Visible-light mediated directed perfluoroalkylation of hydrazones

Article abstract of DOI:10.1039/c7ob01144j

Perfluoroalkylation of N-alkylhydrazones has been achieved via visible light mediated photoredox reactions between the hydrazone and perfluoroalkyl iodide (R_fI). This protocol provides a convenient and efficient access to a series of perfluoroalkylated aromatic aldehyde hydrazones which tolerates a wide range of functional groups on the aromatic ring, and allows the use different types of primary and secondary perfluoroalkyl iodides with up to eight carbon atoms. Furthermore, aliphatic aldehyde hydrazones and N-monosubstituted hydrazones which are unreactive in previously reported hydrazone perfluoroalkylation reactions now take part in the reaction under our reaction conditions to give a satisfactory yield of products. Stern-Volmer quenching studies and spin-trapping experiments indicated that these reactions proceed by free radical addition of the R_f radical to the azomethine atom followed by one electron oxidation of the hydrazyl radical and deprotonation of the diazenium cation.

Full text of DOI:10.1039/c7ob01144j

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Takeharu Haino et al.
Solvent-induced emission of organogels based on tris(phenylisoxazolyl)
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Visible‐light mediated directed perfluoroalkylation of hydrazones
†
Received 00th January 20xx,
Accepted 00th January 20xx
‡
‡
Heng Ji, a, b Hui‐qiong Ni, a Peng Zhi,b Zi‐wei Xi,b Wei Wang,c Jian‐jun Shi*a and Yong‐miao Shen*b
DOI: 10.1039/x0xx00000x
Pefluoroalkylation of N‐alkylhydrazones have been achieved via visible light mediated photoredox reactions between the
hydrazone and perfluoroalkyl iodide (RfI). This protocol provides a convenient and efficient access of a series of
perfluoroalkylated aromatic aldehyde hydrazones which tolerates a wide range of functional groups on the aromatic ring,
and allows the use different types of primary and secondary perfluoroalkyl iodides with up to eight carbon atoms.
Furthermore, aliphatic aldehyde hydrazones and N‐monosubstituted hydrazones which are unreactive in previously
reported hydrazone perfluoroalkylation reactions now take part in the reaction under our reaction conditions to give
satisfactory yield of products. Stern‐Volmer quenching studies and spin‐trapping experiments indicated that these
reactions proceed by free radical addition of the Rf radical to the azomethine atom followed by one electron oxidation of
www.rsc.org/
the
hydrazyl
radical
and
deprotonation
of
the
diazenium
cation.
valuable functionalized compounds as fuluoroalkyl‐containing
ketones and hydrazines.9 These syntheses of α‐fluoroalkylated
hydrazones are mainly realized by free radical addition10 of the
electrophilic fluoroalkyl radical to the C=N bond of N,N‐
dialkylhydrazones. The fluoroalkyl radicals can be generated
from the easily available and inexpensive fluoroalkyl bromide
or iodide with extrusion of bromide or iodide anion in a single
electron reduction process with either a cuprous salt as
reductant5b,7 in a thermal reaction or in a light induced
photoredox reaction11 with an excited transition metal
complex as the reductant6. For the perfluoroalkylation of
hydrazones, Hashmi and his coworkers reported that a wide
range of N,N‐dialkylhydrazones could be perfluoroalkylated in
the presence of perfluoroalkyl bromides as the fluoroalkyl
source and the gold(I) complex [Au2(m‐dppm)2](OTf)2 as a
photocatalyst under UVA light irradiation.6a Furthermore, they
found that the perfluoroalkylation reactions might even be
achieved with perfluoroalkyl iodide as fluoroalkyl source under
UVA irradiation without the gold complex catalyst.8 They
proposed that in this case, direct single electron transfer
between the photoexcited hydrazone and perfluoroalkyliodide
took place to generate thefluoroalkyl radical. These reactions
provided efficient strategies to access the perfluoroalkylated
hydrazones from simple starting materials. Meanwhile, we
have noticed that In these reported perfluoroalkylation
protocols of hydrazones,6a,8 UVA light has to be used to excite
the gold(I) complex catalyst or the hydrazone because neither
has strong absorptions in the visible light region. Also, the
synthetic scope is limited by two facts. First, only aromatic
aldehyde derived hydrazones are suitable substrates, while
aliphatic aldehyde hydrazones are unreactive in the reactions.
Second, perfluoroalkylation of N‐monoalkylated hydrazones
Introduction,
Hydrazones constitute an important class of reagents in
organic synthesis by virtue of their easy accessibility, stability
and diverse reactivity depending on their structure, the
property of the reaction partner, and reaction conditions.1
They are widely applied for the construction of various
heterocycle skeletons and serve as precursors of
functionalized carbonyl compounds and hydrazines. The
multifaceted biological reactivity of many natural and synthetic
hydrazones such as antimicrobial, antiinflammatory,
anticonvulsant, antidepressant, analgesic, antimalarial,
antimycobacterial and anticancer activities, among others, has
made them interesting target compounds for developing new
drugs.2 Hydrazones have also found wide applications in
material science.3 For all these reasons, continuous research
effort has been paid to the development of useful synthetic
methods of functionalized hydrazones.1 In this area, in account
of the special properties that fluorine‐containing groups may
impart to the compound4, the synthesis of α‐
difluoroalkylated5,6 and α‐perfluoroalkylated hydrazones6a,7,8
has recently drawn much attention because they serve as
versatile synthetic intermediates and are precursors of such
a. School of Chemical Engineering, Anhui University of Science and Technology,
Huainan, P. R. China
b. Key Laboratory of Clean Dyeing and Finishing Technology of Zhejiang Province,
School of Chemistry and Chemical Engineering, Shaoxing University, Shaoxing
312000, China. E‐mail: shenyongmiao@usx.edu.cn
c. School of Chemical and Biological Engineering, Yancheng Institute of Technology,
Yancheng, P. R. China
†Electronic Supplementary Information (ESI) available: 1 H, C, F NMR spectra
of compounds, and data on mechanism study and geometry determination. See
DOI: 10.1039/x0xx00000x
13
19
‡These authors contributed equally to this work.
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ARTICLE
Organic Biomolecular Chemistry
are not reported. We now report here a visible light induced
perfluoroalkylation of hydrazones
1
2
3
4
5
6
7
Ir(ppy)3
[Ru(bpy)3](PF6)2
[Ir(ppy)2(dtppy)3]PF6 Na2HPO4
Ir(ppy)3
Ir(ppy)3
Ir(ppy)3
Ir(ppy)3
Na2HPO4
Na2HPO4
DMF
DMF
DMF
DMF
DMF
DMF
DMF
87
80
85
64
79
35
36
DABCO
K3PO4
KOAc
Previous work:
n‐
Bu4NOAc
K2HPO4
Na2HPO4
Na2HPO4
Na2HPO4
Na2HPO4
Na2HPO4
Na2HPO4
8
9
Ir(ppy)3
Ir(ppy)3
Ir(ppy)3
Ir(ppy)3
Ir(ppy)3
Ir(ppy)3
none
DMF
CH3CN
DMSO
dioxane 71
CH3OH
DMF
85
40
75
10
11
12
13
14
Imidazole (3 equiv), MeCN
N
N
H
N
N
RfI
+
UVA light (315-400 nm)
from 3x24W lamps
74
0[c]
0
Ar
Rf
Ar
This Work:
DMF
[a] The reactions were carried out with 1a (19.0 mg, 0.1
mmol), C4F9I (69.2mg, 0.2 mmol, 2.0 equiv), base (0.2 mmol,
2.0 equiv), photocatalyst (0.001 mmol, 1 mol%), solvent (2
mL), at room temperature, 3W blue LEDs, 24h. [b] Determined
by HPLC (area normalization method). [c] In dark. bpy =
bipyridine, DMF
dimethylsulfoxide, ppy = phenylpyridine, dtbpy = 4,4’‐di‐
tertbutyl‐2,2’‐bipyridine.
