4-tert-Butyl-2,6-bis­(piperidino­methyl)­phenol

The title compound, C₂₂H₃₆N₂O, contains piperidine as a major constituent. The two piperidine rings attached to the phenyl ring are in chair conformations. The structure is stabilized by van der Waals forces as well as O—H...N intramolecular hydrogen bonds.

Key indicators

• Single-crystal X-ray study
• T = 293 K
• Mean [sigma](C-C) = 0.003 Å
• R factor = 0.057
• wR factor = 0.176
• Data-to-parameter ratio = 16.7

checkCIF results

No syntax errors found

ADDSYM reports no extra symmetry

---

S1. Comment

Piperidine derivatives are found to possess pharmacological activities and generally form an essential part of the molecular structure of important drugs. For example, the piperidine ring is a feature of antihistaminic agents, oral anesthetics (McElvain, 1927) and narcotic analgesics (Lu et al., 1991). Clebopride, a 1,4-disubstituted piperidine, is used clinically to prevent post-operative vomiting, to speed up gastric emptying before anesthesia or to facilitate radiological evaluation and to correct a variety of disturbances of gastrointestinal function (Robinson, 1973). Several 2,6-disubstituted piperidines are found to be useful as tranquilizers (Bochringer & Soehne, 1961) and possess hypotensive activity. In addition, it has also a combination of stimulant and depressant effects on the central nervous system (Ganellin & Spickett, 1965), as well as bactericidal, fungicidal and herbicidal activities (Mobio et al., 1990). Many piperidine derivatives also form the skeleton of several alkaloids (Hootele et al., 1980). This compound also acts as a bridging molecule in polymetallic complexes. This property has application in the design of novel magnetic and electronic solid-state materials. Also, the complexes adopt the role of polymetallic sites in biological processes (Willet et al., 1985; Marcus & Sutin, 1985). Synthetic binuclear ligands and their complexes can serve as suitable models for the natural binuclear metal centers when they mimic some physical and chemical properties of the protein site and thereby provide an improved understanding of the biological analogue (Fenton et al., 1982). In view of this, the title compound, (I), was synthesized and characterized by X-ray diffraction analysis.

The piperidine ring system offers a wide variety of conformational flexibility such as chair, boat and twist conformation (Hofer, 1976; Potapov, 1979), though the chair or slightly distorted chair conformations has been found to be the most favoured (Mulekar & Berlin, 1989). As in the related compound 2,6-bis(N-methylenepiperidino)-4-nitrophenol (Shanmuga Sundra Raj et al., 1994), the piperidine rings B and C adopt chair conformation [in the notation of Cremer and Pople (1975): Q_T = 0.574 (2) Å, q₂ = 0.014 (2), q₃ = -0.573 (2) and ϕ₂ = -128 (9)° for ring B; Q_T = 0.561 (2) Å, q₂ = 0.027 (2), q₃ = 0.560 (2) and ϕ₂ = 28 (5)° for ring C]. The mean bond length for the phenyl ring is 1.392 Å. In the tert-butyl system, C24 is in a (-)synclinal position with respect to the C4—C5 bond. There is a an O—H···N intramolecular hydrogen bond [H21···N15 = 1.76 (2) Å, O21···N15 = 2.649 (2) Å and angle at H21 = 156 (2)°].

S2. Experimental

To a 250 ml round-bottomed flask, methylphenol (5.4 g, 0.05 mol), bromophenol (8.6 g, 0.05 mol) in ethanol (150 ml) and piperidine (8.7 g, 0.1 mol) were added. The solution was stirred as formaldehyde (3.0 g, 0.1 mol) was added slowly. The solution was refluxed for 24 h, during which time 2.5 ml formaldehyde was added at time intervals of 8 h. The ethanol was evaporated under vacuum, the resulting oil washed with sodium carbonate solution, extracted with dimethyl ether and evaporated to yield a colourless solid (m.p. 393 K). Crystals were obtained by the slow evaporation of an acetone solution of the compound.

