# Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry.
# This journal is © The Royal Society of Chemistry 2018

####################################################################### 
# 
# This file contains crystal structure data downloaded from the 
# Cambridge Structural Database (CSD) hosted by the Cambridge 
# Crystallographic Data Centre (CCDC).
# 
# Full information about CCDC data access policies and citation 
# guidelines are available at http://www.ccdc.cam.ac.uk/access/V1 
# 
# Audit and citation data items may have been added by the CCDC. 
# Please retain this information to preserve the provenance of 
# this file and to allow appropriate attribution of the data. 
# 
#######################################################################

data_ohj328_a
_database_code_depnum_ccdc_archive 'CCDC 1450620'
_audit_update_record             
;
2016-01-28 deposited with the CCDC.
2018-05-15 downloaded from the CCDC.
;

_audit_creation_method           SHELXL-2014/7
_shelx_SHELXL_version_number     2014/7
_chemical_name_systematic        Febrifugine
_chemical_name_common            Febrifugine
_chemical_melting_point          ?
_chemical_formula_moiety         'C16 H19 N3 O3'
_chemical_formula_sum            'C16 H19 N3 O3'
_chemical_formula_weight         301.34

loop_
_atom_type_symbol
_atom_type_description
_atom_type_scat_dispersion_real
_atom_type_scat_dispersion_imag
_atom_type_scat_source
C C 0.0181 0.0091 'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4'
H H 0.0000 0.0000 'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4'
N N 0.0311 0.0180 'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4'
O O 0.0492 0.0322 'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4'

_space_group_crystal_system      orthorhombic
_space_group_IT_number           61
_space_group_name_H-M_alt        'P b c a'
_space_group_name_Hall           '-P 2ac 2ab'

_shelx_space_group_comment       
; 
The symmetry employed for this shelxl refinement is uniquely defined 
by the following loop, which should always be used as a source of 
symmetry information in preference to the above space-group names. 
They are only intended as comments. 
;

loop_
_space_group_symop_operation_xyz
'x, y, z'
'-x+1/2, -y, z+1/2'
'-x, y+1/2, -z+1/2'
'x+1/2, -y+1/2, -z'
'-x, -y, -z'
'x-1/2, y, -z-1/2'
'x, -y-1/2, z-1/2'
'-x-1/2, y-1/2, z'

_cell_length_a                   10.2591(6)
_cell_length_b                   9.6617(5)
_cell_length_c                   30.5377(16)
_cell_angle_alpha                90
_cell_angle_beta                 90
_cell_angle_gamma                90
_cell_volume                     3026.9(3)
_cell_formula_units_Z            8
_cell_measurement_temperature    100(2)
_cell_measurement_reflns_used    2758
_cell_measurement_theta_min      5.19
_cell_measurement_theta_max      66.49