=
N,N‐dimethylformamide, DMSO
=
Scheme 1 The strategies for perfluoroalkylation of hydrazones
with fac‐Ir(ppy)3 as a catalyst, which works well not only on
N,N‐dialkylated aromatic aldehyde hydrazones, but also give
satisfactory results for aliphatic aldehyde hydrazones and N‐
monoalkylated hydrazone.
With these optimized reaction conditions in hand, we then
carry out the reactions with C4H9I as the fluoroalkyl source for
different aromatic aldehyde hydrazones, and the results are
shown in Entries 1
～ 17 in Table 2. We can see that
hydrazones with either electron‐withdrawing or electron‐
donating substituent(s) on the aromatic ring take part in the
Results and discussion
We started our work by examining the visible light induced
reactions of the 4‐(Benzylideneamino)morpholine 2a with
nonafluorobutyl iodide in DMF in the presence of three
different photocatalysts Ir(ppy)3, [Ir(ppy)2(dtbpy)3]PF6 and
[Ru(bpy)3](PF6)2 respectively with a 3W blue LED as a light
source. We found that with 2 eq. of Na2HPO4 as a base, all the
three catalysts induced the reaction to afford the desired
fluoroalkylatedhydrazone 3a in good yields (Entries 1, 2, 3 in
Table 1) with Ir(ppy)3 giving a slightly better result of 87% yield.
We then use Ir(ppy)3 as a catalyst to optimize the reaction
conditions in regard to solvent and added base. It is seen from
Table 1 that the reaction gave higher yield in DMF as a solvent
than in acetonitrile, dioxane, DMSO or in methanol, while
Na2HPO4 as a base turned out to be superior than all the other
inorganic and organic bases (K3PO4, KOAc, K2HPO4, (n‐
Bu)4NOAc and DABCO). The optimized reaction conditions are
therefore set to be irradiation of the DMF solution of a
hydrazone, a perfluoroalkyl iodide (2 eq.), the base Na2HPO4 (2
eq.) and Ir(ppy)3 (1 mol%) with a 3W blue LED as the light
source at room temperature.
reaction smoothly to afford the perfuoroalkylated products
in satisfactory yields, with the hydrazones with EWG (halogen
atom(s), CN, CF3, see entries 9 17) giving significantly higher
3
～
yields than those with EDW. However, even such strong EDG
as methoxy and Me2N is tolerated to give moderate yield of
product 3f and 3h, respectively (Entries 6 and 8), and the 2,3‐
dihydrobenzofuran‐5‐carboxaldehyde derived hydrazine 1r
afforded the product 3r in 45% yield. Also, significant steric
hindrance of the ortho‐substituent on the phenyl was not
observed, products 3g and 3o are formed in 70 % and 83%
yield (Entries 7 and 15), and 2‐naphthaldehyde derived
hydrazone gave the products 3s in 68% total yield (vide infra).
The 4‐methyl piperazine derived benzaldehyde hydrazone
gave the product 3t in 52% yield (Scheme 2). The reaction
scope in regard to the perfluoroalkyl iodide was then
investigated with the prototype hydrazone 1a. As shown in
Table 2, both primary and secondary perfuoroalkyl iodides
behave well in the reaction. Although a slight decrease in
product yield was observed as the perfluoroalkyl chain length
increases (comparing the results in entries 1 and 21, 22), even
the product 3x with a perfluoroalkyl chain of eight carbon
atoms gave a 47% yield. The somewhat lower yield of C3F7I as
compared with C4F9I is probably the result of the lower boiling
point of the former (41.2°C) which causes considerable loss of
the reagent by evaporation during the degassing manipulation
of the reaction mixture prior and during the reaction.
Table 1. Optimization Studiesa
entr
y
photocatalyst
base
solvent yield[%
[b]
]
2 | Org. Biomol. Chem., 2017, 00, 1‐3
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Table 2. Visible light mediated Perfluoroalkylation of morpholin
‐4‐amine
cyclopropanecarboxaldehyde and 4‐morpholinamine reacted
with C4F9I under our standard conditions to give the product
in 65 % yield. Similar reactions (N‐butylidene)morpholin‐4‐
amine afforded the product in 73% yield. Moreover, N‐
monoalkylated hydrazone turned out to be also suitable
derived
from
Hydrazonesa
4
5
substrate
in
the
reaction.
Accordingly,
in 67% yield.
Benzylidenephenylhydrazine gave the product
6
Entr
R1
Yield
/ %b
82
69
62
R2
R3
1
R4
2
3
The trifluoromethylation reactions of the hydrazones were
then studied. To avoid the experimental inconvenience of
using the low boiling point MeI, we chose to use CF3SO2Cl as
the trifluoromethyl source. With a half‐wave reduction
potential of ‐0.18 V (SCE)13, CF3SO2Cl is easily reduced by the
excited Ir(ppy)3 to its anion radical, which gives the
trifluoromethyl radical by losing a stable SO2 and a chloride
anion. The reactions proceed by irradiation of a MeCN solution
of the hydrazone, CF3SO2Cl (2 eq.) and Na2HPO4 (2 eq.) in the
presence of Ir(ppy)3 (1 mol%) with a 3W blue LED. As shown in
Scheme 3, a series of hydrazones are trifluoromethylated
under these conditions, and the products are formed in
y
1
2
3
4
5
H
Me
H
Me
t‐Bu
Me
O
H
H
Me
Me
H
H
H
H
H
H
1a
1b
1c
1d
1e
n‐C4F9
n‐C4F9
n‐C4F9
n‐C4F9
n‐C4F9
2a 3a
2a 3b
2a 3c
2a 3d
2a 3e
62
68
6
7
8
H
H
H
H
1f
n‐C4F9
n‐C4F9
n‐C4F9
2a 3f
2a 3g
2a 3h
62
61
45
M
e
O
H
1g
1h
N(C
H3)2
Cl
satisfactory yields (
1H–1H NOESY NMR experiment of 3b (see the Supporting
Information for details) and the X‐ray crystal structure of 3x
7b (Fig. 1.), and comparisons of the spectral data of the other
products showed that all the fluoroalkylated products are
7 and 8
)12.
H
9
H
Cl
Cl
H
H
Br
H
H
F
H
H
H
H
H
H
1i
1j
1k
1l
1m
1n
n‐C4F9
n‐C4F9
n‐C4F9
n‐C4F9
n‐C4F9
n‐C4F9
n‐C4F9
n‐C4F9
n‐C4F9
2a 3i
2a 3j
2a 3k
2a 3l
2a 3m
2a 3n
2a 3o
2a 3p
2a 3q
92
85
85
90
84
82
83
85
87
,
10
11
12
13
14
15
16
17
H
Cl
CN
CF3
H
H
H
F
3～6
in the more stable E‐ configuration except 3s, which are
formed as a mixture of E‐ and Z‐ isomers in a 43 : 26 ratio.
Br 1o
F
F
1p
1q
R1,R2
OCH2CH2
=
18
H
1r
n‐C4F9
2a 3r
45
19
20
21
22
H
H
H
H
H
H
H
H
H
H
H
H
1a
1a
1a
1a
n‐C3F7
i‐C3F7
n‐C5F11
n‐C8F17
2b 3u
2c 3v
2d 3w
76
67
63
2e 3x12 47
[a] The reactions were carried out with 1a (0.4 mmol), C4F9I
(0.8 mmol, 2.0 equiv), base (0.8 mmol, 2.0 equiv), Ir(ppy)3 (2.6
mg, 0.004 mmol, 1 mol%), DMF (8 mL), at room temperature,
3W blue LEDs. [b] Yield of isolated product.
