Synthesis of sulfanyl derivatives of 1,2,4-triazoles via an acid catalyzed intramolecular cyclization of isothiosemicarbazones: structural characterization, E/Z isomerism, mechanistic insights and in vitro cytotoxicity
Snisha, Kallivalappil; Karthikeyan, Mano Chitra; Bhuvanesh, Nattamai; Arockiam, Antony Joseph Velanganni; Karvembu, Ramasamy; RSC Advances 16 (2026) 13433–13446; doi:10.1039/D6RA00822D

data_7251781
_publ_section_title
;
 Synthesis of sulfanyl derivatives of 1,2,4-triazoles via an acid
 catalyzed intramolecular cyclization of isothiosemicarbazones: structural
 characterization, E/Z isomerism, mechanistic insights and in vitro
 cytotoxicity
;
_journal_issue                   15
_journal_name_full               'RSC Advances'
_journal_page_first              13433
_journal_page_last               13446
_journal_paper_doi               10.1039/D6RA00822D
_journal_volume                  16
_journal_year                    2026
_chemical_formula_moiety         'Br, C16 H16 N3 S'
_chemical_formula_sum            'C16 H16 Br N3 S'
_chemical_formula_weight         362.29
_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     dual
_audit_creation_date             2024-10-15
_audit_creation_method
;
Olex2 1.5
(compiled 2023.08.24 svn.re1ec1418 for OlexSys, GUI svn.r6817)
;
_audit_update_record
;
2025-11-28 deposited with the CCDC.	2026-03-04 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 94.7090(10)
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   10.97500(10)
_cell_length_b                   13.76310(10)
_cell_length_c                   10.49770(10)
_cell_measurement_reflns_used    22385
_cell_measurement_temperature    99.98(10)
_cell_measurement_theta_max      78.9530
_cell_measurement_theta_min      3.1520
_cell_volume                     1580.33(2)
_computing_cell_refinement       'CrysAlisPro 1.171.43.98a (Rigaku OD, 2023)'
_computing_data_collection
'CrysAlisPro system (CCD 43.128a 64-bit (release 20-06-2024))'
_computing_data_reduction        'CrysAlisPro 1.171.43.98a (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 2019/1 (Sheldrick, 2015)'
_computing_structure_solution    'SHELXT  (Sheldrick, 2015)'
_diffrn_ambient_environment      N~2~
_diffrn_ambient_temperature      99.98(10)
_diffrn_detector                 'Hybrid Pixel Array Detector'
_diffrn_detector_area_resol_mean 10.0000
_diffrn_detector_type            HyPix
_diffrn_measured_fraction_theta_full 1.000
_diffrn_measured_fraction_theta_max 1.000
_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    -77.00  25.00   0.50    0.05    --  -47.48  92.00  -3.00  204
  2  \w    -19.00  77.00   0.50    0.05    --   47.48 -92.00-116.00  192
  3  \w    -19.00  77.00   0.50    0.05    --   47.48 -92.00-116.00  192
  4  \w    -79.00 -19.00   0.50    0.20    --  -91.75  92.00  -3.00  120
  5  \w     42.00 105.00   0.50    0.20    --  113.25 -92.00-116.00  126
  6  \w    102.00 178.00   0.50    0.20    --  113.25  92.00  -3.00  152
  7  \w    -12.00  28.00   0.50    0.05    --  -47.48  19.00 -60.00   80
  8  \w    -12.00  28.00   0.50    0.05    --  -47.48  19.00 -30.00   80
  9  \w    -12.00  28.00   0.50    0.05    --  -47.48  19.00  90.00   80
 10  \w    -27.00  12.00   0.50    0.05    --   47.48 -19.00-120.00   78
 11  \w    -27.00  12.00   0.50    0.05    --   47.48 -19.00 120.00   78
 12  \w    -49.00 -20.00   0.50    0.20    --  -91.75  45.00-150.00   58
 13  \w    -49.00 -20.00   0.50    0.20    --  -91.75  45.00-180.00   58
 14  \w   -163.00 -80.00   0.50    0.20    --  -91.75 -92.00-116.00  166
 15  \w   -163.00 -80.00   0.50    0.20    --  -91.75 -92.00-116.00  166
