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_7251023
_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         'C11 H14 N2 O'
_chemical_formula_sum            'C11 H14 N2 O'
_chemical_formula_weight         190.24
_space_group_crystal_system      orthorhombic
_space_group_IT_number           61
_space_group_name_Hall           '-P 2ac 2ab'
_space_group_name_H-M_alt        'P b c a'
_atom_sites_solution_hydrogens   mixed
_atom_sites_solution_primary     iterative
_audit_creation_date             2024-04-17
_audit_creation_method
;
Olex2 1.5
(compiled 2024.02.16 svn.r378c4104 for OlexSys, GUI svn.r6928)
;
_audit_update_record
;
2024-04-17 deposited with the CCDC.	2025-10-09 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 90
_cell_angle_gamma                90
_cell_formula_units_Z            8
_cell_length_a                   10.4817(4)
_cell_length_b                   12.0401(5)
_cell_length_c                   16.6754(6)
_cell_measurement_reflns_used    4337
_cell_measurement_temperature    100.00(10)
_cell_measurement_theta_max      74.9480
_cell_measurement_theta_min      5.2970
_cell_volume                     2104.45(14)
_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 1.5 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 1.5 (Dolomanov et al., 2009)'
_computing_structure_refinement  'SHELXL 2014/7 (Sheldrick, 2015)'
_computing_structure_solution    'olex2.solve 1.5 (Bourhis et al., 2015)'
_diffrn_ambient_environment      N~2~
_diffrn_ambient_temperature      100.00(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 0.960
_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     42.00  95.00   0.50    0.08    --  105.85 -77.00 120.00  106
  2  \w     45.00  72.00   0.50    0.08    --  105.85 -61.00  30.00   54
  3  \w     41.00  72.00   0.50    0.08    --  105.85 -61.00   0.00   62
  4  \w     35.00  67.00   0.50    0.08    --  105.85 -61.00 -60.00   64
  5  \w    -18.00   9.00   0.50    0.05    --   44.84 -19.00  60.00   54
  6  \w     84.00 168.00   0.50    0.08    --  105.85 129.00  56.00  168
  7  \w    -15.00  28.00   0.50    0.05    --   44.84 -19.00 -60.00   86
  8  \w   -126.00 -83.00   0.50    0.08    -- -100.00 -82.00-132.00   86
  9  \w   -118.00 -87.00   0.50    0.05    --  -44.84-141.00 171.00   62
 10  \w   -152.00 -89.00   0.50    0.08    -- -100.00 -39.00  37.00  126
 11  \w    -20.00   5.00   0.50    0.05    --  -44.84  19.00-120.00   50
 12  \w    -42.00  29.00   0.50    0.05    --  -44.84  39.00-168.00  142
 13  \w    -68.00 -38.00   0.50    0.08    -- -100.00  61.00 -90.00   60
 14  \w    -68.00 -37.00   0.50    0.08    -- -100.00 129.00  56.00   62
;
_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      0.0296926000
_diffrn_orient_matrix_UB_12      0.0354567000
_diffrn_orient_matrix_UB_13      0.0868527000
_diffrn_orient_matrix_UB_21      -0.0664446000
_diffrn_orient_matrix_UB_22      -0.1055014000
_diffrn_orient_matrix_UB_23      0.0314838000
_diffrn_orient_matrix_UB_31      0.1275467000
_diffrn_orient_matrix_UB_32      -0.0631198000
_diffrn_orient_matrix_UB_33      -0.0039032000
_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  0.0315
_diffrn_reflns_av_unetI/netI     0.0322
_diffrn_reflns_Laue_measured_fraction_full 0.998
_diffrn_reflns_Laue_measured_fraction_max 0.960
_diffrn_reflns_limit_h_max       13
_diffrn_reflns_limit_h_min       -9
_diffrn_reflns_limit_k_max       15
_diffrn_reflns_limit_k_min       -15
