Synthesis of pyrrolo[3,4-c]pyridines via metal-free cross-coupling/cyclization cascades of β-ketothioamides with 2aroylmalononitrile at room temperature
Yadav, Anup Kumar; Kumar, Vipin; Singh, Saurabh; Samai, Subhasis; Singh, Maya Shankar; Chemical Communications  (2025) –; doi:10.1039/D5CC04230E

data_7135161
_publ_section_title
;
 Synthesis of pyrrolo[3,4-c]pyridines via metal-free
 cross-coupling/cyclization cascades of \b-ketothioamides with
 2aroylmalononitrile at room temperature
;
_journal_name_full               'Chemical Communications'
_journal_paper_doi               10.1039/D5CC04230E
_journal_year                    2025
_chemical_formula_moiety         'C27 H19 N3 O2 S, C2 H6 O S, H2 O'
_chemical_formula_sum            'C29 H27 N3 O4 S2'
_chemical_formula_weight         545.65
_space_group_crystal_system      monoclinic
_space_group_IT_number           15
_space_group_name_Hall           '-I 2ya'
_space_group_name_H-M_alt        'I 1 2/a 1'
_atom_sites_solution_hydrogens   mixed
_atom_sites_solution_primary     dual
_audit_creation_date             2024-07-24
_audit_creation_method
;
Olex2 1.5
(compiled 2024.02.16 svn.r378c4104 for OlexSys, GUI svn.r6928)
;
_audit_update_record
;
2024-07-25 deposited with the CCDC.	2025-11-11 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 94.8060(10)
_cell_angle_gamma                90
_cell_formula_units_Z            8
_cell_length_a                   21.6291(2)
_cell_length_b                   8.63670(10)
_cell_length_c                   30.4166(2)
_cell_measurement_reflns_used    20888
_cell_measurement_temperature    100
_cell_measurement_theta_max      67.8010
_cell_measurement_theta_min      2.4010
_cell_volume                     5661.97(9)
_computing_cell_refinement       'CrysAlisPro 1.171.42.90a (Rigaku OD, 2023)'
_computing_data_collection       'CrysAlisPro 1.171.42.90a (Rigaku OD, 2023)'
_computing_data_reduction        'CrysAlisPro 1.171.42.90a (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    'SHELXT 2018/2 (Sheldrick, 2018)'
_diffrn_ambient_temperature      100
_diffrn_detector                 'Hybrid Pixel Array Detector'
_diffrn_detector_area_resol_mean 10.0000
_diffrn_detector_type            HyPix3000
_diffrn_measured_fraction_theta_full 1.000
_diffrn_measured_fraction_theta_max 0.998
_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    105.00 170.00   0.50    0.20    --   96.04  96.00-150.00  130
  2  \w    105.00 170.00   0.50    0.20    --   96.04  96.00 120.00  130
  3  \w    -25.00  44.00   0.50    0.20    --   40.83 -39.00  92.00  138
  4  \w    -27.00  37.00   0.50    0.20    --   40.83 -32.00   0.00  128
  5  \w    -27.00  64.00   0.50    0.20    --   40.83 -65.00 -60.00  182
  6  \w     44.00 127.00   0.50    0.20    --   96.04-145.00 -30.00  166
  7  \w     41.00 100.00   0.50    0.20    --   40.83-138.00-120.00  118
  8  \w     23.00 106.00   0.50    0.20    --   96.04 -96.00 -60.00  166
  9  \w     41.00 100.00   0.50    0.20    --   40.83-138.00 150.00  118
 10  \w     26.00 127.00   0.50    0.20    --   96.04 -87.00 120.00  202
 11  \w     32.00 110.00   0.50    0.20    --   96.04-117.00  90.00  156
 12  \w     27.00 105.00   0.50    0.20    --   96.04 -77.00  30.00  156
 13  \w     28.00  83.00   0.50    0.20    --   96.04 -68.00   0.00  110
 14  \w     28.00  83.00   0.50    0.20    --   96.04 -68.00 -60.00  110
 15  \w     29.00  57.00   0.50    0.20    --   96.04 -50.00 -60.00   56
 16  \w     28.00  83.00   0.50    0.20    --   96.04 -68.00 -90.00  110
 17  \w     29.00  57.00   0.50    0.20    --   96.04 -50.00-150.00   56
 18  \w     28.00  68.00   0.50    0.20    --   96.04 -59.00-180.00   80
 19  \w     28.00  68.00   0.50    0.20    --   96.04 -59.00-150.00   80
 20  \w     29.00  57.00   0.50    0.20    --   96.04 -50.00 -30.00   56
 21  \w     29.00  57.00   0.50    0.20    --   96.04 -50.00   0.00   56
 22  \w     29.00  57.00   0.50    0.20    --   96.04 -50.00  60.00   56
 23  \w     29.00  57.00   0.50    0.20    --   96.04 -50.00  90.00   56
 24  \w     29.00  57.00   0.50    0.20    --   96.04 -50.00 120.00   56
 25  \w     29.00  57.00   0.50    0.20    --   96.04 -50.00 150.00   56
 26  \w     82.00 164.00   0.50    0.20    --   96.04  33.00  90.00  164
 27  \w     74.00 163.00   0.50    0.20    --   96.04  59.00 120.00  178
