(2S,4R)-4-Fluoro­pyrrolidinium-2-carboxyl­ate

Hobart Jr, D.B.; Merola, J.S.

doi:10.1107/S1600536812031741

organic compounds

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ISSN: 2056-9890

Volume 68| Part 8| August 2012| Page o2490

https://doi.org/10.1107/S1600536812031741

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(2S,4R)-4-Fluoropyrrolidinium-2-carboxylate

David B. Hobart Jr ^a ^* and Joseph S. Merola ^a

^aDepartment of Chemistry, Virginia Tech, Blacksburg, VA 24061, USA
^*Correspondence e-mail: dhobart@vt.edu

(Received 27 June 2012; accepted 11 July 2012; online 18 July 2012)

The crystal structure of the title compound, C₅H₈FNO₂, at 100 K, displays intermolecular N—H⋯O hydrogen bonding between the ammonium and carboxylate groups as a result of its zwitterionic nature in the solid state. The five-membered ring adopts an envelope conformation with the C atom at the 3-position as the flap. The compound is of interest with respect to the synthesis and structural properties of synthetic collagens. The absolute structure was determined by comparison with the commercially available material.

Related literature

For the synthesis of the title compound, see: Gottlieb et al. (1965 ); Azad et al. (2012 ). For its applications and properties with respect to synthetic collagens, see: Hodges & Raines (2003 , 2005 ); Holmgren et al. (1999 ); Kim et al. (2005 ); Mooney et al. (2002 ); Persikov et al. (2003 ); Raines (2005 ); Shoulders & Raines (2009 ); Shoulders et al. (2006 ); Takeuchi & Prockop (1969 ).

Experimental

Crystal data

C₅H₈FNO₂
M_r = 133.12
Orthorhombic, P 2₁ 2₁ 2₁
a = 7.6530 (6) Å
b = 8.4128 (6) Å
c = 8.6286 (6) Å
V = 555.54 (7) Å³
Z = 4
Mo Kα radiation
μ = 0.14 mm⁻¹
T = 100 K
0.26 × 0.05 × 0.03 mm

Data collection

Oxford Diffraction Gemini Ultra diffractometer
Absorption correction: Gaussian (CrysAlis PRO; Agilent, 2011 ) T_min = 0.977, T_max = 0.996
10227 measured reflections
959 independent reflections
832 reflections with I > 2σ(I)
R_int = 0.082

Refinement

R[F² > 2σ(F²)] = 0.038
wR(F²) = 0.073
S = 1.07
959 reflections
114 parameters
All H-atom parameters refined
Δρ_max = 0.32 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
N6—H6B⋯O2ⁱ	0.92 (3)	1.90 (3)	2.744 (2)	152 (2)
N6—H6A⋯O2ⁱⁱ	0.91 (3)	2.01 (3)	2.899 (2)	164 (2)
Symmetry codes: (i) $[-x+1, y+{\script{1\over 2}}, -z+{\script{1\over 2}}]$ ; (ii) $[x-{\script{1\over 2}}, -y+{\script{3\over 2}}, -z]$ .

Data collection: CrysAlis PRO (Agilent, 2011); cell refinement: CrysAlis PRO; data reduction: CrysAlis PRO; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: OLEX2 (Dolomanov et al., 2009 ); software used to prepare material for publication: OLEX2.

Supporting information

Crystal structure: contains datablocks I, global. DOI: https://doi.org/10.1107/S1600536812031741/im2392sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S1600536812031741/im2392Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S1600536812031741/im2392Isup3.cdx

Supporting information file. DOI: https://doi.org/10.1107/S1600536812031741/im2392Isup4.cml

checkCIF report

Comment top

The title compound is a useful building block in the synthesis of synthetic collagens. Collagen is the most abundant protein found in animals and exists as a triple helix comprised of three strands. The amino acid encoding of the strands follows the X—Y-Gly pattern. Trans-4-fluoroproline has been shown to induce hyperstability of the triple helix when substituted for the Y codon.

