Methyl gallate as the framework for the construction of fluorous building blocks

Article abstract of DOI:10.1080/00397910902964858

Methyl gallate was used as the framework for the construction of the building blocks 3-5 with three fluorous ponytails. Fluorous gallate 3 was prepared from methyl gallate in three different pathways. The first is based on perfluorohexyl iodide addition t

Full text of DOI:10.1080/00397910902964858

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Methyl Gallate as the Framework for the
Construction of Fluorous Building Blocks
Robert Kaplánek a , Martin Havlík a , Vladimír Král a c , Pavel
Martásek b & Tomáš Bříza a b
a Department of Analytical Chemistry, Institute of Chemical
Technology in Prague, Prague, Czech Republic
b First Faculty of Medicine, Charles University in Prague, Prague,
Czech Republic
c Zentiva Research and Development, Prague, Czech Republic
Published online: 29 Dec 2009.
To cite this article: Robert Kaplánek , Martin Havlík , Vladimír Král , Pavel Martásek & Tomáš Bříza
(2009): Methyl Gallate as the Framework for the Construction of Fluorous Building Blocks, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
40:2, 247-256
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Synthetic Communications1, 40: 247–256, 2010
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910902964858
METHYL GALLATE AS THE FRAMEWORK FOR THE
CONSTRUCTION OF FLUOROUS BUILDING BLOCKS
1
Robert Kaplanek, Martin Havlık, Vladimır Kral,
1
1,3
ꢀ
´
´
ꢀ
2
1,2
ˇ
´
ꢀ
ꢀꢁ
Pavel Martasek, and Tomas Brıza
1Department of Analytical Chemistry, Institute of Chemical Technology in
Prague, Prague, Czech Republic
2First Faculty of Medicine, Charles University in Prague, Prague,
Czech Republic
3Zentiva Research and Development, Prague, Czech Republic
Methyl gallate was used as the framework for the construction of the building blocks 3–5
with three fluorous ponytails. Fluorous gallate 3 was prepared from methyl gallate in three
different pathways. The first is based on perfluorohexyl iodide addition to the corresponding
allylderivative 1 and reduction of C-I bond in adduct 2; other ways are based on direct
O-alkylation of methyl gallate by 3-(perfluorohexyl)propyl triflate and 3-(perfluorohexyl)-
propyl iodide, respectively. Reduction of polyfluoroalkylated gallate 3 provided benzyl
alcohol 4, which can be easily converted to corresponding benzyl bromide 5.
Keywords: Dendron; fluorinated gallate; fluorous building blocks; methyl gallate; polyfluoroalkylation
INTRODUCTION
Many synthetic chemists interested in chemistry of highly fluorinated
compounds utilize various polyfluorinated building blocks for the construction of
sophisticated target structures. Unfortunately, required polyfluorinated units are
not commercially available and therefore in all cases must be synthesized. Polyfluori-
nated blocks based on the gallate unit have been already used for the constructions
of highly fluorinated complex structures by some research groups.[1–11] The advan-
tages of the gallate as framework for the construction of polyfluorinated building
blocks are the following: first, there is a possibility to connect three polyfluorinated
chains. Second, connection of polyfluorinated chains via an ether bond to the gallate
is sufficiently stable for the next synthetic transformations, and third, the ester group
of the gallate can further easily modified into other reactive functional group.
The most frequently used polyfluorinated gallate has three polyfluorinated
chains, which are each separated from the aromatic part by butylene-oxo
spacers.[1–6] In 2008, we described utilization of the gallate with a three-carbon
Received February 5, 2009.
Address correspondence to Robert Kaplanek, Department of Analytical Chemistry, Institute of
ꢀ
Chemical Technology in Prague, Technicka 5, Prague, 6 16628, Czech Republic. E-mail: robert.
ꢀ
kaplanek@vscht.cz (R. Kaplanek); ftor@seznam.cz (T. Brıza)
ꢀ
ˇ´
247

´
R. KAPLANEK ET AL.
248
spacer,[11] but no mention of its preparation and utilization have been published yet.
