[1-(Carboxy­meth­yl)cyclo­hexyl]­methan­aminium dihydrogen phosphate

In the title salt, C₉H₁₈NO₂⁺·H₂PO₄⁻, the cyclo­hexane ring is puckered, the total puckering amplitude Q_T being 0.555 (4) Å, and an intra­molecular N—H...O hydrogen bond generates an S(7) ring. In the crystal structure, inter­molecular N—H...O and O—H...O hydrogen bonds lead to R₂²(14), R₃³(8) and R₄²(8) rings, generating a two-dimensional layer.

Key indicators

• Single-crystal X-ray study
• T = 296 K
• Mean [sigma](C-C) = 0.005 Å
• R factor = 0.051
• wR factor = 0.155
• Data-to-parameter ratio = 17.9

checkCIF/PLATON results

No syntax errors found



Alert level B
PLAT919_ALERT_3_B Reflection(s) # Likely Affected by the Beamstop           1

Alert level C
PLAT241_ALERT_2_C Check High      Ueq as Compared to Neighbors for         C6
PLAT340_ALERT_3_C Low Bond Precision on  C-C Bonds (x 1000) Ang ..          5
PLAT912_ALERT_4_C Missing # of FCF Reflections Above STh/L=  0.600          7

Alert level G
PLAT860_ALERT_3_G Note: Number of Least-Squares Restraints .......          6
PLAT960_ALERT_3_G Number of Intensities with I .LT. - 2*sig(I) ..           1

   0 ALERT level A = In general: serious problem
   1 ALERT level B = Potentially serious problem
   3 ALERT level C = Check and explain
   2 ALERT level G = General alerts; check

   0 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   1 ALERT type 2 Indicator that the structure model may be wrong or deficient
   4 ALERT type 3 Indicator that the structure quality may be low
   1 ALERT type 4 Improvement, methodology, query or suggestion
   0 ALERT type 5 Informative message, check

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S1. Comment

The title compound is a salt of gabapentin (Ibers, 2001; Reece & Levendis, 2008) an antiepileptic drug has potential application in treatment of neuropathic pain. Herein we report the synthesis and crystal structure of title compound (I).

The molecular structure and atom-labelling scheme are shown in Fig. 1. Selected bond distances and angles are given in Table 1. The C9—O6 bond length [1.310 (4) Å] indicate significant single-bond character, whereas the C9—O5 bond length [1.213 (3) Å] is indicative of significant double-bond character. The cyclohexane ring exhibits a puckered conformation, with puckering parameters (Cremer & Pople, 1975) q₂ = 0.0246 (42) Å, q₃ = 0.5544 (42) Å, Q_T = 0.5547 (42) Å, φ = 318 (10)° and θ = 1.81 (43)°. The O—P—O angles lie in the range 106.35 (14)–115.00 (12)°. Linkages P1—O1 and P1—O2 constitute POH groups, as confirmed both by the location of H atoms in the difference Fourier maps and by bond-valence calculations (Brese & O'Keeffe, 1991).

The atom N1 in the molecule at (x, y, z) acts as a hydrogen-bond donor (Table 2) to atom O5^iv so forming a centrosymmetric R₂²(14) ring (Bernstein et al., 1995) centred at (1/2, 0, 1/2). The combination of N—H···O and O—H···O hydrogen bonds generates R₃³(8) and R₄²(8) rings parallel to the [010] direction (Fig. 2).

Related literature

For related structures and medicinal background, see: Reece & Levendis (2008); Ibers (2001). For the graph-set analysis of hydrogen-bond patterns, see: Bernstein et al. (1995). For details of ring-puckering analysis, see: Cremer & Pople (1975). For bond-valence analysis and the positioning of H atoms, see: Brese & O'Keeffe (1991).

S2. Experimental

To a 10 ml methanolic solution (0.002 M) of gabapentin was added 4 drops of phosphoric acid (85%). The mixture was heated and stirred for 30 min. Colourless prisms of (I) were obtained by slow evaporation from methanol.

S3. Refinement

All H atoms bound to C atoms were refined using a riding model, with C—H = 0.97 Å and U_iso(H) = 1.2U_eq(C) for methylene C atoms. Other H atoms bound to N and O atoms were located in difference maps and refined subject to a DFIX restraint of O—H = 0.82 (2) Å and N—H = 0.87 (2) Å.