Related literature top

For the synthesis of the title compound, see: Gottlieb et al. (1965); Azad et al. (2012). For its applications and properties with respect to synthetic collagens, see: Hodges & Raines (2003, 2005); Holmgren et al. (1999); Kim et al. (2005); Mooney et al. (2002); Persikov et al. (2003); Raines (2005); Shoulders & Raines (2009); Shoulders et al. (2006); Takeuchi & Prockop (1969).

Experimental top

The title compound was purchased commercially from Bachem Americas, Inc., 3132 Kashiwa Street, Torrance, CA 90505 USA. Single crystals suitable for diffraction were grown via slow evaporation from a 50/50 (v/v) solution of acetone and water.

Structure description top

For the synthesis of the title compound, see: Gottlieb et al. (1965); Azad et al. (2012). For its applications and properties with respect to synthetic collagens, see: Hodges & Raines (2003, 2005); Holmgren et al. (1999); Kim et al. (2005); Mooney et al. (2002); Persikov et al. (2003); Raines (2005); Shoulders & Raines (2009); Shoulders et al. (2006); Takeuchi & Prockop (1969).

Computing details top

Data collection: CrysAlis PRO (Agilent, 2011); cell refinement: CrysAlis PRO (Agilent, 2011); data reduction: CrysAlis PRO (Agilent, 2011); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: OLEX2 (Dolomanov et al., 2009); software used to prepare material for publication: OLEX2 (Dolomanov et al., 2009).

Figures top

	Fig. 1. View of the title compound showing displacement ellipsoids at the 50% probability level.
	Fig. 2. A view of a section of the crystal packing of the title compound along [101] showing N6–H6B···O2ⁱ and N6–H6A···O2ⁱⁱ hydrogen bonds [Symmetry code (i) 3/2 - x, 1 - y, 1/2 + z; (ii) +x, +y, 1 + z].

(2S,4R)-4-Fluoropyrrolidinium-2-carboxylate top

Crystal data top

C₅H₈FNO₂	D_x = 1.592 Mg m⁻³
M_r = 133.12	Mo Kα radiation, λ = 0.71073 Å
Orthorhombic, P2₁2₁2₁	Cell parameters from 1887 reflections
a = 7.6530 (6) Å	θ = 3.6–30.0°
b = 8.4128 (6) Å	µ = 0.14 mm⁻¹
c = 8.6286 (6) Å	T = 100 K
V = 555.54 (7) Å³	Prism, clear light colourless
Z = 4	0.26 × 0.05 × 0.03 mm
F(000) = 280

Data collection top

Oxford Diffraction Gemini Ultra diffractometer	959 independent reflections
Radiation source: fine-focus sealed tube, fine-focus sealed tube	832 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.082
Detector resolution: 16.0122 pixels mm^-1	θ_max = 30.1°, θ_min = 3.6°
phi and ω scans	h = −10→10
Absorption correction: gaussian (CrysAlis PRO; Agilent, 2011)	k = −11→11
T_min = 0.977, T_max = 0.996	l = −12→12
10227 measured reflections

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)] = 0.038	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.073	All H-atom parameters refined
S = 1.07	w = 1/[σ²(F_o²) + (0.0203P)² + 0.2288P] where P = (F_o² + 2F_c²)/3
959 reflections	(Δ/σ)_max < 0.001
114 parameters	Δρ_max = 0.32 e Å⁻³
0 restraints	Δρ_min = −0.23 e Å⁻³

Crystal data top

C₅H₈FNO₂	V = 555.54 (7) Å³
M_r = 133.12	Z = 4
Orthorhombic, P2₁2₁2₁	Mo Kα radiation
a = 7.6530 (6) Å	µ = 0.14 mm⁻¹
b = 8.4128 (6) Å	T = 100 K
c = 8.6286 (6) Å	0.26 × 0.05 × 0.03 mm

Data collection top

Oxford Diffraction Gemini Ultra diffractometer	959 independent reflections
Absorption correction: gaussian (CrysAlis PRO; Agilent, 2011)	832 reflections with I > 2σ(I)
T_min = 0.977, T_max = 0.996	R_int = 0.082
10227 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.038	0 restraints
wR(F²) = 0.073	All H-atom parameters refined
S = 1.07	Δρ_max = 0.32 e Å⁻³
959 reflections	Δρ_min = −0.23 e Å⁻³
114 parameters

Special details top

Experimental. Recrystallized from 50/50 acetone/water.