_exptl_crystal_description       Plate
_exptl_crystal_colour            colourless
_exptl_crystal_density_meas      ?
_exptl_crystal_density_method    ?
_exptl_crystal_density_diffrn    1.323
_exptl_crystal_F_000             1280
_exptl_transmission_factor_min   ?
_exptl_transmission_factor_max   ?
_exptl_crystal_size_max          0.200
_exptl_crystal_size_mid          0.080
_exptl_crystal_size_min          0.040
_exptl_absorpt_coefficient_mu    0.762
_shelx_estimated_absorpt_T_min   0.863
_shelx_estimated_absorpt_T_max   0.970
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_correction_T_min  0.82
_exptl_absorpt_correction_T_max  0.99
_exptl_absorpt_process_details   sadabs
_exptl_absorpt_special_details   ?
_diffrn_ambient_temperature      100(2)
_diffrn_radiation_wavelength     1.54178
_diffrn_radiation_type           CuK\a
_diffrn_source                   ?
_diffrn_measurement_device_type  'Bruker APEX-II CCD'
_diffrn_measurement_method       'φ and ω scans'
_diffrn_detector_area_resol_mean ?
_diffrn_reflns_number            12393
_diffrn_reflns_av_unetI/netI     0.0895
_diffrn_reflns_av_R_equivalents  0.1251
_diffrn_reflns_limit_h_min       -11
_diffrn_reflns_limit_h_max       12
_diffrn_reflns_limit_k_min       -11
_diffrn_reflns_limit_k_max       11
_diffrn_reflns_limit_l_min       -29
_diffrn_reflns_limit_l_max       36
_diffrn_reflns_theta_min         2.894
_diffrn_reflns_theta_max         66.664
_diffrn_reflns_theta_full        66.664
_diffrn_measured_fraction_theta_max 0.994
_diffrn_measured_fraction_theta_full 0.994
_diffrn_reflns_Laue_measured_fraction_max 0.994
_diffrn_reflns_Laue_measured_fraction_full 0.994
_diffrn_reflns_point_group_measured_fraction_max 0.994
_diffrn_reflns_point_group_measured_fraction_full 0.994
_reflns_number_total             2658
_reflns_number_gt                1725
_reflns_threshold_expression     'I > 2σ(I)'
_reflns_Friedel_coverage         0.000
_reflns_Friedel_fraction_max     .
_reflns_Friedel_fraction_full    .

_reflns_special_details          
; 
 Reflections were merged by SHELXL according to the crystal 
 class for the calculation of statistics and refinement. 
  
 _reflns_Friedel_fraction is defined as the number of unique 
 Friedel pairs measured divided by the number that would be 
 possible theoretically, ignoring centric projections and 
 systematic absences. 
;

_computing_data_collection       'Bruker APEX2'
_computing_cell_refinement       'Bruker SAINT'
_computing_data_reduction        'Bruker SAINT'
_computing_structure_solution    'SHELXS-97 (Sheldrick 2008)'
_computing_structure_refinement  'SHELXL-2014/7 (Sheldrick, 2014)'
_computing_molecular_graphics    'Bruker SHELXTL'
_computing_publication_material  'Bruker SHELXTL'
_refine_special_details          ?
_refine_ls_structure_factor_coef Fsqd
_refine_ls_matrix_type           full
_refine_ls_weighting_scheme      calc
_refine_ls_weighting_details     'w=1/[σ²(Fo²)] where P=(Fo²+2Fc²)/3'
_atom_sites_solution_primary     ?
_atom_sites_solution_secondary   ?
_atom_sites_solution_hydrogens   mixed
_refine_ls_hydrogen_treatment    constr
_refine_ls_extinction_method     none
_refine_ls_extinction_coef       .
_refine_ls_number_reflns         2658
_refine_ls_number_parameters     200
_refine_ls_number_restraints     0
_refine_ls_R_factor_all          0.1345
_refine_ls_R_factor_gt           0.0784
_refine_ls_wR_factor_ref         0.0889
_refine_ls_wR_factor_gt          0.0831
_refine_ls_goodness_of_fit_ref   1.517
_refine_ls_restrained_S_all      1.517
_refine_ls_shift/su_max          0.000
_refine_ls_shift/su_mean         0.000

