Synthesis, structure and in vitro cytotoxicity testing of some 2-aroylbenzofuran-3-ols

Article abstract of DOI:10.1107/S2053229620011018

Five 2-aroyl-5-bromobenzo[b]furan-3-ol compounds (two of which are new) and four new 2-aroyl-5-iodobenzo[b]furan-3-ol compounds were synthesized starting from salicylic acid. The compounds were characterized by mass spectrometry and 1H NMR and 13C NMR spectroscopy. Single-crystal X-ray diffraction studies of four compounds, namely, (5-bromo-3-hydroxybenzofuran-2-yl)(4-fluorophenyl)methanone, C15H8BrFO3, (5-bromo-3-hydroxybenzofuran-2-yl)(4-chlorophenyl)methanone, C15H8BrClO3, (5-bromo-3-hydroxybenzofuran-2-yl)(4-bromophenyl)methanone, C15H8Br2O3, and (4-bromophenyl)(3-hydroxy-5-iodobenzofuran-2-yl)methanone, C15H8BrIO3, were also carried out. The compounds were tested for their in vitro cytotoxicity on the four human cancer cell lines KB, Hep-G2, Lu-1 and MCF7. Six compounds show good inhibiting abilities on Hep-G2 cells, with IC50 values of 1.39-8.03?μM.

Full text of DOI:10.1107/S2053229620011018

research papers
Synthesis, structure and in vitro cytotoxicity testing
of some 2-aroylbenzofuran-3-ols
ISSN 2053-2296
Nguyen Tien Cong,a* Huynh Thi Xuan Trang,a Pham Duc Dung,a Tran Hoang
Phuong,b Vu Quoc Trung,c Nguyen Dang Dat,c Dang Thi Tuyet Anh,d Nguyen Van
Tuyend and Luc Van Meervelte*
Received 17 July 2020
aFaculty of Chemistry, Ho Chi Minh City University of Education, 280 An Duong Vuong Street, District No. 5, Ho Chi
Minh City, Vietnam, bFaculty of Chemistry, University of Sciences, Vietnam National University, 227 Nguyen Van Cu
Street, District No. 5, Ho Chi Minh City 721337, Vietnam, cFaculty of Chemistry, Hanoi National University of Education,
136 Xuan Thuy, Cau Giay District, Hanoi 100000, Vietnam, dInstitute of Chemistry, Viet Nam Academy of Science and
Technology, 18 Hoang Quoc Viet, Cau Giay District, Hanoi 100000, Vietnam, and eDepartment of Chemistry, KU
Leuven, Celestijnenlaan 200F, PO box 2404, Leuven (Heverlee), B-3001, Belgium. *Correspondence e-mail:
congnt@hcmue.edu.vn, luc.vanmeervelt@kuleuven.be
Accepted 11 August 2020
Edited by A. L. Spek, Utrecht University, The
Netherlands
Keywords: 2-aroylbenzofuran-3-ol; bromo-
salicylate; iodosalicylate; crystal structure;
cytotoxicity.
Five 2-aroyl-5-bromobenzo[b]furan-3-ol compounds (two of which are new) and
four new 2-aroyl-5-iodobenzo[b]furan-3-ol compounds were synthesized
starting from salicylic acid. The compounds were characterized by mass
CCDC references: 2022658; 2022657;
2022656; 2022655
1
spectrometry and H NMR and 13C NMR spectroscopy. Single-crystal X-ray
diffraction studies of four compounds, namely, (5-bromo-3-hydroxybenzofuran-
2-yl)(4-fluorophenyl)methanone, C15H8BrFO3, (5-bromo-3-hydroxybenzofuran-
2-yl)(4-chlorophenyl)methanone, C15H8BrClO3, (5-bromo-3-hydroxybenzofuran-
2-yl)(4-bromophenyl)methanone, C15H8Br2O3, and (4-bromophenyl)(3-hydroxy-
5-iodobenzofuran-2-yl)methanone, C15H8BrIO3, were also carried out. The
compounds were tested for their in vitro cytotoxicity on the four human cancer
cell lines KB, Hep-G2, Lu-1 and MCF7. Six compounds show good inhibiting
abilities on Hep-G2 cells, with IC50 values of 1.39–8.03 mM.
Supporting information: this article has
supporting information at journals.iucr.org/c
1. Introduction
Benzofurans have been considered as fundamental units in
numerous bioactive compounds and are present in a large
number of bioactive natural compounds. The benzofuran
nucleus is present in a huge number of bioactive natural
compounds. For example, (+)-liphagal is a selective phospho-
inositide-3-kinase ꢀ-inhibitor (Marion et al., 2006), cyclo-
penta[b]benzofuran compounds possess antitumour and
antiviral activities (Kim et al., 2006), while derivatives of
egonol have antioxidant and anti-inflammatory activities
(Timmers et al., 2015). Synthetic benzofuran derivatives are
found to possess antitumour and anticancer (Shi et al., 2016;
`
´
Marques et al., 2016; Napiorkowska et al., 2019; Asadi et al.,
2017), antimicrobial (Asadi et al., 2017; He et al., 2017; Xu et
al., 2019) and antitubercular (Xu et al., 2019) activities. Some
synthetic benzofuran derivatives have been investigated in the
`
role of osteogenic (Marques et al., 2016; Kushwaha et al., 2018;
Modukuri et al., 2017) or vasorelaxant (Hassan et al., 2014)
agents. 2-Aroylbenzofuran-3-ols, being a class of typical
benzofuran derivatives, not only possess antimicrobial (Kulk-
arni et al., 2014), antitumour (Sargolzaei et al., 2016) and ꢀ-
glucosidase inhibition (Spasov et al., 2017) properties, but are
also useful intermediates for the synthesis of several
compounds having various biological activities (Shi et al., 2016;
Dong et al., 2013; Rashmi et al., 2015). Although many
2-aroylbenzofuran-3-ols have been synthesized and studied for
# 2020 International Union of Crystallography
874 https://doi.org/10.1107/S2053229620011018
Acta Cryst. (2020). C76, 874–882

research papers
their biological activities, the structural characteristics and
cytotoxic activity of 2-aroyl-5-bromobenzo[b]furan-3-ol and
2-aroyl-5-iodobenzo[b]furan-3-ol compounds have not been
studied much. We present here the synthesis of nine 2-aroyl-5-
bromo/iodobenzofuran-3-ol compounds starting from salicylic
acid. In addition to the synthesis and structure analysis of these
compounds, the in vitro toxicity on the four human cancer cell
lines KB, Hep-G2, Lu-1 and MCF7 has been tested.
8.5 Hz, 4J = 2.5 Hz, H4), 6.82 (1H, d, 3J = 9.0 Hz, H3), 3.87 (3H,
s, OCH3).
2.1.1. General procedure for the synthesis of 2-aroyl-5-
halobenzo[b]furan-3-ol compounds 4a–4i. Anhydrous po-
tassium carbonate (0.896 mg, 6.4 mmol) was added to a
mixture of methyl 5-halosalicylate (2.1 mmol) and substituted
phenacyl bromide (2.1 mmol) in dried dimethylformamide
(DMF, 10 ml) at room temperature while stirring. After 1 h of
stirring, the reaction mixture was poured into ice-cold water
and acidified with 1 N HCl. The precipitate obtained was
filtered off and crystallized from an appropriate solvent to give
the corresponding products 4a–4i.
2. Experimental
All chemicals were obtained from commercial sources and
were used without further purification. The melting points
were determined in open capillaries and are uncorrected. The
IR spectra were recorded on an FT–IR Shimadzu 8400-S.
NMR spectra were measured on a Bruker Avance 500 MHz in
DMSO-d6 using residual solvent DMSO-d6 signals as the
internal references. Mass spectra were recorded on a Sciex
X500 QTOF mass spectrometer.
The crystals of 4a, 4b, 4c and 4h were suitable for X-ray
diffraction.
(5-Bromo-3-hydroxybenzofuran-2-yl)(4-fluorophenyl)metha-
none (4a): yellow crystals, recrystallized from a mixture of
ethanol and water; m.p. 391–393 K [melting point according to
Kulkarni et al. (2014): 393 K]; yield 84%. IR (ꢁ, cmꢀ1): 3057
(Csp2—H), 1614 (C O), 1597, 1528 (C C), 625 (C—Br); 1H
NMR: 8.06 (3H, m, Ar-H), 7.71 (1H, m, Ar-H), 7.64 (1H, m,
Ar-H), 7.40 (2H, m, Ar-H); 13C NMR: 181.8, 166.1, 164.1,
152.4, 148.3, 136.4, 134.2, 132.8, 132.4, 132.3, 124.4, 123.7, 115.9,
115.8, 115.6, 115.3; MS: m/z 332.9564 [M ꢀ H]+; calculation for
C15H7BrFO3: M = 332.9568 a.u.
2.1. Synthesis and crystallization
Benzofuran derivatives 4a–4i were synthesized as shown in
Fig. 1. Methyl salicylate (2) (Cong et al., 2012), methyl
5-bromo-2-hydroxybenzoate (3a) (Thin et al., 2018) and
methyl 2-hydroxy-5-iodobenzoate (3b) (Cong et al., 2018)
were synthesized according to previously reported methods.
Methyl salicylate (2): liquid; b.p. 494–495 K, yield 73%.
Methyl 5-bromo-2-hydroxybenzoate (methyl 5-bromosali-
cylate) (3a): white needles, m.p. 332–333 K, yield 92%; IR (ꢁ,
(5-Bromo-3-hydroxybenzofuran-2-yl)(4-chlorophenyl)me-
thanone (4b): yellow crystals, recrystallized from a mixture of
ethanol and water; m.p. 436–437 K [melting point according to
Kulkarni et al. (2014): 435–438 K]; yield 93%. IR (ꢁ, cmꢀ1):
3254 (O—H), 3078 (Csp2—H), 1599, 1566 (C O, C C), 660
(C—Br); 1H NMR: 8.13 (1H, d, 4J = 2.0 Hz, Ar-H), 7.98 (2H, d,
1
4
cmꢀ1): 3188, 2957, 1680, 1605, 625; H NMR (ꢂ, ppm): 10.50
3J = 8.5 Hz, Ar-H), 7.72 (1H, dd, 3J = 8.5, J = 2.0 Hz, Ar-H),
(1H, br, OH), 7.82 (1H, d, 4J = 2.5 Hz, H6), 7.64 (1H, dd, 3J =
8.0 Hz, 4J = 2.5 Hz, H4), 6.96 (1H, d, 3J = 8.0 Hz, H3), 3.88 (3H,
s, OCH3).
7.63 (3H, m, Ar-H); 13C NMR: 181.9, 152.5, 148.4, 137.8, 136.4,
132.9, 131.3, 128.9, 124.5, 123.7, 115.6, 115.3; MS: m/z 350.9434
[M + H]+; calculation for C15H9BrClO3: M = 350.9424 a.u.
(5-Bromo-3-hydroxybenzofuran-2-yl)(4-bromophenyl)me-
thanone (4c): yellow crystals, recrystallized from a mixture of
ethanol and water; m.p. 426–427 K [melting point according to
Kulkarni et al. (2014): 425–426 K]; yield 91%. IR (ꢁ, cmꢀ1):
Methyl 2-hydroxy-5-iodobenzoate (methyl 5-iodosalicylate)
(3b): white needles, m.p. 347–348 K, yield 85%; IR (ꢁ, cmꢀ1):
1
3156, 3080, 2949, 1676, 1604, 527; H NMR (ꢂ, ppm): 10.46,
4
(1H, s, OH), 7.98 (1H, d, J = 2.0 Hz, H6), 7.75 (1H, d, J =
3
Figure 1
The synthetic route for the preparation of benzofuran derivatives 4a–4i.
ꢁ
Acta Cryst. (2020). C76, 874–882
Cong et al.
In vitro cytotoxicity testing of 2-aroylbenzofuran–3-ols 875