Absorption correction: CrysAlisPro, Agilent Technologies, Version 1.171.34.49 (release 20-01-2011 CrysAlis171 .NET) (compiled Jan 20 2011,15:58:25) Numerical absorption correction based on gaussian integration over a multifaceted crystal model

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
F1	0.24111 (16)	0.73474 (16)	0.53792 (14)	0.0194 (3)
O2	0.58809 (19)	0.59578 (17)	0.07960 (17)	0.0143 (3)
O3	0.4982 (2)	0.82996 (18)	−0.01402 (17)	0.0177 (3)
N6	0.2662 (2)	0.8837 (2)	0.2162 (2)	0.0109 (3)
C4	0.3974 (3)	0.7510 (2)	0.2345 (2)	0.0104 (4)
C5	0.5019 (3)	0.7239 (2)	0.0854 (2)	0.0104 (4)
C7	0.1571 (3)	0.6913 (3)	0.3970 (2)	0.0130 (4)
C8	0.1078 (3)	0.8427 (3)	0.3133 (2)	0.0124 (4)
C9	0.2903 (3)	0.6117 (3)	0.2947 (2)	0.0137 (4)
H4	0.480 (3)	0.787 (3)	0.317 (3)	0.010 (6)*
H8A	0.011 (3)	0.822 (3)	0.247 (3)	0.013 (6)*
H7	0.056 (3)	0.629 (3)	0.424 (3)	0.011 (6)*
H8B	0.084 (3)	0.927 (3)	0.387 (3)	0.008 (6)*
H9A	0.233 (3)	0.560 (3)	0.208 (3)	0.020 (7)*
H9B	0.358 (3)	0.540 (3)	0.353 (3)	0.022 (7)*
H6A	0.231 (3)	0.895 (3)	0.115 (3)	0.026 (7)*
H6B	0.314 (3)	0.975 (3)	0.256 (3)	0.020 (7)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
F1	0.0170 (6)	0.0320 (8)	0.0092 (6)	0.0011 (6)	0.0006 (5)	0.0004 (5)
O2	0.0151 (7)	0.0142 (7)	0.0136 (7)	0.0048 (6)	0.0027 (6)	0.0023 (6)
O3	0.0248 (8)	0.0158 (7)	0.0124 (7)	0.0051 (7)	0.0053 (7)	0.0031 (6)
N6	0.0115 (8)	0.0101 (8)	0.0112 (8)	0.0008 (7)	0.0000 (7)	−0.0014 (7)
C4	0.0110 (8)	0.0110 (9)	0.0091 (8)	0.0004 (8)	−0.0003 (7)	−0.0002 (8)
C5	0.0094 (8)	0.0113 (9)	0.0106 (8)	−0.0034 (8)	0.0000 (7)	−0.0015 (8)
C7	0.0119 (9)	0.0158 (10)	0.0114 (9)	−0.0018 (8)	0.0018 (8)	−0.0003 (8)
C8	0.0106 (9)	0.0153 (9)	0.0112 (9)	0.0017 (8)	0.0007 (8)	−0.0022 (8)
C9	0.0149 (10)	0.0118 (9)	0.0144 (10)	0.0009 (8)	0.0013 (8)	0.0035 (9)