S3. Refinement

The phenol H atom was located from a difference map and refined freely. H atoms bonded to C atoms were placed in calculated positions, refined using a riding model and given an isotropic displacement parameter equal to 1.2 times the equivalent isotropic displacement parameter of the CH and CH₂ groups, and 1.5 times of the equivalent isotropic displacement parameter of the CH₃ groups.

Computing details

Data collection: CAD-4 Software (Enraf-Nonius, 1989); cell refinement: SDP (Frenz, 1978); data reduction: CAD-4 Software; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEPIII (Burnett & Johnson, 1996); software used to prepare material for publication: PARST97 (Nardelli, 1995).

Figures

Fig. 1. The molecular structure of (I) showing displacement ellipsoids at the 30% probability level. H atoms have been omitted for clarity.

4-tert-Butyl-2,6-bis(piperidinomethyl)phenol

Crystal data

C22H36N2O	Z = 2
Mr = 344.53	F(000) = 380
Triclinic, P1	Dx = 1.070 Mg m^−3
a = 10.540 (2) Å	Cu Kα radiation, λ = 1.5418 Å
b = 12.153 (3) Å	Cell parameters from 25 reflections
c = 9.786 (2) Å	θ = 15–30°
α = 106.20 (3)°	µ = 0.50 mm^−1
β = 116.89 (3)°	T = 293 K
γ = 87.18 (4)°	Needle, colourless
V = 1069.2 (4) Å^3	0.40 × 0.20 × 0.20 mm

Data collection

Enraf-Nonius CAD-4 diffractometer	Rint = 0.017
Radiation source: fine-focus sealed tube	θmax = 69.9°, θmin = 4.7°
Graphite monochromator	h = −12→11
ω–2θ scans	k = −14→14
4237 measured reflections	l = 0→11
3904 independent reflections	3 standard reflections every 120 min
3680 reflections with I > 2σ(I)	intensity decay: <1%

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)] = 0.057	H atoms treated by a mixture of independent and constrained refinement
wR(F^2) = 0.176	w = 1/[σ^2(Fo^2) + (0.0939P)^2 + 0.2502P] where P = (Fo^2 + 2Fc^2)/3
S = 1.09	(Δ/σ)max = 0.001
3904 reflections	Δρmax = 0.27 e Å^−3
234 parameters	Δρmin = −0.18 e Å^−3
0 restraints	Extinction correction: SHELXL97, Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.022 (4)

