Dimethyl cis-4-hydroxy­methyl­piperidine-2,6-dicarboxyl­ate

Hartung, J.; Stapf, G.; Bergsträsser, U.

doi:10.1107/S1600536810010925

organic compounds

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Volume 66| Part 5| May 2010| Page o1013

https://doi.org/10.1107/S1600536810010925

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Dimethyl cis-4-hydroxymethylpiperidine-2,6-dicarboxylate

Jens Hartung,^a ^* Georg Stapf ^a and Uwe Bergsträsser ^a

^aFachbereich Chemie, Organische Chemie, Technische Universität Kaiserslautern, Erwin-Schrödinger-Strasse, D-67663 Kaiserslautern, Germany
^*Correspondence e-mail: hartung@chemie.uni-kl.de

(Received 13 January 2010; accepted 23 March 2010; online 2 April 2010)

The heterocyclic core of the title compound, C₁₀H₁₇NO₅, adopts a chair conformation with its three C substituents positioned equatorially. In the crystal, intermolecular O—H⋯N hydrogen bonds between neighbouring molecules lead to chains along b. These chains are connected by hydrophobic interactions, forming infinite layers and N—H⋯O=C contacts between molecules of adjacent layers give rise to a three-dimensional structure.

Related literature

For structures of related N-heterocyclic compounds, see: Parkin et al. (2004 ). For the synthetic procedure, see: Tang et al. (2006 ).

Experimental

Crystal data

C₁₀H₁₇NO₅
M_r = 231.25
Monoclinic, P 2₁ /c
a = 9.1403 (4) Å
b = 7.9153 (3) Å
c = 16.0199 (6) Å
β = 90.503 (4)°
V = 1158.97 (8) Å³
Z = 4
Mo Kα radiation
μ = 0.11 mm⁻¹
T = 150 K
0.35 × 0.25 × 0.20 mm

Data collection

Oxford Diffraction Xcalibur diffractometer with a Sapphire CCD detector
9123 measured reflections
3542 independent reflections
1862 reflections with I > 2σ(I)
R_int = 0.045

Refinement

R[F² > 2σ(F²)] = 0.044
wR(F²) = 0.146
S = 0.89
3542 reflections
149 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.41 e Å⁻³
Δρ_min = −0.40 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O91—H91⋯N1ⁱ	0.82	2.07	2.883 (2)	171
N1—H1⋯O4ⁱⁱ	0.98 (2)	2.19 (2)	3.144 (2)	165 (2)
Symmetry codes: (i) x, y+1, z; (ii) -x+2, -y, -z.

Data collection: CrysAlis CCD (Oxford Diffraction, 2007 $[Oxford Diffraction (2007). CrysAlis CCD and CrysAlis RED. Oxford Diffraction Ltd, Abingdon, England.]$ ); cell refinement: CrysAlis CCD; data reduction: CrysAlis RED (Oxford Diffraction, 2007 $[Oxford Diffraction (2007). CrysAlis CCD and CrysAlis RED. Oxford Diffraction Ltd, Abingdon, England.]$ ); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 (Farrugia, 1997 ); software used to prepare material for publication: WinGX (Farrugia, 1999 ).

Supporting information

Crystal structure: contains datablocks global, I. DOI: https://doi.org/10.1107/S1600536810010925/im2176sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S1600536810010925/im2176Isup2.hkl

checkCIF report

Comment top

The all-cis-isomer of 4-(hydroxymethyl)-piperidine-2,6-dicarboxylic acid dimethyl ester, (I), represents a potential tridentate ONO-donor ligand for development of a new generation of solid phase-bound oxidation catalysts. Its three C substituents were equatorially attached to piperidine adopting a ¹C₄-chair conformation (Figure 1). A quartett structure (J = 12.4 Hz) in the nuclear magnetic resonance (NMR) spectrum for axially connected protons to C3 and C5 provided evidence that this arrangement corresponded to the most significantly populated conformer of (I) in solution (CDCl₃, 298 K). The amino H-atom was found in axial position. The arrangement that is thermodynamically favored, i.e. equatorial NH positioning, was reported for the crystal structure of piperidine and its structurally closely related derivatives morpholine and piperazine (Parkin et al., 2004).

