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_2108576
_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     dual
_audit_creation_date             2019-03-04
_audit_creation_method
;
Olex2 1.2
(compiled 2018.05.29 svn.r3508 for OlexSys, GUI svn.r5506)
;
_cell_angle_alpha                90
_cell_angle_beta                 91.55(6)
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   8.24(3)
_cell_length_b                   5.4015(9)
_cell_length_c                   19.519(3)
_cell_measurement_reflns_used    690
_cell_measurement_temperature    298(2)
_cell_measurement_theta_max      20.5740
_cell_measurement_theta_min      4.1420
_cell_volume                     868(3)
_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    'ShelXT (Sheldrick, 2015)'
_diffrn_ambient_environment      air
_diffrn_ambient_temperature      298(2)
_diffrn_detector                 'CCD plate'
_diffrn_detector_area_resol_mean 16.2413
_diffrn_detector_type            Eos
_diffrn_measured_fraction_theta_full 0.178
_diffrn_measured_fraction_theta_max 0.157
_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   20.00   0.00 -30.00   0.00    --    73
  2  \f    140.00 200.00   0.75   20.00   0.00 -30.00   0.00    --    80
  3  \f    160.00 217.00   0.75   20.00   0.00  30.00   0.00    --    76
  4  \f    -20.00  34.75   0.75   20.00   0.00  30.00   0.00    --    73
  5  \w    -24.00  24.00   0.75   20.00    --   30.00  39.46 -12.90   64
  6  \w    -24.00  24.00   0.75   20.00    --   30.00  39.46 167.10   64
  7  \w    -50.00  10.00   0.75   20.00    --  -30.00  39.46 167.10   80
  8  \w    -50.00  10.00   0.75   20.00    --  -30.00  39.46 -12.90   80
  9  \w    -64.00  -8.50   0.75   20.00    --  -30.00  81.40 -28.90   74
 10  \w    -64.00  -8.50   0.75   20.00    --  -30.00  81.40 151.10   74
 11  \w    -19.00   8.00   0.75   20.00    --   30.00  81.40 151.10   36
 12  \w    -19.00   8.00   0.75   20.00    --   30.00  81.40 -28.90   36
 13  \w    -43.00 -21.25   0.75   20.00    --   30.00 134.60 -56.90   29
 14  \w    -43.00 -21.25   0.75   20.00    --   30.00 134.60 123.10   29
 15  \w    -90.00 -36.00   0.75   20.00    --  -30.00 134.60 123.10   72
 16  \w    -90.00 -36.00   0.75   20.00    --  -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      0.0867600000
_diffrn_orient_matrix_UB_12      0.0020964000
_diffrn_orient_matrix_UB_13      -0.0008945000
_diffrn_orient_matrix_UB_21      -0.0041789000
_diffrn_orient_matrix_UB_22      0.0874305000
_diffrn_orient_matrix_UB_23      -0.0269222000
_diffrn_orient_matrix_UB_31      0.0019983000
_diffrn_orient_matrix_UB_32      0.0971558000
_diffrn_orient_matrix_UB_33      0.0242020000
_diffrn_radiation_monochromator  graphite
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           MoK\a
_diffrn_radiation_wavelength     0.71073
_diffrn_reflns_av_R_equivalents  0.0382
_diffrn_reflns_av_unetI/netI     0.0152
_diffrn_reflns_Laue_measured_fraction_full 0.178
_diffrn_reflns_Laue_measured_fraction_max 0.157
_diffrn_reflns_limit_h_max       1
_diffrn_reflns_limit_h_min       -1
_diffrn_reflns_limit_k_max       6
_diffrn_reflns_limit_k_min       -6
_diffrn_reflns_limit_l_max       24
_diffrn_reflns_limit_l_min       -23
_diffrn_reflns_number            2925
_diffrn_reflns_point_group_measured_fraction_full 0.178
_diffrn_reflns_point_group_measured_fraction_max 0.157
_diffrn_reflns_theta_full        25.242
_diffrn_reflns_theta_max         26.821
_diffrn_reflns_theta_min         3.914