We have further found that, under our reaction conditions, not
only hydrazones derived from aromatic aldehydes, but those
derived from aliphatic aldehydes also can be smoothly
perfluoroalkylated. Therefore, (E)‐N‐(cyclopropylmethylene)‐
Scheme 3
O
O
N
N
N
N
N
N
N
CF2(CF2)2CF3
CF2(CF2)2CF3
CF2(CF2)2CF3
O
3s-(E) 43%
3s-(Z) 26%
68
52
3t
3r
45
N
CF2(CF2)2CF3
N
R
N
N
NH
O
O
N
CH3
CF2(CF2)2CF3
4a R = CF2(CF2)2CF3 65
4b R = CF2(CF2)4CF3 46%
67
5
73
6
Scheme 2
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Scheme 5
Fig. 1 ORTEP drawing of product 3x (up) and 7b (down).
a) Gram‐scale reaction
b) Transformation of 3b
Fig. 2 X‐band EPR spectrum (298 K) of the radical trapping of a
DMPO (0.2 mmol), DMSO (1.5 mL); b C4F9I (0.2 mmol), base
(0.2 mmol), Ir(ppy)3 (1 mg), DMSO (1.5 mL), DMPO (0.2 mmol);
c) Photoredox three‐component reaction
Scheme 4 Synthetic utility of methodology.
c
1b (0.1 mmol), C4F9I (0.2 mmol), base (0.2 mmol), Ir(ppy)3 (1
mg), DMSO (1.5 mL), DMPO (0.2 mmol).
Second, a fluorescent‐quenching experiment was conducted
with 1a and 2a as the quencher of the photoexcited Ir(ppy)3,
respectively. Not surprisingly, perfluorobutyl iodide behaves as
a strong quencher of the excited iridium catalyst. The
quenching rate constant of perfluorobutyl iodide is 8.6×107
L/mol∙S. Meanwhile, the hydrazone only gives half quenching
rate constant.14
To demonstrate the synthetic utility of this reaction, a gram-
scale reaction was carried out under standard reaction
conditions. We were delighted to find that the synthesis of 3b
proceeded smoothly with a good yield of 72 % on a 5 mmol
scale (Scheme 4a). Hydrazones are significant and versatile
reagents in organic chemistry. The hydrazine 3b could be easily
converted to the corresponding perfluorobutyl aryl ketone
9
(Scheme 4b) by simple acidic treatment. Moreover, a direct
one-pot three-component coupling reaction between aldehyde,
amine and
n-C4F9I proceeded smoothly to give an excellent
yield (65 %) of product 3b (Scheme 4c).
To help to clarify the reaction mechanism, the following
control experiments were carried out. First, a radical‐trapping
experiment was conducted under the optimized conditions.
When a stoichiometric amount of radical scavenger 2,2,6,6‐
tetramethylpiperidine N‐oxide (TEMPO) was added to the
perfluoroalkylation reaction, no desired product was detected.
The TEMPO‐C4F9 adduct was formed in 23% yield (Determined
by GC‐MS, based on area normalization method) (Scheme 5).
These results suggested that our reaction is likely to involve a
radical process. Moreover, the perfluorobutyl radical
intermediate was observed in an EPR (Electron Paramagnetic
Resonance) spin‐trapping experiment with 5,5‐dimethyl‐1‐
pyrroline N‐oxide (DMPO) (Fig. 2). These results show that
perfluorobutyl radical is formed at the beginning of the
reaction.
Fig. 3 Fluorescence Quenching Data
A light on/off experiment showed that the continuous
irradiation of visible light is necessity and suggested that chain
propagation is not the predominant mechanistic pathway.
4 | Org. Biomol. Chem., 2017, 00, 1‐3
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In summary, perfluoroalkylation of a wide range of hydrazones
have been realized by visible light induced redox reactions
between hydrazine and perfuoroalkyliodide (RfI). When
applied to the aromatic aldehyde hydrazones, these reactions
showed good tolerance toward the fuctional groups on the
aromatic ring, and different RfI with primary (with up to eight
carbon atoms) and secondary Rf can be used. Furthermore,
aliphatic aldehyde hyrazones and N‐monosubstituted
hydrazones, which are unreactive in the up‐to‐now known
hydrazine perfluoroalkylation reactions, are found to be
suitable substrates under our reaction conditions to give
satisfactory yield of products. Stern‐Volmer quenching studies
of the excited Ir(ppy)3 with RfI and the hydrazone as the
quencher respectively, meanwhile spin trapping experiments
of the Rf radical by TEMPO and EPR spin‐trapping experiment
all suggest that these reactions take place via Rf radical
addition to the azomethine atom of the hydrazone followed by
oxidation of the hydrazyl radical and the deprotonation of the
diazenium cation.
Fig. 4 Time profile of perfluoroalkylation of 1b with and
without light.
Based on these results and taking into account of previous
work,6
a
plausible mechanism for these hydrazone
perfluoroalkylation reactions is proposed in Scheme 6. The
reaction commences by a single electron transfer (SET)
between the excited Ir(ppy)3 and the perfluoroalkyl iodide to
lead to the oxidized form of the former (IrIV) and the anion
radical of the later. This SET process is heavily exergonic
considering that the excited Ir(ppy)3 has an oxidation of ‒1.73
V (SCE) while the reduction potential of C4F9I is approximately
‒1.27 V (SCE) by using the value of C6F13I in DMF 15. The anion
radical of C4F9I releases the nonafluorobutyl radical and the
iodide anion. Free radical addition of the former to the
azomethine position of the hydrazone to furnish the
Experimental
General procedures for the perfluoroalkylation of hydrazones
In a vial Ir(ppy)3 (2.6 mg, 0.004 mmol, 1 mol%), hydrazone (0.4
mmol), Na2HPO4 (113.6mg, 0.8 mmol) and perfluoroalkyliodide
2
(0.8 mmol) were dissolved in 8mL DMF. The reaction mixture
was stirred under irradiation with a 3 W blue LED lamp for 24
hours. After the reaction was completed, the reaction mixture
was poured into 60mL water and extracted with EtOAc (8
mL×3). The combined organic layers were dried with
anhydrous MgSO4. The solvent was removed under reduced
pressure, and the crude mixture was directly charged on silica
gel and purified by column chromatography with petroleum
ether/ethyl acetate as eluents (gradient elution).
perfluoroalkylaminyl radical
species gives the cationic intermediate
Ir(ppy)3 catalyst. Deprotonation of under the action of the
A
, which upon oxidation by the IrIV
and regenerates the
B
B
base affords the product. Since the hydrazine can also quench
the excited photocatalyst, although only inefficiently, a
reaction pathway involving combination of the perfluoroalkyl
radical with the hydrazone anion radical could not excluded to
make a minor contribution to the reaction.16
General procedures for the trifluoromethylation of
hydrazones
In a vial Ir(ppy)3 (2.6 mg, 0.004 mmol, 1 mol%), hydrazone (0.4
mmol), Na2HPO4 (113.6mg, 0.8 mmol) and CF3SO2Cl (0.8
mmol) were dissolved in 8mL CH3CN. The reaction mixture was
stirred under irradiation with a 3 W blue LED lamp for 24
hours. After the reaction was completed, the solvent was
removed under reduced pressure, and the residum was
dissolved in 8 mL EtOAc. The reaction mixture was washed by
20mL water and the aqueous phase was extracted with EtOAc
(8 mL×3). The combined organic layers were dried with
anhydrous MgSO4. And the crude mixture was directly charged
on silica gel and purified by column chromatography with
petroleum ether/ethyl acetate as eluents (gradient elution).
(E)‐N‐(2,2,3,3,4,4,5,5,5‐nonafluoro‐1‐
phenylpentylidene)morpholin‐4‐amine (E:Z>33:1)
(
3a):Yellow
liquid; 134.0 mg; IR (KBr) ν 2970, 2851, 1575, 1444 cm–1; H
NMR (CDCl3, 400 MHz) δ(ppm) 2.98 (t, 4H, J = 5.0 Hz), 3.60 (t,
4H, J = 4.8 Hz), 7.34 – 7.37 (m, 2H), 7.39 – 7.43 (m, 3H); 19F
NMR (CDCl3, 376 MHz) δ(ppm) ‐81.10 (t, J= 9.78 Hz), ‐106.64 (t,
J=12.4 Hz), ‐120.01 – ‐120.08 (m), ‐124.41 (q, JC,F= 7.5 Hz); 13C
NMR (CDCl3, 100 MHz) δ54.2, 66.0, 128.7, 128.9, 129.7, 131.8,
1
Scheme 6 Plausible mechanism.
Conclusions
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135.2 (t, J= 27.5Hz); HRMS (ESI) Calcd forC15H13F9N2O [M+H]+ : 1235, 1132, 1005 cm–1; 1H NMR (CDCl3, 400 MHz) δ(ppm) 3.05
409.0962, found 409.0960.
