A supramolecular ladder motif in 2-(2,2,6,6-tetra­methyl­piperidin-1-yl­oxy)­propane-1,3-diol

An O—H...O hydrogen-bonded step-ladder motif was observed in the crystal structure of the title compound, C₁₂H₂₅NO₃. The ladder arrangement is typical of 1,2- and 1,3-diols with a synclinal orientation of the diol functionality.

S1. Comment

Hydrogen-bonding motifs play an important role in the interaction, recognition and conformation of both small and large molecules (e.g. in biologically active molecules (Watson & Crick, 1953; Zeng et al., 2000)). These motifs have frequently been used as supramolecular synthons to direct solid-state structures (crystal engineering; Steiner, 2002; Aakeröy & Seddon, 1993) and for synthesis of complex supramolecules. The predictability of such interactions (N—H···N, N—H···O, O—H···N and O—H···O bonds) depends on the robustness and reproducibility of such interactions.

Simple dialcohols are increasingly becoming important synthons for the preparation of unidirectional architectures, such as ladders, in the solid state (Nguyen et al., 2001; Schmittel et al., 2003). Depending on the arrangement of the rung region, ladders usually adopt two distinct shapes, with a clear distinction between the `staircase' or the `step ladder' types. In staircase ladders, the rung region is made up of chains of (OH)_n groups, while in step ladders, it contains discrete (OH)₄ rings.

Unfortunately, there is no general trend in the substitution pattern that would enable us to exploit hydrogen-bonding interactions for building ladder structures, except that 1,3-diols tend to form ladder-like structures more easily than 1,2-diols; furthermore, racemic, achiral or 2-substituted 1,3-propane diols form step ladders.

From a Newman projection analysis of 1,3-diols known to form ladders (Nguyen et al., 2001), it appears that the antiperiplanar conformation leads to chain structures, whereas in the synclinal conformation, ladder-like structures are preferred (Chart 1: Newman projection analysis of hydrogen bonding interactions of diols leading either to a chain or ladder like structure.)

Our long-standing interest in building highly ordered and predictable supramolecular aggregates based on metal complexation (Schmittel et al., 2002a; Schmittel et al., 2002b; Schmittel et al., 2001) and more recently on hydrogen-bonded motifs (Schmittel et al. 2003) encouraged us to synthesize the achiral 1,3-diol (II) [2-(2,2,6,6-tetramethylpiperidin-1-yloxy)propane-1,3-diol] and to investigate its structural properties.

Compound (II) was prepared in reasonable yields starting from diethylmalonate via a method involving an initial trapping of a carbon- centred radical by the 2,2,6,6-tetramethylpiperidin-1-yloxy radical (Jahn et al., 2002) followed by lithium aluminium hydride reduction of diethyl-2-(2,2,6,6-tetramethylpiperidin-1-yloxy)malonate, (I) (Chart 2).

The crystal structure shows one molecule in the asymmetric unit. The piperidinoxy ring adopts the usual chair conformation. Atom O1 is antiperiplanar with atom O2 [−178.12 (s.u.?)°], whereas it is synclinal with atom O3 [−58.52 (s.u.?) °; Fig. 1]. Intramolecular C—H···O interactions (H···O = 2.44 Å) were observed between the axial methyl groups of the piperidinoxy group (C10 and C12) and atoms O1.

Intermolecular O—H···O hydrogen-bonding interactions predominate in the extended structure of (II); the primary O atoms act as both acceptor and donor (Table 1). The net effect is to connect the molecules into a chain structure parallel to [001], with a C¹₁(6) graph set designator; two such chains are linked to form a two-dimensional hydrogen-bonding network with a supramolecular ladder-like arrangement (Fig. 2), as expected of a symmetrically substituted achiral 1,3-diol, with (OH)₄ rings in the rung region. The intrastrand O···O distance [A = 2.7494 (10) Å; Fig. 2 and Table 1] is slightly greater than the interstrand O···O distance [B = 2.7133 (10) Å; Fig. 2 and Table 1], and the same is necessarily true of the H···O distances; the interstrand hydrogen bonding is thus presumably slightly stronger. The intramolecular O···O distance (C) is about 3.6371 (10) Å (Fig. 2 and Table 1), which is in the usual range for step-ladder motifs (Nguyen et al., 2001).

