Chemoselective Minisci alkylation in aqueous medium: a general strategy for functionalization of complex N-heteroarenes and biomolecules
Hu, Qi-Long; Deng, Jun-Jie; Ye, Jia; Li, Jian; Chan, Albert S. C.; Su, Hang; Xiong, Xiao-Feng; Green Chemistry 27 (2025) 13944–13952; doi:10.1039/D5GC04621A

data_7251025
_publ_section_title
;
 Chemoselective Minisci alkylation in aqueous medium: a general strategy
 for functionalization of complex N-heteroarenes and biomolecules
;
_journal_issue                   43
_journal_name_full               'Green Chemistry'
_journal_page_first              13944
_journal_page_last               13952
_journal_paper_doi               10.1039/D5GC04621A
_journal_volume                  27
_journal_year                    2025
_chemical_formula_moiety         'C2 F3 O2, C11 H15 N2'
_chemical_formula_sum            'C13 H15 F3 N2 O2'
_chemical_formula_weight         288.27
_space_group_crystal_system      triclinic
_space_group_IT_number           2
_space_group_name_Hall           '-P 1'
_space_group_name_H-M_alt        'P -1'
_atom_sites_solution_hydrogens   mixed
_atom_sites_solution_primary     dual
_audit_creation_date             2023-12-14
_audit_creation_method
;
Olex2 1.3
(compiled 2020.11.12 svn.r5f609507 for OlexSys, GUI svn.r6408)
;
_audit_update_record
;
2024-03-13 deposited with the CCDC.	2025-10-09 downloaded from the CCDC.
;
_cell_angle_alpha                81.611(3)
_cell_angle_beta                 78.193(3)
_cell_angle_gamma                67.255(3)
_cell_formula_units_Z            4
_cell_length_a                   9.8820(3)
_cell_length_b                   11.9858(4)
_cell_length_c                   12.7550(4)
_cell_measurement_reflns_used    9836
_cell_measurement_temperature    99.99(10)
_cell_measurement_theta_max      75.2580
_cell_measurement_theta_min      3.5340
_cell_volume                     1360.05(8)
_computing_cell_refinement       'CrysAlisPro 1.171.43.95a (Rigaku OD, 2023)'
_computing_data_collection       'CrysAlisPro 1.171.43.95a (Rigaku OD, 2023)'
_computing_data_reduction        'CrysAlisPro 1.171.43.95a (Rigaku OD, 2023)'
_computing_molecular_graphics    'Olex2 1.3 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 1.3 (Dolomanov et al., 2009)'
_computing_structure_refinement  'SHELXL 2018/3 (Sheldrick, 2015)'
_computing_structure_solution    'SHELXT  (Sheldrick, 2015)'
_diffrn_ambient_environment      N~2~
_diffrn_ambient_temperature      99.99(10)
_diffrn_detector                 'Hybrid Pixel Array Detector'
_diffrn_detector_area_resol_mean 10.0000
_diffrn_detector_type            HyPix
_diffrn_measured_fraction_theta_full 0.998
_diffrn_measured_fraction_theta_max 0.958
_diffrn_measurement_details
;
List of Runs (angles in degrees, time in seconds):

  # Type    Start    End  Width  t~exp~   \w     \q     \k     \f   Frames
  1  \w     54.00 102.00   0.50    0.05    --   44.84-137.00-149.00   96
  2  \w     84.00 114.00   0.50    0.50    --  105.85-137.00-149.00   60
  3  \w     55.00  80.00   0.50    0.50    --  105.85-137.00-149.00   50
  4  \w     64.00 111.00   0.50    0.50    --  105.85-125.00 -60.00   94
  5  \w     36.00 112.00   0.50    0.50    --  105.85-133.00  28.00  152
  6  \w     62.00 103.00   0.50    0.50    --  105.85-125.00  90.00   82
  7  \w     66.00 108.00   0.50    0.50    --  105.85-125.00 120.00   84