Computing details

Data collection: APEX2 (Bruker, 2009); cell refinement: SAINT (Bruker, 2009); data reduction: SAINT (Bruker, 2009); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997); software used to prepare material for publication: WinGX (Farrugia, 1999).

Figures

	Fig. 1. A view of one molecule of (I), showing displacement ellipsoids drawn at the 30% probability level. Hydrogen bonds are indicated by dashed lines.
	Fig. 2. Part of the crystal structure of (I), showing the formation of a hydrogen-bonded sheet built from R3^3(8) and R4^2(8) rings. For the sake of clarity, H atoms not involved in the motif shown have been omitted.

[1-(Carboxymethyl)cyclohexyl]methanaminium dihydrogen phosphate

Crystal data

C9H18NO2^+·H2O4P^−	F(000) = 1152
Mr = 269.23	Dx = 1.392 Mg m^−3
Orthorhombic, Pbca	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ac 2ab	Cell parameters from 1923 reflections
a = 10.473 (5) Å	θ = 3.0–21.6°
b = 9.269 (3) Å	µ = 0.23 mm^−1
c = 26.468 (5) Å	T = 296 K
V = 2569.4 (16) Å^3	Prism, colourless
Z = 8	0.31 × 0.25 × 0.22 mm

Data collection

Bruker Kappa APEXII CCD diffractometer	1853 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.071
Graphite monochromator	θmax = 28.3°, θmin = 1.5°
φ and ω scans	h = −13→7
14659 measured reflections	k = −11→12
3185 independent reflections	l = −35→35

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)] = 0.051	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.155	H atoms treated by a mixture of independent and constrained refinement
S = 1.06	w = 1/[σ^2(Fo^2) + (0.0712P)^2] where P = (Fo^2 + 2Fc^2)/3
3185 reflections	(Δ/σ)max < 0.001
178 parameters	Δρmax = 0.34 e Å^−3
6 restraints	Δρmin = −0.45 e Å^−3

Special details

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.