S2. Experimental

For the preparation of (I), diethylmalonate (240 mg, 1.50 mmol) was added to a solution of butyllithium (780 µl, 1.95 mmol) and diisopropylamine (197 mg, 1.95 mmol) in dry dimethoxyethane (30 ml) cooled to 195 K. After 30 min, 2,2,6,6-tetramethylpiperidin-1-oxyl (328 mg, 2.10 mmol) was added. The reaction mixture was warmed slowly to 273 K and dry copper (II) chloride was added portionwise (large excess, until a green colour persisted) over a period 10 min. The reaction mixture was stirred at 273 K for 2 h, quenched with saturated ammonium chloride solution (10 ml) and extracted with ether (3 × 25 ml). The combined organic layer was washed with water (5 × 100 ml), dried over Na₂SO₄ (anhydrous) and concentrated under reduced pressure. The crude product was purified by flash column chromatography with 2% ethyl acetate in hexane as eluant, yielding a colourless low-melting solid (m.p. 301–303 K). IR (cm⁻¹, KBr): 2977, 2935, 1767, 1746, 1468, 1367, 1213, 1183, 1097, 1028, 960; ¹H NMR (200 MHz, CDCl₃): δ 1.08, 1.20 (2 s, 12H, CH₃), 1.29, (t, J = 7.1 Hz, 6H, CH₃), 1.46 (bs, 6H, CH₂), 4.20–4.27 (m, 4H, CH₂), 4.92 (s, 1H, CH); ¹³C NMR (50 MHz, CDCl₃): δ 15.1, 18.0, 21.1, 33.6, 41.1, 61.3, 62.6, 87.7, 168.3. Analysis calculated for C₁₆H₂₉NO₅: C 60.93, H 9.27, N 4.44%; found: C 61.04, H 9.38, N 4.57%. For the preparation of (II), lithium aluminium hydride (133 mg, 3.50 mmol) was added to a solution of (1) (420 mg, 1.30 mmol) in 20 ml of dry THF at 273 K. After 1 h, ethyl acetate (15 ml) was added to the reaction mixture at 273 K. After 30 min, the reaction mixture was poured into water and extracted with dichloromethane (3 × 25 ml). The combined organic layer was dried over Na₂SO₄ (anhydrous) and concentrated under reduced pressure. The crude product was purified by flash column chromatography with 50% ethyl acetate in hexane as eluant, yielding a colourless solid (m.p. 354 K). IR (cm⁻¹, KBr): 3310, 2920, 1360, 1244, 1133, 1112, 1094, 1039, 975, 959; ¹H NMR (200 MHz, CDCl₃): δ 1.15, 1.33 (2 s, 12H, CH₃), 1.52 (bs, 6H, CH₂), 3.61 (bs, 4H, CH₂ and OH), 3.83 (t, J = 7.1 Hz, 2H, CH₂), 4.38 (t, J = 7.1 Hz, 1H, CH); ¹³C NMR (50 MHz, CDCl₃): δ 18.0, 21.3, 34.5, 41.2, 61.9, 65.1, 82.0. Analysis calculated for C₁₂H₂₅NO₃: C 62.30, H 10.89, N 6.05%; found C 61.70, H 11.17, N 5.99%. Single crystals of (II) suitable for X-ray analysis were obtained upon evaporation of the solvent (hexane:ethylacetate, 50%) under reduced pressure (313 K).

S3. Refinement

C-bound H atoms were placed in idealized positions and included in the refinement as riding atoms, with U_iso(H) values of 1.2U_eq of the parent C atoms. The positions of the hydroxy H atoms were found from difference Fourier maps and refined, with U_iso(H) values fixed to 1.5U_eq of the parent O atoms.

Computing details

Data collection: EXPOSE in IPDS Software (Stoe & Cie, 1999); cell refinement: CELL and SELECT in IPDS Software; data reduction: X-RED (Stoe & Cie, 1999); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: DIAMOND (Crystal Impact, 1999); software used to prepare material for publication: enCIFer (Allen et al., 2004).

Figures

	Fig. 1. The molecular structure of (II), with 50% probability displacement ellipsoids. H atoms are shown as spheres of arbitrary size.
	Fig. 2. The hydrogen-bonded secondary structure of (II), showing a step-ladder arrangement in different presentations, viz. (a) a ball-and-stick model and (b) a schematic representation.