(E)‐N‐(2,2,3,3,4,4,5,5,5‐nonafluoro‐1‐(p‐
tolyl)pentylidene)morpholin‐4‐amine
116.5 mg; IR (KBr) ν 2959, 1575, 1416 cm–1; H NMR (CDCl3, δ(ppm) ‐81.06 – ‐81.18(m), ‐105.28 (dt, J = 276.7, 12.0 Hz), ‐
400 MHz) δ(ppm) 2.38 (s, 3H), 2.99 (t, 4H, J = 4.8 Hz), 3.61 (t, 109.04 (dt, J = 276.4, 13.1 Hz), ‐120.33 – ‐120.50 (m), ‐124.48 –
4H, J = 4.8 Hz), 7.19–7.26 (m, 4H); 19F NMR (CDCl3, 376 MHz) ‐124.57 (m); 13C NMR (CDCl3, 100 MHz) δ 53.5, 55.6, 66.2,
δ(ppm) ‐81.10 (t, J=10.0 Hz), ‐106.77 (t, J= 12.3 Hz), ‐120.00 – ‐ 111.0, 120.6, 121.2, 130.4, 131.4, 157.7; HRMS (ESI) Calcd for
120.05 (m), ‐124.34– ‐124.43 (m); 13C NMR (CDCl3, 100 MHz) δ C16H15F9N2O2 [M+H]+: 439.1068, found 439.1073.
(t, 4H, J = 4.8 Hz), 3.61 (t, 4H, J = 4.8 Hz), 3.83 (s, 3H), 6.92 (d,
1H, J = 8.4Hz), 6.96 (td, 1H, J = 7.2, 0.93 Hz), 7.18 (d, 1H, J = 7.0
(
3b): Yellow liquid; Hz), 7.38 (td, 1H, J = 8.0, 1.8 Hz); 19F NMR (CDCl3, 376 MHz)
1
21.4, 54.1, 66.0, 128.7, 128.8, 129.4, 135.7(t, JC,F = 27.0Hz),
(E)‐N‐(1‐(4‐(dimethylamino)phenyl)‐2,2,3,3,4,4,5,5,5‐
139.9; HRMS (ESI) Calcd forC16H15F9N2O[M+H]+ : 423.1119, nonafluoropentylidene)morpholin‐4‐amine
(
3h) Yellow liquid;
found 423.1116.
(E)‐N‐(2,2,3,3,4,4,5,5,5‐nonafluoro‐1‐(m‐
81.2 mg; IR (KBr) ν 3003, 2931, 2845, 1577, 1438, 1135 cm–1;
1H NMR (CDCl3, 400 MHz) δ(ppm) 3.00 (s, 6H), 3.00 (t, 4H, J =
tolyl)pentylidene)morpholin‐4‐amine
(
3c): Yellow liquid; 4.8 Hz), 3.60 (tt, 4H, J = 5.0, 3.2 Hz), 6.68 (d, 2H, J = 8.8 Hz),
104.7 mg; IR (KBr) ν 2975, 2857, 1576, 1443 cm–1; H NMR 7.25 (d, 1H, J = 8.4 Hz); 19F NMR (CDCl3, 376 MHz) δ(ppm) ‐
(CDCl3, 400 MHz) δ(ppm) 2.37 (s, 3H), 2.99 (t, 4H, J = 4.8 Hz), 81.10 (t, J = 9.8 Hz), ‐106.93 (t, J = 12.0 Hz), ‐119.96 – ‐120.04
3.60 (tt, 4H, J = 4.8, 1.6 Hz), 7.15 (d, 2H, J = 8.0 Hz),7.21 (d, 1H, (m), ‐124.28 – ‐124.35 (m); 13C NMR (CDCl3, 100 MHz) δ 40.1,
J = 7.6 Hz),7.28 (t, 1H, J = 7.6 Hz); 19F NMR (CDCl3, 376 MHz) 54.0, 66.1, 111.5, 118.2, 129.6, 137.8, 150.7; HRMS (ESI) Calcd
δ(ppm) ‐81.16 (t, J=10.2 Hz), ‐106.48 (t, J= 12.7 Hz), ‐119.90 – ‐ for C17H18F9N3O [M+H]+: 452.1384, found 452.1384.
1
119.98 (m), ‐124.27 – ‐124.36 (m); 13C NMR (CDCl3, 100 MHz) δ
54.2, 66.1, 126.1, 128.6, 129.4, 130.6, 131.8, 135.4 (t, JC,F
27.5 Hz), 138.6; HRMS (ESI) Calcd for C16H15F9N2O [M+H]+ : (KBr) ν 2972, 2857, 1576, 1446 cm–1; 1H NMR (CDCl3, 400 MHz)
(E)‐1‐(4‐chlorophenyl)‐2,2,3,3,4,4,5,5,5‐nonafluoro‐N‐
morpholinopentan‐1‐imine 3i) Yellow liquid; 162.9 mg; IR
=
(
423.1119, found423.1116.
(E)‐1‐(3,4‐dimethylphenyl)‐2,2,3,3,4,4,5,5,5‐nonafluoro‐N‐
δ(ppm) 3.0 (t, 4H, J = 4.8 Hz), 3.62 (tt, 4H, J = 4.8, 1.8 Hz), 7.31
(d, 2H, J = 8.8 Hz), 7.40 (dt, 2H, J = 8.4, 2.4 Hz); 19F NMR (CDCl3,
morpholinopentan‐1‐imine (3d) Yellow liquid; 108.2 mg; IR 376 MHz) δ(ppm) ‐81.20 (t, J = 10.5 Hz), ‐106.69 (t, J = 12.0 Hz),
(KBr) ν 2982, 2931, 2851, 1577, 1439 cm–1; 1H NMR (CDCl3, 400 ‐120.07 – ‐120.20 (m), ‐124.46 – ‐124.56 (m); 13C NMR (CDCl3,
MHz) δ(ppm) 2.27 (s, 3H), 2.28 (s, 3H), 2.99 (t, 3H, J = 5.0 Hz), 100 MHz) δ 54.2, 65.9, 129.1, 130.1, 130.3, 133.6 (t, JC,F = 27.5
3.61 (tt, 3H, J = 4.8, 1.6 Hz), 7.07–7.16 (m, 3H); 19F NMR (CDCl3, Hz), 136.0; HRMS (ESI) Calcd for C15H12ClF9N2O [M+H]+:
376 MHz) δ(ppm) ‐81.14 (t, J = 9.78 Hz), ‐106.57 (t, J = 12.2 Hz), 443.0573, found 443.0572.
‐119.87 – ‐119.99 (m), ‐124.25 – ‐124.36 (m); 13C NMR (CDCl3,
100 MHz) δ 19.8, 54.1, 66.1, 126.4, 129.1, 129.7, 129.9, 135.8 nonafluoropentylidene)morpholin‐4‐amine
(E)‐N‐(1‐(3‐chlorophenyl)‐2,2,3,3,4,4,5,5,5‐
(
3j) Yellow liquid;
(t, JC,F = 27.5 Hz), 137.2, 138.6; HRMS (ESI) Calcd for 150.5 mg; IR (KBr) ν 2855, 1618, 1400, 1384, 1236, 1007 cm–1;
C17H17F9N2O[M+H]+: 437.1275, found 437.1272.
