Aromatic fluoro-de-triazenation with boron trifluoride diethyl etherate under non-protic acid conditions

Article abstract of DOI:10.1016/j.jfluchem.2013.01.012

Fluoro-de-triazenation of 3,3-diethyl-1-aryltriazenes can be achieved by conventional or under microwave heating in carbon tetrachloride, in the presence of boron trifluoride diethyl etherate without any protic acid to avoid corresponding unwanted byproduct formation.

Full text of DOI:10.1016/j.jfluchem.2013.01.012

Journal of Fluorine Chemistry 147 (2013) 5–9
Contents lists available at SciVerse ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Aromatic fluoro-de-triazenation with boron trifluoride diethyl etherate under
non-protic acid conditions
Mitja Kovac a,b, Marko Anderluh b, Johnny Vercouillie a, Denis Guilloteau a,
Patrick Emond a, Sylvie Mavel a,
*
a Universite´ Franc¸ois-Rabelais de Tours, INSERM U930, CHRU, Hoˆpital Bretonneau, Service de Me´decine Nucle´aire, 37000 Tours, France
b
ˇ
ˇ
University of Ljubljana, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Askerceva 7, 1000 Ljubljana, Slovenia
A R T I C L E I N F O
A B S T R A C T
Article history:
Fluoro-de-triazenation of 3,3-diethyl-1-aryltriazenes can be achieved by conventional or under
microwave heating in carbon tetrachloride, in the presence of boron trifluoride diethyl etherate without
any protic acid to avoid corresponding unwanted byproduct formation.
Received 19 October 2012
Received in revised form 9 January 2013
Accepted 12 January 2013
Available online 21 January 2013
ß 2013 Elsevier B.V. All rights reserved.
Keywords:
Fluorination
Triazene
Diazonium
Boron trifluoride
Arylfluoride
1. Introduction
triazenes [10,14,15]. The 3,3-dialkyl-1-aryltriazenes are
regarded as protected form of aryldiazonium ions and therefore
Most of the pharmacologically active fluorinated drugs are
aromatic, bearing a fluoro or a trifluoromethyl substituent [1].
The efficient regioselective introduction of fluorine in electron-
rich arenes under mild conditions continues to be a challenge
[2,3]. Fluoro-de-triazenation (so called Wallach reaction) repre-
sents one of the few regioselective nucleophilic routes yielding
arylfluorides (Ar-F) [4]. The triazenes have been known for more
than a century and have been studied for their versatility in
organic synthesis, especially after their biological activities were
first reported in the beginning of the 1960s [5,6]. The 3,3-
dialkyl-1-aryltriazenes (Ar–N55N–NR0R00) are regarded as pro-
tected form of aryldiazonium ions and therefore their acid-
triggered thermal decomposition parallels that of the corre-
sponding diazonium ionic reactions [4,7–10]. The use of 3,3-
dialkyl-1-aryltriazenes (Ar–N55N–NR0R00) has an essential ad-
vantage over the aryldiazonium ions because of their solubility
in a number of anhydrous organic and ionic solvents [4,9,11].
Moreover, they can be safely and readily prepared in moderate
to high yields [5,12,13]. In parallel, solid-phase methodologies
were also applied for the synthesis and reactivity of resin-bound
their acid-triggered thermal decomposition parallels that of the
corresponding diazonium ionic reactions. The reactivity of
aryltriazenes is well described, especially the competition
between ionic (heterolytic) and radical (homolytic) de-triazena-
tion and de-diazoniation pathways during fluoro-de-diazonia-
tion, mechanism strongly dependents upon the reaction
conditions [4,7–10]. As protic acid is usually required to
decompose aryltriazene, and since the formed phenyl cation
intermediate is highly reactive, fluoro-de-triazenation is often
accompanied by the formation of a substantial amount of the
acid counterion substituted byproduct (Ar-A) [9,11].