_diffrn_reflns_limit_l_max       20
_diffrn_reflns_limit_l_min       -20
_diffrn_reflns_number            7313
_diffrn_reflns_point_group_measured_fraction_full 0.998
_diffrn_reflns_point_group_measured_fraction_max 0.960
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         75.413
_diffrn_reflns_theta_min         5.305
_diffrn_source                   'Rotating-anode X-ray tube'
_diffrn_source_type              'Rigaku (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    0.627
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.85766
_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    1.201
_exptl_crystal_description       block
_exptl_crystal_F_000             816
_exptl_crystal_size_max          0.1
_exptl_crystal_size_mid          0.1
_exptl_crystal_size_min          0.05
_refine_diff_density_max         0.239
_refine_diff_density_min         -0.312
_refine_diff_density_rms         0.044
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.065
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     163
_refine_ls_number_reflns         2087
_refine_ls_number_restraints     72
_refine_ls_restrained_S_all      1.065
_refine_ls_R_factor_all          0.0589
_refine_ls_R_factor_gt           0.0511
_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^)+(0.0735P)^2^+0.7220P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1398
_refine_ls_wR_factor_ref         0.1465
_reflns_Friedel_coverage         0.000
_reflns_number_gt                1769
_reflns_number_total             2087
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d5gc04621a2.cif
_cod_data_source_block           huql_int_240125_auto
_cod_depositor_comments
'Adding full bibliography for 7251023--7251025.cif.'
_cod_database_code               7251023
_shelx_shelxl_version_number     2014/7
_chemical_oxdiff_usercomment     'C H N F'
_shelx_estimated_absorpt_t_max   0.969
_shelx_estimated_absorpt_t_min   0.940
_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. Restrained distances
 N1-C4 \\sim N1-C4A
 with sigma of 0.02
 C3-C4 \\sim C3-C4A
 with sigma of 0.02
 C3-C2 \\sim C3-C2A
 with sigma of 0.02
 C3-C1 \\sim C3-C1A
 with sigma of 0.02
 N2-C4 \\sim N2-C4A
 with sigma of 0.02
 N1-C4A \\sim N1-C4
 with sigma of 0.02
 C4A-C3 \\sim C4-C3
 with sigma of 0.02
 C3-C1 \\sim C3-C1A \\sim C3-C2 \\sim C3-C2A
 with sigma of 0.02
3. Uiso/Uaniso restraints and constraints
Uanis(C1A) \\sim Ueq: with sigma of 0.01 and sigma for terminal atoms of 0.05
4. Rigid body (RIGU) restrains
 C4, C3, C1, C2, N1, N2
 with sigma for 1-2 distances of 0.01 and sigma for 1-3 distances of 0.02
 C4A, N1, N2, C3, C1A, C2A
 with sigma for 1-2 distances of 0.01 and sigma for 1-3 distances of 0.02
5. Others
 Sof(H2B)=Sof(H3B)=Sof(C4A)=Sof(H4A)=Sof(C2A)=Sof(H2AA)=Sof(H2AB)=Sof(H2AC)=
 Sof(C1A)=Sof(H1AA)=Sof(H1AB)=Sof(H1AC)=1-FVAR(1)
 Sof(H2A)=Sof(H3A)=Sof(C4)=Sof(H4)=Sof(C2)=Sof(H2C)=Sof(H2D)=Sof(H2E)=Sof(C1)=
 Sof(H1A)=Sof(H1B)=Sof(H1C)=FVAR(1)
6.a Ternary CH refined with riding coordinates:
 C3(H3A), C3(H3B), C4(H4), C4A(H4A)
6.b Aromatic/amide H refined with riding coordinates:
 N2(H2A), N2(H2B), C6(H6), C7(H7), C8(H8), C9(H9)
6.c Idealised Me refined as rotating group:
 C2(H2C,H2D,H2E), C1(H1A,H1B,H1C), C2A(H2AA,H2AB,H2AC), C1A(H1AA,H1AB,H1AC)
;
_shelx_res_checksum              1538
_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 1.266
_oxdiff_exptl_absorpt_empirical_full_min 0.760