(E)‐N‐(1‐(4‐(tert‐butyl)phenyl)‐2,2,3,3,4,4,5,5,5‐
1H NMR (CDCl3, 400 MHz) δ(ppm) 3.02 (t, 4H, J = 4.8 Hz), 3.63
(t, 4H, J = 4.8 Hz), 7.25 (d, 1H, J = 7.3 Hz), 7.33 – 7.42(m, 3H);
nonafluoropentylidene)morpholin‐4‐amine
126.3mg; IR (KBr) ν 2969, 2854, 1577, 1439, 1236, 1133 cm–1; (t, J = 12.3Hz), ‐120.02 – ‐120.09 (m), ‐124.39 – ‐124.46 (m); 13
(
3e) Yellow liquid; 19F NMR (CDCl3, 376 MHz) δ(ppm) ‐81.17(t, J = 9.7Hz), ‐106.40
C
1H NMR (CDCl3, 400 MHz) δ(ppm) 1.33 (s, 9H), 2.99 (t, 4H, J = NMR (CDCl3, 100 MHz) δ 54.2, 65.9, 127.2, 129.0, 130.0, 132.7
4.8 Hz), 3.61 (t, 4H, J = 4.8 Hz), 7.28 (d, 2H, J = 8.0 Hz), 7.40 (d, (t, JC,F = 27.6 Hz), 133.5, 134.8; HRMS (ESI) Calcd for
2H, J = 6.8 Hz);19F NMR (CDCl3, 376 MHz) δ(ppm) ‐81.14 (t, J = C15H12ClF9N2O [M+H]+: 443.0573, found 443.0590.
9.8 Hz), ‐106.57 (t, J = 12.0 Hz), ‐119.93 – ‐120.00 (m), ‐124.29
(E)‐1‐(3,4‐dichlorophenyl)‐2,2,3,3,4,4,5,5,5‐nonafluoro‐N‐
3k) Yellow liquid; 162.2 mg; IR
– ‐124.34 (m); 13C NMR (CDCl3, 100 MHz) δ 31.1, 34.8, 54.2, morpholinopentan‐1‐imine
(
65.9, 125.6, 128.5, 128.6, 135.8 (t, JC,F = 27.0 Hz), 153.0; HRMS (KBr) ν 2976, 2857, 1578, 1425 cm–1; 1H NMR (CDCl3, 400 MHz)
(ESI) Calcd for C19H21F9N2O [M+H]+: 465.1588, found 465.1585. δ(ppm) 2.23 (s, 1H), 3.04 (t, 4H, J = 4.8 Hz), 3.65 (tt, 4H, J = 4.8,
(E)‐N‐(2,2,3,3,4,4,5,5,5‐nonafluoro‐1‐(4‐
methoxyphenyl)pentylidene)morpholin‐4‐amine (3f)
1.8 Hz), 7.22 (dd, 1H, J = 8.3, 1.9 Hz),7.48 (d, 1H, J = 1.6 Hz),
7.50 (d, 1H, J = 8.3 Hz); 19F NMR (CDCl3, 376 MHz) δ(ppm) ‐
Yellow liquid; 101.6 mg; IR (KBr) ν 2969, 2580, 1607, 1576, 81.12 (t, J = 10.5 Hz),‐106.40 (t, J = 12.0 Hz), ‐120.03 – ‐120.16
1510, 1444 cm–1; 1H NMR (CDCl3, 400 MHz) δ(ppm) 2.99 (t, 4H, (m), ‐124.40 – ‐124.52 (m); 13C NMR (CDCl3, 100 MHz) δ 54.2,
J = 4.6 Hz), 3.62 (t, 4H, J = 4.8 Hz), 6.92 (dd, 2H, J = 7.2, 2.8 Hz), 65.9, 128.4, 130.8, 131.4 (t, JC,F = 27.5 Hz), 131.5, 133.3, 134.4;
7.30 (d, 2H, J = 8.8 Hz); 19F NMR (CDCl3, 376 MHz) δ(ppm) ‐ HRMS (ESI) Calcd for C15H11Cl2F9N2O [M+H]+: 477.0183, found
81.15(t, J = 9.6 Hz), ‐176.96 (t, J = 12.2 Hz), ‐120.06 – ‐120.13 477.0185.
(m), ‐124.41 – ‐124.48 (m); 13C NMR (CDCl3, 100 MHz) δ54.1,
55.2, 66.0, 114.1, 123.6, 130.2, 136.0 (t, JC,F = 26.5 Hz), 160.4; (morpholinoimino)pentyl)benzonitrile
(E)‐4‐(2,2,3,3,4,4,5,5,5‐nonafluoro‐1‐
(3l)
HRMS (ESI) Calcd for C16H15F9N2O2 [M+H]+: 439.1068, found Yellow liquid; 156.0 mg; IR (KBr) ν2972, 2858, 2232, 1608,
439.1065.
1454, 1236, 1118, 1004 cm–1; 1H NMR (CDCl3, 400 MHz) δ(ppm)
3.01 (t, 4H, J = 4.8 Hz), 3.63 (t, 4H, J = 4.8 Hz), 7.51 (d, 2H, J =
3g) Yellow 8.0 Hz), 7.73 (d, 2H, J = 8.3 Hz); 19F NMR (CDCl3, 376 MHz)
(E)‐N‐(2,2,3,3,4,4,5,5,5‐nonafluoro‐1‐(2‐
methoxyphenyl)pentylidene)morpholin‐4‐amine
(
liquid; 99.3 mg; IR (KBr) ν 2970, 2847, 1638, 1618, 1491, 1400, δ(ppm) ‐81.12(t, J = 9.7Hz), ‐106.26 (t, J = 12.6Hz), ‐120.09– ‐
6 | Org. Biomol. Chem., 2017, 00, 1‐3
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ARTICLE
120.16(m), ‐124.47– ‐124.55(m); 13C NMR (CDCl3, 100 MHz) δ 139.3 (t, JC,F = 15.0 Hz), 141.9 (t, JC,F = 15.0 Hz), 150.0 (q, JC,F
=
54.3, 65.8, 113.8, 117.8, 130.0, 131.7 (t, JC,F = 27.8 Hz), 132.4, 4.3 Hz), 152.6 (q, JC,F = 4.0 Hz); HRMS (ESI) Calcd for
136.6; HRMS (ESI) Calcd for C16H12F9N3O [M+H]+: 434.0915, C15H10F12N2O [M+H]+: 463.0680, found 463.0688.
found 434.0916.
(E)‐N‐(2,2,3,3,4,4,5,5,5‐nonafluoro‐1‐(4‐
(trifluoromethyl)phenyl)pentylidene)morpholin‐4‐amine
(E)‐N‐(1‐(2,3‐dihydrobenzofuran‐5‐yl)‐2,2,3,3,4,4,5,5,5‐
nonafluoropentylidene)morpholin‐4‐amine 3r) Yellow liquid;
81.1 mg; IR (KBr) ν 2977, 2852, 1577, 1442 cm–1; 1H NMR
(
(
3m)
Yellow liquid; 160.0 mg; IR (KBr) ν 3126, 2858, 1638, 1618, (CDCl3, 400 MHz) δ(ppm) 3.01 (t, 4H, J = 4.8 Hz), 3.24 (t, 2H, J =
1400, 1327, 1237, 1133 cm–1; 1H NMR (CDCl3, 400 MHz) δ(ppm) 8.8 Hz), 3.60 (tt, 4H, J = 4.8, 1.6 Hz), 4.62 (t, 2H, J = 9.0 Hz),
3.01 (t, 4H, J = 4.8 Hz), 3.63 (t, 4H, J = 5.0 Hz), 7.50 (d, 2H, J = 6.79 (d, 1H, J = 8.4 Hz), 7.12 (d, 1H, J = 8.0 Hz), 7.19 (s); 19F
8.1 Hz), 7.69(d, 2H, J = 8.1 Hz); 19F NMR (CDCl3, 376 MHz) NMR (CDCl3, 376 MHz) δ(ppm) ‐81.14(t, J = 10.0 Hz), ‐106.73 (t,
δ(ppm) ‐62.73 – ‐63.27 (m), ‐81.08 (dd, J = 13.9, 6.3Hz), ‐ J = 12.2 Hz), ‐119.90– ‐119.98 (m), ‐124.28– ‐124.38 (m); 13C
106.35 (t, J = 12.4Hz), ‐119.69 – ‐120.59 (m), ‐124.11 – ‐125.03 NMR (CDCl3, 100 MHz) δ 29.4, 54.1, 66.0, 71.5, 109.6, 123.3,
(m); 13C NMR (CDCl3, 100 MHz) δ 54.3, 65.9, 125.71, 125.74, 125.4, 127.7, 129.2, 136.3 (t, JC,F = 27.0 Hz), 161.2; HRMS (ESI)
129.6, 135.6; HRMS (ESI) Calcd for C16H12F12N2O [M+H]+: Calcd for C17H15F9N2O2 [M+H]+: 451.1068, found 451.1059.
