Solvent-Free Fluorination of Electron-Rich Aromatic Compounds with F-TEDA-BF4: Toward “Dry” Processes

Article abstract of DOI:10.1002/ejoc.201700179

An effective protocol for the solvent-free fluorination of electron-rich aromatic compounds with 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) (F-TEDA-BF₄) is described. The protocol allows the easy and efficie

Full text of DOI:10.1002/ejoc.201700179

A Journal of
Accepted Article
Title: Solvent-free Fluorination of Electron Rich Aromatic Compounds
with F-TEDA-BF4 Reagent: Toward "Dry" Processes
Authors: Pavel A. Zaikin, Ok Ton Dyan, Darya V. Evtushok, Andrey
N. Usoltsev, Elena V. Karpova, Gennady I. Borodkin, and
Vyacheslav G. Shubin
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201700179
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10.1002/ejoc.201700179
European Journal of Organic Chemistry
FULL PAPER
Solvent-free Fluorination of Electron Rich Aromatic Compounds
with F-TEDA-BF4 Reagent: Toward “Dry” Processes
Pavel A. Zaikin,*[a] Ok Ton Dyan,[a] Darya V. Evtushok,[c] Andrey N. Usoltsev,[c] Gennady I. Borodkin,[a, b]
Elena V. Karpova,[a, b] and Vyacheslav G. Shubin[a]
Abstract: Effective protocol of solvent-free fluorination of electron
rich aromatic compounds with F-TEDA-BF4 reagent is described.
The protocol allows easy and efficient isolation of fluorinated
products by vacuum sublimation without use of any solvent with high
yields and purity and low E-factor values. Solid-state fluorination of
naphthalene-2-ol was suggested by differential thermal analysis.
Scanning electron microscopy is used to obtain evidences for the
solid-state process. Crucial influence of alkali metal carbonates on
the rate of solvent-free fluorination of hydroxynaphthalenes and
estrone was demonstrated.
supercritical carbon dioxide,[14] water[15,16] and PEG-400, H2O-
PEG-400[17,18] use of microwave irradiation for low energy
consumption.[19-21] But possibly the most significant decrease of
the environmental footprint of most industrial processes would
be the complete elimination of the solvent. Avoiding the use of
solvents is
synthesis.[22]
a crucial point for sustainability of organic
Despite the rapidly growing interest to the solvent-free and
mechanochemical organic synthesis in last decade[23,24] only
limited data concerning solvent-free aromatic fluorination has
been published to date.[22, 25-29]
As a part of our ongoing effort to develop environmentally
benign methods of electrophilic aromatic fluorination[12,15,28-30] we
began to investigate a solvent-free fluorination of electron rich
Introduction
aromatic
compounds
with
1-chloromethyl-4-fluoro-1,4-
Fluorination of aromatic compounds is of great practical
importance as fluoroaromatic compounds constitute a class of
widespread organic intermediates as well as fine chemicals with
applications as pharmaceuticals, materials and dyes.[1,2]
diazoniabicyclo[2.2.2]octane bis (tetrafluoroborate) F-TEDA-BF4
(SelectfluorTM) reagent 1.
Herein we describe a protocol of solvent-free fluorination of
electron rich aromatic compounds with F-TEDA-BF4 reagent.
The protocol allows easy and efficient isolation of fluorinated
products by vacuum sublimation without use of any solvent at
any stage of the process. More effective conditions that could be
achieved for this reaction are important for development of
sustainable fluorine chemistry.
