One-pot two-step sequential transformation: Highly efficient construction of o-2,3,5,6-tetrafluorobenzonitrile substituted oximes ethers

Article abstract of DOI:10.1016/j.jfluchem.2014.06.011

A practical variety of o-2,3,5,6-tetrafluorobenzonitrile substituted oximes ethers bearing broad functional groups were synthesized in moderate to good yields. The key highlight of this disclosure involving a one-pot two-step tandem procedure in aqueous media: the in situ formation of aryl aldehydes or ketones oximes followed by the S_NAr reaction with pentafluorobenzonitrile via the high selective CF bond cleavage.

Full text of DOI:10.1016/j.jfluchem.2014.06.011

Journal of Fluorine Chemistry 165 (2014) 101–108
Contents lists available at ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
One-pot two-step sequential transformation: Highly efficient
construction of o-2,3,5,6-tetrafluorobenzonitrile substituted
oximes ethers
Cuibo Liu a, Xuguang Yin a, Jing Chang a, Xiangyang Tang a, , Bin Zhang
*
a,b,**
a Department of Chemistry, School of Science, Tianjin University, Tianjin 300072, China
b Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300072, China
A R T I C L E I N F O
A B S T R A C T
practical variety of o-2,3,5,6-tetrafluorobenzonitrile substituted oximes ethers bearing broad
Article history:
A
Received 18 April 2014
Received in revised form 19 May 2014
Accepted 13 June 2014
Available online 26 June 2014
functional groups were synthesized in moderate to good yields. The key highlight of this disclosure
involving a one-pot two-step tandem procedure in aqueous media: the in situ formation of aryl
aldehydes or ketones oximes followed by the SNAr reaction with pentafluorobenzonitrile via the high
selective C–F bond cleavage.
ß 2014 Elsevier B.V. All rights reserved.
Keywords:
Polyfluoroarenes
C–F bond cleavage
One-pot two-step
o-Arylated oximes
1. Introduction
for photoaffinity labeling (PAL) used in biochemistry and
molecular biology to study the proximity of components within
Compounds with a polyfluoroarylated moiety are a class of
important fluorine-containing species due to their unique
chemical and structural properties [1]. Among these polyfluor-
oarylated compounds, 2,3,5,6-tetrafluorobenzonitrile-derived
molecules demonstrate excellent applications in the materials
science, pharmaceutical and agricultural. For example, N-
2,3,5,6-tetrafluorobenzonitrile substituted dihydroquinoline
biological systems [4] (Fig.
1). Given the importance of
polyfluoroarylated skeletons, development of an efficient
method to access such valuable molecules is of great synthetic
interest.
Recently, the nucleophilic aromatic substitution (SNAr) reaction
has been proved to be a direct and efficient protocol in organic
syntheses and many complex molecules are synthesized using this
method [5]. As a simple, mild and environmentally benign
strategy, the SNAr reaction has gradually become an outstanding
procedure for the creation of polyfluoroarylated compounds
utilizing polyfluoroarenes as the starting materials via the C–F
bond cleavage with diverse electrophiles [6]. However, up to date,
only a limited number of reactions related to pentafluorobenzoni-
trile for further transformations based on this strategy [7]. For
instance, Sandford and coworkers reported an annelation reaction
between pentafluorobenzonitrile and N-H containing substrates to
give a series of ring-fused systems [8]. The Leyve group developed a
microwave-assisted fast synthesis of substituted fluorophenyl
mono- and diazides by SNAr to prepare photoaffinity labeling and
crosslinking reagents [9]. Although the elegant work has been
achieved, most of the present studies are focused on two
components reactions for the creation of new bonds, and the
compound
I possesses good inhibitory activities for many
STAT3 target genes in the JAK-STAT (Janus kinase-signal
transducers and activators of transcription) pathway [2].
Polyfluoroarylated UA derivatives II could inhibit the formation
of mammalian poly(ADP-ribose)polymerase 1, which is
a
nuclear protein involved in a number of cell processes such
as transcription, replication, DNA repair, and cell death [3].
Compounds III is selected as a kind of good photolabel reagent
*
Corresponding author at: Department of Chemistry, School of Science, Tianjin
University, Tianjin 300072, China. Fax: +86 22 27403475.
E-mail address: txy@tju.edu.cn.
**
Corresponding author at: Department of Chemistry, School of Science, Tianjin
University, Tianjin 300072, China. Tel.: +86 22 27406140; fax: +86 22 27403475.
E-mail address: bzhang@tju.edu.cn (B. Zhang).
http://dx.doi.org/10.1016/j.jfluchem.2014.06.011
0022-1139/ß 2014 Elsevier B.V. All rights reserved.

102
C. Liu et al. / Journal of Fluorine Chemistry 165 (2014) 101–108
H
O
N
O
F
F
O
OEt
N3
O
O
F
OH
F
F
F
F
NC
F
F
OH
F
F
F
F
O
CN
F
F
O
CN
I
II
III
Fig. 1. Three examples of 2,3,5,6-tetrafluorobenzonitrile-containing bioactive and material compounds.
one-pot multi-components reactions involving pentafluorobenzo-
nitrile are still rare. One recent investigation by Cao realized a three
synthesis of o-arylated oxime ethers, our method exhibits
simple, efficient, and green characteristics.
components assemble via VNSAr-SNAr process fabricated
a-C-
2,3,5,6-tetrafluorobenzonitrile substituted arylacetates in NMP
[10]. Consequently, the development of one-pot multi-compo-
nents reactions for introducing 2,3,5,6-tetrafluorobenzonitrile
groups into organic molecules has been the subject of intense
research.
Herein, we reported for the first time a one-pot two-step
sequential protocol for the construction of o-2,3,5,6-tetrafluor-
obenzonitrile substituted oxime ethers. This method involving
the in situ formation of aryl oximes from aldehydes/ketones
with hydroxylamine hydrochloride followed by the SNAr
reaction of pentafluorobenzonitrile via the selective C–F bond
cleavage. With this strategy, a series of the corresponding
products with broad functional groups were furnished in mild to
good yields. Furthermore, the procedure was accomplished in
aqueous media, which was distinct from the previous reports.
Additionally, compared with the present methodologies for the
2. Results and discussion
From the point of synthetic simplicity, one-pot multi-
components tandem reaction could provide
a far more
efficient and straightforward access to the target molecules.
In the connection with our study on polyfluoroaryl ethers [11],
we envisioned that aryl oximes produced in situ from
aldehyde/ketone with hydroxylamine hydrochloride may stereo-
selectively react with electron-withdrawing group substituted
polyfluoroarenes to form C–F functionalized products. Initially,
the reaction was treated with 1a (1.0 equiv), 2 (1.3 equiv), and
NaOH (4.0 equiv) in DMF at 70 8C for 8 h. Then followed by
the addition of 3 (1.5 equiv) to this mixture and stirred at the
same temperature for 6 h. However, to our disappointment, only
trace mount of the corresponding product was detected under
the primary selected conditions (Table 1, entry 1). We then
Table 1
Screening of the solvents and bases for the one-pot two-step sequential reaction of benzaldehyde, hydroxylamine hydrochloride, and
pentafluorobenzonitrilea.
.
Entry
Base
Solvent
T (8C)
Yieldb (%)
1
2
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
K2CO3
KOH
DMF
DMSO
CH3CN
CH3OH
THF
70
70
70
70
70
70
70
70
70
70
70
70
70
Trace
Trace
<10
43
3
4
5
Trace
51
6
Toluene
H2O
7
69
8
H2O
59
9
H2O
56
10
12
13
14
K3PO4
LiOHꢀH2O
NaOtBu
DABCO
H2O
36
H2O
76
H2O
Trace
–
H2O
a
Reaction conditions: benzaldehyde (0.2 mmol, hydroxylamine hydrochloride (0.26 mmol), base (0.8 mmol), solvent (0.3 mL), 70 8C 8 h, then
pentafluorobenzonitrile (0.3 mmol) was added and stirred at 70 8C for 6 h.
b
Isolated yield.

