1-(tert-But­oxy­carbon­yl)piperidine-4-carb­oxy­lic acid

Fun, H.-K.; Arshad, S.; Dinesh; Vivek, S.; Nagaraja, G.K.

doi:10.1107/S1600536811030145

organic compounds

CRYSTALLOGRAPHIC
COMMUNICATIONS

ISSN: 2056-9890

Volume 67| Part 9| September 2011| Page o2215

doi:10.1107/S1600536811030145

Open

access

1-(tert-Butoxycarbonyl)piperidine-4-carboxylic acid

Hoong-Kun Fun,^a ^*‡ Suhana Arshad,^a Dinesh,^b S. Vivek ^b and G. K. Nagaraja ^b

^aX-ray Crystallography Unit, School of Physics, Universiti Sains Malaysia, 11800 USM, Penang, Malaysia, and ^bDepartment of Chemistry, Mangalore University, Karnataka, India
^*Correspondence e-mail: hkfun@usm.my

(Received 18 July 2011; accepted 26 July 2011; online 2 August 2011)

In the title compound, C₁₁H₁₉NO₄, the piperidine ring adopts a chair conformation. In the crystal, molecules are linked by intermolecular O—H⋯O and C—H⋯O hydrogen bonds, forming a layer parallel to the bc plane.

Related literature

For general background and application of helical peptides, see: Albrecht & Stortz (2005 ); Garner & Harding (2007 ); Wang et al. (2008 ); Walensky et al. (2004 ); Boal et al. (2007 ). For bond-length data, see: Allen et al. (1987 ). For ring conformations, see: Cremer & Pople (1975 ). For stability of the temperature controller used for data collection, see: Cosier & Glazer (1986 ).

Experimental

Crystal data

C₁₁H₁₉NO₄
M_r = 229.27
Monoclinic, P 2₁ /c
a = 10.7006 (3) Å
b = 6.5567 (2) Å
c = 17.9297 (6) Å
β = 104.564 (2)°
V = 1217.54 (6) Å³
Z = 4
Mo Kα radiation
μ = 0.10 mm⁻¹
T = 100 K
0.57 × 0.21 × 0.08 mm

Data collection

Bruker SMART APEXII CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2009 ) T_min = 0.948, T_max = 0.993
5360 measured reflections
2116 independent reflections
1762 reflections with I > 2σ(I)
R_int = 0.027

Refinement

R[F² > 2σ(F²)] = 0.039
wR(F²) = 0.092
S = 1.07
2116 reflections
152 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.18 e Å⁻³
Δρ_min = −0.22 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O4—H1O4⋯O1ⁱ	0.86 (2)	1.82 (2)	2.6562 (16)	164 (2)
C5—H5B⋯O4ⁱⁱ	0.99	2.56	3.476 (2)	154
Symmetry codes: (i) $[x, -y-{\script{1\over 2}}, z+{\script{1\over 2}}]$ ; (ii) -x+1, -y, -z+1.

Data collection: APEX2 (Bruker, 2009); cell refinement: SAINT (Bruker, 2009); data reduction: SAINT; program(s) used to solve structure: SHELXTL (Sheldrick, 2008 ); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL and PLATON (Spek, 2009 ).

Supporting information

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536811030145/is2754sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536811030145/is2754Isup2.hkl

Supporting information file. DOI: 10.1107/S1600536811030145/is2754Isup3.cml

checkCIF report

Comment top

An intramolecular side-chain metal ligation is a useful method for stabilizing β-sheet, turn and helical structures in short peptides (Albrecht & Stortz, 2005; Garner & Harding, 2007). The stabilization of helical structure may enhance biological activities and protease resistance in vitro or in vivo (Wang et al., 2008; Walensky et al., 2004). The present compound, 1-(tert-butoxycarbonyl)piperidine-4-carboxylic acid, may be used as a rigid backbone to design the metal-ligating 3₁₀-helical peptide. In this way we may be able to design, synthesize and characterize a dynamically optically inactive 3₁₀-helical peptide which possess a metal-chelating ability (Boal et al., 2007).

In the molecular structure (Fig. 1), the piperidine ring (N1/C1–C5) adopts a chair conformation with puckering amplitude Q = 0.5505 (16) Å, Θ= 179.17 (18)° and ϕ= 90 (11)° (Cremer & Pople, 1975). The bond lengths (Allen et al., 1987) and angles are within normal ranges.