research papers
Table 1
Experimental details.
Experiments were carried out with Mo Kꢀ radiation using a Rigaku OD SuperNova Single source diffractometer with an Eos detector. H atoms were treated by a
mixture of independent and constrained refinement.
4a
4b
4c
4h
Crystal data
Chemical formula
Mr
C15H8BrFO3
335.12
C15H8BrClO3
351.57
C15H8Br2O3
396.03
C15H8BrIO3
443.02
Crystal system, space group
Temperature (K)
Monoclinic, P21/c
293
3.8598 (4), 11.7229 (10),
27.679 (2)
90, 93.255 (9), 90
Monoclinic, P21/c
294
26.4034 (10), 3.9818 (1),
26.2773 (10)
90, 104.605 (4), 90
Triclinic, P1
294
Monoclinic, I2/a
293
26.4214 (8), 4.76309 (13),
46.6213 (14)
90, 106.034 (3), 90
˚
a, b, c (A)
7.0725 (4), 7.0884 (5),
14.6069 (8)
92.230 (5), 103.091 (5),
101.219 (6)
696.98 (8)
ꢀ, ꢃ, ꢄ (ꢂ)
3
˚
V (A )
1250.38 (19)
4
3.30
0.5 ꢃ 0.15 ꢃ 0.05
2673.34 (17)
8
3.28
0.4 ꢃ 0.15 ꢃ 0.05
5638.9 (3)
16
5.11
0.35 ꢃ 0.15 ꢃ 0.05
Z
2
5.82
ꢅ (mmꢀ1
Crystal size (mm)
)
0.35 ꢃ 0.15 ꢃ 0.05
Data collection
Absorption correction
Multi-scan (CrysAlis PRO;
Rigaku OD, 2018)
0.447, 1.000
Multi-scan (CrysAlis PRO;
Rigaku OD, 2018)
0.572, 1.000
Multi-scan (CrysAlis PRO;
Rigaku OD, 2018)
0.523, 1.000
Gaussian (CrysAlis PRO;
Rigaku OD, 2018)
0.582, 1.000
Tmin, Tmax
No. of measured, indepen-
dent and observed [I >
2ꢆ(I)] reflections
Rint
7646, 2543, 1873
27661, 5419, 3168
14183, 2840, 1867
30966, 5733, 4448
0.040
0.625
0.064
0.625
0.046
0.625
0.036
0.625
ꢀ1
˚
(sin ꢇ/ꢈ)max (A
)
Refinement
R[F2 > 2ꢆ(F2)], wR(F2), S
No. of reflections
0.045, 0.097, 1.07
2543
0.052, 0.102, 1.01
5419
0.046, 0.109, 1.04
2840
0.048, 0.123, 1.07
5733
No. of parameters
No. of restraints
185
0
0.44, ꢀ0.45
369
0
0.56, ꢀ0.42
185
0
369
2
1.78, ꢀ1.21
ꢀ3
˚
Áꢉmax, Áꢉmin (e A
)
0.44, ꢀ0.40
Computer programs: CrysAlis PRO (Rigaku OD, 2018), olex2.solve (Bourhis et al., 2015), SHELXS (Sheldrick, 2008), SHELXT (Sheldrick, 2015a), SHELXL2016 (Sheldrick, 2015b)
and OLEX2 (Dolomanov et al., 2009).
3337 (O—H), 3076 (Csp2—H), 1601, 1562 (C O, C C), 658
(C—Br); 1H NMR: 8.13 (1H, d, 4J = 2.0 Hz, Ar-H), 7.90 (2H, d,
3J = 8.5 Hz, Ar-H), 7.77 (1H, dd, J = 8.5, J = 2.0 Hz, Ar-H),
7.72 (2H, d, 4J = 2.0 Hz, Ar-H), 7.62 (1H, d, 3J = 8.5 Hz, Ar-H);
13C NMR: 182.0, 152.5, 148.4, 136.8, 136.4, 132.9, 131.5, 126.8,
124.5, 123.7, 115.6, 115.4; MS: m/z 394.8757 [M + H]+; calcu-
lation for C15H9Br2O3: M = 394.8918 a.u.
125.4, 124.9, 123.8, 116.3, 115.6, 115.3; MS: m/z 359.9510
[M ꢀ H]+; calculation for C15H7BrNO5: M = 359.9513 a.u.
(3-Hydroxy-5-iodobenzofuran-2-yl)(phenyl)methanone (4f):
yellow crystals, recrystallized from a mixture of acetone and
water; m.p. 411–412 K; yield 78%. IR (ꢁ, cmꢀ1): 3084 (OH),
3
4
1
1609 (C O), 1572, 1520 (C C), 561 (C—I); H NMR: 8.30
(1H, d, 4J = 1.5 Hz, Ar-H), 7.97 (2H, d, 3J = 7.0 Hz, Ar-H), 7.84
(1H, m, Ar-H), 7.65 (1H, dd, 3J1 = 3J2 = 7.0, Ar-H), 7.56 (2H, d,
(5-Bromo-3-hydroxybenzofuran-2-yl)(3-nitrophenyl)metha-
none (4d): yellow crystals, recrystallized from a mixture of
ethanol and water; m.p. 428–431 K; yield 76%. IR (ꢁ, cmꢀ1):
3274 (O—H), 1631 (C O), 1613, 1577, 1530 (C C), 659
3J = 7.0 Hz, Ar-H), 7.49 (1H, dd, 3J1 = 9.0, 4J2 = 5.0, Ar-H); 13
C
NMR: 183.2, 152.9, 148.0, 138.3, 138.7, 136.1, 132.9, 130.4, 129.4,
128.8, 124.4, 115.6, 87.3; MS: m/z 364.9652 [M + H]+; calculation
for C19H16ClIN2NaO4: M = 364.9675 a.u.
1
(C—Br); H NMR: 8.62 (1H, m, Ar-H), 8.38 (1H, s, Ar-H),
8.24 (2H, m, Ar-H), 8.12 (1H, d, 3J = 8.5 Hz, Ar-H), 7.89 (1H,
m, Ar-H), 7.75 (1H, m, Ar-H); 13C NMR: 180.5, 152.9, 148.0,
139.2, 136.2, 135.8, 133.2, 130.5, 127.1, 124.8, 124.1, 123.7, 115.5,
115.3; MS: m/z 361.9642 [M + H]+; calculation for C15H9BrNO5:
M = 361.9664 a.u.
(5-Bromo-3-hydroxybenzofuran-2-yl)(4-nitrophenyl)metha-
none (4e): yellow crystals, recrystallized from a mixture of
acetone and water; m.p. 438–439 K; yield 83%. IR (ꢁ, cmꢀ1):
3292 (O—H), 3098 (Csp2—H), 1624 (C O), 1597, 1547
(C C), 660 (C—Br); 1H NMR: 8.37 (2H, d, 3J = 8.5 Hz, Ar-H),
8.23 (1H, d, 4J = 2.5 Hz, Ar-H), 8.12 (2H, d, 3J = 8.5 Hz, Ar-H),
7.74 (1H, dd, 3J = 8.5, 4J = 2.5 Hz, Ar-H), 7.63 (1H, 3J = 9.0 Hz,
Ar-H); 13C NMR: 181.3, 152.9, 149.7, 143.5, 136.3, 133.3, 130.6,
(4-Chlorophenyl)(3-hydroxy-5-iodobenzofuran-2-yl)metha-
none (4g): yellow crystals, recrystallized from a mixture of
ethanol and water; m.p. 443–444 K; yield 88%. IR (ꢁ, cmꢀ1):
3231 (OH), 1616 (C O), 1591, 1567, 1531 (C C), 565 (C—I);
4
3
1H NMR: 8.29 (1H, d, J = 1.5 Hz, Ar-H), 7.97 (2H, d, J =
3
9.0 Hz, Ar-H), 7.84 (1H, dd, J = 9.0, 4J = 2.0 Hz, Ar-H), 7.62
(2H, d, 3J = 9.0 Hz, Ar-H), 7.48 (1H, d, 3J = 9.0 Hz, Ar-H); 13
C
NMR: 181.4, 152.5, 147.6, 137.9, 137.2, 135.9, 135.4, 130.8,
130.0, 128.3, 123.8, 115.0, 86.7; MS: m/z 396.9119 [M ꢀ H]+;
calculation for C15H7ClIO3: M = 396.9134 a.u.
(4-Bromophenyl)(3-hydroxy-5-iodobenzofuran-2-yl)metha-
none (4h): yellow crystals, recrystallized from a mixture of
acetone and water; m.p. 441–442 K; yield 91%. IR (ꢁ, cmꢀ1):
ꢁ
876 Cong et al. In vitro cytotoxicity testing of 2-aroylbenzofuran–3-ols
Acta Cryst. (2020). C76, 874–882

research papers
Table 2
Hydrogen-bond geometry (A, ) for 4a.
All the experiments were performed four or five times and
the mean absorbance values were calculated. The results are
expressed as the percentage of inhibition that produced a
reduction in the absorbance by the treatment of the com-
pounds compared to the untreated controls. A dose–response
curve was generated and the inhibitory concentration of 50%
(IC50) was determined for each compound, as well as each cell
line.
ꢂ
˚
D—Hꢅ ꢅ ꢅA
D—H
Hꢅ ꢅ ꢅA
Dꢅ ꢅ ꢅA
D—Hꢅ ꢅ ꢅA
O19—H19ꢅ ꢅ ꢅO11
C17—H17ꢅ ꢅ ꢅO1
C16—H16ꢅ ꢅ ꢅO11i
C5—H5ꢅ ꢅ ꢅO19ii
0.77 (5)
0.93
0.93
2.03 (4)
2.32
2.51
2.692 (4)
2.942 (4)
3.428 (4)
3.454 (5)
144 (4)
124
170
0.93
2.61
150
1
2
1
2
Symmetry codes: (i) ꢀx þ 2; y ꢀ ; ꢀz þ ; (ii) ꢀx þ 1; ꢀy þ 1; ꢀz þ 1.
3447 (O—H), 1614 (C O), 1584, 1561, 1522 (C C), 561
(C—I); 1H NMR: 8.31 (1H, d, 4J = 1.5 Hz, Ar-H), 7.87 (3H, m,
Ar-H), 7.78 (2H, d, 3J = 8.5 Hz, Ar-H), 7.50 (1H, d, 3J = 9.0 Hz,
Ar-H); 13C NMR: 181.8, 152.9, 148.0, 138.3, 136.9, 135.9, 131.8,
131.5, 130.6, 128.1, 126.7, 124.4, 115.6, 87.3; MS: m/z 442.8761
[M + H]+; calculation for C15H9BrIO3: M = 442.8780 a.u.
(3-Hydroxy-5-iodobenzofuran-2-yl)(3-nitrophenyl)metha-
none (4i): yellow crystals, recrystallized from a mixture of
ethanol and water; m.p. 435–436 K; yield 80%. IR (ꢁ, cmꢀ1):
3245 (O—H), 3072 (Csp2—H), 1614 (C O), 1577, 1527
(C C), 560 (C—I); 1H NMR: 8.59 (1H, s, Ar-H), 8.39 (1H, dd,
3. Results and discussion
3.1. Synthesis of 2-aroyl-5-halobenzo[b]furan-3-ol) com-
pounds 4a–4i
Nine 2-aroyl-5-halobenzofuran-3-ol derivatives, 4a–4i, were
synthesized with yields between 76 and 93% starting from
salicylic acid 1 (Fig. 1). Methyl salicylate (2), methyl
5-bromo-2-hydroxybenzoate (3a) and methyl 2-hydroxy-5-
iodobenzoate (3a) were synthesized previously by our
research group (Cong et al., 2012, 2018; Thin et al., 2018). The
IR spectra of 3a–3b show a strong band at 1680 cmꢀ1 corre-
sponding to a C O stretching vibration of the ester group.
4
4
3J = 8.0, J = 2.0 Hz, Ar-H), 8.26 (1H, d, J = 8.0 Hz, Ar-H),
1
3
8.08 (1H, s, Ar-H), 7.76 (1H, dd, J1 = J2 = 8.0 Hz, Ar-H),
3
The H NMR spectra of 3a and 3b show the presence of the
methoxy group as a singlet signal (3H) at ꢂ 3.88 and 3.87,
respectively. The three signals in the aromatic area, including a
3
4
3
7.66 (1H, dd, J = 8.0, J = 1.5 Hz, Ar-H), 7.56 (1H, d, J =
8.0 Hz, Ar-H); 13C NMR: 180.4, 153.6, 148.4, 147.8, 138.8,
137.3, 136.4, 135.6, 130.3, 129.7, 127.4, 124.2, 118.1, 115.4, 87.1;
MS: m/z 407.9374 [M ꢀ H]ꢀ; calculation for C15H7INO5: M =
407.9374 a.u.
4
doublet signal (1H, J = 2.0 Hz), a doublet of doublet signals
3
4
3
(1H, J = 8.0, J = 2.0 Hz) and a doublet signal (1H, J =
8.0 Hz), are typical for a benzene ring with three substituents
at positions 1, 2 and 5.
To obtain the desired (5-halo-3-hydroxybenzo[b]furan-2-
yl)(substituted phenyl)methanones (4a–4i), methyl 5-bromo-
salicylate (3a) or methyl 5-iodosalicylate (3b) were reacted
with a substituted phenacyl bromide compound in DMF in the
presence of potassium carbonate. This is considered an
effective synthesis method for the preparation of 2-aroyl-
benzofuran-3-ol compounds (Kulkarni et al., 2014). The
physical and spectral properties of 4a–4c were available in the
literature (Kulkarni et al., 2014).
In the IR spectra of 4a–4i, the OH group often shows only a
weak absorption. The reason is that these compounds may
exist in the 2-aroylbenzofuran-3(2H)-one form (Kulkarni et
al., 2014). The C O bond in the aroyl group absorbs at low
2.2. Refinement
Crystal data, data collection and structure refinement
details for 4a, 4b, 4c and 4h are summarized in Table 1. The
O-bound H atoms (H19 and also H39 for 4b and 4h) were
located from a difference Fourier map and refined freely for
˚
4a–4c or with O—H = 0.78 ꢄ 0.01 A for 4h. The C-bound H
˚
atoms were placed in calculated positions (C—H = 0.93 A)
and were refined using a riding model, with Uiso(H) values set
at 1.2Ueq(C).
2.3. In vitro cell tests
Compounds 4a, 4b and 4d–4i were evaluated for their
cytotoxicity against four human cancer cell lines, namely, KB
(epidermoid carcinoma cancer), Hep-G2 (hepatoma carci-
noma cancer), Lu (human lung adenocarcinoma cells) and
MCF7 (human breast cancer cells). The cell lines were
obtained from the American Type Culture Collection (USA)
ATCC. The cells were grown in RPMI 1640 medium supple-
mented with 10% fetal bovine serum, 100 U mlꢀ1 penicillin
and 100 mg mlꢀ1 streptomycin at 310 K in a humidified
atmosphere (95% air and 5% CO2). The exponentially
growing cells were used throughout the experiments. The
inhibitory effects of the compounds on the growth of the
human cancer cell lines were determined by measuring the
metabolic activity using a 3-(4,5-dimethylthiazol-2-yl)-2,5-di-
phenyltetrazolium bromide (MTT) assay, as reported pre-
viously (Cong et al., 2018).
Figure 2
The molecular structure of 4a, showing the atom-labelling scheme.
Displacement ellipsoids are drawn at the 50% probability level.
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In vitro cytotoxicity testing of 2-aroylbenzofuran–3-ols 877