Fluorinated aromatic compounds are of great importance for
pharmaceutical industry[1-3] due to unique influence of fluorine
substituent on biological properties.[4,5] As many as 30-40%
agrochemicals and 20% of pharmaceuticals on the market are
estimated to contain fluorine.[6] Development of new safe and
environmentally benign methods of fluorination is on the
agenda.[7] The development of electrophilic fluorinating agents of
NF class to tame the reactivity of elemental fluorine resulted in
great advancements in direct fluorination of C-H bonds.[8a,b,9]
Turn from volatile organic solvents to more “green” alternatives
is one of the most demanding areas of research.[10,11] Recent
advances in “green” fluorination with NF-reagents includes
reactions in room-temperature ionic liquids (IL), IL-alcohol,[12,13]
Results and Discussion
The first substrate we used was naphthalene-2-ol 2a as one of
the most reactive aromatic compounds in electrophilic
fluorination.[31]
Fluorinated naphthalene derivatives were used in synthesis of
nematic liquid crystals,[32] quinonoid molecules[33] and modern
anticancer drugs.[34] For example, fluorination of 6-
bromonaphthalene-2-ol with F-TEDA-BF4 reagent in solvents
was employed for preparation of fluorinated liquid crystals.[32]
Solvent-free fluorination of naphthalene-2-ol 2a with equimolar
quantity of F-TEDA-BF4 resulted in formation of 1-
fluoronaphthalene-2-ol 3a and 1,1-difluoro-2(1H)-naphthalenone
4a with 29 and 21% yield respectively (Scheme 1).
[a]
P.A. Zaikin, O.T. Dyan, Dr. E.V. Karpova, Prof. Dr. G.I. Borodkin,
Prof. Dr. V.G. Shubin
N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry of the
Siberian Branch of Russian Academy of Sciences
9 Acad. Lavrentiev Ave., Novosibirsk, 630090, Russian Federation
E-mail: zaikin@nioch.nsc.ru
[b]
[c]
Prof. G.I. Borodkin
Department of Natural Sciences
Novosibirsk State University
2 Pirogov St, Novosibirsk, 630090, Russian Federation
D.V. Evtushok, A.N. Usoltsev
A.V. Nikolaev Institute of Inorganic Chemistry of the Siberian Branch
of Russian Academy of Sciences
3 Acad. Lavrentiev Ave., Novosibirsk, 630090, Russian Federation
Supporting information for this article is given via a link at the end of
the document.((Please delete this text if not appropriate))
Scheme 1. Fluorination of substituted naphthalene-2-ols with F-TEDA-BF4.
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10.1002/ejoc.201700179
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To improve the selectivity of 1,1-difluoro-2(1H)-naphthalenone
formation we carried out fluorination of naphthalene-2-ol with 2.2
equivalents of fluorinating reagent. Increase of NF-reagent
loading resulted in complete conversion of aromatic substrate
and exclusive formation of 1,1-difluoro-2(1H)-naphthalenone.
Direct fluorination is potentially very efficient in terms of
utilization of reagents: the C–H is replaced directly with C–F.[35]
Solvents account for 75-80% of the waste associated with the
synthesis of active pharmaceutical ingredients and solvent
waste disposal adds substantial cost to production of
pharmaceutical ingredients.[7] Solventless reactions with high
yield of pure product are the better choice. A true ‘‘solventless
synthesis’’ must exclude any solvent when reactants interact to
the pure product. This requires a quantitative reaction to one
product without solvent-consuming chromatography after a
stoichiometric reaction.[36] Efficiency of combination of solvent-
free synthesis and solvent-free isolation by vacuum sublimation
has been demonstrated on the synthesis of nitroso
compounds.[37] We tried to implement solventless concept with
the use of sublimation technique to obtain pure 1,1-difluoro-
2(1H)-naphthalenone from the reaction mixture. The target
naphthalenone was obtained in 70% yield. Even with large
excess of fluorinating reagent the E-factor for this process could
be estimated to 5,7 KgwasteKgprod-1. compare to the
processes in manufacturing of fine chemicals in which a large
The possibility of truly solid-state reactions between two organic
compounds is quite controversial.[39] Differential scanning
calorimetry (DSC) have been proposed to be useful method of
detection of formation of liquid eutectic melts during the solvent-
free organic reactions.[40] To ensure that the fluorination of
naphthalene-2-ol takes place without macroscopic melting we
investigated reaction mixture with differential thermal analysis
method (Figure 1). As one can see there was no endothermal
effect corresponding to melting of reagents and formation of
eutectic mixture
Scanning electron microscopy (SEM) is another tool to obtain
evidences of solid-state process. SEM imaging could help us to
fix any signs of macroscopic melting of the reaction mixture
during mechanochemical reaction. We took series of images of
reagents alone and the reaction mixture after 10, 15, 20 and 30
minutes of grinding (Figure 2, b, c, d and e,f respectively). As
one could see during the reaction large particles of naphthalene-
2-ol disappeared with formation of finely ground mixture without
any signs of macroscopic melting.
amount of waste is produced (the
KgwasteKgproduct-1).[38]
E factor is 5–100
To prove the scalability of the reaction studied we carried out
fluorination of naphthalene-2-ol on gram and 10-gram scale.
