Synthesis of polyfluorinated benzofurans

Article abstract of DOI:10.1016/j.jfluchem.2019.109371

A simple and efficient approach to the synthesis of fluorinated benzofurans including the Sonogashira cross-coupling of o-iodophenols with terminal Ph- and n-Bu-acetylenes, followed by intramolecular cyclization, in good to excellent yields is reported.

Full text of DOI:10.1016/j.jfluchem.2019.109371

JournalofFluorineChemistry227(2019)109371
Contents lists available at ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Synthesis of polyfluorinated benzofurans
⁎
Larisa Politanskayaa,b, , Nadezhda Troshkovaa, Evgeny Tretyakova,b, Chanjuan Xic
a N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of Russian Academy of Sciences, Ac. Lavrentiev Ave., 9, Novosibirsk, 630090, Russian
Federation
b Novosibirsk State University, Pirogova Str., 2, Novosibirsk, 630090, Russian Federation
c MOE Key Laboratory of Bioorganic Phosphorus Chemistry&Chemical Biology, Department of Chemistry, Tsinghua University, Beijing, 100084, China
A R T I C L E I N F O
A B S T R A C T
Keywords:
A simple and efficient approach to the synthesis of fluorinated benzofurans including the Sonogashira cross-
coupling of o-iodophenols with terminal Ph- and n-Bu-acetylenes, followed by intramolecular cyclization, in
good to excellent yields is reported.
Fluoroheterocycles
o-Iodophenols
Iodination
Cross-coupling
Benzofurans
1. Introduction
2. Results and discussion
Heterocyclic compounds have, of course, found many applications
in all part of the chemical industry and significantly impact on our daily
lives as components of medicines, agrochemicals, natural products and
commodity chemicals. Among them, fluorinated heterocyclic com-
pounds are known to modify their pharmacological properties and their
therapeutical potency due to the particular properties of fluorine, in
many cases, increased lipophilicity of fluorine containing organic mo-
lecules in a biological environment [1]. Therefore, synthesis of fluorine
containing heterocyclic compounds came into the focus of organic
chemists [2].
The starting materials for this study (a representative series of io-
dophenols 2a–f with different fluorine contents) were prepared via the
aromatic electrophilic substitution of a hydrogen atom with iodine in
fluorophenols 1a–e (Table 1). In the present work we used a simple and
convenient iоdination system, well proven earlier in obtaining fluori-
nated iodoanilines [8a] (compare [9]).
Phenols reacted with elemental iodine in aqueous medium in the
presence of NaHCO3 at room temperature. Since fluorinated phenolic
derivatives are extremely volatile compounds, it is important that the
reactions are carried out in a closed vessel. The carbon dioxide formed
in the cause of interaction of HI with NaHCO3 was released from the
reaction flask through a needle inserted into the septa. Another im-
portant point in the preparation of fluorinated iodophenols is the
thorough purification of the reaction products from the impurity of the
elemental iodine by the action of a saturated aqueous solution of
Na2S2O3. Otherwise, elemental iodine, readily soluble in the aromatic
substrates, increases the already high volatility of iodophenols, which
dramatically decreases the yields of target products.
The broad spectrum of pharmacological activity of benzofurans in-
dicates that the search for new biologically active compounds in this
series of compounds is of undoubted interest [3]. Although several
protocols for the production of monofluorinated derivatives have been
reported [4], there are very a few examples for the synthesis of poly-
fluorinated benzofurans [5].
Previously, we have developed efficient strategies for preparation of
polyfluorinated heterocyclic derivatives (indoles [6], indazoles [7] and
2,3-dihydroquinolinones [8]), via the common methods based on
transformations of fluorinated iodoanilines into alkynylanilines with
further heterocyclization. Herein we describe a simple, effective and
universal pathway of conversion of fluorinated iodophenols into ben-
zofurans.
In order to obtain the monoiodinated derivatives of phenols 1a and
1d in the aqueous medium we carried out these reactions at 0 °C using
the half amount of iodine in relation to aromatic substrates. However,
our attempts failed: under these conditions, only products 2b and 2e
were formed. For this reason, we replaced H2O as a solvent with aqu-
eous dioxane. This allowed us to obtain the target iodophenol 2a even
when the reaction proceeded at room temperature (Table 1, entry 1). A
⁎ Corresponding author at: N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of Russian Academy of Sciences, Ac. Lavrentiev Ave., 9,
Novosibirsk, 630090, Russian Federation.
E-mail address: plv@nioch.nsc.ru (L. Politanskaya).
https://doi.org/10.1016/j.jfluchem.2019.109371
Received 28 July 2019; Received in revised form 9 September 2019; Accepted 9 September 2019
Availableonline10September2019
0022-1139/©2019ElsevierB.V.Allrightsreserved.

L. Politanskaya, et al.
JournalofFluorineChemistry227(2019)109371
Table 1
Synthesis of fluorinated iodophenols 2a–f.
Entry
1
Phenole 1
Iodophenole 2
I2 (equiv)
0.9
Solvent
Yield (%)
63
dioxane (aq)
2
3
4
5
6
2.2
1.1
1.1
2.2
1.1
H2O
H2O
H2O
H2O
H2O
98
90
93
85
82
possible reason for the decrease in the reactivity of phenol 1a in di-
oxane compared to that in the water is a decrease in the degree of
dissociation of the alcohol function with a decrease in the permittivity
of the solvent. However, phenol 1d interacted with the iodine giving
diiodophenol 2e, even when the reaction is carried out in dioxane.
At present there are a large number of examples of benzofurans
production by the interaction of o-iodophenols with terminal alkynes
[10]. It is noteworthy that Pd catalysts used in these cross-coupling
reactions were overwhelmingly of unusual structure such as: graphene
oxide-grafted aminobisphosphine − Pd(II) complex [10a], palladium
nanoparticles (Pd-NPs) [10b], nanoparticles Pd0-AmP-MCF [10c], Pd-
NPs on N,O-dual-doped hierarchical porous carbon [10d],
[(PhCH2O)2PNiPr2]2PdCl2 [10e], Pd(II) complex catalyst [10f] and so
on.
3. Conclusion
In conclusion, we carried out a highly efficient and simple synthesis
of polyfluorinated iodophenols using readily available reagents. On the
basis of iodophenols we have realized the classic cross-coupling reac-
tion with acetylene using the simplest catalysts (bis(triphenylpho-
sphine) palladium dichloride, copper(I) iodide, triethylamine), which
made it possible to obtain a representative series of fluorinated ben-
zofurans.
4. Experimental section
4.1. General
In our work, we used the most common Sonogashira reaction con-
ditions: bis(triphenylphosphine) palladium dichloride, copper(I) iodide,
and triethylamine as catalysts in dry acetonitrile as a solvent caused the
cross-coupling of iodophenols 2a–f with the acetylene, followed by
intramolecular cyclization thus yielding fluorinated benzofurans 3a–l
(Table 2). The reactions were carried out at room temperature in a
tightly closed Schlenk flask in an argon atmosphere. Target compounds
3 were isolated by thin-layer chromatography (TLC).
All solvents were purified using standard procedures. Et3N, MeCN
were distilled and kept over CaH2 before to use. 2,3,4,5-
Tetrafluorophenol 1e was synthesized according to previously de-
scribed methods [11]. Other chemicals were obtained from commercial
sources and were used without further purification. Preparative thin-
layer chromatography was performed on Merck precoated silica gel 60
PF254 containing gypsum. Visualization of the developed chromato-
grams was performed by UV light.