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Table 3
Hydrogen-bond geometry (A, ) for 4b.
ꢂ
˚
D—Hꢅ ꢅ ꢅA
D—H
Hꢅ ꢅ ꢅA
Dꢅ ꢅ ꢅA
D—Hꢅ ꢅ ꢅA
O19—H19ꢅ ꢅ ꢅO11
C17—H17ꢅ ꢅ ꢅO1
O39—H39ꢅ ꢅ ꢅO31
C37—H37ꢅ ꢅ ꢅO21
C36—H36ꢅ ꢅ ꢅO11
C8—H8ꢅ ꢅ ꢅO39i
0.86 (5)
0.93
0.91 (6)
0.93
0.93
1.87 (5)
2.29
1.80 (6)
2.25
2.40
2.631 (5)
2.951 (5)
2.627 (6)
2.926 (6)
3.235 (6)
3.434 (6)
147 (5)
128
150 (7)
129
149
0.93
2.67
140
1
1
Symmetry code: (i) x; ꢀy þ ; z ꢀ .
2
2
Table 4
Hydrogen-bond geometry (A, ) for 4c.
ꢂ
˚
D—Hꢅ ꢅ ꢅA
D—H
Hꢅ ꢅ ꢅA
Dꢅ ꢅ ꢅA
D—Hꢅ ꢅ ꢅA
O19—H19ꢅ ꢅ ꢅO11
C17—H17ꢅ ꢅ ꢅO1
0.84 (6)
0.93
0.84 (6)
0.93
0.93
1.93 (6)
2.28
2.60 (6)
3.05
2.61
2.669 (5)
2.948 (5)
3.174 (5)
3.959 (5)
3.287 (6)
146 (5)
129
127
165
130
O19—H19ꢅ ꢅ ꢅO11i
C14—H14ꢅ ꢅ ꢅBr20ii
C16—H16ꢅ ꢅ ꢅO11iii
Figure 4
Symmetry codes: (i) ꢀx; ꢀy; ꢀz þ 1; (ii) x; y; z þ 1; (iii) x; y þ 1; z.
The molecular structure of 4b, showing the atom-labelling scheme for
both crystallographically unique molecules. Displacement ellipsoids are
drawn at the 50% probability level.
frequency (around 1610 cmꢀ1) due to conjugation with both
the benzene and the benzofuran rings. In the 1H NMR spectra
of 4a–4i, the signal of the OH proton is also rarely observed,
which can be explained by the exchangeable character of the
proton and/or hydrogen-bond formation. Apart from the Csp2
signals in the aromatic area, the C O carbon signal of the
aroyl group usually appears at ꢂ 180–182 in the 13C NMR
spectra of 4a–4i. In the mass spectra, the pseudo-molecular
peaks [M + H]+ or [M ꢀ H]ꢀ of 4a–4i are in agreement with
their molecular formulae.
Compound 4a crystallizes in the space group P21/c with one
molecule in the asymmetric unit (Fig. 2). The dihedral angle
between the best planes through the benzofuran (atoms O1–
C9) and phenyl (C12–C17) rings is 23.00 (16)ꢂ. The intra-
molecular O19—H19ꢅ ꢅ ꢅO11 hydrogen bond (Table 2) keeps
the last atom close to the benzofuran plane [deviation =
˚
0.123 (3) A]. The small value for the O11—C10—C12—C13
torsion angle [17.1 (5)ꢂ] causes a second intramolecular C17—
H17ꢅ ꢅ ꢅO1 interaction (Table 2).
The crystal packing of 4a is characterized by Fꢅ ꢅ ꢅBr contacts
3.2. Crystal structures of 2-aroyl-5-halobenzofuran-3-ol
derivatives 4a–4c and 4h
˚
[3.136 (2) A], resulting in chain formation in the c direction
(Fig. 3). Parallel chains interact through two types of C—
Hꢅ ꢅ ꢅO interactions (Table 2), of which one involves the
formation of an inversion dimer generating an R22(10) loop.
The resulting layers are almost parallel to the (102) plane and
For compounds 4a–4c and 4h, crystals suitable for X-ray
diffraction were obtained during crystallization experiments
using ethanol–water and acetone–water mixtures.
Figure 3
Packing diagram for 4a, viewed along the a axis, showing the Fꢅ ꢅ ꢅBr (green), O—Hꢅ ꢅ ꢅO (red) and C—Hꢅ ꢅ ꢅO (red) interactions. [Symmetry codes: (i)
1
2
1
2
1
2
1
2
1
2
1
2
ꢀx + 1, ꢀy + 1, ꢀz + 1; (ii) ꢀx + 2, y + , ꢀz + ; (iii) x + 1, ꢀy + , z ꢀ ; (iv) x ꢀ 1, ꢀy + , z + .]
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Figure 6
The molecular structure of 4c, showing the atom-labelling scheme.
Displacement ellipsoids are drawn at the 50% probability level.
Br20 and B for that containing atoms O21–Br40) in the
asymmetric unit (Fig. 4). An overlay of both structures gives
˚
an r.m.s. deviation of 0.0899 A. Compared to 4a, both mol-
ecules are more planar, as indicated by the smaller dihedral
angle between the two ring systems of 6.58 (19)ꢂ in molecule A
and 15.98 (18)ꢂ in molecule B. Atoms O11 and O31 deviate by
˚
only ꢀ0.033 (3) and 0.030 (4) A, respectively, from the
Figure 5
benzofuran plane. Also, the O11—C10—C12—C13 [11.6 (6)ꢂ]
and O31—C30—C32—C33 [3.5 (7)ꢂ] torsion angles are
reduced. The intramolecular O—Hꢅ ꢅ ꢅO hydrogen bonds are
shorter compared to those in 4a (Table 3).
Packing diagram for 4b, viewed along the b axis, showing the O—Hꢅ ꢅ ꢅO
(red) and C—Hꢅ ꢅ ꢅO (red) interactions. Letters A and B indicate
molecules A (atoms O1–Br20) and B (atoms O21–Br40). [Symmetry
codes: (i) x, ꢀy + , z ꢀ ; (ii) x, ꢀy + , z + .]
1
2
1
2
1
2
1
2
Molecules A and B are linked via C36—H36ꢅ ꢅ ꢅO11
hydrogen-bond interactions. These A–B dimers form chains
running in the c direction through C8—H8ꢅ ꢅ ꢅO39i hydrogen
bonds (Table 3 and Fig. 5). The planes of neighbouring A–B
dimers in this chain make an angle of 113.0 (2)ꢂ. Parallel
stack further along the a axis with centroid-to-centroid
˚
distances between stacking rings of 3.860 (2) A.
Compound 4b also crystallizes in the space group P21/c, but
with two molecules (denoted A for that containing atoms O1–
Figure 7
Packing diagram for 4c, viewed along the a axis, showing the O—Hꢅ ꢅ ꢅO (red), C—Hꢅ ꢅ ꢅO (red) and C—Hꢅ ꢅ ꢅBr (brown) interactions. [Symmetry codes:
(i) ꢀx, ꢀy, ꢀz + 1; (ii) x, y, z + 1; (iii) x, y + 1, z.]
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In vitro cytotoxicity testing of 2-aroylbenzofuran–3-ols 879

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Table 5
Hydrogen-bond geometry (A, ) for 4h.
ꢂ
˚
D—Hꢅ ꢅ ꢅA
D—H
Hꢅ ꢅ ꢅA
Dꢅ ꢅ ꢅA
D—Hꢅ ꢅ ꢅA
O19—H19ꢅ ꢅ ꢅO11
C17—H17ꢅ ꢅ ꢅO1
O39—H39ꢅ ꢅ ꢅO31
C37—H37ꢅ ꢅ ꢅO21
C13—H13ꢅ ꢅ ꢅO39i
0.76 (10)
0.93
0.79 (7)
0.93
0.93
2.05 (9)
2.24
1.90 (9)
2.28
2.50
2.680 (7)
2.919 (8)
2.617 (7)
2.950 (8)
3.231 (9)
140 (9)
129
151
128
135
Symmetry code: (i) x; y þ 1; z.
formed by O19—H19ꢅ ꢅ ꢅO11i interactions. At the other side of
the chain, C16—H16ꢅ ꢅ ꢅO11iii interactions extend further the
layer of molecules parallel to the (720) plane (Table 4 and
Fig. 7). The rings in the layers stack on top of each other. The
shortest centroid-to-centroid distance is observed for the
stacking of the benzofuran and phenyl rings [Cgꢅ ꢅ ꢅCg =
Figure 8
The molecular structure of 4h, showing the atom-labelling scheme for
both crystallographically unique molecules. Displacement ellipsoids are
drawn at the 50% probability level.
˚
˚
3.483 (2) A and slippage = 0.399 A].
Compound 4h crystallizes in the space group I2/a and
comprises two equivalents of the molecule (denoted A for that
containing atoms O1–I20 and B for that containing atoms
O21–I40) in the asymmetric unit, as shown in Fig. 8. An
˚
chains show close Br20ꢅ ꢅ ꢅBr20 [3.5934 (7) A] and Cl18ꢅ ꢅ ꢅCl38
˚
[3.452 (2) A] contacts, and form a corrugated board-like layer
extending in the ac plane.
Compound 4c crystallizes in the space group P1 and is
quasi-planar (Fig. 6). The r.m.s. deviation of the best plane
˚
overlay of both structures gives an r.m.s. deviation of 0.1233 A.
The dihedral angle between the two ring systems is 1.6 (3)ꢂ in
A and 7.1 (3)ꢂ in B. Atoms O11 and O31 deviate by 0.113 (5)
˚
through all the non-H atoms is 0.024 A, with atom O1
˚
˚
deviating most (0.049 A). The ring systems are inclined to
and ꢀ0.037 (5) A, respectively, from the benzofuran plane.
each other by only 1.74 (18)ꢂ and the O11—C10—C12—C13
torsion angle is 0.0 (6)ꢂ. The quasi-planarity of the molecule
does not further shorten the intramolecular hydrogen bonds
(Table 4).
The O11—C10—C12—C13 [0.4 (9)ꢂ] and O31—C30—C32—
C33 [7.0 (9)ꢂ] torsion angles are small. The intramolecular
O—Hꢅ ꢅ ꢅO hydrogen bonds are comparable to those in 4a and
4c (Table 5).
The crystal packing of 4c is built up by C14—H14ꢅ ꢅ ꢅBr20ii
interactions, resulting in chains of molecules running in the c
direction. At one side of the chain, inversion dimers are
Molecules of 4h are held together in the solid state by Xꢅ ꢅ ꢅꢊ
i
˚
interactions (with X = I, Br and O): I40ꢅ ꢅ ꢅCg6 [3.992 (3) A],
ii
Br38ꢅ ꢅ ꢅCg7ii [3.684 (3) A], O11ꢅ ꢅ ꢅCg1 [3.411 (5) A] and
˚
˚
Figure 9
Partial packing diagram for 4h, showing the Xꢅ ꢅ ꢅꢊ interactions, with X = I, Br and O (grey), and O—Hꢅ ꢅ ꢅO (red) interactions. Cg1, Cg6 and Cg7 are the
centroids of the O1/C2–C4/C9, C24–C29 and C32–C37 rings, respectively. [Symmetry codes: (i) x, y ꢀ 1, z; (ii) x, y + 1, z.]
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880 Cong et al. In vitro cytotoxicity testing of 2-aroylbenzofuran–3-ols
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Table 6
Inhibition capacity of compounds 4a, 4b and 4d–4i against four human
Table 7
Cytotoxicity of compounds 4a, 4b and 4d–4i (IC50a, mM).
cancer cell lines at a concentration of 128 mg mlꢀ1
.
Compound
KB
Hep-G2
Lu-1
MCF-7
Inhibition percentage (%)
Compound
4a
4b
4d
4e
4f
4g
15.72 ꢄ 0.36
13.72 ꢄ 0.31
17.56 ꢄ 0.33
12.27 ꢄ 0.22
21.98 ꢄ 0.38
20.07 ꢄ 0.48
42.93 ꢄ 0.93
43.72 ꢄ 0.86
1.22 ꢄ 0.08
5.69 ꢄ 0.12
8.03 ꢄ 0.23
13.16 ꢄ 0.28
1.39 ꢄ 0.02
11.14 ꢄ 0.26
3.2 ꢄ 0.09
60.61 ꢄ 1.20
34.06 ꢄ 0.60
210.91 ꢄ 5.01
62.86 ꢄ 1.33
48.55 ꢄ 0.71
49.60 ꢄ 0.98
115.08 ꢄ 2.31
56.44 ꢄ 1.30
1.83 ꢄ 0.20
23.95 ꢄ 0.45
14.86 ꢄ 0.23
88.65 ꢄ 1.58
5.54 ꢄ 0.08
21.98 ꢄ 0.44
10.54 ꢄ 0.20
18.10 ꢄ 0.32
42.67 ꢄ 0.81
2.15 ꢄ 0.20
KB
Hep-G2
Lu-1
MCF-7
4a
4b
4d
4e
4f
4g
4h
4i
88
93
96
95
85
82
76
90
88
96
90
88
92
92
85
92
90
100
97
87
96
92
95
97
96
100
74
85
4h
4i
Ellipticine
5.50 ꢄ 0.11
3.25 ꢄ 0.07
1.34 ꢄ 0.08
100
100
94
98
Note: (a) IC50 is the concentration of the compound required to inhibit cell growth by
50%. Values < 10 mM are indicated in bold.
i
˚
O31ꢅ ꢅ ꢅCg7 [3.890 (6) A] [Fig. 9; Cg1, Cg6 and Cg7 are the
centroids of the O1/C2–C4/C9, C24–C29 and C32–C37 rings,
respectively; symmetry codes: (i) x, y ꢀ 1, z; (ii) x, y + 1, z].
This is complemented by an intermolecular C13—H13ꢅ ꢅ ꢅO39i
hydrogen bond between molecules A and B (Fig. 9 and
Table 5).
MS and NMR spectroscopy. Crystals suitable for X-ray
diffraction were obtained for compounds 4a, 4b, 4c and 4h. An
intramolecular O—Hꢅ ꢅ ꢅO hydrogen bond keeps the mol-
ecules close to being planar, with dihedral angles between the
planes of the benzofuran and phenyl rings ranging from 1.6 (3)
to 23.00 (16)ꢂ. In the solid state, molecules are held together
by halogen–halogen and C—Hꢅ ꢅ ꢅO/Br interactions, com-
plemented by ꢊ–ꢊ interactions for 4c and Xꢅ ꢅ ꢅꢊ interactions
in the case of 4h (with X = I, Br and O). Compounds 4a, 4b and
4d–4i were evaluated for their cytotoxicity against four human
cancer cell lines. Six compounds showed significant inhibiting
abilities on Hep-G2 cells, with IC50 values of 1.39–8.03 mM.
With a shape similar to DAPI (40,6-diamidino-2-phenyl-
indole), these compounds can bind to DNA as a minor-groove
binder (Vlieghe et al., 1999), which could explain the cyto-
toxicity. However, it cannot be excluded that the compounds
intercalate between DNA base pairs in a way similar to
ellipticine (Canals et al., 2005).
No voids are observed in the crystal packings of these
compounds.
3.3. In vitro cytotoxicity of compounds 4a, 4b and 4d–4i
Compounds 4a, 4b and 4d–4i were evaluated for their
cytotoxicity against the four cancer cell lines KB (mouth
epidermal carcinoma cells), Hep-G2 (human liver hepatocel-
lular carcinoma cells), Lu-1 (human lung adenocarcinoma
cells) and MCF7 (human breast cancer cells). The cytotoxic
effects of these compounds were estimated in terms of growth
inhibition percentage and expressed as IC50, which is the
concentration of a compound which reduces the absorbance of
treated cells by 50% with reference to the control (untreated
cells). The inhibition capacities against the four human cancer
cell lines are listed in Table 6. All of compounds 4a, 4b and 4d–
4i displayed significant growth inhibition in the range 74–
100% at 128 mg mlꢀ1 on the four cancer cell lines. In particular,
compound 4b expressed an inhibition ability in the range 93–
100% at the same concentration.
The IC50 values in Table 7 indicate that most of the exam-
ined compounds possess at least moderate cytotoxic activity,
and some compounds even display a promising activity profile.
It is important to note that the separate pharmacophores
display considerably less potent cytotoxic activities compared
to the most promising compounds, i.e. 4a, 4b, 4e and 4g–4i
(IC50 values between 1.39 and 8.03 mM), which show a
reasonable activity against the two human cancer cell lines
Hep-G2 and MCF7. In particular, compound 4e exhibits a
strong anticancer effect against Hep-G2 cells, with an IC50
value (1.39 mM) similar to ellipticine (1.34 mM).
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882 Cong et al. In vitro cytotoxicity testing of 2-aroylbenzofuran–3-ols
Acta Cryst. (2020). C76, 874–882