 28  \w     69.00 165.00   0.50    0.20    --   96.04  77.00  90.00  192
 29  \w     74.00 163.00   0.50    0.20    --   96.04  59.00 150.00  178
 30  \w     74.00 163.00   0.50    0.20    --   96.04  59.00  30.00  178
 31  \w     69.00 165.00   0.50    0.20    --   96.04  77.00  60.00  192
 32  \w     69.00 165.00   0.50    0.20    --   96.04  77.00   0.00  192
 33  \w     77.00 163.00   0.50    0.20    --   96.04  50.00 -30.00  172
 34  \w     79.00 162.00   0.50    0.20    --   96.04  42.00 -60.00  166
 35  \w     74.00 163.00   0.50    0.20    --   96.04  59.00 -90.00  178
 36  \w     74.00 163.00   0.50    0.20    --   96.04  59.00-150.00  178
 37  \w     77.00 163.00   0.50    0.20    --   96.04  50.00-180.00  172
 38  \w     80.00 162.00   0.50    0.20    --   96.04  39.00-113.00  164
 39  \w     79.00 162.00   0.50    0.20    --   96.04  42.00   0.00  166
 40  \w     28.00 109.00   0.50    0.20    --   40.83  32.00  90.00  162
 41  \w     14.00 110.00   0.50    0.20    --   40.83  77.00 150.00  192
 42  \w     21.00 108.00   0.50    0.20    --   40.83  54.00   0.00  174
 43  \w     14.00 110.00   0.50    0.20    --   40.83  77.00   0.00  192
 44  \w     14.00 110.00   0.50    0.20    --   40.83  77.00 -90.00  192
 45  \w     14.00 110.00   0.50    0.20    --   40.83  77.00-150.00  192
 46  \w     25.00 107.00   0.50    0.20    --   40.83  39.00-113.00  164
 47  \w     21.00 108.00   0.50    0.20    --   40.83  54.00 150.00  174
 48  \w    -24.00  35.00   0.50    0.20    --  -40.83  11.00   0.00  118
 49  \w    -47.00 -15.00   0.50    0.20    --  -82.50  42.00  30.00   64
 50  \w    -47.00 -15.00   0.50    0.20    --  -82.50  42.00 -90.00   64
 51  \w    -44.00 -16.00   0.50    0.20    --  -82.50  39.00-113.00   56
 52  \w    -44.00  25.00   0.50    0.20    --  -40.83  39.00-113.00  138
 53  \w    -61.00  26.00   0.50    0.20    --  -40.83  54.00-120.00  174
 54  \w    -84.00 -18.00   0.50    0.20    --  -82.50 117.00 -90.00  132
 55  \w   -109.00 -14.00   0.50    0.20    --  -40.83 -77.00 -90.00  190
 56  \w   -109.00 -14.00   0.50    0.20    --  -40.83 -77.00   0.00  190
 57  \w   -109.00 -14.00   0.50    0.20    --  -40.83 -77.00  30.00  190
 58  \w   -109.00 -14.00   0.50    0.20    --  -40.83 -77.00  60.00  190
 59  \w   -107.00 -25.00   0.50    0.20    --  -40.83 -39.00  92.00  164
 60  \w   -148.00 -67.00   0.50    0.20    --  -82.50 -39.00  92.00  162
 61  \w   -151.00 -55.00   0.50    0.20    --  -82.50 -77.00 -30.00  192
 62  \w   -151.00 -83.00   0.50    0.20    --  -82.50 -77.00 -60.00  136
 63  \w   -151.00 -55.00   0.50    0.20    --  -82.50 -77.00-120.00  192
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'XtaLAB Synergy, Dualflex, HyPix3000'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_type
'CrysAlisPro convention (1999,Acta A55,543-557)'
_diffrn_orient_matrix_UB_11      0.0623142000
_diffrn_orient_matrix_UB_12      0.0856842000
_diffrn_orient_matrix_UB_13      -0.0011340000
_diffrn_orient_matrix_UB_21      -0.0047145000
_diffrn_orient_matrix_UB_22      -0.0140163000
_diffrn_orient_matrix_UB_23      -0.0506606000
_diffrn_orient_matrix_UB_31      -0.0346934000
_diffrn_orient_matrix_UB_32      0.1558274000
_diffrn_orient_matrix_UB_33      -0.0039292000
_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  0.0336
_diffrn_reflns_av_unetI/netI     0.0169
_diffrn_reflns_Laue_measured_fraction_full 1.000
_diffrn_reflns_Laue_measured_fraction_max 0.998
_diffrn_reflns_limit_h_max       25
_diffrn_reflns_limit_h_min       -26
_diffrn_reflns_limit_k_max       10
_diffrn_reflns_limit_k_min       -10
_diffrn_reflns_limit_l_max       36
_diffrn_reflns_limit_l_min       -36
_diffrn_reflns_number            45758
_diffrn_reflns_point_group_measured_fraction_full 1.000
_diffrn_reflns_point_group_measured_fraction_max 0.998
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         68.089
_diffrn_reflns_theta_min         2.916
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_type              'PhotonJet (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    2.020
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.69623
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.42.90a (Rigaku Oxford Diffraction, 2023)
Empirical absorption correction using spherical harmonics,
implemented in SCALE3 ABSPACK scaling algorithm.