The similar reaction conditions caused the cross-coupling of io-
doanilines 2a,c with trimethylsilylacetylene. Scheme 1 shows the pro-
ducts of these transformations. The yield of the target trimethylsily-
lethynylphenol 4a is relatively small due to the high volatility of this
fluorinated hydroxyderivative. The result of the interaction of tri-
methylsilylacetylene with 2c was the formation in addition to 4b more
and dimeric benzofuran 3 m, which was, apparently, a consequence of
the dimerization of 2-ethynyl-4,6-difluorophenol (by-product), fol-
lowed by subsequent cyclization reaction (Scheme 2).
NMR spectra were recorded on a Bruker Avance-300 (300.13 MHz
for 1H and 282.37 MHz for 19F), Avance-400 (400.13 MHz for 1H,
376.44 MHz for 19F and 100.62 MHz for 13C) and DRX-500
(500.13 MHz for 1H, 125.76 MHz for 13C) spectrometers.
Deuterochloroform (CDCl3) and acetone-d6 were used as solvents, with
residual CHCl3 (δH =7.26 ppm) or CDCl3 (δC =77.0 ppm) and acetone
(δH =2.15 ppm) or acetone-d6 (δC = 28.6 and 205.0 ppm) being em-
ployed as internal standards. C6F6 (δF 163.0 ppm) was used as external
references (19F NMR). 13C NMR spectra were registered with CeH spin
decoupling. Masses of molecular ions were determined by HRMS on a
DFS Thermo scientific instrument (EI, 70 eV) Melting points were
2

L. Politanskaya, et al.
JournalofFluorineChemistry227(2019)109371
Table 2
Synthesis of fluorinated benzofurans 3a–l.
Entry
1
Iodophenole 2
Benzofurane 3
Yield (%)
96
2
3
80
78
4
80
5
6
70
65
7
8
9
95
93
63
10
88
11
12
66
75
3

L. Politanskaya, et al.
JournalofFluorineChemistry227(2019)109371
Scheme 1. The interaction of iodophenols 2a and 2c with trimethylsilylacetylene.
(ddt, 1J (C5,F5) =244.1 Hz, 2J (C5,F4) =10.6 Hz, C5), 141.2 (dm, 1J
(C3,F3) =249.6 Hz, 2J (C3,F2) ≈ 2J (C3,F4) =13 Hz, C3), 141.0 (tt, 2J
(C1,F2) =11.8 Hz, C1), 137.5 (dddd, 1J (C2,F2) =240.5 Hz, 2J (C2,F3)
=11.9 Hz, C2), 133.9 (dm, 1J (C4,F4) =244.0 Hz, 2J (C4,F5) ≈ 2J
(C4,F3) =15 Hz, C4), 99.8 (d, 2J (C6,F5) =21.9 Hz, C6). 19F NMR
(282 MHz, CDCl3): δ = –142.8 (m, J (F5,F4) =22 Hz, J (F5,H6)
=11.5 Hz, 1 F, F5), –159.1 (tm, J (F3,F2) ≈ J (F3,F4) =20 Hz, 1 F, F3);
–165.7 (m, J (F2,F3) =20.4 Hz, 1 F, F2); –171.7 (tm, J (F4,F5) =22.1 Hz,
J (F4,F3) =20.3 Hz, J (F4,H6) =7.3 Hz, 1 F, F4). HRMS (EI): m/z [M]+
calcd for C6H2F4O: 166.0036; found: 166.0037.
4.2.2. 4,5-Difluoro-2-iodophenol (2a)
To a stirred solution of phenol 1a (2 g, 15 mmol) in dioxane
(20 mL), a solution of NaHCO3 (1.1 g, 13 mmol) in H2O (7 mL) and then
finely ground I2 (3.3 g, 13 mmol) were added. The reaction flask was
closed with rubber septa, in which a needle was inserted. The reaction
mixture was stirred at room temperature for 24 h. Then saturated
aqueous solutions of Na2S2O3 (50 mL) was added and the mixture was
stirred for 1 h. The reaction product was extracted with CH2Cl2
(2 × 100 mL). The combined organic layers were washed with H2O
(70 mL), dried (MgSO4) and filtered. Solvent was removed under va-
cuum to a constant weight.
Scheme 2. The hypothetical scheme of 3 m formation.
recorded on a Melter-Toledo FP81 Thermosystem apparatus. The IR
spectra were recorded on a Bruker Vector 22 spectrometer (KBr or thin
layer).
The structures of all polyfluorinated compounds prepared here were
corroborated by their 19F, 1H and 13C NMR, high-resolution mass
spectrometry, and IR-spectroscopy data (see Supplementary data).
Signals in the NMR spectra of 1e, 2, 3 and 4 were assigned on the basis
of spin coupling constants, which are typical for polyfluorinated ben-
zenes [6–8].
Colorless oil; yield: 2.1 g (63%). IR (neat): 3591, 3487, 1601, 1516,
1502, 1489, 1408, 1319, 1300, 1238, 1198, 1142, 991, 960, 870, 802,
781, 735, 622, 567 cm–1. NMR spectra are close to those published
earlier [9]. 1H NMR (300 MHz, Acetone-d6): δ = 9.44 (s, 1 H, OH), 7.65
(dd, J (H3,F4) =9.9 Hz, J (H3,F5) =9.0 Hz, 1 H, H3), 6.88 (dd, J (H6,F5)
=12.0 Hz, J (H6,F4) =7.1 Hz, 1 H, H6). 13C NMR (126 MHz, Acetone-
d6): δ = 154.9 (dd, 2J (C1,F2) =8.8 Hz, C1), 151.6 (dd, 1J (C5,F5)
=246.8 Hz, 2J (C5,F4) =13.6 Hz, C5), 145.3 (dd, 1J (C4,F4) =241.6 Hz,
2J (C4,F5) =13.4 Hz, C4), 127.8 (dd, 2J (C3,F4) =20.2 Hz, C3), 104.9 (d,
2J (C6,F5) =20.3 Hz, C6), 76.9 (dd, 3J (C2,F4) =6.4 Hz, C2). 19F NMR
(282 MHz, Acetone-d6): δ = –135.9 (m, J (F5,F4) =21.0 Hz, J (F5,H6)
=12.0 Hz, J (F5,H3) =9.0 Hz,1 F, F5), –147.9 (m, J (F4,F5) =21 Hz, J
(F4,H3) =9.9 Hz, J (F4,H6) =7.1 Hz,1 F, F4). HRMS (EI): m/z [M]+
calcd for C6H3F2IO: 255.9191; found: 255.9195.
4.2. Synthetic procedures
4.2.1. 2,3,4,5-Tetrafluorophenol (1e)
To a stirred solution of 1,2,3,4-tetrafluorobenzene [11] (5.0 g,
33 mmol) in dry tetrahydrofuran (25 mL) 2.5 M solution of butyl-li-
thium in hexane (15 mL, 38 mmol)) in a Schlenk flask under argon at
–70 °C was added. The mixture was stirred at –70 °C for 1.5 h, then a
solution of trimethylborate (3.9 g, 38 mmol) in dry tetrahydrofuran (5
mL) was added over 0.5 h. The mixture was stirred at –70 °C for 1 h,
then 45% w/w hydrogen peroxide (9 mL, ˜30 mmol) was added and the
mixture was warmed to room temperature. A solution of NaOH (1.7 g,
40 mmol) in H2O (20 mL) was added with stirring to obtain a three-
layer system. Top layer was discarded, the two lower layers were ex-
tracted with CH2Cl2 (2 × 50 mL), acidified with hydrochloric acid
(˜5 mL), washed with H2O (50 mL) and dried (MgSO4). The solvent was
evaporated to small volume to obtain the target product (since 1f is
very volatile, its yield was determined based on the 19F NMR spectrum
recorded with a quantity of the internal standard – C6F6).