loop_
_atom_site_label
_atom_site_type_symbol
_atom_site_fract_x
_atom_site_fract_y
_atom_site_fract_z
_atom_site_U_iso_or_equiv
_atom_site_adp_type
_atom_site_occupancy
_atom_site_site_symmetry_order
_atom_site_calc_flag
_atom_site_refinement_flags_posn
_atom_site_refinement_flags_adp
_atom_site_refinement_flags_occupancy
_atom_site_disorder_assembly
_atom_site_disorder_group
O1 O 0.7899(2) 0.61182(18) 0.39422(7) 0.0330(6) Uani 1 1 d . . . . .
O2 O 0.5283(2) 0.64816(19) 0.46846(6) 0.0311(5) Uani 1 1 d . . . . .
O3 O 0.64824(17) 1.00179(17) 0.57609(7) 0.0260(5) Uani 1 1 d . . . . .
H3 H 0.7201 1.0388 0.5700 0.039 Uiso 1 1 calc R U . . .
N1 N 0.6127(2) 0.7492(2) 0.38691(7) 0.0210(6) Uani 1 1 d . . . . .
N2 N 0.4668(2) 0.7372(2) 0.32693(8) 0.0251(6) Uani 1 1 d . . . . .
N3 N 0.6122(2) 0.6229(2) 0.56458(7) 0.0193(6) Uani 1 1 d . . . . .
H3N H 0.5799 0.5574 0.5420 0.023 Uiso 1 1 d R U . . .
C1 C 0.6954(3) 0.6467(3) 0.37203(9) 0.0218(7) Uani 1 1 d . . . . .
C2 C 0.6610(3) 0.5916(3) 0.32926(9) 0.0192(7) Uani 1 1 d . . . . .
C3 C 0.7379(3) 0.4902(3) 0.30933(10) 0.0327(9) Uani 1 1 d . . . . .
H3A H 0.8139 0.4571 0.3237 0.039 Uiso 1 1 calc R U . . .
C4 C 0.7043(4) 0.4383(3) 0.26927(11) 0.0390(10) Uani 1 1 d . . . . .
H4 H 0.7567 0.3689 0.2560 0.047 Uiso 1 1 calc R U . . .
C5 C 0.5939(4) 0.4868(3) 0.24801(10) 0.0391(9) Uani 1 1 d . . . . .
H5 H 0.5714 0.4512 0.2200 0.047 Uiso 1 1 calc R U . . .
C6 C 0.5173(3) 0.5857(3) 0.26716(10) 0.0309(8) Uani 1 1 d . . . . .
H6 H 0.4416 0.6179 0.2524 0.037 Uiso 1 1 calc R U . . .
C7 C 0.5494(3) 0.6399(3) 0.30831(9) 0.0214(7) Uani 1 1 d . . . . .
C8 C 0.5035(3) 0.7863(3) 0.36417(9) 0.0238(7) Uani 1 1 d . . . . .
H8 H 0.4495 0.8549 0.3771 0.029 Uiso 1 1 calc R U . . .
C9 C 0.6443(3) 0.8195(3) 0.42776(8) 0.0274(8) Uani 1 1 d . . . . .
H9A H 0.5990 0.9100 0.4282 0.033 Uiso 1 1 calc R U . . .
H9B H 0.7392 0.8380 0.4284 0.033 Uiso 1 1 calc R U . . .
C10 C 0.6078(3) 0.7407(3) 0.46837(9) 0.0209(7) Uani 1 1 d . . . . .
C11 C 0.6749(3) 0.7927(3) 0.50871(9) 0.0228(8) Uani 1 1 d . . . . .
H11A H 0.6901 0.8932 0.5051 0.027 Uiso 1 1 calc R U . . .
H11B H 0.7614 0.7476 0.5104 0.027 Uiso 1 1 calc R U . . .
C12 C 0.6061(3) 0.7707(3) 0.55209(9) 0.0196(7) Uani 1 1 d . . . . .
H12 H 0.5127 0.7984 0.5489 0.024 Uiso 1 1 calc R U . . .
C13 C 0.6687(3) 0.8588(3) 0.58748(9) 0.0204(7) Uani 1 1 d . . . . .
H13 H 0.7645 0.8397 0.5880 0.024 Uiso 1 1 calc R U . . .
C14 C 0.6128(3) 0.8302(3) 0.63246(9) 0.0257(8) Uani 1 1 d . . . . .
H14A H 0.5225 0.8660 0.6338 0.031 Uiso 1 1 calc R U . . .
H14B H 0.6650 0.8800 0.6547 0.031 Uiso 1 1 calc R U . . .
C15 C 0.6125(3) 0.6764(3) 0.64303(9) 0.0263(8) Uani 1 1 d . . . . .
H15A H 0.7032 0.6433 0.6464 0.032 Uiso 1 1 calc R U . . .
H15B H 0.5662 0.6606 0.6710 0.032 Uiso 1 1 calc R U . . .
C16 C 0.5460(3) 0.5967(3) 0.60690(9) 0.0254(7) Uani 1 1 d . . . . .
H16A H 0.5485 0.4965 0.6136 0.030 Uiso 1 1 calc R U . . .
H16B H 0.4536 0.6253 0.6049 0.030 Uiso 1 1 calc R U . . .