;
_exptl_crystal_colour            yellow
_exptl_crystal_colour_primary    yellow
_exptl_crystal_density_diffrn    1.280
_exptl_crystal_description       block
_exptl_crystal_F_000             2288
_exptl_crystal_size_max          0.156
_exptl_crystal_size_mid          0.122
_exptl_crystal_size_min          0.102
_refine_diff_density_max         1.143
_refine_diff_density_min         -0.367
_refine_diff_density_rms         0.048
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.055
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     393
_refine_ls_number_reflns         5159
_refine_ls_number_restraints     42
_refine_ls_restrained_S_all      1.088
_refine_ls_R_factor_all          0.0537
_refine_ls_R_factor_gt           0.0471
_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^)+(0.0811P)^2^+3.8154P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1372
_refine_ls_wR_factor_ref         0.1434
_reflns_Friedel_coverage         0.000
_reflns_number_gt                4394
_reflns_number_total             5159
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d5cc04230e3.cif
_cod_data_source_block           4me-cn2_auto
_cod_database_code               7135161
_shelx_shelxl_version_number     2014/7
_chemical_oxdiff_formula         'C H N O S'
_shelx_estimated_absorpt_t_max   0.820
_shelx_estimated_absorpt_t_min   0.743
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups
 At 1.5 times of:
  All C(H,H,H) groups, All O(H) groups, All O(H,H) groups
2. Restrained distances
 S2-O3 \\sim S2A-O3A
 with sigma of 0.02
 S2-C29 \\sim S2A-C29A
 with sigma of 0.02
 S2-C28 \\sim S2A-C28A
 with sigma of 0.02
 O3-C29 \\sim O3A-C29A
 with sigma of 0.04
 O3-C28 \\sim O3A-C28A
 with sigma of 0.04
 C29-C28 \\sim C29A-C28A
 with sigma of 0.04
3. Rigid body (RIGU) restrains
 C28A, S2, O3, C29, C28, C29A, S2A, O3A
 with sigma for 1-2 distances of 0.001 and sigma for 1-3 distances of 0.001
4. Others
 Sof(C28A)=Sof(H28D)=Sof(H28E)=Sof(H28F)=Sof(S2A)=Sof(O3A)=Sof(C29A)=Sof(H29D)=
 Sof(H29E)=Sof(H29F)=1-FVAR(1)
 Sof(S2)=Sof(O3)=Sof(C29)=Sof(H29A)=Sof(H29B)=Sof(H29C)=Sof(C28)=Sof(H28A)=
 Sof(H28B)=Sof(H28C)=FVAR(1)
5.a Free rotating group:
 O4(H4A,H4B)
5.b Aromatic/amide H refined with riding coordinates:
 C12(H12), C16(H16), C13(H13), C14(H14), C24(H24), C15(H15), C19(H19),
 C10(H10), C20(H20), C6(H6), C23(H23), C8(H8), C9(H9), C7(H7)
5.c Idealised Me refined as rotating group:
 C22(H22A,H22B,H22C), C29(H29A,H29B,H29C), C28(H28A,H28B,H28C), C28A(H28D,H28E,
 H28F), C29A(H29D,H29E,H29F)
5.d Idealised tetrahedral OH refined as rotating group:
 O2(H2)
;
_shelx_res_checksum              61619
_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 1.229
_oxdiff_exptl_absorpt_empirical_full_min 0.830