477.0836, found 477.0854.
(E)‐N‐(1‐(3‐bromophenyl)‐2,2,3,3,4,4,5,5,5‐
nonafluoropentylidene)morpholin‐4‐amine
159.8mg; IR (KBr) ν 1576, 1425 cm–1; 1H NMR (CDCl3, 400 MHz) δ(ppm) 2.93 (t, 4H, J = 4.8 Hz), 3.58 (t, 4H, J = 4.8 Hz), 7.47 (dd,
δ(ppm) 3.02 (t, 4H, J = 4.8 Hz), 3.63 (t, 4H, J = 4.8 Hz), 7.27 – 1H, J = 8.8, 0.8 Hz),7.52 – 7.58 (m, 2H), 7.84 –7.88 (m, 4H); 19
(E)‐N‐(2,2,3,3,4,4,5,5,5‐nonafluoro‐1‐(naphthalen‐2‐
yl)pentylidene)morpholin‐4‐amine 3s‐( ) Yellow liquid; 74.2
(
3n): Yellow liquid; mg; IR (KBr) ν 2977, 1577, 1430 cm–1; 1H NMR (CDCl3, 400 MHz)
(
E)
F
7.30 (m, 2H), 7.53 – 7.58 (m, 2H); 19F NMR (CDCl3, 376 MHz) NMR (CDCl3, 376 MHz) δ(ppm) ‐81.13 (t, J= 9.8Hz), ‐106.34 (t,
δ(ppm) ‐81.11 (t, J = 10.0 Hz), ‐106.33 (t, J = 12.3 Hz), ‐120.01 – J= 12.4Hz), ‐119.90– ‐119.95 (m), ‐124.30 – ‐124.36 (m); 13C
‐120.05 (m), ‐124.35 – ‐124.41 (m), 133.0, 133.9; 13C NMR NMR (CDCl3, 100 MHz) δ 54.3, 66.0, 125.7, 126.9, 127.5, 127.8,
(CDCl3, 100 MHz) δ 54.4, 66.0, 122.9, 127.8, 130.33, 130.36, 128.47, 128.48, 128.8, 129.1, 132.8, 133.4;HRMS (ESI) Calcd
132.0, 132.8 (t, JC,F = 28.0Hz), 133.9; HRMS (ESI) Calcd for for C19H15F9N2O[M+H]+: 459.1119, found 459.1124.
C15H12BrF9N2O[M+H]+ : 487.0068, found 487.0073.
(E)‐N‐(1‐(2‐bromophenyl)‐2,2,3,3,4,4,5,5,5‐
(Z)‐N‐(2,2,3,3,4,4,5,5,5‐nonafluoro‐1‐(naphthalen‐2‐
yl)pentylidene)morpholin‐4‐amine 3s‐(
(
Z))
nonafluoropentylidene)morpholin‐4‐amine(E:Z>7:1)
(
3o
)
Yellow liquid; 44.5 mg; IR (KBr) ν 2965, 2854, 1637, 1618, 1510,
Yellow liquid; 161.7 mg; IR (KBr) ν 3127, 2857, 1617, 1400, 1452, 1238, 1059, 1010 cm–1; 1H NMR (CDCl3, 400 MHz) δ(ppm)
1
1235 cm–1; H NMR (CDCl3, 400 MHz) δ(ppm) 3.03 – 3.11 (m, 3.25 (t, 4H, J = 5.0 Hz), 3.90 (tt, 4H, J = 4.8, 1.6 Hz),7.47 – 7.56
4H), 3.64 (t, 4H, J = 4.6 Hz), 7.26 – 7.37 (m, 3H), 7.62(d, 1H, J = (m, 2H), 7.83 (dd, 1H, J=8.0, 1.6 Hz), 7.94 (d, 1H, J= 8.8 Hz),
8.0 Hz); 19F NMR (CDCl3, 376 MHz) δ(ppm) ‐81.06 (t, J = 10.1 8.00 (t, 1H, J= 5.0 Hz), 8.22 (t, 2H, J= 9.2Hz); 19F NMR (CDCl3,
Hz),‐103.77 (dt, J = 280.5, 12.9 Hz), ‐107.03 (dt, J = 280.8, 12.8 376 MHz) δ(ppm) ‐80.71 –‐80.78 (m), ‐94.86 (s), ‐120.20 (d,
Hz), ‐119.85– ‐120.00 (m), ‐124.16– ‐124.24 (m); 13C NMR J=7.1Hz), ‐125.72 – ‐125.81 (m); 13C NMR (CDCl3, 100 MHz) δ
(CDCl3, 100 MHz) δ53.4, 66.3, 124.6, 127.3, 131.2, 131.4, 132.9, 51.6, 66.4, 124.8, 126.2, 127.6, 128.8, 132.7, 133.8; HRMS (ESI)
133.8; HRMS (ESI) Calcd for C15H12BrF9N2O [M+H]+: 487.0068, Calcd for C19H15F9N2O [M+H]+: 459.1119, found 459.1131.
found 487.0078.
(E)‐2,2,3,3,4,4,5,5,5‐nonafluoro‐N‐(4‐methylpiperazin‐1‐yl)‐
(E)‐N‐(2,2,3,3,4,4,5,5,5‐nonafluoro‐1‐(2‐
fluorophenyl)pentylidene)morpholin‐4‐amine
1‐phenylpentan‐1‐imine (3t) Yellow liquid; 87.6 mg; IR (KBr) ν
(
3p): Yellow 2943, 1638, 1573, 1446 cm–1; 2.23 (s, 1H), 2.33 (t, 4H, J = 5.2
liquid; 144.9 mg; IR (KBr) ν 2933, 1575, 1444 cm–1; H NMR Hz), 3.05 (t, 4H, J = 5.0 Hz), 7.33 – 7.36 (m, 2H), 7.38 – 7.42 (m,
(CDCl3, 400 MHz) δ(ppm) 3.08 (t, 4H, J = 4.8 Hz), 3.64 (t, 4H, J = 3H); 19F NMR (CDCl3, 376 MHz) δ(ppm) ‐81.12 (t, J = 9.78 Hz), ‐
5.0 Hz), 7.13 (t, 1H, J = 8.6Hz), 7.19 (td, 1H, J = 7.6, 0.8Hz), 7.29 106.29 (t, J = 12.0 Hz), ‐119.94 – ‐120.06 (m), ‐124.34 – ‐124.37
(t, 1H, J = 6.4Hz),7.41–7.46 (m, 1H); 19F NMR (CDCl3, 376 MHz) (m); 13C NMR (CDCl3, 100 MHz) δ 45.7, 53.3, 53.9, 128.6, 129.0,
δ(ppm) ‐81.12 (t, J=10.5 Hz), ‐109.78 (s), ‐120.52 (s), ‐124.48 – 129.6, 132.1, 133.6 (t, J = 27.5 Hz); HRMS (ESI) Calcd for
‐124.56 (m); 13C NMR (CDCl3, 100 MHz) δ 53.5, 66.1, 115.9 (d, C16H16F9N3[M+H]+: 422.1279, found 422.1282.
1
JC,F = 21.0 Hz), 119.9 (d, JC,F = 18.0 Hz), 124.3 (d, JC,F = 3.0 Hz),
126.4 (t, JC,F = 29.0 Hz), 131.0 (d, JC,F = 2.0 Hz), 132.0 (d, JC,F
(E)‐N‐(2,2,3,3,4,4,4‐heptafluoro‐1‐
phenylbutylidene)morpholin‐4‐amine
8.0 Hz), 160.0 (d, JC,F = 248.0 Hz); HRMS (ESI) Calcd for 108.9 mg; IR (KBr) ν 2976, 2856, 1577, 1444 cm–1; H NMR
=
(
3u)
Yellow liquid;
1
C15H12F10N2O [M+H]+: 427.0868, found 427.0871.