4.2.3. Iodophenols 2; general procedure
To a stirred solution of phenol 1 (20 mmol) in H2O (40 mL), NaHCO3
(2.2 g, 26 mmol or 4.4 g, 52 mmol for 2b,e), I2 (5.6 g, 22 mmol or 11.2 g,
44 mmol for 2b,e) were added. The reaction flask was closed with rubber
septa, in which a needle was inserted and reaction mixture was stirred at
room temperature for 24 h. Then a saturated aqueous solutions of
Na2S2O3 (40 mL) was added and the mixture was stirred for 1 h. The
reaction product was extracted with CH2Cl2 or Et2O (2 × 100 mL). The
combined organic layers were washed with saturated aqueous solutions
of Na2S2O3 (50 mL), H2O (2 × 70 mL), dried (MgSO4), filtered and sol-
vent was removed under vacuum to a constant weight.
Colorless oil; yield: 2.9 g (53%). IR (neat): 3589, 3375, 2889, 1642,
1529, 1510, 1319, 1273, 1240, 1068, 953, 883, 837, 713 cm–1. 1H NMR
(300 MHz, CDCl3): δ = 8.88 (s, 1 H, OH), 6.49 (m, J (H6,F5) =11.5 Hz,
J (H6,F4) =7.3 Hz, 1 H, H6). 13C NMR (126 MHz, CDCl3): δ = 146.5
4

L. Politanskaya, et al.
JournalofFluorineChemistry227(2019)109371
4.2.3.1. 3,4-Difluoro-2,6-diiodophenol (2b). White solid; yield: 7.5 g
(98%); mp 82.1 °C (decomp.) (mp 86 °C [9]). IR (KBr): 3450, 2926,
1601, 1466, 1400, 1340, 1290, 1209, 1194, 1165, 1012, 860, 748, 700,
652, 619 cm–1. NMR spectra are close to those published earlier [11].
1H NMR (300 MHz, Acetone-d6): δ = 8.44 (s, 1 H, OH), 7.78 (dd, J
(H5,F4) =9.4 Hz, J (H5,F3) =8.8 Hz, 1 H, H5). 13C NMR (126 MHz,
Acetone-d6): δ = 154.1 (t, 3J (C1,F3) =3.1 Hz, C1), 151.4 (dd, 1J (C3,F3)
=243.2 Hz, 2J (C3,F4) =14.4 Hz, C3), 144.6 (dd, 1J (C4,F4) =246.9 Hz,
2J (C4,F3) =15.8 Hz, C4), 127.1 (dd, 2J (C5,F4) =20.5 Hz, C5), 76.3 (dd,
3J (C6,F4) =6.3 Hz, C6), 74.8 (d, 2J (C2,F3) =24.1 Hz, C2). 19F NMR
(282 MHz, Acetone-d6): δ = –111.6 (dd, J (F3,F4) =23.2 Hz, J (F3,H5)
=8.8 Hz, 1 F, F3), –143.0 (dd, J (F4,F5) =23.2 Hz, J (F4,H5) =9.4 Hz,
1 F, F4). HRMS (EI): m/z [M]+ calcd for C6H2F2I2O: 381.8158; found:
381.8161.
=12 Hz, C1), 136.1 (dddd, 1J (C2,F2) =245 Hz, 2J (C2,F3) =12.8 Hz,
C2), 134.3 (dddd, 1J (C4,F4) =250 Hz, 2J (C4,F5) ≈ 2J (C4,F3) =19 Hz,
C4), 67.5 (dd, 2J (C6,F5) =26.8 Hz, C6). 19F NMR (282 MHz, CDCl3): δ
= –120.1 (ddd, J (F5,F4) =23.7 Hz, J (F5,F2) =7.7 Hz, J (F5,F3)
=2.3 Hz, 1 F, F5), –155.7 (tm, J (F3,F2) ≈ J (F3,F4) =20.4 Hz, J
(F3,F5) =2.3 Hz, 1 F, F3); –161.2 (ddd, J (F2,F3) =20.4 Hz, J (F2,F5)
=7.7 Hz, J (F2,F4) =3.9 Hz, 1 F, F2); –166.2 (tm, J (F4,F5) =24 Hz, J
(F4,F3) =20.4 Hz, J (F4,F2) =3.9 Hz, 1 F, F4). HRMS (EI): m/z [M]+
calcd for C6H1F4IO: 291.9003; found: 291.9005.
4.2.4. Cross-coupling reactions of iodophenols 2 with acetylene; general
procedure
To a solution of iodophenol 2 (1.5 mmol) and acetylene (1.6 mmol
or 3.3 mmol for 3c,d,i,j) in MeCN (10 mL) in a Schlenk flask under
argon, Pd(PPh3)2Cl2 (52 mg, 0.07 mmol), CuI (28 mg, 0.15 mmol) and
Et3N (3 mL) were added. The mixture was stirred at room temperature
for 24÷48 h. Then, the reaction suspension was placed directly onto a
chromatography plates (silica gel) and air-dried. The reaction products
were isolated by preparative TLC using hexane as an eluent.
4.2.3.2. 2,4-Difluoro-6-iodophenol (2c). White solid; yield: 4.6 g (90%);
mp 36.6–41.7 °C (liquid [11]). IR (KBr): 3234, 30,91, 1695, 1599, 1489,
1431, 1394, 1294, 1209, 1165, 1103, 985, 850, 829, 779, 702, 592,
519, 457 cm–1
.
NMR spectra are close to those published earlier [9]. 1H NMR
(300 MHz, Acetone-d6): δ = 7.37 (dm, J (H5,F4) =7.8 Hz, J (H5,H3)
=3.0 Hz, 1 H, H5), 7.11 (m, J (H3,F2) =10.6 Hz, J (H3,F4) =8.5 Hz, J
(H3,H5) =3.0 Hz, 1 H, H3). 13C NMR (126 MHz, Acetone-d6): δ = 156.1
(dd, 1J (C4,F4) =242.8 Hz, 3J (C4,F2) =11.2 Hz, C4), 150.4 (dd, 1J
(C2,F2) =245.5 Hz, 3J (C2,F4) =12.7 Hz, C2), 142.7 (dd, 2J (C1,F2)
=15.6 Hz, C1), 121.3 (dd, 2J (C5,F4) =24.6 Hz, C5), 105.2 (dd, 2J
(C3,F2) =27.0 Hz, 2J (C3,F4) =23.5 Hz, C3), 85.0 (dd, 3J (C6,F4)
=10.4 Hz, C6). 19F NMR (282 MHz, Acetone-d6): δ = –121.1 (m, J
(F4,H3) =8.5 Hz, J (F4,H5) =7.8 Hz,1 F, F4), –128.2 (dm, J (F2,H3)
=10.6 Hz, 1 F, F2). HRMS (EI): m/z [M]+ calcd for C6H3F2IO:
255.9191; found: 255.9192.