Fluorination of 1 g of naphthalene-2-ol with 2.2-fold excess of F-
TEDA-BF4 followed by sublimation resulted in obtaining of target
1,1-difluoronaphthalen-2(1H)-one with exceptional purity of 99%
by GC and 71% preparative yield. Fluorination on 10-gram scale
resulted in formation of 1,1-difluoronaphthalen-2(1H)-one with
slightly higher yield of 75%.
Heat flow rate/(W/g)
exo
2.0
1.6
1.2
0.8
0.4
0
Figure 2. SEM images of the reaction mixture of naphthalene-2-ol – F-TEDA-
BF4 (1 : 2.2) during mechanochemical synthesis. Initial mixture (a), after 10 (b),
15 (c), 20 (d) and 30 (e x2500 ,f x1000) minutes of grinding.
60
70
80
90
T/°C
100
110
120
It was a bit surprising that fluorination of naphthalene-2-ol
proceeded even without continuous grinding. Holding of 1:2.2
mixture of naphthalene-2-ol and F-TEDA-BF4 at room
temperature without any additional grinding resulted in 75%
conversion after a week and 85% conversion after 16 days
(Figure 3).
Figure 1. DSC curve obtained on 1:2 mixture of naphthalene-2-ol - F-TEDA-
BF4 at 6.7°C/min heating rate.
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10.1002/ejoc.201700179
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Scheme 2. Fluorination of naphthalene-2,7-diol with F-TEDA-BF4.
Table 1. Solvent-free fluorination of phenols.
Figure 3. Dependence of conversion of reagents on holding time, red line: 1,
blue line: 2a.
Entry
2
Substrate
ArH : NF
molar ratio
Time,
min
Products[a]
2a
1:1
30
1,1-difluoronaphthalen-2(1H)-
To obtain deeper insights into non-stimulated fluorination
process we investigated the reaction mixture of naphthalene-2-ol
with 2.2-fold excess of F-TEDA-BF4 by in situ scanning electron
microscopy (Figure 4). On the initial image large darker particle
of 2-naphthalene-2-ol is surrounded by smaller lighter particles
one
4a
(21%),
1-
fluoronaphthalene-2-ol
(29%)
3a
3
4
5
2a
2c
5
1:2.2
1:2.2
1:3
30
90
30
1,1-difluoronaphthalen-2(1H)-
one 4a (94%, [70%]b), 1-
fluoronaphthalene-2-ol 3a (1%)
of F-TEDA-BF4. After 60
h the naphthalene-2-ol particle
transformed into conglomerate of much smaller particles of
products similar as in grinding experiments (Figure 4,area a).
6-bromo-1,1-difluoro-2(1H)-
naphthalenone
[84%]b)
4b
(95%,
7-hydroxy-1,1-
difluoronaphthalene-2(1H)-one
(47%), 7-hydroxy-1,1,8-
7
trifluoronaphthalene-2(1H)-one
9 (44%)
6
7
10
13
1:1
1:1
30
30
2-fluoro-4-methylphenol
(41%), 4-fluoro-4-
methylcyclohexa-2,5-diene-1-
one 12 (16%)
11
Figure 4. In situ SEM imaging of non-stimulated fluorination of 2-naphtol.
3,4-dimethylcyclohexa-2,5-
Starting reaction mixture (left) and reaction mixture after 60 h (right).
diene-1-one 14 (29%), 6-
fluoro-3,4-dimethylphenol 15
(3%),
2-fluoro-3,4-
dimethylphenol 16 (7%)
Fluorination of 6-bromonaphthalene-2-ol with 2.2-fold excess of
F-TEDA-BF4 required longer reaction time. Full conversion of
starting materials was achieved after 90 min of total grinding
time leading to 95% NMR yield. Exploiting of the grinding-
sublimation sequence on a gram scale allowed to obtain target
6-bromo-1,1-difluoronaphthalen-2(1H)-one in 84% isolated yield.
