A new high-pressure benzocaine polymorph — towards understanding the molecular aggregation in crystals of an important active pharmaceutical ingredient (API)
Patyk-Kaźmierczak, Ewa; Kaźmierczak, Michał; Acta Crystallographica Section B 76 (2020) –; doi:10.1107/S2052520619016548

data_2108582
_publ_section_title
;
 A new high-pressure benzocaine polymorph --- towards understanding the
 molecular aggregation in crystals of an important active pharmaceutical
 ingredient (API)
;
_journal_coeditor_code           LO5062SUP1
_journal_issue                   1
_journal_name_full               'Acta Crystallographica Section B'
_journal_page_first
;
;
_journal_paper_doi               10.1107/S2052520619016548
_journal_volume                  76
_journal_year                    2020
_chemical_formula_moiety         'C9 H11 N O2'
_chemical_formula_sum            'C9 H11 N O2'
_chemical_formula_weight         165.19
_chemical_name_common            Benzocaine
_chemical_name_systematic        '4-aminobenzoic acid ethyl ester'
_space_group_crystal_system      monoclinic
_space_group_IT_number           14
_space_group_name_Hall           '-P 2ybc'
_space_group_name_H-M_alt        'P 1 21/c 1'
_atom_sites_solution_hydrogens   mixed
_atom_sites_solution_primary     direct
_audit_creation_date             2019-03-14
_audit_creation_method
;
Olex2 1.2
(compiled 2018.05.29 svn.r3508 for OlexSys, GUI svn.r5506)
;
_cell_angle_alpha                90
_cell_angle_beta                 96.58(6)
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   6.3399(8)
_cell_length_b                   5.1789(6)
_cell_length_c                   24.80(7)
_cell_measurement_reflns_used    1183
_cell_measurement_temperature    298(2)
_cell_measurement_theta_max      26.2030
_cell_measurement_theta_min      3.2040
_cell_volume                     809(2)
_computing_cell_refinement       'CrysAlisPro 1.171.38.41 (Rigaku OD, 2015)'
_computing_data_collection       'CrysAlisPro 1.171.38.41 (Rigaku OD, 2015)'
_computing_data_reduction        'CrysAlisPro 1.171.38.41 (Rigaku OD, 2015)'
_computing_molecular_graphics    'Olex2 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 (Dolomanov et al., 2009)'
_computing_structure_refinement  'ShelXL (Sheldrick, 2015)'
_computing_structure_solution    'ShelXS (Sheldrick, 2008)'
_diffrn_ambient_temperature      298(2)
_diffrn_detector                 'CCD plate'
_diffrn_detector_area_resol_mean 8.0772
_diffrn_detector_type            Eos
_diffrn_measured_fraction_theta_full 0.214
_diffrn_measured_fraction_theta_max 0.208
_diffrn_measurement_details
;
List of Runs (angles in degrees, time in seconds):

  # Type    Start    End  Width  t~exp~   \w     \q     \k     \f   Frames
--------------------------------------------------------------------------
  1  \f    -35.00  19.75   0.75   32.00   0.00 -30.00   0.00    --    73
  2  \f    140.00 200.00   0.75   32.00   0.00 -30.00   0.00    --    80
  3  \f    160.00 217.00   0.75   32.00   0.00  30.00   0.00    --    76
  4  \f    -20.00  34.75   0.75   32.00   0.00  30.00   0.00    --    73
  5  \w    -24.00  24.00   0.75   32.00    --   30.00  39.46 -12.90   64
  6  \w    -24.00  24.00   0.75   32.00    --   30.00  39.46 167.10   64
  7  \w    -50.00  10.00   0.75   32.00    --  -30.00  39.46 167.10   80
  8  \w    -50.00  10.00   0.75   32.00    --  -30.00  39.46 -12.90   80
  9  \w    -64.00  -8.50   0.75   32.00    --  -30.00  81.40 -28.90   74
 10  \w    -64.00  -8.50   0.75   32.00    --  -30.00  81.40 151.10   74
 11  \w    -19.00   8.00   0.75   32.00    --   30.00  81.40 151.10   36
 12  \w    -19.00   8.00   0.75   32.00    --   30.00  81.40 -28.90   36
 13  \w    -43.00 -21.25   0.75   32.00    --   30.00 134.60 -56.90   29
 14  \w    -43.00 -21.25   0.75   32.00    --   30.00 134.60 123.10   29
 15  \w    -90.00 -36.00   0.75   32.00    --  -30.00 134.60 123.10   72
 16  \w    -90.00 -36.00   0.75   32.00    --  -30.00 134.60 -56.90   72
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'Xcalibur, Eos'
_diffrn_measurement_method       '\w and \f scans'
_diffrn_orient_matrix_type
'CrysAlisPro convention (1999,Acta A55,543-557)'
_diffrn_orient_matrix_UB_11      -0.0100594000
_diffrn_orient_matrix_UB_12      -0.0070403000
_diffrn_orient_matrix_UB_13      -0.0290503000
_diffrn_orient_matrix_UB_21      -0.0911743000
_diffrn_orient_matrix_UB_22      0.0790266000
_diffrn_orient_matrix_UB_23      -0.0014090000
_diffrn_orient_matrix_UB_31      0.0643353000
_diffrn_orient_matrix_UB_32      0.1107245000
_diffrn_orient_matrix_UB_33      -0.0007739000
_diffrn_radiation_monochromator  graphite
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           MoK\a
_diffrn_radiation_wavelength     0.71073
_diffrn_reflns_av_R_equivalents  0.1179
_diffrn_reflns_av_unetI/netI     0.0625
_diffrn_reflns_Laue_measured_fraction_full 0.214
_diffrn_reflns_Laue_measured_fraction_max 0.208
_diffrn_reflns_limit_h_max       7
_diffrn_reflns_limit_h_min       -7
_diffrn_reflns_limit_k_max       6
_diffrn_reflns_limit_k_min       -6
_diffrn_reflns_limit_l_max       6
_diffrn_reflns_limit_l_min       -6
_diffrn_reflns_number            2846
_diffrn_reflns_point_group_measured_fraction_full 0.214
_diffrn_reflns_point_group_measured_fraction_max 0.208
_diffrn_reflns_theta_full        25.242
_diffrn_reflns_theta_max         25.935
_diffrn_reflns_theta_min         3.235
_diffrn_source                   'fine-focus sealed X-ray tube'
_diffrn_source_type              'Enhance (Mo) X-ray Source'
_exptl_absorpt_coefficient_mu    0.096
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.41496
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.38.41 (Rigaku Oxford Diffraction, 2015)
Empirical absorption correction using spherical harmonics,
 implemented in SCALE3 ABSPACK scaling algorithm.
