Design, Synthesis, and Evaluation of a Series of Novel Benzocyclobutene Derivatives as General Anesthetics.
Zhang, Chen; Li, Fangqiong; Yu, Yan; Huang, Anbang; He, Ping; Lei, Ming; Wang, Jianmin; Huang, Longbin; Liu, Zhenhong; Liu, Jianyu; Wei, Yonggang; Journal of medicinal chemistry  (2017) –; doi:10.1021/acs.jmedchem.7b00253

data_1545901
_publ_section_title
;
 Design, Synthesis, and Evaluation of a Series of Novel Benzocyclobutene
 Derivatives as General Anesthetics.
;
_journal_name_full               'Journal of medicinal chemistry'
_journal_paper_doi               10.1021/acs.jmedchem.7b00253
_journal_year                    2017
_chemical_absolute_configuration unk
_chemical_formula_moiety         'C22 H28 O4'
_chemical_formula_sum            'C22 H28 O4'
_chemical_formula_weight         356.44
_space_group_crystal_system      orthorhombic
_space_group_IT_number           19
_space_group_name_Hall           'P 2ac 2ab'
_space_group_name_H-M_alt        'P 21 21 21'
_symmetry_space_group_name_Hall  'P 2ac 2ab'
_symmetry_space_group_name_H-M   'P 21 21 21'
_atom_sites_solution_hydrogens   geom
_atom_sites_solution_primary     iterative
_audit_creation_date             2016-06-16
_audit_creation_method
;
Olex2 1.2
(compiled 2016.02.19 svn.r3266 for OlexSys, GUI svn.r5155)
;
_audit_update_record
;
2016-09-27 deposited with the CCDC.
2017-02-15 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 90
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   6.1077(7)
_cell_length_b                   15.287(2)
_cell_length_c                   21.901(2)
_cell_measurement_reflns_used    1682
_cell_measurement_temperature    293(2)
_cell_measurement_theta_max      22.7570
_cell_measurement_theta_min      3.4500
_cell_volume                     2044.9(4)
_computing_cell_refinement
;
CrysAlisPro, Agilent Technologies,
Version 1.171.37.35 (release 13-08-2014 CrysAlis171 .NET)
(compiled Aug 13 2014,18:06:01)
;
_computing_data_collection
;
CrysAlisPro, Agilent Technologies,
Version 1.171.37.35 (release 13-08-2014 CrysAlis171 .NET)
(compiled Aug 13 2014,18:06:01)
;
_computing_data_reduction
;
CrysAlisPro, Agilent Technologies,
Version 1.171.37.35 (release 13-08-2014 CrysAlis171 .NET)
(compiled Aug 13 2014,18:06:01)
;
_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    'olex2.solve (Bourhis et al., 2015)'
_diffrn_ambient_temperature      293.15
_diffrn_detector                 'CCD plate'
_diffrn_detector_area_resol_mean 16.0874
_diffrn_detector_type            Eos
_diffrn_measured_fraction_theta_full 0.997
_diffrn_measured_fraction_theta_max 0.998
_diffrn_measurement_details
;
  1 omega  -43.00  -16.00   1.0000   10.0000
omega____ theta____ kappa____ phi______ frames
    -       16.6856  -57.0000 -120.0000 27

  2 omega  -21.00    6.00   1.0000   10.0000
omega____ theta____ kappa____ phi______ frames
    -      -14.9669  -99.0000 -120.0000 27

  3 omega  -78.00    2.00   1.0000   10.0000
omega____ theta____ kappa____ phi______ frames
    -      -14.9669  -19.0000 -180.0000 80