The E-factor of 3.7, calculated for the fluorination of 6-
bromonaphthalene-2-ol was even smaller than that for
fluorination of naphthalene-2-ol.
8
17
1:1
30
10β-fluoro-1,4-estradiene-
3,17-dione 18 (21%), 2-
fluoroestron 19 (2%), 4-
fluoroestron 20 (2%)
[a] NMR yield determined by addition of weight standard are given in
parenthesis. [b] Isolated yield
Fluorination of more reactive naphthalene-2,7-diol with two-fold
excess of F-TEDA-BF4 led to formation of complex mixture,
which contains besides of 1-fluoronaphthalene-2,7-diol and 7-
hydroxy-1,1-difluoronaphthalene-2(1H)-one substantial amounts
Fluorination of para-cresol 10 resulted in 41% conversion and
formation of 2-fluoro-4-methylphenol 11 with 16% yield along
with trace amounts of 4-fluoro-4-methylcyclohexa-2,5-diene-1-
one 12 – product of ipso-attack of electrophilic fluorine at 4-
position. Ipso-fluorination became mainstream in the case of
3,4-dimethylphenol 13, which reacted with equimolar amount of
of
1,8-difluoronaphthalene-2,7-diol
and
7-hydroxy-1,1,8-
trifluoronaphthalene-2(1H)-one. Increase of excess of F-TEDA-
BF4 to 3 resulted in formation of mixture of only naphthalenones
7 and 9 in 1:0.93 ratio.
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10.1002/ejoc.201700179
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F-TEDA-BF4 upon grinding for 30 min with formation of 4-fluoro-
3,4-dimethylcyclohexa-2,5-diene-1-one 14 with 29% yield along
with 7% of 6-fluoro- and 3% of 2-fluoro isomers 15 and 16
respectively. Similarly, formation of large amounts of ipso-
fluorinated product was observed in fluorination of such a
substrate in solutions.[41] Solvent-free fluorination leads to
relatively larger amount of 2-fluoro-4-methylphenol compare to
fluorination in acetonitrile and close to ipso-/ortho- ratio obtained
in MeOH.[41]
Estrone 17 undergone fluorination similarly to its analog -
5,6,7,8-tetrahydro-2-naphthol[42] with formation of main product
of electrophilic ipso-attack – ketone 18 along with substantially
lower amounts of ortho-fluorinated products 19 and 20 (Scheme
3).
resulted in considerable increase of nucleophilicity of such
substances.[43]
Grinding of unreactive naphthalene-1-ol with equimolar amount
of potassium carbonate for 10 min. followed by typical
fluorination procedure led to activation of the substrate and
formation of mixture of products (see Table 2).
In case of 7-bromonaphthalene-2-ol 10-min. advance grinding
with cesium carbonate led to substantial increase of activity of
aromatic substrate and formation of 7-bromo-1,1-difluoro-2(1H)-
naphthalenone with 78% yield.
We investigated the influence of alkali metal cation on the
reactivity of estrone. Fluorination of estrone in the presence
К2СО3 led to approximately 1.5-fold increase of products yields
comparing to fluorination without carbonate wheares in the case
of sodium or rubidium carbonates approximately two-fold
decrease of products yields is observed. It has been previously
shown that the nature of the alkali metal cation influenced the
transformation of F-TEDA-BF4, the highest being with Li+, Na+
Cs+ and the lowest with K+.[44]
Scheme 3. Fluorination of estrone.
Conclusions
Efficient and ecologically benign method of fluorination of
activated aromatic compounds was developed. Solventless
fluorination of naphthalene-2-ols was performed by implication of
vacuum sublimation for isolation of fluorinated products with high
yields and purity. Solid-state fluorination of naphthalene-2-ol was
suggested by differential thermal analysis and scanning electron
microscopy. The influence of alkali metal carbonates on the rate
of solvent-free fluorination of naphthalenols and estrone was
demonstrated.
Table 2. Effect of alkali metal carbonates.