Therefore, we decided to deeply explore possibilities of preparation of the polyfluori-
nated gallate with the three-carbon spacer and try to judge which pathway is most
suitable regarding yields and synthetic workability. A further criterion was price of
polyfluoroalkylating agents: perfluorohexyl iodide is approximately 10 times cheaper
than polyfluorinated alkanol (precursor for the preparation of corresponding
triflate) or 3-(perfluorohexyl)propyl iodide, respectively.
RESULTS AND DISCUSSION
There exist two general possibilities for substituting gallate with polyfluori-
nated chains. The first one is a simple alkylation by means of polyfluorinated alkylat-
ing agent as a iodide or triflate. The second possibility is based on radical addition
of perfluoroalkyl iodide on corresponding allyl gallate derivative. Our synthetic
strategy to reach the final fluorous gallate 3 (Scheme 1) was devided into individual
three synthetic pathways. The first one is based on an addition–reduction method,
the second utilizes 3-(perfluoroalkyl)propyl triflate, and the third pathway uses
3-(perfluoroalkyl)propyl iodide.
The first pathway is based on perfluorohexyl iodide addition to the correspond-
ing allylderivative 1 and following reduction of C-I bond of adduct 2. First, methyl
gallate was transformed into triallyl derivative 1 by reaction with twofold molar
excess of allyl bromide in the presence of potassium carbonate in acetonitrile.[12,13]
The reaction afforded methyl ester of 3,4,5-tris(allyloxy)benzoic acid 1 in quantita-
tive yield (Scheme 1). In the next step, radical addition of perfluorohexyl iodide
to the double bond of allyl group was used for the connection of the fluorinated
chains. There are exist many approaches for the radical initiation.[14] We used
three different radical initiators: sodium dithionite,[15,16] azobisisobutyronitrile
(AIBN),[14,16] and triethyl borane[17,18] (Scheme 1). While using sodium dithionite
in the acetonitrile–water system, yields of additions were greater (84%) in the case
of using of triethyl borane in hexane or AIBN without any solvent, yields were
lower; (79% and 64% respectively). In the case of using Et3B and AIBN, the conver-
sion of triallyl derivative to desired tris(polyfluoroalkyl) derivative was not complete,
and the reaction mixture included tris- and bis(polyfluoroalkyl) derivatives, even if
the reaction time was prolonged or greater excess of perfluorohexyl iodide was used.
Other systems for initiating the radical addition of C6F13I [Pd(PPh)4, Ph3P, diben-
zoyl peroxide, irradiation] failed.
For the reduction of C-I bond in adduct 2, we used a method successfully
applied previously on threefold polyfluoroalkylated iododerivatives,[16] hydrogena-
tion on a palladium catalyst under atmospheric pressure. Reaction runs in a
methanol–ethyl acetate mixture in the presence of sodium acetate (Scheme 1). The
reduction afforded polyfluorinated gallate 3 in a yield of 96%. Owerall yield of this
three-step pathway leading to fluorous gallate 3 was around 90%.
Next, two pathways were based on direct O-alkylation of the gallate. The
second way to polyfluorinated gallate 3 is based on the reaction of methyl gallate
with 3-(perfluorohexyl)propyl triflate (Scheme 1). We have already published this
approach.[11,19] In the original work,[11,19] the triflate afforded polyfluorinated gallate
3 in 80% yield. We focused our effort on increasing the yield. The original method,

PREPARATION OF FLUOROUS BUILDING BLOCKS
249
Scheme 1. Three approaches to polyfluoroalkylated gallate.
which we recently published,[11] utilizes tetrahydrofuran (THF) as a solvent for the
alkylation. We tried to replace the THF by another solvent or mixtures of solvents.
The selection of the solvent is strongly limited by solubility of methyl gallate. Herein
we report an improved method for the preparation of this compound as follows:
methyl gallate was transformed to sodium salt by reaction with sodium hydride in
dimethylformamide (DMF) and subsequently reacted with solution of 3-(perfluoro-
hexyl)propyl triflate in DMF. Desired product 3 was obtained in the yield of 91%
(lit.[11] 80%). On the other hand, when sodium salt of methyl gallate was generated
in DMF and polyfluoroalkylated triflate was added in THF, the yield was less, 85%.