4.2.4.1. 2-Butyl-5,6-difluorobenzofuran (3a). Colorless oil; yield: 0.30 g
(96%); Rf = 0.75 (hexane). IR (neat): 2960, 2933, 2671, 1604, 1481,
1458, 1358, 1207, 1188, 1338, 1101, 947, 862, 764, 629 cm–1. 1H NMR
(500 MHz, Acetone-d6): δ = 7.42 (m, J (H7,F6) =10.4 Hz, J (H7,F5)
=6.6 Hz, 1 H, H7), 7.39 (dd, J (H4,F5) =10.4 Hz, J (H4,F6) =8.0 Hz, 1
H, H4), 6.50 (m, 1 H, H3), 2.75 (t, J (H8,H9) =7.6 Hz, 2 H, H8), 1.72 –
1.66 (m, 2 H, H9), 1.41 – 1.36 (m, 2 H, H10), 0.93 (t, J (H11,H10
)
=7.3 Hz, 3 H, H11). 13C NMR (126 MHz, Acetone-d6): δ = 162.9 (d, C2),
150.3 (dd, 3J (C7a,F6) =11.4 Hz, C7a), 148.6 (dd, 1J (C6,F6) =241.7 Hz,
2J (C6,F5) =15.7 Hz, C6), 148.4 (dd, 1J (C5,F5) =238.5 Hz, 2J (C5,F6)
=14.2 Hz, C5), 125.7 (dd, 3J (C3a,F5) =8.9 Hz, C3a), 107.9 (d, 2J (C4,F5)
=20.6 Hz, C4), 102.8 (dd, C3), 100.7 (d, 2J (C7,F6) =22.4 Hz, C7), 30.4
(s, C8), 29.5 (s, C9), 22.8 (s, C10), 14.0 (s, C11). 19F NMR (282 MHz,
Acetone-d6): δ = –142.5 (m, J (F6,F5) =18.3 Hz, J (F6,H7) =10.4 Hz, J
(F6,H4) =8.0 Hz, 1 F, F6), –144.9 (m, J (F5,F6) =18.3 Hz, J (F5,H4)
=10.4 Hz, J (F5,H7) =6.6 Hz, 1 F, F5). HRMS (EI): m/z [M]+ calcd for
4.2.3.3. 2,3,4-Trifluoro-6-iodophenol (2d). Colorless oil; yield: 5.1 g
(93%). IR (neat): 3572, 3483, 1697, 1612, 1514, 1473, 1360, 1333,
1298, 1255, 1215, 1188, 1076, 997, 850, 798, 710, 652, 536, 469 cm–1
.
NMR spectra are close to those published earlier [9]. 1H NMR
(300 MHz, Acetone-d6): δ = 9.91 (s, 1 H, OH), 7.51 (m, J (H5,F4)
=9.7 Hz, J (H5,F3) =8.2 Hz, J (H5,F2) =2.6 Hz, 1 H, H5). 13C NMR
(126 MHz, Acetone-d6): δ = 145.3 (ddd, 1J (C4,F4) =243.8 Hz, 2J
(C4,F3) =10.6 Hz, C4), 143.7 (dd, 2J (C1,F2) =12.6 Hz, C1), 141.0
(ddd, 1J (C3,F3) =245.5 Hz, 2J (C3,F2) =16.4 Hz, 2J (C3,F4) =13.9 Hz,
C3), 140.8 (ddd, 1J (C2,F2) =246.5 Hz, 2J (C2,F3) =11.8 Hz, C2), 121.1
(dd, 2J (C5,F4) =20.2 Hz, C5), 77.2 (dd, 3J (C6,F4) =7.9 Hz, C6). 19F
NMR (282 MHz, CDCl3): δ = –145.5 (dd, J (F4,F3) =20.8 Hz, J (F4,H5)
=9.2 Hz, 1 F, F4), –153.9 (dd, J (F2,F3) =19.5 Hz, J (F2,H5) =2.6 Hz,
1 F, F2), –158.2 (m, J (F3,F4) =20.8 Hz, J (F3,F2) =19.5 Hz, J (F3,H5)
=8.2 Hz, 1 F, F3). HRMS (EI): m/z [M]+ calcd for C6H2F3IO: 273.9097;
found: 273.9096.
C12H12F2O: 210.0851; found: 210.0854.
4.2.4.2. (E)-2,3,5,6-Tetrafluoro-4-(1-(2-(perfluorophenyl)hydrazono)
ethyl)aniline (3b). White solid; yield: 0.28 g (80%); Rf = 0.81 (hexane,
twice); mp 137.6–140.8 °C. IR (KBr): 3106, 3058, 2926, 1602, 1566,
1480, 1461, 1441, 1356, 1273, 1230, 1191, 1143, 1112, 1073, 1020,
916, 863, 803, 765, 689, 636, 493 cm–1
.
1H NMR (300 MHz, Acetone-
d6): δ = 7.91 – 7.88 (m, 2 H, Hm), 7.60 (m, J (H7,F6) =10.3 Hz, J
(H7,F5) =6.5 Hz, 1 H, H7), 7.56 (dd, J (H4,F5) =10.4 Hz, J (H4,F6)
=8.0 Hz, 1 H, H4), 7.51 – 7.46 (m, 2 H, Ho), 7.41 (tm, J (Hp,Hm)
=7.3 Hz, 1 H, Hp), 7.29 (m, 1 H, H3). 13C NMR (126 MHz, CDCl3):
δ = 157.7 (d, C2), 149.6 (dd, 3J (C7a,F6) =12 Hz, C7a), 148.6 (dd, 1J
(C6,F6) =245.4 Hz, 2J (C6,F5) =15.7 Hz, C6), 148.0 (dd, 1J (C5,F5)
=241.3 Hz, 2J (C5,F6) =14.3 Hz, C5), 129.7 (s, C8), 128.8 (s, C11),
128.7 (s, C9), 124.7 (s, C10), 124.5 (dd, 3J (C3a,F5) =8.8 Hz, C3a), 107.3
(d, 2J (C4,F5) =20.5 Hz, C4), 100.9 (m, C3), 100.3 (d, 2J (C7,F6)
=22.3 Hz, C7). 19F NMR (282 MHz, Acetone-d6): δ = –140.3 (m, J
(F6,F5) =19.8 Hz, J (F6,H7) =10.3 Hz, J (F6,H4) =8.0 Hz, 1 F, F6),
–143.8 (m, J (F5,F6) =19.8 Hz, J (F5,H4) =10.4 Hz, J (F5,H7) =6.5 Hz,
1 F, F5). HRMS (EI): m/z [M]+ calcd for C14H8F2O: 230.0538; found:
230.0539.