Entry
1
Substrate
Products[a]
[b]
Naphthalene-1-ol/К2СО3
2-fluoronaphthalene-1-ol
fluoronaphthalene-1-ol
difluoronaphthalene-1-ol
(1%),
(1%),
(1%), 2,2-
(19%),
4-
2,4-
difluoronaphthalen-1(2H)-one
4,4-difluoronaphthalen-1(4H)-one (2%)
Estrone/Li2СО3
Estrone/Na2СО3
Estrone/К2СО3
Estrone/Rb2СО3
Estrone/Cs2СО3
10β-fluoro-1,4-estradiene-3,17-dione
2
3
4
5
(18%),
fluoroestrone (1%)
10β-fluoro-1,4-estradiene-3,17-dione
(12%), 2-fluoroestrone (1%),
fluoroestrone (1%)
10β-fluoro-1,4-estradiene-3,17-dione
(32%), 2-fluoroestrone (3%),
fluoroestrone (3%)
10β-fluoro-1,4-estradiene-3,17-dione
2-fluoroestrone
(1%),
4-
4-
4-
Experimental Section
1H, 13C and 19F NMR spectra were recorded in CDCl3 or acetone-d6 on
Bruker AV-300 and AV-400 spectrometers and chemical shifts are given
in ppm relative to TMS and CFCl3 respectively with C6F6 (19F, -162.9
ppm) or residual solvent signals (1H, 13C) as secondary external
standards. GC/MS spectra were recorded on an Agilent instrument
operating at 70eV. High resolution mass spectra (HRMS) were measured
using DFS instrument. IR spectra were recorded on Bruker Vector 22
spectrometer and UV-Vis spectra were recorded on Varian Cary 5000
spectrophotometer (lgε is indicated in brackets). Elemental analysis was
performed on EA-3028 analyzer. SEM images were obtained on Hitachi
TM-1000 instrument, DTA analysis was performed on Netzsch STA 409
thermoanalyser. Melting points were recorded on Mettler-Toledo FP81.
All reactants were obtained from commercial sources and used without
further purification. Spectral data of products obtained were consistent
with literature data (see Supporting Information).
(12%), 2-fluoroestrone (<1%), 4-
fluoroestrone (<1%)
Complex mixture
6
7
8
6-bromonaphthalene-2-ol
/Cs2CO3
7-bromonaphthalene-2-ol
/Cs2CO3
6-bromo-1,1-difluoro-2(1H)-
naphthalenone (76%)
7-bromo-1,1-difluoro-2(1H)-
naphthalenone (78%)
[a] NMR yield determined by addition of weight standard are given in
parenthesis.
In contrast to naphthalenols studied 7-bromonaphthalene-2-ol
2b and naphthalene-1-ol reacted with F-TEDA-BF4 only in little
extent. To improve the yields of fluorinated products we
attempted to enhance reactivity of phenols by complexing with
alkali metal carbonates. It has been previously shown that
complexation of phenols with potassium carbonate in DMF
General procedure for room-temperature fluorination of phenols
with F-TEDA-BF4. A mixture of aromatic substrate (0.5 mmol) and
fluorination reagent was ground in agate mortar for the time indicated in
Table 1. Reaction mixture was then extracted with ether and the solvent
was removed in vacuo to yield crude products which were analyzed by
1H, 19F NMR spectroscopy and GC/MS. Yields were determined by
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10.1002/ejoc.201700179
European Journal of Organic Chemistry
FULL PAPER
integration of signals of products in NMR spectra with comparison of
signal intensity of weight standard (PhCF3) added.
1,1,8-trifluoro-7-hydroxy-2(1H)-naphthalenone.