We have been investigating the fluoro-de-triazenation reaction
as part of a program toward the synthesis of 5-fluoro-3-(4-
phenylpiperidin-1-yl)-1,2,3,4-tetrahydro-naphthalen-2-ol (5-
FBVM) [16]. Therein we have proposed that 3,3-diethyl-1-
aryltriazene could be thermally decomposed and subsequently
regioselectively fluorinated using boron trifluoride diethyl ethe-
rate (BF3ꢀEt2O) as both Lewis acid and fluorinating agent. Thus, the
main advantage of the protocol is the avoidance of the competitive
formation of the unwanted compound Ar-A. Using 3,3-diethyl-1-
naphthyltriazene as a model, the influence of different organic
solvents was studied. Furthermore, to demonstrate the versatility
of the method, a fluoro-de-triazenation was successfully per-
formed using conventional and microwave heating on several 4-
substituted 3,3-diethyl-1-aryltriazenes.
* Corresponding author at: Faculte´ de Pharmacie, INSERM U930, 31 Avenue
Monge, 37200 Tours, France. Tel.: +33 2 47 36 72 40; fax: +33 2 47 36 72 24.
E-mail address: sylvie.mavel@univ-tours.fr (S. Mavel).
0022-1139/$ – see front matter ß 2013 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.jfluchem.2013.01.012

6
M. Kovac et al. / Journal of Fluorine Chemistry 147 (2013) 5–9
Table 1
2. Results and discussion
Synthesis of 3,3-diethyl-1-aryltriazenes 2a-g. .
1. HCl 37 %, 2. NaNO2 aq. , 0 - 5 oC, 45 min
3. NHEt2, Na2CO3 aq. , 0 - 5 oC to rt, 1 h
2.1. Preparation of 3,3-diethyl-1-aryltriazenes
Ar-N=N-NEt2
Ar NH2
1a-g
2a-g
All 3,3-diethyl-1-aryltriazenes 2a-g were prepared according to
known procedure [13], involving diazotization of aromatic amines
1a-g with sodium nitrite in acidic aqueous medium at 0–5 8C
followed by addition of diethylamine to yield the corresponding
triazenes 2a-g (Table 1).
Ar-NH2
Triazene (isolated yield %)
1a [16]
2a (69)
HO
N
2.2. Fluoro-de-triazenation with polyphosphoric acid and boron
trifluoride diethyl etherate
H2N
Triflic acid (TfOH) is not an optimal acid for aromatic fluoro-de-
triazenation. Besides its incompatibility with the acid-sensitive
functional groups, substantial amounts of aryl triflate (Ar-OTf) is
usually produced [9,11]. Polyphosphoric acid (PPA) presents a
weaker nucleophilic conjugated base (Aꢁ) and with a suitable
redox potential to avoid the radical decomposition pathways [4].
Refluxing by using chloroform (CHCl3) instead of dichloromethane
(CH2Cl2), and by using PPA in the presence of BF3ꢀEt2O instead of
TfOH, the yield of 3a (5-FBVM) was increased from 25% as
previously described [16] to 34% yield (Table 2). We used 3,3-
diethyl-1-naphthyltriazene 2b as a model precursor for 5-FBVM, as
in CHCl3, 3b was obtained in 28% yield compared to only 5% in
CH2Cl2. PPA looked promising, although it has never been used in
fluoro-de-triazenation before. Because of its polymeric nature, we
assumed its counter anion (Aꢁ) is a non-nucleophilic species that
would prevent the formation of the Ar-A byproduct.
1b
1c
1d
1e
1f
1-Naphthylamine
4-Me-C6H4NH2
4-NO2-C6H4NH2
4-O-C4H9-C6H4NH2
4-I-C6H4NH2
2b (34)
2c (76)
2d (47)
2e (53)
2f (31)
2g (56)
1g
4-CN-C6H4NH2
Table 2
Fluoro-de-triazenation using polyphosphoric acid and boron trifluoride diethyl
etherate. .
.