The crystal packing is shown in Fig. 2. The molecules are linked by intermolecular O4—H1O4···O1 and C5—H5B···O4 (Table 1) hydrogen bonds, forming two-molecular sheets parallel to the bc plane.

Related literature top

For general background and application of helical peptides, see: Albrecht & Stortz (2005); Garner & Harding (2007); Wang et al. (2008); Walensky et al. (2004); Boal et al. (2007). For bond-length data, see: Allen et al. (1987). For ring conformations, see: Cremer & Pople (1975). For stability of the temperature controller used for data collection, see: Cosier & Glazer (1986).

Experimental top

To isopicotinic acid (1 eq) dissolved in a dichloromethane (10 ml), triethylamine (3 eq) was added. The reaction mixture was stirred at room temperature for half an hour. BOC-anhydride (2 eq) was then added and the reaction mixture heated at 40 °C for 12 h. Completion of the reaction was confirmed by TLC and the solvent content was evaporated away under reduced pressure. The reaction mixture was acidified with diluted. HCl and the solid obtained was filtered off. M. p.: 135–137 °C.

Computing details top

Data collection: APEX2 (Bruker, 2009); cell refinement: SAINT (Bruker, 2009); data reduction: SAINT (Bruker, 2009); program(s) used to solve structure: SHELXTL (Sheldrick, 2008); program(s) used to refine structure: SHELXTL (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008) and PLATON (Spek, 2009).

Figures top

	Fig. 1. The molecular structure of the title compound, showing 30% probability displacement ellipsoids and the atom-numbering scheme.
	Fig. 2. The crystal packing of the title compound showing a two-molecular thick sheet. Dashed lines represent the intermolecular hydrogen bonds.

1-(tert-Butoxycarbonyl)piperidine-4-carboxylic acid top

Crystal data top

C₁₁H₁₉NO₄	F(000) = 496
M_r = 229.27	D_x = 1.251 Mg m⁻³
Monoclinic, P2₁/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 1750 reflections
a = 10.7006 (3) Å	θ = 2.4–28.5°
b = 6.5567 (2) Å	µ = 0.10 mm⁻¹
c = 17.9297 (6) Å	T = 100 K
β = 104.564 (2)°	Plate, colourless
V = 1217.54 (6) Å³	0.57 × 0.21 × 0.08 mm
Z = 4

Data collection top

Bruker SMART APEXII CCD area-detector diffractometer	2116 independent reflections
Radiation source: fine-focus sealed tube	1762 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.027
ϕ and ω scans	θ_max = 25.0°, θ_min = 2.0°
Absorption correction: multi-scan (SADABS; Bruker, 2009)	h = −12→11
T_min = 0.948, T_max = 0.993	k = −7→7
5360 measured reflections	l = −16→21

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F² > 2σ(F²)] = 0.039	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.092	H atoms treated by a mixture of independent and constrained refinement
S = 1.07	w = 1/[σ²(F_o²) + (0.0362P)² + 0.3737P] where P = (F_o² + 2F_c²)/3
2116 reflections	(Δ/σ)_max < 0.001
152 parameters	Δρ_max = 0.18 e Å⁻³
0 restraints	Δρ_min = −0.22 e Å⁻³

Crystal data top

C₁₁H₁₉NO₄	V = 1217.54 (6) Å³
M_r = 229.27	Z = 4
Monoclinic, P2₁/c	Mo Kα radiation
a = 10.7006 (3) Å	µ = 0.10 mm⁻¹
b = 6.5567 (2) Å	T = 100 K
c = 17.9297 (6) Å	0.57 × 0.21 × 0.08 mm
β = 104.564 (2)°

Data collection top

Bruker SMART APEXII CCD area-detector diffractometer	2116 independent reflections
Absorption correction: multi-scan (SADABS; Bruker, 2009)	1762 reflections with I > 2σ(I)
T_min = 0.948, T_max = 0.993	R_int = 0.027
5360 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.039	0 restraints
wR(F²) = 0.092	H atoms treated by a mixture of independent and constrained refinement
S = 1.07	Δρ_max = 0.18 e Å⁻³
2116 reflections	Δρ_min = −0.22 e Å⁻³
152 parameters

Special details top

Experimental. The crystal was placed in the cold stream of an Oxford Cryosystems Cobra open-flow nitrogen cryostat (Cosier & Glazer, 1986) operating at 100.0 (1) K.