4.2.3.4. 3,4,5-Trifluoro-2,6-diiodophenol (2e). White solid; yield: 6.8 g
(85%); mp 79.8–81.2 °C (mp 81 °C [11]). IR (KBr): 3437, 1583, 1483,
1441, 1381, 1294, 1228, 1207, 1066, 872, 723, 654, 465 cm–1. NMR
spectra are close to those published earlier [9]. 1H NMR (300 MHz,
CDCl3): δ = 5.83 (s, OH). 13C NMR (126 MHz, Acetone-d6): δ = 153.6
(td, C1), 152.1 (ddd, 1J (C3,F3) =241.7 Hz, C3), 133.8 (dt, 1J (C4,F4)
=2482.9 Hz, 2J (C4,F3) =18.9 Hz, C4), 68.3 (dm, 2J (C2,F3) =27.2 Hz,
C2). 19F NMR (282 MHz, CDCl3): δ = –108.6 (d, J (F3,F4) =22.4 Hz,
2 F, F3), –161.3 (t, J (F4,F3) =22.4 Hz, 1 F, F4). HRMS (EI): m/z [M]+
calcd for C6H1F3I2O: 399.8063; found: 399.8059.
4.2.4.3. 2-Butyl-5,6-difluoro-7-(hept-1-ynyl)benzofuran (3c). Colorless
oil; yield: 0.34 g (78%); Rf = 0.65 (hexane). IR (neat): 2958, 2933,
2873, 2252, 1606, 1483, 1448, 1196, 1147, 1101, 955, 850, 746,
4.2.3.5. 2,3,4,5-Tetrafluoro-6-iodophenol (2f). Colorless oil; yield: 4.8 g
(82%). IR (neat): 3568, 3493, 1622, 1514, 1485, 1431, 1309, 1219,
671 cm–1
.
1H NMR (300 MHz, Acetone-d6): δ = 7.40 (dd, J (H4,F5)
1080, 972, 908, 796, 735, 650 cm–1
.
1H NMR (300 MHz, CDCl3):
=10.2 Hz, J (H4,F6) =7.7 Hz, 1 H, H4), 6.55 (m, 1 H, H3), 2.79 (t, J
(H14,H15) =9 Hz, 2 H, H14), 2.57 (t, J (H8,H9) =6.4 Hz, 2 H, H8), 1.76 –
1.36 (m, 8 H, 2H9 + 2H10 + 2H15 + 2H16), 0.99 – 0.92 (m, 6 H, 3H11
+ 3H17). 13C NMR (126 MHz, Acetone-d6): δ = 163.1 (d, C2), 150.6
δ = 6.23 (s, OH). 13C NMR (126 MHz, CDCl3): δ = 147.1 (ddt, 1J
(C5,F5) =242.5 Hz, 2J (C5,F4) =11.8 Hz, C5), 141.2 (dtd, 1J (C3,F3)
=252.8 Hz, 2J (C3,F2) ≈ 2J (C3,F4) =14 Hz, C3), 140.8 (dm, 2J (C1,F2)
5

L. Politanskaya, et al.
JournalofFluorineChemistry227(2019)109371
(dd, 3J (C7a,F6) =5.4 Hz, C7a), 149.0 (dd, 1J (C6,F6) =245.8 Hz, 2J
(C6,F5) =16.1 Hz, C6), 148.2 (dd, 1J (C5,F5) =238.9 Hz, 2J (C5,F6)
=13.9 Hz, C5), 124.9 (dd, 3J (C3a,F5) =9.6 Hz, C3a), 107.5 (d, 2J (C4,F5)
=20.9 Hz, C4), 103.1 (dd, C3), 102.0 (d, C12), 99.3 (dd, 2J (C7,F6)
=17.9 Hz, C7), 68.8 (dd, C13), 31.2 (s, C14), 30.3 (s, C8), 28.4 (s, C9),
4.2.4.7. 2-Butyl-5,6,7-trifluorobenzofuran (3 g). Colorless oil; yield:
0.32 g (95%); Rf = 0.85 (hexane). IR (neat): 2960, 2935, 2874, 1637,
1610, 1514, 1471, 1385, 1329, 1196, 1149, 1080, 960, 941, 847, 796,
731, 673 cm–1
.
1H NMR (300 MHz, Acetone-d6): δ = 7.32 (m, J (H4,F5)
=9.8 Hz, J (H4,F6) =6.9 Hz, J (H4,H3) =2.1 Hz, 1 H, H4), 6.64 (dm, J
(H3,H4) =2.1 Hz, 1 H, H3), 2.82 (t, J (H8,H9) =7.5 Hz, 2 H, H8), 1.77 –
22.8 (s, C10), 22.5 (s, C15), 19.7 (s, C16), 13.9 (s, C17), 13.8 (s, C11). 19
F
NMR (282 MHz, Acetone-d6): δ = –141.9 (dd, J (F6,F5) =19.7 Hz, J
(F6,H4) =10.2 Hz, 1 F, F6), –144.0 (dd, J (F5,F6) =19.7 Hz, J (F5,H4)
=10.2 Hz, 1 F, F5). HRMS (EI): m/z [M]+ calcd for C18H20F2O:
290.1477; found: 290.1475.
1.67 (m, 2 H, H9), 1.48 – 1.38 (m, 2 H, H10), 0.94 (t, J (H11,H10
)
=7.4 Hz, 3 H, H11). 13C NMR (126 MHz, Acetone-d6): δ = 164.2 (dd,
C2), 148.9 (ddd, 1J (C5,F5) =240.6 Hz, 2J (C5,F6) =11.6 Hz, C5), 138.7
(dm, 2J (C7a,F7) =8 Hz, C7a), 138.0 (ddd, 1J (C6,F6) =243.0 Hz, 2J
(C6,F5) =18.4 Hz, 2J (C6,F7) =12.5 Hz, C6), 137.8 (ddd, 1J (C7,F7)
=251.6 Hz, 2J (C7,F6) =13.9 Hz, C7), 126.5 (ddd, 3J (C3a,F5) =10.3 Hz,
C3a), 103.4 (m, C3), 103.0 (dd, 2J (C4,F5) =20.8 Hz, C4), 30.3 (s, C8),
28.4 (s, C9), 22.8 (s, C10), 13.9 (s, C11). 19F NMR (282 MHz, Acetone-
d6): δ = –141.8 (m, J (F5,F6) =19.5 Hz, J (F5,H4) =9.8 Hz, 1 F, F5),
–158.2 (dm, J (F7,F6) =19.2 Hz, 1 F, F7), –167.3 (tm, J (F6,F7) ≈ J
(F6,F5) =19.3 Hz, J (F6,H4) =6.9 Hz, 1 F, F6). HRMS (EI): m/z [M]+
calcd for C12H11F3O: 228.0757; found: 228.0759.
4.2.4.4. 5,6-Difluoro-2-phenyl-7-(phenylethynyl)benzofuran (3d). White
solid; yield: 0.40 g (80%); Rf
= 0.50 (hexane); mp 119.1 °C
(decomp.). IR (KBr): 3433, 3074, 3034, 2922, 2222, 1705, 1601,
1500, 1454, 1437, 1370, 1340, 1267, 1225, 1201, 1174, 1115, 1070,
1022, 937, 912, 856, 760, 740, 688, 582, 565, 490 cm–1
.
1H NMR
(300 MHz, Acetone-d6): δ = 7.96 – 7.93 (m, 2 H, Hm), 7.72 – 7.69 (m, 2
H, H’m), 7.61 (dd, J (H4,F5) =10.0 Hz, J (H4,F6) =7.8 Hz, 1 H, H4), 7.53
– 7.40 (m, 6 H, H’p + 2Ho + 2H’o + Hp), 7.34 (s, 1 H, H3).