Special details

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
C1	0.72334 (16)	−0.00083 (13)	0.45577 (18)	0.0461 (4)
C2	0.82952 (16)	−0.01431 (13)	0.60038 (18)	0.0465 (4)
C3	0.80763 (16)	−0.10284 (13)	0.65378 (18)	0.0477 (4)
H3	0.8774	−0.1111	0.7507	0.057*
C4	0.68568 (16)	−0.17951 (13)	0.56811 (18)	0.0461 (4)
C5	0.58284 (16)	−0.16262 (13)	0.42497 (18)	0.0495 (4)
H5	0.4999	−0.2125	0.3654	0.059*
C6	0.59874 (17)	−0.07498 (13)	0.36760 (18)	0.0483 (4)
C7	0.4822 (2)	−0.05780 (15)	0.2142 (2)	0.0613 (5)
H7A	0.4193	−0.0045	0.2400	0.074*
H7B	0.5255	−0.0229	0.1657	0.074*
N8	0.39737 (13)	−0.16342 (11)	0.09812 (15)	0.0485 (3)
C9	0.48005 (19)	−0.23846 (18)	0.0321 (2)	0.0646 (5)
H9A	0.5635	−0.2557	0.1185	0.078*
H9B	0.5127	−0.1989	−0.0213	0.078*
C10	0.3937 (3)	−0.34948 (19)	−0.0855 (3)	0.0799 (6)
H10A	0.3670	−0.3920	−0.0307	0.096*
H10B	0.4514	−0.3963	−0.1291	0.096*
C11	0.2602 (2)	−0.32599 (19)	−0.2207 (2)	0.0737 (6)
H11A	0.2863	−0.2937	−0.2856	0.088*
H11B	0.2008	−0.3974	−0.2884	0.088*
C12	0.1787 (2)	−0.24332 (19)	−0.1528 (2)	0.0703 (5)
H12A	0.1397	−0.2809	−0.1028	0.084*
H12B	0.0994	−0.2220	−0.2390	0.084*
C13	0.27125 (19)	−0.13614 (17)	−0.0310 (2)	0.0618 (5)
H13A	0.3015	−0.0939	−0.0835	0.074*
H13B	0.2158	−0.0872	0.0140	0.074*
C14	0.97089 (17)	0.05913 (15)	0.6921 (2)	0.0569 (4)
H14A	1.0118	0.0612	0.8038	0.068*
H14B	1.0361	0.0236	0.6513	0.068*
N15	0.95811 (13)	0.17729 (11)	0.68092 (15)	0.0484 (3)
C16	0.89039 (18)	0.24444 (16)	0.7748 (2)	0.0581 (4)
H16A	0.9490	0.2498	0.8869	0.070*
H16B	0.7981	0.2059	0.7404	0.070*
C17	0.8712 (2)	0.36361 (17)	0.7546 (3)	0.0782 (6)
H17A	0.8278	0.4072	0.8193	0.094*
H17B	0.8077	0.3585	0.6436	0.094*
C18	1.0137 (2)	0.42514 (18)	0.8046 (3)	0.0864 (7)
H18A	0.9991	0.4995	0.7839	0.104*
H18B	1.0739	0.4378	0.9184	0.104*
C19	1.0858 (2)	0.35312 (19)	0.7117 (3)	0.0784 (6)
H19A	1.0308	0.3486	0.5994	0.094*
H19B	1.1801	0.3896	0.7497	0.094*
C20	1.09879 (18)	0.23394 (16)	0.7303 (2)	0.0608 (5)
H20A	1.1412	0.1886	0.6657	0.073*
H20B	1.1613	0.2380	0.8412	0.073*
O21	0.74069 (14)	0.08386 (10)	0.39626 (14)	0.0593 (4)
H21	0.817 (3)	0.134 (2)	0.486 (3)	0.086 (7)*
C22	0.66688 (18)	−0.28185 (15)	0.6221 (2)	0.0544 (4)
C23	0.7545 (4)	−0.2597 (3)	0.8016 (3)	0.1203 (12)
H23A	0.7254	−0.1928	0.8560	0.180*