1H NMR
(300 MHz,
CD3CN, 25°C, TMS): δ=6.09 (dt, J=10.2, 3.0 Hz, 1H, H3) 7.11 - 7.24 (m,
2H, H5,6) 7.54 (dd, J=10.2, 2.1 Hz, 1H, H4) 8.13 (br. s., 1H, OH); 13C (101
MHz, CD3CN, 25°C, TMS): δ= 105.7 (td, J=244.6, 1.8 Hz, C1) 121.1 (td,
J=22.3, 9.3 Hz, C8a) 121.5 (td, J=2.5, 0.8 Hz, C3) 121.7 (dt, J=3.8, 1.6 Hz,
C6) 124.1 (td, J=5.4, 1.8 Hz, C4a) 128.6 (d, J=3.2 Hz, C5) 147.7 (dt, J=3.4,
1.6 Hz, C4) 149.0 (dt, J=12.7, 2.0 Hz, C7) 152.6 (dt, J=254.5, 2.0 Hz, C8)
186.9 (t, J=24.0 Hz, C2); 19F (282 MHz, CDCl3, 25°C, CFCl3): -102.5 (d,
2F, J = 15 Hz), -150.5 (dt, 1F, J1 = 15 Hz, J2 = 8 Hz). UV-vis (CH3OH),
λmax nm, (lg ε): 243 (4.26), 266 (4.18), 459 (3.98). IR (KBr, cm-1):
ν¯= 3325 (OH); 1672 (C=O); 1603; 1572; 1514; 1473; 1317; 1289; 1214;
1173; 1119; 1063; 1007; 853. HRMS: calcd. for C10H5F3O2
m/z= 214.0242, found: m/z 214.0240 [M+].
General procedure for fluorination of naphthalene-2-ols with F-
TEDA-BF4 followed by vacuum sublimation. Naphthalene-2-ol (1.00 g,
7 mmol) and F-TEDA-BF4 (5.46 g, 10 mmol) were ground in mortar at
room temperature for 30 min. the mixture was maintained at room
temperature overnight and then sublimed in vacuo at 70˚С to yield 1,1-
difluoronaphthalen-2(1H)-one as yellow needles (0.88 g, 70%). mp 51˚С
(cf. 50˚С [45]).
General procedure for fluorination of naphthalenols and estron with
F-TEDA-BF4 in the presence of alkali metal carbonates. A mixture of
phenol (0.5 mmol) and metal carbonate (0.5 mmol) was ground in agate
mortar for 10 min. Then fluorination reagent (0.5 mmol) was added and
the reaction mixture was ground for additional 30 min., then was
extracted with ether, the solvent was removed in vacuo to yield a crude
product. Residue was dissolved in CDCl3 or acetone-d6 and directly
analyzed by 1H, 19F NMR spectroscopy and GC/MS. Yields were
determined by integration of signals of products in NMR spectra with
comparison of signal intensity of weight standard added (-
trifluorotoluene, PhCF3, or C6F6 for 19F, CH2Br2 for 1H).
Acknowledgements
Financial support from the Russian Foundation for Basic
Research [grant number 16-33-00944] and the Chemistry and
Material Science Department of the Russian Academy of
Sciences (project no. 5.1.4) is gratefully acknowledged. Authors
thank Chemical Service Center of the Siberian Branch of the
Russian Academy of Sciences at N.N. Vorozhtsov Novosibirsk
Institute of Organic Chemistry SB RAS for spectral analysis.
6-bromo-1,1-difluoro-2(1H)-naphthalenone. m.p. 67.4-68.3°C; 1H NMR
(300 MHz, CDCl3, 25°C, TMS): δ=6.28 (dt, J=10.2, 2.7 Hz, 1H, H3) 7.57
(d, J=10.2 Hz, 1H, H4) 7.63 - 7.88 (m, 3H, H5,7,8); 13C NMR (126 MHz,
CDCl3, 25°C, TMS) δ=105.1 (t, J=245.3 Hz, C1) 124.5 (t, J=2.4 Hz, C8)
126.4 (t, J=2.5 Hz, C6) 129.1 (t, J=3.3 Hz, C3) 131.7 (t, J=23.9 Hz, C8a)
131.9 (t, J=5.5 Hz, C4a) 132.5 (s, C5) 133.6 (t, J=1.8 Hz, C7) 143.9 (s, C4)
186.6 (t, 2J(C,F)=25.1 Hz, C2) 19F (282 MHz, CDCl3, 25°C, CFCl3): δ -
101.4 (s); IR (KBr): 1699 cm−1 (C=O); UV/Vis (CHCl3): λmax (ε,
mol−1dm3cm−1) 240 (300), 320 nm (54); elemental analysis: calcd (%) for
C10H5BrF2O (259.1): С 46.36, Н 1.95, F 14.67, Br 30.85; found: С 46.07,
Н 1.80, F 14.64, Br 31.01.
