Nifedipine-pyrazine (2/1).

In the title compound, 2C(17)H(18)N(2)O(6)·C(4)H(4)N(2) [systematic name: 3,5-dimethyl 2,6-dimethyl-4-(2-nitro-phen-yl)-1,4-di-hydro-pyridine-3,5-dicarboxyl-ate-pyrazine (2/1)], the complete pyrazine molecule is generated by crystallographic inversion symmetry. The center of the pyrazine ring lies on an inversion center. The nifedipine mol-ecules are linked into chains along the c axis through N-H⋯O hydrogen bonds, while the pyrazine mol-ecules are organized in the structure through van der Waals inter-actions.

Related literature

Co-crystalline materials are of pharmaceutical inter­est due to their ability to alter the physicochemical properties of active pharmaceutical ingredients (APIs) (Schultheiss et al., 2009 ▶) and provide drug repositioning or life-cycle management (Trask, 2007 ▶). The corresponding crystal structure of nifedipine has been reported (Triggle et al., 2003 ▶) and it also forms chains through N—H⋯O hydrogen bonds. Other crystalline forms also exist: polymorphs (Burger et al., 1996 ▶) solvates/hydrates (Caira et al., 2003 ▶) and a metal complex (Bontchev et al., 2003 ▶), as well as a non-crystalline, amorphous phase (Miyazaki et al., 2007 ▶).

Experimental

Crystal data

C19H20N3O6

M = 386.38

Monoclinic,

a = 13.6278 (14) Å

b = 9.1594 (9) Å

c = 14.4432 (14) Å

β = 94.841 (4)°

V = 1796.4 (3) Å3

Z = 4

Mo Kα radiation

μ = 0.11 mm−1

T = 120 K

0.24 × 0.18 × 0.10 mm

Data collection

Bruker APEXII CCD diffractometer

27572 measured reflections

6070 independent reflections

4916 reflections with I > 2σ(I)

R int = 0.036

Refinement

R[F 2 > 2σ(F 2)] = 0.043

wR(F 2) = 0.125

S = 1.07

6070 reflections

261 parameters

H atoms treated by a mixture of independent and constrained refinement

Δρmax = 0.48 e Å−3

Δρmin = −0.24 e Å−3

Data collection: APEX2 (Bruker, 2007 ▶); cell refinement: SAINT (Bruker, 2007 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: PLATON (Spek, 2009 ▶); software used to prepare material for publication: SHELXTL (Sheldrick, 2008 ▶), PLATON and Mercury (Macrae et al., 2006 ▶).

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536810031703/kj2152sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810031703/kj2152Isup2.hkl

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

C19H20N3O6	F(000) = 812
Mr = 386.38	Dx = 1.429 Mg m−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 9767 reflections
a = 13.6278 (14) Å	θ = 2.6–31.7°
b = 9.1594 (9) Å	µ = 0.11 mm−1
c = 14.4432 (14) Å	T = 120 K
β = 94.841 (4)°	Prism, colourless
V = 1796.4 (3) Å3	0.24 × 0.18 × 0.10 mm
Z = 4

Bruker APEXII CCD diffractometer	4916 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.036
graphite	θmax = 31.8°, θmin = 2.6°
φ and ω scans	h = −20→19
27572 measured reflections	k = −13→13
6070 independent reflections	l = −17→21