Intermolecular O–H···N bridges between proximate molecules lead to chains along b. The chains are additionally connected by hydrophobic interactions to form layers. N–H···O═C contacts between molecules of adjascent layers give rise to a three dimensional structure (Figure 2).

Related literature top

For structures of related N-heterocyclic compounds, see: Parkin et al. (2004). For the synthetic procedure, see: Tang et al. (2006).

Experimental top

Pd/C [200 mg, 10 % (w/w)] was added to a solution of dimethyl 4-(hydroxymethyl)-pyridine-2,5-dicarboxylate (400 mg, 1.78 mmol; Tang et al., 2006) in AcOEt (100 ml). The mixture was transferred into a hydrogenating apparatus and stirred at a pressure of 3.5 bar for 14 h at 298 K in an atmosphere of H₂. The hydrogen pressure constantly decrased until a constant value of 2.4 bar was reached when the reaction stopped. The reaction mixture was filtrated through a short pad of celite. The filtrate was concentrated under reduced pressure. The remaining oil was covered with a layer of AcOEt (5 ml) and allowed to rest for 1 h at 277 K. Colorless crystals that deposited were collected by filtration. Yield: 139 mg (34 %); mp 372 K. ¹H NMR (400 MHz, CDCl₃, δ_H p.p.m.): 1.15 (q, J = 12.4 Hz, 2H), 1.78 (m, 1H), 2.13 (d, J = 12.4 Hz, 2H), 3.43 (dd, J = 11.7 Hz, 2.5 Hz, 2H), 3.55 (d, J = 6.3 Hz, 2H), 3.74 (s, 6H). ¹³C NMR (101 MHz, CDCl₃ δ_C p.p.m.): 31.7, 38.7, 52.1, 57.9, 67.4, 172.7. Analytical data calculated for all-cis-4-(hydroxymethyl)-piperidine-2,6-dicarboxylic acid dimethyl ester: C, 51.94; H, 7.41; N, 6.06; found: C, 52.34; H, 7.46; N, 6.02.

Structure description top

For structures of related N-heterocyclic compounds, see: Parkin et al. (2004). For the synthetic procedure, see: Tang et al. (2006).

Computing details top

Data collection: CrysAlis CCD (Oxford Diffraction, 2007); cell refinement: CrysAlis CCD (Oxford Diffraction, 2007); data reduction: CrysAlis CCD (Oxford Diffraction, 2007); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 (Version 1.08; Farrugia, 1997); software used to prepare material for publication: WinGX (Farrugia, 1999).

Figures top

	Fig. 1. View of (I) (50% probability displacement ellipsoids)
	Fig. 2. Three dimensional structure of (I) in the solid state with intermolecular O–H···N bridges and N–H···O═C contacts (50% probability displacement ellipsoids for all non H-atoms).

Dimethyl cis-4-hydroxymethylpiperidine-2,6-dicarboxylate top

Crystal data top

C₁₀H₁₇NO₅	F(000) = 496
M_r = 231.25	D_x = 1.325 Mg m⁻³
Monoclinic, P2₁/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 2439 reflections
a = 9.1403 (4) Å	θ = 3.6–31.2°
b = 7.9153 (3) Å	µ = 0.11 mm⁻¹
c = 16.0199 (6) Å	T = 150 K
β = 90.503 (4)°	Prism, colourless
V = 1158.97 (8) Å³	0.35 × 0.25 × 0.20 mm
Z = 4

Data collection top

Oxford Diffraction Xcalibur diffractometer with a Sapphire CCD detector	1862 reflections with I > 2σ(I)
Radiation source: Enhance (Mo) X-ray Source	R_int = 0.045
Graphite monochromator	θ_max = 31.1°, θ_min = 3.6°
Detector resolution: 16.1399 pixels mm^-1	h = −13→13
Rotation method data acquisition using ω and phi scans	k = −11→11
9123 measured reflections	l = −23→23
3542 independent reflections

