tert-Butyl 1-hy­dr­oxy­piperidine-2-carboxyl­ate

The title compound, C₁₀H₁₉NO₃, is a disubstituted piperidine bearing substituents in two equatorial positions. One of the substituents is a hy­droxy group bound to nitro­gen and the second a tert-butyl ester group bound to the carbon next to the endocyclic nitro­gen. Enanti­omers of the title compound form hydrogen-bridged dimers across a center of inversion.

Related literature

For bond lengths, see: Allen et al. (1987). For structural features associated with hydroxyl­amine, see: Chung-Phillips & Jebber (1995). For details of vanadium(V)- and molybdenum(VI)-catalysed oxidations, see: Hartung & Greb (2002); Reinhardt (2006). For a related structure, see: Kliegel et al. (2002). For the synthesis of 1-hy­droxy piperidine-2-carboxyl­ic acid, see: Murahashi & Shiota (1987).

Experimental

Crystal data

• C₁₀H₁₉NO₃

• M_r = 201.26

• Monoclinic, P 2₁ /n

• a = 10.1685 (3) Å

• b = 12.1271 (2) Å

• c = 10.2083 (3) Å

• β = 110.377 (3)°

• V = 1180.06 (5) ų

• Z = 4

• Cu Kα radiation

• μ = 0.68 mm⁻¹

• T = 150 K

• 0.24 × 0.21 × 0.19 mm

Data collection

• Oxford Diffraction Gemini S Ultra diffractometer

• Absorption correction: multi-scan (CrysAlis RED; Oxford Diffraction, 2008) T_min = 0.854, T_max = 0.882

• 5815 measured reflections

• 1851 independent reflections

• 1440 reflections with I > 2σ(I)

• R_int = 0.026

Refinement

• R[F² > 2σ(F²)] = 0.049

• wR(F²) = 0.146

• S = 1.09

• 1851 reflections

• 131 parameters

• H-atom parameters constrained

• Δρ_max = 0.39 e Å⁻³

• Δρ_min = −0.23 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O3—H3⋯N1^i	0.84	2.12	2.8136 (19)	139
Symmetry code: (i) -x, -y+2, -z.

Data collection: CrysAlis CCD (Oxford Diffraction, 2008); cell refinement: CrysAlis RED (Oxford Diffraction, 2008); data reduction: CrysAlis RED; 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: SHELXL97.

Supporting information

S1. Comment

1-Hydroxypiperidine-2-carboxylate (Murahashi & Shiota, 1987) attracted our attention, because the compound was expected to bind as dianion to early transition metal ions, such as vanadium(V) or molybdenum(VI). Complexes formed from vanadium(V) or molybdenum(VI) ions are formaly d⁰-metal centers. Complexes having such an electron configuration are able to activate peroxides at low temperatures, which is of importance for modern sustainable oxidation catalysis, for example in natural product synthesis (Hartung & Greb, 2002) or bleaching (Reinhardt, 2006). Since impurities from the synthesis of 1-hydroxypiperidine-2-carboxylate were difficult to separate from standard liquid/liquid and liquid/solid partitioning processes, we chose to convert this acid into a derived O-tert-butyl ester for subsequent sublimination. Colorless crystals of the title compound that deposited from the sublimation process were investigated via X-ray diffraction, in order to obtain a deeper structural insight into the product class of N-hydroxy α-aminocarboxylic acid esters.

The central structural element of the title compound, is a disubstituted piperidine ring. The N-heterocycle bears a hydroxy substituent at nitrogen and a tert-butyl O-ester substituent at the carbon next to the endocyclic nitrogen. Both substituents are bond to equatorial sites in piperidine (Figure 1). A distorted gauche arrangement of subunits C6–N1–O3–H3 = -90.30 ° and C2–N1–O3–H3 151.18 °, in combination with a N1–O3 distance of 1.4477 (18) Å, reflect typical structural characteristics of with compounds having a nitrogen oxygen single bond, such as hydroxylamine (Chung-Phillips & Jebber, 1995) or N-hydroxypiperidinium chloride (Kliegel et al., 2002). The geometrical parameters for the tert-butyl O-ester group in terms of bond distances and angles agree with reference data reported previously (Allen et al., 1987).

In the crystal, association of the title compound, occurs predominantly via H-bonding. Enantiomers of the title compound thus form H-bridged dimers (Figure 2 and Table 1) across a center of inversion [N1ⁱ···H3–O3 = 2.12 Å, N1ⁱ···O3 = 2.8136 (19)].