H23B	0.8539	−0.2474	0.8309	0.180*
H23C	0.7397	−0.3250	0.8314	0.180*
C24	0.5126 (2)	−0.3062 (3)	0.5805 (4)	0.1067 (10)
H24A	0.5060	−0.3609	0.6319	0.160*
H24B	0.4578	−0.3372	0.4667	0.160*
H24C	0.4760	−0.2362	0.6165	0.160*
C25	0.7177 (4)	−0.3855 (2)	0.5399 (5)	0.1194 (12)
H25A	0.7099	−0.4500	0.5750	0.179*
H25B	0.8155	−0.3691	0.5662	0.179*
H25C	0.6599	−0.4034	0.4262	0.179*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C1	0.0499 (8)	0.0419 (8)	0.0464 (8)	0.0039 (6)	0.0207 (7)	0.0149 (6)
C2	0.0424 (8)	0.0444 (8)	0.0490 (8)	0.0034 (6)	0.0176 (6)	0.0136 (6)
C3	0.0435 (8)	0.0507 (8)	0.0443 (8)	0.0062 (6)	0.0135 (6)	0.0188 (6)
C4	0.0447 (8)	0.0475 (8)	0.0466 (8)	0.0050 (6)	0.0189 (6)	0.0179 (6)
C5	0.0437 (8)	0.0481 (8)	0.0487 (8)	−0.0018 (6)	0.0132 (7)	0.0151 (7)
C6	0.0480 (8)	0.0464 (8)	0.0438 (8)	0.0034 (6)	0.0148 (7)	0.0140 (6)
C7	0.0632 (10)	0.0527 (9)	0.0507 (9)	−0.0001 (8)	0.0079 (8)	0.0204 (7)
N8	0.0433 (7)	0.0533 (7)	0.0420 (7)	0.0033 (5)	0.0124 (5)	0.0161 (6)
C9	0.0490 (9)	0.0801 (12)	0.0575 (10)	0.0105 (8)	0.0196 (8)	0.0181 (9)
C10	0.0879 (15)	0.0713 (13)	0.0655 (12)	0.0175 (11)	0.0296 (11)	0.0091 (10)
C11	0.0752 (13)	0.0779 (13)	0.0511 (10)	−0.0097 (10)	0.0207 (9)	0.0054 (9)
C12	0.0489 (9)	0.0932 (14)	0.0537 (10)	−0.0060 (9)	0.0126 (8)	0.0160 (9)
C13	0.0512 (9)	0.0722 (11)	0.0501 (9)	0.0107 (8)	0.0112 (7)	0.0220 (8)
C14	0.0428 (8)	0.0535 (9)	0.0663 (10)	0.0027 (7)	0.0165 (7)	0.0198 (8)
N15	0.0436 (7)	0.0474 (7)	0.0517 (7)	−0.0028 (5)	0.0203 (6)	0.0121 (6)
C16	0.0483 (9)	0.0649 (10)	0.0572 (9)	−0.0001 (7)	0.0242 (7)	0.0108 (8)
C17	0.0599 (11)	0.0563 (11)	0.0958 (15)	0.0037 (8)	0.0271 (10)	0.0033 (10)
C18	0.0737 (13)	0.0519 (11)	0.1082 (18)	−0.0070 (9)	0.0269 (12)	0.0092 (11)
C19	0.0746 (13)	0.0726 (13)	0.0852 (14)	−0.0203 (10)	0.0314 (11)	0.0233 (11)
C20	0.0495 (9)	0.0633 (11)	0.0681 (11)	−0.0077 (7)	0.0290 (8)	0.0107 (8)
O21	0.0642 (7)	0.0542 (7)	0.0538 (7)	−0.0056 (6)	0.0164 (6)	0.0239 (5)
C22	0.0516 (9)	0.0558 (9)	0.0590 (9)	0.0021 (7)	0.0213 (7)	0.0275 (8)
C23	0.135 (2)	0.132 (2)	0.0777 (16)	−0.043 (2)	0.0102 (16)	0.0637 (16)
C24	0.0648 (13)	0.130 (2)	0.157 (3)	0.0051 (13)	0.0445 (15)	0.098 (2)
C25	0.188 (3)	0.0670 (14)	0.175 (3)	0.0439 (17)	0.130 (3)	0.0631 (18)