Refinement on F2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.043	Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.125	H atoms treated by a mixture of independent and constrained refinement
S = 1.07	w = 1/[σ2(Fo2) + (0.070P)2 + 0.250P] where P = (Fo2 + 2Fc2)/3
6070 reflections	(Δ/σ)max < 0.001
261 parameters	Δρmax = 0.48 e Å−3
0 restraints	Δρmin = −0.24 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
N11	0.91012 (7)	0.66064 (10)	0.58015 (6)	0.01904 (17)
H11	0.9275 (12)	0.6672 (17)	0.6420 (12)	0.033 (4)*
C12	0.96337 (7)	0.73800 (11)	0.52067 (6)	0.01680 (18)
C13	0.92963 (7)	0.74418 (11)	0.42914 (6)	0.01588 (17)
C14	0.82937 (7)	0.68380 (10)	0.39640 (6)	0.01536 (17)
H14	0.8323	0.6431	0.3324	0.018*
C15	0.80215 (7)	0.56174 (10)	0.46039 (6)	0.01635 (17)
C16	0.83786 (7)	0.56204 (11)	0.55095 (7)	0.01793 (18)
C22	1.05495 (8)	0.80615 (12)	0.56668 (7)	0.0214 (2)
H22A	1.0559	0.9104	0.5515	0.032*
H22B	1.1129	0.7586	0.5444	0.032*
H22C	1.0558	0.7940	0.6342	0.032*
C23	0.98313 (7)	0.80823 (11)	0.35653 (7)	0.01736 (18)
O23	1.06719 (5)	0.87616 (9)	0.38444 (5)	0.02116 (16)
O24	0.95391 (6)	0.80104 (11)	0.27468 (5)	0.0315 (2)
C25	0.73593 (7)	0.44528 (11)	0.42414 (7)	0.01813 (18)
O25	0.71443 (6)	0.45992 (8)	0.33133 (5)	0.02199 (16)
O26	0.70447 (6)	0.34517 (9)	0.46697 (6)	0.02589 (17)
C26	0.80877 (9)	0.46176 (12)	0.62596 (7)	0.0237 (2)
H26A	0.7373	0.4660	0.6291	0.036*
H26B	0.8418	0.4921	0.6858	0.036*
H26C	0.8282	0.3616	0.6121	0.036*
C27	1.11954 (9)	0.93700 (14)	0.31148 (8)	0.0264 (2)
H27A	1.1818	0.9789	0.3380	0.040*
H27B	1.0795	1.0136	0.2795	0.040*
H27C	1.1330	0.8601	0.2671	0.040*
C28	0.65577 (9)	0.34450 (13)	0.28780 (8)	0.0276 (2)
H28A	0.6401	0.3676	0.2219	0.041*
H28B	0.5946	0.3347	0.3184	0.041*
H28C	0.6926	0.2526	0.2934	0.041*
C31	0.75049 (7)	0.80317 (10)	0.39303 (6)	0.01571 (17)
C32	0.67448 (7)	0.82130 (11)	0.32317 (7)	0.01755 (18)
N32	0.66655 (7)	0.73025 (10)	0.23900 (6)	0.01976 (17)
O32	0.73861 (6)	0.71650 (9)	0.19529 (5)	0.02539 (17)
O33	0.58615 (6)	0.67540 (9)	0.21593 (6)	0.02713 (18)
C33	0.60043 (8)	0.92431 (12)	0.32730 (7)	0.0219 (2)
H33	0.5497	0.9320	0.2782	0.026*
C34	0.60109 (8)	1.01542 (12)	0.40326 (8)	0.0239 (2)
H34	0.5512	1.0872	0.4068	0.029*
C35	0.67529 (8)	1.00121 (12)	0.47455 (7)	0.0227 (2)
H35	0.6763	1.0634	0.5273	0.027*
C36	0.74769 (8)	0.89694 (11)	0.46907 (7)	0.01926 (19)
H36	0.7975	0.8886	0.5189	0.023*
N41	0.45265 (8)	0.46068 (12)	0.41368 (7)	0.0302 (2)
C42	0.45577 (9)	0.37242 (13)	0.48684 (9)	0.0289 (2)
H42	0.4248	0.2796	0.4805	0.035*
C43	0.50253 (9)	0.41122 (14)	0.57190 (8)	0.0297 (2)
H43	0.5027	0.3439	0.6220	0.036*