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 (Å²) top

	x	y	z	U_iso*/U_eq
O1	0.26358 (11)	−0.05214 (18)	0.13924 (6)	0.0249 (3)
O2	0.20095 (11)	0.21800 (16)	0.20083 (6)	0.0229 (3)
O3	0.34156 (12)	−0.53547 (17)	0.46087 (7)	0.0265 (3)
O4	0.35972 (11)	−0.25776 (18)	0.53522 (6)	0.0244 (3)
N1	0.34480 (13)	−0.0015 (2)	0.26790 (7)	0.0188 (3)
C1	0.42896 (16)	−0.1805 (2)	0.27802 (9)	0.0213 (4)
H1A	0.5202	−0.1364	0.2948	0.026*
H1B	0.4167	−0.2525	0.2282	0.026*
C2	0.39922 (16)	−0.3257 (2)	0.33783 (9)	0.0195 (4)
H2A	0.4628	−0.4385	0.3473	0.023*
H2B	0.3123	−0.3855	0.3176	0.023*
C3	0.40397 (15)	−0.2158 (2)	0.41359 (9)	0.0178 (4)
H3A	0.4949	−0.1705	0.4361	0.021*
C4	0.31744 (15)	−0.0254 (2)	0.39936 (9)	0.0186 (4)
H4A	0.2259	−0.0677	0.3819	0.022*
H4B	0.3284	0.0509	0.4482	0.022*
C5	0.35063 (16)	0.1126 (2)	0.33908 (9)	0.0202 (4)
H5A	0.2891	0.2280	0.3280	0.024*
H5B	0.4385	0.1690	0.3591	0.024*
C6	0.26959 (15)	0.0473 (2)	0.19822 (9)	0.0190 (4)
C7	0.10863 (15)	0.2991 (3)	0.13127 (9)	0.0221 (4)
C8	0.06014 (17)	0.4903 (3)	0.16286 (10)	0.0288 (4)
H8A	0.0189	0.4528	0.2039	0.043*
H8B	−0.0027	0.5596	0.1214	0.043*
H8C	0.1330	0.5818	0.1837	0.043*
C9	0.17864 (18)	0.3540 (3)	0.07020 (10)	0.0330 (5)
H9A	0.2538	0.4391	0.0932	0.049*
H9B	0.1201	0.4294	0.0285	0.049*
H9C	0.2073	0.2291	0.0495	0.049*
C10	0.00063 (17)	0.1463 (3)	0.10281 (10)	0.0303 (4)
H10A	−0.0400	0.1137	0.1446	0.046*
H10B	0.0361	0.0215	0.0861	0.046*
H10C	−0.0639	0.2048	0.0594	0.046*
C11	0.36557 (14)	−0.3565 (2)	0.47085 (9)	0.0183 (4)
H1O4	0.333 (2)	−0.340 (4)	0.5652 (13)	0.058 (7)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O1	0.0329 (7)	0.0282 (7)	0.0148 (6)	0.0004 (5)	0.0084 (5)	−0.0034 (5)
O2	0.0274 (6)	0.0221 (6)	0.0170 (6)	0.0056 (5)	0.0018 (5)	0.0005 (5)
O3	0.0390 (7)	0.0190 (7)	0.0240 (7)	−0.0008 (5)	0.0125 (6)	0.0008 (5)
O4	0.0353 (7)	0.0226 (7)	0.0175 (6)	−0.0008 (5)	0.0109 (6)	0.0003 (5)
N1	0.0264 (8)	0.0164 (7)	0.0138 (7)	0.0028 (6)	0.0056 (6)	0.0008 (6)
C1	0.0253 (9)	0.0206 (9)	0.0201 (9)	0.0064 (7)	0.0099 (7)	−0.0003 (7)
C2	0.0234 (9)	0.0174 (8)	0.0191 (9)	0.0044 (7)	0.0082 (7)	0.0014 (7)
C3	0.0181 (8)	0.0183 (9)	0.0168 (8)	−0.0005 (7)	0.0043 (7)	0.0012 (7)
C4	0.0218 (9)	0.0189 (9)	0.0153 (8)	0.0010 (7)	0.0051 (7)	−0.0019 (7)
C5	0.0271 (9)	0.0166 (8)	0.0164 (8)	0.0002 (7)	0.0048 (7)	−0.0011 (7)
C6	0.0215 (9)	0.0184 (9)	0.0190 (9)	−0.0017 (7)	0.0086 (7)	0.0033 (7)
C7	0.0205 (9)	0.0276 (9)	0.0159 (8)	0.0012 (7)	0.0006 (7)	0.0046 (7)
C8	0.0264 (10)	0.0274 (10)	0.0296 (10)	0.0053 (8)	0.0017 (8)	0.0026 (8)
C9	0.0311 (10)	0.0395 (11)	0.0297 (10)	0.0074 (9)	0.0101 (8)	0.0152 (9)
C10	0.0257 (10)	0.0341 (11)	0.0295 (10)	−0.0009 (8)	0.0039 (8)	−0.0021 (8)
C11	0.0167 (8)	0.0204 (9)	0.0170 (8)	0.0034 (7)	0.0025 (7)	−0.0003 (7)