C. Liu et al. / Journal of Fluorine Chemistry 165 (2014) 101–108
103
Table 2
One-pot two-step sequential reaction of aldehydes, hydroxylamine hydrochloride, and pentafluorobenzonitrile.a
a
Reaction conditions: aldehydes (0.2 mmol, hydroxylamine hydrochloride (0.26 mmol), LiOHꢀH2O (0.8 mmol), water (0.3 mL), 70 8C 8 h, then pentafluorobenzonitrile
(0.3 mmol) was added and stirred at 70 8C for 6 h. Isolated yields are reported.
investigated the influence of solvents, and found that only H2O
was critical for the reaction efficiency (Table 1, entry 7). The use of
other solvents, such as acetonitrile, methanol, tetrahydrofuran,
toluene, and dimethylsulfoxide led to a lower yield or even no
product (Table 1, entries 2–6), which was very different from
the previous reports. As we all know, water is very green
and environmental, and using water as the solvent for the
organic synthesis could avoid the employment of some toxic
solvents, such as DMF, toluene, etc. Many significant reactions
were conducted in aqueous media [12]. Next, a further examina-
tion of the bases revealed that only LiOHꢀH2O gave the best
result and the other inorganic or organic bases were observed
to be inferior to LiOHꢀH2O. Thus, it illustrated that the solvent
and the base played an important role in our one-pot three-
component sequential reaction system.
With the optimum conditions in hand, we firstly evaluated
the substrate scope with respect to the aldehydes. As depicted in
Table 2, versatile functional groups such as methyl, dimethyl,
methoxyl, chloride and bromide were compatible with the
reaction system (Table 2, entries 4b–k), and good results were
obtained no matter where the substituted group lay. Not that,
the products bearing the chloro or bromo group could easily be
further functionalized by transition-metal-catalyzed methods or
the other techniques to form new carbon–carbon or carbon–
heteroatom bonds (Table 2, entries 4d, 4e, 4g, 4h, 4j). In
particular, the cinnamaldehyde was also effective for this
transformation and generated the corresponding product in a
promising yield.
After having screened a range of aldehydes, we subsequently
turned our attention to the ketones substrates. As expected, we
were pleased to find that the optimal conditions worked well for
different types of ketones. A number of the desired products were
furnished in acceptable yields regardless of the ketones possessing
electron-donating groups or electron-withdrawing groups, indi-
cating that the electronic effects of the substituents had no
influence on the effectiveness of the reaction (Table 3, entries 4a0–
k0). In addition, the heterocyclic reagents, e.g. 2-acetylpyridine, 2-
acetylfuran, and 2-acetyl thiophene were all tolerated, giving rise
to the corresponding products in 67–75% yields (Table 3, entries
4l0–n0). The aromatic ketones containing long-chain and cycle were
good candidates, too. And they provided the products in mild to
good yields (Table 3, entries 4o0–q0). Interestingly, the aliphatic
ketones, such as cyclohexanone and cyclooctanone were also
suitable in this system, albeit in moderate yields of the products
(Table 3, entries 4r0 and 4s0). Noteworthy, most of the products
were new compounds, and they were all characterized by mass
spectroscopy, 1H, 13C and 19F NMR spectroscopy (see the
Supporting Information).

104
C. Liu et al. / Journal of Fluorine Chemistry 165 (2014) 101–108
Table 3
One-pot two-step sequential reaction of ketones, hydroxylamine hydrochloride, and pentafluorobenzonitrile.a
a
Reaction conditions: ketones (0.2 mmol, hydroxylamine hydrochloride (0.26 mmol), LiOHꢀH2O (0.8 mmol), water (0.3 mL), 70 8C 8 h, then pentafluorobenzonitrile
(0.3 mmol) was added and stirred at 70 8C for 6 h. Isolated yields are reported.
3. Conclusions
(triplet), q (quartet), m (multiplet), dd (doublet of doublet), br
(broad). Coupling constants were reported in Hertz (Hz).
Tetrahydrofuran (THF) and toluene were distilled from sodium/
benzophenone; CH3CN were distilled from P2O5. All purchased
reagents were used without further purification. Analytical thin
layer chromatography was performed on 0.20 mm Qingdao
Haiyang silica gel plates. Silica gel (200–300 mesh) (from Qingdao
Haiyang Chem. Company, Ltd.) was used for flash chromatogra-
phy. Standard reagents and solvents were purified according to
known procedures.
In conclusion, we have developed a simple and practical
method for direct synthesis of o-2,3,5,6-tetrafluorobenzonitrile
substituted oxime ethers via the selective C–F bond cleavage of
pentafluorobenzonitrile. With this strategy, both different types of
aldehydes and ketones substrates were employed and a variety of
the corresponding products were obtained in good yields.
Moreover, the reaction proceeded through a one-pot two-step
domino procedure and by using water as the solvent, which may
reach to the extent of the green chemistry.
4.1. General procedure for the synthesis of the products
4. Experimental
Benzaldehyde 1a (98%, 21.6 mg, 0.2 mmol), hydroxylamine
hydrochloride 2 (98%, 18.4 mg, 0.26 mmol), and lithium hydroxide
monohydrate (90%, 37.3 mg, 0.8 mmol) were weighed to a sealed
Schlenk flask (25 mL), and water (0.3 mL) was added via syringe at
room temperature. After that the Schlenk flask was immersed in an
oil bath at 70 8C and stirred until the total conversion of
1H, 13C, 19F NMR were recorded on Varian Mercury Plus 400
instruments at 400 MHz (1H NMR), 100 MHz (13C NMR), as well as
376 MHz (19F NMR). Chemical shifts were reported in ppm down
field from internal Me4Si and external CCl3F, respectively.
Multiplicity was indicated as follows: s (singlet), d (doublet), t

C. Liu et al. / Journal of Fluorine Chemistry 165 (2014) 101–108
105
benzaldehyde (by TLC). And then pentafluorobenzonitrile 3 (98%,
4.1.5. (E)-4-(2-Bromobenzylideneaminooxy)-2,3,5,6-
59.1 mg, 0.3 mmol) was added to the mixture and the reaction
system was stirred at 70 8C until it was completed. Water (5 mL)
was added to the Schlenk flask and extracted with ethyl acetate
(3 ꢁ 10 mL). The organic extracts were combined, dried with
anhydrous magnesium sulfate and then concentrated in vacuo.