Geometric parameters (Å, º)

C1—O21	1.3715 (18)	C14—H14A	0.97
C1—C6	1.392 (2)	C14—H14B	0.97
C1—C2	1.400 (2)	N15—C16	1.462 (2)
C2—C3	1.390 (2)	N15—C20	1.474 (2)
C2—C14	1.515 (2)	C16—C17	1.507 (3)
C3—C4	1.389 (2)	C16—H16A	0.97
C3—H3	0.93	C16—H16B	0.97
C4—C5	1.394 (2)	C17—C18	1.516 (3)
C4—C22	1.534 (2)	C17—H17A	0.97
C5—C6	1.383 (2)	C17—H17B	0.97
C5—H5	0.93	C18—C19	1.512 (3)
C6—C7	1.512 (2)	C18—H18A	0.97
C7—N8	1.455 (2)	C18—H18B	0.97
C7—H7A	0.97	C19—C20	1.502 (3)
C7—H7B	0.97	C19—H19A	0.97
N8—C9	1.453 (2)	C19—H19B	0.97
N8—C13	1.464 (2)	C20—H20A	0.97
C9—C10	1.510 (3)	C20—H20B	0.97
C9—H9A	0.97	O21—H21	0.95 (3)
C9—H9B	0.97	C22—C24	1.510 (3)
C10—C11	1.516 (3)	C22—C25	1.510 (3)
C10—H10A	0.97	C22—C23	1.518 (3)
C10—H10B	0.97	C23—H23A	0.96
C11—C12	1.499 (3)	C23—H23B	0.96
C11—H11A	0.97	C23—H23C	0.96
C11—H11B	0.97	C24—H24A	0.96
C12—C13	1.509 (3)	C24—H24B	0.96
C12—H12A	0.97	C24—H24C	0.96
C12—H12B	0.97	C25—H25A	0.96
C13—H13A	0.97	C25—H25B	0.96
C13—H13B	0.97	C25—H25C	0.96
C14—N15	1.465 (2)
O21—C1—C6	118.56 (14)	C2—C14—H14B	108.9
O21—C1—C2	120.97 (14)	H14A—C14—H14B	107.7
C6—C1—C2	120.47 (14)	C16—N15—C14	111.63 (14)
C3—C2—C1	118.62 (14)	C16—N15—C20	110.76 (13)
C3—C2—C14	119.70 (14)	C14—N15—C20	110.78 (14)
C1—C2—C14	121.52 (14)	N15—C16—C17	110.76 (16)
C2—C3—C4	122.59 (14)	N15—C16—H16A	109.5
C2—C3—H3	118.7	C17—C16—H16A	109.5
C4—C3—H3	118.7	N15—C16—H16B	109.5
C3—C4—C5	116.74 (14)	C17—C16—H16B	109.5
C3—C4—C22	122.24 (14)	H16A—C16—H16B	108.1
C5—C4—C22	120.95 (14)	C16—C17—C18	110.61 (17)
C6—C5—C4	122.89 (14)	C16—C17—H17A	109.5
C6—C5—H5	118.6	C18—C17—H17A	109.5
C4—C5—H5	118.6	C16—C17—H17B	109.5
C5—C6—C1	118.68 (14)	C18—C17—H17B	109.5
C5—C6—C7	120.99 (15)	H17A—C17—H17B	108.1
C1—C6—C7	120.31 (14)	C19—C18—C17	109.48 (17)
N8—C7—C6	113.98 (14)	C19—C18—H18A	109.8
N8—C7—H7A	108.8	C17—C18—H18A	109.8
C6—C7—H7A	108.8	C19—C18—H18B	109.8
N8—C7—H7B	108.8	C17—C18—H18B	109.8
C6—C7—H7B	108.8	H18A—C18—H18B	108.2
H7A—C7—H7B	107.7	C20—C19—C18	111.11 (18)
C9—N8—C7	111.54 (14)	C20—C19—H19A	109.4
C9—N8—C13	109.86 (14)	C18—C19—H19A	109.4
C7—N8—C13	109.93 (14)	C20—C19—H19B	109.4
N8—C9—C10	111.82 (16)	C18—C19—H19B	109.4
N8—C9—H9A	109.3	H19A—C19—H19B	108.0
C10—C9—H9A	109.3	N15—C20—C19	111.15 (16)
N8—C9—H9B	109.3	N15—C20—H20A	109.4
C10—C9—H9B	109.3	C19—C20—H20A	109.4