  4 omega  -10.00   27.00   1.0000   10.0000
omega____ theta____ kappa____ phi______ frames
    -       16.6856   77.0000   60.0000 37
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'Xcalibur, Eos'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_UB_11      -0.0412487000
_diffrn_orient_matrix_UB_12      0.0035038000
_diffrn_orient_matrix_UB_13      0.0301871000
_diffrn_orient_matrix_UB_21      0.0258742000
_diffrn_orient_matrix_UB_22      -0.0445676000
_diffrn_orient_matrix_UB_23      0.0052933000
_diffrn_orient_matrix_UB_31      0.1054146000
_diffrn_orient_matrix_UB_32      0.0123842000
_diffrn_orient_matrix_UB_33      0.0105039000
_diffrn_radiation_monochromator  graphite
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           MoK\a
_diffrn_radiation_wavelength     0.71073
_diffrn_reflns_av_R_equivalents  0.0543
_diffrn_reflns_av_unetI/netI     0.0824
_diffrn_reflns_Laue_measured_fraction_full 0.997
_diffrn_reflns_Laue_measured_fraction_max 0.998
_diffrn_reflns_limit_h_max       5
_diffrn_reflns_limit_h_min       -7
_diffrn_reflns_limit_k_max       17
_diffrn_reflns_limit_k_min       -19
_diffrn_reflns_limit_l_max       24
_diffrn_reflns_limit_l_min       -27
_diffrn_reflns_number            7051
_diffrn_reflns_point_group_measured_fraction_full 0.953
_diffrn_reflns_point_group_measured_fraction_max 0.940
_diffrn_reflns_theta_full        25.242
_diffrn_reflns_theta_max         26.371
_diffrn_reflns_theta_min         3.092
_diffrn_source                   'Enhance (Mo) X-ray Source'
_exptl_absorpt_coefficient_mu    0.078
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.56632
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
CrysAlisPro, Agilent Technologies,
Version 1.171.37.35 (release 13-08-2014 CrysAlis171 .NET)
(compiled Aug 13 2014,18:06:01)
Empirical absorption correction using spherical harmonics,
 implemented in SCALE3 ABSPACK scaling algorithm.
;
_exptl_crystal_density_diffrn    1.158
_exptl_crystal_density_method    'not measured'
_exptl_crystal_description       block
_exptl_crystal_F_000             768
_exptl_crystal_size_max          0.4
_exptl_crystal_size_mid          0.3
_exptl_crystal_size_min          0.2
_refine_diff_density_max         0.207
_refine_diff_density_min         -0.202
_refine_diff_density_rms         0.051
_refine_ls_abs_structure_details
;
 Flack x determined using 689 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons and Flack (2004), Acta Cryst. A60, s61).
;
_refine_ls_abs_structure_Flack   3.1(10)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.045
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     241
_refine_ls_number_reflns         3946
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.045
_refine_ls_R_factor_all          0.1090
_refine_ls_R_factor_gt           0.0720
_refine_ls_shift/su_max          0.001
_refine_ls_shift/su_mean         0.000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
;
 w=1/[\s^2^(Fo^2^)+(0.0847P)^2^+0.0711P]
 where P=(Fo^2^+2Fc^2^)/3
;
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1654
_refine_ls_wR_factor_ref         0.2010
_reflns_Friedel_coverage         0.627
_reflns_Friedel_fraction_full    0.891
_reflns_Friedel_fraction_max     0.860
_reflns_number_gt                2475
_reflns_number_total             3946
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            jm7b00253_si_004.cif
_cod_data_source_block           160526_s1_hsk_hp
_cod_database_code               1545901
_shelxl_version_number           2013-2
_chemical_oxdiff_formula         c12h12o2
_shelx_estimated_absorpt_t_max   0.985
_shelx_estimated_absorpt_t_min   0.969
_reflns_odcompleteness_completeness 99.67
_reflns_odcompleteness_iscentric 1
_reflns_odcompleteness_theta     26.32
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All C(H,H) groups
 At 1.5 times of:
  All C(H,H,H) groups
2.a Ternary CH refined with riding coordinates:
 C13(H13), C20(H20)
2.b Secondary CH2 refined with riding coordinates:
 C2(H2A,H2B), C3(H3A,H3B), C14(H14A,H14B)
2.c Aromatic/amide H refined with riding coordinates:
 C16(H16), C17(H17)
2.d Idealised Me refined as rotating group:
 C7(H7A,H7B,H7C), C8(H8A,H8B,H8C), C9(H9A,H9B,H9C), C19(H19A,H19B,H19C),
 C21(H21A,H21B,H21C), C22(H22A,H22B,H22C)
;
_shelx_res_checksum              85615
_shelx_hkl_checksum              81552
_olex2_submission_special_instructions 'No special instructions were received'