	U11	U22	U33	U12	U13	U23
N11	0.0221 (4)	0.0250 (4)	0.0100 (3)	−0.0011 (3)	0.0008 (3)	0.0011 (3)
C12	0.0176 (4)	0.0209 (4)	0.0119 (4)	0.0010 (3)	0.0011 (3)	−0.0001 (3)
C13	0.0159 (4)	0.0201 (4)	0.0116 (4)	−0.0002 (3)	0.0012 (3)	0.0004 (3)
C14	0.0169 (4)	0.0183 (4)	0.0109 (4)	−0.0003 (3)	0.0015 (3)	−0.0002 (3)
C15	0.0170 (4)	0.0175 (4)	0.0147 (4)	0.0003 (3)	0.0025 (3)	0.0005 (3)
C16	0.0199 (4)	0.0197 (4)	0.0145 (4)	0.0015 (3)	0.0032 (3)	0.0013 (3)
C22	0.0200 (5)	0.0293 (5)	0.0143 (4)	−0.0021 (4)	−0.0014 (3)	−0.0011 (4)
C23	0.0174 (4)	0.0215 (4)	0.0132 (4)	0.0005 (3)	0.0014 (3)	−0.0002 (3)
O23	0.0211 (3)	0.0285 (4)	0.0141 (3)	−0.0065 (3)	0.0031 (3)	−0.0004 (3)
O24	0.0279 (4)	0.0550 (6)	0.0111 (3)	−0.0138 (4)	−0.0004 (3)	0.0043 (3)
C25	0.0182 (4)	0.0187 (4)	0.0178 (4)	0.0024 (3)	0.0029 (3)	−0.0004 (3)
O25	0.0246 (4)	0.0240 (4)	0.0170 (3)	−0.0059 (3)	−0.0004 (3)	−0.0019 (3)
O26	0.0308 (4)	0.0224 (4)	0.0247 (4)	−0.0055 (3)	0.0037 (3)	0.0025 (3)
C26	0.0300 (5)	0.0242 (5)	0.0173 (4)	−0.0007 (4)	0.0043 (4)	0.0057 (4)
C27	0.0270 (5)	0.0335 (6)	0.0196 (5)	−0.0097 (4)	0.0066 (4)	0.0014 (4)
C28	0.0273 (5)	0.0295 (5)	0.0256 (5)	−0.0089 (4)	0.0003 (4)	−0.0067 (4)
C31	0.0166 (4)	0.0175 (4)	0.0131 (4)	−0.0010 (3)	0.0018 (3)	0.0015 (3)
C32	0.0188 (4)	0.0202 (4)	0.0135 (4)	−0.0018 (3)	0.0001 (3)	0.0002 (3)
N32	0.0221 (4)	0.0224 (4)	0.0142 (4)	0.0003 (3)	−0.0022 (3)	0.0010 (3)
O32	0.0270 (4)	0.0339 (4)	0.0155 (3)	0.0015 (3)	0.0033 (3)	−0.0017 (3)
O33	0.0249 (4)	0.0304 (4)	0.0245 (4)	−0.0054 (3)	−0.0067 (3)	−0.0025 (3)
C33	0.0204 (5)	0.0244 (5)	0.0204 (5)	0.0022 (4)	−0.0012 (3)	0.0022 (4)
C34	0.0252 (5)	0.0227 (5)	0.0237 (5)	0.0054 (4)	0.0014 (4)	0.0010 (4)
C35	0.0276 (5)	0.0208 (4)	0.0197 (5)	0.0031 (4)	0.0017 (4)	−0.0029 (4)
C36	0.0223 (5)	0.0204 (4)	0.0149 (4)	0.0009 (3)	0.0002 (3)	−0.0008 (3)
N41	0.0291 (5)	0.0373 (5)	0.0247 (5)	−0.0013 (4)	0.0058 (4)	−0.0037 (4)
C42	0.0283 (6)	0.0271 (5)	0.0327 (6)	−0.0038 (4)	0.0101 (4)	−0.0035 (5)
C43	0.0313 (6)	0.0325 (6)	0.0264 (5)	0.0000 (5)	0.0093 (4)	0.0046 (5)