13C NMR (126 MHz, Acetone-d6): δ = 159.1 (d, C2), 150.5 (d, C7a),
149.4 (dd, 1J (C6,F6) =249.1 Hz, 2J (C6,F5) =16.5 Hz, C6), 148.6 (dd,
1J (C5,F5) =240.5 Hz, 2J (C5,F6) =13.8 Hz, C5), 132.6 (s, C15), 130.3 (s,
C17), 130.2 (s, C8), 130.1 (s, C11), 129.9 (s, C16), 129.6 (s, C9), 125.7 (s,
C10), 125.5 (dd, 3J (C3a,F5) =9.8 Hz, C3a), 122.9 (s, C14), 109.1 (d, 2J
(C4,F5) =21.0 Hz, C4), 102.7 (dd, C3), 100.2 (d, C12), 99.0 (dd, 2J
(C7,F6) =17.9 Hz, C7), 77.0 (dd, C13). 19F NMR (282 MHz, Acetone-d6):
δ = –138.8 (dd, J (F6,F5) =19.6 Hz, J (F6,H4) =7.8 Hz, 1 F, F6), –142.5
(dd, J (F5,F6) =19.6 Hz, J (F5,H4) =10.0 Hz, 1 F, F5). HRMS (EI): m/z
[M]+ calcd for C22H12F2O: 330.0851; found: 330.0847.
4.2.4.8. 5,6,7-Trifluoro-2-phenylbenzofuran (3 h). White solid; yield:
0.34 g (93%); Rf = 0.53 (hexane); mp 93.4–95.1 °C. IR (KBr): 3115,
3074, 2924, 2854, 1649, 1614, 1512, 1466, 1442, 1379, 1338, 1255,
1217, 1174, 1082, 1020, 953, 910, 858, 808, 767, 729, 690, 677, 594,
555, 499 cm–1
.
1H NMR (300 MHz, Acetone-d6): δ = 7.91 – 7.88 (m, 2
H, Hm), 7.53 – 7.37 (m, 4 H, Hp + 2Ho+ H4), 7.34 (d, J (H3,H4) =3 Hz,
1 H, H3). 13C NMR (126 MHz, Acetone-d6): δ = 159.8 (dd, C2), 149.3
(ddd, 1J (C5,F5) =241.7 Hz, 2J (C5,F6) =11.7 Hz, C5), 139.0 (dm, C7a),
138.9 (ddd, 1J (C6,F6) =244.6 Hz, 2J (C6,F5) =18.3 Hz, 2J (C6,F7)
=12.2 Hz, C6), 138.0 (ddd, 1J (C7,F7) =252.7 Hz, 2J (C7,F6) =13.8 Hz,
C7), 130.4 (s, C9), 130.0 (s, C8), 129.9 (s, C11), 126.7 (dt, 3J (C3a,F5)
=10.6 Hz, C3a), 125.9 (s, C10), 103.6 (dd, 2J (C4,F5) =20.9 Hz, C4),
102.7 (m, C3). 19F NMR (282 MHz, Acetone-d6): δ = –143.6 (m, J
(F5,F6) =19.4 Hz, J (F5,H4) =9.8 Hz, 1 F, F5), –160.5 (dm, J (F7,F6)
=19.0 Hz, 1 F, F7), –168.2 (tm, J (F6,F7) ≈ J (F6,F5) =19.1 Hz, J
(F6,H4) =6.9 Hz, 1 F, F6). HRMS (EI): m/z [M]+ calcd for C14H7F3O:
248.0444; found: 248.0446.
4.2.4.5. 2-Butyl-5,7-difluorobenzofuran (3e). Colorless oil; yield: 0.22 g
(70%); Rf = 0.70 (hexane). IR (neat): 2960, 2933, 2674, 1641, 1606,
1487, 1439, 1360, 1213, 1182, 1144, 1111, 1078, 978, 945, 843, 733,
607 cm–1. 1H NMR (300 MHz, CDCl3): δ = 6.91 (dm, J (H4,F5) =8.3 Hz, J
(H4,H6) =2.4 Hz, 1 H, H4), 6.71 (m, J (H6,F7) =10.6 Hz, J (H6,F5)
=9.5 Hz, J (H6,H4) =2.4 Hz, 1 H, H6), 6.36 (dm, J (H3,F7) =3 Hz,1 H,
H3), 2.75 (t, J (H8,H9) =7.9 Hz, 2 H, H8), 1.75 – 1.67 (m, 2 H, H9), 1.45 –
1.37 (m, 2 H, H10), 0.94 (t, J (H11,H10) =7.4 Hz, 3 H, H11). 13C NMR
(126 MHz, CDCl3): δ = 162.5 (d, C2), 158.3 (dd, 1J (C5,F5) =239.8 Hz, 3J
(C5,F7) =9.2 Hz, C5), 146.5 (dd, 1J (C7,F7) =251.0 Hz, 3J (C7,F5)
=14.0 Hz, C7), 137.9 (dd, 2J (C7a,F7) =10.9 Hz, C7a), 132.0 (dd, 3J
(C3a,F5) =12.0 Hz, C3a), 102.5 (dd, C3), 101.4 (dd, 2J (C4,F5) =24.7 Hz,
C4), 98.7 (dd, 2J (C6,F5) =29.7 Hz, 2J (C6,F7) =20.4 Hz,C6), 29.5 (s, C8),
28.0 (s, C9), 22.1 (s, C10), 13.6 (s, C11). 19F NMR (282 MHz, CDCl3): δ =
–119.7 (m, J (F5,H6) =9.5 Hz, J (F5,H4) =8.3 Hz, J (F5,F7) =3 Hz, 1 F, F5),
–135.4 (dm, J (F7,H6) =10.6 Hz, J (F7,H3) ≈ J (F7,F5) =3 Hz, 1 F, F7).
HRMS (EI): m/z [M]+ calcd for C12H12F2O: 210.0851; found: 210.0848.
4.2.4.9. 2-Butyl-4,5,6-trifluoro-7-(hex-1-ynyl)benzofuran (3i). Colorless
oil; yield: 0.29 g (63%); Rf = 0.68 (hexane). IR (neat): 2960, 2935,
2873, 2243, 1601, 1518, 1456, 1379, 1350, 1327, 1255, 1196, 1176,
1120, 1034, 987, 945, 897, 785, 742 cm–1
.