Refinement top

Refinement on F²	0 restraints
Least-squares matrix: full	H atoms treated by a mixture of independent and constrained refinement
R[F² > 2σ(F²)] = 0.044	w = 1/[σ²(F_o²) + (0.0827P)²] where P = (F_o² + 2F_c²)/3
wR(F²) = 0.146	(Δ/σ)_max < 0.001
S = 0.89	Δρ_max = 0.41 e Å⁻³
3542 reflections	Δρ_min = −0.40 e Å⁻³
149 parameters

Crystal data top

C₁₀H₁₇NO₅	V = 1158.97 (8) Å³
M_r = 231.25	Z = 4
Monoclinic, P2₁/c	Mo Kα radiation
a = 9.1403 (4) Å	µ = 0.11 mm⁻¹
b = 7.9153 (3) Å	T = 150 K
c = 16.0199 (6) Å	0.35 × 0.25 × 0.20 mm
β = 90.503 (4)°

Data collection top

Oxford Diffraction Xcalibur diffractometer with a Sapphire CCD detector	1862 reflections with I > 2σ(I)
9123 measured reflections	R_int = 0.045
3542 independent reflections

Refinement top

R[F² > 2σ(F²)] = 0.044	0 restraints
wR(F²) = 0.146	H atoms treated by a mixture of independent and constrained refinement
S = 0.89	Δρ_max = 0.41 e Å⁻³
3542 reflections	Δρ_min = −0.40 e Å⁻³
149 parameters

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
N1	0.74419 (16)	0.02707 (16)	0.01230 (8)	0.0237 (3)
C2	0.64855 (17)	0.13614 (18)	0.06151 (9)	0.0220 (3)
H2	0.5507	0.133	0.0361	0.026*
O4	0.94904 (13)	−0.11150 (15)	−0.09219 (7)	0.0312 (3)
C8	0.85668 (18)	−0.01946 (19)	−0.12238 (10)	0.0249 (3)
C7	0.63717 (18)	0.0686 (2)	0.14932 (9)	0.0255 (3)
O1	0.51869 (14)	0.13296 (16)	0.18655 (7)	0.0320 (3)
C5	0.80958 (17)	0.27664 (19)	−0.07663 (10)	0.0241 (3)
H5A	0.9091	0.2831	−0.0554	0.029*
H5B	0.8093	0.3154	−0.1341	0.029*
C4	0.71060 (17)	0.39036 (18)	−0.02456 (9)	0.0223 (3)
H4	0.6126	0.3887	−0.0498	0.027*
O91	0.67225 (15)	0.67327 (15)	0.02363 (8)	0.0405 (3)
H91	0.7015	0.7712	0.0231	0.061*
O3	0.72305 (16)	−0.02473 (18)	0.18282 (8)	0.0434 (4)
C6	0.75608 (17)	0.09224 (19)	−0.07327 (9)	0.0226 (3)
H6	0.6588	0.0873	−0.0994	0.027*