Related literature

For reference on bond lengths, see: Allen et al. (1987). For structural features associated with hydroxylamine, see: Chung-Phillips & Jebber (1995). For details of vanadium(V)- and molybdenum(VI)-catalysed oxidations, see: Hartung & Greb (2002);Reinhardt (2006) . For a related structure, see: Kliegel et al. (2002). For the synthesis of 1-hydroxy piperidine-2-carboxylate, see: Murahashi & Shiota (1987). .

S2. Experimental

To a suspension of crude N-hydroxypiperidine-2-carboxylic acid (1.15 g, 8 mmol) (Murahashi & Shiota, 1987) in tert-butyl acetate (20 ml) was added at 298 K HClO₄ [0.2 ml, 70% (w/w)]. The mixture was stirred for 10 min at 298 K and treated with a second batch of HClO₄ [2 ml, 70% (w/w)]. Stirring was continued for 20 h at 298 K. pH of the reaction mixture was adjusted to 8–9 by addition of satd. aq. NaHCO₃ [150 ml, 10% (w/w)] and NaOH pellets (0.8 g, 20 mmol). The resulting mixture was extracted with EtOAc (4 x 40 ml). Combined organic washings were dried (MgSO₄) and concentrated under reduced pressure to furnish a brown oily residue that was purified by chromatography [SiO₂, pentane/EtOAc = 2:1 (v/v)]. Yield: 412 mg (25%); mp 356 K; ¹H NMR (600 MHz, CDCl₃, δ_H p.p.m.): 1.20–1.30 (m, 1H), 1.47 (s, 9H), 1.52–1.78 (m, 4H), 1.97 (d, J = 11.1 Hz, 1H), 2.52 (t, J = 9.1 Hz, 1H), 3.02 (d, J = 10.6 Hz, 1H), 3.37 (d, J = 10.2 Hz, 1H), 6.56 (br s, 1H, OH). ¹³C NMR (151 MHz, CDCl₃, δ_C p.p.m.): 23.1, 25.1, 28.0, 29.3, 57.4, 71.2, 81.2, 171.9. Anal. calcd. for C₁₅H₂₃NO₂: C, 59.68; H, 9.52; N, 6.96%; Found C, 59.96; H, 9.49; N 6.94%. Crystalls suitable for X-ray diffraction were obtained by slow sublimation of (I) at 340 K and 0.1 mbar.

S3. Refinement

All H atoms were positioned geometrically and treated as riding atoms, with C—H distances in the range 0.98–1.00Å and with U_iso(H) set at 1.2U_eq (CH₂, CH) or 1.5U_eq (CH₃ and OH) of the parent atom. A free rotating group refinement was used for CH₃ and OH H atoms.

Computing details

Data collection: CrysAlis CCD (Oxford Diffraction, 2008); cell refinement: CrysAlis RED (Oxford Diffraction, 2008); data reduction: CrysAlis RED (Oxford Diffraction, 2008); 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: SHELXL97 (Sheldrick, 2008).

Figures

	Fig. 1. Molecular structure of title compound in the solid state. Displacement ellipsoids are drawn at the 50% probability level.
	Fig. 2. H-bridged dimers of title compound in the solid state [hydrogen bonds shown as dashed lines symmetry code: (i) -x, -y + 2, -z].

tert-Butyl 1-hydroxypiperidine-2-carboxylate

Crystal data

C10H19NO3	F(000) = 440
Mr = 201.26	Dx = 1.133 Mg m^−3
Monoclinic, P21/n	Melting point: 356 K
Hall symbol: -P 2yn	Cu Kα radiation, λ = 1.54184 Å
a = 10.1685 (3) Å	Cell parameters from 2751 reflections
b = 12.1271 (2) Å	θ = 3.6–62.6°
c = 10.2083 (3) Å	µ = 0.68 mm^−1
β = 110.377 (3)°	T = 150 K
V = 1180.06 (5) Å^3	Indifferent fragment, colourless
Z = 4	0.24 × 0.21 × 0.19 mm

Data collection

Oxford Diffraction Gemini S Ultra diffractometer	1851 independent reflections
Radiation source: fine-focus sealed tube	1440 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.026
Detector resolution: 16.1399 pixels mm^-1	θmax = 62.7°, θmin = 6.4°
ω–scans	h = −11→11
Absorption correction: multi-scan (CrysAlis RED; Oxford Diffraction, 2008)	k = −13→12
Tmin = 0.854, Tmax = 0.882	l = −11→11
5815 measured reflections

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)] = 0.049	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.146	H-atom parameters constrained
S = 1.09	w = 1/[σ^2(Fo^2) + (0.1003P)^2] where P = (Fo^2 + 2Fc^2)/3
1851 reflections	(Δ/σ)max = 0.001
131 parameters	Δρmax = 0.39 e Å^−3
0 restraints	Δρmin = −0.23 e Å^−3

Special details

Experimental. CrysAlis RED, Oxford Diffraction Ltd., (Version 1.171.31.8) Empirical absorption correction using spherical harmonics,implemented in SCALE3 ABSPACK scaling algorithm.

