(R)-(–)-Mepivacaine hydro­chloride enantiomer: a low-temperature study

Low-temperature structural data are reported for the anaesthetic (2R)-(−)-2-(2,6-di­methyl­phenyl­amino­carbonyl)-1-methyl­piperidinium chloride, C₁₅H₂₃N₂O⁺·Cl⁻, which complement existing room-temperature data for the S enantiomer. Crystal packing is largely controlled by infinite N—H...Cl hydrogen-bonded chains.

Key indicators

• Single-crystal X-ray study
• T = 180 K
• Mean [sigma](C-C) = 0.003 Å
• R factor = 0.022
• wR factor = 0.047
• Data-to-parameter ratio = 9.1

checkCIF/PLATON results

No syntax errors found



Alert level A
PLAT027_ALERT_3_A _diffrn_reflns_theta_full (too) Low ............      59.03 Deg.

Author Response: 'see _publ_section_exptl_refinement'

Alert level B
THETM01_ALERT_3_B  The value of sine(theta_max)/wavelength is less than 0.575
            Calculated sin(theta_max)/wavelength =    0.5561
PLAT023_ALERT_3_B Resolution (too) Low [sin(th)/Lambda < 0.6].....      59.03 Deg.

Alert level C
PLAT063_ALERT_3_C Crystal Probably too Large for Beam Size .......       0.80 mm
PLAT125_ALERT_4_C No _symmetry_space_group_name_Hall Given .......          ?

Alert level G
REFLT03_ALERT_4_G Please check that the estimate of the number of Friedel pairs is
            correct. If it is not, please give the correct count in the
            _publ_section_exptl_refinement section of the submitted CIF.
           From the CIF: _diffrn_reflns_theta_max           59.03
           From the CIF: _reflns_number_total               2201
           Count of symmetry unique reflns         1318
           Completeness (_total/calc)            167.00%
           TEST3: Check Friedels for noncentro structure
           Estimate of Friedel pairs measured       883
           Fraction of Friedel pairs measured     0.670
           Are heavy atom types Z>Si present          yes

   1 ALERT level A = In general: serious problem
   2 ALERT level B = Potentially serious problem
   2 ALERT level C = Check and explain
   1 ALERT level G = General alerts; check

   0 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   0 ALERT type 2 Indicator that the structure model may be wrong or deficient
   4 ALERT type 3 Indicator that the structure quality may be low
   2 ALERT type 4 Improvement, methodology, query or suggestion

---

Computing details

Data collection: CrysAlis CCD (Oxford Diffraction, 2001); cell refinement: CrysAlis CCD; data reduction: CrysAlis RED (Oxford Diffraction, 2001); program(s) used to solve structure: SIR97 (Altomare et al., 1999); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEP-3 (Farrugia, 1997); software used to prepare material for publication: SHELXL97.

(2R)-2-(2,6-dimethylphenylaminocarbonyl)-1-methylpiperidinium chloride

Crystal data

C15H23N2O^+·Cl^−	Dx = 1.194 Mg m^−3
Mr = 282.80	Cu Kα radiation, λ = 1.54180 Å
Orthorhombic, P212121	Cell parameters from 952 reflections
a = 9.7378 (10) Å	θ = 6–58°
b = 10.5790 (9) Å	µ = 2.10 mm^−1
c = 15.2761 (15) Å	T = 180 K
V = 1573.7 (3) Å^3	Elongated prism, colorless
Z = 4	0.80 × 0.30 × 0.30 mm
F(000) = 608

Data collection

Oxford Diffraction CCD diffractometer	2201 independent reflections
Radiation source: fine-focus sealed tube	1989 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.030
ω scans	θmax = 59.0°, θmin = 5.1°
Absorption correction: multi-scan (SADABS; Sheldrick, 1986)	h = −10→9
Tmin = 0.331, Tmax = 0.533	k = −11→9
6079 measured reflections	l = −15→16

Refinement

Refinement on F^2	Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: full	Only H-atom coordinates refined
R[F^2 > 2σ(F^2)] = 0.022	w = 1/[σ^2(Fo^2) + (0.0218P)^2] where P = (Fo^2 + 2Fc^2)/3
wR(F^2) = 0.047	(Δ/σ)max < 0.001
S = 0.96	Δρmax = 0.14 e Å^−3
2201 reflections	Δρmin = −0.11 e Å^−3
242 parameters	Extinction correction: SHELXL97, Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
0 restraints	Extinction coefficient: 0.0167 (5)
Primary atom site location: structure-invariant direct methods	Absolute structure: Flack (1983), 883 Friedel pairs
Secondary atom site location: difference Fourier map	Absolute structure parameter: 0.023 (11)