The third way to polyfluorinated gallate 3 is based on alkylation of methyl gal-
late by 3-(perfluorohexyl)propyl iodide. Several examples of polyfluoroalkylation of
phenolic ꢀOH group by polyfluoroalkylated iodides have already been published,
using Cs2CO3 in DMF,[20] K2CO3 in MeCN,[21,22] or K2CO3 in DMF.[2] 3-(Per-
fluoroalkyl)propyl iodides have been also used for direct polyfluoroalkylation of
N–,[23,24] C–,[8,25] and S-nucleophiles.[26] For polyfluoroalkylation, we used potassium
carbonate as a base in DMF (Scheme 1). The reaction was carried out with the excess
of polyfluorinated iodide (1.5 molar equivalent per phenolic –OH group). Under these
conditions, the conversion of methyl gallate was complete, and the reaction provided
tris(polyfluoroalkylated) gallate 3 in quantitative yield. Part of the excess of
3-(perfluorohexyl)propyl iodide was recovered by column chromatography and
reused. The same results were obtained when sodium hydride in DMF was used.
When using less then 1.2 molar equivalents of 3-(perfluorohexyl)propyl iodide per phe-
nolic –OH group, the conversion of methyl gallate to target tris(polyfluoroalkyl)
derivative was not complete.
Further utilization of the polyfluoroalkylated methyl-gallate 3 as a building
block depends on the reactive functional group, which was generated from ester,
because the ester group in itself is not suitable for connection to the substrate. On
the other hand, the ester function of the gallate can be easily transformed into
another more reactive benzylic function as an alcohol or an bromide. Thus, in the

´
R. KAPLANEK ET AL.
250
Scheme 2. Preparation of fluorous benzyl alcohol 4 and benzyl bromide 5.
first step, we reduced the ester group, providing corresponding benzyl alcohol 4.
Recently we reported[11] this preparation using lithium aluminium hydride in diethyl
ether (ꢀ78ꢁC to rt, 1 h) with the yield of 93%. Herein we presented an improved
method for the reduction using lithium aluminium hydride in anhydrous THF
(0ꢁC to rt, overnight) with the greater yield, 98% (Scheme 2).
In the next step, polyfluoroalkylated benzyl alcohol 4 was transformed into
corresponding benzyl bromide 5 by the reaction with phosphorus tribromide in
diethyl ether.[27] The bromination afforded a corresponding bromide in almost
quantitative yield (98%) (Scheme 2).
CONCLUSIONS
Gallate 3 with three fluorous ponytails was prepared from methyl gallate in
three different pathways. The most economically advantageous pathway appeared
to be a three-step reaction sequence including perfluorohexyl iodide addition, which
afforded final product 3 in an overall yield of 90%. In terms of ease of the synthesis
of 3, using commercially available 3-(perfluorohexyl)propyl iodide as polyfluoro-
alkylating agent appeared as the better choice. It is surprising that the third pathway,
which utilized the most reactive polyfluoroalkylating agent, polyfluorinated triflate,
afforded desired gallate 3 in less yield than corresponding iodide, probably due to

PREPARATION OF FLUOROUS BUILDING BLOCKS
251
side elimination of the triflate under basic conditions. Polyfluoroalkylated gallate 3
can be easily converted into polyfluoroalkylated benzyl alcohol 4 and benzyl bro-
mide 5, respectively. Compounds 3–5 can be used as prospective building blocks
in dendrimer and supramolecular chemistry or as the fluorous tags or reagents in
organic synthesis, including fluorous separation techniques.
EXPERIMENTAL
General Comments and Chemicals
NMR spectra were recorded on a Varian Gemini 300 HC (FT, 1H at 300 MHz,
13C at 75 MHz, 19F at 281 MHz) instrument using TMS and CFCl3 as the internal
standards. Chemical shifts are quoted in parts per million (d scale; s singlet, bs broad
singlet, d doublet, t triplet, q quadruplet, m multiplet), coupling constants J, in hertz,
and solvents were CDCl3 and CD3COCD3.
All chemicals were purchased from Sigma-Aldrich; silica gel (60–100 mm) was
from Merck. Solvents were purchased from Penta and dried according to standard
procedures.