  8  \w     82.00 112.00   0.50    0.50    --  105.85-125.00 150.00   60
  9  \w     53.00  86.00   0.50    0.05    --   44.84-133.00  28.00   66
 10  \w     70.00  97.00   0.50    0.50    --  105.85 -94.00   0.00   54
 11  \w     42.00  67.00   0.50    0.50    --  105.85 -94.00   0.00   50
 12  \w     44.00  83.00   0.50    0.50    --  105.85-125.00 -30.00   78
 13  \w     87.00 112.00   0.50    0.50    --  105.85-125.00 -30.00   50
 14  \w     60.00 104.00   0.50    0.50    --  105.85-125.00-120.00   88
 15  \w     34.00  82.00   0.50    0.50    --  105.85 -77.00-120.00   96
 16  \w     34.00  75.00   0.50    0.50    --  105.85 -77.00-180.00   82
 17  \w     33.00  71.00   0.50    0.50    --  105.85 -61.00  30.00   76
 18  \w     35.00  70.00   0.50    0.50    --  105.85 -61.00  90.00   70
 19  \w     34.00  71.00   0.50    0.50    --  105.85 -61.00  60.00   74
 20  \w     37.00  67.00   0.50    0.50    --  105.85 -61.00   0.00   60
 21  \w     47.00  72.00   0.50    0.50    --  105.85 -61.00-180.00   50
 22  \w    -32.00  18.00   0.50    0.05    --   44.84 -19.00 -60.00  100
 23  \w    -31.00  27.00   0.50    0.05    --   44.84 -19.00-120.00  116
 24  \w     89.00 157.00   0.50    0.50    --  105.85  61.00   0.00  136
 25  \w    145.00 176.00   0.50    0.50    --  105.85  45.00 -30.00   62
 26  \w    133.00 176.00   0.50    0.50    --  105.85   0.00  60.00   86
 27  \w     88.00 113.00   0.50    0.50    --  105.85  45.00 -30.00   50
 28  \w     44.00  69.00   0.50    0.50    --  105.85   0.00  60.00   50
 29  \w     84.00 122.00   0.50    0.50    --  105.85 133.00  96.00   76
 30  \w     92.00 118.00   0.50    0.05    --   44.84 137.00 -85.00   52
 31  \w    101.00 126.00   0.50    0.50    --  105.85 137.00 -85.00   50
 32  \w   -117.00 -20.00   0.50    0.05    --  -44.84 -77.00  30.00  194
 33  \w   -175.00 -76.00   0.50    0.50    -- -100.00 -15.00 150.00  198
 34  \w   -169.00 -81.00   0.50    0.50    -- -100.00 -61.00 120.00  176
 35  \w   -174.00 -78.00   0.50    0.50    -- -100.00 -15.00-120.00  192
 36  \w   -137.00-111.00   0.50    0.50    -- -100.00 -61.00 -60.00   52
 37  \w   -113.00 -67.00   0.50    0.05    --  -44.84-137.00-149.00   92
 38  \w   -144.00-119.00   0.50    0.50    -- -100.00-137.00-149.00   50
 39  \w   -116.00 -74.00   0.50    0.05    --  -44.84-133.00  28.00   84
 40  \w   -143.00-118.00   0.50    0.50    -- -100.00-133.00  28.00   50
 41  \w    -23.00  32.00   0.50    0.05    --  -44.84  19.00 120.00  110
 42  \w    -89.00 -55.00   0.50    0.05    --  -44.84 133.00  96.00   68
 43  \w    -60.00 -27.00   0.50    0.50    -- -100.00  61.00  30.00   66
 44  \w    -77.00 -50.00   0.50    0.05    --  -44.84 137.00 -85.00   54
 45  \w    -99.00 -29.00   0.50    0.50    -- -100.00  77.00-120.00  140
 46  \w    -92.00 -67.00   0.50    0.50    -- -100.00 137.00 -85.00   50
 47  \w    -87.00 -57.00   0.50    0.50    -- -100.00 133.00  96.00   60
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'XtaLAB Synergy R, DW system, HyPix'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_type
'CrysAlisPro convention (1999,Acta A55,543-557)'
_diffrn_orient_matrix_UB_11      0.1327557000
_diffrn_orient_matrix_UB_12      0.0350259000
_diffrn_orient_matrix_UB_13      -0.0570929000
_diffrn_orient_matrix_UB_21      -0.0393368000
_diffrn_orient_matrix_UB_22      -0.0043493000
_diffrn_orient_matrix_UB_23      -0.1097562000