Geometric parameters (Å, º) top

O1—C6	1.2303 (18)	C4—C5	1.519 (2)
O2—C6	1.3457 (19)	C4—H4A	0.9900
O2—C7	1.4815 (18)	C4—H4B	0.9900
O3—C11	1.2050 (19)	C5—H5A	0.9900
O4—C11	1.3384 (18)	C5—H5B	0.9900
O4—H1O4	0.86 (2)	C7—C9	1.517 (2)
N1—C6	1.344 (2)	C7—C10	1.518 (2)
N1—C1	1.463 (2)	C7—C8	1.519 (2)
N1—C5	1.4669 (19)	C8—H8A	0.9800
C1—C2	1.526 (2)	C8—H8B	0.9800
C1—H1A	0.9900	C8—H8C	0.9800
C1—H1B	0.9900	C9—H9A	0.9800
C2—C3	1.527 (2)	C9—H9B	0.9800
C2—H2A	0.9900	C9—H9C	0.9800
C2—H2B	0.9900	C10—H10A	0.9800
C3—C11	1.512 (2)	C10—H10B	0.9800
C3—C4	1.537 (2)	C10—H10C	0.9800
C3—H3A	1.0000

C6—O2—C7	121.57 (12)	C4—C5—H5B	109.6
C11—O4—H1O4	109.2 (15)	H5A—C5—H5B	108.1
C6—N1—C1	120.84 (13)	O1—C6—N1	124.22 (15)
C6—N1—C5	124.88 (13)	O1—C6—O2	124.04 (15)
C1—N1—C5	114.27 (12)	N1—C6—O2	111.74 (13)
N1—C1—C2	110.93 (12)	O2—C7—C9	110.31 (13)
N1—C1—H1A	109.5	O2—C7—C10	109.63 (13)
C2—C1—H1A	109.5	C9—C7—C10	112.73 (15)
N1—C1—H1B	109.5	O2—C7—C8	101.56 (12)
C2—C1—H1B	109.5	C9—C7—C8	110.50 (14)
H1A—C1—H1B	108.0	C10—C7—C8	111.56 (14)
C1—C2—C3	111.36 (13)	C7—C8—H8A	109.5
C1—C2—H2A	109.4	C7—C8—H8B	109.5
C3—C2—H2A	109.4	H8A—C8—H8B	109.5
C1—C2—H2B	109.4	C7—C8—H8C	109.5
C3—C2—H2B	109.4	H8A—C8—H8C	109.5
H2A—C2—H2B	108.0	H8B—C8—H8C	109.5
C11—C3—C2	111.22 (13)	C7—C9—H9A	109.5
C11—C3—C4	110.67 (12)	C7—C9—H9B	109.5
C2—C3—C4	110.60 (13)	H9A—C9—H9B	109.5
C11—C3—H3A	108.1	C7—C9—H9C	109.5
C2—C3—H3A	108.1	H9A—C9—H9C	109.5
C4—C3—H3A	108.1	H9B—C9—H9C	109.5
C5—C4—C3	111.29 (12)	C7—C10—H10A	109.5
C5—C4—H4A	109.4	C7—C10—H10B	109.5
C3—C4—H4A	109.4	H10A—C10—H10B	109.5
C5—C4—H4B	109.4	C7—C10—H10C	109.5
C3—C4—H4B	109.4	H10A—C10—H10C	109.5
H4A—C4—H4B	108.0	H10B—C10—H10C	109.5
N1—C5—C4	110.43 (12)	O3—C11—O4	122.99 (15)
N1—C5—H5A	109.6	O3—C11—C3	125.29 (14)
C4—C5—H5A	109.6	O4—C11—C3	111.72 (13)
N1—C5—H5B	109.6