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
Cl	0.21641 (4)	0.51729 (4)	0.87349 (3)	0.03400 (15)
N1	−0.09933 (14)	0.26043 (15)	0.69728 (9)	0.0246 (4)
H1N	−0.1038 (18)	0.1807 (17)	0.6759 (11)	0.029*
C1'	−0.1655 (2)	0.2570 (3)	0.78545 (13)	0.0377 (5)
H71	−0.114 (2)	0.199 (2)	0.8240 (13)	0.057*
H72	−0.256 (2)	0.216 (2)	0.7769 (13)	0.057*
H73	−0.172 (2)	0.340 (2)	0.8081 (14)	0.057*
C2	0.04679 (18)	0.30285 (18)	0.70399 (11)	0.0260 (4)
H2	0.0474 (17)	0.3791 (18)	0.7346 (12)	0.031*
C3	0.1101 (2)	0.3215 (2)	0.61335 (13)	0.0387 (5)
H31	0.118 (2)	0.237 (2)	0.5860 (12)	0.046*
H32	0.199 (2)	0.3595 (17)	0.6236 (12)	0.046*
C4	0.0237 (2)	0.4076 (2)	0.55541 (15)	0.0427 (6)
H41	0.022 (2)	0.490 (2)	0.5813 (13)	0.051*
H42	0.066 (2)	0.415 (2)	0.4989 (14)	0.051*
C5	−0.1190 (2)	0.3523 (2)	0.54786 (13)	0.0358 (5)
H51	−0.182 (2)	0.3992 (19)	0.5131 (12)	0.043*
H52	−0.1182 (19)	0.267 (2)	0.5217 (12)	0.043*
C6	−0.18483 (19)	0.3401 (2)	0.63616 (13)	0.0303 (5)
H61	−0.2762 (18)	0.2948 (16)	0.6352 (12)	0.036*
H62	−0.1920 (19)	0.4185 (19)	0.6655 (12)	0.036*
C7	0.12812 (18)	0.19953 (19)	0.75059 (11)	0.0265 (4)
O7	0.10466 (13)	0.08763 (13)	0.73431 (8)	0.0373 (4)
N8	0.22762 (16)	0.24068 (15)	0.80354 (10)	0.0279 (4)
H8N	0.2255 (19)	0.3171 (18)	0.8185 (12)	0.033*
C9	0.32758 (17)	0.15887 (17)	0.84329 (11)	0.0264 (5)
C10	0.42577 (18)	0.10045 (19)	0.79009 (12)	0.0303 (5)
C11	0.52297 (19)	0.0242 (2)	0.83062 (14)	0.0362 (5)
H11	0.5883 (19)	−0.0202 (18)	0.7963 (12)	0.043*
C12	0.52420 (19)	0.0087 (2)	0.92023 (13)	0.0385 (5)
H12	0.596 (2)	−0.0410 (18)	0.9486 (13)	0.046*
C13	0.4263 (2)	0.06752 (19)	0.97126 (14)	0.0361 (5)
H13	0.4241 (19)	0.0596 (18)	1.0312 (14)	0.043*
C14	0.32559 (17)	0.14369 (18)	0.93404 (12)	0.0287 (5)
C15	0.2167 (3)	0.2058 (2)	0.98935 (14)	0.0413 (5)
H81	0.122 (2)	0.193 (2)	0.9667 (14)	0.062*
H82	0.234 (2)	0.296 (2)	0.9926 (13)	0.062*
H83	0.215 (2)	0.171 (2)	1.0457 (15)	0.062*
C16	0.4275 (2)	0.1189 (3)	0.69241 (14)	0.0453 (6)
H91	0.520 (2)	0.089 (2)	0.6653 (14)	0.068*
H92	0.420 (2)	0.210 (2)	0.6766 (14)	0.068*
H93	0.359 (2)	0.075 (2)	0.6671 (14)	0.068*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
Cl	0.0326 (3)	0.0294 (3)	0.0400 (3)	0.0004 (2)	−0.0024 (2)	0.0017 (2)
N1	0.0229 (9)	0.0238 (9)	0.0270 (8)	0.0020 (8)	0.0002 (7)	−0.0015 (7)
C1'	0.0367 (13)	0.0434 (14)	0.0330 (13)	0.0021 (12)	0.0084 (9)	0.0005 (11)
C2	0.0214 (10)	0.0261 (11)	0.0306 (11)	−0.0002 (9)	−0.0041 (8)	−0.0009 (9)
C3	0.0269 (10)	0.0504 (14)	0.0386 (12)	0.0000 (11)	0.0014 (10)	0.0114 (12)
C4	0.0418 (13)	0.0526 (15)	0.0338 (12)	0.0012 (12)	0.0037 (10)	0.0129 (12)
C5	0.0386 (12)	0.0378 (14)	0.0309 (12)	0.0068 (11)	−0.0097 (9)	0.0014 (10)
C6	0.0239 (10)	0.0287 (12)	0.0382 (12)	0.0054 (9)	−0.0081 (9)	−0.0006 (10)
C7	0.0233 (10)	0.0292 (12)	0.0269 (11)	0.0006 (9)	0.0001 (9)	0.0017 (9)
O7	0.0354 (8)	0.0273 (8)	0.0494 (9)	0.0004 (7)	−0.0151 (7)	0.0001 (7)
N8	0.0269 (9)	0.0252 (8)	0.0315 (9)	0.0000 (9)	−0.0063 (7)	−0.0022 (8)
C9	0.0219 (10)	0.0245 (11)	0.0328 (11)	−0.0016 (9)	−0.0074 (8)	0.0001 (9)
C10	0.0213 (10)	0.0351 (12)	0.0345 (11)	−0.0018 (10)	−0.0022 (9)	0.0037 (9)
C11	0.0261 (11)	0.0406 (14)	0.0420 (13)	0.0041 (11)	−0.0005 (9)	0.0009 (11)
C12	0.0291 (10)	0.0397 (14)	0.0467 (14)	0.0058 (11)	−0.0096 (9)	0.0057 (11)
C13	0.0376 (12)	0.0384 (13)	0.0323 (11)	−0.0017 (11)	−0.0114 (10)	0.0029 (10)
C14	0.0261 (10)	0.0285 (12)	0.0316 (11)	−0.0002 (9)	−0.0078 (9)	−0.0029 (9)
C15	0.0469 (13)	0.0448 (14)	0.0322 (12)	0.0103 (13)	−0.0030 (11)	−0.0035 (10)
C16	0.0348 (13)	0.0633 (17)	0.0377 (13)	0.0083 (13)	0.0054 (10)	0.0061 (12)