PPA, BF3 Et2O
Ar
N
N
NEt2
Ar F
CH2Cl2 or CHCl3, reflux, Ar, 1h
2a-b
3a-b
Triazene
Arylfluoride
3a
Yield in CH2Cl2 (%)
Yield in CHCl3 (%)
2a
2b
34
5
39
28
In the presence of PPA, we observed that the triazenes 2a,b were
stable before the addition of BF3ꢀEt2O. With this observation in
hand, along with the theoretical study of the coordination
chemistry of triazene derivatives [17–19], and electron donor–
acceptor (EDA) complexes between BF3 and methylated ammonia
derivatives [20–22], we proposed that the fluorination of the 3,3-
dialkyl-1-aryltriazenes was possible using BF3ꢀEt2O only, as
depicted by the proposed reaction mechanism in Scheme 1.
The first rate limiting step is probably the reversible coordina-
tion of the BF3, due to its electrophilicity and affinity toward
nitrogen, at N(3) triazene which destabilizes the N(2)–-N(3) bond
by inhibiting delocalization across the triazene linkage [23] and,
therefore, induces its breakage, expelling BF2NEt2 followed in the
second step by the formation of the aryldiazonium ion (Scheme 1).
As suggested in the literature, the ‘‘reorganization energy’’ present
during the pyramidalization (sp2–sp3) of the boron atom probably
contributes to a reduction in the exothermicity of the complexa-
tion reaction [20–22]. Thus, boron trifluoride plays two roles
during the reaction: (i) it serves as an electron acceptor toward
aryltriazenes to enhance the reactivity of the N(2)–N(3) bond; (ii) it
serves as a fluoride source for the regioselective fluorination of the
arene.
3b
can be successfully accomplished without any protic acid or
catalyst and only in the presence of BF3ꢀEt2O.
2.3. Fluoro-de-triazenation of 3,3-diethyl-1-aryltriazenes by boron
trifluoride diethyl etherate in various solvents
As shown in Table 3 where 2b was selected as the model
precursor, fluorination of 2b-g was carried out using 1.5
equivalents of BF3ꢀEt2O at reflux temperature under argon for
1 h in various organic solvents.
By increasing the reaction temperature, reduced cleavage of 2b,
leading to naphthalene 4 as ‘‘traceless’’ byproduct, was suppressed,
while the ionic reaction was favored (Table 3). Interesting, in
carbon tetrachloride (CCl4), no radical reaction was observed since
4 was not detected. On the other hand, the radical decomposition
pathway was favored over the ionic one in tetrahydrofuran (THF),
as THF could act as a reducer as suggested in the literature [4,9,25].
On the contrary, redox potential of CH3CN is not in favor of any
reduction of 2b or its aryldiazonium ion. But, as proposed and
rationalized by Pages et al. [9], 4 could also be the result of redox
process(es) between non-complexated triazene and diazonium
ion. Furthermore, solvent competition was observed with t-
butanol (t-BuOH), besides 35% of 3b, formation of 1-t-butox-
ynaphthalene was observed (data not shown).
In spite of a previous work of Saeki et al. [24] where after several
tentative experiments, ‘‘1-aryltriazenes did not react with boron
trifluoride in the absence of either the palladium catalyst or
boronic acid’’, this work gives proofs that fluoro-de-triazenation
- N2 (g)
- BF2NEt2
Ar N(1) N(2) N(3)Et2
Ar N(1) N(2) N(3)Et2
Ar
N
N, F
Ar F
B
F
F
F
F
F
B
F
O
Et
Et
Scheme 1. Proposed reaction mechanism of fluoro-de-triazenation with 3,3-diethyl-1-aryl triazene and BF3ꢀEt2O.

M. Kovac et al. / Journal of Fluorine Chemistry 147 (2013) 5–9
7
Table 3
Solvent influence on the yields of 3b-g in fluoro-de-triazenation of 2b-g. Ratio of ionic pathway (3b) were compared to radical pathway (4). .
.
BF3 Et2O
solvent
Ar-N=N-NEt2
+
Ar-H
Ar-F
3b-g
reflux, Ar, 1 h
2b-g
4
Triazene
Aryl-fluoride
Yield in CH2Cl2 (%)
Yield in CHCl3 (%)
Yield in
CCl4 (%)
Yield in THF or CH3CN (%)
Yield in
t-BuOH (%)
2b
3b
8
31
59
Trace
35
c
3b/4a: ꢃ1/2
3b/4a: ꢃ1/1
4: not obs.b
4: main pdt
4: not obs.b
2c-e
2f
3c-e
3f
–
–
–
–
–
–
0
–
–
–
0
30
0
17
23
2g
3g
a
Crude molar ratio determined by HPLC analysis, 4 was naphthalene.
