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_7251784
_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         'C17 H17 N3 O S'
_chemical_formula_sum            'C17 H17 N3 O S'
_chemical_formula_weight         311.39
_space_group_crystal_system      monoclinic
_space_group_IT_number           15
_space_group_name_Hall           '-C 2yc'
_space_group_name_H-M_alt        'C 1 2/c 1'
_atom_sites_solution_hydrogens   geom
_atom_sites_solution_primary     dual
_audit_creation_date             2024-10-22
_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                 93.1190(10)
_cell_angle_gamma                90
_cell_formula_units_Z            8
_cell_length_a                   35.0245(3)
_cell_length_b                   8.18130(10)
_cell_length_c                   10.79360(10)
_cell_measurement_reflns_used    19227
_cell_measurement_temperature    100.0(4)
_cell_measurement_theta_max      79.1950
_cell_measurement_theta_min      2.4580
_cell_volume                     3088.28(5)
_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 2018/2 (Sheldrick, 2018)'
_diffrn_ambient_environment      N~2~
_diffrn_ambient_temperature      100.0(4)
_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 0.997
_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     49.00  74.00   0.50    0.20    --  113.25-125.00 120.00   50
  2  \w     67.00  93.00   0.50    0.20    --  113.25-125.00  90.00   52
  3  \w     64.00  89.00   0.50    0.20    --  113.25-125.00  60.00   50
  4  \w     45.00  84.00   0.50    0.20    --  113.25-125.00  30.00   78
  5  \w     44.00 106.00   0.50    0.20    --  113.25 -95.00  90.00  124
  6  \w     53.00  79.00   0.50    0.20    --  113.25 -95.00 120.00   52
  7  \w     43.00  74.00   0.50    0.20    --  113.25 -95.00 150.00   62
  8  \w     50.00  76.00   0.50    0.20    --  113.25 -95.00  60.00   52
  9  \w     43.00  69.00   0.50    0.20    --  113.25 -95.00 -60.00   52
 10  \w     45.00  94.00   0.50    0.20    --  113.25-125.00-120.00   98
 11  \w     44.00 106.00   0.50    0.20    --  113.25 -95.00-120.00  124
 12  \w     43.00  84.00   0.50    0.20    --  113.25 -88.00 -99.18   82
 13  \w     95.00 125.00   0.50    0.20    --  113.25 -88.00 -99.18   60
 14  \w     95.00 121.00   0.50    0.20    --  113.25 -88.00-172.80   52
 15  \w    -21.00  75.00   0.50    0.05    --   47.48 -87.00 -48.00  192
 16  \w    -21.00  75.00   0.50    0.05    --   47.48 -87.00 -48.00  192
 17  \w     42.00  98.00   0.50    0.20    --  113.25 -88.00  97.11  112
 18  \w     93.00 119.00   0.50    0.20    --  113.25 -84.00   3.90   52
 19  \w     42.00 141.00   0.50    0.20    --  113.25 -87.00 -48.00  198
 20  \w     86.00 132.00   0.50    0.20    --  113.25 -77.00 -60.00   92
 21  \w    111.00 136.00   0.50    0.20    --  113.25 -77.00 -30.00   50
 22  \w     65.00  91.00   0.50    0.20    --  113.25 -77.00   0.00   52
 23  \w     65.00  91.00   0.50    0.20    --  113.25 -77.00 -30.00   52
 24  \w     66.00 135.00   0.50    0.20    --  113.25 -76.00-128.31  138
 25  \w     46.00  74.00   0.50    0.20    --  113.25 -61.00 -90.00   56
 26  \w     47.00  72.00   0.50    0.20    --  113.25 -61.00 -60.00   50
 27  \w    -27.00  12.00   0.50    0.05    --   47.48 -19.00 -60.00   78
 28  \w    -27.00  12.00   0.50    0.05    --   47.48 -19.00-120.00   78
 29  \w     42.00  71.00   0.50    0.20    --  113.25 -61.00   0.00   58
 30  \w     44.00  75.00   0.50    0.20    --  113.25 -61.00  30.00   62
 31  \w     43.00  71.00   0.50    0.20    --  113.25 -61.00  90.00   56
 32  \w    115.00 141.00   0.50    0.20    --  113.25  77.00 120.00   52
 33  \w    139.00 175.00   0.50    0.20    --  113.25  77.00 150.00   72
 34  \w    148.00 177.00   0.50    0.20    --  113.25  77.00  90.00   58
 35  \w    107.00 140.00   0.50    0.20    --  113.25  61.00  30.00   66
 36  \w    115.00 160.00   0.50    0.20    --  113.25  77.00 -60.00   90
 37  \w    106.00 178.00   0.50    0.20    --  113.25  61.00   0.00  144
 38  \w    106.00 175.00   0.50    0.20    --  113.25  61.00 -90.00  138
 39  \w    107.00 144.00   0.50    0.20    --  113.25  61.00-150.00   74
 40  \w    107.00 143.00   0.50    0.20    --  113.25  61.00-180.00   72
 41  \w    119.00 160.00   0.50    0.20    --  113.25  77.00-150.00   82
 42  \w    126.00 175.00   0.50    0.20    --  113.25  77.00-180.00   98
 43  \w    144.00 170.00   0.50    0.20    --  113.25  45.00-150.00   52
 44  \w    147.00 178.00   0.50    0.20    --  113.25  30.00 -60.00   62
 45  \w    134.00 167.00   0.50    0.20    --  113.25  15.00 -90.00   66
 46  \w    102.00 137.00   0.50    0.20    --  113.25  45.00  30.00   70
 47  \w    104.00 178.00   0.50    0.20    --  113.25  45.00 150.00  148
 48  \w    103.00 163.00   0.50    0.20    --  113.25  45.00 120.00  120
 49  \w    104.00 147.00   0.50    0.20    --  113.25  30.00  60.00   86