The residue was purified on silica gel to afford the product 4a
(44.7 mg, 76% yield).
tetrafluorobenzonitrile (4e)
M: 58.2 mg, Yield: 78%; 1H NMR (400 MHz, CDCl3) [ppm]
d
8.97
(s, 1H), 7.92–7.84 (m, 1H), 7.69–7.63 (m, 1H), 7.38 (p, J = 7.1 Hz,
2H); 19F NMR (376 MHz, CDCl3) [ppm]
d
ꢂ132.83 to ꢂ132.94 (m,
2F), ꢂ150.95 to ꢂ151.06 (m, 2F); 13C NMR (100 MHz, CDCl3) [ppm]
d
155.0, 149.0–149.2 (m), 146.4–146.6 (m), 142.4–142.6 (m),
141.6–141.9 (m), 139.0–139.3 (m), 133.5, 133.0, 128.9, 128.2,
127.9, 124.8, 107.3 (t, JC–F = 4.0 Hz), 89.3–89.6 (m); IR (KBr)
(cmꢂ1): 3450.98, 2926.98, 2854.48, 2245.04, 1645.44, 1589.51,
1498.85, 1431.96, 1130.07, 964.76, 900.27, 762.71, 587.40; HRMS
(ESI) found: m/z 372.9594 [M+H]+; calcd. for C14H5BrF4N2O + H
372.9599.
n
4.1.1. (E)-4-(Benzylideneaminooxy)-2,3,5,6-tetrafluorobenzonitrile
(4a)
M: 44.7 mg, Yield: 76%; 1H NMR (400 MHz, CDCl3) [ppm]
d
8.56
(s, 1H), 7.67 (d, J = 7.1 Hz, 2H), 7.53 (t, J = 7.3 Hz, 1H), 7.47 (t,
J = 7.3 Hz, 2H); 19F NMR (376 MHz, CDCl3) [ppm]
d
ꢂ130.01 to
ꢂ130.12 (m, 2F), ꢂ150.91 to ꢂ151.02 (m, 2F); 13C NMR
4.1.6. (E)-2,3,5,6-Tetrafluoro-4-(3-
(100 MHz, CDCl3) [ppm]
d
155.7, 149.1–149.3 (m), 146.4–
methoxybenzylideneaminooxy)benzonitrile (4f)
146.6 (m), 142.6–142.8 (m), 141.7–141.9 (m), 139.1–139.4
M: 46.0 mg, Yield: 71%; 1H NMR (400 MHz, CDCl3) [ppm]
d
8.52
(m), 131.9, 129.3, 129.1, 128.0, 107.4 (t, JC–F = 6.0 Hz), 89.0–
(s, 1H), 7.38 (t, J = 8.1 Hz, 1H), 7.24–7.18 (m, 2H), 7.06 (dd, J = 8.2,
89.4 (m); IR (KBr)
n
(cmꢂ1): 3647.37, 3034.31, 2926.43, 2317.50,
2.1 Hz, 1H), 3.86 (s, 3H); 19F NMR (376 MHz, CDCl3) [ppm]
d
2242.07, 1649.60, 1506.09, 1437.95, 1209.78, 1004.44, 961.24,
894.45, 846.57, 789.55, 693.88, 582.70, 507.86; HRMS (EI) found:
m/z 294.0414 [M]; calcd. for C14H6F4N2O 294.0416.
ꢂ133.05 to ꢂ133.16 (m, 2F), ꢂ150.89 to ꢂ151.00 (m, 2F); 13C NMR
(100 MHz, CDCl3) [ppm]
d 160.0, 155.5, 149.0–149.2 (m), 146.4–
146.7 (m), 142.6–142.8 (m), 141.7–141.9 (m), 139.1–139.4 (m),
130.5, 130.1, 121.2, 118.2, 112.0, 107.4 (t, JC–F = 4.0 Hz), 89.1–89.4
4.1.2. (E)-2,3,5,6-Tetrafluoro-4-(2-
(m), 55.4; IR (KBr) n
(cmꢂ1): 3448.87, 2969.51, 2920.18, 2239.29,
methylbenzylideneaminooxy)benzonitrile(4b)
1647.85, 1610.17, 1572.56, 1485.28, 1437.88, 1270.99, 1131.07,
1010.82, 969.88, 921.53, 859.15, 684.75, 569.94; HRMS (EI) found:
m/z 304.0453 [MꢂHF]; calcd. for C15H8F4N2O2 ꢂ HF 304.0460.
M: 46.8 mg, Yield: 76%; 1H NMR (400 MHz, CDCl3) [ppm]
d
8.80
(s, 1H), 7.68 (d, J = 7.7 Hz, 1H), 7.41 (t, J = 7.3 Hz, 1H), 7.29 (t,
J = 6.4 Hz, 2H), 2.52 (s, 3H); 19F NMR (376 MHz, CDCl3) [ppm]
d
ꢂ133.06 to ꢂ133.17 (m, 2F), ꢂ150.98 to ꢂ151.09 (m, 2F); 13C NMR
4.1.7. (E)-4-(3-Chlorobenzylideneaminooxy)-2,3,5,6-
tetrafluorobenzonitrile (4g)
(100 MHz, CDCl3) [ppm]
d 155.1, 149.0–149.3 (m), 146.4–146.8
(m), 142.6–142.9 (m), 141.6–141.8 (m), 139.1–139.3 (m), 138.3,
M: 53.2 mg, Yield: 81%; 1H NMR (400 MHz, CDCl3) [ppm]
d
8.51
131.5, 131.3, 128.5, 127.6, 126.4, 107.4 (t, JC–F = 4.0 Hz), 89.0–89.2
(s, 1H), 7.68 (s, 1H), 7.54 (d, J = 7.6 Hz, 1H), 7.49 (d, J = 8.1 Hz, 1H),
(m), 20.3; IR (KBr)
n
(cmꢂ1): 3740.66, 3674.72, 3648.59, 3620.77,
7.41 (t, J = 7.8 Hz, 1H); 19F NMR (376 MHz, CDCl3) [ppm]
d
ꢂ132.78
2960.49, 2928.68, 2361.05, 2243.11, 1698.88, 1648.28, 1501.95,
1436.22, 1128.80, 1005.00, 963.53, 761.75, 670.42, 420.50; HRMS
(ESI) found: m/z 309.0646 [M+H]+; calcd. for C15H8F4N2O + H
309.0651.
to ꢂ132.89 (m, 2F), ꢂ150.86 to ꢂ150.97 (m, 2F); 13C NMR
(100 MHz, CDCl3) [ppm]
d 154.3, 149.0–149.2 (m), 146.4–146.8
(m), 142.3–142.5 (m), 141.7–142.0 (m), 139.1–139.4 (m), 135.3,
131.8, 131.0, 130.4, 127.6, 107.3 (t, JC–F = 3.0 Hz), 89.4–89.7 (m); IR
(KBr)
n
(cmꢂ1): 3454.35, 2926.21, 2244.09, 1646.50, 1564.54,
4.1.3. (E)-2,3,5,6-Tetrafluoro-4-(2-
1500.48, 1435.64, 1344.21, 1208.58, 1131.11, 1044.53, 963.48,
788.80, 720.73, 683.16, 586.28; HRMS (EI) found: m/z 307.9967
[MꢂHF]; calcd. for C14H5ClF4N2O ꢂ HF 37.9964.
methoxybenzylideneaminooxy)benzonitrile (4c)
M: 52.5 mg, Yield: 81%; 1H NMR (400 MHz, CDCl3) [ppm]
d 8.95
(s, 1H), 7.78 (d, J = 7.7 Hz, 1H), 7.48 (t, J = 7.9 Hz, 1H), 7.00 (dd,
J = 14.1, 7.8 Hz, 2H), 3.92 (s, 3H); 19F NMR (376 MHz, CDCl3) [ppm]
4.1.8. (E)-4-(3-Bromobenzylideneaminooxy)-2,3,5,6-
tetrafluorobenzonitrile (4h)
d
ꢂ133.28 to ꢂ133.39 (m, 2F), ꢂ150.95 to ꢂ151.06 (m, 2F); 13C
NMR (100 MHz, CDCl3) [ppm]
d
158.4, 151.8, 149.0–149.2 (m),
M: 64.2 mg, Yield: 86%; 1H NMR (400 MHz, CDCl3) [ppm]
d
8.50
146.4–146.7 (m), 142.8–143.1 (m), 141.6–141.8 (m), 139.0–139.3
(s, 1H), 7.83 (s, 1H), 7.65 (d, J = 7.9 Hz, 1H), 7.59 (d, J = 7.7 Hz, 1H),
(m), 133.3, 127.1, 120.0, 117.7, 111.4, 107.5 (t, JC–F = 4.0 Hz), 88.6–
7.35 (t, J = 7.9 Hz, 1H); 19F NMR (376 MHz, CDCl3) [ppm]
d
ꢂ132.74
89.0 (m), 55.7; IR (KBr)
n
(cmꢂ1): 3451.14, 2965.62, 2847.84,
to ꢂ132.85 (m, 2F), ꢂ150.82 to ꢂ150.93 (m, 2F); 13C NMR
2240.79, 1647.17, 1600.17, 1500.60, 1436.13, 1289.31, 1253.31,
1155.78, 1129.92, 1047.32, 1005.66, 965.19, 759.99, 587.42; HRMS
(EI) found: m/z 304.0453 [MꢂHF]; calcd. for C15H8F4N2O2 ꢂ HF
304.0460.