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
C1	0.6575 (4)	0.1582 (5)	0.67421 (15)	0.0667 (12)
H1A	0.6569	0.2315	0.6481	0.080*
H1B	0.7457	0.1334	0.6812	0.080*
C2	0.5874 (3)	0.0253 (4)	0.65538 (12)	0.0413 (8)
H2A	0.5967	−0.0514	0.6801	0.050*
H2B	0.6266	−0.0070	0.6242	0.050*
C3	0.4441 (3)	0.0522 (3)	0.64599 (10)	0.0301 (7)
C4	0.3859 (4)	0.1206 (4)	0.69378 (12)	0.0477 (9)
H4A	0.2983	0.1474	0.6866	0.057*
H4B	0.3842	0.0485	0.7204	0.057*
C5	0.4563 (4)	0.2527 (4)	0.71319 (15)	0.0667 (12)
H5A	0.4489	0.3303	0.6888	0.080*
H5B	0.4178	0.2847	0.7446	0.080*
C6	0.5961 (5)	0.2189 (6)	0.72201 (16)	0.0874 (16)
H6A	0.6039	0.1492	0.7492	0.105*
H6B	0.6406	0.3061	0.7321	0.105*
C7	0.4205 (3)	0.1584 (3)	0.60270 (11)	0.0329 (7)
H7A	0.3293	0.1639	0.5966	0.040*
H7B	0.4487	0.2533	0.6133	0.040*
C8	0.3736 (3)	−0.0923 (3)	0.63691 (13)	0.0445 (9)
H8A	0.3624	−0.1395	0.6693	0.053*
H8B	0.2891	−0.0705	0.6239	0.053*
C9	0.4354 (3)	−0.1977 (3)	0.60166 (12)	0.0343 (7)
N1	0.4845 (2)	0.1225 (3)	0.55463 (9)	0.0296 (6)
H3	0.5685 (19)	0.141 (4)	0.5561 (14)	0.067 (12)*
H4	0.473 (4)	0.027 (2)	0.5469 (13)	0.069 (13)*
H5	0.454 (3)	0.173 (4)	0.5291 (11)	0.066 (12)*
O5	0.4571 (2)	−0.1736 (2)	0.55742 (8)	0.0417 (6)
O6	0.4610 (3)	−0.3214 (3)	0.62334 (10)	0.0537 (7)
H6	0.500 (4)	−0.373 (4)	0.6027 (13)	0.085 (15)*
O1	0.8667 (2)	0.1053 (2)	0.47674 (8)	0.0366 (5)
H1	0.929 (3)	0.066 (4)	0.4646 (16)	0.091 (16)*
O2	0.7236 (2)	−0.0726 (2)	0.51893 (10)	0.0413 (6)
H2	0.739 (5)	−0.149 (3)	0.5316 (16)	0.102 (18)*
O3	0.92807 (17)	−0.00007 (19)	0.56151 (7)	0.0279 (5)
O4	0.74292 (18)	0.17523 (19)	0.55177 (8)	0.0324 (5)
P1	0.81774 (6)	0.05253 (7)	0.52950 (3)	0.0242 (2)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C1	0.050 (2)	0.093 (3)	0.057 (2)	−0.009 (2)	−0.0153 (19)	−0.020 (2)
C2	0.0434 (18)	0.050 (2)	0.0308 (17)	0.0091 (16)	−0.0039 (14)	0.0055 (15)
C3	0.0353 (15)	0.0273 (16)	0.0277 (16)	0.0039 (13)	0.0068 (13)	−0.0017 (12)
C4	0.064 (2)	0.045 (2)	0.0339 (19)	0.0084 (18)	0.0157 (17)	−0.0015 (16)
C5	0.094 (3)	0.063 (3)	0.043 (2)	0.002 (2)	0.006 (2)	−0.0247 (19)
C6	0.101 (4)	0.106 (4)	0.055 (3)	−0.017 (3)	−0.016 (3)	−0.035 (3)
C7	0.0310 (15)	0.0361 (18)	0.0317 (16)	0.0113 (13)	0.0044 (13)	0.0009 (13)
C8	0.0446 (19)	0.0364 (19)	0.052 (2)	−0.0021 (15)	0.0225 (17)	−0.0022 (15)
C9	0.0320 (16)	0.0271 (17)	0.044 (2)	−0.0051 (13)	0.0077 (14)	−0.0016 (14)
N1	0.0291 (14)	0.0331 (16)	0.0265 (14)	0.0046 (12)	0.0017 (11)	0.0030 (12)
O5	0.0501 (14)	0.0350 (13)	0.0399 (14)	0.0027 (10)	0.0078 (11)	−0.0013 (10)
O6	0.0788 (18)	0.0353 (15)	0.0471 (15)	0.0119 (13)	0.0221 (14)	0.0026 (12)
O1	0.0325 (11)	0.0383 (12)	0.0391 (13)	0.0121 (10)	0.0096 (10)	0.0117 (10)
O2	0.0331 (11)	0.0184 (12)	0.0724 (17)	−0.0029 (9)	−0.0180 (11)	0.0081 (11)
O3	0.0233 (9)	0.0249 (10)	0.0356 (11)	0.0022 (8)	0.0001 (8)	0.0001 (9)
O4	0.0273 (10)	0.0182 (10)	0.0516 (13)	0.0048 (8)	0.0121 (9)	0.0033 (9)
P1	0.0193 (3)	0.0157 (4)	0.0377 (4)	0.0022 (3)	0.0025 (3)	0.0031 (3)

Geometric parameters (Å, º)