Geometric parameters (Å, º)

N1—C1'	1.494 (2)	C7—O7	1.231 (2)
N1—C2	1.495 (2)	C7—N8	1.335 (2)
N1—C6	1.508 (2)	N8—C9	1.437 (2)
N1—H1N	0.905 (17)	N8—H8N	0.841 (18)
C1'—H71	0.99 (2)	C9—C14	1.396 (2)
C1'—H72	0.99 (2)	C9—C10	1.399 (2)
C1'—H73	0.95 (2)	C10—C11	1.389 (3)
C2—C7	1.526 (2)	C10—C16	1.505 (3)
C2—C3	1.528 (3)	C11—C12	1.379 (3)
C2—H2	0.932 (18)	C11—H11	0.949 (19)
C3—C4	1.523 (3)	C12—C13	1.380 (3)
C3—H31	0.99 (2)	C12—H12	0.979 (19)
C3—H32	0.97 (2)	C13—C14	1.391 (2)
C4—C5	1.512 (3)	C13—H13	0.92 (2)
C4—H41	0.96 (2)	C14—C15	1.507 (3)
C4—H42	0.96 (2)	C15—H81	0.99 (2)
C5—C6	1.499 (3)	C15—H82	0.97 (3)
C5—H51	0.95 (2)	C15—H83	0.94 (2)
C5—H52	0.98 (2)	C16—H91	1.04 (2)
C6—H61	1.011 (17)	C16—H92	1.00 (2)
C6—H62	0.946 (19)	C16—H93	0.90 (2)
C1'—N1—C2	110.85 (14)	C5—C6—H62	112.5 (11)
C1'—N1—C6	109.49 (15)	N1—C6—H62	103.8 (11)
C2—N1—C6	113.57 (14)	H61—C6—H62	110.9 (16)
C1'—N1—H1N	106.4 (11)	O7—C7—N8	124.79 (17)
C2—N1—H1N	110.5 (12)	O7—C7—C2	119.88 (16)
C6—N1—H1N	105.7 (11)	N8—C7—C2	115.19 (17)
N1—C1'—H71	109.6 (12)	C7—N8—C9	123.45 (16)
N1—C1'—H72	106.1 (12)	C7—N8—H8N	117.4 (13)
H71—C1'—H72	105.1 (17)	C9—N8—H8N	118.7 (13)
N1—C1'—H73	109.6 (14)	C14—C9—C10	122.40 (17)
H71—C1'—H73	113.1 (18)	C14—C9—N8	118.66 (16)
H72—C1'—H73	113.0 (18)	C10—C9—N8	118.92 (16)
N1—C2—C7	108.11 (15)	C11—C10—C9	117.60 (18)
N1—C2—C3	111.13 (15)	C11—C10—C16	120.63 (18)
C7—C2—C3	107.80 (15)	C9—C10—C16	121.77 (18)
N1—C2—H2	107.5 (11)	C12—C11—C10	121.2 (2)
C7—C2—H2	112.5 (11)	C12—C11—H11	118.9 (11)
C3—C2—H2	109.9 (11)	C10—C11—H11	119.8 (11)
C4—C3—C2	112.37 (17)	C11—C12—C13	120.1 (2)
C4—C3—H31	109.6 (12)	C11—C12—H12	120.7 (12)
C2—C3—H31	107.4 (11)	C13—C12—H12	119.2 (11)
C4—C3—H32	109.9 (11)	C12—C13—C14	121.2 (2)