supporting information
supporting information
Acta Cryst. (2020). C76, 874-882 [https://doi.org/10.1107/S2053229620011018]
Synthesis, structure and in vitro cytotoxicity testing of some 2-aroylbenzo-
furan-3-ols
Nguyen Tien Cong, Huynh Thi Xuan Trang, Pham Duc Dung, Tran Hoang Phuong, Vu Quoc
Trung, Nguyen Dang Dat, Dang Thi Tuyet Anh, Nguyen Van Tuyen and Luc Van Meervelt
Computing details
For all structures, data collection: CrysAlis PRO (Rigaku OD, 2018); cell refinement: CrysAlis PRO (Rigaku OD, 2018);
data reduction: CrysAlis PRO (Rigaku OD, 2018). Program(s) used to solve structure: olex2.solve (Bourhis et al., 2015)
for (4a); SHELXS (Sheldrick, 2008) for (4b); SHELXT (Sheldrick, 2015a) for (4c), (4h). For all structures, program(s)
used to refine structure: SHELXL2016 (Sheldrick, 2015b); molecular graphics: OLEX2 (Dolomanov et al., 2009);
software used to prepare material for publication: OLEX2 (Dolomanov et al., 2009).
(5-Bromo-3-hydroxybenzofuran-2-yl)(4-fluorophenyl)methanone (4a)
Crystal data
C15H8BrFO3
Mr = 335.12
F(000) = 664
Dx = 1.780 Mg m−3
Mo Kα radiation, λ = 0.71073 Å
Cell parameters from 2736 reflections
θ = 2.9–25.3°
Monoclinic, P21/c
a = 3.8598 (4) Å
b = 11.7229 (10) Å
c = 27.679 (2) Å
β = 93.255 (9)°
V = 1250.38 (19) Å3
Z = 4
µ = 3.30 mm−1
T = 293 K
Needle, yellow
0.5 × 0.15 × 0.05 mm
Data collection
Rigaku OD SuperNova Single source
diffractometer with an Eos detector
Radiation source: micro-focus sealed X-ray
tube, SuperNova (Mo) X-ray Source
Mirror monochromator
Detector resolution: 15.9631 pixels mm-1
ω scans
Tmin = 0.447, Tmax = 1.000
7646 measured reflections
2543 independent reflections
1873 reflections with I > 2σ(I)
R
int = 0.040
θmax = 26.4°, θmin = 2.8°
h = −4→4
Absorption correction: multi-scan
(CrysAlis PRO; Rigaku OD, 2018)
k = −14→14
l = −34→33
Refinement
Refinement on F2
Least-squares matrix: full
R[F2 > 2σ(F2)] = 0.045
wR(F2) = 0.097
S = 1.07
2543 reflections
185 parameters
0 restraints
Primary atom site location: iterative
Hydrogen site location: mixed
H atoms treated by a mixture of independent
and constrained refinement
Acta Cryst. (2020). C76, 874-882
sup-1

supporting information
2
w = 1/[σ2(Fo ) + (0.0352P)2 + 0.4417P]
Δρmax = 0.44 e Å−3
Δρmin = −0.45 e Å−3
where P = (Fo + 2Fc2)/3
2
(Δ/σ)max = 0.001
Special details
Geometry. 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.
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2)
x
y
z
Uiso*/Ueq
O1
C2
C3
C4
C5
H5
1.0511 (7)
0.9792 (10)
0.8510 (10)
0.8335 (9)
0.7327 (10)
0.648929
0.33866 (19)
0.4552 (3)
0.4728 (3)
0.3665 (3)
0.3302 (3)
0.381124
0.35954 (8)
0.36548 (12)
0.40944 (12)
0.43395 (12)
0.47925 (13)
0.501555
0.0346 (6)
0.0331 (9)
0.0356 (9)
0.0307 (8)
0.0356 (9)
0.043*
C6
C7
H7
C8
H8
C9
0.7633 (10)
0.8901 (10)
0.905416
0.9913 (11)
1.076432
0.9610 (9)
1.0400 (10)
0.9820 (8)
1.1635 (9)
1.2995 (10)
1.319832
1.4041 (10)
1.497366
1.3676 (11)
1.2279 (10)
1.200229
1.1296 (10)
1.040261
1.4709 (7)
0.7528 (9)
0.63812 (11)
0.805 (12)
0.2170 (3)
0.1380 (3)
0.061294
0.1730 (3)
0.121809
0.2874 (3)
0.5412 (3)
0.6415 (2)
0.5177 (3)
0.6084 (3)
0.679808
0.5935 (4)
0.653718
0.4884 (4)
0.3965 (3)
0.326544
0.4116 (3)
0.350361
0.4732 (2)
0.5730 (2)
0.16145 (4)
0.618 (4)
0.48907 (12)
0.45616 (13)
0.464530
0.41188 (13)
0.389793
0.40168 (12)
0.33035 (12)
0.34270 (9)
0.28145 (12)
0.25606 (13)
0.270563
0.20979 (13)
0.192927
0.18939 (13)
0.21210 (13)
0.196515
0.25904 (12)
0.275726
0.14395 (7)
0.42805 (11)
0.55017 (2)
0.4097 (15)
0.0363 (9)
0.0394 (10)
0.047*
0.0383 (9)
0.046*
0.0319 (8)
0.0350 (9)
0.0525 (8)
0.0318 (8)
0.0375 (9)
0.045*
0.0433 (10)
0.052*
0.0420 (10)
0.0401 (10)
0.048*
0.0372 (9)
0.045*
0.0633 (8)
0.0509 (8)
0.04886 (17)
0.053 (15)*
C10
O11
C12
C13
H13
C14
H14
C15
C16
H16
C17
H17
F18
O19
Br20
H19
Atomic displacement parameters (Å2)
U11
U22
U33
U12
U13
U23
O1
C2
C3
C4
0.0478 (16)
0.041 (2)
0.041 (2)
0.031 (2)
0.0302 (12)
0.0301 (19)
0.032 (2)
0.0266 (13)
0.0289 (19)
0.035 (2)
0.0059 (13)
0.0024 (18)
0.0031 (19)
0.0021 (17)
0.0097 (11)
0.0076 (17)
0.0037 (18)
0.0047 (16)
0.0023 (10)
−0.0044 (15)
−0.0042 (16)
−0.0016 (15)
0.0329 (19)
0.0286 (18)
Acta Cryst. (2020). C76, 874-882
sup-2

supporting information
C5
C6
C7
C8
0.037 (2)
0.033 (2)
0.047 (3)
0.052 (3)
0.034 (2)
0.044 (2)
0.088 (2)
0.031 (2)
0.044 (2)
0.045 (3)
0.041 (2)
0.053 (3)
0.047 (2)
0.090 (2)
0.080 (2)
0.0552 (3)
0.038 (2)
0.042 (2)
0.032 (2)
0.033 (2)
0.036 (2)
0.032 (2)
0.0311 (15)
0.0325 (19)
0.032 (2)
0.049 (3)
0.056 (3)
0.034 (2)
0.035 (2)
0.0692 (16)
0.0301 (15)
0.0534 (3)
0.0318 (19)
0.034 (2)
0.039 (2)
0.003 (2)
0.0079 (17)
0.0049 (17)
0.0029 (19)
0.0091 (18)
0.0038 (16)
0.0060 (17)
0.0131 (15)
0.0004 (16)
0.0028 (18)
0.009 (2)
0.0053 (18)
0.0037 (19)
0.0053 (18)
0.0262 (13)
0.0208 (16)
0.0172 (2)
−0.0037 (17)
0.0035 (17)
0.0052 (16)
−0.0004 (16)
−0.0002 (16)
−0.0022 (16)
−0.0022 (12)
0.0037 (15)
0.0031 (16)
0.0125 (19)
0.0043 (18)
−0.0029 (17)
0.0041 (16)
0.0011 (12)
−0.0018 (14)
0.01369 (19)
−0.002 (2)
0.0041 (19)
0.006 (2)
0.0014 (18)
−0.0017 (19)
0.0041 (15)
0.0009 (17)
0.0002 (19)
−0.002 (2)
0.005 (2)
0.030 (2)
C9
0.0262 (18)
0.0295 (19)
0.0398 (16)
0.0317 (19)
0.037 (2)
0.037 (2)
0.029 (2)
0.033 (2)
0.030 (2)
C10
O11
C12
C13
C14
C15
C16
C17
F18
O19
Br20
0.003 (2)
−0.001 (2)
0.0089 (16)
0.0080 (16)
0.0052 (2)
0.0332 (13)
0.0444 (17)
0.0396 (3)
Geometric parameters (Å, º)
O1—C2
O1—C9
C2—C3
C2—C10
C3—C4
C3—O19
C4—C5
C4—C9
C5—H5
C5—C6
C6—C7
C6—Br20
C7—H7
C7—C8
C8—H8
1.406 (4)
C8—C9
1.374 (5)
1.374 (4)
1.355 (5)
1.429 (5)
1.422 (5)
1.345 (4)
1.400 (5)
1.397 (5)
0.9300
1.358 (5)
1.406 (5)
1.900 (3)
0.9300
C10—O11
C10—C12
C12—C13
C12—C17
C13—H13
C13—C14
C14—H14
C14—C15
C15—C16
C15—F18
C16—H16
C16—C17
C17—H17
O19—H19
1.249 (4)
1.486 (5)
1.393 (5)
1.393 (5)
0.9300
1.376 (5)
0.9300
1.360 (6)
1.373 (5)
1.353 (4)
0.9300
1.385 (5)
0.9300
0.77 (4)
1.370 (5)
0.9300
C9—O1—C2
O1—C2—C10
C3—C2—O1
C3—C2—C10
C2—C3—C4
O19—C3—C2
O19—C3—C4
C5—C4—C3
C9—C4—C3
C9—C4—C5
C4—C5—H5
C6—C5—C4
C6—C5—H5
105.3 (2)
124.4 (3)
109.7 (3)
125.9 (3)
108.9 (3)
127.0 (3)
124.1 (3)
135.8 (3)
104.4 (3)
119.8 (3)
121.6
C8—C9—C4
123.1 (3)
124.3 (3)
116.1 (3)
119.7 (3)
117.9 (3)
119.0 (3)
122.9 (3)
119.6
120.8 (4)
119.6
120.9
118.2 (4)
120.9
C2—C10—C12
O11—C10—C2
O11—C10—C12
C13—C12—C10
C13—C12—C17
C17—C12—C10
C12—C13—H13
C14—C13—C12
C14—C13—H13
C13—C14—H14
C15—C14—C13
C15—C14—H14
116.8 (3)
121.6
Acta Cryst. (2020). C76, 874-882
sup-3

supporting information
C5—C6—C7
C5—C6—Br20
C7—C6—Br20
C6—C7—H7
C8—C7—C6
C8—C7—H7
C7—C8—H8
C7—C8—C9
C9—C8—H8
O1—C9—C4
C8—C9—O1
122.9 (3)
119.3 (3)
117.8 (3)
119.7
120.7 (3)
119.7
121.6
116.8 (3)
121.6
C14—C15—C16
F18—C15—C14
F18—C15—C16
C15—C16—H16
C15—C16—C17
C17—C16—H16
C12—C17—H17
C16—C17—C12
C16—C17—H17
C3—O19—H19
123.7 (3)
118.5 (3)
117.8 (4)
121.1
117.7 (3)
121.1
119.8
120.5 (3)
119.8
111.6 (3)
125.3 (3)
105 (3)
O1—C2—C3—C4
O1—C2—C3—O19
O1—C2—C10—O11
O1—C2—C10—C12
C2—O1—C9—C4
C2—O1—C9—C8
C2—C3—C4—C5
C2—C3—C4—C9
C2—C10—C12—C13
C2—C10—C12—C17
C3—C2—C10—O11
C3—C2—C10—C12
C3—C4—C5—C6
C3—C4—C9—O1
C3—C4—C9—C8
C4—C5—C6—C7
C4—C5—C6—Br20
C5—C4—C9—O1
C5—C4—C9—C8
C5—C6—C7—C8
C6—C7—C8—C9
C7—C8—C9—O1
−0.2 (5)
179.9 (4)
−175.6 (4)
4.6 (6)
C7—C8—C9—C4
C9—O1—C2—C3
C9—O1—C2—C10
C9—C4—C5—C6
C10—C2—C3—C4
C10—C2—C3—O19
C10—C12—C13—C14
C10—C12—C17—C16
O11—C10—C12—C13
O11—C10—C12—C17
C12—C13—C14—C15
C13—C12—C17—C16
C13—C14—C15—C16
C13—C14—C15—F18
C14—C15—C16—C17
C15—C16—C17—C12
C17—C12—C13—C14
F18—C15—C16—C17
O19—C3—C4—C5
−0.2 (6)
0.0 (4)
178.9 (4)
−0.6 (6)
−179.2 (4)
1.0 (7)
−177.1 (4)
175.6 (4)
17.1 (6)
−158.9 (4)
0.7 (6)
−0.4 (6)
0.9 (7)
−179.8 (3)
−2.1 (6)
1.8 (6)
−1.0 (6)
178.6 (3)
−1.4 (8)
−179.8 (4)
−178.7 (3)
0.3 (4)
−179.4 (4)
178.8 (4)
0.4 (4)
−163.1 (4)
20.9 (6)
3.2 (6)
−176.6 (4)
−178.8 (4)
−0.4 (4)
179.3 (4)
0.2 (6)
179.1 (3)
−179.1 (3)
0.6 (6)
0.2 (6)
−0.2 (6)
179.5 (3)
O19—C3—C4—C9
Br20—C6—C7—C8
Hydrogen-bond geometry (Å, º)
D—H···A
D—H
H···A
D···A
D—H···A
O19—H19···O11
C17—H17···O1
C16—H16···O11i
C5—H5···O19ii
0.77 (5)
0.93
0.93
2.03 (4)
2.32
2.51
2.692 (4)
2.942 (4)
3.428 (4)
3.454 (5)
144 (4)
124
170
0.93
2.61
150
Symmetry codes: (i) −x+2, y−1/2, −z+1/2; (ii) −x+1, −y+1, −z+1.
Acta Cryst. (2020). C76, 874-882
sup-4