Chemistry
Preparation of 3-(perfluorohexyl)propyl triflate. Solution of triflic anhy-
dride (42.81 g, 152 mmol) in DCM (250 mL) was cooled to ꢀ30ꢁC (dry ice–ethanol
bath), and a solution of 3-(perfluorohexyl)propanol (52.16 g; 138 mmol) and pyridine
(10.92 g; 138 mmol) in DCM (250 mL) was added dropwise while stirring at ꢀ30ꢁC.
The reaction mixture was stirred for an additional 30 min at ꢀ30ꢁC and slowly
warmed up to rt (45 min). Insoluble salts were filtered and washed with pentane
(150 mL). Volatile compounds were removed under reduced pressure, and the crude
product was distilled under high vacuum (bp ¼ 71–76ꢁC=2 Torr) yielded 62.05 g
(88%) of colorless liquid.
1H NMR (CDCl3, d ppm): 2.36–2.09 (m, 4H, CH2CH2RF), 4.60 (t, 2H,
3
3JHH ¼ 5.72 Hz, CH2OTf); 13C NMR (CDCl3, d ppm): 20.9 (t, 1C, JCF ¼ 4 Hz),
2
1
27.1 (t, 1C, JCF ¼ 22 Hz), 75.3 (s, 1C), 118.7 (q, 1C, JCF ¼ 319 Hz), 105.0–125.0
(m, 6C); 19F NMR (CDCl3, d ppm): ꢀ75.3 (s, 3 F), ꢀ81.5 (t, 3 F, JFF ¼ 10.6 Hz),
3
ꢀ114.9 (m, 2 F), ꢀ122.4 (m, 2 F), ꢀ123.4 (m, 2 F), ꢀ124.0 (m, 2 F), ꢀ126.7 (m,
2 F). Anal. calcd. for C10H6F16O3S: C, 23.54; H, 1.19. Found: C, 23.67; H, 1.07.
Preparation of methyl ester of 3,4,5-tris(allyloxy)benzoic acid (1). Methyl
gallate (3655 mg; 19.8 mmol), K2CO3 (12,300 mg; 89 mmol), allyl bromide
(14,300 mg; 118.2 mmol; 20 mL), and anhydrous acetonitrile (150 mL) were stirred
at reflux for 1 h. Then volatile compounds were removed under reduced pressure.
The pasty residue was suspended in toluene (200 mL), and insoluble salts were fil-
tered and washed with additional portions of toluene (3 ꢂ 100 mL). Toluene was
removed under reduced pressure; the crude product was passed through a short col-
umn of silica gel (eluent: diethyl ether). Product 1 was obtained as a yellowish honey,
which solidified after several days in refrigerator (6034 mg; 100%) (lit.[5] using K2CO3
in DMF: 83%).
1H NMR (CDCl3, d ppm): 3.85 (s, 3H, CH3), 4.59 (m, 6H, OCH2), 5.12–5.46
(m, 6H, CH2), 5.95–6.14 (m, 3H, ¼CHꢀ), 7.26 (s, 2H, ArH); 13C NMR (CDCl3, d

´
R. KAPLANEK ET AL.
252
ppm): 52.0 (s, 1C), 69.8 (s, 2C), 73.9 (s, 1C), 108.6 (s, 1C), 117.5 (s, 2C), 117.7 (s, 1C),
124.9 (s, 1C), 132.8 (s, 2C), 134.1 (s, 1C), 141.7 (s, 1C), 152.1 (s, 2C), 166.5 (s, 1C).
Anal. calcd. for C17H20O5: C, 67.09; H, 6.62. Found: C, 67.00; H, 6.71.
Addition of perfluorohexyl iodide to allyl derivative 1
Via sodium dithionite. Allyl derivative 1 (152 mg; 0.5 mmol) and perfluoro-
hexyl iodide (1338 mg; 3 mmol) were dissolved in acetonitrile (12 mL), and water
(4 mL) was added, followed by Na2S2O4 (653 mg; 3 mmol) and NaHCO3 (252 mg;
3 mmol). The reaction mixture was vigorously stirred at rt overnight. Then water
(100 mL) was added and extracted with diethyl ether (5 ꢂ 50 mL). Combined organic
fractions were then extracted with brine (50 mL) and dried over Na2SO4. After
filtration, volatile compounds were removed under reduced pressure. The crude pro-
duct was purified by column chromatography on silica gel (eluent: toluene). Product
2 was obtained as a yellowish wax (686 mg; 84%).