2-(2, 2, 6, 6-Tetramethylpiperidin-1-yloxy)propane-1,3-diol

Crystal data

C12H25NO3	F(000) = 512
Mr = 231.33	Dx = 1.162 Mg m^−3
Monoclinic, P21/n	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2yn	Cell parameters from 8000 reflections
a = 14.6525 (13) Å	θ = 2.8–30.4°
b = 14.6357 (8) Å	µ = 0.08 mm^−1
c = 6.1793 (5) Å	T = 173 K
β = 93.801 (10)°	Needles, colourless
V = 1322.23 (17) Å^3	0.2 × 0.1 × 0.08 mm
Z = 4

Data collection

Stoe IPDS diffractometer	2635 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.043
Graphite monochromator	θmax = 30.5°, θmin = 3.1°
143 exposures, Δϕ=1.4° scans	h = −20→20
15527 measured reflections	k = −20→19
3992 independent reflections	l = −8→8

Refinement

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F^2 > 2σ(F^2)] = 0.036	H atoms treated by a mixture of independent and constrained refinement
wR(F^2) = 0.093	w = 1/[σ^2(Fo^2) + (0.0619P)^2] where P = (Fo^2 + 2Fc^2)/3
S = 0.93	(Δ/σ)max < 0.001
3992 reflections	Δρmax = 0.25 e Å^−3
158 parameters	Δρmin = −0.19 e Å^−3
0 restraints	Extinction correction: SHELXL97
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.019 (2)

Special details

Experimental. M·P. 81 °C. IR cm⁻¹ (KBr): 3310, 2920, 1360, 1244, 1133, 1112, 1094, 1039, 975, 959. ¹H-NMR (200 MHz, CDCl₃): δ in p.p.m., 1.15, 1.33 (2 s, 12H, CH₃), 1.52 (bs, 6H, CH₂), 3.61 (bs, 4H, CH₂ & OH), 3.83 (t, J = 7.1 Hz, 2H, CH₂), 4.38 (t, J = 7.1 Hz, 1H, CH). ¹³C-NMR (50 MHz, CDCl₃): δ in p.p.m., 18.0, 21.3, 34.5, 41.2, 61.9, 65.1, 82.0. EA (C₁₂H₂₅NO₃): Calculated C 62.30, H 10.89, N 6.05, Found C 61.70, 11.17, 5.99.

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.