;
_exptl_crystal_colour            colourless
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    1.356
_exptl_crystal_description       plate
_exptl_crystal_F_000             352
_exptl_crystal_recrystallization_method
; Crystal grown at high-pressure in diamond-anvil cell from 97.5% DMSO 
solution in water, at 0.52 GPa
;
_exptl_crystal_size_max          0.47
_exptl_crystal_size_mid          0.31
_exptl_crystal_size_min          0.1
_refine_diff_density_max         0.178
_refine_diff_density_min         -0.143
_refine_diff_density_rms         0.044
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.164
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     99
_refine_ls_number_reflns         328
_refine_ls_number_restraints     134
_refine_ls_restrained_S_all      0.991
_refine_ls_R_factor_all          0.1348
_refine_ls_R_factor_gt           0.0931
_refine_ls_shift/su_max          0.000
_refine_ls_shift/su_mean         0.000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'w=1/[\s^2^(Fo^2^)+(0.1640P)^2^+0.6950P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.2298
_refine_ls_wR_factor_ref         0.2797
_reflns_Friedel_coverage         0.000
_reflns_number_gt                209
_reflns_number_total             328
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            lo5062sup1.cif
_cod_data_source_block           BZC_b3
_cod_database_code               2108582
_cod_database_fobs_code          2108582
_shelx_shelxl_version_number     2014/7
_chemical_oxdiff_formula         'C36  H44  N4  O8  '
_shelx_estimated_absorpt_t_max   0.990
_shelx_estimated_absorpt_t_min   0.956
_reflns_odcompleteness_completeness 18.39
_reflns_odcompleteness_iscentric 1
_reflns_odcompleteness_theta     27.94
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All C(H,H) groups, All N(H,H) groups
 At 1.5 times of:
  All C(H,H,H) groups
2. Restrained distances
 C7-C4
 1.5 with sigma of 0.002
3. Rigid bond restraints
 N1, C1
 with sigma for 1-2 distances of 0.01 and sigma for 1-3 distances of 0.01
4. Uiso/Uaniso restraints and constraints
C6 \\sim C1 \\sim C2 \\sim C3 \\sim C4 \\sim C5: within 2A with sigma of 0.02
and sigma for terminal atoms of 0.04
O1 \\sim C7 \\sim O2 \\sim C8 \\sim C9: within 2A with sigma of 0.01 and sigma
for terminal atoms of 0.02
Uanis(N1) \\sim Ueq: with sigma of 0.01 and sigma for terminal atoms of 0.02
Uanis(C4) \\sim Ueq, Uanis(O1) \\sim Ueq, Uanis(C7) \\sim Ueq, Uanis(O2) \\sim
Ueq, Uanis(C8) \\sim Ueq, Uanis(C5) \\sim Ueq, Uanis(C3) \\sim Ueq, Uanis(C9)
\\sim Ueq, Uanis(C6) \\sim Ueq, Uanis(C2) \\sim Ueq, Uanis(C1) \\sim Ueq: with
sigma of 0.04 and sigma for terminal atoms of 0.08
5.a Rotating group:
 N1(H1A,H1B)
5.b Secondary CH2 refined with riding coordinates:
 C8(H8A,H8B)
5.c Aromatic/amide H refined with riding coordinates:
 C5(H5), C6(H6), C2(H2), C3(H3)
5.d Fitted hexagon refined as free rotating group:
 C4(C5,C6,C1,C2,C3)
5.e Idealised Me refined as rotating group:
 C9(H9A,H9B,H9C)
;
_shelx_res_checksum              68846
_shelx_hkl_checksum              97763
_olex2_exptl_crystal_mounting_method
'Crystal mounted in diamond-anvil cell at 0.52 GPa'
_olex2_submission_special_instructions 'No special instructions were received'
_oxdiff_exptl_absorpt_empirical_details
;
Empirical correction (ABSPACK) includes:
- Absorption correction using spherical harmonics
- Frame scaling
;
_oxdiff_exptl_absorpt_empirical_full_max 2.306
_oxdiff_exptl_absorpt_empirical_full_min 0.509