C2—C3—H32	105.6 (12)	C12—C13—H13	122.6 (12)
H31—C3—H32	111.9 (16)	C14—C13—H13	116.3 (12)
C5—C4—C3	108.69 (18)	C13—C14—C9	117.56 (18)
C5—C4—H41	111.6 (12)	C13—C14—C15	121.32 (17)
C3—C4—H41	108.4 (13)	C9—C14—C15	121.10 (18)
C5—C4—H42	111.0 (12)	C14—C15—H81	113.4 (13)
C3—C4—H42	109.6 (12)	C14—C15—H82	109.5 (13)
H41—C4—H42	107.6 (19)	H81—C15—H82	108.5 (19)
C6—C5—C4	110.95 (18)	C14—C15—H83	111.0 (13)
C6—C5—H51	105.8 (12)	H81—C15—H83	104.2 (18)
C4—C5—H51	115.6 (12)	H82—C15—H83	110.1 (19)
C6—C5—H52	106.9 (11)	C10—C16—H91	111.5 (12)
C4—C5—H52	112.1 (11)	C10—C16—H92	111.4 (13)
H51—C5—H52	104.8 (17)	H91—C16—H92	105.2 (17)
C5—C6—N1	111.67 (15)	C10—C16—H93	110.6 (15)
C5—C6—H61	113.8 (10)	H91—C16—H93	108.6 (19)
N1—C6—H61	103.3 (10)	H92—C16—H93	109 (2)
C1'—N1—C2—C7	68.55 (19)	C7—N8—C9—C14	−113.3 (2)
C6—N1—C2—C7	−167.68 (15)	C7—N8—C9—C10	68.6 (2)
C1'—N1—C2—C3	−173.34 (18)	C14—C9—C10—C11	0.5 (3)
C6—N1—C2—C3	−49.6 (2)	N8—C9—C10—C11	178.55 (17)
N1—C2—C3—C4	52.7 (2)	C14—C9—C10—C16	−179.3 (2)
C7—C2—C3—C4	170.97 (17)	N8—C9—C10—C16	−1.3 (3)
C2—C3—C4—C5	−57.3 (3)	C9—C10—C11—C12	−1.2 (3)
C3—C4—C5—C6	59.2 (2)	C16—C10—C11—C12	178.7 (2)
C4—C5—C6—N1	−57.2 (2)	C10—C11—C12—C13	1.1 (3)
C1'—N1—C6—C5	176.99 (17)	C11—C12—C13—C14	−0.3 (3)
C2—N1—C6—C5	52.5 (2)	C12—C13—C14—C9	−0.3 (3)
N1—C2—C7—O7	39.7 (2)	C12—C13—C14—C15	178.7 (2)
C3—C2—C7—O7	−80.5 (2)	C10—C9—C14—C13	0.2 (3)
N1—C2—C7—N8	−144.20 (15)	N8—C9—C14—C13	−177.81 (16)
C3—C2—C7—N8	95.59 (19)	C10—C9—C14—C15	−178.77 (18)
O7—C7—N8—C9	5.0 (3)	N8—C9—C14—C15	3.2 (3)
C2—C7—N8—C9	−170.83 (15)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1N···Cl^i	0.905 (17)	2.182 (18)	3.0140 (16)	152.5 (16)
N8—H8N···Cl	0.841 (18)	2.280 (19)	3.1172 (17)	174.1 (17)

Symmetry code: (i) −x, y−1/2, −z+3/2.