(100 MHz, CDCl3) [ppm] d 154.2, 149.0–149.2 (m), 146.4–146.6
(m), 142.3–142.6 (m), 141.7–142.0 (m), 139.2–139.4 (m), 134.8,
131.2, 130.6, 126.8, 127.6, 123.2, 107.3 (t, JC–F = 3.0 Hz), 89.4–89.8
(m); IR (KBr)
n
(cmꢂ1): 3734.48, 3651.58, 3061.64, 2961.74,
2244.81, 1648.76, 1555.61, 1490.11, 1436.91, 1206.99, 1128.10,
1009.39, 965.89, 907.19, 868.30, 743.99, 682.58, 471.61, 426.33;
HRMS (ESI) found: m/z 372.9594 [M+H]+; calcd. for
4.1.4. (E)-4-(2-Chlorobenzylideneaminooxy)-2,3,5,6-
tetrafluorobenzonitrile (4d)
M: 46.7 mg, Yield: 71%; 1H NMR (400 MHz, CDCl3) [ppm]
d
9.00
C14H5BrF4N2O + H 372.9599.
(s, 1H), 7.89 (d, J = 7.9 Hz, 1H), 7.46 (q, J = 8.1 Hz, 2H), 7.34 (t,
J = 7.2 Hz, 1H); 19F NMR (376 MHz, CDCl3) [ppm]
d
ꢂ132.83 to
4.1.9. (E)-2,3,5,6-Tetrafluoro-4-(4-
methoxybenzylideneaminooxy)benzonitrile (4i)
M: 46.0 mg, Yield: 71%; 1H NMR (400 MHz, CDCl3) [ppm]
d 8.49
ꢂ132.94 (m, 2F), ꢂ150.95 to ꢂ151.06 (m, 2F); 13C NMR (100 MHz,
CDCl3) [ppm]
d
152.8, 149.0–149.3 (m), 146.4–146.6 (m), 142.4–
142.6 (m), 141.6–141.8 (m), 139.1–139.3 (m), 135.0, 132.8, 130.2,
127.8, 127.3, 127.2, 107.3 (t, JC–F = 4.0 Hz), 89.3–89.6 (m); IR (KBr)
(cmꢂ1): 3449.20, 2929.25, 2243.58, 1646.05, 1493.31, 1433.29,
1207.72, 1131.24, 1005.08, 966.51, 764.45, 587.61, 481.23; HRMS
(EI) found: m/z 307.9967 [MꢂHF]; calcd. for C14H5ClF4N2O ꢂ HF
307.9964.
(s, 1H), 7.61 (d, J = 8.7 Hz, 2H), 6.97 (d, J = 8.7 Hz, 2H), 3.88 (s, 3H);
n
19F NMR (376 MHz, CDCl3) [ppm]
d
ꢂ133.22 to ꢂ133.32 (m, 2F),
ꢂ150.99 to ꢂ151.10 (m, 2F); 13C NMR (100 MHz, CDCl3) [ppm]
d
162.6, 155.1, 149.0–149.3 (m), 146.4–146.6 (m), 142.8–142.9 (m),
141.6–141.9 (m), 139.1–139.3 (m), 130.0, 121.6, 114.6, 107.5 (t, JC–
F = 3.0 Hz), 88.7–89.1 (m), 55.4; IR (KBr)
n
(cmꢂ1): 3736.13,

106
C. Liu et al. / Journal of Fluorine Chemistry 165 (2014) 101–108
3647.09, 2967.49, 2928.18, 2850.30, 2240.84, 1649.55, 1603.64,
1503.92, 1438.43, 1356.83, 1307.06, 1254.14, 1172.54, 1129.44,
1005.09, 968.10, 900.19, 836.53, 531.28; HRMS (EI) found: m/z
304.0453 [MꢂHF]; calcd. for C15H8F4N2O2 ꢂ HF 304.0460.
19F NMR (376 MHz, CDCl3) [ppm]
d
ꢂ133.34 to ꢂ133.45 (m, 2F),
ꢂ151.09 to ꢂ151.20 (m, 2F); 13C NMR (100 MHz, CDCl3) [ppm]
d
166.1, 148.9–149.2 (m), 146.4–146.6 (m), 143.0–143.1 (m), 142.0–
142.2 (m), 139.4–139.7 (m), 135.9, 134.5, 131.0, 129.7, 128.1,
126.1, 107.5 (t, JC–F = 3.0 Hz), 88.9–89.1 (m), 19.9, 17.3; IR (KBr)
(cmꢂ1): 3741.41, 3676.61, 3648.97, 3621.28, 2959.88, 2927.10,
2361.14, 1649.80, 1505.84, 1369.87, 1264.09, 1156.19, 985.70,
798.78, 672.06, 420.52; HRMS (ESI) found: m/z 323.0802 [M+H]+;
calcd. for C16H10F4N2O + H 323.0807.
n
4.1.10. (E)-4-(4-Chlorobenzylideneaminooxy)-2,3,5,6-
tetrafluorobenzonitrile (4j)
M: 44.0 mg, Yield: 67%; 1H NMR (400 MHz, CDCl3) [ppm]
d
8.53
(s, 1H), 7.61 (d, J = 8.3 Hz, 2H), 7.45 (d, J = 8.3 Hz, 2H); 19F NMR
(376 MHz, CDCl3) [ppm]
d
ꢂ132.87 to ꢂ132.97 (m, 2F), ꢂ150.93 to
ꢂ151.03 (m, 2F); 13C NMR (100 MHz, CDCl3) [ppm]
d
154.4, 149.0–
4.1.15. (E)-2,3,5,6-Tetrafluoro-4-(1-m-
tolylethylideneaminooxy)benzonitrile (4c0)
149.2 (m), 146.4–146.6 (m), 142.4–142.6 (m), 141.7–141.9 (m),
139.1–139.4 (m), 138.1, 129.5, 129.2, 127.7, 107.3 (t, JC–F = 3.0 Hz),
89.2–89.6 (m); IR (KBr)
1645.37, 1592.06, 1484.88, 1435.21, 1400.78, 1209.85, 1153.91,
11,227.59, 1008.29, 968.36, 900.32, 832.50, 515.98; HRMS (EI)
found: m/z 307.9967 [MꢂHF]; calcd. for C14H5ClF4N2O ꢂ HF
307.9964.