C3	0.69913 (18)	0.32103 (19)	0.06401 (9)	0.0244 (3)
H3A	0.6298	0.388	0.0954	0.029*
H3B	0.7936	0.3284	0.0918	0.029*
O2	0.83440 (15)	−0.00053 (17)	−0.20437 (7)	0.0370 (3)
C9	0.7656 (2)	0.5714 (2)	−0.02568 (11)	0.0312 (4)
H9A	0.8647	0.576	−0.0036	0.037*
H9B	0.7667	0.6132	−0.0826	0.037*
C10	0.4996 (2)	0.0889 (3)	0.27333 (10)	0.0396 (5)
H10A	0.4118	0.1406	0.2937	0.059*
H10B	0.582	0.1285	0.3053	0.059*
H10C	0.4921	−0.0316	0.2786	0.059*
C11	0.9277 (2)	−0.1006 (3)	−0.25831 (11)	0.0452 (5)
H11A	0.903	−0.0782	−0.3156	0.068*
H11B	0.9136	−0.2184	−0.2467	0.068*
H11C	1.0282	−0.0712	−0.2482	0.068*
H1	0.844 (2)	0.032 (2)	0.0344 (10)	0.029 (5)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
N1	0.0317 (7)	0.0181 (6)	0.0214 (6)	−0.0003 (5)	0.0046 (5)	0.0005 (5)
C2	0.0248 (7)	0.0212 (7)	0.0200 (7)	0.0011 (6)	0.0032 (5)	0.0000 (6)
O4	0.0339 (7)	0.0266 (6)	0.0333 (6)	0.0032 (5)	0.0035 (5)	−0.0026 (5)
C8	0.0287 (8)	0.0208 (7)	0.0251 (7)	−0.0036 (6)	0.0040 (6)	−0.0041 (6)
C7	0.0321 (8)	0.0213 (7)	0.0232 (7)	−0.0057 (7)	0.0031 (6)	0.0016 (6)
O1	0.0380 (7)	0.0373 (7)	0.0207 (5)	−0.0014 (5)	0.0079 (5)	0.0013 (5)
C5	0.0274 (8)	0.0190 (7)	0.0259 (7)	−0.0013 (6)	0.0064 (6)	0.0014 (6)
C4	0.0253 (7)	0.0184 (7)	0.0231 (7)	−0.0027 (6)	0.0043 (6)	0.0002 (6)
O91	0.0442 (8)	0.0196 (5)	0.0581 (8)	0.0000 (5)	0.0194 (6)	−0.0033 (6)
O3	0.0477 (8)	0.0485 (8)	0.0339 (7)	0.0122 (7)	0.0056 (6)	0.0150 (6)
C6	0.0251 (7)	0.0217 (7)	0.0212 (7)	−0.0027 (6)	0.0033 (5)	−0.0021 (6)
C3	0.0313 (9)	0.0189 (7)	0.0230 (7)	−0.0006 (6)	0.0033 (6)	−0.0009 (6)
O2	0.0438 (7)	0.0435 (7)	0.0237 (6)	0.0123 (6)	0.0059 (5)	−0.0065 (5)
C9	0.0373 (9)	0.0213 (7)	0.0352 (9)	−0.0015 (7)	0.0100 (7)	0.0010 (7)
C10	0.0503 (11)	0.0494 (11)	0.0193 (7)	−0.0053 (9)	0.0072 (7)	0.0037 (8)
C11	0.0501 (12)	0.0546 (12)	0.0312 (9)	0.0183 (10)	0.0096 (8)	−0.0111 (9)