supporting information
(5-Bromo-3-hydroxybenzofuran-2-yl)(4-chlorophenyl)methanone (4b)
Crystal data
C15H8BrClO3
Mr = 351.57
F(000) = 1392
Dx = 1.747 Mg m−3
Monoclinic, P21/c
a = 26.4034 (10) Å
b = 3.9818 (1) Å
c = 26.2773 (10) Å
β = 104.605 (4)°
V = 2673.34 (17) Å3
Z = 8
Mo Kα radiation, λ = 0.71073 Å
Cell parameters from 6124 reflections
θ = 3.1–24.1°
µ = 3.28 mm−1
T = 294 K
Plate, yellow
0.4 × 0.15 × 0.05 mm
Data collection
Rigaku OD SuperNova Single source
diffractometer with an Eos detector
Radiation source: micro-focus sealed X-ray
tube, SuperNova (Mo) X-ray Source
Mirror monochromator
Tmin = 0.572, Tmax = 1.000
27661 measured reflections
5419 independent reflections
3168 reflections with I > 2σ(I)
R
int = 0.064
Detector resolution: 15.9631 pixels mm-1
ω scans
θmax = 26.4°, θmin = 2.4°
h = −33→33
k = −4→4
Absorption correction: multi-scan
(CrysAlis PRO; Rigaku OD, 2018)
l = −32→32
Refinement
Refinement on F2
Least-squares matrix: full
R[F2 > 2σ(F2)] = 0.052
wR(F2) = 0.102
S = 1.01
5419 reflections
369 parameters
0 restraints
Primary atom site location: structure-invariant
direct methods
Hydrogen site location: mixed
H atoms treated by a mixture of independent
and constrained refinement
2
w = 1/[σ2(Fo ) + (0.029P)2 + 2.0591P]
2
where P = (Fo + 2Fc2)/3
(Δ/σ)max = 0.001
Δρmax = 0.56 e Å−3
Δρmin = −0.42 e Å−3
Special details
Geometry. 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.
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2)
x
y
z
Uiso*/Ueq
O1
C2
C3
C4
C5
H5
C6
C7
0.74798 (10)
0.76425 (16)
0.72831 (17)
0.68645 (16)
0.63911 (17)
0.628733
0.1478 (6)
0.20663 (11)
0.25631 (16)
0.28464 (18)
0.25260 (17)
0.25851 (19)
0.289505
0.0451 (7)
0.0414 (10)
0.0474 (11)
0.0435 (10)
0.0520 (12)
0.062*
0.2959 (10)
0.2377 (11)
0.0499 (10)
−0.0788 (11)
−0.049134
0.60870 (16)
0.62345 (17)
−0.2499 (10)
−0.3027 (11)
0.2169 (2)
0.17041 (18)
0.0506 (12)
0.0522 (12)
Acta Cryst. (2020). C76, 874-882
sup-5

supporting information
H7
C8
H8
C9
0.601560
0.67037 (16)
0.680793
0.70068 (16)
0.81144 (17)
0.82009 (13)
0.84822 (16)
0.89643 (17)
0.905122
0.93111 (17)
0.963255
0.91812 (16)
0.87094 (18)
0.862349
−0.424167
−0.1771 (10)
−0.210610
0.0011 (9)
0.4852 (10)
0.5813 (8)
0.5771 (10)
0.7151 (11)
0.738409
0.8166 (12)
0.907700
0.7830 (11)
0.6494 (11)
0.630215
0.143395
0.16363 (18)
0.132745
0.20560 (17)
0.27453 (19)
0.32146 (13)
0.24301 (17)
0.26866 (18)
0.305052
0.063*
0.0488 (11)
0.059*
0.0422 (11)
0.0504 (12)
0.0703 (9)
0.0438 (10)
0.0563 (12)
0.068*
0.0614 (13)
0.074*
0.0515 (12)
0.0575 (12)
0.069*
C10
O11
C12
C13
H13
C14
H14
C15
C16
H16
C17
H17
Cl18
O19
Br20
O21
C22
C23
C24
C25
H25
C26
C27
H27
C28
H28
C29
C30
O31
C32
C33
H33
C34
H34
C35
C36
H36
C37
H37
Cl38
O39
Br40
H19
H39
0.2408 (2)
0.258215
0.18708 (19)
0.16089 (18)
0.124446
0.18891 (18)
0.171240
0.15236 (6)
0.33357 (14)
0.22329 (2)
0.44584 (11)
0.49411 (17)
0.51387 (17)
0.47749 (17)
0.47435 (18)
0.500961
0.43063 (19)
0.39031 (18)
0.361263
0.39319 (18)
0.366871
0.43690 (17)
0.51808 (19)
0.56258 (13)
0.49538 (18)
0.52436 (19)
0.557867
0.5049 (2)
0.525226
0.4553 (2)
0.4251 (2)
0.391294
0.44501 (19)
0.424512
0.42988 (7)
0.55988 (14)
0.42371 (2)
0.343 (2)
0.83643 (17)
0.804676
0.5441 (11)
0.449286
0.0520 (12)
0.062*
0.96251 (5)
0.73115 (15)
0.54377 (2)
0.70963 (11)
0.72238 (19)
0.6799 (2)
0.63657 (18)
0.58370 (18)
0.568715
0.55481 (17)
0.57635 (19)
0.555187
0.62855 (18)
0.643551
0.65764 (18)
0.77303 (19)
0.77683 (13)
0.81848 (18)
0.8658 (2)
0.867985
0.9090 (2)
0.940408
0.90609 (19)
0.8598 (2)
0.9144 (4)
0.3394 (9)
−0.42670 (12)
0.8529 (7)
1.0222 (11)
1.0408 (11)
0.8860 (10)
0.8345 (10)
0.905525
0.6758 (11)
0.5631 (11)
0.455037
0.6108 (11)
0.534760
0.7764 (11)
1.1543 (11)
1.2897 (9)
1.1521 (11)
1.2824 (12)
1.366531
1.2900 (14)
1.375615
1.1710 (13)
1.0437 (13)
0.964976
0.0778 (4)
0.0678 (10)
0.06821 (19)
0.0543 (8)
0.0510 (12)
0.0540 (12)
0.0481 (11)
0.0537 (12)
0.064*
0.0527 (12)
0.0589 (13)
0.071*
0.0571 (12)
0.069*
0.0499 (11)
0.0567 (13)
0.0736 (10)
0.0541 (12)
0.0662 (14)
0.079*
0.0784 (16)
0.094*
0.0669 (14)
0.0691 (14)
0.083*
0.857813
0.81681 (19)
0.785654
0.96020 (6)
0.67804 (16)
0.48242 (2)
0.7620 (18)
0.711 (2)
1.0340 (11)
0.946543
0.0631 (14)
0.076*
0.1069 (6)
0.0726 (11)
0.07029 (19)
0.08 (2)*
1.1822 (5)
1.1817 (9)
0.59410 (13)
0.424 (12)
1.268 (17)
0.570 (3)
0.14 (3)*
Acta Cryst. (2020). C76, 874-882
sup-6

supporting information
Atomic displacement parameters (Å2)
U11
U22
U33
U12
U13
U23
O1
C2
C3
C4
C5
C6
C7
C8
0.0443 (16)
0.045 (2)
0.058 (3)
0.043 (2)
0.056 (3)
0.050 (3)
0.049 (3)
0.052 (3)
0.040 (2)
0.052 (3)
0.073 (2)
0.042 (2)
0.056 (3)
0.044 (3)
0.045 (3)
0.062 (3)
0.045 (3)
0.0611 (8)
0.070 (2)
0.0535 (3)
0.0570 (19)
0.063 (3)
0.076 (3)
0.060 (3)
0.070 (3)
0.058 (3)
0.066 (3)
0.067 (3)
0.062 (3)
0.070 (3)
0.080 (2)
0.063 (3)
0.074 (3)
0.062 (3)
0.062 (3)
0.068 (3)
0.062 (3)
0.0789 (10)
0.093 (3)
0.0627 (3)
0.0494 (18)
0.047 (3)
0.049 (3)
0.042 (2)
0.048 (3)
0.037 (2)
0.046 (3)
0.045 (3)
0.040 (3)
0.047 (3)
0.095 (3)
0.044 (2)
0.064 (3)
0.071 (3)
0.049 (3)
0.064 (3)
0.058 (3)
0.0974 (10)
0.092 (3)
0.0522 (3)
0.062 (2)
0.056 (3)
0.055 (3)
0.045 (3)
0.047 (3)
0.047 (3)
0.058 (3)
0.061 (3)
0.049 (3)
0.051 (3)
0.088 (3)
0.050 (3)
0.066 (3)
0.090 (4)
0.073 (4)
0.086 (4)
0.071 (3)
0.1375 (15)
0.084 (3)
0.0649 (3)
0.0441 (19)
0.034 (3)
0.038 (3)
0.047 (3)
0.059 (3)
0.068 (4)
0.057 (3)
0.051 (3)
0.048 (3)
0.050 (3)
0.042 (2)
0.043 (3)
0.043 (3)
0.063 (4)
0.059 (3)
0.044 (3)
0.051 (3)
0.0795 (10)
0.044 (2)
0.1076 (5)
0.042 (2)
0.030 (3)
0.029 (3)
0.039 (3)
0.047 (3)
0.053 (3)
0.046 (3)
0.045 (3)
0.038 (3)
0.041 (3)
0.045 (2)
0.043 (3)
0.049 (3)
0.074 (4)
0.063 (4)
0.051 (3)
0.049 (3)
0.1097 (13)
0.043 (2)
0.0813 (4)
0.0027 (14)
0.007 (2)
0.012 (2)
0.012 (2)
0.016 (2)
0.007 (2)
0.004 (2)
0.003 (2)
0.0076 (19)
0.008 (2)
−0.016 (2)
0.008 (2)
0.002 (3)
−0.005 (2)
0.002 (2)
−0.008 (3)
−0.008 (2)
−0.0114 (7)
−0.007 (2)
0.0021 (2)
−0.0063 (16)
−0.005 (2)
−0.001 (3)
−0.001 (2)
0.004 (2)
−0.003 (2)
−0.008 (3)
−0.004 (3)
−0.005 (2)
0.000 (3)
−0.006 (2)
−0.005 (2)
−0.012 (3)
−0.019 (3)
−0.012 (3)
−0.017 (3)
−0.016 (3)
−0.0319 (10)
−0.009 (2)
−0.0056 (3)
0.0158 (14)
0.013 (2)
0.017 (2)
0.014 (2)
0.027 (3)
0.021 (3)
0.007 (2)
0.017 (2)
0.012 (2)
0.008 (2)
0.0125 (18)
0.006 (2)
0.001 (3)
0.002 (3)
0.010 (2)
0.008 (3)
0.008 (2)
0.0261 (7)
0.0203 (19)
0.0364 (3)
0.0098 (16)
0.006 (2)
0.010 (3)
0.010 (2)
0.020 (3)
0.013 (3)
0.004 (3)
0.016 (3)
0.010 (2)
0.000 (3)
0.0018 (19)
0.000 (3)
−0.001 (3)
0.000 (3)
0.011 (3)
0.010 (3)
0.000 (3)
0.0336 (9)
0.021 (2)
0.0145 (3)
−0.0022 (14)
0.003 (2)
0.006 (2)
0.007 (2)
0.011 (2)
0.005 (2)
0.000 (2)
0.000 (2)
0.003 (2)
C9
C10
O11
C12
C13
C14
C15
C16
C17
Cl18
O19
Br20
O21
C22
C23
C24
C25
C26
C27
C28
C29
C30
O31
C32
C33
C34
C35
C36
C37
Cl38
O39
Br40
0.002 (2)
−0.0123 (19)
−0.001 (2)
−0.005 (2)
−0.005 (3)
0.002 (2)
−0.003 (2)
−0.002 (2)
0.0049 (8)
−0.0046 (19)
0.0067 (3)
−0.0054 (15)
−0.001 (2)
0.007 (2)
0.006 (2)
0.007 (2)
0.013 (2)
0.000 (2)
−0.006 (2)
0.002 (2)
0.003 (2)
−0.0140 (19)
0.000 (2)
−0.011 (3)
−0.010 (3)
−0.004 (3)
−0.014 (3)
−0.006 (3)
−0.0211 (11)
−0.0099 (18)
0.0078 (3)
Geometric parameters (Å, º)
O1—C2
O1—C9
1.398 (4)
1.373 (4)
O21—C22
O21—C29
1.400 (5)
1.367 (5)
Acta Cryst. (2020). C76, 874-882
sup-7

supporting information
C2—C3
C2—C10
C3—C4
C3—O19
C4—C5
C4—C9
C5—H5
C5—C6
C6—C7
C6—Br20
C7—H7
1.366 (5)
1.431 (6)
1.421 (6)
1.332 (5)
1.395 (5)
1.392 (5)
0.9300
1.364 (6)
1.389 (6)
1.899 (4)
0.9300
C22—C23
C22—C30
C23—C24
C23—O39
C24—C25
C24—C29
C25—H25
C25—C26
C26—C27
C26—Br40
C27—H27
C27—C28
C28—H28
C28—C29
C30—O31
C30—C32
C32—C33
C32—C37
C33—H33
C33—C34
C34—H34
C34—C35
C35—C36
C35—Cl38
C36—H36
C36—C37
C37—H37
O39—H39
1.352 (6)
1.427 (6)
1.432 (6)
1.345 (5)
1.393 (6)
1.392 (6)
0.9300
1.364 (6)
1.397 (6)
1.902 (4)
0.9300
C7—C8
C8—H8
C8—C9
1.389 (5)
0.9300
1.374 (6)
0.9300
1.384 (5)
1.256 (5)
1.473 (6)
1.394 (5)
1.383 (5)
0.9300
1.369 (6)
0.9300
1.373 (6)
1.370 (6)
1.738 (5)
0.9300
1.378 (6)
1.268 (5)
1.469 (6)
1.388 (6)
1.395 (6)
0.9300
1.365 (6)
0.9300
1.369 (6)
1.376 (6)
1.724 (5)
0.9300
C10—O11
C10—C12
C12—C13
C12—C17
C13—H13
C13—C14
C14—H14
C14—C15
C15—C16
C15—Cl18
C16—H16
C16—C17
C17—H17
O19—H19
1.374 (6)
0.9300
0.86 (5)
1.366 (6)
0.9300
0.90 (6)
C9—O1—C2
O1—C2—C10
C3—C2—O1
C3—C2—C10
C2—C3—C4
O19—C3—C2
O19—C3—C4
C5—C4—C3
C9—C4—C3
C9—C4—C5
C4—C5—H5
C6—C5—C4
C6—C5—H5
C5—C6—C7
C5—C6—Br20
C7—C6—Br20
C6—C7—H7
C8—C7—C6
C8—C7—H7
105.2 (3)
124.8 (4)
110.2 (4)
125.0 (4)
108.0 (4)
126.6 (4)
125.3 (4)
135.4 (4)
104.8 (4)
119.8 (4)
121.4
117.2 (4)
121.4
122.8 (4)
118.5 (4)
118.8 (4)
119.5
C29—O21—C22
O21—C22—C30
C23—C22—O21
C23—C22—C30
C22—C23—C24
O39—C23—C22
O39—C23—C24
C25—C24—C23
C29—C24—C23
C29—C24—C25
C24—C25—H25
C26—C25—C24
C26—C25—H25
C25—C26—C27
C25—C26—Br40
C27—C26—Br40
C26—C27—H27
C28—C27—C26
C28—C27—H27
105.3 (3)
124.2 (4)
109.9 (4)
125.9 (4)
108.7 (4)
126.1 (4)
125.2 (5)
136.3 (5)
103.9 (4)
119.8 (4)
121.4
117.2 (4)
121.4
122.7 (4)
119.7 (4)
117.7 (4)
119.7
121.0 (4)
119.5
120.6 (4)
119.7
Acta Cryst. (2020). C76, 874-882
sup-8