Keywords: Aromatic substitution • Electrophilic substitution •
Fluorine • Solid-state reactions • Sustainable Chemistry
[1]
[2]
I. Ojima, Fluorine in Medicinal Chemistry and Chemical Biology;
Blackwell, 2009, p. 1.
J. Wang, M. Sánchez-Roselló, J. L. Aceña, C. del Pozo, A. E.
Sorochinsky, S. Fustero, V. A. Soloshonok, H. Liu, Chem. Rev. 2014,
114, 2432-2506.
7-bromo-1,1-difluoro-2(1H)-naphthalenone. Rf=0.54 (SiO2, CHCl3); m.p.
92.2-96.7°C; 1H NMR (300 MHz, CDCl3, 25°C, TMS): δ=6.28 (dt,
3J(H,H)=10.2 Hz, 4J(H,F)=2.7 Hz, 1Н, H3), 7.24-7.28 (m, 1Н, H5), 7.42 (d,
3J(H,H)=10.2 Hz, 1Н, H4), 7.66-7.75 (m, 1Н, H6), 7.95-8.01 (m, 1Н, H8);
13C (101 MHz, CDCl3, 25°C, TMS): δ=104.8 (t, 1J(C,F)=246.4 Hz, C1),
123.7 (t, J(C,F)=2.4 Hz, C3), 125.7 (t, J(C,F)=2.3 Hz, C7), 129.1 (t,
J(C,F)=5.6 Hz, C4a), 131.0 (t, J(C,F)=3.6 Hz, C8), 131.1 (s, C5), 134.7 (t,
2J(C,F)=23.6 Hz, C8a), 135.4 (t, J(C,F)=2.0 Hz, C6), 144.7 (t, J(C,F)=1.5
Hz, C4), 186.4 (t, 2J(C,F)=24.6 Hz, C2); 19F (282 MHz, CDCl3, 25°C,
CFCl3): δ=-101.4 (s); IR (KBr): =1693 cm−1 (C=O); UV/Vis (CHCl3): λmax
(ε)=240 (300), 320 nm (54 mol−1dm3cm−1); elemental analysis: calcd (%)
for C10H5BrF2O (259.1): С 46.36, Н 1.95, F 14.67, Br 30.85; found: С
46.40, Н 1.99, F 14.39, Br 31.00.
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1,1-difluoro-7-hydroxy-2(1H)-naphthalenone. mp 147.1-147.2°C; 1H NMR
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(300 MHz, CDCl3, 25°C, TMS): δ=6.06 (dt, J(H,H)=10.0 Hz, J(H,F)=2.7
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(101 MHz, CDCl3, 25°C, TMS): 105.3 (t, J(C,F)=245.6 Hz, C1) 115.8 (t,
J(C,F)=3.5 Hz, C8) 118.7 (t, J(C,F)=1.7 Hz, C6) 120.9 (t, J(C,F)=2.3 Hz,
C3) 123.4 (t, J(C,F)=5.2 Hz, C4a) 132.1 (s, C5) 135.7 (t, J(C,F)=23.5 Hz,
C8a) 146.1 (s, C4) 158.6 (t, J(C,F)=1.7 Hz, C7) 187.8 (t, J(C,F)=24.1 Hz,
C2); 19F (282 MHz, CDCl3, 25°C, CFCl3): -102.0 (s, 2F).; IR (KBr): 3354;
2924; 1684; 1612; 1558; 1510; 1346; 1315; 1250; 1227; 1190; 1149;
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Entry for the Table of Contents (Please choose one layout)
Layout 2:
FULL PAPER
Pavel A. Zaikin,* Ok Ton Dyan, Darya V.
Evtushok, Andrey N. Usoltsev, Gennady
I. Borodkin, Elena V. Karpova and
Vyacheslav G. Shubin
Page No. – Page No.
Solvent-free Fluorination of Electron
Rich Aromatic Compounds with F-
TEDA-BF4 Reagent: Toward “Dry”
Processes
Text for Table of Contents
Efficient and ecologically benign method of fluorination of activated aromatic compounds was
developed. Solventless fluorination of naphthalene-2-ols was performed by implication of vacuum
sublimation for isolation of fluorinated products with high yields and purity.
Key Topic
Green Chemistry; Fluorination
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