_geom_special_details            
; 
 All esds (except the esd in the dihedral angle between two l.s. planes) 
 are estimated using the full covariance matrix.  The cell esds are taken 
 into account individually in the estimation of esds in distances, angles 
 and torsion angles; correlations between esds in cell parameters are only 
 used when they are defined by crystal symmetry.  An approximate (isotropic) 
 treatment of cell esds is used for estimating esds involving l.s. planes. 
;

loop_
_geom_bond_atom_site_label_1
_geom_bond_atom_site_label_2
_geom_bond_distance
_geom_bond_site_symmetry_2
_geom_bond_publ_flag
O1 C1 1.230(3) . ?
O2 C10 1.210(3) . ?
O3 C13 1.441(3) . ?
O3 H3 0.8400 . ?
N1 C8 1.366(3) . ?
N1 C1 1.381(3) . ?
N1 C9 1.457(3) . ?
N2 C8 1.288(3) . ?
N2 C7 1.388(3) . ?
N3 C12 1.479(3) . ?
N3 C16 1.482(3) . ?
N3 H3N 0.9923 . ?
C1 C2 1.453(4) . ?
C2 C7 1.392(4) . ?
C2 C3 1.398(4) . ?
C3 C4 1.366(4) . ?
C3 H3A 0.9500 . ?
C4 C5 1.387(4) . ?
C4 H4 0.9500 . ?
C5 C6 1.368(4) . ?
C5 H5 0.9500 . ?
C6 C7 1.401(4) . ?
C6 H6 0.9500 . ?
C8 H8 0.9500 . ?
C9 C10 1.503(3) . ?
C9 H9A 0.9900 . ?
C9 H9B 0.9900 . ?
C10 C11 1.498(4) . ?
C11 C12 1.516(3) . ?
C11 H11A 0.9900 . ?
C11 H11B 0.9900 . ?
C12 C13 1.518(3) . ?
C12 H12 1.0000 . ?
C13 C14 1.514(3) . ?
C13 H13 1.0000 . ?
C14 C15 1.521(3) . ?
C14 H14A 0.9900 . ?
C14 H14B 0.9900 . ?
C15 C16 1.508(3) . ?
C15 H15A 0.9900 . ?
C15 H15B 0.9900 . ?
C16 H16A 0.9900 . ?
C16 H16B 0.9900 . ?