M: 47.1 mg, Yield: 73%; 1H NMR (400 MHz, CDCl3) [ppm]
(d, J = 12.2 Hz, 2H), 7.32 (dt, J = 16.1, 5.8 Hz, 2H), 2.53 (s, 3H), 2.42
d
7.49
n
(cmꢂ1): 3448.27, 2924.46, 2239.90,
(s, 3H); 19F NMR (376 MHz, CDCl3) [ppm]
d
ꢂ133.29 to ꢂ133.40 (m,
2F), ꢂ151.09 to ꢂ151.20 (m, 2F); 13C NMR (100 MHz, CDCl3) [ppm]
d
162.6, 149.0–149.2 (m), 146.4–146.7 (m), 143.0–143.3 (m),
141.8–142.1 (m), 139.3–139.5 (m), 138.6, 133.8, 131.6, 128.7,
127.2, 123.9, 107.5 (t, JC–F = 3.5 Hz), 88.9–89.1 (m), 21.4, 13.7; IR
4.1.11. (E)-4-(3,4-Dmethylbenzylideneaminooxy)-2,3,5,6-
tetrafluorobenzonitrile (4k)
(KBr) n
(cmꢂ1): 3453.34, 2929.22, 2858.83, 2239.51, 1645.51,
1500.05, 1437.19, 1373.83, 1325.91, 1154.37, 1130.68, 1005.57,
892.91, 791.37, 696.23; HRMS (ESI) found: m/z 323.0802 [M+H]+;
calcd. for C16H10F4N2O + H 323.0807.
M: 44.5 mg, Yield: 69%; 1H NMR (400 MHz, CDCl3) [ppm]
d
8.49
(s, 1H), 7.44 (s, 1H), 7.38 (d, J = 7.8 Hz, 1H), 7.22 (d, J = 7.7 Hz, 1H),
2.33 (d, J = 5.4 Hz, 6H); 19F NMR (376 MHz, CDCl3) [ppm]
d
ꢂ133.18
to ꢂ133.28 (m, 2F), ꢂ150.91 to ꢂ151.01 (m, 2F); 13C NMR
4.1.16. (E)-2,3,5,6-Tetrafluoro-4-(1-(3-
(100 MHz, CDCl3) [ppm]
d
155.7, 149.0–149.2 (m), 146.4–146.6
methoxyphenyl)ethylideneaminooxy)benzonitrile (4d0)
(m), 142.6–143.0 (m), 141.7–141.9 (m), 141.3, 139.1–139.4 (m),
M: 46.7 mg, Yield: 69%; 1H NMR (400 MHz, CDCl3) [ppm]
d
7.37
137.6, 130.3, 128.8, 126.7, 125.9, 107.4 (t, JC–F = 3.5 Hz), 88.9–89.1
(t, J = 7.9 Hz, 1H), 7.28–7.21 (m, 2H), 7.03 (dd, J = 8.1, 1.9 Hz, 1H),
(m), 19.9, 19.6; IR (KBr)
n
(cmꢂ1): 3654.50, 2954.65, 2925.69,
3.86 (s, 3H), 2.53 (s, 3H); 19F NMR (376 MHz, CDCl3) [ppm]
d
2239.65, 1648.40, 1503.25, 1438.25, 1346.61, 1152.60, 1130.03,
1006.61, 968.65, 937.55, 889.98, 828.56, 801.60, 710.61, 573.01,
473.00, 441.90; HRMS (ESI) found: m/z 323.0802 [M+H]+; calcd. for
ꢂ133.23 to ꢂ133.34 (m, 2F), ꢂ151.13 to ꢂ151.24 (m, 2F); 13C
NMR (100 MHz, CDCl3) [ppm]
d 162.3, 159.8, 149.0–149.3 (m),
146.4–146.6 (m), 142.9–143.1 (m), 141.8–142.0 (m), 139.3–
C
16H10F4N2O + H 323.0807.
139.5 (m), 135.1, 129.8, 119.2, 116.5, 112.1, 107.5 (t, JC–
F = 3.5 Hz), 88.6–89.2 (m), 55.4, 13.7; IR (KBr)
n
(cmꢂ1):
4.1.12. 2,3,5,6-Tetrafluoro-4-((E)-((E)-3-
phenylallylidene)aminooxy)benzonitrile (4l)
M: 50.6 mg, Yield: 79%; 1H NMR (400 MHz, CDCl3) [ppm]
(d, J = 9.9 Hz, 1H), 7.52 (d, J = 5.9 Hz, 2H), 7.42 (d, J = 5.9 Hz, 3H),
7.08 (d, J = 16.0 Hz, 1H), 6.85 (dd, J = 15.9, 10.0 Hz, 1H); 19F NMR
3735.88, 3647.03, 3022.28, 2975.87, 1649.15, 1573.15,
1488.43, 1370.48, 1287.53, 1225.96, 1177.10, 1006.65, 889.84,
784.71, 694.65, 571.98, 419.13; HRMS (EI) found: m/z 338.0689
[M]; calcd. for C16H10F4N2O2 338.0678.
d
8.34
(376 MHz, CDCl3) [ppm]
d
ꢂ133.00 to ꢂ133.10 (m, 2F), ꢂ150.99 to
4.1.17. (E)-4-(1-(3-Chlorophenyl)ethylideneaminooxy)-2,3,5,6-
tetrafluorobenzonitrile (4e0)
ꢂ151.09 (m, 2F); 13C NMR (100 MHz, CDCl3) [ppm]
d 157.1, 149.0–
149.2 (m), 146.4–146.6 (m), 143.9, 142.5–142.7 (m), 141.7–141.9
M: 48.7 mg, Yield: 71%; 1H NMR (400 MHz, CDCl3) [ppm]
d
7.69
(m), 139.1–139.4 (m), 135.0, 130.0, 129.0, 127.5, 118.6, 107.4 (t, JC–
(s, 1H), 7.58 (d, J = 7.7 Hz, 1H), 7.47 (d, J = 8.1 Hz, 1H), 7.39 (t,
F = 3.0 Hz), 89.0–89.5 (m); IR (KBr)
n
(cmꢂ1): 3646.79, 2922.70,
J = 7.9 Hz, 1H), 2.53 (s, 3H); 19F NMR (376 MHz, CDCl3) [ppm]
d
2853.16, 2241.50, 1647.00, 1580.07, 1502.02, 1438.71, 1368.41,
1166.93, 1121.84, 1004.54, 964.72, 878.29, 787.57, 753.51, 690.90,
512.31, 420.79; HRMS (ESI) found: m/z 321.0646 [M+H]+; calcd. for
ꢂ132.98 to ꢂ133.09 (m, 2F), ꢂ151.08 to ꢂ151.19 (m, 2F); 13C NMR
(100 MHz, CDCl3) [ppm]
d 161.2, 149.0–149.2 (m), 146.4–146.7
(m), 142.8–143.0 (m), 141.8–142.0 (m), 139.3–139.5 (m), 135.6,
C
16H8F4N2O + H 321.0651.
14.9, 130.8, 130.0, 126.8, 124.9, 107.4 (t, JC–F = 3.0 Hz), 89.0–89.5
(m), 13.7; IR (KBr)
n
(cmꢂ1): 3740.46, 3064.45, 2924.29, 2856.12,
4.1.13. (E)-2,3,5,6-Tetrafluoro-4-(1-
2361.16, 2241.52, 1641.23, 1558.44, 1488.39, 1438.69, 1372.39,
1297.00, 1154.08, 1125.88, 964.07, 892.17, 831.05, 797.72, 718.80,
685.58, 477.13, 422.07; HRMS (ESI) found: m/z 343.0256 [M+H]+;
calcd. for C15H7ClF4N2O + H 343.0261.
phenylethylideneaminooxy)benzonitrile (4a0)
M: 45.0 mg, Yield: 73%; 1H NMR (400 MHz, CDCl3) [ppm]
d
7.70
(d, J = 6.9 Hz, 2H), 7.52–7.42 (m, 3H), 2.55 (s, 3H); 19F NMR
(376 MHz, CDCl3) [ppm]
d
ꢂ133.23 to ꢂ133.34 (m, 2F), ꢂ151.12 to
ꢂ151.23 (m, 2F); 13C NMR (100 MHz, CDCl3) [ppm]
d
162.4, 149.0–
4.1.18. (E)-2,3,5,6-Tetrafluoro-4-(1-p-
tolylethylideneaminooxy)benzonitrile (4f0)
149.2 (m), 146.4–146.7 (m), 143.0–143.3 (m), 141.8–142.0 (m),
139.2–139.5 (m), 133.8, 130.8, 128.8, 126.7, 107.6 (t, JC–F = 4.5 Hz),
88.7–89.1 (m), 13.6; IR (KBr)
2243.01, 1647.23, 1491.14, 1436.35, 1305.61, 1137.14, 998.97,
960.27, 877.38, 761.44, 693.24, 564.79, 418.71; HRMS (ESI) found:
m/z 309.0646 [M+H]+; calcd. for C15H8F4N2O + H 309.0651.
