 (2)
C2—C1	1.4043 (15)	C13—H13A	0.96 (2)
C2—C7	1.5028 (15)	C13—H13B	0.99 (2)
C3—C4	1.3774 (17)	C13—H13C	0.99 (2)

C1—O1—H1	101.0 (13)	C11—C12—N2	120.72 (11)
C8—N2—C12	122.84 (10)	C11—C12—H12	125.8 (11)
C8—N2—H2	122.9 (12)	N2—C12—H12	113.5 (11)
C12—N2—H2	114.2 (12)	C3—C4—C5	121.16 (11)
C8—N1—H1A	119.3 (11)	C3—C4—Cl	119.99 (10)
C8—N1—H1B	117.4 (10)	C5—C4—Cl	118.84 (10)
H1A—N1—H1B	123.3 (15)	C12—C11—C10	117.81 (11)
N1—C8—N2	117.81 (10)	C12—C11—H11	122.3 (10)
N1—C8—C9	123.44 (10)	C10—C11—H11	119.9 (10)
N2—C8—C9	118.76 (9)	C5—C6—C1	120.24 (11)
C3—C2—C1	119.13 (10)	C5—C6—H6	119.6 (10)
C3—C2—C7	120.27 (9)	C1—C6—H6	120.2 (10)
C1—C2—C7	120.59 (10)	C9—C10—C11	122.50 (11)
O3—C7—O2	124.20 (10)	C9—C10—H10	118.9 (10)
O3—C7—C2	119.34 (10)	C11—C10—H10	118.6 (10)
O2—C7—C2	116.46 (9)	C6—C5—C4	119.68 (11)
C4—C3—C2	119.90 (10)	C6—C5—H5	123.0 (11)
C4—C3—H3	122.4 (9)	C4—C5—H5	117.2 (11)
C2—C3—H3	117.7 (9)	C9—C13—H13A	109.3 (12)
C10—C9—C8	117.36 (10)	C9—C13—H13B	111.7 (11)
C10—C9—C13	123.34 (11)	H13A—C13—H13B	110.6 (16)
C8—C9—C13	119.30 (10)	C9—C13—H13C	111.3 (12)
O1—C1—C6	118.94 (10)	H13A—C13—H13C	109.0 (17)
O1—C1—C2	121.19 (10)	H13B—C13—H13C	104.9 (16)
C6—C1—C2	119.87 (11)

C12—N2—C8—N1	−179.32 (10)	C3—C2—C1—C6	−1.56 (17)
C12—N2—C8—C9	0.82 (16)	C7—C2—C1—C6	177.71 (10)
C3—C2—C7—O3	3.52 (16)	C8—N2—C12—C11	0.10 (18)
C1—C2—C7—O3	−175.75 (10)	C2—C3—C4—C5	0.77 (18)
C3—C2—C7—O2	−176.66 (10)	C2—C3—C4—Cl	−179.44 (8)
C1—C2—C7—O2	4.08 (15)	N2—C12—C11—C10	−0.70 (19)
C1—C2—C3—C4	0.64 (16)	O1—C1—C6—C5	−179.95 (12)
C7—C2—C3—C4	−178.64 (10)	C2—C1—C6—C5	1.10 (19)
N1—C8—C9—C10	179.07 (11)	C8—C9—C10—C11	0.50 (18)
N2—C8—C9—C10	−1.08 (15)	C13—C9—C10—C11	−179.30 (12)
N1—C8—C9—C13	−1.13 (17)	C12—C11—C10—C9	0.4 (2)
N2—C8—C9—C13	178.72 (10)	C1—C6—C5—C4	0.3 (2)
C3—C2—C1—O1	179.51 (10)	C3—C4—C5—C6	−1.2 (2)
C7—C2—C1—O1	−1.22 (16)	Cl—C4—C5—C6	178.96 (11)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O1—H1···O2	0.90 (2)	1.63 (2)	2.49 (13)	159 (2)
N1—H1A···O1ⁱ	0.85 (18)	2.20 (17)	3.02 (15)	162.2 (16)
N1—H1B···O2ⁱⁱ	0.89 (17)	1.95 (17)	2.84 (15)	170.3 (16)
N2—H2···O3ⁱⁱ	0.92 (19)	1.79 (2)	2.70 (14)	172.2)
C3—H3···O3	0.95 (16)	2.49 (16)	2.81 (15)	100.0 (11)