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	0.22238 (18)	0.85238 (14)	−0.04530 (19)	0.0323 (4)
O1	0.11112 (15)	0.80571 (12)	−0.08516 (16)	0.0512 (5)
O2	0.32151 (13)	0.84628 (10)	−0.10296 (13)	0.0368 (4)
C2	0.27379 (18)	0.92188 (14)	0.08639 (18)	0.0330 (4)
H2	0.3532	0.9699	0.0850	0.040*
N1	0.15807 (15)	0.98997 (12)	0.09477 (14)	0.0313 (4)
O3	0.12723 (13)	1.06522 (10)	−0.02218 (14)	0.0401 (4)
H3	0.0425	1.0839	−0.0481	0.060*
C3	0.3223 (2)	0.84527 (16)	0.2126 (2)	0.0439 (5)
H3A	0.2449	0.7946	0.2093	0.053*
H3B	0.4019	0.8002	0.2085	0.053*
C4	0.3675 (2)	0.9091 (2)	0.3492 (2)	0.0541 (6)
H4A	0.4526	0.9528	0.3590	0.065*
H4B	0.3901	0.8572	0.4289	0.065*
C5	0.2493 (2)	0.9855 (2)	0.3503 (2)	0.0529 (6)
H5A	0.1686	0.9411	0.3532	0.063*
H5B	0.2814	1.0323	0.4351	0.063*
C6	0.2036 (2)	1.05791 (16)	0.2217 (2)	0.0427 (5)
H6A	0.1254	1.1060	0.2230	0.051*
H6B	0.2826	1.1056	0.2217	0.051*
C7	0.3043 (2)	0.77301 (16)	−0.22421 (19)	0.0386 (5)
C8	0.1799 (2)	0.8114 (2)	−0.3490 (2)	0.0554 (6)
H8A	0.1910	0.8897	−0.3664	0.083*
H8B	0.0931	0.8008	−0.3292	0.083*
H8C	0.1755	0.7683	−0.4317	0.083*
C9	0.2929 (3)	0.65452 (17)	−0.1852 (2)	0.0519 (6)
H9A	0.2054	0.6440	−0.1668	0.078*
H9B	0.3728	0.6360	−0.1012	0.078*
H9C	0.2932	0.6065	−0.2623	0.078*
C10	0.4397 (2)	0.79292 (19)	−0.2509 (2)	0.0509 (6)
H10A	0.5193	0.7704	−0.1688	0.076*
H10B	0.4481	0.8715	−0.2691	0.076*
H10C	0.4395	0.7498	−0.3322	0.076*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C1	0.0292 (9)	0.0312 (9)	0.0348 (10)	0.0023 (7)	0.0091 (8)	−0.0018 (8)
O1	0.0362 (8)	0.0574 (9)	0.0610 (10)	−0.0095 (7)	0.0185 (7)	−0.0249 (7)
O2	0.0354 (7)	0.0415 (7)	0.0341 (7)	−0.0039 (5)	0.0131 (6)	−0.0072 (5)
C2	0.0282 (9)	0.0354 (9)	0.0346 (10)	0.0003 (7)	0.0099 (7)	−0.0031 (8)
N1	0.0323 (8)	0.0312 (8)	0.0297 (8)	0.0030 (6)	0.0100 (6)	0.0012 (6)
O3	0.0359 (7)	0.0372 (7)	0.0476 (8)	0.0030 (5)	0.0151 (6)	0.0163 (6)
C3	0.0411 (11)	0.0414 (10)	0.0452 (12)	0.0090 (8)	0.0097 (9)	0.0070 (9)
C4	0.0517 (12)	0.0692 (13)	0.0336 (11)	0.0100 (11)	0.0052 (9)	0.0044 (10)
C5	0.0500 (12)	0.0755 (14)	0.0312 (11)	0.0035 (11)	0.0117 (9)	−0.0094 (10)
C6	0.0361 (10)	0.0424 (11)	0.0490 (12)	−0.0018 (8)	0.0144 (9)	−0.0150 (9)
C7	0.0433 (11)	0.0444 (10)	0.0280 (9)	−0.0017 (8)	0.0120 (8)	−0.0086 (8)
C8	0.0564 (14)	0.0666 (14)	0.0355 (11)	−0.0055 (11)	0.0063 (10)	−0.0027 (10)
C9	0.0704 (15)	0.0476 (12)	0.0461 (12)	−0.0023 (10)	0.0307 (11)	−0.0073 (10)
C10	0.0546 (13)	0.0609 (13)	0.0411 (11)	−0.0055 (10)	0.0217 (10)	−0.0095 (10)