N11—C12	1.3682 (13)	C27—H27A	0.9800
N11—C16	1.3759 (13)	C27—H27B	0.9800
N11—H11	0.906 (17)	C27—H27C	0.9800
C12—C13	1.3636 (13)	C28—H28A	0.9800
C12—C22	1.4996 (14)	C28—H28B	0.9800
C13—C23	1.4507 (13)	C28—H28C	0.9800
C13—C14	1.5125 (13)	C31—C32	1.3937 (13)
C14—C15	1.5165 (13)	C31—C36	1.3973 (13)
C14—C31	1.5311 (13)	C32—C33	1.3865 (14)
C14—H14	1.0000	C32—N32	1.4706 (13)
C15—C16	1.3566 (13)	N32—O32	1.2180 (12)
C15—C25	1.4651 (14)	N32—O33	1.2257 (12)
C16—C26	1.4989 (14)	C33—C34	1.3778 (15)
C22—H22A	0.9800	C33—H33	0.9500
C22—H22B	0.9800	C34—C35	1.3871 (15)
C22—H22C	0.9800	C34—H34	0.9500
C23—O24	1.2170 (12)	C35—C36	1.3802 (14)
C23—O23	1.3357 (12)	C35—H35	0.9500
O23—C27	1.4342 (12)	C36—H36	0.9500
C25—O26	1.2050 (12)	N41—C42	1.3282 (17)
C25—O25	1.3544 (12)	N41—C43i	1.3311 (17)
O25—C28	1.4377 (13)	C42—C43	1.3819 (18)
C26—H26A	0.9800	C42—H42	0.9500
C26—H26B	0.9800	C43—N41i	1.3311 (17)
C26—H26C	0.9800	C43—H43	0.9500
C12—N11—C16	123.46 (8)	O23—C27—H27B	109.5
C12—N11—H11	118.4 (10)	H27A—C27—H27B	109.5
C16—N11—H11	117.8 (10)	O23—C27—H27C	109.5
C13—C12—N11	118.48 (9)	H27A—C27—H27C	109.5
C13—C12—C22	127.75 (9)	H27B—C27—H27C	109.5
N11—C12—C22	113.77 (8)	O25—C28—H28A	109.5
C12—C13—C23	124.66 (9)	O25—C28—H28B	109.5
C12—C13—C14	120.65 (8)	H28A—C28—H28B	109.5
C23—C13—C14	114.68 (8)	O25—C28—H28C	109.5
C13—C14—C15	109.88 (8)	H28A—C28—H28C	109.5
C13—C14—C31	111.23 (8)	H28B—C28—H28C	109.5
C15—C14—C31	109.79 (8)	C32—C31—C36	115.33 (9)
C13—C14—H14	108.6	C32—C31—C14	125.80 (8)
C15—C14—H14	108.6	C36—C31—C14	118.66 (8)
C31—C14—H14	108.6	C33—C32—C31	123.31 (9)
C16—C15—C25	120.41 (9)	C33—C32—N32	114.74 (9)
C16—C15—C14	119.99 (9)	C31—C32—N32	121.95 (9)
C25—C15—C14	119.60 (8)	O32—N32—O33	123.91 (9)
C15—C16—N11	119.08 (9)	O32—N32—C32	118.74 (9)
C15—C16—C26	126.89 (9)	O33—N32—C32	117.32 (9)
N11—C16—C26	114.01 (9)	C34—C33—C32	119.38 (10)
C12—C22—H22A	109.5	C34—C33—H33	120.3
C12—C22—H22B	109.5	C32—C33—H33	120.3
H22A—C22—H22B	109.5	C33—C34—C35	119.32 (10)
C12—C22—H22C	109.5	C33—C34—H34	120.3
H22A—C22—H22C	109.5	C35—C34—H34	120.3
H22B—C22—H22C	109.5	C36—C35—C34	120.14 (10)
O24—C23—O23	121.36 (9)	C36—C35—H35	119.9
O24—C23—C13	122.49 (9)	C34—C35—H35	119.9
O23—C23—C13	116.15 (8)	C35—C36—C31	122.51 (9)
C23—O23—C27	115.24 (8)	C35—C36—H36	118.7