Geometric parameters (Å, º) top

N1—C2	1.4640 (19)	C4—C3	1.526 (2)
N1—C6	1.4696 (19)	C4—H4	0.98
N1—H1	0.98 (2)	O91—C9	1.420 (2)
C2—C7	1.509 (2)	O91—H91	0.82
C2—C3	1.535 (2)	C6—H6	0.98
C2—H2	0.98	C3—H3A	0.97
O4—C8	1.212 (2)	C3—H3B	0.97
C8—O2	1.3358 (19)	O2—C11	1.454 (2)
C8—C6	1.503 (2)	C9—H9A	0.97
C7—O3	1.201 (2)	C9—H9B	0.97
C7—O1	1.341 (2)	C10—H10A	0.96
O1—C10	1.4452 (18)	C10—H10B	0.96
C5—C4	1.529 (2)	C10—H10C	0.96
C5—C6	1.540 (2)	C11—H11A	0.96
C5—H5A	0.97	C11—H11B	0.96
C5—H5B	0.97	C11—H11C	0.96
C4—C9	1.519 (2)

C2—N1—C6	110.16 (12)	N1—C6—C5	113.04 (12)
C2—N1—H1	110.1 (10)	C8—C6—C5	110.08 (12)
C6—N1—H1	104.3 (10)	N1—C6—H6	108.1
N1—C2—C7	109.83 (12)	C8—C6—H6	108.1
N1—C2—C3	113.27 (12)	C5—C6—H6	108.1
C7—C2—C3	109.67 (12)	C4—C3—C2	109.98 (12)
N1—C2—H2	108	C4—C3—H3A	109.7
C7—C2—H2	108	C2—C3—H3A	109.7
C3—C2—H2	108	C4—C3—H3B	109.7
O4—C8—O2	124.00 (14)	C2—C3—H3B	109.7
O4—C8—C6	124.87 (14)	H3A—C3—H3B	108.2
O2—C8—C6	111.10 (14)	C8—O2—C11	115.98 (14)
O3—C7—O1	124.19 (14)	O91—C9—C4	109.19 (13)
O3—C7—C2	125.75 (15)	O91—C9—H9A	109.8
O1—C7—C2	110.01 (13)	C4—C9—H9A	109.8
C7—O1—C10	116.17 (14)	O91—C9—H9B	109.8
C4—C5—C6	110.44 (12)	C4—C9—H9B	109.8
C4—C5—H5A	109.6	H9A—C9—H9B	108.3
C6—C5—H5A	109.6	O1—C10—H10A	109.5
C4—C5—H5B	109.6	O1—C10—H10B	109.5
C6—C5—H5B	109.6	H10A—C10—H10B	109.5
H5A—C5—H5B	108.1	O1—C10—H10C	109.5
C9—C4—C3	112.07 (13)	H10A—C10—H10C	109.5
C9—C4—C5	110.57 (13)	H10B—C10—H10C	109.5
C3—C4—C5	109.96 (13)	O2—C11—H11A	109.5
C9—C4—H4	108	O2—C11—H11B	109.5
C3—C4—H4	108	H11A—C11—H11B	109.5
C5—C4—H4	108	O2—C11—H11C	109.5
C9—O91—H91	109.5	H11A—C11—H11C	109.5
N1—C6—C8	109.41 (13)	H11B—C11—H11C	109.5

C6—N1—C2—C7	−179.88 (13)	O2—C8—C6—N1	159.66 (13)
C6—N1—C2—C3	−56.88 (17)	O4—C8—C6—C5	102.51 (18)
N1—C2—C7—O3	21.3 (2)	O2—C8—C6—C5	−75.56 (17)
C3—C2—C7—O3	−103.81 (18)	C4—C5—C6—N1	−55.54 (18)
N1—C2—C7—O1	−160.97 (13)	C4—C5—C6—C8	−178.22 (13)
C3—C2—C7—O1	73.94 (16)	C9—C4—C3—C2	−177.93 (13)
O3—C7—O1—C10	2.2 (2)	C5—C4—C3—C2	−54.53 (17)
C2—C7—O1—C10	−175.62 (14)	N1—C2—C3—C4	57.03 (17)
C6—C5—C4—C9	178.34 (13)	C7—C2—C3—C4	−179.89 (13)
C6—C5—C4—C3	54.06 (17)	O4—C8—O2—C11	0.9 (2)
C2—N1—C6—C8	179.01 (13)	C6—C8—O2—C11	178.96 (15)
C2—N1—C6—C5	55.96 (17)	C3—C4—C9—O91	−56.50 (19)
O4—C8—C6—N1	−22.3 (2)	C5—C4—C9—O91	−179.57 (13)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O91—H91···N1ⁱ	0.82	2.07	2.883 (2)	171
N1—H1···O4ⁱⁱ	0.98 (2)	2.19 (2)	3.144 (2)	165 (2)

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

Experimental details

Crystal data
Chemical formula	C₁₀H₁₇NO₅
M_r	231.25
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	150
a, b, c (Å)	9.1403 (4), 7.9153 (3), 16.0199 (6)
β (°)	90.503 (4)
V (Å³)	1158.97 (8)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.11
Crystal size (mm)	0.35 × 0.25 × 0.20

Data collection
Diffractometer	Oxford Diffraction Xcalibur diffractometer with a Sapphire CCD detector
Absorption correction	–
No. of measured, independent and observed [I > 2σ(I)] reflections	9123, 3542, 1862
R_int	0.045
(sin θ/λ)_max (Å⁻¹)	0.726

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.044, 0.146, 0.89
No. of reflections	3542
No. of parameters	149
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.41, −0.40

Computer programs: CrysAlis CCD (Oxford Diffraction, 2007), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), ORTEP-3 (Version 1.08; Farrugia, 1997), WinGX (Farrugia, 1999).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O91—H91···N1ⁱ	0.82	2.07	2.883 (2)	170.9
N1—H1···O4ⁱⁱ	0.98 (2)	2.19 (2)	3.144 (2)	165 (2)

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

Acknowledgements

This work was supported by the Deutsche Forschungsgemeinschaft (grant Ha1705/8-2).

References

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