1H NMR (400 MHz, CDCl3):
δ = 6.42 (s, 1 H, H3), 2.74 (t, J (H14,H15) =7.6 Hz, 2 H, H14), 2.51 (t, J
(H8,H9) =7.0 Hz, 2 H, H8), 1.74 – 1.35 (m, 8 H, 2H9 + 2H10 + 2H15
+
2H16), 0.96 – 0.91 (m, 6 H, 3H11 + 3H17). 13C NMR (126 MHz, CDCl3):
δ = 161.6 (d, C2), 149.6 (ddd, C7a), 149.3 (ddd, 1J (C6,F6) =248.4 Hz,
2J (C6,F5) =12.8 Hz, C6), 142.2 (ddd, 1J (C4,F4) =253.5 Hz, 2J (C4,F5)
=12.5 Hz, C4), 136.8 (ddd, 1J (C5,F5) =242.9 Hz, 2J (C5,F6) =16.7 Hz,
2J (C5,F4) =14.7 Hz, C5), 113.8 (dm, 2J (C3a,F4) =18.6 Hz, C3a), 100.5
(dd, C12), 98.2 (m, C3), 94.7 (dd, 2J (C7,F6) =18.5 Hz, C7), 67.3 (t, C13),
30.4 (s, C14), 29.4 (s, C8), 27.9 (s, C9), 22.1 (s, C10), 21.8 (s, C15), 19.4
(s, C16), 13.6 (s, C17), 13.4 (s, C11). 19F NMR (282 MHz, CDCl3): δ =
–137.5 (dd, J (F6,F5) =20.0 Hz, J (F6,F4) =2.0 Hz, 1 F, F6), –140.6 (dd,
J (F4,F5) =20.7 Hz, J (F4,F6) =2.0 Hz, 1 F, F4), –166.3 (dd, J (F5,F4)
=20.7 Hz, J (F5,H6) =20.0 Hz, 1 F, F5). HRMS (EI): m/z [M]+ calcd for
4.2.4.6. 5,7-Difluoro-2-phenylbenzofuran (3f). White solid; yield: 0.22 g
(65%); Rf = 0.75 (hexane); mp 67.3 °C (decomp.). IR (KBr): 3440,
3095, 2926, 1643, 1603, 1498, 1475, 1435, 1358, 1213, 1169, 1115,
1082, 1039, 978, 910, 858, 848, 827, 767, 731, 690, 605, 482 cm–1. 1H
NMR (300 MHz, CDCl3): δ = 7.87 – 7.84 (m, 2 H, Hm), 7.48 – 7.36 (m, 3
H, Hp + 2Ho), 7.02 (dm, J (H4,F5) =8.1 Hz, J (H4,H6) =2.3 Hz, 1 H,
H4), 7.00 (d, J (H3,F7) =2.8 Hz,1 H, H3), 6.80 (m, J (H6,F7) =10.5 Hz, J
(H6,F5) =9.4 Hz, J (H6,H4) =2.3 Hz, 1 H, H6). 13C NMR (126 MHz,
CDCl3): δ = 158.5 (dd, 1J (C5,F5) =240.9 Hz, 3J (C5,F7) =9.1 Hz, C5),
158.4 (d, C2), 147.0 (dd, 1J (C7,F7) =252.0 Hz, 3J (C7,F5) =14.0 Hz,
C7), 138.3 (dd, 2J (C7a,F7) =11.0 Hz, C7a), 132.1 (dd, 3J (C3a,F5)
=12.1 Hz, C3a), 129.2 (s, C8), 128.8 (s, C9), 128.3 (s, C11), 125.1 (s,
C10), 102.0 (dd, 2J (C4,F5) =24.8 Hz, C4), 101.6 (dd, C3), 99.9 (dd, 2J
(C6,F5) =29.8 Hz, 2J (C6,F7) =20.2 Hz,C6). 19F NMR (282 MHz,
Acetone-d6): δ = –116.6 (m, J (F5,H6) =9.4 Hz, J (F5,H4) =8.1 Hz, J
(F5,F7) =3 Hz, 1 F, F5), –133.3 (dm, J (F7,H6) =10.5 Hz, J (F7,H3) ≈ J
(F7,F5) =3 Hz, 1 F, F7). HRMS (EI): m/z [M]+ calcd for C14H8F2O:
230.0538; found: 230.0540.
C
18H19F3O: 308.1383; found: 308.1390.
4.2.4.10. 4,5,6-Trifluoro-2-phenyl-7-(phenylethynyl)benzofuran
(3 j). White solid; yield: 0.46 g (88%); Rf = 0.35 (hexane); mp 121.8 °C
(decomp.). IR (KBr): 3115, 3078, 3032, 2220, 1622, 1597, 1520, 1458,
1346, 1267, 1203, 1132, 1115, 1041, 1024, 980, 912, 802, 764, 739,
688, 557, 524, 486 cm–1
.
1H NMR (300 MHz, Acetone-d6): 8.00 – 7.97
(m, 2 H, Hm), 7.71 – 7.68 (m, 2 H, H’m), 7.55 – 7.46 (m, 7 H, Hp + H’p
+ 2Ho + 2H’o + H3). 13C NMR (126 MHz, Acetone-d6): δ = 159.7 (d,
C2), 151.0 (dd, C7a), 150.8 (ddd, 1J (C6,F6) =249.6 Hz, 2J (C6,F5)
=13.1 Hz, C6), 144.7 (ddd, 1J (C4,F4) =225.0 Hz, 2J (C4,F5) =12.5 Hz,
C4), 138.6 (ddd, 1J (C5,F5) =242.7 Hz, 2J (C5,F6) =16.5 Hz, 2J (C5,F4)
6

L. Politanskaya, et al.
JournalofFluorineChemistry227(2019)109371
=14.7 Hz, C5), 133.1 (s, C15), 131.1 (s, C17), 130.9 (s, C11), 130.5 (s,
C16), 130.2 (s, C8), 130.2 (s, C9), 126.2 (s, C10), 123.4 (s, C14), 116.5 (d,
2J (C3a,F4) =18.7 Hz, C3a), 100.5 (t, C12), 99.1 (t, C3), 96.1 (dd, 2J
(C7,F6) =18.6 Hz, C7), 76.7 (m, C13). 19F NMR (282 MHz, Acetone-d6):
δ = –136.6 (dd, J (F6,F5) =19.5 Hz, J (F6,F4) =2.6 Hz, 1 F, F6), –140.0
(dd, J (F4,F5) =20.2 Hz, J (F4,F6) =2.6 Hz, 1 F, F4), –166.8 (t, J (F5,F4)
≈ J (F5,H6) =19.8 Hz, 1 F, F5). HRMS (EI): m/z [M]+ calcd for
4.2.4.14. 4,5-Difluoro-2-((trimethylsilyl)ethynyl)phenol (4a). Yellowish
oil; yield: 0.24 g (70%); Rf = 0.34 (hexane, twice). IR (neat): 3510,
2950, 2900, 2150, 1610, 1581, 1527, 1504, 1481, 1425, 1400, 1325,
1252, 1219, 1192, 872, 845, 760, 729, 700, 633 cm–1
.
1H NMR
(300 MHz, Acetone-d6): δ = 7.25 (dd, J (H3,F4) =10.8 Hz, J (H3,F5)
=9.1 Hz, 1 H, H3), 6.83 (dd, J (H6,F5) =12.0 Hz, J (H6,F4) =7.0 Hz, 1
H, H6), 0.21 (s, 9 H, CH3). 13C NMR (126 MHz, Acetone-d6): δ = 156.4
(d, 3J (C1,F5) =9.7 Hz, C1), 151.5 (dd, 1J (C5,F5) =249.3 Hz, 2J (C5,F4)
=14.0 Hz, C5), 144.2 (dd, 1J (C4,F4) =238.2 Hz, 2J (C4,F5) =13.4 Hz,
C4), 121.3 (dd, 2J (C3,F4) =19.3 Hz, C3), 107.5 (ddd, 3J (C2,F4)
=7.2 Hz, C2), 105.5 (d, 2J (C6,F5) =20.2 Hz, C6), 99.8 (m, C7 + C8),
–0.1 (s, C9). 19F NMR (282 MHz, Acetone-d6): δ = –133.2 (m, J (F5,F4)
=22.0 Hz, J (F5,H6) =12.0 Hz, J (F5,H3) =9.1 Hz,1 F, F5), –149.2 (m, J
(F4,F5) =22.0 Hz, J (F4,H3) =10.8 Hz, J (F4,H6) =7.0 Hz,1 F, F4).