(E)‐N‐(1‐(3,4‐difluorophenyl)‐2,2,3,3,4,4,5,5,5‐
(CDCl3, 400 MHz) δ(ppm) 2.98 (t, 4H, J = 4.8 Hz), 3.60 (tt, 4H, J
= 5.0, 1.8 Hz), 7.34 – 7.36 (m, 2H), 7.40– 7.42 (m, 3H); 19F NMR
nonafluoropentylidene)morpholin‐4‐amine (3q) Yellow liquid; (CDCl3, 376 MHz) δ(ppm) ‐79.58(t, J =10.0Hz), ‐107.43 (q, J
160.8 mg; IR (KBr) ν 2924, 2858, 1616, 1577, 1530, 1432 cm–1; =9.4Hz), ‐123.82(s); 13C NMR (CDCl3, 100 MHz) δ 54.2, 66.0,
1H NMR (CDCl3, 400 MHz) δ(ppm) 3.05 (t, 4H, J = 5.0 Hz), 3.67 128.7, 128.8, 128.9, 129.8, 130.9, 131.8; HRMS (ESI) Calcd for
(td, 4H, J = 4.8, 3.0 Hz), 7.04 (t, 2H, J = 6.8 Hz);19F NMR (CDCl3, C14H13F7N2O [M+H]+: 359.0994, found 359.0997.
376 MHz) δ(ppm) ‐81.17 (t, J = 9.8 Hz), ‐106.45 (t, J = 12.2 Hz), ‐
(E)‐N‐(2,3,3,3‐tetrafluoro‐1‐phenyl‐2‐
120.17 – ‐120.24 (m), ‐124.50 – ‐124.60 (m), ‐131.99 – ‐132.08 (trifluoromethyl)propylidene)morpholin‐4‐amine (3v) Yellow
(m), ‐156.48 – ‐126.62 (m); 13C NMR (CDCl3, 100 MHz) δ 54.2, liquid; 96.01mg; IR (KBr) ν2997, 2934, 1577, 1426, 1134 cm–1;
65.8,113.8 (q, JC,F = 7.3 Hz), 127.3 (m), 130.2 (t, JC,F = 28.0 Hz), 1H NMR (CDCl3, 400 MHz) δ(ppm)2.93 (td, 4H, J = 4.8, 3.0 Hz),
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Organic Biomolecular Chemistry
3.58 (td, 4H, J = 4.8, 3.0 Hz), 7.28 – 7.31 (m, 2H), 7.39–7.40 (m, 1572, 1416, 1133 cm–1; 1H NMR (CDCl3, 400 MHz) δ(ppm) 6.95
3H); 19F NMR (CDCl3, 376 MHz) δ(ppm) ‐74.32(d, J=7.1Hz), ‐ (tt, 1H, J = 7.8, 1.2 Hz), 7.02 (dd, 2H, J = 8.4, 0.8 Hz),7.24 – 7.28
176.97 (d, J=7.1Hz); 13C NMR (CDCl3, 100 MHz) δ 54.4, 65.7, (m, 2H), 7.36 – 7.38 (m, 2H),7.54 – 7.59 (m, 3H), 7.83 (s, 1H);
128.66, 128.73, 128.75, 131.9, 136.0 (t, JC,F = 60.5 Hz);HRMS 19F NMR (CDCl3, 376 MHz) δ(ppm) ‐80.96 – ‐81.02 (m), ‐107.67
(ESI) Calcd for C14H13F7N2O [M+H]+: 359.0994, found 359.0996. (t, J = 12.8 Hz), ‐120.68 – ‐120.76 (m), ‐124.99 – ‐125.06 (m);
(E)‐N‐(2,2,3,3,4,4,5,5,6,6,6‐undecafluoro‐1‐
phenylhexylidene)morpholin‐4‐amine 3w
13C NMR (CDCl3, 100 MHz) δ 113.4, 113.6, 122.0, 127.2, 129.2,
Yellow liquid; 129.3, 129.4, 129.8, 130.5, 130.9, 131.6 (t, JC,F = 27.5), 142.8;
133.8 mg; IR (KBr) ν 2857, 1577, 1446 cm–1; H NMR (CDCl3, HRMS (ESI) Calcd for C17H11F9N2[M+H]+: 415.0857, found
(
)
1
400 MHz) δ(ppm) 2.98 (t, 4H, J = 4.8 Hz), 3.60 (td, 4H, J = 4.8, 415.0862.
3.2 Hz), 7.34 –7.37 (m, 2H), 7.39 – 7.41 (m, 3H); 19F NMR
(CDCl3, 376 MHz) δ(ppm) ‐80.82 (t, J = 9.8 Hz), ‐106.60 (t, J = amine (E:Z=13:1)
(E)‐N‐(2,2,2‐trifluoro‐1‐phenylethylidene)morpholin‐4‐
7a) Yellow liquid; 116.2 mg; IR (KBr) ν 2969,
(
13.3Hz), ‐119.46, ‐121.25 – ‐121.35 (m), ‐126.28 – ‐126.35 (m); 2921, 2854, 1577, 1446 cm–1; 1H NMR (CDCl3, 400 MHz) δ(ppm)
13C NMR (CDCl3, 100 MHz) δ 54.2, 66.0, 128.7, 128.9, 129.7, 2.97 – 3.00 (m, 4H), 3.60 – 3.63 (m, 4H), 7.42 (s, 5H); 19F NMR
131.9, 135.3 (t, JC,F = 27.0 Hz); HRMS (ESI) Calcd for (CDCl3, 376 MHz) δ(ppm) ‐66.75 (s); 13C NMR (CDCl3, 100 MHz)
C16H13F11N2O[M+H]+: 459.0930, found 459.0930.
(E)‐N‐(2,2,3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10‐
δ54.2, 66.1, 128.4, 128.8, 129.8, 131.6, 136.2 (q, JC,F = 33.0 Hz);
HRMS (ESI) Calcd for C12H14F3N2O [M+H]+ : 259.1058, found
259.1057.
nonadecafluoro‐1‐phenyldecylidene)morpholin‐4‐amine
(3x)
o
Yellow solid, 114.4 mg; M.P. 39–41 C; IR (KBr) ν 2976, 2860,
(E)‐4‐(2,2,2‐trifluoro‐1‐
1638, 1618, 1365, 1266, 1145, 1115, 995 cm–1; 1H NMR (CDCl3, (morpholinoimino)ethyl)benzonitrile(E:Z=13:1)
(7b) Yellow
400 MHz) δ(ppm) 2.98 (t, 4H, J = 4.8 Hz), 3.60 (t, 4H, J = 5.0 Hz), Solid; 134.7 mg; M.p. 130‐132 oC; IR (KBr) ν 2843, 2233, 1617,
7.34 – 7.42 (m, 5H); 19F NMR (CDCl3, 376 MHz) δ(ppm) ‐80.81 1180, 1117, 1007 cm–1; 1H NMR (CDCl3, 400 MHz) δ(ppm) 3.01
(t, J = 10.0 Hz), ‐106.55 (t, J = 14.0 Hz), ‐119.2, ‐120.3, 121.8, (t, 4H, J = 4.8 Hz), 3.64 (t, 4H, J = 5.0 Hz), 7.68 (d, 2H, J = 8.0 Hz),
122.8, ‐126.03 – ‐126.26 (m); 13C NMR (CDCl3, 100 MHz) δ 54.0, 7.73 (d, 2H, J = 8.4 Hz); 19F NMR (CDCl3, 376 MHz) δ(ppm) ‐
66.0, 128.7, 128.9, 129.7, 131.9, 135.3 (t, JC,F = 26.5 Hz); HRMS 66.22 (s); 13C NMR (CDCl3, 100 MHz) δ55.3, 66.0, 113.8, 117.8,
(ESI) Calcd for C20H13F19N2O [M+H]+: 609.0835, found 609.0844. 129.4, 132.6, 136.3; HRMS (ESI) Calcd for C13H13F3N3O [M+H]+ :
(E)‐1‐cyclopropyl‐2,2,3,3,4,4,5,5,5‐nonafluoro‐N‐
morpholinopentan‐1‐imine 4a) Yellow liquid; 96.8 mg; IR (KBr)
284.1011, found 284.1004.