C1—C2	1.519 (5)	C7—N1	1.476 (4)
C1—C6	1.526 (6)	C7—H7A	0.9700
C1—H1A	0.9700	C7—H7B	0.9700
C1—H1B	0.9700	C8—C9	1.498 (4)
C2—C3	1.541 (4)	C8—H8A	0.9700
C2—H2A	0.9700	C8—H8B	0.9700
C2—H2B	0.9700	C9—O5	1.213 (3)
C3—C7	1.531 (4)	C9—O6	1.310 (4)
C3—C4	1.541 (4)	N1—H3	0.897 (18)
C3—C8	1.549 (4)	N1—H4	0.912 (18)
C4—C5	1.519 (5)	N1—H5	0.881 (18)
C4—H4A	0.9700	O6—H6	0.83 (4)
C4—H4B	0.9700	O1—P1	1.566 (2)
C5—C6	1.515 (6)	O1—H1	0.817 (19)
C5—H5A	0.9700	O2—P1	1.548 (2)
C5—H5B	0.9700	O2—H2	0.799 (19)
C6—H6A	0.9700	O3—P1	1.513 (2)
C6—H6B	0.9700	O4—P1	1.502 (2)
C2—C1—C6	111.5 (3)	C5—C6—H6B	109.5
C2—C1—H1A	109.3	C1—C6—H6B	109.5
C6—C1—H1A	109.3	H6A—C6—H6B	108.1
C2—C1—H1B	109.3	N1—C7—C3	115.2 (2)
C6—C1—H1B	109.3	N1—C7—H7A	108.5
H1A—C1—H1B	108.0	C3—C7—H7A	108.5
C1—C2—C3	113.1 (3)	N1—C7—H7B	108.5
C1—C2—H2A	109.0	C3—C7—H7B	108.5
C3—C2—H2A	109.0	H7A—C7—H7B	107.5
C1—C2—H2B	109.0	C9—C8—C3	117.0 (2)
C3—C2—H2B	109.0	C9—C8—H8A	108.0
H2A—C2—H2B	107.8	C3—C8—H8A	108.0
C7—C3—C2	112.5 (2)	C9—C8—H8B	108.0
C7—C3—C4	106.6 (2)	C3—C8—H8B	108.0
C2—C3—C4	108.6 (3)	H8A—C8—H8B	107.3
C7—C3—C8	111.3 (3)	O5—C9—O6	123.0 (3)
C2—C3—C8	110.5 (3)	O5—C9—C8	124.2 (3)
C4—C3—C8	107.1 (2)	O6—C9—C8	112.7 (3)
C5—C4—C3	114.7 (3)	C7—N1—H3	111 (2)
C5—C4—H4A	108.6	C7—N1—H4	111 (2)
C3—C4—H4A	108.6	H3—N1—H4	109 (3)
C5—C4—H4B	108.6	C7—N1—H5	112 (2)
C3—C4—H4B	108.6	H3—N1—H5	107 (3)
H4A—C4—H4B	107.6	H4—N1—H5	107 (3)
C6—C5—C4	110.7 (3)	C9—O6—H6	109 (3)
C6—C5—H5A	109.5	P1—O1—H1	118 (3)
C4—C5—H5A	109.5	P1—O2—H2	118 (3)
C6—C5—H5B	109.5	O4—P1—O3	115.00 (12)
C4—C5—H5B	109.5	O4—P1—O2	107.84 (12)
H5A—C5—H5B	108.1	O3—P1—O2	110.23 (12)
C5—C6—C1	110.8 (3)	O4—P1—O1	106.50 (11)
C5—C6—H6A	109.5	O3—P1—O1	110.49 (12)
C1—C6—H6A	109.5	O2—P1—O1	106.35 (14)
C6—C1—C2—C3	55.9 (4)	C2—C1—C6—C5	−56.5 (5)
C1—C2—C3—C7	65.8 (4)	C2—C3—C7—N1	53.0 (4)
C1—C2—C3—C4	−51.9 (4)	C4—C3—C7—N1	172.0 (3)
C1—C2—C3—C8	−169.2 (3)	C8—C3—C7—N1	−71.5 (3)
C7—C3—C4—C5	−69.4 (4)	C7—C3—C8—C9	80.2 (3)
C2—C3—C4—C5	52.0 (4)	C2—C3—C8—C9	−45.5 (4)
C8—C3—C4—C5	171.4 (3)	C4—C3—C8—C9	−163.7 (3)
C3—C4—C5—C6	−54.9 (4)	C3—C8—C9—O5	−61.3 (4)
C4—C5—C6—C1	55.2 (5)	C3—C8—C9—O6	120.4 (3)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O6—H6···O3^i	0.83 (4)	1.77 (2)	2.602 (3)	173 (4)
O1—H1···O3^ii	0.82 (2)	1.76 (2)	2.569 (3)	173 (5)
N1—H5···O1^iii	0.88 (2)	2.26 (3)	2.929 (4)	133 (3)
N1—H5···O2^iv	0.88 (2)	2.44 (3)	2.959 (3)	118 (3)
N1—H5···O5^iv	0.88 (2)	2.47 (3)	3.065 (3)	125 (3)
N1—H4···O5	0.91 (2)	1.89 (2)	2.760 (4)	158 (3)
N1—H3···O4	0.90 (2)	1.86 (2)	2.752 (3)	174 (3)

Symmetry codes: (i) −x+3/2, y−1/2, z; (ii) −x+2, −y, −z+1; (iii) x−1/2, −y+1/2, −z+1; (iv) −x+1, −y, −z+1.