Naphthalene was not observed.
b
c
Naphthalene was the main product.
From the solvent effect studies, CCl4 and t-BuOH were chosen as
were detected in both solvents. As 4-nitrophenyl-cation is
electronically more destabilized than the corresponding arene-
diazonium ion, we assumed that rapid access to 110 8C and
uniform MW dielectric heating allowed immediate formation of
aryl cation after triazene complexation which is crucial for a
successful fluorination. Efficient MW-assisted fluorination was
also observed with 2e in CCl4 to give 3e in 64% yield, but only a 15%
yield was observed in t-BuOH (Table 4). The reaction in t-BuOH of
3c did not yield the corresponding fluoroarene, but rather 1-t-
butoxy-4-methylbenzene (data not shown). Yields of the 3b under
MW in both solvents were comparable to the yields obtained under
conventional heating. MW fluoro-de-triazenation of 2g in CCl4 also
afforded 41% yield of 3g and comparable 16% yield to conventional
heating in t-BuOH. Under these conditions, reactions afforded
significantly higher yields of fluorovesamicol derivative 3a from
previous 25% to 72% in CCl4 and 54% in t-BuOH.
prime solvents to extend the method to (4-substituted phenyl)-
triazenes 2c-g (Table 3). Carrying reactions in CCl4 and t-BuOH did
not afford the corresponding Ar-F derivative under chosen reaction
conditions for 2c,d and 2e. Especially for 2d and 2e, no triazene
decomposition in both examined solvents was detected. In general,
the low reactivity of triazenes is reflected in their high temperature
of decomposition (>130 8C) [8] and correlates with diazonium
salts decomposition (>90 8C) [26], and so is responsible for poor
reproducible yields of fluoro-de-diazoniation. On the other hand,
2f underwent fluoro-de-triazenation successfully in CCl4 and t-
BuOH with yields 30% and 17% of 1-fluoro-4-iodobenzene 3f,
respectively. Conducting reactions in t-BuOH, 4-fluorobenzonitrile
3g was produced in 23% yield (Table 3). Unreacted triazene
precursor 2g was found after reflux in CCl4 in the quenched
mixture. Noteworthy, 1-t-butoxy-4-iodobenzene and 4-t-butox-
ybenzonitrile were formed in t-BuOH (data not shown), coming
from solvent competition.
3. Conclusion
2.4. Microwave assisted fluoro-de-triazenation
We have performed studies towardrapid and synthetically useful
fluorination to obtain 1-fluoronaphthalene, 4-substituted-1-fluoro-
benzenes and validated the method by obtention of 5-fluoro-3-(4-
phenylpiperidin-1-yl)-1,2,3,4-tetrahydro-naphthalen-2-ol from the
corresponding 3,3-diethyl-1-aryltriazene precursors in CCl4 with
only boron trifluoride diethyl etherate complex. This advantage
distinguishes the present method from numerous precedents where
protic acid was necessary. The use of the controlled MW heating
could be implemented successfully leading to significant improve-
ment in the reaction efficiency and reaction time in cases where
conventional heating in CCl4 and t-BuOH has failed.
Based on the observation that the main problem of the protocol
is the high temperature of triazene decomposition, we performed a
fluoro-de-triazenation by microwave irradiation to compare
results with conventional heating conditions in CCl4 and t-BuOH.
As predicted, microwave irradiation (MW) facilitated the
fluorination of 2a-g using 1.5 equivalent of BF3ꢀEt2O in CCl4 and
t-BuOH under anhydrous conditions at 110 8C for 10 min (Table 4).
For unreacted compounds in conventional heating, the reaction
succeeded, and afforded 27% in CCl4 and 17% in t-BuOH of 3d
(Table 4). No reducing products derived from radical pathways
4. Experimental
4.1. General information
Table 4
Microwave assisted fluoro-de-triazenation of 2a-g. .
