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_7251785
_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         'C16 H14 N4 O2 S'
_chemical_formula_sum            'C16 H14 N4 O2 S'
_chemical_formula_weight         326.37
_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   geom
_atom_sites_solution_primary     dual
_audit_creation_date             2024-03-22
_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                 106.138(2)
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   18.0524(4)
_cell_length_b                   7.4997(2)
_cell_length_c                   11.6915(2)
_cell_measurement_reflns_used    8546
_cell_measurement_temperature    100.00(10)
_cell_measurement_theta_max      78.6230
_cell_measurement_theta_min      2.5320
_cell_volume                     1520.51(6)
_computing_cell_refinement       'CrysAlisPro 1.171.43.98a (Rigaku OD, 2023)'
_computing_data_collection
'CrysAlisPro system (CCD 43.103a 64-bit (release 20-12-2023))'
_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      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 0.999
_diffrn_measured_fraction_theta_max 0.996
_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   -119.00 -30.00   0.50    0.50    --  -46.64 -57.00-164.00  178
  2  \w    -63.00  26.00   0.50    0.50    --  -46.64  57.00 -23.00  178
  3  \w    -25.00  63.00   0.50    0.50    --   46.64 -57.00-164.00  176
  4  \w    -67.00 -19.00   0.50    2.00    --  -91.75  57.00 -23.00   96
  5  \w   -164.00 -75.00   0.50    2.00    --  -91.75 -57.00-164.00  178
  6  \w     97.00 178.00   0.50    2.00    --  113.25  57.00 -23.00  162
  7  \w     41.00  68.00   0.50    2.00    --  113.25 -57.00-164.00   54
  8  \w    -13.00  29.00   0.50    0.50    --  -46.64  19.00 150.00   84
  9  \w    -13.00  29.00   0.50    0.50    --  -46.64  19.00 120.00   84
 10  \w    -29.00  12.00   0.50    0.50    --   46.64 -19.00-150.00   82
 11  \w    -49.00 -19.00   0.50    2.00    --  -91.75  45.00 150.00   60
 12  \w    -49.00 -19.00   0.50    2.00    --  -91.75  45.00-180.00   60
 13  \w    110.00 178.00   0.50    2.00    --  113.25  77.00  30.00  136
 14  \w     95.00 178.00   0.50    2.00    --  113.25 125.00 -90.00  166
 15  \w     41.00  75.00   0.50    2.00    --  113.25 -61.00  90.00   68
 16  \w     41.00  75.00   0.50    2.00    --  113.25 -61.00-120.00   68
 17  \w     96.00 176.00   0.50    2.00    --  113.25  15.00 120.00  160
 18  \w     41.00  75.00   0.50    2.00    --  113.25 -61.00 120.00   68
 19  \w     41.00  75.00   0.50    2.00    --  113.25 -61.00-180.00   68
 20  \w     96.00 176.00   0.50    2.00    --  113.25  15.00 150.00  160
 21  \w     96.00 176.00   0.50    2.00    --  113.25  15.00 150.00  160
 22  \w     41.00 106.00   0.50    2.00    --  113.25 -95.00 -60.00  130
 23  \w     95.00 178.00   0.50    2.00    --  113.25 125.00   0.00  166
 24  \w     95.00 178.00   0.50    2.00    --  113.25 125.00-150.00  166
 25  \w     99.00 124.00   0.50    2.00    --  113.25 125.00-150.00   50
 26  \w     48.00  75.00   0.50    2.00    --  113.25 -77.00 -60.00   54
 27  \w    110.00 137.00   0.50    2.00    --  113.25 -77.00 -60.00   54
 28  \w     43.00  72.00   0.50    2.00    --  113.25 -61.00   0.00   58
 29  \w    151.00 176.00   0.50    2.00    --  113.25  77.00  30.00   50
 30  \w     41.00  74.00   0.50    2.00    --  113.25 -61.00 150.00   66
;
_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      -0.0870622000
_diffrn_orient_matrix_UB_12      -0.0096711000
_diffrn_orient_matrix_UB_13      -0.0118562000
_diffrn_orient_matrix_UB_21      -0.0097235000
_diffrn_orient_matrix_UB_22      -0.1398325000
_diffrn_orient_matrix_UB_23      -0.0995645000
_diffrn_orient_matrix_UB_31      0.0147664000
_diffrn_orient_matrix_UB_32      -0.1501806000
_diffrn_orient_matrix_UB_33      0.0935748000
_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  0.0306
_diffrn_reflns_av_unetI/netI     0.0247
_diffrn_reflns_Laue_measured_fraction_full 0.999
_diffrn_reflns_Laue_measured_fraction_max 0.996
_diffrn_reflns_limit_h_max       22
_diffrn_reflns_limit_h_min       -22
_diffrn_reflns_limit_k_max       8
_diffrn_reflns_limit_k_min       -9
_diffrn_reflns_limit_l_max       14
_diffrn_reflns_limit_l_min       -13
_diffrn_reflns_number            15216
_diffrn_reflns_point_group_measured_fraction_full 0.999
_diffrn_reflns_point_group_measured_fraction_max 0.996
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         74.492
_diffrn_reflns_theta_min         2.548
_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    2.030
_exptl_absorpt_correction_T_max  1.000
_exptl_absorpt_correction_T_min  0.678
_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            yellow
_exptl_crystal_colour_primary    yellow
_exptl_crystal_density_diffrn    1.426
_exptl_crystal_description       block
_exptl_crystal_F_000             680
_exptl_crystal_size_max          0.168
_exptl_crystal_size_mid          0.055
_exptl_crystal_size_min          0.016
_refine_diff_density_max         1.398
_refine_diff_density_min         -0.472
_refine_diff_density_rms         0.076
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.050
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     209
_refine_ls_number_reflns         3116
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.050
_refine_ls_R_factor_all          0.0588
_refine_ls_R_factor_gt           0.0549
_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^)+(0.0979P)^2^+1.3456P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1547
_refine_ls_wR_factor_ref         0.1592
_reflns_Friedel_coverage         0.000
_reflns_number_gt                2828
_reflns_number_total             3116
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d6ra00822d2.cif
_cod_data_source_block           rk_tl5a
_cod_database_code               7251785
_shelx_shelxl_version_number     2019/1
_chemical_oxdiff_formula         CHNOS
_shelx_estimated_absorpt_t_max   0.968
_shelx_estimated_absorpt_t_min   0.727
_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 Secondary CH2 refined with riding coordinates:
 C10(H10A,H10B)
2.b Aromatic/amide H refined with riding coordinates:
 C5(H5), C6(H6), C8(H8), C9(H9), C12(H12), C13(H13), C14(H14), C15(H15),
 C16(H16)
2.c Idealised Me refined as rotating group:
 C3(H3A,H3B,H3C)
;
_shelx_res_checksum              12051
_olex2_exptl_crystal_mounting_method
'The crystal was mounted on a MITIGEN holder'
_olex2_submission_original_sample_id RKB_240321_SDc_TL5A
_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
- Detector area scaling
- B-factor correction
;
_oxdiff_exptl_absorpt_empirical_full_max 1.346
_oxdiff_exptl_absorpt_empirical_full_min 0.768