Via AIBN. Allyl derivative 1 (152 mg; 0.5 mmol), perfluorohexyl iodide
(1338 mg; 3 mmol), and AIBN [30 mg; three portions (3 ꢂ 10 mg) were added over
an hour] were heated under argon atmosphere at 85ꢁC for 6 h. Then excess of
perfluorohexyl iodide was removed under reduced pressure. The crude product
was purified by column chromatography on silica gel (eluent: toluene). Product 2
was obtained as a yellowish wax (523 mg; 64%).
Via Et3B. Allyl derivative 1 (99 mg; 0.32 mmol), perfluorohexyl iodide (562 mg;
1.26 mmol), and hexane (0.5 mL) were mixed. Triethyl borane (1 M in hexanes;
0.2 mL; 0.2 mmol) were added, and the reaction mixture was stirred under an argon
atmosphere at rt overnight. The reaction mixture was directly introduced into a
column with silica gel and eluted with toluene. Product 2 was obtained as a white
wax (417 mg; 79%).
1H NMR (CDCl3, d ppm): 2.55–3.50 (m, 6H, CH2RF), 3.92 (s, 3H, CH3),
4.20–4.44 (m, 6H, 3ꢂ OCH2), 4.45–4.63 (m, 3H, CHI), 7.30 (s, 2H, ArH); 13C
3
NMR (CDCl3, d ppm): 12.1 (s, 3C), 37.8 (t, 3C, JCF ¼ 21 Hz), 52.5 (s, 1C), 73.5
(s, 2C), 77.6 (s, 1C), 105.0–125.0 (m, 18C), 108.7 (s, 2C), 126.2 (s, 1C), 140.5
(s, 1C), 151.2 (s, 2C), 165.9 (s, 1C); 19F NMR (CDCl3, d ppm): ꢀ81.7 (m, 9 F),
ꢀ115.1 (m, 6 F), ꢀ122.5 (m, 6 F), ꢀ123.5 (m, 6 F), ꢀ124.0 (m, 6 F), ꢀ126.6
(m, 6 F). Anal. calcd. for C35H20F39I3O5: C, 25.60; H, 1.23. Found: C, 25.44; H, 1.31.
Reduction of C-I bond in 2 produced methyl gallate 3. Iodo derivative 2
(613 mg; 0.373 mmol) and sodium acetate (305 mg; 3.73 mmol) were dissolved in
MeOH (20 mL) and ethyl acetate (20 mL). Pd=C [10%; 400 mg; previously suspended
in MeOH (20 mL)] was added, and the black suspension was stirred under a hydro-
gen atmosphere overnight. The Reaction mixture was filtered: Pd=C was washed
with methanol (40 mL) and ethyl acetate (40 mL). Solvents were removed under
reduced pressure. Solid residue was suspended in petroleum ether (150 mL), and
insoluble salts were filtered and washed with additional portions of petroleum ether
(3 ꢂ 50 mL). Petroleum ether was removed under reduced pressure; product 3 was
obtained as a white wax (453 mg; 96%).
1H NMR (CDCl3, d ppm): 1.96–2.20 (m, 6H, CH2CH2RF), 2.20–2.48 (m, 6H,
CH2RF), 3.90 (s, 3H, CH3), 4.06 (t, 2H, 3JHH ¼ 6.0 Hz, O4CH2), 4.11 (t, 4H, O3CH2

PREPARATION OF FLUOROUS BUILDING BLOCKS
253
3
and O5CH2, JHH ¼ 5.9 Hz), 7.29 (s, 2H, ArH); 13C NMR (CDCl3, d ppm): 20.6
3
(s, 2C), 21.4 (s, 1C), 27.8 (t, 3C, JCF ¼ 22 Hz), 52.3 (s, 1C), 67.6 (s, 2C), 71.9
(s, 1C), 105.0–125.0 (m, 18C), 108.3 (s, 2C), 125.6 (s, 1C), 141.5 (s, 1C), 152.2 (s,
3
2C), 166.4 (s, 1C); 19F NMR (CDCl3, d ppm): ꢀ81.6 (t, 6 F, JFF ¼ 10.4 Hz),
3
ꢀ81.7 (t, 3 F, JFF ¼ 9.8 Hz), ꢀ115.0 (m, 6 F), ꢀ122.5 (m, 6 F), ꢀ123.5 (m, 6 F),
ꢀ124.1 (m, 6 F), ꢀ126.8 (m, 6 F). Anal. calcd. for C35H23F39O5: C, 33.25; H, 1.83.
