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_2108578
_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             2019-03-12
_audit_creation_method
;
Olex2 1.2
(compiled 2018.05.29 svn.r3508 for OlexSys, GUI svn.r5506)
;
_cell_angle_alpha                90
_cell_angle_beta                 96.25(6)
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   6.3679(8)
_cell_length_b                   5.1671(6)
_cell_length_c                   24.58(8)
_cell_measurement_reflns_used    880
_cell_measurement_temperature    298(2)
_cell_measurement_theta_max      23.3280
_cell_measurement_theta_min      4.0310
_cell_volume                     804(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_temperature      298(2)
_diffrn_detector                 'CCD plate'
_diffrn_detector_area_resol_mean 16.2413
_diffrn_detector_type            Eos
_diffrn_measured_fraction_theta_full 0.194
_diffrn_measured_fraction_theta_max 0.176
_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      0.0071361000
_diffrn_orient_matrix_UB_12      -0.0088220000
_diffrn_orient_matrix_UB_13      0.0290095000
_diffrn_orient_matrix_UB_21      -0.1067769000
_diffrn_orient_matrix_UB_22      0.0396716000
_diffrn_orient_matrix_UB_23      -0.0007471000
_diffrn_orient_matrix_UB_31      -0.0328409000
_diffrn_orient_matrix_UB_32      -0.1309254000
_diffrn_orient_matrix_UB_33      -0.0021934000
_diffrn_radiation_monochromator  graphite
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           MoK\a
_diffrn_radiation_wavelength     0.71073
_diffrn_reflns_av_R_equivalents  0.0492
_diffrn_reflns_av_unetI/netI     0.0343
_diffrn_reflns_Laue_measured_fraction_full 0.194
_diffrn_reflns_Laue_measured_fraction_max 0.176
_diffrn_reflns_limit_h_max       8
_diffrn_reflns_limit_h_min       -7
_diffrn_reflns_limit_k_max       6
_diffrn_reflns_limit_k_min       -6
_diffrn_reflns_limit_l_max       5
_diffrn_reflns_limit_l_min       -5
_diffrn_reflns_number            2457
_diffrn_reflns_point_group_measured_fraction_full 0.194
_diffrn_reflns_point_group_measured_fraction_max 0.176
_diffrn_reflns_theta_full        25.242
_diffrn_reflns_theta_max         26.544
_diffrn_reflns_theta_min         4.031
_diffrn_source                   'fine-focus sealed X-ray tube'
_diffrn_source_type              'Enhance (Mo) X-ray Source'
_exptl_absorpt_coefficient_mu    0.097
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.05406
_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    1.365
_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 0.78 GPa was decompressed to 0.65 GPa and measured
;
_exptl_crystal_size_max          0.43
_exptl_crystal_size_mid          0.31
_exptl_crystal_size_min          0.1
_refine_diff_density_max         0.083
_refine_diff_density_min         -0.081
_refine_diff_density_rms         0.019
_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         296
_refine_ls_number_restraints     142
_refine_ls_restrained_S_all      0.915
_refine_ls_R_factor_all          0.0626
_refine_ls_R_factor_gt           0.0435
_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^)+(0.0471P)^2^+0.3983P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0970
_refine_ls_wR_factor_ref         0.1044
_reflns_Friedel_coverage         0.000
_reflns_number_gt                223
_reflns_number_total             296
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            lo5062sup1.cif
_cod_data_source_block           BZC_a4
_cod_database_code               2108578
_cod_database_fobs_code          2108578
_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   0.959
_reflns_odcompleteness_completeness 17.26
_reflns_odcompleteness_iscentric 1
_reflns_odcompleteness_theta     26.49
_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. Rigid bond restraints
 C1, C2, C3, C4, C5, C6, C7
 with sigma for 1-2 distances of 0.01 and sigma for 1-3 distances of 0.01
 O1, O2, C7, C8, C9
 with sigma for 1-2 distances of 0.01 and sigma for 1-3 distances of 0.01
3. Uiso/Uaniso restraints and constraints
C1 \\sim C2 \\sim C3 \\sim C4 \\sim C5 \\sim C6 \\sim C7: within 2A with sigma
of 0.04 and sigma for terminal atoms of 0.08
C8 \\sim C9: within 2A with sigma of 0.04 and sigma for terminal atoms of 0.08
O1 \\sim O2 \\sim C7 \\sim C8 \\sim C9: within 2A with sigma of 0.02 and sigma
for terminal atoms of 0.04
Uanis(O1) \\sim Ueq: with sigma of 0.02 and sigma for terminal atoms of 0.04
Uanis(C2) \\sim Ueq, Uanis(C1) \\sim Ueq, Uanis(C6) \\sim Ueq, Uanis(N1) \\sim
Ueq, Uanis(C5) \\sim Ueq, Uanis(C4) \\sim Ueq, Uanis(C3) \\sim Ueq, Uanis(C7)
\\sim Ueq: with sigma of 0.02 and sigma for terminal atoms of 0.04
4.a Rotating group:
 N1(H1A,H1B)
4.b Secondary CH2 refined with riding coordinates:
 C8(H8A,H8B)
4.c Aromatic/amide H refined with riding coordinates:
 C5(H5), C6(H6), C2(H2), C3(H3)
4.d Fitted hexagon refined as free rotating group:
 C4(C5,C6,C1,C2,C3)
4.e Idealised Me refined as rotating group:
 C9(H9A,H9B,H9C)
;
_shelx_res_checksum              90867
_shelx_hkl_checksum              64591
_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 13.388
_oxdiff_exptl_absorpt_empirical_full_min 0.583