loop_
_geom_angle_atom_site_label_1
_geom_angle_atom_site_label_2
_geom_angle_atom_site_label_3
_geom_angle
_geom_angle_site_symmetry_1
_geom_angle_site_symmetry_3
_geom_angle_publ_flag
C13 O3 H3 109.5 . . ?
C8 N1 C1 121.6(2) . . ?
C8 N1 C9 119.7(2) . . ?
C1 N1 C9 118.7(3) . . ?
C8 N2 C7 115.6(3) . . ?
C12 N3 C16 111.7(2) . . ?
C12 N3 H3N 115.0 . . ?
C16 N3 H3N 110.1 . . ?
O1 C1 N1 119.9(3) . . ?
O1 C1 C2 125.9(3) . . ?
N1 C1 C2 114.2(3) . . ?
C7 C2 C3 119.9(3) . . ?
C7 C2 C1 119.4(3) . . ?
C3 C2 C1 120.7(3) . . ?
C4 C3 C2 120.3(3) . . ?
C4 C3 H3A 119.8 . . ?
C2 C3 H3A 119.8 . . ?
C3 C4 C5 120.1(3) . . ?
C3 C4 H4 120.0 . . ?
C5 C4 H4 120.0 . . ?
C6 C5 C4 120.3(3) . . ?
C6 C5 H5 119.8 . . ?
C4 C5 H5 119.8 . . ?
C5 C6 C7 120.6(3) . . ?
C5 C6 H6 119.7 . . ?
C7 C6 H6 119.7 . . ?
N2 C7 C2 122.7(3) . . ?
N2 C7 C6 118.5(3) . . ?
C2 C7 C6 118.8(3) . . ?
N2 C8 N1 126.3(3) . . ?
N2 C8 H8 116.8 . . ?
N1 C8 H8 116.8 . . ?
N1 C9 C10 114.5(2) . . ?
N1 C9 H9A 108.6 . . ?
C10 C9 H9A 108.6 . . ?
N1 C9 H9B 108.6 . . ?
C10 C9 H9B 108.6 . . ?
H9A C9 H9B 107.6 . . ?
O2 C10 C11 123.7(3) . . ?
O2 C10 C9 123.0(3) . . ?
C11 C10 C9 113.2(2) . . ?
C10 C11 C12 117.2(2) . . ?
C10 C11 H11A 108.0 . . ?
C12 C11 H11A 108.0 . . ?
C10 C11 H11B 108.0 . . ?
C12 C11 H11B 108.0 . . ?
H11A C11 H11B 107.2 . . ?
N3 C12 C11 109.9(2) . . ?
N3 C12 C13 109.9(2) . . ?
C11 C12 C13 110.3(2) . . ?
N3 C12 H12 108.9 . . ?
C11 C12 H12 108.9 . . ?
C13 C12 H12 108.9 . . ?
O3 C13 C14 109.8(2) . . ?
O3 C13 C12 107.7(2) . . ?
C14 C13 C12 112.5(2) . . ?
O3 C13 H13 108.9 . . ?
C14 C13 H13 108.9 . . ?
C12 C13 H13 108.9 . . ?
C13 C14 C15 111.8(2) . . ?
C13 C14 H14A 109.3 . . ?
C15 C14 H14A 109.3 . . ?
C13 C14 H14B 109.3 . . ?
C15 C14 H14B 109.3 . . ?
H14A C14 H14B 107.9 . . ?
C16 C15 C14 110.2(2) . . ?
C16 C15 H15A 109.6 . . ?
C14 C15 H15A 109.6 . . ?
C16 C15 H15B 109.6 . . ?
C14 C15 H15B 109.6 . . ?
H15A C15 H15B 108.1 . . ?
N3 C16 C15 110.1(2) . . ?
N3 C16 H16A 109.6 . . ?
C15 C16 H16A 109.6 . . ?
N3 C16 H16B 109.6 . . ?
C15 C16 H16B 109.6 . . ?
H16A C16 H16B 108.2 . . ?

loop_
_geom_hbond_atom_site_label_D
_geom_hbond_atom_site_label_H
_geom_hbond_atom_site_label_A
_geom_hbond_distance_DH
_geom_hbond_distance_HA
_geom_hbond_distance_DA
_geom_hbond_angle_DHA
_geom_hbond_site_symmetry_A
O3 H3 N3 0.84 1.91 2.744(3) 172.3 8_765
N3 H3N O2 0.99 2.47 3.069(3) 118.5 .
N3 H3N O2 0.99 2.30 3.155(3) 144.0 5_666
C8 H8 O3 0.95 2.23 3.154(3) 164.2 5_676
C9 H9A O1 0.99 2.48 3.079(3) 118.2 8_765
C14 H14A O1 0.99 2.54 3.457(4) 153.2 4_466

_refine_diff_density_max         0.276
_refine_diff_density_min         -0.313
_refine_diff_density_rms         0.069



_exptl_crystal_recrystallization_method 
'Re-crystallisation from solvent: ethyl acetate'
_chemical_properties_physical    Heat-sensitive