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

	x	y	z	Uiso*/Ueq
N1	0.83695 (5)	0.19447 (5)	0.09459 (13)	0.01920 (17)
O1	0.87895 (4)	0.28244 (4)	0.15085 (10)	0.01944 (15)
O2	0.93334 (5)	0.40403 (5)	−0.35090 (11)	0.02823 (18)
H2	0.9614 (10)	0.4535 (10)	−0.303 (2)	0.042*
O3	0.97076 (5)	0.44377 (5)	0.22922 (11)	0.02349 (16)
H3	0.9485 (9)	0.4193 (9)	0.340 (2)	0.035*
C1	0.73809 (6)	0.20290 (7)	0.14236 (16)	0.0225 (2)
C2	0.69463 (7)	0.10860 (7)	0.0970 (2)	0.0314 (2)
H2A	0.6300	0.1105	0.1342	0.038*
H2B	0.6953	0.0953	−0.0600	0.038*
C3	0.74314 (8)	0.03201 (8)	0.2232 (2)	0.0393 (3)
H3A	0.7143	−0.0273	0.1826	0.047*
H3B	0.7382	0.0415	0.3806	0.047*
C4	0.84318 (8)	0.03101 (7)	0.1719 (2)	0.0356 (3)
H4A	0.8472	0.0155	0.0169	0.043*
H4B	0.8753	−0.0175	0.2589	0.043*
C5	0.89214 (7)	0.12252 (7)	0.21828 (17)	0.0246 (2)
C6	0.93335 (6)	0.31733 (6)	−0.01723 (14)	0.01936 (18)
H6	0.9619	0.2649	−0.0916	0.023*
C7	0.87718 (7)	0.37361 (7)	−0.18464 (16)	0.0233 (2)
H7A	0.8262	0.3361	−0.2497	0.028*
H7B	0.8507	0.4271	−0.1133	0.028*
C8	1.00801 (6)	0.37259 (6)	0.10436 (16)	0.02108 (19)
H8A	1.0455	0.3316	0.2017	0.025*
H8B	1.0485	0.3996	−0.0008	0.025*
C9	0.69230 (7)	0.27123 (8)	−0.01684 (18)	0.0282 (2)
H9A	0.7163	0.3326	0.0152	0.034*
H9B	0.6261	0.2707	−0.0027	0.034*
H9C	0.7051	0.2542	−0.1652	0.034*
C10	0.72040 (7)	0.23651 (8)	0.37195 (17)	0.0303 (2)
H10A	0.7340	0.1872	0.4765	0.036*
H10B	0.6562	0.2546	0.3765	0.036*
H10C	0.7598	0.2891	0.4089	0.036*
C11	0.98569 (7)	0.11664 (7)	0.12177 (19)	0.0290 (2)
H11A	0.9771	0.1122	−0.0365	0.035*
H11B	1.0184	0.0624	0.1789	0.035*
H11C	1.0214	0.1715	0.1613	0.035*
C12	0.90958 (8)	0.13938 (8)	0.46359 (18)	0.0347 (3)
H12A	0.9248	0.2039	0.4890	0.042*
H12B	0.9606	0.1011	0.5203	0.042*
H12C	0.8545	0.1239	0.5375	0.042*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
N1	0.0186 (3)	0.0187 (4)	0.0204 (4)	−0.0051 (3)	0.0015 (3)	−0.0027 (3)
O1	0.0233 (3)	0.0193 (3)	0.0160 (3)	−0.0070 (2)	0.0036 (2)	−0.0028 (3)
O2	0.0402 (4)	0.0294 (4)	0.0155 (3)	−0.0138 (3)	0.0047 (3)	−0.0014 (3)
O3	0.0307 (3)	0.0229 (3)	0.0173 (3)	−0.0085 (3)	0.0049 (3)	−0.0022 (3)
C1	0.0191 (4)	0.0286 (5)	0.0200 (4)	−0.0043 (3)	0.0033 (3)	−0.0021 (4)
C2	0.0232 (5)	0.0347 (6)	0.0364 (6)	−0.0105 (4)	0.0043 (4)	−0.0040 (5)
C3	0.0344 (6)	0.0290 (5)	0.0550 (8)	−0.0130 (4)	0.0068 (5)	0.0037 (5)
C4	0.0328 (5)	0.0227 (5)	0.0514 (7)	−0.0052 (4)	0.0035 (5)	0.0028 (5)
C5	0.0241 (5)	0.0216 (4)	0.0280 (5)	−0.0023 (4)	0.0018 (4)	0.0033 (4)
C6	0.0207 (4)	0.0210 (4)	0.0169 (4)	−0.0041 (3)	0.0052 (3)	−0.0009 (4)
C7	0.0253 (4)	0.0286 (5)	0.0158 (4)	−0.0062 (4)	0.0007 (3)	0.0004 (4)
C8	0.0190 (4)	0.0239 (4)	0.0203 (4)	−0.0023 (3)	0.0013 (3)	0.0011 (4)
C9	0.0204 (4)	0.0380 (5)	0.0259 (5)	−0.0001 (4)	0.0007 (4)	−0.0001 (5)
C10	0.0277 (5)	0.0413 (6)	0.0228 (5)	−0.0026 (4)	0.0083 (4)	−0.0033 (5)
C11	0.0246 (5)	0.0243 (5)	0.0380 (6)	0.0012 (4)	0.0020 (4)	0.0003 (4)
C12	0.0353 (6)	0.0421 (6)	0.0262 (5)	0.0007 (5)	−0.0018 (4)	0.0087 (5)

Geometric parameters (Å, º)