supporting information
C7—C8—H8
C9—C8—C7
C9—C8—H8
O1—C9—C4
O1—C9—C8
C8—C9—C4
122.0
116.0 (4)
122.0
C27—C28—H28
C27—C28—C29
C29—C28—H28
O21—C29—C24
O21—C29—C28
C28—C29—C24
C22—C30—C32
O31—C30—C22
O31—C30—C32
C33—C32—C30
C33—C32—C37
C37—C32—C30
C32—C33—H33
C34—C33—C32
C34—C33—H33
C33—C34—H34
C33—C34—C35
C35—C34—H34
C34—C35—C36
C34—C35—Cl38
C36—C35—Cl38
C35—C36—H36
C37—C36—C35
C37—C36—H36
C32—C37—H37
C36—C37—C32
C36—C37—H37
C23—O39—H39
121.5
116.9 (4)
121.5
111.8 (4)
125.0 (4)
123.2 (4)
125.8 (4)
114.6 (4)
119.6 (4)
118.5 (4)
123.0 (4)
118.4 (4)
119.7
120.7 (4)
119.7
120.2
119.6 (4)
120.2
119.0 (4)
121.0 (4)
120.1 (4)
120.3
112.1 (4)
125.0 (4)
122.8 (4)
126.1 (4)
114.3 (5)
119.6 (4)
119.3 (4)
117.1 (5)
123.6 (4)
119.2
121.6 (5)
119.2
120.1
119.8 (5)
120.1
120.4 (5)
120.4 (4)
119.2 (4)
120.3
C2—C10—C12
O11—C10—C2
O11—C10—C12
C13—C12—C10
C17—C12—C10
C17—C12—C13
C12—C13—H13
C14—C13—C12
C14—C13—H13
C13—C14—H14
C13—C14—C15
C15—C14—H14
C14—C15—Cl18
C16—C15—C14
C16—C15—Cl18
C15—C16—H16
C15—C16—C17
C17—C16—H16
C12—C17—H17
C16—C17—C12
C16—C17—H17
C3—O19—H19
119.4 (4)
120.3
119.5
121.0 (4)
119.5
102 (4)
119.4 (5)
120.3
119.2
121.6 (4)
119.2
99 (4)
O1—C2—C3—C4
O1—C2—C3—O19
O1—C2—C10—O11
O1—C2—C10—C12
C2—O1—C9—C4
C2—O1—C9—C8
C2—C3—C4—C5
C2—C3—C4—C9
C2—C10—C12—C13
C2—C10—C12—C17
C3—C2—C10—O11
C3—C2—C10—C12
C3—C4—C5—C6
C3—C4—C9—O1
C3—C4—C9—C8
C4—C5—C6—C7
C4—C5—C6—Br20
C5—C4—C9—O1
C5—C4—C9—C8
−1.0 (4)
179.5 (4)
−176.3 (4)
5.1 (6)
−0.1 (4)
−179.6 (4)
−178.8 (4)
0.8 (4)
O21—C22—C23—C24
O21—C22—C23—O39
O21—C22—C30—O31
O21—C22—C30—C32
C22—O21—C29—C24
C22—O21—C29—C28
C22—C23—C24—C25
C22—C23—C24—C29
C22—C30—C32—C33
C22—C30—C32—C37
C23—C22—C30—O31
C23—C22—C30—C32
C23—C24—C25—C26
C23—C24—C29—O21
C23—C24—C29—C28
C24—C25—C26—C27
C24—C25—C26—Br40
C25—C24—C29—O21
C25—C24—C29—C28
−1.3 (5)
179.0 (4)
−177.9 (4)
3.6 (7)
−0.6 (5)
179.4 (4)
−177.8 (5)
0.9 (5)
−169.9 (4)
12.6 (6)
4.6 (6)
−178.1 (4)
3.8 (7)
2.3 (7)
−174.0 (4)
179.7 (4)
−0.5 (4)
179.1 (4)
1.0 (6)
−179.6 (3)
179.3 (3)
−1.2 (6)
−176.2 (4)
178.5 (5)
−0.1 (5)
179.9 (4)
0.7 (6)
179.6 (3)
178.8 (4)
−1.2 (7)
Acta Cryst. (2020). C76, 874-882
sup-9

supporting information
C5—C6—C7—C8
C6—C7—C8—C9
C7—C8—C9—O1
C7—C8—C9—C4
C9—O1—C2—C3
C9—O1—C2—C10
C9—C4—C5—C6
C10—C2—C3—C4
C10—C2—C3—O19
C10—C12—C13—C14
C10—C12—C17—C16
O11—C10—C12—C13
O11—C10—C12—C17
C12—C13—C14—C15
C13—C12—C17—C16
C13—C14—C15—C16
C13—C14—C15—Cl18
C14—C15—C16—C17
C15—C16—C17—C12
C17—C12—C13—C14
Cl18—C15—C16—C17
O19—C3—C4—C5
O19—C3—C4—C9
Br20—C6—C7—C8
−1.0 (7)
−0.1 (6)
−179.4 (3)
1.2 (6)
0.7 (4)
−178.5 (4)
0.1 (6)
178.2 (4)
−1.3 (7)
−177.4 (4)
176.6 (4)
11.6 (6)
−166.0 (4)
0.2 (7)
−1.0 (6)
0.0 (7)
179.8 (4)
−0.8 (7)
1.3 (7)
C25—C26—C27—C28
−0.3 (7)
−0.8 (7)
−178.4 (4)
1.6 (7)
1.1 (5)
−178.7 (4)
0.0 (6)
178.6 (4)
−1.2 (7)
−179.2 (5)
178.5 (4)
3.5 (7)
−174.6 (4)
0.9 (8)
0.4 (7)
C26—C27—C28—C29
C27—C28—C29—O21
C27—C28—C29—C24
C29—O21—C22—C23
C29—O21—C22—C30
C29—C24—C25—C26
C30—C22—C23—C24
C30—C22—C23—O39
C30—C32—C33—C34
C30—C32—C37—C36
O31—C30—C32—C33
O31—C30—C32—C37
C32—C33—C34—C35
C33—C32—C37—C36
C33—C34—C35—C36
C33—C34—C35—Cl38
C34—C35—C36—C37
C35—C36—C37—C32
C37—C32—C33—C34
Cl38—C35—C36—C37
O39—C23—C24—C25
O39—C23—C24—C29
Br40—C26—C27—C28
0.0 (8)
179.4 (4)
−0.6 (8)
0.4 (8)
−1.0 (7)
180.0 (4)
2.0 (8)
0.3 (6)
179.5 (3)
0.7 (8)
−179.6 (4)
179.6 (3)
−179.4 (4)
−179.2 (3)
Hydrogen-bond geometry (Å, º)
D—H···A
D—H
H···A
D···A
D—H···A
O19—H19···O11
C17—H17···O1
O39—H39···O31
C37—H37···O21
C36—H36···O11
C8—H8···O39i
0.86 (5)
0.93
0.91 (6)
0.93
0.93
0.93
1.87 (5)
2.29
1.80 (6)
2.25
2.40
2.67
2.631 (5)
2.951 (5)
2.627 (6)
2.926 (6)
3.235 (6)
3.434 (6)
147 (5)
128
150 (7)
129
149
140
Symmetry code: (i) x, −y+1/2, z−1/2.
(5-Bromo-3-hydroxybenzofuran-2-yl)(4-bromophenyl)methanone (4c)
Crystal data
C15H8Br2O3
Z = 2
Mr = 396.03
Triclinic, P1
F(000) = 384
Dx = 1.887 Mg m−3
a = 7.0725 (4) Å
b = 7.0884 (5) Å
c = 14.6069 (8) Å
α = 92.230 (5)°
β = 103.091 (5)°
γ = 101.219 (6)°
V = 696.98 (8) Å3
Mo Kα radiation, λ = 0.71073 Å
Cell parameters from 3969 reflections
θ = 2.9–25.0°
µ = 5.82 mm−1
T = 294 K
Plate, yellow
0.35 × 0.15 × 0.05 mm
Acta Cryst. (2020). C76, 874-882
sup-10

supporting information
Data collection
Rigaku OD SuperNova Single source
diffractometer with an Eos detector
Radiation source: micro-focus sealed X-ray
tube, SuperNova (Mo) X-ray Source
Mirror monochromator
Tmin = 0.523, Tmax = 1.000
14183 measured reflections
2840 independent reflections
1867 reflections with I > 2σ(I)
R
int = 0.046
Detector resolution: 15.9631 pixels mm-1
ω scans
θmax = 26.4°, θmin = 2.9°
h = −8→8
k = −8→8
l = −18→18
Absorption correction: multi-scan
(CrysAlis PRO; Rigaku OD, 2018)
Refinement
Refinement on F2
Least-squares matrix: full
R[F2 > 2σ(F2)] = 0.046
wR(F2) = 0.109
S = 1.03
Hydrogen site location: mixed
H atoms treated by a mixture of independent
and constrained refinement
2
w = 1/[σ2(Fo ) + (0.0415P)2 + 0.4345P]
2
where P = (Fo + 2Fc2)/3
2840 reflections
185 parameters
0 restraints
(Δ/σ)max = 0.001
Δρmax = 0.44 e Å−3
Δρmin = −0.40 e Å−3
Special details
Geometry. 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.
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2)
x
y
z
Uiso*/Ueq
O1
C2
C3
C4
C5
H5
C6
C7
H7
C8
H8
C9
C10
O11
C12
C13
H13
C14
H14
C15
C16
0.2698 (4)
0.2236 (6)
0.1893 (6)
0.2133 (6)
0.1950 (6)
0.162112
0.2283 (6)
0.2745 (7)
0.294088
0.2919 (7)
0.322333
0.2605 (6)
0.2117 (6)
0.1679 (5)
0.2445 (5)
0.2243 (6)
0.190559
0.2529 (6)
0.239823
0.3015 (6)
0.3218 (6)
0.5503 (4)
0.3699 (6)
0.2269 (6)
0.3147 (6)
0.2465 (7)
0.115376
0.3842 (8)
0.5815 (8)
0.668302
0.6517 (7)
0.783073
0.5113 (6)
0.3412 (6)
0.1689 (4)
0.4957 (6)
0.4393 (7)
0.308580
0.5720 (7)
0.532483
0.7652 (7)
0.8272 (7)
0.38600 (19)
0.4205 (3)
0.3496 (3)
0.2657 (3)
0.1721 (3)
0.152601
0.1110 (3)
0.1380 (3)
0.093245
0.2302 (3)
0.249141
0.2925 (3)
0.5157 (3)
0.5325 (2)
0.5920 (3)
0.6802 (3)
0.688378
0.7550 (3)
0.813584
0.7422 (3)
0.6564 (3)
0.0488 (7)
0.0451 (10)
0.0492 (10)
0.0467 (10)
0.0538 (11)
0.065*
0.0603 (13)
0.0644 (13)
0.077*
0.0583 (12)
0.070*
0.0470 (10)
0.0471 (10)
0.0672 (9)
0.0432 (10)
0.0528 (11)
0.063*
0.0562 (12)
0.067*
0.0516 (11)
0.0538 (11)
Acta Cryst. (2020). C76, 874-882
sup-11