Geometric parameters (Å, º)

C1—O1	1.202 (2)	C5—H5A	0.9900
C1—O2	1.335 (2)	C5—H5B	0.9900
C1—C2	1.517 (2)	C6—H6A	0.9900
O2—C7	1.484 (2)	C6—H6B	0.9900
C2—N1	1.464 (2)	C7—C9	1.506 (3)
C2—C3	1.524 (3)	C7—C10	1.514 (3)
C2—H2	1.0000	C7—C8	1.522 (3)
N1—O3	1.4477 (18)	C8—H8A	0.9800
N1—C6	1.468 (2)	C8—H8B	0.9800
O3—H3	0.8400	C8—H8C	0.9800
C3—C4	1.520 (3)	C9—H9A	0.9800
C3—H3A	0.9900	C9—H9B	0.9800
C3—H3B	0.9900	C9—H9C	0.9800
C4—C5	1.521 (3)	C10—H10A	0.9800
C4—H4A	0.9900	C10—H10B	0.9800
C4—H4B	0.9900	C10—H10C	0.9800
C5—C6	1.512 (3)
O1—C1—O2	126.22 (16)	H5A—C5—H5B	108.1
O1—C1—C2	123.69 (16)	N1—C6—C5	110.36 (16)
O2—C1—C2	109.97 (14)	N1—C6—H6A	109.6
C1—O2—C7	120.89 (13)	C5—C6—H6A	109.6
N1—C2—C1	109.21 (13)	N1—C6—H6B	109.6
N1—C2—C3	108.94 (15)	C5—C6—H6B	109.6
C1—C2—C3	108.69 (15)	H6A—C6—H6B	108.1
N1—C2—H2	110.0	O2—C7—C9	110.40 (15)
C1—C2—H2	110.0	O2—C7—C10	101.79 (14)
C3—C2—H2	110.0	C9—C7—C10	110.98 (17)
O3—N1—C2	104.77 (12)	O2—C7—C8	109.72 (16)
O3—N1—C6	106.58 (13)	C9—C7—C8	113.25 (18)
C2—N1—C6	110.82 (13)	C10—C7—C8	110.10 (17)
N1—O3—H3	109.5	C7—C8—H8A	109.5
C4—C3—C2	111.74 (16)	C7—C8—H8B	109.5
C4—C3—H3A	109.3	H8A—C8—H8B	109.5
C2—C3—H3A	109.3	C7—C8—H8C	109.5
C4—C3—H3B	109.3	H8A—C8—H8C	109.5
C2—C3—H3B	109.3	H8B—C8—H8C	109.5
H3A—C3—H3B	107.9	C7—C9—H9A	109.5
C3—C4—C5	109.27 (17)	C7—C9—H9B	109.5
C3—C4—H4A	109.8	H9A—C9—H9B	109.5
C5—C4—H4A	109.8	C7—C9—H9C	109.5
C3—C4—H4B	109.8	H9A—C9—H9C	109.5
C5—C4—H4B	109.8	H9B—C9—H9C	109.5
H4A—C4—H4B	108.3	C7—C10—H10A	109.5
C6—C5—C4	110.60 (17)	C7—C10—H10B	109.5
C6—C5—H5A	109.5	H10A—C10—H10B	109.5
C4—C5—H5A	109.5	C7—C10—H10C	109.5
C6—C5—H5B	109.5	H10A—C10—H10C	109.5
C4—C5—H5B	109.5	H10B—C10—H10C	109.5
O1—C1—O2—C7	−3.0 (3)	C1—C2—C3—C4	−176.65 (16)
C2—C1—O2—C7	173.14 (14)	C2—C3—C4—C5	54.3 (2)
O1—C1—C2—N1	−42.6 (2)	C3—C4—C5—C6	−53.9 (3)
O2—C1—C2—N1	141.07 (14)	O3—N1—C6—C5	−175.52 (14)
O1—C1—C2—C3	76.1 (2)	C2—N1—C6—C5	−62.1 (2)
O2—C1—C2—C3	−100.19 (17)	C4—C5—C6—N1	58.1 (2)
C1—C2—N1—O3	−65.86 (16)	C1—O2—C7—C9	−61.7 (2)
C3—C2—N1—O3	175.55 (13)	C1—O2—C7—C10	−179.57 (16)
C1—C2—N1—C6	179.56 (14)	C1—O2—C7—C8	63.8 (2)
C3—C2—N1—C6	60.98 (19)	C2—N1—O3—H3	152.19
N1—C2—C3—C4	−57.7 (2)	C6—N1—O3—H3	−90.30

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O3—H3···N1^i	0.84	2.12	2.8136 (19)	139

Symmetry code: (i) −x, −y+2, −z.