 50  \w    125.00 150.00   0.50    0.20    --  113.25  15.00  30.00   50
 51  \w    128.00 154.00   0.50    0.20    --  113.25  15.00  90.00   52
 52  \w    145.00 176.00   0.50    0.20    --  113.25  15.00-120.00   62
 53  \w    100.00 176.00   0.50    0.20    --  113.25  15.00-120.00  152
 54  \w    101.00 134.00   0.50    0.20    --  113.25  15.00-150.00   66
 55  \w    139.00 165.00   0.50    0.20    --  113.25  15.00-180.00   52
 56  \w    106.00 131.00   0.50    0.20    --  113.25 125.00 -90.00   50
 57  \w    135.00 166.00   0.50    0.20    --  113.25 125.00 -90.00   62
 58  \w    153.00 178.00   0.50    0.20    --  113.25 125.00 120.00   50
 59  \w    152.00 177.00   0.50    0.20    --  113.25 125.00 150.00   50
 60  \w    123.00 148.00   0.50    0.20    --  113.25 125.00 150.00   50
 61  \w    102.00 139.00   0.50    0.20    --  113.25 125.00 120.00   74
 62  \w    101.00 178.00   0.50    0.20    --  113.25  87.00  68.00  154
 63  \w    110.00 158.00   0.50    0.20    --  113.25 125.00 -60.00   96
 64  \w    -12.00  28.00   0.50    0.05    --  -47.48  19.00-120.00   80
 65  \w    -39.00  26.00   0.50    0.05    --  -47.48  38.00-180.00  130
 66  \w    -39.00  26.00   0.50    0.05    --  -47.48  38.00 -90.00  130
 67  \w    -75.00  25.00   0.50    0.05    --  -47.48  87.00  68.00  200
 68  \w   -119.00 -19.00   0.50    0.20    --  -91.75  87.00  68.00  200
 69  \w   -120.00 -34.00   0.50    0.05    --  -47.48 -38.00 150.00  172
 70  \w   -163.00 -79.00   0.50    0.20    --  -91.75 -87.00 -48.00  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      -0.0087010000
_diffrn_orient_matrix_UB_12      0.1662707000
_diffrn_orient_matrix_UB_13      -0.0623967000
_diffrn_orient_matrix_UB_21      0.0431260000
_diffrn_orient_matrix_UB_22      0.0292037000
_diffrn_orient_matrix_UB_23      -0.0112032000
_diffrn_orient_matrix_UB_31      -0.0022172000
_diffrn_orient_matrix_UB_32      -0.0833945000
_diffrn_orient_matrix_UB_33      -0.1281245000
_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  0.0443
_diffrn_reflns_av_unetI/netI     0.0236
_diffrn_reflns_Laue_measured_fraction_full 1.000
_diffrn_reflns_Laue_measured_fraction_max 0.997
_diffrn_reflns_limit_h_max       44
_diffrn_reflns_limit_h_min       -44
_diffrn_reflns_limit_k_max       10
_diffrn_reflns_limit_k_min       -10
_diffrn_reflns_limit_l_max       12
_diffrn_reflns_limit_l_min       -13
_diffrn_reflns_number            32973
_diffrn_reflns_point_group_measured_fraction_full 1.000
_diffrn_reflns_point_group_measured_fraction_max 0.997
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         80.135
_diffrn_reflns_theta_min         2.527
_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    1.899
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.78873
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.43.98a (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    1.339
_exptl_crystal_description       block
_exptl_crystal_F_000             1312
_exptl_crystal_size_max          0.212
_exptl_crystal_size_mid          0.104
_exptl_crystal_size_min          0.064
_refine_diff_density_max         0.239
_refine_diff_density_min         -0.333
_refine_diff_density_rms         0.051
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.108
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     201
_refine_ls_number_reflns         3365
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.108
_refine_ls_R_factor_all          0.0381
_refine_ls_R_factor_gt           0.0367
_refine_ls_shift/su_max          0.002
_refine_ls_shift/su_mean         0.000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'w=1/[\s^2^(Fo^2^)+(0.0445P)^2^+3.0571P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0972
_refine_ls_wR_factor_ref         0.0982
_reflns_Friedel_coverage         0.000
_reflns_number_gt                3175
_reflns_number_total             3365
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d6ra00822d2.cif
_cod_data_source_block           rk_skvtl2me
_cod_database_code               7251784
_shelx_shelxl_version_number     2019/1
_chemical_oxdiff_formula         'C17  H19  N3  O1  S1  '
_shelx_estimated_absorpt_t_max   0.888
_shelx_estimated_absorpt_t_min   0.689
_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:
 C11(H11A,H11B)
2.b Aromatic/amide H refined with riding coordinates:
 C13(H13), C5(H5), C14(H14), C6(H6), C3(H3), C15(H15), C2(H2), C17(H17),
 C16(H16)
2.c Idealised Me refined as rotating group:
 C10(H10A,H10B,H10C), C7(H7A,H7B,H7C)
;
_shelx_res_checksum              53709
_olex2_exptl_crystal_mounting_method
'The crystal was mounted on a MITIGEN holder'
_olex2_submission_original_sample_id RKB_241022_Sc_SKVTL2Me
_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
;
_oxdiff_exptl_absorpt_empirical_full_max 1.455
_oxdiff_exptl_absorpt_empirical_full_min 0.709