M: 51.6 mg, Yield: 80%; 1H NMR (400 MHz, CDCl3) [ppm]
(d, J = 8.1 Hz, 2H), 7.25 (d, J = 8.0 Hz, 2H), 2.52 (s, 3H), 2.42 (s, 3H);
d
7.60
n
(cmꢂ1): 3728.25, 3646.25, 2961.55,
19F NMR (376 MHz, CDCl3) [ppm]
d
ꢂ133.42 to ꢂ133.53 (m, 2F),
ꢂ151.20 to ꢂ151.31 (m, 2F); 13C NMR (100 MHz, CDCl3) [ppm]
d
162.3, 149.0–149.2 (m), 146.4–146.7 (m), 143.1–143.3 (m), 141.8–
142.0 (m), 141.2, 139.2–139.5 (m), 130.9, 129.5, 126.6, 107.5 (t, JC–
4.1.14. (E)-2,3,5,6-Tetrafluoro-4-(1-o-
F = 3.0 Hz), 88.7–88.8 (m), 21.3, 13.5; IR (KBr) n
(cmꢂ1): 3449.82,
2935.02, 2861.25, 2238.87, 1646.26, 1500.22, 1438.26, 1128.68,
1001.90, 874.56, 820.20, 560.80; HRMS (ESI) found: m/z 323.0802
[M+H]+; calcd. for C16H10F4N2O + H 323.0807.
tolylethylideneaminooxy)benzonitrile (4b0)
M: 53.5 mg, Yield: 83%; 1H NMR (400 MHz, CDCl3) [ppm]
(dd, J = 9.2, 4.4 Hz, 1H), 7.31–7.23 (m, 3H), 2.50 (s, 3H), 2.43 (s, 3H);
d
7.35

C. Liu et al. / Journal of Fluorine Chemistry 165 (2014) 101–108
107
4.1.19. (E)-2,3,5,6-Tetrafluoro-4-(1-(4-
1503.81, 1434.54, 1343.79, 1271.29, 1156.61, 1137.97, 984.07,
799.17, 766.03, 600.39, 419.23; HRMS (ESI) found: m/z 359.0802
[M+H]+; calcd. for C19H10F4N2O + H 359.0807.
methoxyphenyl)ethylideneaminooxy)benzonitrile (4g0)
M: 53.4 mg, Yield: 79%; 1H NMR (400 MHz, CDCl3) [ppm]
d
7.66
(d, J = 8.8 Hz, 2H), 6.95 (d, J = 8.8 Hz, 2H), 3.87 (s, 3H), 2.51 (s, 3H);
19F NMR (376 MHz, CDCl3) [ppm]
d
ꢂ133.41 to ꢂ133.52 (m, 2F),
4.1.24. (E)-2,3,5,6-Tetrafluoro-4-(1-(pyridin-2-
yl)ethylideneaminooxy)benzonitrile (4l0)
ꢂ151.21 to ꢂ151.32 (m, 2F); 13C NMR (100 MHz, CDCl3) [ppm]
d
161.8, 161.7, 149.0–149.3 (m), 146.4–146.7 (m), 143.2–143.3 (m),
M: 43.9 mg, Yield: 71%; 1H NMR (400 MHz, CDCl3) [ppm]
d
8.69
141.7–142.0 (m), 139.3–139.4 (m), 128.2, 126.0, 114.2, 107.6 (t, JC–
(d, J = 3.9 Hz, 1H), 7.90 (d, J = 7.9 Hz, 1H), 7.75 (t, J = 7.7 Hz, 1H),
F = 3.5 Hz), 88.5–88.8 (m), 55.4, 13.4; IR (KBr)
n
(cmꢂ1): 3488.67,
7.44–7.33 (m, 1H), 2.64 (s, 3H); 19F NMR (376 MHz, CDCl3) [ppm]
d
3132.43, 2964.59, 2929.54, 2238.99, 1648.24, 1501.67, 1435.14,
1401.23, 1153.77, 1129.75, 1002.72, 960.98, 820.76, 781.83,
562.16, 506.98, 419.21; HRMS (EI) found: m/z 338.0689 [M];
calcd. for C16H10F4N2O2 338.0678.
ꢂ133.07 to ꢂ133.18 (m, 2F), ꢂ151.12 to ꢂ151.22 (m, 2F); 13C NMR
(100 MHz, CDCl3) [ppm]
d 163.3, 151.8, 149.4, 149.0–149.4 (m),
146.4–146.6 (m), 142.9–143.1 (m), 141.8–141.9 (m), 139.2–139.4
(m), 136.6, 125.1, 121.4, 107.5 (t, JC–F = 3.0 Hz), 89.0–89.3 (m),
12.1; IR (KBr)
n
(cmꢂ1): 3714.63, 3677.07, 3649.27, 3621.97,
4.1.20. (E)-2,3,5,6-Tetrafluoro-4-(1-(4-
2361.24, 2243.17, 1647.66, 1559.09, 1504.95, 1433.53, 1366.68,
1129.68, 1010.94, 974.14, 890.98, 783.71, 678.09, 571.95, 398.57;
HRMS (ESI) found: m/z 310.0598 [M+H]+; calcd. for
fluorophenyl)ethylideneaminooxy)benzonitrile (4h0)
M: 43.7 mg, Yield: 67%; 1H NMR (400 MHz, CDCl3) [ppm]
(dd, J = 8.6, 5.4 Hz, 2H), 7.13 (t, J = 8.6 Hz, 2H), 2.53 (s, 3H); 19F NMR
d
7.71
C14H7F4N3O + H 310.0603.
(376 MHz, CDCl3) [ppm]
d
ꢂ109.17 to ꢂ109.25 (m, F), ꢂ133.26 to
ꢂ133.37 (m, 2F), ꢂ151.25 to ꢂ151.36 (m, 2F); 13C NMR (100 MHz,
4.1.25. (E)-2,3,5,6-Tetrafluoro-4-(1-(furan-2-
yl)ethylideneaminooxy)benzonitrile (4m0)
1
CDCl3) [ppm]
d
164.4 (d, JC–F = 228 Hz), 161.3, 149.0–149.2 (m),
146.4–146.7 (m), 142.9–143.2 (m), 141.8–142.0 (m), 139.2–139.4
M: 44.7 mg, Yield: 75%; 1H NMR (400 MHz, CDCl3) [ppm]
d 7.56
(s, 1H), 6.89 (d, J = 3.4 Hz, 1H), 6.54 (dd, J = 3.1, 1.6 Hz, 1H), 2.47 (s,
(m), 129.9 (d, 4JC–F = 4.0 Hz), 128.8 (d, 3JC–F = 9.0 Hz), 115.9 (d, 2JC–
F = 22.0 Hz), 107.4 (t, JC–F = 2.5 Hz), 88.8–89.2 (m), 13.5; IR (KBr)
n
3H); 19F NMR (376 MHz, CDCl3) [ppm]
d
ꢂ133.11 to ꢂ133.22 (m,
(cmꢂ1): 3073.40, 2933.53, 2859.42, 2243.27, 1646.85, 1598.31,
1501.41, 1438.10, 1373.92, 1304.46, 1230.81, 1156.57, 1128.31,
1007.38, 963.60, 888.92, 845.09, 558.71; HRMS (EI) found: m/z
326.0485 [M]; calcd. for C15H7F5N2O 326.0479.