supporting information
H16
C17
H17
Br18
O19
Br20
H19
0.354165
0.2934 (6)
0.307233
0.34142 (8)
0.1385 (5)
0.20857 (10)
0.127 (9)
0.958359
0.6921 (6)
0.732746
0.94907 (8)
0.0365 (5)
0.30111 (10)
0.030 (8)
0.648961
0.5815 (3)
0.523116
0.84645 (4)
0.3552 (3)
−0.01643 (4)
0.411 (4)
0.065*
0.0485 (10)
0.058*
0.0757 (2)
0.0671 (9)
0.0906 (3)
0.10 (2)*
Atomic displacement parameters (Å2)
U11
U22
U33
U12
U13
U23
O1
C2
C3
C4
C5
C6
C7
C8
0.0533 (18)
0.044 (2)
0.051 (3)
0.038 (2)
0.051 (3)
0.054 (3)
0.064 (3)
0.067 (3)
0.040 (2)
0.045 (3)
0.099 (3)
0.036 (2)
0.056 (3)
0.056 (3)
0.046 (3)
0.055 (3)
0.050 (3)
0.0838 (4)
0.102 (3)
0.1167 (5)
0.0470 (17)
0.044 (3)
0.048 (3)
0.053 (3)
0.056 (3)
0.084 (4)
0.075 (4)
0.057 (3)
0.057 (3)
0.049 (3)
0.0453 (19)
0.052 (3)
0.054 (3)
0.069 (3)
0.060 (3)
0.047 (3)
0.052 (3)
0.0774 (4)
0.046 (2)
0.1131 (5)
0.0475 (16)
0.048 (2)
0.053 (3)
0.052 (3)
0.055 (3)
0.044 (2)
0.056 (3)
0.052 (3)
0.046 (2)
0.048 (2)
0.0565 (19)
0.043 (2)
0.053 (3)
0.047 (3)
0.049 (3)
0.058 (3)
0.044 (2)
0.0631 (3)
0.059 (2)
0.0462 (3)
0.0062 (14)
0.008 (2)
0.011 (2)
0.011 (2)
0.010 (2)
0.016 (3)
0.011 (3)
0.007 (2)
0.008 (2)
0.010 (2)
0.0070 (18)
0.010 (2)
0.011 (2)
0.011 (2)
0.008 (2)
0.006 (2)
0.009 (2)
0.0050 (3)
0.0128 (18)
0.0303 (4)
0.0175 (13)
0.0135 (19)
0.020 (2)
0.0147 (19)
0.015 (2)
0.012 (2)
0.019 (2)
0.021 (2)
0.0142 (19)
0.0123 (19)
0.0227 (17)
0.0116 (18)
0.018 (2)
0.018 (2)
0.013 (2)
0.013 (2)
0.0085 (13)
0.009 (2)
0.010 (2)
0.009 (2)
0.002 (2)
0.006 (3)
0.021 (3)
0.014 (2)
0.007 (2)
0.013 (2)
0.0145 (15)
0.013 (2)
0.018 (2)
0.014 (2)
0.002 (2)
0.008 (2)
0.011 (2)
−0.0112 (3)
0.0083 (16)
0.0072 (3)
C9
C10
O11
C12
C13
C14
C15
C16
C17
Br18
O19
Br20
0.0131 (19)
0.0248 (3)
0.031 (2)
0.0227 (3)
Geometric parameters (Å, º)
O1—C2
O1—C9
C2—C3
C2—C10
C3—C4
C3—O19
C4—C5
C4—C9
C5—C6
C6—C7
C6—Br20
1.399 (5)
C7—C8
C8—C9
1.387 (6)
1.368 (5)
1.367 (6)
1.432 (5)
1.425 (5)
1.338 (5)
1.400 (6)
1.387 (6)
1.370 (6)
1.393 (7)
1.896 (4)
1.394 (6)
1.248 (5)
1.478 (6)
1.394 (5)
1.391 (6)
1.365 (6)
1.376 (6)
1.372 (6)
1.899 (4)
1.379 (6)
C10—O11
C10—C12
C12—C13
C12—C17
C13—C14
C14—C15
C15—C16
C15—Br18
C16—C17
C9—O1—C2
O1—C2—C10
105.3 (3)
124.7 (4)
O1—C9—C4
O1—C9—C8
112.3 (3)
124.3 (4)
Acta Cryst. (2020). C76, 874-882
sup-12

supporting information
C3—C2—O1
C3—C2—C10
C2—C3—C4
O19—C3—C2
O19—C3—C4
C5—C4—C3
C9—C4—C3
C9—C4—C5
C6—C5—C4
C5—C6—C7
C5—C6—Br20
C7—C6—Br20
C8—C7—C6
C7—C8—C9
109.8 (3)
125.5 (4)
108.2 (4)
127.2 (4)
124.6 (4)
135.0 (4)
104.4 (4)
120.6 (4)
116.2 (4)
123.1 (4)
118.2 (4)
118.7 (4)
121.5 (4)
115.2 (5)
C4—C9—C8
123.4 (4)
125.6 (4)
114.9 (4)
119.5 (4)
117.3 (4)
124.5 (3)
118.2 (4)
121.3 (4)
119.0 (4)
118.7 (3)
121.6 (4)
119.6 (3)
119.0 (4)
120.8 (4)
C2—C10—C12
O11—C10—C2
O11—C10—C12
C13—C12—C10
C17—C12—C10
C17—C12—C13
C14—C13—C12
C13—C14—C15
C14—C15—Br18
C16—C15—C14
C16—C15—Br18
C15—C16—C17
C16—C17—C12
O1—C2—C3—C4
O1—C2—C3—O19
O1—C2—C10—O11
O1—C2—C10—C12
C2—O1—C9—C4
C2—O1—C9—C8
C2—C3—C4—C5
C2—C3—C4—C9
C2—C10—C12—C13
C2—C10—C12—C17
C3—C2—C10—O11
C3—C2—C10—C12
C3—C4—C5—C6
C3—C4—C9—O1
C3—C4—C9—C8
C4—C5—C6—C7
C4—C5—C6—Br20
C5—C4—C9—O1
C5—C4—C9—C8
C5—C6—C7—C8
C6—C7—C8—C9
C7—C8—C9—O1
0.0 (5)
C7—C8—C9—C4
C9—O1—C2—C3
C9—O1—C2—C10
C9—C4—C5—C6
C10—C2—C3—C4
C10—C2—C3—O19
C10—C12—C13—C14
C10—C12—C17—C16
O11—C10—C12—C13
O11—C10—C12—C17
C12—C13—C14—C15
C13—C12—C17—C16
C13—C14—C15—C16
C13—C14—C15—Br18
C14—C15—C16—C17
C15—C16—C17—C12
C17—C12—C13—C14
Br18—C15—C16—C17
O19—C3—C4—C5
−0.6 (6)
0.5 (4)
−178.7 (4)
0.6 (6)
179.2 (4)
0.2 (7)
179.6 (4)
−179.9 (4)
0.0 (6)
−179.0 (4)
179.8 (4)
0.5 (6)
−0.8 (4)
178.3 (4)
−178.7 (4)
−0.4 (4)
179.3 (4)
−0.6 (6)
0.7 (6)
−178.6 (4)
178.7 (4)
0.8 (4)
−178.4 (4)
−1.1 (6)
179.3 (3)
179.4 (3)
0.2 (6)
−179.9 (4)
0.4 (6)
0.2 (6)
0.0 (6)
−179.9 (3)
−0.3 (6)
0.2 (6)
−0.5 (6)
179.7 (3)
0.3 (7)
0.7 (7)
0.2 (7)
−179.7 (4)
O19—C3—C4—C9
Br20—C6—C7—C8
178.6 (4)
−179.7 (3)
Hydrogen-bond geometry (Å, º)
D—H···A
D—H
H···A
D···A
D—H···A
O19—H19···O11
C17—H17···O1
O19—H19···O11i
C14—H14···Br20ii
C16—H16···O11iii
0.84 (6)
0.93
0.84 (6)
0.93
1.93 (6)
2.28
2.60 (6)
3.05
2.669 (5)
2.948 (5)
3.174 (5)
3.959 (5)
3.287 (6)
146 (5)
129
127
165
130
0.93
2.61
Symmetry codes: (i) −x, −y, −z+1; (ii) x, y, z+1; (iii) x, y+1, z.
Acta Cryst. (2020). C76, 874-882
sup-13

supporting information
(4-Bromophenyl)(3-hydroxy-5-iodobenzofuran-2-yl)methanone (4h)
Crystal data
C15H8BrIO3
Mr = 443.02
F(000) = 3360
Dx = 2.087 Mg m−3
Monoclinic, I2/a
a = 26.4214 (8) Å
b = 4.76309 (13) Å
c = 46.6213 (14) Å
β = 106.034 (3)°
V = 5638.9 (3) Å3
Z = 16
Mo Kα radiation, λ = 0.71073 Å
Cell parameters from 11835 reflections
θ = 2.7–27.2°
µ = 5.11 mm−1
T = 293 K
Needle, yellow
0.35 × 0.15 × 0.05 mm
Data collection
Rigaku OD SuperNova Single source
diffractometer with an Eos detector
Radiation source: micro-focus sealed X-ray
tube, SuperNova (Mo) X-ray Source
Mirror monochromator
Tmin = 0.582, Tmax = 1.000
30966 measured reflections
5733 independent reflections
4448 reflections with I > 2σ(I)
R
int = 0.036
Detector resolution: 15.9631 pixels mm-1
ω scans
θmax = 26.4°, θmin = 2.7°
h = −32→33
k = −5→5
Absorption correction: gaussian
(CrysAlis PRO; Rigaku OD, 2018)
l = −58→58
Refinement
Refinement on F2
Least-squares matrix: full
R[F2 > 2σ(F2)] = 0.048
wR(F2) = 0.123
Hydrogen site location: mixed
H atoms treated by a mixture of independent
and constrained refinement
2
w = 1/[σ2(Fo ) + (0.0486P)2 + 38.6563P]
2
S = 1.07
where P = (Fo + 2Fc2)/3
5733 reflections
369 parameters
2 restraints
(Δ/σ)max = 0.002
Δρmax = 1.78 e Å−3
Δρmin = −1.21 e Å−3
Primary atom site location: dual
Special details
Geometry. 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.
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2)
x
y
z
Uiso*/Ueq
O1
C2
C3
C4
C5
H5
C6
C7
H7
0.31437 (17)
0.3471 (2)
0.3360 (2)
0.2954 (2)
0.2670 (2)
0.274146
0.2279 (3)
0.2174 (3)
0.191032
−0.1296 (9)
0.0161 (13)
−0.0703 (13)
−0.2773 (12)
−0.4364 (13)
−0.425178
−0.6110 (14)
−0.6343 (15)
−0.755200
0.62348 (9)
0.60926 (12)
0.58016 (13)
0.57509 (12)
0.55069 (14)
0.532280
0.55498 (14)
0.58299 (16)
0.585119
0.0509 (10)
0.0440 (14)
0.0442 (14)
0.0423 (13)
0.0501 (15)
0.060*
0.0519 (16)
0.0606 (18)
0.073*
Acta Cryst. (2020). C76, 874-882
sup-14

supporting information
C8
H8
C9
0.2457 (3)
0.239390
−0.4804 (15)
−0.496240
−0.3023 (13)
0.2278 (13)
0.3384 (10)
0.3180 (12)
0.5229 (15)
0.602010
0.6151 (15)
0.746849
0.5055 (14)
0.3006 (14)
0.225725
0.60729 (15)
0.625887
0.0592 (18)
0.071*
0.2837 (3)
0.3842 (2)
0.40906 (18)
0.3956 (2)
0.4331 (3)
0.449736
0.4469 (3)
0.473533
0.4200 (3)
0.3822 (3)
0.365082
0.60254 (14)
0.62289 (13)
0.60636 (9)
0.65444 (13)
0.66462 (15)
0.651387
0.69416 (15)
0.700905
0.71317 (13)
0.70382 (14)
0.717047
0.0489 (15)
0.0426 (13)
0.0561 (11)
0.0434 (13)
0.0568 (17)
0.068*
0.0577 (17)
0.069*
0.0505 (15)
0.0536 (16)
0.064*
C10
O11
C12
C13
H13
C14
H14
C15
C16
H16
C17
H17
Br18
O19
I20
O21
C22
C23
C24
C25
H25
C26
C27
H27
C28
H28
C29
C30
O31
C32
C33
H33
C34
H34
C35
C36
H36
C37
H37
Br38
O39
I40
0.3699 (3)
0.344307
0.2079 (14)
0.070224
0.67478 (15)
0.668447
0.0533 (16)
0.064*
0.43363 (3)
0.3584 (2)
0.18141 (2)
0.59407 (16)
0.5739 (2)
0.5344 (2)
0.5269 (2)
0.4916 (2)
0.466170
0.4964 (3)
0.5355 (3)
0.538039
0.5702 (3)
0.596072
0.5646 (2)
0.5924 (2)
0.57006 (18)
0.6364 (2)
0.6541 (3)
0.637978
0.6958 (3)
0.707602
0.7195 (2)
0.7020 (3)
0.717881
0.64613 (18)
0.0240 (12)
−0.84287 (11)
0.3302 (9)
0.3006 (13)
0.1034 (13)
0.0073 (12)
−0.1762 (14)
−0.274141
−0.2045 (14)
−0.0663 (15)
−0.097817
0.1147 (15)
0.208781
0.1500 (13)
0.4426 (14)
0.3832 (11)
0.6516 (13)
0.7459 (17)
0.682757
0.75258 (2)
0.55955 (10)
0.51858 (2)
0.61452 (9)
0.63934 (13)
0.63325 (13)
0.60347 (13)
0.58424 (13)
0.590511
0.55608 (14)
0.54646 (14)
0.527223
0.56484 (15)
0.558524
0.59361 (13)
0.66678 (13)
0.68662 (10)
0.67412 (13)
0.70387 (15)
0.718059
0.71181 (16)
0.731405
0.69098 (15)
0.66182 (16)
0.647729
0.0687 (2)
0.0569 (12)
0.06610 (17)
0.0479 (10)
0.0447 (14)
0.0450 (14)
0.0448 (14)
0.0481 (14)
0.058*
0.0507 (15)
0.0560 (16)
0.067*
0.0571 (17)
0.069*
0.0459 (14)
0.0473 (14)
0.0601 (12)
0.0456 (14)
0.066 (2)
0.079*
0.069 (2)
0.082*
0.0523 (16)
0.0592 (17)
0.071*
0.0504 (15)
0.061*
0.0785 (3)
0.0583 (12)
0.06144 (16)
0.14 (5)*
0.9338 (17)
0.996950
1.0266 (14)
0.9403 (15)
1.008713
0.6611 (3)
0.649775
0.77726 (3)
0.50813 (19)
0.43898 (2)
0.521 (4)
0.7523 (14)
0.691805
0.65349 (14)
0.633777
1.27828 (18)
0.0169 (11)
−0.44310 (11)
0.109 (19)
0.16 (2)
0.70198 (2)
0.65218 (11)
0.52517 (2)
0.6664 (11)
0.566 (2)
H39
H19
0.372 (4)
0.12 (4)*
Acta Cryst. (2020). C76, 874-882
sup-15

