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_2108575
_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
_cell_angle_alpha                90
_cell_angle_beta                 91.47(4)
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   8.1928(6)
_cell_length_b                   5.4539(5)
_cell_length_c                   20.07(5)
_cell_measurement_reflns_used    592
_cell_measurement_temperature    295
_cell_measurement_theta_max      21.5190
_cell_measurement_theta_min      4.4560
_cell_volume                     896(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      295
_diffrn_detector                 'CCD plate'
_diffrn_detector_area_resol_mean 16.2413
_diffrn_detector_type            Eos
_diffrn_measured_fraction_theta_full 0.190
_diffrn_measured_fraction_theta_max 0.169
_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      -0.0067068000
_diffrn_orient_matrix_UB_12      0.0025911000
_diffrn_orient_matrix_UB_13      -0.0357084000
_diffrn_orient_matrix_UB_21      0.0748404000
_diffrn_orient_matrix_UB_22      -0.0632422000
_diffrn_orient_matrix_UB_23      -0.0018759000
_diffrn_orient_matrix_UB_31      -0.0421601000
_diffrn_orient_matrix_UB_32      -0.1127391000
_diffrn_orient_matrix_UB_33      0.0001331000
_diffrn_radiation_monochromator  graphite
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           MoK\a
_diffrn_radiation_wavelength     0.71073
_diffrn_reflns_av_R_equivalents  0.0989
_diffrn_reflns_av_unetI/netI     0.0663
_diffrn_reflns_Laue_measured_fraction_full 0.190
_diffrn_reflns_Laue_measured_fraction_max 0.169
_diffrn_reflns_limit_h_max       10
_diffrn_reflns_limit_h_min       -10
_diffrn_reflns_limit_k_max       6
_diffrn_reflns_limit_k_min       -6
_diffrn_reflns_limit_l_max       4
_diffrn_reflns_limit_l_min       -4
_diffrn_reflns_number            442
_diffrn_reflns_point_group_measured_fraction_full 0.190
_diffrn_reflns_point_group_measured_fraction_max 0.169
_diffrn_reflns_theta_full        25.242
_diffrn_reflns_theta_max         26.972
_diffrn_reflns_theta_min         3.872
_diffrn_source                   'fine-focus sealed X-ray tube'
_diffrn_source_type              'Enhance (Mo) X-ray Source'
_exptl_absorpt_coefficient_mu    0.087
_exptl_absorpt_correction_type   none
_exptl_crystal_colour            colourless
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    1.224
_exptl_crystal_description       needle
_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 0.10 GPa
;
_exptl_crystal_size_max          0.43
_exptl_crystal_size_mid          0.1
_exptl_crystal_size_min          0.1
_refine_diff_density_max         0.086
_refine_diff_density_min         -0.070
_refine_diff_density_rms         0.024
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   0.962
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     100
_refine_ls_number_reflns         442
_refine_ls_number_restraints     123
_refine_ls_restrained_S_all      0.863
_refine_ls_R_factor_all          0.1218
_refine_ls_R_factor_gt           0.0610
_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^)+(0.1127P)^2^] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1485
_refine_ls_wR_factor_ref         0.1681
_reflns_Friedel_coverage         0.000
_reflns_number_gt                238
_reflns_number_total             442
_reflns_threshold_expression     'I > 2\s(I)'
_twin_special_details
;
Component 2 rotated by 179.9860\% 
 around [0.00 -0.00 1.00] (reciprocal) or [0.07 0.00 1.00] (direct)
;
_cod_data_source_file            lo5062sup1.cif
_cod_data_source_block           BZC_a1
_cod_database_code               2108575
_cod_database_fobs_code          2108575
_chemical_oxdiff_formula         'C36  H44  N4  O8  '
_shelx_estimated_absorpt_t_max   0.991
_shelx_estimated_absorpt_t_min   0.964
_olex2_refinement_description
;
1. Twinned data refinement
 Scales: 0.725(7)
 0.275(7)
2. 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
3. Restrained planarity
 N1, C1, C6, C5, C4, C7, C3, C2
 with sigma of 0.01
4. Rigid bond restraints
 C8, C9, O2
 with sigma for 1-2 distances of 0.01 and sigma for 1-3 distances of 0.02
 N1, C1
 with sigma for 1-2 distances of 0.01 and sigma for 1-3 distances of 0.01
5. Uiso/Uaniso restraints and constraints
C9 \\sim C8: within 2A with sigma of 0.01 and sigma for terminal atoms of 0.02
O1 \\sim O2: within 2A with sigma of 0.01 and sigma for terminal atoms of 0.02
O1 \\sim C7 \\sim O2: within 2A with sigma of 0.01 and sigma for terminal atoms
of 0.02
C4 \\sim C5 \\sim C6 \\sim C1 \\sim C3 \\sim C2: within 2A with sigma of 0.04
and sigma for terminal atoms of 0.08
Uanis(C8) \\sim Ueq, Uanis(C9) \\sim Ueq: with sigma of 0.05 and sigma for
terminal atoms of 0.1
Uanis(C7) \\sim Ueq, Uanis(C4) \\sim Ueq, Uanis(C5) \\sim Ueq, Uanis(C6) \\sim
Ueq, Uanis(C1) \\sim Ueq, Uanis(C2) \\sim Ueq, Uanis(C3) \\sim Ueq, Uanis(N1)
\\sim Ueq: with sigma of 0.1 and sigma for terminal atoms of 0.2
6.a Rotating group:
 N1(H1A,H1B)
6.b Secondary CH2 refined with riding coordinates:
 C8(H8A,H8B)
6.c Aromatic/amide H refined with riding coordinates:
 C3(H3), C2(H2), C6(H6), C5(H5)
6.d Fitted hexagon refined as free rotating group:
 C4(C3,C2,C1,C6,C5)
6.e Idealised Me refined as rotating group:
 C9(H9A,H9B,H9C)
;
_shelx_res_checksum              35986
_shelx_hkl_checksum              60226
_olex2_submission_special_instructions 'No special instructions were received'
_oxdiff_exptl_absorpt_empirical_details
;
Empirical correction (ABSPACK) includes:
- Frame scaling
;
_oxdiff_exptl_absorpt_empirical_full_max 1.266
_oxdiff_exptl_absorpt_empirical_full_min 0.865
_oxdiff_twin_integration_method  simultaneous
_oxdiff_twin_items               2