2F), ꢂ150.91 to ꢂ151.02 (m, 2F); 13C NMR (100 MHz, CDCl3) [ppm]
d
153.9, 149.0–149.2 (m), 147.2, 146.3–146.6 (m), 145.3, 142.7–
143.0 (m), 142.1–142.3 (m), 139.5–139.7 (m), 113.4, 111.8, 107.4
(t, JC–F = 3.5 Hz), 89.2–89.6 (m), 12.4; IR (KBr)
(cmꢂ1): 3159.07,
n
3115.71, 2240.60, 1649.00, 1591.01, 1499.72, 1437.91, 1308.37,
1174.68, 1129.05, 1009.13, 966.99, 885.11, 723.65, 595.36, 425.24;
HRMS (ESI) found: m/z 299.0438 [M+H]+; calcd. for
4.1.21. (E)-4-(1-(4-Chlorophenyl)ethylideneaminooxy)-2,3,5,6-
tetrafluorobenzonitrile (4i0)
M: 50.0 mg, Yield: 73%; 1H NMR (400 MHz, CDCl3) [ppm]
d
7.65
C13H6F4N2O2 + H 299.0443.
(d, J = 8.3 Hz, 2H), 7.42 (d, J = 8.3 Hz, 2H), 2.53 (s, 3H); 19F NMR
(376 MHz, CDCl3) [ppm]
d
ꢂ133.15 to ꢂ133.26 (m, 2F), ꢂ151.18 to
4.1.26. (E)-2,3,5,6-Tetrafluoro-4-(1-(thiophen-2-
yl)ethylideneaminooxy)benzonitrile (4n0)
ꢂ151.29 (m, 2F); 13C NMR (100 MHz, CDCl3) [ppm]
d 161.3, 149.0–
149.2 (m), 146.4–146.7 (m), 142.9–143.1 (m), 141.8–142.0 (m),
139.2–139.4 (m), 137.1, 132.2, 129.0, 128.0, 107.4 (t, JC–F = 3.0 Hz),
88.9–89.3 (m), 13.4; IR (KBr)
2241.28, 1647.75, 1591.66, 1497.41, 1437.88, 1400.91, 1155.89,
1128.95, 1007.80, 837.87, 799.52, 558.75; HRMS (ESI) found: m/z
343.0256 [M+H]+; calcd. for C15H7ClF4N2O + H 343.0261.
M: 42.1 mg, Yield: 67%; 1H NMR (400 MHz, CDCl3) [ppm]
d 7.45
(d, J = 5.6 Hz, 2H), 7.12 (s, 1H), 2.56 (s, 3H); 19F NMR (376 MHz,
n
(cmꢂ1): 3449.36, 2934.05, 2860.68,
CDCl3) [ppm]
d
ꢂ133.07 to ꢂ133.25 (m, 2F), ꢂ151.16 to ꢂ151.27
157.8, 149.0–149.3
(m, 2F); 13C NMR (100 MHz, CDCl3) [ppm]
d
(m), 146.4–146.7 (m), 142.7–143.0 (m), 141.8–142.0 (m), 139.2–
139.4 (m), 129.4, 129.2, 127.4, 126.4, 107.5 (t, JC-F = 2.5 Hz), 88.9–
89.2 (m), 13.7; IR (KBr)
n
(cmꢂ1): 3646.03, 2932.61, 2317.30,
4.1.22. (E)-4-(1-(4-Bromophenyl)ethylideneaminooxy)-2,3,5,6-
tetrafluorobenzonitrile (4j0)
2242.63, 1646.97, 1497.29, 1435.81, 1302.86, 1130.85, 997.81,
959.81, 867.98, 784.40, 717.29, 419.41; HRMS (ESI) found: m/z
315.0210 [M+H]+; calcd. for C13H6F4N2OS + H 315.0215.
M: 58.1 mg, Yield: 75%; 1H NMR (400 MHz, CDCl3) [ppm]
d 7.59
(d, J = 7.2 Hz, 4H), 2.52 (s, 3H); 19F NMR (376 MHz, CDCl3) [ppm]
d
ꢂ133.08 to ꢂ133.19 (m, 2F), ꢂ151.15 to ꢂ151.26 (m, 2F); 13C NMR
4.1.27. (E)-4-(3,4-Dihydronaphthalen-1(2H)-ylideneaminooxy)-
2,3,5,6-tetrafluorobenzonitrile (4o0)
(100 MHz, CDCl3) [ppm]
d 161.8, 161.7, 149.0–149.3 (m), 146.4–
146.7 (m), 143.2–143.3 (m), 141.7–142.0 (m), 139.3–139.4 (m),
M: 55.5 mg, Yield: 83%; 1H NMR (400 MHz, CDCl3) [ppm]
d 7.94
128.2, 126.0, 114.2, 107.6 (t, JC–F = 3.5 Hz), 88.5–88.8 (m), 55.4,
13.4; IR (KBr)
1645.97, 1587.10, 1496.16, 1435.77, 1395.00, 1153.84, 1127.95,
1067.90, 1005.37, 961.90, 831.47, 558.10; HRMS (ESI) found: m/z
386.9751 [M+H]+; calcd. for C15H7BrF4N2O + H 386.9756.
(d, J = 7.8 Hz, 1H), 7.38 (t, J = 7.3 Hz, 1H), 7.26 (dd, J = 14.4, 6.7 Hz,
2H), 3.07 (t, J = 6.6 Hz, 2H), 2.90–2.82 (m, 2H), 2.04–1.94 (m, 2H);
n
(cmꢂ1): 3442.83, 2934.09, 2860.37, 2238.77,
19F NMR (376 MHz, CDCl3) [ppm]
d
ꢂ133.46 to ꢂ133.56 (m, 2F),
ꢂ151.28 to ꢂ151.39 (m, 2F); 13C NMR (100 MHz, CDCl3) [ppm]
d
161.2, 149.0–149.3 (m), 146.4–146.7 (m), 143.2–143.6 (m), 141.8–
142.0 (m), 140.8, 139.2–139.4 (m), 130.9, 128.9, 128.0, 126.7,
125.0, 107.6 (t, JC–F = 3.0 Hz), 88.5–89.8 (m), 29.5, 24.7, 21.1; IR
4.1.23. (E)-2,3,5,6-Tetrafluoro-4-(1-(naphthalen-1-
yl)ethylideneaminooxy)benzonitrile (4k0)
(KBr)
n
(cmꢂ1): 3450.25, 2936.36, 2870.30, 2240.93, 1646.92,
M: 38.0 mg, Yield: 53%; 1H NMR (400 MHz, CDCl3) [ppm]
d
8.06
1498.13, 1437.77, 1329.37, 1153.28, 1122.09, 1004.67, 963.00,
730.33, 557.02; HRMS (ESI) found: m/z 335.0802 [M+H]+; calcd. for
(d, J = 8.2 Hz, 1H), 7.95 (dd, J = 13.1, 6.3 Hz, 2H), 7.60 (dd, J = 16.0,
7.6 Hz, 2H), 7.54 (d, J = 4.3 Hz, 2H), 2.68 (s, 3H); 19F NMR (376 MHz,
C17H10F4N2O + H 335.0807.