N1—O1	1.4591 (9)	C5—C12	1.5403 (16)
N1—C1	1.5024 (12)	C6—C8	1.5187 (13)
N1—C5	1.5050 (13)	C6—C7	1.5209 (13)
O1—C6	1.4438 (10)	C6—H6	1.0000
O2—C7	1.4293 (12)	C7—H7A	0.9900
O2—H2	0.873 (15)	C7—H7B	0.9900
O3—C8	1.4263 (12)	C8—H8A	0.9900
O3—H3	0.855 (15)	C8—H8B	0.9900
C1—C9	1.5266 (14)	C9—H9A	0.9800
C1—C2	1.5380 (14)	C9—H9B	0.9800
C1—C10	1.5397 (14)	C9—H9C	0.9800
C2—C3	1.5155 (17)	C10—H10A	0.9800
C2—H2A	0.9900	C10—H10B	0.9800
C2—H2B	0.9900	C10—H10C	0.9800
C3—C4	1.5201 (16)	C11—H11A	0.9800
C3—H3A	0.9900	C11—H11B	0.9800
C3—H3B	0.9900	C11—H11C	0.9800
C4—C5	1.5374 (14)	C12—H12A	0.9800
C4—H4A	0.9900	C12—H12B	0.9800
C4—H4B	0.9900	C12—H12C	0.9800
C5—C11	1.5330 (14)
O1—N1—C1	106.12 (6)	O1—C6—H6	109.1
O1—N1—C5	107.00 (7)	C8—C6—H6	109.1
C1—N1—C5	116.76 (7)	C7—C6—H6	109.1
C6—O1—N1	112.64 (6)	O2—C7—C6	110.25 (8)
C7—O2—H2	107.2 (10)	O2—C7—H7A	109.6
C8—O3—H3	107.8 (9)	C6—C7—H7A	109.6
N1—C1—C9	108.39 (7)	O2—C7—H7B	109.6
N1—C1—C2	106.46 (8)	C6—C7—H7B	109.6
C9—C1—C2	108.14 (8)	H7A—C7—H7B	108.1
N1—C1—C10	115.51 (8)	O3—C8—C6	111.57 (7)
C9—C1—C10	106.91 (8)	O3—C8—H8A	109.3
C2—C1—C10	111.21 (8)	C6—C8—H8A	109.3
C3—C2—C1	113.30 (9)	O3—C8—H8B	109.3
C3—C2—H2A	108.9	C6—C8—H8B	109.3
C1—C2—H2A	108.9	H8A—C8—H8B	108.0
C3—C2—H2B	108.9	C1—C9—H9A	109.5
C1—C2—H2B	108.9	C1—C9—H9B	109.5
H2A—C2—H2B	107.7	H9A—C9—H9B	109.5
C2—C3—C4	109.01 (9)	C1—C9—H9C	109.5
C2—C3—H3A	109.9	H9A—C9—H9C	109.5
C4—C3—H3A	109.9	H9B—C9—H9C	109.5
C2—C3—H3B	109.9	C1—C10—H10A	109.5
C4—C3—H3B	109.9	C1—C10—H10B	109.5
H3A—C3—H3B	108.3	H10A—C10—H10B	109.5
C3—C4—C5	113.41 (9)	C1—C10—H10C	109.5
C3—C4—H4A	108.9	H10A—C10—H10C	109.5
C5—C4—H4A	108.9	H10B—C10—H10C	109.5
C3—C4—H4B	108.9	C5—C11—H11A	109.5
C5—C4—H4B	108.9	C5—C11—H11B	109.5
H4A—C4—H4B	107.7	H11A—C11—H11B	109.5
N1—C5—C11	107.81 (8)	C5—C11—H11C	109.5
N1—C5—C4	106.65 (8)	H11A—C11—H11C	109.5
C11—C5—C4	107.27 (9)	H11B—C11—H11C	109.5
N1—C5—C12	115.86 (8)	C5—C12—H12A	109.5
C11—C5—C12	107.31 (8)	C5—C12—H12B	109.5
C4—C5—C12	111.59 (9)	H12A—C12—H12B	109.5
O1—C6—C8	104.26 (7)	C5—C12—H12C	109.5
O1—C6—C7	112.41 (7)	H12A—C12—H12C	109.5
C8—C6—C7	112.81 (8)	H12B—C12—H12C	109.5
C1—N1—O1—C6	−131.78 (7)	C1—N1—C5—C11	172.01 (8)
C5—N1—O1—C6	102.87 (8)	O1—N1—C5—C4	175.73 (8)
O1—N1—C1—C9	67.31 (9)	C1—N1—C5—C4	57.08 (11)
C5—N1—C1—C9	−173.57 (8)	O1—N1—C5—C12	50.86 (10)
O1—N1—C1—C2	−176.56 (7)	C1—N1—C5—C12	−67.79 (11)
C5—N1—C1—C2	−57.44 (10)	C3—C4—C5—N1	−54.73 (12)
O1—N1—C1—C10	−52.58 (10)	C3—C4—C5—C11	−170.02 (10)
C5—N1—C1—C10	66.55 (11)	C3—C4—C5—C12	72.71 (12)
N1—C1—C2—C3	55.63 (11)	N1—O1—C6—C8	−149.61 (7)
C9—C1—C2—C3	171.93 (9)	N1—O1—C6—C7	87.88 (9)
C10—C1—C2—C3	−70.98 (11)	O1—C6—C7—O2	−178.12 (7)
C1—C2—C3—C4	−56.80 (13)	C8—C6—C7—O2	64.33 (10)
C2—C3—C4—C5	56.36 (14)	O1—C6—C8—O3	−58.52 (9)
O1—N1—C5—C11	−69.35 (9)	C7—C6—C8—O3	63.73 (10)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O2—H2···O3	0.873 (15)	3.287 (15)	3.6371 (10)	106.8 (11)
C10—H10C···O1	0.98	2.44	2.8524 (12)	105
C12—H12A···O1	0.98	2.44	2.8645 (13)	106
O2—H2···O3^i	0.873 (15)	1.844 (15)	2.7133 (10)	173.3 (14)
O3—H3···O2^ii	0.855 (15)	1.952 (15)	2.7494 (10)	154.8 (13)

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