supporting information
Atomic displacement parameters (Å2)
U11
U22
U33
U12
U13
U23
O1
C2
C3
C4
C5
C6
C7
C8
0.063 (3)
0.050 (3)
0.046 (3)
0.047 (3)
0.052 (4)
0.050 (4)
0.063 (4)
0.075 (5)
0.058 (4)
0.047 (3)
0.060 (3)
0.041 (3)
0.058 (4)
0.061 (4)
0.061 (4)
0.061 (4)
0.058 (4)
0.0813 (5)
0.061 (3)
0.0611 (3)
0.047 (2)
0.046 (3)
0.044 (3)
0.047 (3)
0.045 (3)
0.050 (4)
0.061 (4)
0.062 (4)
0.047 (3)
0.046 (3)
0.065 (3)
0.044 (3)
0.079 (5)
0.069 (5)
0.044 (3)
0.059 (4)
0.054 (4)
0.0571 (4)
0.066 (3)
0.0614 (3)
0.050 (3)
0.047 (4)
0.043 (3)
0.040 (3)
0.048 (4)
0.045 (4)
0.053 (4)
0.055 (4)
0.041 (4)
0.041 (3)
0.063 (3)
0.039 (3)
0.059 (4)
0.058 (4)
0.047 (4)
0.058 (4)
0.048 (4)
0.0782 (5)
0.070 (3)
0.0597 (3)
0.052 (3)
0.045 (4)
0.047 (4)
0.038 (3)
0.049 (4)
0.045 (4)
0.063 (4)
0.062 (4)
0.044 (3)
0.049 (4)
0.072 (3)
0.042 (3)
0.076 (5)
0.080 (5)
0.049 (4)
0.055 (4)
0.053 (4)
0.0704 (5)
0.060 (3)
0.0613 (3)
0.040 (2)
0.035 (3)
0.044 (3)
0.038 (3)
0.047 (3)
0.052 (4)
0.064 (4)
0.051 (4)
0.048 (3)
0.043 (3)
0.047 (2)
0.050 (3)
0.055 (4)
0.054 (4)
0.041 (3)
0.046 (3)
0.055 (4)
0.0436 (4)
0.041 (2)
0.0616 (3)
0.047 (2)
0.042 (3)
0.046 (3)
0.048 (3)
0.047 (3)
0.050 (4)
0.045 (3)
0.054 (4)
0.047 (3)
0.046 (3)
0.046 (2)
0.048 (3)
0.045 (4)
0.050 (4)
0.061 (4)
0.068 (4)
0.045 (3)
0.1037 (6)
0.051 (3)
0.0563 (3)
−0.011 (2)
0.001 (3)
0.010 (3)
0.008 (3)
0.014 (3)
0.016 (2)
0.012 (3)
0.012 (3)
0.008 (3)
0.009 (3)
0.000 (3)
0.014 (4)
0.022 (3)
0.014 (3)
0.017 (3)
0.016 (2)
0.013 (3)
0.020 (3)
0.017 (3)
0.009 (3)
0.021 (3)
0.017 (3)
0.0122 (3)
0.016 (2)
−0.0096 (2)
0.0178 (19)
0.011 (3)
0.016 (3)
0.011 (3)
0.009 (3)
0.003 (3)
0.016 (3)
0.025 (3)
0.015 (3)
0.012 (3)
0.020 (2)
0.008 (3)
0.021 (4)
0.006 (4)
0.011 (3)
0.025 (4)
0.016 (3)
0.0152 (4)
0.019 (2)
0.0073 (2)
−0.0027 (19)
0.002 (3)
0.008 (3)
0.003 (2)
0.006 (3)
−0.002 (3)
0.001 (3)
−0.004 (3)
−0.001 (3)
0.007 (3)
0.003 (2)
0.003 (3)
0.000 (3)
−0.006 (3)
−0.001 (3)
0.000 (3)
0.003 (3)
−0.009 (3)
−0.013 (4)
0.000 (3)
C9
C10
O11
C12
C13
C14
C15
C16
C17
Br18
O19
I20
O21
C22
C23
C24
C25
C26
C27
C28
C29
C30
O31
C32
C33
C34
C35
C36
C37
Br38
O39
I40
0.006 (3)
−0.010 (2)
−0.002 (3)
−0.011 (3)
−0.015 (3)
0.005 (3)
−0.009 (3)
−0.010 (3)
−0.0039 (4)
−0.005 (3)
0.0046 (2)
−0.009 (2)
0.000 (3)
0.000 (3)
−0.0089 (3)
−0.003 (2)
−0.0056 (2)
−0.005 (2)
0.003 (3)
0.008 (3)
0.005 (3)
0.002 (3)
−0.005 (3)
−0.006 (3)
−0.010 (3)
−0.003 (3)
0.003 (3)
0.001 (3)
0.001 (3)
−0.001 (3)
0.001 (3)
−0.004 (3)
−0.009 (3)
−0.005 (3)
0.005 (3)
−0.007 (2)
0.003 (3)
−0.009 (4)
−0.005 (4)
0.006 (3)
−0.010 (3)
−0.004 (3)
−0.0097 (4)
−0.012 (2)
−0.0061 (2)
0.003 (2)
−0.004 (3)
−0.015 (4)
−0.030 (4)
−0.014 (3)
−0.010 (3)
−0.007 (3)
−0.0352 (5)
0.004 (2)
−0.0138 (2)
Geometric parameters (Å, º)
O1—C2
O1—C9
1.410 (7)
1.360 (7)
O21—C22
O21—C29
1.409 (7)
1.369 (7)
Acta Cryst. (2020). C76, 874-882
sup-16

supporting information
C2—C3
C2—C10
C3—C4
C3—O19
C4—C5
C4—C9
C5—H5
C5—C6
C6—C7
C6—I20
1.370 (8)
1.427 (9)
1.427 (9)
1.339 (7)
1.400 (9)
1.402 (8)
0.9300
1.383 (9)
1.412 (10)
2.111 (6)
0.9300
C22—C23
C22—C30
C23—C24
C23—O39
C24—C25
C24—C29
C25—H25
C25—C26
C26—C27
C26—I40
C27—H27
C27—C28
C28—H28
C28—C29
C30—O31
C30—C32
C32—C33
C32—C37
C33—H33
C33—C34
C34—H34
C34—C35
C35—C36
C35—Br38
C36—H36
C36—C37
C37—H37
O39—H39
1.373 (9)
1.410 (9)
1.423 (8)
1.330 (7)
1.404 (9)
1.385 (8)
0.9300
1.360 (9)
1.399 (9)
2.112 (6)
0.9300
C7—H7
C7—C8
C8—H8
C8—C9
1.383 (9)
0.9300
1.373 (9)
0.9300
1.379 (9)
1.258 (7)
1.481 (8)
1.379 (9)
1.410 (8)
0.9300
1.395 (9)
0.9300
1.383 (9)
1.378 (9)
1.894 (6)
0.9300
1.400 (9)
1.260 (7)
1.495 (9)
1.409 (9)
1.388 (9)
0.9300
1.388 (11)
0.9300
1.367 (10)
1.372 (9)
1.897 (7)
0.9300
C10—O11
C10—C12
C12—C13
C12—C17
C13—H13
C13—C14
C14—H14
C14—C15
C15—C16
C15—Br18
C16—H16
C16—C17
C17—H17
O19—H19
1.375 (9)
0.9300
0.78 (11)
1.376 (9)
0.9300
0.79 (2)
C9—O1—C2
O1—C2—C10
C3—C2—O1
C3—C2—C10
C2—C3—C4
O19—C3—C2
O19—C3—C4
C5—C4—C3
C5—C4—C9
C9—C4—C3
C4—C5—H5
C6—C5—C4
C6—C5—H5
C5—C6—C7
C5—C6—I20
C7—C6—I20
C6—C7—H7
C8—C7—C6
C8—C7—H7
106.3 (4)
125.0 (5)
109.0 (5)
126.0 (6)
108.6 (5)
126.4 (6)
125.1 (6)
135.9 (6)
119.5 (6)
104.6 (5)
121.2
117.5 (6)
121.2
121.8 (6)
119.4 (5)
118.9 (5)
119.5
C29—O21—C22
O21—C22—C30
C23—C22—O21
C23—C22—C30
C22—C23—C24
O39—C23—C22
O39—C23—C24
C25—C24—C23
C29—C24—C23
C29—C24—C25
C24—C25—H25
C26—C25—C24
C26—C25—H25
C25—C26—C27
C25—C26—I40
C27—C26—I40
C26—C27—H27
C28—C27—C26
C28—C27—H27
104.6 (4)
125.5 (5)
109.7 (5)
124.7 (6)
108.4 (5)
125.5 (6)
126.1 (6)
135.4 (6)
104.3 (5)
120.3 (6)
121.4
117.2 (6)
121.4
122.4 (6)
118.2 (5)
119.3 (5)
119.3
121.1 (7)
119.5
121.4 (6)
119.3
Acta Cryst. (2020). C76, 874-882
sup-17

supporting information
C7—C8—H8
C9—C8—C7
C9—C8—H8
O1—C9—C4
O1—C9—C8
C8—C9—C4
121.7
116.6 (6)
121.7
C27—C28—H28
C27—C28—C29
C29—C28—H28
O21—C29—C24
O21—C29—C28
C24—C29—C28
C22—C30—C32
O31—C30—C22
O31—C30—C32
C33—C32—C30
C37—C32—C30
C37—C32—C33
C32—C33—H33
C34—C33—C32
C34—C33—H33
C33—C34—H34
C35—C34—C33
C35—C34—H34
C34—C35—C36
C34—C35—Br38
C36—C35—Br38
C35—C36—H36
C35—C36—C37
C37—C36—H36
C32—C37—H37
C36—C37—C32
C36—C37—H37
C23—O39—H39
121.8
116.3 (6)
121.8
111.5 (5)
124.9 (6)
123.6 (6)
125.0 (5)
115.7 (5)
119.3 (6)
118.4 (5)
117.7 (6)
123.8 (6)
119.0
122.0 (6)
119.0
120.9
118.3 (6)
120.9
119.6 (5)
121.4 (6)
118.9 (5)
120.3
113.1 (5)
124.5 (6)
122.4 (6)
125.5 (6)
116.2 (6)
118.3 (6)
117.6 (6)
123.7 (5)
118.7 (6)
120.3
119.4 (7)
120.3
119.8
120.3 (6)
119.8
120.8 (6)
120.3 (5)
118.8 (5)
120.1
C2—C10—C12
O11—C10—C2
O11—C10—C12
C13—C12—C10
C13—C12—C17
C17—C12—C10
C12—C13—H13
C12—C13—C14
C14—C13—H13
C13—C14—H14
C15—C14—C13
C15—C14—H14
C14—C15—Br18
C16—C15—C14
C16—C15—Br18
C15—C16—H16
C17—C16—C15
C17—C16—H16
C12—C17—H17
C16—C17—C12
C16—C17—H17
C3—O19—H19
119.4 (6)
120.3
119.4
121.1 (6)
119.4
104 (8)
119.9 (7)
120.1
119.6
120.8 (6)
119.6
101 (4)
O1—C2—C3—C4
O1—C2—C3—O19
O1—C2—C10—O11
O1—C2—C10—C12
C2—O1—C9—C4
C2—O1—C9—C8
C2—C3—C4—C5
C2—C3—C4—C9
C2—C10—C12—C13
C2—C10—C12—C17
C3—C2—C10—O11
C3—C2—C10—C12
C3—C4—C5—C6
C3—C4—C9—O1
C3—C4—C9—C8
C4—C5—C6—C7
C4—C5—C6—I20
C5—C4—C9—O1
C5—C4—C9—C8
−0.3 (7)
178.9 (6)
−178.5 (5)
2.8 (10)
O21—C22—C23—C24
O21—C22—C23—O39
O21—C22—C30—O31
O21—C22—C30—C32
C22—O21—C29—C24
C22—O21—C29—C28
C22—C23—C24—C25
C22—C23—C24—C29
C22—C30—C32—C33
C22—C30—C32—C37
C23—C22—C30—O31
C23—C22—C30—C32
C23—C24—C25—C26
C23—C24—C29—O21
C23—C24—C29—C28
C24—C25—C26—C27
C24—C25—C26—I40
C25—C24—C29—O21
C25—C24—C29—C28
−2.1 (7)
177.5 (6)
−178.4 (6)
0.7 (10)
0.5 (7)
0.0 (7)
−179.4 (6)
178.4 (7)
0.6 (7)
178.5 (6)
−175.9 (7)
2.0 (7)
−172.1 (6)
6.6 (10)
179.0 (6)
−1.4 (10)
−1.4 (9)
179.9 (6)
−177.0 (6)
−0.7 (7)
179.2 (6)
−1.4 (9)
177.3 (4)
−178.9 (5)
1.0 (10)
−1.0 (9)
178.1 (6)
177.4 (7)
−1.2 (7)
−179.8 (6)
2.1 (10)
−173.4 (4)
177.1 (5)
−1.5 (10)
Acta Cryst. (2020). C76, 874-882
sup-18

supporting information
C5—C6—C7—C8
C6—C7—C8—C9
0.6 (11)
0.9 (11)
C25—C26—C27—C28
−2.5 (11)
0.7 (10)
C26—C27—C28—C29
C27—C28—C29—O21
C27—C28—C29—C24
C29—O21—C22—C23
C29—O21—C22—C30
C29—C24—C25—C26
C30—C22—C23—C24
C30—C22—C23—O39
C30—C32—C33—C34
C30—C32—C37—C36
O31—C30—C32—C33
O31—C30—C32—C37
C32—C33—C34—C35
C33—C32—C37—C36
C33—C34—C35—C36
C33—C34—C35—Br38
C34—C35—C36—C37
C35—C36—C37—C32
C37—C32—C33—C34
Br38—C35—C36—C37
O39—C23—C24—C25
O39—C23—C24—C29
I40—C26—C27—C28
C7—C8—C9—O1
C7—C8—C9—C4
C9—O1—C2—C3
C9—O1—C2—C10
C9—C4—C5—C6
178.2 (6)
−1.7 (11)
−0.1 (7)
177.4 (6)
0.6 (9)
−177.8 (6)
1.4 (10)
−178.6 (6)
−179.9 (6)
0.4 (9)
179.9 (6)
−3.2 (11)
−0.3 (10)
3.1 (11)
−175.1 (5)
−1.7 (10)
0.3 (10)
−177.1 (6)
1.2 (10)
1.3 (6)
179.0 (6)
−0.2 (9)
−179.8 (6)
−0.2 (10)
178.2 (7)
−178.7 (6)
7.0 (9)
−174.3 (6)
0.0 (12)
0.0 (10)
C10—C2—C3—C4
C10—C2—C3—O19
C10—C12—C13—C14
C10—C12—C17—C16
O11—C10—C12—C13
O11—C10—C12—C17
C12—C13—C14—C15
C13—C12—C17—C16
C13—C14—C15—C16
C13—C14—C15—Br18
C14—C15—C16—C17
C15—C16—C17—C12
C17—C12—C13—C14
Br18—C15—C16—C17
O19—C3—C4—C5
O19—C3—C4—C9
I20—C6—C7—C8
1.2 (11)
−178.9 (6)
−1.7 (11)
1.1 (11)
−0.6 (11)
178.3 (5)
4.5 (12)
1.8 (10)
176.5 (5)
−0.8 (11)
−178.6 (6)
−178.1 (6)
−177.6 (6)
173.0 (5)
Hydrogen-bond geometry (Å, º)
D—H···A
D—H
H···A
D···A
D—H···A
O19—H19···O11
C17—H17···O1
O39—H39···O31
C37—H37···O21
C13—H13···O39i
0.76 (10)
0.93
0.79 (7)
0.93
2.05 (9)
2.24
1.90 (9)
2.28
2.680 (7)
2.919 (8)
2.617 (7)
2.950 (8)
3.231 (9)
140 (9)
129
151
128
135
0.93
2.50
Symmetry code: (i) x, y+1, z.
Acta Cryst. (2020). C76, 874-882
sup-19