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_7251783
_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 H17 N3 S'
_chemical_formula_sum            'C16 H17 N3 S'
_chemical_formula_weight         283.38
_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             2023-10-04
_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                 92.8390(10)
_cell_angle_gamma                90
_cell_formula_units_Z            8
_cell_length_a                   24.8331(2)
_cell_length_b                   11.78700(10)
_cell_length_c                   10.07740(10)
_cell_measurement_reflns_used    13765
_cell_measurement_temperature    100.00(10)
_cell_measurement_theta_max      79.5230
_cell_measurement_theta_min      3.5620
_cell_volume                     2946.11(5)
_computing_cell_refinement       'CrysAlisPro 1.171.43.68a (Rigaku OD, 2023)'
_computing_data_collection
'CrysAlisPro system (CCD 42.101a 64-bit (release 31-08-2023))'
_computing_data_reduction        'CrysAlisPro 1.171.43.68a (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 2018/3 (Sheldrick, 2015)'
_computing_structure_solution    'SHELXT 2018/2 (Sheldrick, 2018)'
_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 0.997
_diffrn_measured_fraction_theta_max 0.967
_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     50.00  75.00   0.50    0.05    --   47.69-141.00-115.00   50
  2  \w     60.00 110.00   0.50    0.09    --  113.25-141.00-115.00  100
  3  \w     38.00  95.00   0.50    0.05    --   47.69-130.00  57.00  114
  4  \w     45.00  80.00   0.50    0.09    --  113.25-126.00 150.00   70
  5  \w     88.00 113.00   0.50    0.09    --  113.25-126.00 150.00   50
  6  \w     49.00 113.00   0.50    0.09    --  113.25-126.00 120.00  128
  7  \w     50.00 116.00   0.50    0.09    --  113.25-130.00  57.00  132
  8  \w     79.00 105.00   0.50    0.09    --  113.25 -95.00  30.00   52
  9  \w     53.00 113.00   0.50    0.09    --  113.25-126.00-180.00  120
 10  \w     -8.00  25.00   0.50    0.05    --   47.69 -19.00 -60.00   66
 11  \w     46.00  71.00   0.50    0.09    --  113.25 -61.00 -60.00   50
 12  \w     44.00  71.00   0.50    0.09    --  113.25 -61.00  90.00   54
 13  \w     44.00  70.00   0.50    0.09    --  113.25 -61.00 120.00   52
 14  \w     42.00  70.00   0.50    0.09    --  113.25 -61.00  30.00   56
 15  \w     96.00 145.00   0.50    0.09    --  113.25 126.00-150.00   98
 16  \w     99.00 125.00   0.50    0.09    --  113.25 130.00 129.00   52
 17  \w    148.00 175.00   0.50    0.09    --  113.25  45.00 120.00   54
 18  \w    101.00 142.00   0.50    0.09    --  113.25  45.00 120.00   82
 19  \w    101.00 136.00   0.50    0.09    --  113.25  30.00  60.00   70
 20  \w    140.00 166.00   0.50    0.09    --  113.25  30.00  60.00   52
 21  \w    104.00 172.00   0.50    0.09    --  113.25  45.00-150.00  136
 22  \w    -26.00  28.00   0.50    0.05    --  -47.69  19.00 -30.00  108
 23  \w    -75.00 -46.00   0.50    0.05    --  -47.69 130.00 129.00   58
 24  \w    -49.00 -22.00   0.50    0.09    --  -91.75  45.00   0.00   54
 25  \w    -43.00  24.00   0.50    0.05    --  -47.69  38.00 -90.00  134
 26  \w   -148.00 -71.00   0.50    0.09    --  -91.75-130.00  57.00  154
 27  \w   -117.00 -81.00   0.50    0.05    --  -47.69-130.00  57.00   72
 28  \w   -102.00 -70.00   0.50    0.05    --  -47.69-141.00-115.00   64
;
_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      -0.0619824000
_diffrn_orient_matrix_UB_12      0.0070307000
_diffrn_orient_matrix_UB_13      -0.0025504000
_diffrn_orient_matrix_UB_21      -0.0032687000
_diffrn_orient_matrix_UB_22      -0.1304491000
_diffrn_orient_matrix_UB_23      0.0058450000
_diffrn_orient_matrix_UB_31      0.0021198000
_diffrn_orient_matrix_UB_32      0.0050641000
_diffrn_orient_matrix_UB_33      0.1528994000
_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  0.0301
_diffrn_reflns_av_unetI/netI     0.0289
_diffrn_reflns_Laue_measured_fraction_full 0.997
_diffrn_reflns_Laue_measured_fraction_max 0.967
_diffrn_reflns_limit_h_max       31
_diffrn_reflns_limit_h_min       -31
_diffrn_reflns_limit_k_max       14
_diffrn_reflns_limit_k_min       -14
_diffrn_reflns_limit_l_max       12
_diffrn_reflns_limit_l_min       -8
_diffrn_reflns_number            21509
_diffrn_reflns_point_group_measured_fraction_full 0.997
_diffrn_reflns_point_group_measured_fraction_max 0.967
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         79.874
_diffrn_reflns_theta_min         3.564
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_current           1
_diffrn_source_type              'PhotonJet (Cu) X-ray Source'
_diffrn_source_voltage           50
_exptl_absorpt_coefficient_mu    1.884
_exptl_absorpt_correction_T_max  1.000
_exptl_absorpt_correction_T_min  0.498
_exptl_absorpt_correction_type   gaussian
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.43.68a (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    1.278
_exptl_crystal_description       block
_exptl_crystal_F_000             1200
_exptl_crystal_size_max          0.319
_exptl_crystal_size_mid          0.232
_exptl_crystal_size_min          0.082
_refine_diff_density_max         0.318
_refine_diff_density_min         -0.361
_refine_diff_density_rms         0.051
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.082
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     363
_refine_ls_number_reflns         6206
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.082
_refine_ls_R_factor_all          0.0377
_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^)+(0.0498P)^2^+0.6852P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0946
_refine_ls_wR_factor_ref         0.0968
_reflns_Friedel_coverage         0.000
_reflns_number_gt                5643
_reflns_number_total             6206
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d6ra00822d2.cif
_cod_data_source_block           rk_tl1a
_cod_database_code               7251783
_shelx_shelxl_version_number     2018/3
_chemical_oxdiff_formula         C16H17N3S
_shelx_estimated_absorpt_t_max   0.861
_shelx_estimated_absorpt_t_min   0.585
_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 Secondary CH2 refined with riding coordinates:
 C7(H7A,H7B), C7B(H7BA,H7BB)
2.b Aromatic/amide H refined with riding coordinates:
 N1(H1), C2(H2), C3(H3), C4(H4), C5(H5), C6(H6), C10(H10), C12(H12), C13(H13),
 C14(H14), C15(H15), C16(H16), N1B(H1B), C2B(H2B), C3B(H3B), C4B(H4B), C5B(H5B),
  C6B(H6B), C10B(H10B), C12B(H12B), C13B(H13B), C14B(H14B), C15B(H15B),
 C16B(H16B)
2.c Idealised Me refined as rotating group:
 C9(H9A,H9B,H9C), C9B(H9BA,H9BB,H9BC)
;
_shelx_res_checksum              50723
_olex2_exptl_crystal_mounting_method
'The crystal was mounted on a MITIGEN holder'
_olex2_submission_original_sample_id RKB_230929_SDC_TL1A
_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 1.312
_oxdiff_exptl_absorpt_empirical_full_min 0.857