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

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.

Key indicators

• Single-crystal X-ray study
• T = 150 K
• Mean [sigma](C-C) = 0.002 Å
• R factor = 0.044
• wR factor = 0.146
• Data-to-parameter ratio = 23.8

checkCIF/PLATON results

No syntax errors found



Alert level B
PLAT029_ALERT_3_B _diffrn_measured_fraction_theta_full Low .......       0.95

Alert level C
PLAT910_ALERT_3_C Missing # of FCF Reflections Below Th(Min) .....          6
PLAT911_ALERT_3_C Missing # FCF Refl Between THmin & STh/L=  0.600         52
PLAT912_ALERT_4_C Missing # of FCF Reflections Above STh/L=  0.600        121

Alert level G
PLAT793_ALERT_4_G The Model has Chirality at C2      (Verify) ....          R
PLAT793_ALERT_4_G The Model has Chirality at C6      (Verify) ....          S

   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
   0 ALERT type 2 Indicator that the structure model may be wrong or deficient
   3 ALERT type 3 Indicator that the structure quality may be low
   3 ALERT type 4 Improvement, methodology, query or suggestion
   0 ALERT type 5 Informative message, check

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S1. Comment

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

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

S2. Experimental

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.

S3. Refinement

The hydrogen bonded to N1 was refined freely. The hydrogen bonded to O91 was positioned as idealized OH group with C—O—H angle tetrahedral and as riding atom with U_iso(H)=1.5 times U_eq(O91). All other H Atoms were positioned geometrically and treated as riding atoms (C—H = 0.97-0.98 Å), with U_iso(H)=1.2 or 1.5 times U_eq(C).

Computing details

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

	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

Crystal data

C10H17NO5	F(000) = 496
Mr = 231.25	Dx = 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) Å^3	0.35 × 0.25 × 0.20 mm
Z = 4

Data collection

Oxford Diffraction Xcalibur diffractometer with a Sapphire CCD detector	1862 reflections with I > 2σ(I)
Radiation source: Enhance (Mo) X-ray Source	Rint = 0.045
Graphite monochromator	θmax = 31.1°, θmin = 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

Refinement on F^2	0 restraints
Least-squares matrix: full	H atoms treated by a mixture of independent and constrained refinement
R[F^2 > 2σ(F^2)] = 0.044	w = 1/[σ^2(Fo^2) + (0.0827P)^2] where P = (Fo^2 + 2Fc^2)/3
wR(F^2) = 0.146	(Δ/σ)max < 0.001
S = 0.89	Δρmax = 0.41 e Å^−3
3542 reflections	Δρmin = −0.40 e Å^−3
149 parameters

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.

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

	x	y	z	Uiso*/Ueq
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 (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
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)

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)

D—H···A	D—H	H···A	D···A	D—H···A
O91—H91···N1^i	0.82	2.07	2.883 (2)	171
N1—H1···O4^ii	0.98 (2)	2.19 (2)	3.144 (2)	165 (2)

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