_diffrn_source                   'fine-focus sealed X-ray tube'
_diffrn_source_type              'Enhance (Mo) X-ray Source'
_exptl_absorpt_coefficient_mu    0.090
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.65044
_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    1.264
_exptl_crystal_description       plate
_exptl_crystal_F_000             352
_exptl_crystal_recrystallization_method
; Crystal grown in diamond-anvil cell from MeOH:EtOH:H2O (VOL. 16:3:1) 
mixture at 0.30 GPa
;
_exptl_crystal_size_max          0.44
_exptl_crystal_size_mid          0.44
_exptl_crystal_size_min          0.1
_refine_diff_density_max         0.054
_refine_diff_density_min         -0.093
_refine_diff_density_rms         0.020
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.163
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     99
_refine_ls_number_reflns         292
_refine_ls_number_restraints     132
_refine_ls_restrained_S_all      0.979
_refine_ls_R_factor_all          0.0730
_refine_ls_R_factor_gt           0.0438
_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^)+(0.0682P)^2^+0.2839P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1085
_refine_ls_wR_factor_ref         0.1308
_reflns_Friedel_coverage         0.000
_reflns_number_gt                197
_reflns_number_total             292
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            lo5062sup1.cif
_cod_data_source_block           BZC_a2
_cod_database_code               2108576
_cod_database_fobs_code          2108576
_shelx_shelxl_version_number     2014/7
_chemical_oxdiff_formula         'C36  H44  N4  O8  '
_shelx_estimated_absorpt_t_max   0.991
_shelx_estimated_absorpt_t_min   0.962
_reflns_odcompleteness_completeness 15.40
_reflns_odcompleteness_iscentric 1
_reflns_odcompleteness_theta     26.76
_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 0.005
3. Rigid bond restraints
 C7, O2, O1
 with sigma for 1-2 distances of 0.01 and sigma for 1-3 distances of 0.01
 C1, N1
 with sigma for 1-2 distances of 0.01 and sigma for 1-3 distances of 0.01
 C7, C4
 with sigma for 1-2 distances of 0.01 and sigma for 1-3 distances of 0.01
4. Uiso/Uaniso restraints and constraints
O2 \\sim C7 \\sim O1: within 2A with sigma of 0.02 and sigma for terminal atoms
of 0.04
C3 \\sim C2 \\sim C1 \\sim C6 \\sim C5 \\sim C4: within 2A with sigma of 0.01
and sigma for terminal atoms of 0.02
C9 \\sim C8: within 2A with sigma of 0.04 and sigma for terminal atoms of 0.08
Uanis(C7) \\sim Ueq: with sigma of 0.01 and sigma for terminal atoms of 0.02
Uanis(C4) \\sim Ueq, Uanis(C3) \\sim Ueq, Uanis(C2) \\sim Ueq, Uanis(C1) \\sim
Ueq, Uanis(C6) \\sim Ueq, Uanis(C5) \\sim Ueq: with sigma of 0.01 and sigma for
terminal atoms of 0.02
Uanis(N1) \\sim Ueq, Uanis(C1) \\sim Ueq, Uanis(C6) \\sim Ueq, Uanis(C5) \\sim
Ueq, Uanis(C4) \\sim Ueq, Uanis(C3) \\sim Ueq, Uanis(C2) \\sim Ueq, Uanis(O1)
\\sim Ueq, Uanis(O2) \\sim Ueq, Uanis(C8) \\sim Ueq, Uanis(C9) \\sim Ueq: with
sigma of 0.05 and sigma for terminal atoms of 0.1
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:
 C6(H6), C5(H5), C3(H3), C2(H2)
5.d Fitted hexagon refined as free rotating group:
 C1(C6,C5,C4,C3,C2)
5.e Idealised Me refined as rotating group:
 C9(H9A,H9B,H9C)
;
_shelx_res_checksum              38490
_shelx_hkl_checksum              89001
_olex2_exptl_crystal_mounting_method 'Crystal mounted in diamond-anvil cell'
_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 1.556
_oxdiff_exptl_absorpt_empirical_full_min 0.823