_diffrn_orient_matrix_UB_31      -0.1008842000
_diffrn_orient_matrix_UB_32      0.1352233000
_diffrn_orient_matrix_UB_33      0.0017975000
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           'Cu K\a'
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_R_equivalents  0.0380
_diffrn_reflns_av_unetI/netI     0.0388
_diffrn_reflns_Laue_measured_fraction_full 0.998
_diffrn_reflns_Laue_measured_fraction_max 0.958
_diffrn_reflns_limit_h_max       12
_diffrn_reflns_limit_h_min       -12
_diffrn_reflns_limit_k_max       15
_diffrn_reflns_limit_k_min       -14
_diffrn_reflns_limit_l_max       15
_diffrn_reflns_limit_l_min       -15
_diffrn_reflns_number            17106
_diffrn_reflns_point_group_measured_fraction_full 0.998
_diffrn_reflns_point_group_measured_fraction_max 0.958
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         75.544
_diffrn_reflns_theta_min         3.550
_diffrn_source                   'Rotating-anode X-ray tube'
_diffrn_source_type              'Rigaku (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    1.067
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.91947
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.43.95a (Rigaku Oxford Diffraction, 2023)
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    1.408
_exptl_crystal_description       block
_exptl_crystal_F_000             600
_exptl_crystal_size_max          0.1
_exptl_crystal_size_mid          0.05
_exptl_crystal_size_min          0.05
_refine_diff_density_max         0.366
_refine_diff_density_min         -0.204
_refine_diff_density_rms         0.050
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.046
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     373
_refine_ls_number_reflns         5402
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.046
_refine_ls_R_factor_all          0.0462
_refine_ls_R_factor_gt           0.0414
_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^)+(0.0639P)^2^+0.2757P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1106
_refine_ls_wR_factor_ref         0.1151
_reflns_Friedel_coverage         0.000
_reflns_number_gt                4767
_reflns_number_total             5402
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d5gc04621a2.cif
_cod_data_source_block           huql_231207_auto
_cod_depositor_comments
'Adding full bibliography for 7251023--7251025.cif.'
_cod_database_code               7251025
_shelx_shelxl_version_number     2018/3
_chemical_oxdiff_formula         CHONS
_chemical_oxdiff_usercomment     CHON
_shelx_estimated_absorpt_t_max   0.949
_shelx_estimated_absorpt_t_min   0.901
_reflns_odcompleteness_completeness 99.84
_reflns_odcompleteness_iscentric 1
_reflns_odcompleteness_theta     66.97
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All N(H) groups
 At 1.5 times of:
  All C(H,H,H) groups
2.a Ternary CH refined with riding coordinates:
 C28(H28), C15(H15), C38(H38), C25(H25)
2.b Aromatic/amide H refined with riding coordinates:
 N18(H18), N16(H16), C30(H30), C23(H23), C17(H17), C20(H20), C21(H21),
 C33(H33), C36(H36), C22(H22), C34(H34), C35(H35)
2.c Idealised Me refined as rotating group:
 C40(H40A,H40B,H40C), C39(H39A,H39B,H39C), C27(H27A,H27B,H27C), C26(H26A,H26B,
 H26C)
;
_shelx_res_checksum              7591
_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 1.717
_oxdiff_exptl_absorpt_empirical_full_min 0.610