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_2108577
_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             2019-03-11
_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(8)
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   6.3050(10)
_cell_length_b                   5.1839(4)
_cell_length_c                   24.94(8)
_cell_measurement_reflns_used    982
_cell_measurement_temperature    298(2)
_cell_measurement_theta_max      26.1700
_cell_measurement_theta_min      3.9550
_cell_volume                     810(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    'ShelXS (Sheldrick, 2008)'
_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 0.172
_diffrn_measured_fraction_theta_max 0.161
_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      -0.0161614000
_diffrn_orient_matrix_UB_12      -0.0041648000
_diffrn_orient_matrix_UB_13      -0.0291109000
_diffrn_orient_matrix_UB_21      -0.1047351000
_diffrn_orient_matrix_UB_22      -0.0443847000
_diffrn_orient_matrix_UB_23      0.0011831000
_diffrn_orient_matrix_UB_31      -0.0367870000
_diffrn_orient_matrix_UB_32      0.1280124000
_diffrn_orient_matrix_UB_33      -0.0004338000
_diffrn_radiation_monochromator  graphite
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           MoK\a
_diffrn_radiation_wavelength     0.71073
_diffrn_reflns_av_R_equivalents  0.0518
_diffrn_reflns_av_unetI/netI     0.0377
_diffrn_reflns_Laue_measured_fraction_full 0.172
_diffrn_reflns_Laue_measured_fraction_max 0.161
_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            2490
_diffrn_reflns_point_group_measured_fraction_full 0.172
_diffrn_reflns_point_group_measured_fraction_max 0.161
_diffrn_reflns_theta_full        25.242
_diffrn_reflns_theta_max         26.476
_diffrn_reflns_theta_min         4.016
_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  0.11144
_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    1.354
_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 0.55 GPa
;
_exptl_crystal_size_max          0.42
_exptl_crystal_size_mid          0.34
_exptl_crystal_size_min          0.1
_refine_diff_density_max         0.113
_refine_diff_density_min         -0.105
_refine_diff_density_rms         0.034
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.062
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     99
_refine_ls_number_reflns         270
_refine_ls_number_restraints     125
_refine_ls_restrained_S_all      0.825
_refine_ls_R_factor_all          0.0712
_refine_ls_R_factor_gt           0.0627
_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^)+(0.1321P)^2^+0.4918P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1584
_refine_ls_wR_factor_ref         0.1717
_reflns_Friedel_coverage         0.000
_reflns_number_gt                225
_reflns_number_total             270
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            lo5062sup1.cif
_cod_data_source_block           BZC_a3
_cod_database_code               2108577
_cod_database_fobs_code          2108577
_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   0.961
_reflns_odcompleteness_completeness 16.01
_reflns_odcompleteness_iscentric 1
_reflns_odcompleteness_theta     26.42
_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
 with sigma for 1-2 distances of 0.01 and sigma for 1-3 distances of 0.01
 N1, C1
 with sigma for 1-2 distances of 0.005 and sigma for 1-3 distances of 0.005
 O1, O2, C7
 with sigma for 1-2 distances of 0.005 and sigma for 1-3 distances of 0.005
 O2, C7
 with sigma for 1-2 distances of 0.01 and sigma for 1-3 distances of 0.01
 O2, C8
 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 0.02 and sigma for terminal atoms of 0.04
C8 \\sim C9: within 2A with sigma of 0.02 and sigma for terminal atoms of 0.04
O2 \\sim O1: within 2A with sigma of 0.02 and sigma for terminal atoms of 0.04
Uanis(N1) \\sim Ueq: with sigma of 0.03 and sigma for terminal atoms of 0.06
Uanis(C9) \\sim Ueq: with sigma of 0.05 and sigma for terminal atoms of 0.1
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(C7) \\sim Ueq, Uanis(C8)
\\sim Ueq: with sigma of 0.1 and sigma for terminal atoms of 0.2
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              54812
_shelx_hkl_checksum              66911
_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 7.215
_oxdiff_exptl_absorpt_empirical_full_min 0.727