O26—C25—O25	121.79 (9)	C31—C36—H36	118.7
O26—C25—C15	127.27 (9)	C42—N41—C43i	115.38 (11)
O25—C25—C15	110.91 (8)	C42—N41—C42ii	106.16 (7)
C25—O25—C28	115.21 (8)	C43i—N41—C42ii	137.11 (8)
C16—C26—H26A	109.5	N41—C42—C43	122.15 (11)
C16—C26—H26B	109.5	N41—C42—H42	118.9
H26A—C26—H26B	109.5	C43—C42—H42	118.9
C16—C26—H26C	109.5	N41i—C43—C42	122.46 (11)
H26A—C26—H26C	109.5	N41i—C43—H43	118.8
H26B—C26—H26C	109.5	C42—C43—H43	118.8
O23—C27—H27A	109.5
C16—N11—C12—C13	15.45 (15)	C14—C15—C25—O26	−176.60 (10)
C16—N11—C12—C22	−164.07 (9)	C16—C15—C25—O25	−175.78 (9)
N11—C12—C13—C23	−173.05 (9)	C14—C15—C25—O25	5.23 (12)
C22—C12—C13—C23	6.40 (17)	O26—C25—O25—C28	−2.79 (14)
N11—C12—C13—C14	7.81 (14)	C15—C25—O25—C28	175.50 (8)
C22—C12—C13—C14	−172.75 (9)	C13—C14—C31—C32	138.67 (9)
C12—C13—C14—C15	−27.91 (12)	C15—C14—C31—C32	−99.50 (11)
C23—C13—C14—C15	152.87 (8)	C13—C14—C31—C36	−46.76 (11)
C12—C13—C14—C31	93.88 (10)	C15—C14—C31—C36	75.07 (11)
C23—C13—C14—C31	−85.35 (10)	C36—C31—C32—C33	−0.04 (14)
C13—C14—C15—C16	28.86 (12)	C14—C31—C32—C33	174.69 (9)
C31—C14—C15—C16	−93.78 (10)	C36—C31—C32—N32	−179.46 (9)
C13—C14—C15—C25	−152.15 (8)	C14—C31—C32—N32	−4.73 (15)
C31—C14—C15—C25	85.21 (10)	C33—C32—N32—O32	130.11 (10)
C25—C15—C16—N11	171.13 (9)	C31—C32—N32—O32	−50.42 (13)
C14—C15—C16—N11	−9.89 (14)	C33—C32—N32—O33	−48.13 (12)
C25—C15—C16—C26	−7.30 (15)	C31—C32—N32—O33	131.33 (10)
C14—C15—C16—C26	171.68 (9)	C31—C32—C33—C34	0.63 (16)
C12—N11—C16—C15	−14.39 (15)	N32—C32—C33—C34	−179.91 (9)
C12—N11—C16—C26	164.24 (9)	C32—C33—C34—C35	−0.67 (16)
C12—C13—C23—O24	173.91 (11)	C33—C34—C35—C36	0.14 (17)
C14—C13—C23—O24	−6.90 (14)	C34—C35—C36—C31	0.48 (16)
C12—C13—C23—O23	−6.01 (15)	C32—C31—C36—C35	−0.51 (14)
C14—C13—C23—O23	173.19 (8)	C14—C31—C36—C35	−175.64 (9)
O24—C23—O23—C27	−0.71 (15)	C43i—N41—C42—C43	−0.10 (19)
C13—C23—O23—C27	179.21 (9)	C42ii—N41—C42—C43	−169.14 (10)
C16—C15—C25—O26	2.38 (16)	N41—C42—C43—N41i	0.1 (2)

D—H···A	D—H	H···A	D···A	D—H···A
N11—H11···O24iii	0.906 (17)	1.942 (17)	2.8444 (12)	173.6 (15)

Table 1

Selected torsion angles (°)

C12—C13—C14—C31	93.88 (10)
C31—C14—C15—C16	−93.78 (10)

Table 2

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N11—H11⋯O24i	0.906 (17)	1.942 (17)	2.8444 (12)	173.6 (15)

Symmetry code: (i) .