 16  \w    110.00 178.00   0.50    0.20    --  113.25  77.00  60.00  136
 17  \w     42.00 106.00   0.50    0.20    --  113.25 -95.00 -60.00  128
 18  \w    110.00 178.00   0.50    0.20    --  113.25  77.00-150.00  136
 19  \w     46.00 111.00   0.50    0.20    --  113.25-125.00-120.00  130
 20  \w     44.00  73.00   0.50    0.20    --  113.25 -61.00 120.00   58
 21  \w     43.00  72.00   0.50    0.20    --  113.25 -61.00  90.00   58
 22  \w    116.00 162.00   0.50    0.20    --  113.25  77.00-120.00   92
 23  \w    106.00 176.00   0.50    0.20    --  113.25  61.00 -60.00  140
 24  \w     43.00 102.00   0.50    0.20    --  113.25 -95.00  30.00  118
 25  \w    102.00 174.00   0.50    0.20    --  113.25  45.00 -30.00  144
 26  \w     77.00 103.00   0.50    0.20    --  113.25 -95.00 -30.00   52
 27  \w     50.00  75.00   0.50    0.20    --  113.25 -61.00 -60.00   50
 28  \w     42.00  75.00   0.50    0.20    --  113.25 -61.00  30.00   66
 29  \w     48.00  82.00   0.50    0.05    --   47.48  38.00-180.00   68
 30  \w    -36.00   8.00   0.50    0.05    --  -47.48  38.00-120.00   88
 31  \w     39.00  89.00   0.50    0.05    --   47.48-125.00  90.00  100
 32  \w     90.00 116.00   0.50    0.05    --   47.48  38.00-180.00   52
 33  \w    -17.00  10.00   0.50    0.05    --   47.48 -19.00   0.00   54
 34  \w    -27.00  -2.00   0.50    0.05    --   47.48 -19.00  30.00   50
 35  \w   -146.00-121.00   0.50    0.20    --  -91.75 -77.00  60.00   50
 36  \w    -46.00 -19.00   0.50    0.20    --  -91.75  61.00 -90.00   54
 37  \w   -104.00 -79.00   0.50    0.20    --  -91.75 -45.00 -90.00   50
 38  \w    121.00 164.00   0.50    0.20    --  113.25  61.00  90.00   86
 39  \w    134.00 178.00   0.50    0.20    --  113.25  45.00   0.00   88
 40  \w     47.00  74.00   0.50    0.20    --  113.25 -61.00 -90.00   54
 41  \w     43.00  71.00   0.50    0.20    --  113.25 -95.00 -90.00   56
 42  \w     63.00 106.00   0.50    0.20    --  113.25 -95.00   0.00   86
 43  \w     68.00 106.00   0.50    0.20    --  113.25 -95.00-120.00   76
 44  \w    116.00 169.00   0.50    0.20    --  113.25  77.00  30.00  106
 45  \w     81.00 106.00   0.50    0.20    --  113.25 -95.00-180.00   50
 46  \w     42.00  67.00   0.50    0.20    --  113.25 -61.00-120.00   50
 47  \w    102.00 127.00   0.50    0.20    --  113.25  30.00  60.00   50
 48  \w     63.00 111.00   0.50    0.20    --  113.25-125.00-150.00   96
 49  \w    142.00 172.00   0.50    0.20    --  113.25  15.00-180.00   60
 50  \w     80.00 106.00   0.50    0.20    --  113.25 -95.00 150.00   52
 51  \w    118.00 165.00   0.50    0.20    --  113.25  15.00  90.00   94
 52  \w     46.00  72.00   0.50    0.20    --  113.25 -61.00 -30.00   52
 53  \w     47.00  75.00   0.50    0.20    --  113.25-125.00   0.00   56
 54  \w     74.00 100.00   0.50    0.20    --  113.25 -95.00  60.00   52
 55  \w    109.00 151.00   0.50    0.20    --  113.25  61.00 120.00   84
 56  \w    129.00 176.00   0.50    0.20    --  113.25  77.00 120.00   94
 57  \w    101.00 176.00   0.50    0.20    --  113.25  15.00 150.00  150
 58  \w     35.00 120.00   0.50    0.05    --   47.48  43.00  31.10  170
 59  \w     35.00 120.00   0.50    0.05    --   47.48  47.00 112.76  170
 60  \w     35.00 119.00   0.50    0.05    --   47.48  44.00-128.06  168
 61  \w     35.00 120.00   0.50    0.05    --   47.48  46.00 -27.26  170
 62  \w     35.00 106.00   0.50    0.05    --   47.48  47.00 142.74  142
 63  \w     35.00 119.00   0.50    0.05    --   47.48  44.00 -58.16  168
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'XtaLAB Synergy, Dualflex, HyPix'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_type