Geometric parameters (Å, º) top

F1—C7	1.423 (2)	C4—H4	1.00 (2)
O2—C5	1.265 (2)	C7—C8	1.512 (3)
O3—C5	1.238 (2)	C7—C9	1.505 (3)
N6—C4	1.509 (3)	C7—H7	0.96 (2)
N6—C8	1.513 (3)	C8—H8A	0.95 (3)
N6—H6A	0.91 (3)	C8—H8B	0.97 (2)
N6—H6B	0.92 (3)	C9—H9A	0.97 (3)
C4—C5	1.532 (3)	C9—H9B	0.94 (3)
C4—C9	1.521 (3)

C4—N6—C8	107.85 (15)	F1—C7—H7	107.3 (14)
C4—N6—H6A	111.6 (17)	C8—C7—H7	111.6 (13)
C4—N6—H6B	108.2 (15)	C9—C7—C8	105.27 (17)
C8—N6—H6A	108.5 (17)	C9—C7—H7	116.6 (14)
C8—N6—H6B	107.5 (15)	N6—C8—H8A	109.4 (15)
H6A—N6—H6B	113 (2)	N6—C8—H8B	110.1 (13)
N6—C4—C5	111.70 (16)	C7—C8—N6	104.86 (16)
N6—C4—C9	104.28 (16)	C7—C8—H8A	109.3 (15)
N6—C4—H4	105.8 (13)	C7—C8—H8B	110.5 (13)
C5—C4—H4	108.2 (13)	H8A—C8—H8B	112.4 (19)
C9—C4—C5	116.93 (17)	C4—C9—H9A	108.9 (15)
C9—C4—H4	109.3 (13)	C4—C9—H9B	112.4 (15)
O2—C5—C4	115.64 (17)	C7—C9—C4	102.86 (17)
O3—C5—O2	126.79 (19)	C7—C9—H9A	110.3 (15)
O3—C5—C4	117.53 (18)	C7—C9—H9B	110.2 (15)
F1—C7—C8	107.72 (17)	H9A—C9—H9B	112 (2)
F1—C7—C9	108.03 (17)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N6—H6B···O2ⁱ	0.92 (3)	1.90 (3)	2.744 (2)	152 (2)
N6—H6A···O2ⁱⁱ	0.91 (3)	2.01 (3)	2.899 (2)	164 (2)

Symmetry codes: (i) −x+1, y+1/2, −z+1/2; (ii) x−1/2, −y+3/2, −z.

Experimental details

Crystal data
Chemical formula	C₅H₈FNO₂
M_r	133.12
Crystal system, space group	Orthorhombic, P2₁2₁2₁
Temperature (K)	100
a, b, c (Å)	7.6530 (6), 8.4128 (6), 8.6286 (6)
V (Å³)	555.54 (7)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.14
Crystal size (mm)	0.26 × 0.05 × 0.03

Data collection
Diffractometer	Oxford Diffraction Gemini Ultra
Absorption correction	Gaussian (CrysAlis PRO; Agilent, 2011)
T_min, T_max	0.977, 0.996
No. of measured, independent and observed [I > 2σ(I)] reflections	10227, 959, 832
R_int	0.082
(sin θ/λ)_max (Å⁻¹)	0.705

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.038, 0.073, 1.07
No. of reflections	959
No. of parameters	114
H-atom treatment	All H-atom parameters refined
Δρ_max, Δρ_min (e Å⁻³)	0.32, −0.23

Computer programs: CrysAlis PRO (Agilent, 2011), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), OLEX2 (Dolomanov et al., 2009).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N6—H6B···O2ⁱ	0.92 (3)	1.90 (3)	2.744 (2)	152 (2)
N6—H6A···O2ⁱⁱ	0.91 (3)	2.01 (3)	2.899 (2)	164 (2)

Symmetry codes: (i) −x+1, y+1/2, −z+1/2; (ii) x−1/2, −y+3/2, −z.

Acknowledgements

The authors would like to thank the Virginia Tech Department of Chemistry and the Virginia Tech Crystallography Laboratory for their support.

References

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