C6—N1—C1—C2	−123.01 (15)	C1—N1—C6—O2	−179.20 (13)
C5—N1—C1—C2	56.56 (17)	C5—N1—C6—O2	1.3 (2)
N1—C1—C2—C3	−53.55 (17)	C7—O2—C6—O1	1.2 (2)
C1—C2—C3—C11	176.11 (13)	C7—O2—C6—N1	−178.49 (13)
C1—C2—C3—C4	52.71 (17)	C6—O2—C7—C9	−61.40 (18)
C11—C3—C4—C5	−177.27 (13)	C6—O2—C7—C10	63.30 (17)
C2—C3—C4—C5	−53.56 (17)	C6—O2—C7—C8	−178.59 (13)
C6—N1—C5—C4	122.38 (16)	C2—C3—C11—O3	4.2 (2)
C1—N1—C5—C4	−57.18 (17)	C4—C3—C11—O3	127.55 (17)
C3—C4—C5—N1	54.71 (17)	C2—C3—C11—O4	−175.19 (13)
C1—N1—C6—O1	1.1 (2)	C4—C3—C11—O4	−51.83 (17)
C5—N1—C6—O1	−178.39 (14)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O4—H1O4···O1ⁱ	0.86 (2)	1.82 (2)	2.6562 (16)	164 (2)
C5—H5B···O4ⁱⁱ	0.99	2.56	3.476 (2)	154

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

Experimental details

Crystal data
Chemical formula	C₁₁H₁₉NO₄
M_r	229.27
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	100
a, b, c (Å)	10.7006 (3), 6.5567 (2), 17.9297 (6)
β (°)	104.564 (2)
V (Å³)	1217.54 (6)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.10
Crystal size (mm)	0.57 × 0.21 × 0.08

Data collection
Diffractometer	Bruker SMART APEXII CCD area-detector diffractometer
Absorption correction	Multi-scan (SADABS; Bruker, 2009)
T_min, T_max	0.948, 0.993
No. of measured, independent and observed [I > 2σ(I)] reflections	5360, 2116, 1762
R_int	0.027
(sin θ/λ)_max (Å⁻¹)	0.595

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.039, 0.092, 1.07
No. of reflections	2116
No. of parameters	152
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.18, −0.22

Computer programs: APEX2 (Bruker, 2009), SAINT (Bruker, 2009), SHELXTL (Sheldrick, 2008) and PLATON (Spek, 2009).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O4—H1O4···O1ⁱ	0.86 (2)	1.82 (2)	2.6562 (16)	164 (2)
C5—H5B···O4ⁱⁱ	0.9900	2.5600	3.476 (2)	154.00

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

Footnotes

‡Thomson Reuters ResearcherID: A-3561-2009.

Acknowledgements

The authors thank Universiti Sains Malaysia (USM) for a Research University Grant (No. 1001/PFIZIK/811160). SA thanks the Malaysian government and USM for the award of a research scholarship.

References

Albrecht, M. & Stortz, P. (2005). Chem. Soc. Rev. 34, 496–506. Web of Science CrossRef CAS Google Scholar
Allen, F. H., Kennard, O., Watson, D. G., Brammer, L., Orpen, A. G. & Taylor, R. (1987). J. Chem. Soc. Perkin Trans. 2, pp. S1–19. CrossRef Web of Science Google Scholar
Boal, A. K., Guryanov, I., Moretto, A., Crisma, M., Lanni, E. L., Toniolo, C., Grubbs, R. H. & O'Leary, D. J. (2007). J. Am. Chem. Soc. 129, 6986–6987. Web of Science CSD CrossRef PubMed CAS Google Scholar
Bruker (2009). SADABS, APEX2 and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Cosier, J. & Glazer, A. M. (1986). J. Appl. Cryst. 19, 105–107. CrossRef CAS Web of Science IUCr Journals Google Scholar
Cremer, D. & Pople, J. A. (1975). J. Am. Chem. Soc. 97, 1354–1358. CrossRef CAS Web of Science Google Scholar
Garner, J. & Harding, M. M. (2007). Org. Biomol. Chem. 5, 3577–3585. CrossRef CAS Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar
Spek, A. L. (2009). Acta Cryst. D65, 148–155. Web of Science CrossRef CAS IUCr Journals Google Scholar
Walensky, L. D., Kung, A. L., Escher, I., Malia, T. J., Barbuto, S., Wright, R. D., Wagner, G., Verdine, G. L. & Korsmeyer, S. J. (2004). Science, 305, 1466–1470. Web of Science CrossRef CAS Google Scholar
Wang, D., Lu, M. & Arora, P. S. (2008). Angew. Chem. Int. Ed. 47, 1879–1882. Web of Science CrossRef CAS Google Scholar