Column chromatography was used for routine purification of
reaction products using silica gel (Merck 60; 0.015–0.040 mm).
Preparative TLC was carried out using 20 cm ꢂ 20 cm glass backed
silica gel F254 plates, 1 mm thickness. High-pressure liquid
chromatography (HPLC) was carried out on a Beckman system
MW / 110 o
BF3 Et2O
C
.
Ar-F
3a-g
Ar-N=N-NEt2
solvent, Ar, 10 min
2a-g
Triazene
Arylfluoride
Isolated yield
Isolated yield in t-BuOH (%)
Gold with XBridgeTM column (5
m
m, 4.6 mm ꢂ 150 mm), at a flow
in CCl4 (%)
rate of 1 mL/min, and a 254 nm ultraviolet detector (0.1 M
NH4+CH3COOꢁ/CH3CN, 55/45). 1H and 13C NMR spectra were
recorded in a CDCl3 solution on a Bruker DPX Avance spectrometer
(300 MHz for 1H, 75 MHz for 13C, and 282 MHz for 19F) at 298 K. 1H
2a
2b
2c
2d
2e
2f
3a
3b
3c
3d
3e
3f
72
52
9
54
21
0
27
64
42
41
17
15
32
16
and 13C chemical shifts (
d) are expressed as part per million (ppm)
relative to TMS as an internal standard and 1H spin-spin coupling
2g
3g
constants (J) are given in Hertz (Hz). HRMS data were recorded on a

8
M. Kovac et al. / Journal of Fluorine Chemistry 147 (2013) 5–9
Thermo Scientific Q-Exactive; analyses were done by infusion at
1400 resolution. Microwave syntheses were carried out on a
Discover1 monomode reactor from CEM Corporation. All reagents,
chemicals and solvents were used as received from commercial
suppliers.
Compounds 2a [16], 2c [13], 2d [27], and 2g [13] were
characterized as previously described. The spectral data of
fluoroaryl derivatives 3b-d, f, g were identical to those obtained
from the commercial product, and could be observed by web
software SciFinder1 (Copyrightß 2012 American Chemical Socie-
ty) in «Experimental Properties» from the CAS REGISTRY.
temperature followed by BF3ꢀEt2O (0.047 mL, 0.375 mmol) addi-
tion. After refluxing for 1 h, the reaction mixture was quenched
with a saturated Na2CO3 aqueous solution (5 mL), extracted with
CH2Cl2 (3ꢂ 5 mL) and dried over MgSO4. After removal of the
solvent under reduced pressure, the residue was purified by
column chromatography (EtOAc/n-heptane, 1/5) to give 3a.
Compound 3b was obtained from the same procedure from 2b
(114 mg, 0.5 mmol), in CH2Cl2 or CHCl3, leading to 3b (4 or 20 mg)
in 5% or 28% yield, respectively. The spectral data of 3b were
identical to those obtained from the commercial product.
4.3.1. 5-Fluoro-3-(4-phenyl-piperidin-1-yl)-1,2,3,4-
tetrahydronaphthalen-2-ol: 3a
4.2. General procedure for preparation of 3,3-diethyl-1-aryltriazenes
2a-g
White powder (34% yield in CH2Cl2, 39% yield in CHCl3).
Identical spectral data to those described in literature [16]. 19F
In a round bottom flask, arylamine 1a-g (35 mmol), aqueous
hydrochloric acid (37%, 8.7 mL, 105 mmol) and water (90 mL) were
added. The resulting mixture was cooled to 0–5 8C and a chilled
water solution of NaNO2 (25 mL, 2.96 g of NaNO2, 42 mmol) was
added dropwise while maintaining the temperature below 5 8C.
The mixture was left to stir for 45 min at 0–5 8C, after which it was
neutralized by the dropwise addition of a cold saturated solution of
Na2CO3 (10 mL) and diethylamine (5.4 mL, 52.5 mmol) in chilled
water (30 mL). After stirring for 1 h, the reaction mixture was
extracted with CH2Cl2 (3ꢂ 90 mL). Combined organic phases were
dried over MgSO4 and concentrated under reduced pressure to give
a crude residue which was chromatographically purified to furnish
2a-g. Triazenes 2a-g were stored at ꢁ20 8C, in the dark to avoid
decomposition.