CDCl3) [ppm]
d
ꢂ133.14 to ꢂ133.25 (m, 2F), ꢂ150.94 to ꢂ151.05
164.8, 149.0–149.2
(m, 2F); 13C NMR (100 MHz, CDCl3) [ppm]
d
4.1.28. (E)-2,3,5,6-Tetrafluoro-4-(1-
(m), 146.4–146.6 (m), 142.9–143.2 (m), 142.0–142.3 (m), 139.5–
139.7 (m), 133.9, 132.4, 130.4, 128.7, 127.2, 126.5, 126.4, 125.1,
phenylbutylideneaminooxy)benzonitrile (4p0)
M: 39.7 mg, Yield: 59%; 1H NMR (400 MHz, CDCl3) [ppm]
d
7.67
124.7, 107.5 (t, JC–F = 3.5 Hz), 89.1–89.4 (m), 18.2; IR (KBr)
n
(d, J = 7.1 Hz, 2H), 7.46 (d, J = 7.6 Hz, 3H), 3.05–2.95 (m, 2H), 1.76
(dt, J = 22.6, 7.5 Hz, 2H), 1.06 (dd, J = 13.2, 5.9 Hz, 3H); 19F NMR
(cmꢂ1): 3643.64, 2956.96, 2924.59, 2853.33, 2238.33, 1651.20,

108
C. Liu et al. / Journal of Fluorine Chemistry 165 (2014) 101–108
(376 MHz, CDCl3) [ppm]
d
ꢂ133.33 to ꢂ133.44 (m, 2F), ꢂ151.07 to
(cmꢂ1): 3615.24, 2933.64, 2861.94, 1645.79, 1498.56, 1436.39,
1401.76, 1131.89, 998.99, 957.89, 859.59, 810.55, 772.82, 730.21,
420.65; HRMS (ESI) found: m/z 315.1115 [M+H]+; calcd. for
ꢂ151.18 (m, 2F); 13C NMR (100 MHz, CDCl3) [ppm]
d
166.2, 149.0–
149.3 (m), 146.4–146.7 (m), 143.1–143.3 (m), 141.9–142.2 (m),
139.3–139.6 (m), 133.1, 130.7, 128.8, 127.0, 107.5 (t, JC–F = 2.5 Hz),
88.7–89.0 (m), 29.4, 20.1, 14.0; IR (KBr)
C15H14F4N2O + H 315.1120.
n
(cmꢂ1): 3739.93,
3674.52, 3647.50, 3619.36, 3132.02, 2964.92, 2928.46, 2360.89,
2238.23, 1648.50, 1503.92, 1398.76, 1260.05, 1152.86, 1001.12,
799.70, 755.95, 693.61, 420.52; HRMS (ESI) found: m/z 337.0959
[M+H]+; calcd. for C17H12F4N2O + H 337.0964.
Acknowledgements
We acknowledge Prof. Jun-An Ma for helpful discussion. This
work was financially supported by NSFC (No. 21373149) and
Innovation Foundation of Tianjin University (No. 20901057).
4.1.29. (E)-2,3,5,6-Tetrafluoro-4-(1-
phenylhexylideneaminooxy)benzonitrile (4q0)
Appendix A. Supplementary data
M: 49.5 mg, Yield: 68%; 1H NMR (400 MHz, CDCl3) [ppm]
d 7.68
(d, J = 6.9 Hz, 2H), 7.53–7.39 (m, 3H), 3.05–2.96 (m, 2H), 1.72 (dq,
J = 22.9, 7.7 Hz, 2H), 1.42 (ddd, J = 20.6, 10.9, 4.8 Hz, 4H), 0.93 (t,
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.jfluchem.2014.06.
011.
J = 6.9 Hz, 3H); 19F NMR (376 MHz, CDCl3) [ppm]
d
ꢂ133.36 to
ꢂ133.47 (m, 2F), ꢂ151.10 to ꢂ151.21 (m, 2F); 13C NMR (100 MHz,
References
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d 166.3, 149.0–149.2 (m), 146.4–146.7 (m), 143.1–
143.4 (m), 141.9–142.1 (m), 139.4–139.6 (m), 133.1, 130.7, 128.8,
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127.0, 107.5 (t, JC–F = 3.0 Hz), 88.7–89.0 (m), 31.7, 27.6, 26.3, 22.2,
13.8; IR (KBr)
n
(cmꢂ1): 3475.28, 2958.75, 2925.57, 2855.18,
2240.53, 2219.94, 1645.58, 1501.15, 1462.98, 1261.13, 1133.27,
1096.64, 1003.66, 961.24, 799.82, 694.87, 421.14; HRMS (ESI)
found: m/z 365.1275 [M+H]+; calcd. for C19H16F4N2O + H 365.1277.
4.1.30. 4-(Cyclohexylideneaminooxy)-2,3,5,6-tetrafluorobenzonitrile
(4r0)
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M: 31.5 mg, Yield: 55%; 1H NMR (400 MHz, CDCl3) [ppm]
d
2.72
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(t, J = 6.4 Hz, 2H), 2.38–2.28 (m, 2H), 1.83–1.75 (m, 4H), 1.69 (d,
J = 4.6 Hz, 2H); 19F NMR (376 MHz, CDCl3) [ppm]
d
ꢂ133.68 to
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(d) H. Jasch, S.B. Ho¨fling, M.R. Heinrich, J. Org. Chem. 77 (2012) 1520–1532;
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ꢂ133.79 (m, 2F), ꢂ151.22 to ꢂ151.33 (m, 2F); 13C NMR (100 MHz,
CDCl3) [ppm]
d 167.9, 148.9–149.2 (m), 146.4–146.6 (m), 143.2–
143.4 (m), 141.9–142.2 (m), 139.4–139.7 (m), 107.6 (t, JC–
F = 3.0 Hz), 88.3–88.6 (m), 31.4, 26.8, 26.0, 25.7, 25.3; IR (KBr)
n
(g) M.S. Deshmukh, B. Das, N. Jain, RSC Adv. 3 (2013) 22389–22396.
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(cmꢂ1): 3740.24, 3675.49, 3648.35, 3620.91, 2932.74, 2860.89,
2360.70, 1741.34, 1700.08, 1647.94, 1554.17, 1503.67, 1259.14,
1000.79, 798.07, 671.91, 420.38; HRMS (ESI) found: m/z 287.0802
[M+H]+; calcd. for C13H10F4N2O + H 287.0807.
(b) J.M. Birchall, R.N. Haszeldine, M.E. Jones, J. Chem. Soc. (1971) 1343–1347;
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Fluor. Chem. 144 (2012) 33–37.
6 (1966)
4.1.31. 4-(Cyclooctylideneaminooxy)-2,3,5,6-tetrafluorobenzonitrile
(4s0)
M: 39.6 mg, Yield: 63%; 1H NMR (400 MHz, CDCl3) [ppm]
d
2.70–2.62 (m, 2H), 2.44–2.36 (m, 2H), 1.95–1.80 (m, 4H), 1.63–1.52
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(m, 6H); 19F NMR (376 MHz, CDCl3) [ppm]
d
ꢂ133.68 to ꢂ133.80
(m, 2F), ꢂ151.29 to ꢂ151.40 (m, 2F); 13C NMR (100 MHz, CDCl3)
[ppm]
d 171.6, 149.0–149.2 (m), 146.4–146.6 (m), 143.3–143.5
(m), 142.0–142.3 (m), 139.5–139.8 (m), 107.6 (t, JC–F = 3.5 Hz),
88.4–88.6 (m), 32.7, 27.9, 27.2, 26.0, 25.3, 25.1, 23.8; IR (KBr)
n