Found: C, 33.43; H, 1.98.
Preparation of gallate 3 via direct o-polyfluoroalkylation by triflate. A
solution of methyl gallate (291 mg; 1.58 mmol) in DMF (10 mL) at room temperature
was added dropwise to suspension of sodium hydride (60% susp. in mineral oil;
215 mg; 5.4 mmol; previously washed with anhydrous hexane) in anhydrous DMF
(10 mL). The slurry was stirred for an additional 30 min. The solution of 3-(perfluor-
ohexyl)propyl triflate (2900 mg; 5.68 mmol) in DMF (20 mL) was added at room
temperature, and the reaction mixture was then stirred at 70ꢁC for 4 h. After cooling
down, water (200 mL) was added, and the mixture was extracted with diethyl ether
(5 ꢂ 50 mL). The organic fraction was then washed with brine (2 ꢂ 30 mL) and dried
over MgSO4. After filtration, volatile compounds were removed under reduced
pressure. Crude product was purified by column chromatography on silica gel
(eluent: DCM.) Product 3 was obtained as a white wax (1817 mg; 91%).
Preparation of gallate 3 via direct o-polyfluoroalkylation by iodide
Via potassium carbonate. Methyl gallate (194 mg; 1.05 mmol), 3-(perfluoro-
hexyl)propyl iodide (2310 mg; 4.73 mmol), and K2CO3 (968 mg; 7 mmol) were stirred
in anhydrous DMF (7 mL) at 60ꢁC overnight. Then diethyl ether (40 mL) was added
and filtered. Salts were washed with the next portion of diethyl ether (3 ꢂ 30 mL).
After evaporation to dryness, the crude product was purified by column chromato-
graphy on silica gel; the column was washed with petroleum ether (unreacted
polyfluorinated iodide obtained in this fraction can be reused), then diethyl ether.
Product 3 was obtained as a pale yellow wax (1328 mg; 100%).
Via sodium hydride. To a suspension of sodium hydride (60% susp. in min-
eral oil; 145 mg; 3.6 mmol; previously washed with anhydrous hexane) in anhydrous
DMF (10 mL), a solution of methyl gallate (185 mg; 1 mmol) in DMF (10 mL) was
added dropwise at room temperature. The slurry was stirred for an additional
30 min. A solution of 3-(perfluorohexyl)propyl iodide (2198 mg; 4.5 mmol) in
DMF (15 mL) was added at room temperature, and the reaction mixture was then
stirred at 70ꢁC for 4 h. After cooling down, water (150 mL) was added, and the mix-
ture was extracted with diethyl ether (5 ꢂ 50 mL). The organic fraction was then
washed with brine (2 ꢂ 30 mL) and dried over MgSO4. After filtration, volatile com-
pounds were removed under reduced pressure. The crude product was purified by
column chromatography (as mentioned previously). Product 3 was obtained as a
white wax (1260 mg; 99%).
Reduction of gallate 3 to benzyl alcohol 4. Polyfluoroalkylated methyl gal-
late 3 (4632 mg; 3.66 mmol) was dissolved in anhydrous THF (60 mL) and cooled to
0ꢁC, and LiAlH4 (1 M in THF; 11 mmol; 11 mL) was added dropwise. The reaction
mixture was strirred at rt overnight. Then excess of LiAlH4 was destroyed by water

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R. KAPLANEK ET AL.
254
(20 mL), and volatile compounds were evaporated. The residue was acidified with
diluted HCl (1:5 v=v; 100 mL) and extracted with diethyl ether (3 ꢂ 100 mL). The
organic fraction was washed with water (50 mL) and brine (50 mL) and dried over
Na2SO4. Diethyl ether was removed under reduced pressure. Crude product was
passed through the short column of silica gel (eluent: diethyl ether). Product 4 was
obtained as yellowish wax (4463 mg; 98%).