'CrysAlisPro convention (1999,Acta A55,543-557)'
_diffrn_orient_matrix_UB_11      -0.0655504000
_diffrn_orient_matrix_UB_12      -0.0518015000
_diffrn_orient_matrix_UB_13      0.1051085000
_diffrn_orient_matrix_UB_21      0.0230283000
_diffrn_orient_matrix_UB_22      0.0886827000
_diffrn_orient_matrix_UB_23      0.0882194000
_diffrn_orient_matrix_UB_31      -0.1225556000
_diffrn_orient_matrix_UB_32      0.0444213000
_diffrn_orient_matrix_UB_33      -0.0534107000
_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  0.0521
_diffrn_reflns_av_unetI/netI     0.0189
_diffrn_reflns_Laue_measured_fraction_full 1.000
_diffrn_reflns_Laue_measured_fraction_max 1.000
_diffrn_reflns_limit_h_max       11
_diffrn_reflns_limit_h_min       -13
_diffrn_reflns_limit_k_max       17
_diffrn_reflns_limit_k_min       -17
_diffrn_reflns_limit_l_max       13
_diffrn_reflns_limit_l_min       -13
_diffrn_reflns_number            31861
_diffrn_reflns_point_group_measured_fraction_full 1.000
_diffrn_reflns_point_group_measured_fraction_max 1.000
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         74.497
_diffrn_reflns_theta_min         4.042
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_current           '1 mA'
_diffrn_source_type              'PhotonJet (Cu) X-ray Source'
_diffrn_source_voltage           '50 kV'
_exptl_absorpt_coefficient_mu    4.743
_exptl_absorpt_correction_T_max  1.000
_exptl_absorpt_correction_T_min  0.432
_exptl_absorpt_correction_type   gaussian
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.43.98a (Rigaku Oxford Diffraction, 2023) 
Numerical absorption correction based on gaussian integration over 
a multifaceted crystal model 
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    1.523
_exptl_crystal_description       block
_exptl_crystal_F_000             736
_exptl_crystal_size_max          0.188
_exptl_crystal_size_mid          0.146
_exptl_crystal_size_min          0.075
_refine_diff_density_max         0.855
_refine_diff_density_min         -1.021
_refine_diff_density_rms         0.091
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.074
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     191
_refine_ls_number_reflns         3223
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.074
_refine_ls_R_factor_all          0.0356
_refine_ls_R_factor_gt           0.0351
_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^)+(0.0674P)^2^+0.6853P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0953
_refine_ls_wR_factor_ref         0.0958
_reflns_Friedel_coverage         0.000
_reflns_number_gt                3132
_reflns_number_total             3223
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d6ra00822d2.cif
_cod_data_source_block           rk_skvcl1
_cod_database_code               7251781
_shelx_shelxl_version_number     2019/1
_chemical_oxdiff_formula         'C16  H16  Br1  N3  S1  '
_shelx_estimated_absorpt_t_max   0.717
_shelx_estimated_absorpt_t_min   0.469
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All C(H,H) groups, All N(H) groups
 At 1.5 times of:
  All C(H,H,H) groups
2.a Riding coordinates:
 N1(H1)
2.b Secondary CH2 refined with riding coordinates:
 C10(H10A,H10B)
2.c Aromatic/amide H refined with riding coordinates:
 C5(H5), C6(H6), C7(H7), C8(H8), C9(H9), C12(H12), C13(H13), C14(H14),
 C15(H15), C16(H16)
2.d Idealised Me refined as rotating group:
 C3(H3A,H3B,H3C)
;
_shelx_res_checksum              853
_olex2_submission_original_sample_id RKB_241015_Rc_SKVCL1
_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 1.496
_oxdiff_exptl_absorpt_empirical_full_min 0.669