NMR (CDCl3)
d
ꢁ117.30 ppm (1F).
4.4. General procedure for the reaction of 3,3-diethyl-1-aryltriazene
2b-g with boron trifluoride diethyl etherate
Under argon atmosphere, 3,3-diethyl-1-aryltriazene 2b-g
(0.50 mmol) was dissolved in 5 mL of solvent (CH2Cl2, CHCl3,
CCl4, THF, CH3CN, or t-BuOH) in a dry two-necked round bottomed.
While stirring, BF3ꢀEt2O (0.10 mL, 0.75 mmol) was added and the
reaction was left to stir for 5 min, at room temperature. The
reaction mixture was then refluxed under argon for 1 h. After
cooling, saturated Na2CO3 aqueous solution (5 mL) was added to
the crude mixture and extracted with CH2Cl2 (3ꢂ 5 mL). The
combined organic extracts were dried over MgSO4 and concen-
trated under reduced pressure. The yields of 3b were determined
by HPLC from standards (8% yield in CH2Cl2, 31% yield in CHCl3, 59%
yield in CCl4, negligible yields in THF and CH3CN, and 35% yield in t-
BuOH). Yields of 3f and 3g were determined by 1H NMR from the
crude products (3f: 30% yield in CCl4 and 17% yield in t-BuOH; 3g:
23% yield in t-BuOH). The spectral data of 3b, 3g, 3f and 4 were
identical to commercial products.
4.2.1. 3,3-Diethyl-1-naphthyltriazene 2b
Compound 2b was purified by column chromatography (EtOAc/
n-heptane, 1/3) to give 2b (34%) as a red oil; 1H NMR (CDCl3):
d 1.38
(t, J = 7.1 Hz, 6H), 3.90 (q, J = 7.1 Hz, 4H), 7.45–7.51 (m, 4HAr), 7.66
(dd, J = 6.6 Hz, J = 2.6 Hz, 1HAr), 7.82–7.86 (m, 1HAr), 8.60–8.63 (m,
1HAr); 13C NMR (CDCl3):
d 11.1 (brs, 2CH3), 42.0 (brs, 2CH2), 111.4,
123.7, 124.8, 125.1, 125.7, 126.0, 127.6, 129.4, 134.3, 146.5; HRMS:
calculated [M+H]+ for C14H17N3: 228.14952, found: 228.15182.
4.5. General procedure for the microwave-assisted fluorination of 3,3-
diethyl-1-(4-substituted aryl)triazenes 2
4.2.2. 3,3-Diethyl-1-(4-butoxyphenyl)triazene 2e
Compound 2e was purified by column chromatography (EtOAc/
n-heptane, 1/5) to give 2e (53% yield) as a red oil; 1H NMR (CDCl3):
Vial (10 mL) containing magnetic stirring bar was charged with
2b-e (1.3 mmol), 4 mL of the solvent (CCl4 or t-BuOH) and BF3ꢀEt2O
(0.25 mL, 1.95 mmol) under an argon atmosphere. The microwave
tube was immediately sealed with a silicon septum and placed in
the microwave (MW) cavity (Discover1, CEM) and subjected to
MW irradiation for 10 min at 110 8C (ramp time 2 min, 20 W). After
cooling to room temperature, the reaction mixture was quenched
with saturated Na2CO3 aqueous solution (5 mL) and extracted with
CH2Cl2 (3ꢂ 5 mL). After drying over MgSO4 and removal of the
solvent under reduced pressure, the crude residues 3c-e were
purified by column chromatography (n-heptane 100% to EtOAc/n-
heptane, 1/5) to obtain pure products (yields in CCl4: 3b: 52%; 3c:
9%; 3d: 27%; 3e: 64%; 3f: 42%; 3g: 41% and yields in t-BuOH: 3b:
21%; 3d: 17%; 3e: 15%; 3e: 32%; 3g: 16%). The spectral data of 3c
and 3d were identical to commercial products.