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

Molecular descriptors of I and II top

Parameters (eV)	Salt I	Salt II
E_HOMO	-6.3983	-5.2748
E_LUMO	-2.3948	-2.6171
Energy gap (ΔE)	4.0035	2.6577
Electron affinity (A)	2.3948	2.6171
Ionization potential (I)	6.3983	5.2748
Electronegativity (χ)	4.3965	3.9459
Electrochemical potential (µ)	-4.3965	-3.9459
Electrophilicity (ω)	4.8280	5.8587
Global hardness (ν)	2.0017	1.3288
Softness (σ)	0.4995	0.7525

QTAIM analysis of I and II top

D—H···A	H···A (Å)	ρ(r) (e Å^-3)	∇²ρ(r) (e Å^-5)	G(r) (a.u.)	V(r) (a.u.)	H(r) (a.u.)	D_e (kJ cal^-1)
N1—H1A···O2	2.16 (19)	0.137	1.977	0.0290	-0.0375	-0.0085	49.21
N1—H1B···O2	1.98 (17)	0.217	2.464	0.0502	-0.0749	-0.0247	98.30
N2—H2A···O1	1.70 (18)	0.401	3.622	0.1176	-0.1977	-0.0801	259.48
C2—H2···O3	2.55 (19)	0.078	0.769	0.0113	-0.0147	-0.0034	19.29
C3—H3···O3	2.46 (18)	0.074	0.856	0.0114	-0.014	-0.0026	18.37
O1—H1···O2	1.63 (2)	0.453	4.226	0.1427	-0.2416	-0.0989	317.1
N1—H1A···O1	2.20 (17)	0.143	2.002	0.0304	-0.0401	-0.0097	52.63
N1—H1B···O2	1.95 (17)	0.210	2.461	0.0485	-0.0715	-0.023	93.84
N2—H2···O3	1.79 (2)	0.326	3.05	0.0866	-0.1416	-0.055	185.85

Results of in-silico ADME prediction for I and II TPSA is topological polar surface area, GI is gastrointestinal and BBB is blood–brain barrier. top

Formula	C₁₀H₁₄N₂O₅	C₁₃H₁₃ClN₂O₃
M_r	241.22	280.71
Heavy atoms	17	19
Aromatic heavy atoms	0	6
Fraction C(sp³)	0.2	0.15
No of rotatable bonds	2	1
No of hydrogen-bond acceptors	6	4
No of hydrogen-bond donors	3	3
TPSA	81.42	75.35
GI absorption	High	High
BBB permeant	No	No
Bioavailability score	0.56	0.55
log K_p (cm s^-1) (skin permeation)	-9.87	-7.26
Lipinski No. of violations	0	0

Subscribe to Acta Crystallographica Section C: Structural Chemistry

Buy online

You may purchase this article in PDF and/or HTML formats. For purchasers in the European Community who do not have a VAT number, VAT will be added at the local rate. Payments to the IUCr are handled by WorldPay, who will accept payment by credit card in several currencies. To purchase the article, please complete the form below (fields marked * are required), and then click on `Continue'.

E-mail address*
Repeat e-mail address* (for error checking)

Format*	PDF (US $40)
	HTML (US $40)
	PDF+HTML (US $50)
In order for VAT to be shown for your country javascript needs to be enabled.

VAT number (non-UK EC countries only)
Country*

Terms and conditions of use
Contact us

Format		BIBTeX
		EndNote
		RefMan
		Refer
		Medline
		CIF
		SGML
		Text
		Plain Text

Format		BIBTeX
		EndNote
		RefMan
		Refer
		Medline
		CIF
		SGML
		Text
		Plain Text

Search IUCr Journals		doi		Advanced search
Author		volume	page

Synthesis and structural investigation of salts of 2-amino-3-methyl­pyridine with carb­oxy­lic acid derivatives: an experimental and theoretical study

Supporting information

Subscribe to Acta Crystallographica Section C: Structural Chemistry

Buy online

Synthesis and structural investigation of salts of 2-amino-3-methylpyridine with carboxylic acid derivatives: an experimental and theoretical study