H9A—C9—H9B	107.9	N15—C20—H20B	109.4
C9—C10—C11	110.87 (18)	C19—C20—H20B	109.4
C9—C10—H10A	109.5	H20A—C20—H20B	108.0
C11—C10—H10A	109.5	C1—O21—H21	103.3 (14)
C9—C10—H10B	109.5	C24—C22—C25	110.0 (2)
C11—C10—H10B	109.5	C24—C22—C23	107.6 (2)
H10A—C10—H10B	108.1	C25—C22—C23	108.3 (2)
C12—C11—C10	109.59 (16)	C24—C22—C4	111.08 (15)
C12—C11—H11A	109.8	C25—C22—C4	108.15 (15)
C10—C11—H11A	109.8	C23—C22—C4	111.65 (16)
C12—C11—H11B	109.8	C22—C23—H23A	109.5
C10—C11—H11B	109.8	C22—C23—H23B	109.5
H11A—C11—H11B	108.2	H23A—C23—H23B	109.5
C11—C12—C13	112.08 (16)	C22—C23—H23C	109.5
C11—C12—H12A	109.2	H23A—C23—H23C	109.5
C13—C12—H12A	109.2	H23B—C23—H23C	109.5
C11—C12—H12B	109.2	C22—C24—H24A	109.5
C13—C12—H12B	109.2	C22—C24—H24B	109.5
H12A—C12—H12B	107.9	H24A—C24—H24B	109.5
N8—C13—C12	111.72 (16)	C22—C24—H24C	109.5
N8—C13—H13A	109.3	H24A—C24—H24C	109.5
C12—C13—H13A	109.3	H24B—C24—H24C	109.5
N8—C13—H13B	109.3	C22—C25—H25A	109.5
C12—C13—H13B	109.3	C22—C25—H25B	109.5
H13A—C13—H13B	107.9	H25A—C25—H25B	109.5
N15—C14—C2	113.29 (13)	C22—C25—H25C	109.5
N15—C14—H14A	108.9	H25A—C25—H25C	109.5
C2—C14—H14A	108.9	H25B—C25—H25C	109.5
N15—C14—H14B	108.9
O21—C1—C2—C3	−178.83 (14)	C9—C10—C11—C12	−53.1 (3)
C6—C1—C2—C3	−0.1 (2)	C10—C11—C12—C13	52.5 (2)
O21—C1—C2—C14	−3.6 (2)	C9—N8—C13—C12	57.9 (2)
C6—C1—C2—C14	175.14 (15)	C7—N8—C13—C12	−179.00 (16)
C1—C2—C3—C4	1.1 (2)	C11—C12—C13—N8	−55.8 (2)
C14—C2—C3—C4	−174.30 (15)	C3—C2—C14—N15	−149.72 (15)
C2—C3—C4—C5	−1.1 (2)	C1—C2—C14—N15	35.1 (2)
C2—C3—C4—C22	175.76 (14)	C2—C14—N15—C16	72.54 (18)
C3—C4—C5—C6	0.3 (2)	C2—C14—N15—C20	−163.52 (14)
C22—C4—C5—C6	−176.62 (15)	C14—N15—C16—C17	−176.98 (14)
C4—C5—C6—C1	0.5 (3)	C20—N15—C16—C17	59.07 (19)
C4—C5—C6—C7	−178.09 (16)	N15—C16—C17—C18	−58.1 (2)
O21—C1—C6—C5	178.09 (14)	C16—C17—C18—C19	55.3 (3)
C2—C1—C6—C5	−0.6 (2)	C17—C18—C19—C20	−54.7 (3)
O21—C1—C6—C7	−3.3 (2)	C16—N15—C20—C19	−58.3 (2)
C2—C1—C6—C7	178.00 (15)	C14—N15—C20—C19	177.27 (16)
C5—C6—C7—N8	−30.3 (2)	C18—C19—C20—N15	56.4 (2)
C1—C6—C7—N8	151.13 (16)	C3—C4—C22—C24	145.9 (2)
C6—C7—N8—C9	−69.1 (2)	C5—C4—C22—C24	−37.4 (3)
C6—C7—N8—C13	168.78 (15)	C3—C4—C22—C25	−93.3 (2)
C7—N8—C9—C10	178.63 (15)	C5—C4—C22—C25	83.4 (2)
C13—N8—C9—C10	−59.2 (2)	C3—C4—C22—C23	25.7 (3)
N8—C9—C10—C11	57.6 (2)	C5—C4—C22—C23	−157.5 (2)