(E)‐N‐(2,2,2‐trifluoro‐1‐(4‐
(
ν 3003, 2976, 2931, 1576, 1427 cm–1; 1H NMR (CDCl3, 400 MHz) methoxyphenyl)ethylidene)morpholin‐4‐amine(E:Z=40:3)
(7c)
δ(ppm) 0.94 – 1.00 (m, 2H), 1.09 – 1.13 (m, 2H), 1.65 (dq, 1H, J Yellow liquid; 102.7 mg; IR (KBr) ν 2966, 2851, 1607, 1510,
= 8.6, 5.8 Hz), 3.19 (tt, 4H, J = 4.8, 2.0 Hz), 3.81 (tt, 4H, J = 4.8, 1176, 1117cm–1; 1H NMR (CDCl3, 400 MHz) δ(ppm) 2.98 (t, 4H,
1.6 Hz); 19F NMR (CDCl3, 376 MHz) δ(ppm) ‐81.16 (t, J = 10.2 J = 4.8 Hz), 3.64 (tt, 4H, J = 5.0, 2.0 Hz), 3.84 (s, 3H), 6.93 (dt,
Hz),‐108.52 (t, J= 12.2 Hz), ‐120.41 – ‐120.53 (m), ‐123.92 – ‐ 2H, J = 8.8, 1.2 Hz), 7.39 (d, 2H, J = 8.4 Hz); 19F NMR (CDCl3, 376
124.00 (m); 13C NMR (CDCl3, 100 MHz) δ 7.8, 10.8, 54.9, 66.1, MHz) δ(ppm) ‐66.80 (s); 13C NMR (CDCl3, 100 MHz) δ 54.1, 55.3,
147.4 (t, JC,F = 25.5 Hz); HRMS (ESI) Calcd for C12H13F9N2O 66.1, 114.2, 123.2, 129.8, 132.0, 137.1 (q, JC,F = 32.6 Hz), 160.5;
[M+H]+: 373.0962, found 373.0964.
(E)‐1‐cyclopropyl‐2,2,3,3,4,4,5,5,6,6,7,7,7‐tridecafluoro‐N‐
HRMS (ESI) Calcd for C13H16F3N2O2 [M+H]+ : 289.1164, found
289.1155.
morpholinoheptan‐1‐imine
(
4b) Yellow liquid; 86.9 mg; IR (KBr)
(E)‐N‐(1‐(2‐bromophenyl)‐2,2,2‐
ν 2964, 2932, 2856, 1458 cm–1; 1H NMR (CDCl3, 400 MHz) trifluoroethylidene)morpholin‐4‐amine
(7d) Yellow solid;
o
δ(ppm) 0.94 – 1.00 (m, 2H), 1.09 – 1.13 (m, 2H), 1.65 (dq, 1H, J 103.0 mg; M.p. 78 ‐79 C; IR (KBr) ν 2919, 2851, 1604, 1465,
= 8.6, 5.8 Hz), 3.19 (tt, 4H, J = 4.8, 2.0 Hz), 3.81 (tt, 4H, J = 4.8, 977, 737 cm–1; H NMR (CDCl3, 400 MHz) δ(ppm) 3.01 – 3.18
1
1.6 Hz); 19F NMR (CDCl3, 376 MHz) δ(ppm) ‐80.31 – ‐81.33 (m), (m, 4H),3.67 (td, 1H, J = 4.4, 2.2 Hz), 7.29 – 7.40 (m, 3H), 7.65
‐108.36 (t, J = 13.3 Hz), ‐119.54 – ‐119.88 (m), ‐120.12 (s), ‐ (dd, 1H, J = 7.9, 0.8 Hz); 19F NMR (CDCl3, 376 MHz) δ(ppm) ‐
122.71 – ‐123.03 (m), ‐125.88 – ‐126.16 (m) ; 13C NMR (CDCl3, 66.08(s); 13C NMR (CDCl3, 100 MHz) δ 53.5, 66.4, 120.0, 124.2,
100 MHz) δ 7.9, 10.9, 55.0, 66.1; HRMS (ESI) Calcd for 127.4, 131.2, 132.9; HRMS (ESI) Calcd for C12H12BrF3N2O
C14H13F13N2O [M+H]+: 473.0899, found 473.0898.
[M+H]+: 337.0163, found 337.0158.
(E)‐N‐(5,5,6,6,7,7,8,8,8‐nonafluorooctan‐4‐
(E)‐N‐(1‐(3,4‐dichlorophenyl)‐2,2,2‐
ylidene)morpholin‐4‐amine (5) Yellow liquid; 109.3 mg; IR trifluoroethylidene)morpholin‐4‐amine (8) Yellow solid; 88.9
(KBr) ν 2970, 2935, 2845, 1577, 1425, 1132 cm–1; 1H NMR mg; M.p. 180 ‐181 oC; IR (KBr) ν2964, 2925, 2855, 1725, 1608,
(CDCl3, 400 MHz) δ(ppm) 0.98 (t, 3H, J = 7.4 Hz), 1.59 – 1.69 (m, 1470, 814, 732cm–1; 1H NMR (CDCl3, 400 MHz) δ(ppm) 2.98 (t,
2H), 2.46 (tt, 2H, J = 8.0, 2.2 Hz), 2.93 (tt, 4H, J = 4.8, 1.8 Hz), 4H, J = 4.4 Hz), 3.64 (t, 4H, J = 4.4 Hz), 7.29 (d, 1H, J = 8.4 Hz),
3.82 (tt, 4H, J = 4.8, 2.2 Hz); 19F NMR (CDCl3, 376 MHz) δ(ppm) 7.52 (d, 1H, J = 8.2 Hz), 7.55 (s, 1H); 19F NMR (CDCl3, 376 MHz)
‐81.14 (d, J = 7.9 Hz), ‐111.63 (t, J = 11.8 Hz), ‐121.15(d, J = 4.1 δ(ppm) ‐66.51(s); 13C NMR (CDCl3, 100 MHz) δ 54.3, 66.0,
Hz), ‐124.50 (d, J = 11.6 Hz); 13C NMR (CDCl3, 100 MHz) δ 14.3, 127.9, 130.4, 131.0, 133.44; HRMS (ESI) Calcd for
19.3, 30.0, 55.0, 66.0, 154.5 (t, JC,F = 25.0 Hz); HRMS (ESI) Calcd C12H11Cl2F3N2O [M+H]+: 327.0279, found 327.0273.
for C12H15F9N2O [M+H]+: 375.1119, found 375.1118.
(E)‐1‐(2,2,3,3,4,4,5,5,5‐nonafluoro‐1‐phenylpentylidene)‐2‐ Yellow liquid; 41 mg; IR (KBr) ν 2923, 2852, 1740, 1632, 1609,
phenylhydrazine
): Yellow liquid; 111.0 mg; IR (KBr) ν 1639, 1458, 1237, 1028 cm–1; 1H NMR (CDCl3, 400 MHz) δ(ppm) 2.46
2,2,3,3,4,4,5,5,5‐nonafluoro‐1‐(p‐tolyl)pentan‐1‐one
(9)
(
6
8 | Org. Biomol. Chem., 2017, 00, 1‐3
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DOI: 10.1039/C7OB01144J
Organic Biomolecular Chemistry
ARTICLE
(s, 3H), 7.33 (d, 2H, J = 8.0 Hz), 7.97 (d, 2H, J =8.0 Hz); 19F NMR
(CDCl3, 376 MHz) δ(ppm) ‐80.91 (t, J = 10.1 Hz), ‐112.87 (t, J =
12.3 Hz), ‐121.76 – ‐122.28 (m), ‐125.07 – ‐125.59 (m); 13C
NMR (CDCl3, 100 MHz) δ21.9, 129.0, 129.8, 130.1, 147.0;
HRMS (ESI) Calcd for C12H7F9O [M+H]+: 339.0431, found
339.0429.
11 For reviews on visible light induced photoredox reactions of
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Acknowledgements
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,
This work was supported by the National Natural Science
Foundation of China (NSFC 21202101), Zhejiang Provincial
Natural Science Foundation (LY16B020006) and China
Postdoctoral Science Foundation (2015M581919).
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1 are
1
However, similar imines such as benzalaniline (half‐wave
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