d
1.00 (t, J = 7.2 Hz, 3H), 1.27 (t, J = 7.2 Hz, 6H), 1.47–1.57 (m, 2H),
1.75–1.82 (m, 2H), 3.75 (q, J = 7.2 Hz, 4H), 3.98 (t, J = 7.2 Hz, 2H),
6.89 (d, J = 6.9 Hz, 2HAr), 7.38 (d, J = 6.9 Hz, 2HAr); 13C NMR (CDCl3):
d
11.2 (brs, 2CH3), 13.8, 19.2, 31.3, 42.2 (brs, 2CH2), 67.9, 114.6
(2CHAr), 121.2 (2CHAr), 144.9, 156.9; HRMS: calculated [M+H]+ for
14H23N3O: 250.19139, found: 250.19389.
C
4.2.3. 3,3-Diethyl-1-(4-iodophenyl)triazene 2f
Compound 2f was purified by column chromatography (EtOAc/
n-heptane, 1/6) to give 2f (31% yield) as a red-orange oil; 1H NMR
(CDCl3):
d
1.28 (t, J = 7.2 Hz, 6H), 3.77 (q, J = 7.2 Hz, 4H), 7.19 (d,
11.4
J = 8.7 Hz, 2HAr), 7.64 (d, J = 8.7 Hz, 2HAr); 13C NMR (CDCl3):
d
(brs, 2CH3), 48.4 (brs, 2CH2), 88.9, 122.4 (2CHAr), 137.6 (2CHAr),
150.8; HRMS: calculated [M+H]+ for C10H14IN3: 304.03052, found:
304.03350.
Compound 3a was obtained from the same procedure from 2a
(30 mg, 0.074 mmol), in CCl4 and t-BuOH, leading, after purifica-
tion on preparative TLC (EtOAc/n-heptane, 1/4), to 3a (17 and
13 mg) in 72% and 54% yield, respectively.
4.3. Typical procedure for the reaction of 3,3-diethyl-1-aryltriazene
2a, 2b with polyphosphoric acid and boron trifluoride diethyl etherate
4.5.1. 1-Butoxy-4-fluorobenzene 3e
In CH2Cl2 or CHCl3 (5 mL), 5-fluoro-3-(4-phenylpiperidin-1-yl)-
1,2,3,4-tetrahydro-naphthalen-2-ol 2a (100 mg, 0.25 mmol) was
dissolved. This solution was added to polyphosphoric acid 115%
(70 mg), under argon atmosphere in a dry two-necked round
bottom flask. The mixture was left stirring for 5 min at room
Pale yellow oil (64% yield in CCl4, 15% yield in t-BuOH); 1H NMR
(CDCl3)
2H), 3.90 (t, J = 6.5 Hz, 2H), 6.79–6.97 (m, 4HAr); 13C NMR (CDCl3):
13.9, 19.2, 31.3, 68.3, 115.4 (d, J = 8 Hz, 2CHAr), 115.7 (d, J = 23 Hz,
2CHAr), 155.9, 156.5 (d, J = 250 Hz); 19F NMR (CDCl3)
ꢁ152.08;
d 0.96 (t, J = 7.4 Hz, 3H), 1.43–1.52 (m, 2H), 1.71–1.78 (m,
d
d

M. Kovac et al. / Journal of Fluorine Chemistry 147 (2013) 5–9
9
HRMS: calculated [M+H]+ for C10H13FO: 169.10232, found:
169.10398.
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This work was supported by Egide for graduate grant (PHC
PROTEUS, 2012 n8 26502QF). The authors would also like to
acknowledge Slovenian Research Agency for financial support of
Slovenian-French bilateral collaboration (project no. BI-FR/12–13-
PROTEUS-007). This work was supported by INSERM. We thank Dr.
Nabyl Merbouh (SFU) for the critical reading of the manuscript. We
´
thank the ‘‘Departement d’Analyses Chimiques et S.R.M. Biologi-
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que et Medicale’’ (PPF, Tours, France) for the chemical analyses and
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Mrs. Nathalie Meheux for her technical assistance.
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