HRMS (EI): m/z [M]+ calcd for C11H12F2SiO: 226.0620; found:
226.0615.
C
22H11F3O: 348.0757; found: 348.0759.
4.2.4.11. 2-Butyl-4,5,6,7-tetrafluorobenzofuran
(3k). Colorless
oil;
yield: 0.24 g (66%); Rf = 0.88 (hexane, twice). IR (neat): 2962,
2936, 2875, 1603, 1531, 1491, 1346, 1321, 1254, 1188, 1140, 1122,
1009, 993, 941, 798, 731, 634 cm–1
.
1H NMR (300 MHz, Acetone-d6):
δ = 6.46(m, 1 H, H3), 2.73 (t, J (H8,H9) =7.7 Hz, 2 H, H8), 1.74 – 1.64
(m, 2 H, H9), 1.45 – 1.35 (m, 2 H, H10), 0.94 (t, J (H11,H10) =7.3 Hz, 3
H, H11). 13C NMR (126 MHz, CDCl3): δ = 162.5 (d, C2), 138.5 (dddd, 1J
(C4,F4) =246.8 Hz, 2J (C4,F5) =12.3 Hz, C4), 138.0 (dm, 1J (C5,F5)
=246.1 Hz, 2J (C5,F6) =14.7 Hz, 2J (C5,F4) =13.4 Hz,C5), 137.4 (m,
C7a), 136.9 (dm, 1J (C6,F6) =244.8 Hz, 2J (C6,F5) =16.7 Hz, 2J (C6,F7)
=14.3 Hz, C6), 133.7 (dddd, 1J (C7,F7) =250.5 Hz, 2J (C7,F6)
=14.0 Hz, C7), 114.9 (dm, 2J (C3a,F4) =19.6 Hz, C3a), 98.3 (m, C3),
29.3 (s, C8), 27.8 (s, C9), 22.0 (s, C10), 13.4 (s, C11). 19F NMR (282 MHz,
CDCl3): δ = –149.9 (m, J (F4,F7) =20.6 Hz, J (F4,F5) =15.9 Hz, 1 F,
F4), –163.8 (m, J (F5,F6) =19.7 Hz, J (F5,F4) =15.9 Hz, 1 F, F5), –165.2
(tm, J (F6,F7) ≈ J (F6,F5) =19.6 Hz, 1 F, F6), –166.7 (m, J (F7,F4)
=20.6 Hz, J (F7,F6) =19.5 Hz, 1 F, F7). HRMS (EI): m/z [M]+ calcd for
4.2.4.15. 2,4-Difluoro-6-((trimethylsilyl)ethynyl)phenol (4b). Yellowish
oil; yield: 50 mg (15%); Rf = 0.65 (hexane). IR (neat): 3570, 3510,
3081, 2962, 2900, 2154, 1632, 1601, 1487, 1444, 1350, 1335, 1252,
1217, 1186, 1122, 1010, 991, 847, 794, 762, 729, 702, 677, 596,
528 cm–1
.
1H NMR (300 MHz, Acetone-d6): δ = 8.82 (s, 1 H, OH), 7.07
(m, J (H3,F2) =10.9 Hz, J (H3,F4) =8.6 Hz, J (H3,H5) =3.0 Hz, 1 H,
H3), 6.94 (dm, J (H5,F4) =8.7 Hz, J (H5,H3) =3.0 Hz, 1 H, H5), 0.22 (s,
9 H, CH3). 13C NMR (126 MHz, CDCl3): δ = 154.8 (dd, 1J (C4,F4)
=241.2 Hz, 3J (C4,F2) =11.4 Hz, C4), 150.0 (dd, 1J (C2,F2) =246.7 Hz,
3J (C2,F4) =13.0 Hz, C2), 141.9 (dd, 2J (C1,F2) =12.8 Hz, C1), 113.0
(dd, 2J (C5,F4) =24.3 Hz, C5), 111.7 (dd, 3J (C6,F4) =11.3 Hz, C6),
106.0 (dd, 2J (C3,F2) =27.1 Hz, 2J (C3,F4) =21.9 Hz, C3), 104.1 (s, C7),
96.7 (m, C8), –0.3 (s, C9). 19F NMR (282 MHz, Acetone-d6): δ = –121.6
(td, J (F4,H3) ≈ J (F4,H5) =8.6 Hz, J (F4,F2) =2.0 Hz,1 F, F4), –130.9
(dm, J (F2,H3) =10.9 Hz, J (F2,F4) =2.0 Hz, 1 F, F2). HRMS (EI): m/z
[M]+ calcd for C11H12F2SiO: 226.0620; found: 226.0617.
C
12H10F4O: 246.0662; found: 246.0660.
4.2.4.12. 4,5,6,7-Tetrafluoro-2-phenylbenzofuran (3 l). White solid;
yield: 0.30 g (75%); Rf = 0.78 (hexane); mp 113.5 °C (decomp.) (mp
112–114 °C [5e]). IR (KBr): 3118, 2926, 2854, 1527, 1483, 1446, 1346,
1311, 1265, 1217, 1134, 1043, 997, 908, 800, 763,7, 727, 688,
559 cm–1
.
1H NMR (300 MHz, CDCl3): δ = 7.84 – 7.82 (m, 2 H, Hm),
7.48 – 7.39 (m, 3 H, Hp + 2Ho), 7.08 (d, J (H3,F4) =2 Hz, 1 H, H3). 13
C
Acknowledgments
NMR (126 MHz, CDCl3): δ = 158.5 (d, C2), 138.9 (ddm, 1J (C4,F4)
=246.5 Hz, 2J (C4,F5) =12 Hz, C4), 138.6 (dtm, 1J (C5,F5) =246.5 Hz,
2J (C5,F6) =14.8 Hz, 2J (C5,F4) =13 Hz,C5), 137.6 (tm, C7a), 137.4
(dtm, 1J (C6,F6) =246.1 Hz, 2J (C6,F5) =15.5 Hz, 2J (C6,F7) =13 Hz,
C6), 134.1 (dddd, 1J (C7,F7) =253.3 Hz, 2J (C7,F6) =16.1 Hz, C7), 132.4
(s, C8), 129.7 (s, C9), 128.9 (s, C11), 125.1 (s, C10), 115.5 (dm, 2J
(C3a,F4) =19.3 Hz, C3a), 97.4 (m, C3). 19F NMR (282 MHz, Acetone-d6:
δ = –147.7 (m, J (F4,F7) =20.0 Hz, J (F4,F5) =15.8 Hz, 1 F, F4), –162.0
(m, J (F5,F6) =19 Hz, J (F5,F4) =15.8 Hz, 1 F, F5), –163.0 (tm, J (F6,F7)
≈ J (F6,F5) =19 Hz, 1 F, F6), –164.8 (m, J (F7,F4) =20 Hz, J (F7,F6)
=19 Hz, 1 F, F7). HRMS (EI): m/z [M]+ calcd for C14H6F4O: 266.0349;
found: 266.0345.
The authors thank the Russian Foundation for Basic Research (grant
№ 19-53-53003) and NSFC (grant № 21911530097) for financial sup-
port and the Chemical Service Center SB RAS for spectral and analytical
measurements.
Appendix A. Supplementary data
Supplementary material related to this article can be found, in the
online version, at doi:https://doi.org/10.1016/j.jfluchem.2019.
109371.
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