1H NMR (CDCl3, d ppm): 1.93–2.16 (m, 6H, CH2CH2RF), 2.18–2.46 (m, 6H,
3
CH2RF), 3.97 (t, 2H, JHH ¼ 5.9 Hz, O4CH2), 4.05 (t, 4H, O3CH2 and O5CH2,
3JHH ¼ 5.9 Hz), 4.60 (s, 2H, CH2OH), 6.60 (s, 2H, ArH); 13C NMR (CDCl3, d
ppm): 20.7 (s, 2C), 21.4 (s, 1C), 27.8 (t, 2C, 3JCF ¼ 22 Hz), 27.9 (t, 1C, 3JCF ¼ 22 Hz),
65.2 (s, 1C), 67.5 (s, 2C), 71.8 (s, 1C), 105.0–125.0 (m, 18C), 105.5 (s, 2C), 136.8
(s, 1C), 137.0 (s, 1C), 152.6 (s, 2C); 19F NMR (CDCl3, d ppm): ꢀ81.5 (t, 6 F,
3
3JFF ¼ 10.4 Hz), ꢀ81.6 (t, 3 F, JFF ¼ 9.8 Hz), ꢀ115.0 (m, 6 F), ꢀ122.5 (m, 6 F),
ꢀ123.5 (m, 6 F), ꢀ124.1 (m, 6 F), ꢀ126.8 (m, 6 F). Anal. calcd. for C34H23F39O4:
C, 33.03; H, 1.87. Found: C, 33.17; H, 1.95.
Preparation of benzyl bromide 5. Polyfluoroalkylated benzyl alcohol 4
(1694 mg; 1.37 mmol) was dissolved in anhydrous diethyl ether (25 mL) and PBr3
(864 mg; 3.19 mmol; 0.3 mL) in diethyl ether (2 mL) was added dropwise. The reac-
tion mixture was strirred at rt overnight. Then water (50 mL) was added and
extracted with diethyl ether (3 ꢂ 50 mL). The organic fraction was washed with water
(50 mL) and brine (50 mL) and dried over Na2SO4. Diethyl ether was removed under
reduced pressure; the crude product was passed through the short column of silica
gel (eluent: diethyl ether). Product 5 was obtained as yellowish wax (1737 mg; 98%).
1H NMR (CD3COCD3, d ppm): 1.98–2.22 (m, 6H, CH2CH2RF), 2.40–2.64 (m,
3
6H, CH2RF), 4.10 (t, 2H, JHH ¼ 5.8 Hz, O4CH2), 4.20 (t, 4H, O3CH2 and O5CH2,
3JHH ¼ 5.9 Hz), 4.60 (s, 2H, CH2Br), 6.86 (s, 2H, ArH); 13C NMR (CD3COCD3, d
ppm): 21.4 (s, 2C), 22.2 (s, 1C), 28.4 (t, 2C, 3JCF ¼ 21 Hz), 28.6 (t, 1C, 3JCF ¼ 21 Hz),
34.9 (s, 1C), 68.3 (s, 2C), 72.2 (s, 1C), 105.0–125.0 (m, 18C), 109.0 (s, 2C), 135.0
(s, 1C), 138.5 (s, 1C), 153.5 (s, 2C); 19F NMR (CD3COCD3, d ppm): ꢀ80.8 (t,
3
9 F, JFF ¼ 10.4 Hz), ꢀ113.9 (m, 6 F), ꢀ121.4 (m, 6 F), ꢀ122.5 (m, 6 F), ꢀ123.0
(m, 6 F), ꢀ125.8 (m, 6 F). Anal. calcd. for C34H22BrF39O3: C, 31.43; H, 1.71. Found:
C, 31.34; H, 1.73.
ACKNOWLEDGMENTS
The authors thank the Ministry of Education, Youth, and Sports of Czech
Republic (Grants LC 512, KAN200200651, MSM 0021620806) and the Grant
Agency of the Czech Republic (Grant No. 203=06=0786) for financial support of this
project.
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