A Novel Route to 2-Arylquinolines: Reductive Cleavage of 2′-Nitroaryl-Δ2 -isoxazolines

Article abstract of DOI:10.1055/s-0036-1588751

A novel synthetic route for the synthesis of quinolines starting from Δ ² -isoxazolines under reductive conditions is reported. The reductive cyclization to quinolines is achieved under both metal and metal-free conditions. The reaction proceeds via an intramolecular N-H?O hydrogen bond intermediate, accelerating the reductive cleavage 1000-fold (DFT calculations) in comparison with non-hydrogen bonded system.

Full text of DOI:10.1055/s-0036-1588751

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© Georg Thieme Verlag Stuttgart · New York
2017, 28, A–E
letter
A
P. Kamath et al.
Letter
Synlett
A Novel Route to 2-Arylquinolines: Reductive Cleavage of
2′-Nitroaryl-∆2-isoxazolines
Prashantha Kamatha
Russell C. Vinerb
Fe/H+, EtOH, H2O
Stephen C. Smithb
Mukul Lal*a
H
O2N
H
N
O
N
O
N
R
N
a Syngenta Biosciences Pvt. Ltd., Santa Monica Works,
Corlim, Ilhas, Goa-403110, India
R
13 examples
R = aryl,
R
b Syngenta Jealott’s Hill International Research Centre,
Bracknell, Berkshire, RG42 6EY, UK
heteroaryl
Na2S2O4 in DMSO
up to 82% yield
mukul.lal@syngenta.com
One-pot conversion
No isolation of intermediate
The article is dedicated to Prof. Dr. Michael Schmittel on
the occasion of his 60th birthday.
Received: 10.01.2017
Accepted after revision: 22.02.2017
Published online: 20.03.2017
To test the approach, conventional nitro group reducing
agents such as iron, zinc, nickel(II) acetate and tin(II) chlo-
ride with or without additives were tested on the model
substrate 1a (Scheme 1).24 Reductive cyclization when car-
ried out with four equivalents of iron–ammonium chloride
(1:1) in an ethanol–water mixture as the solvent did not
yield the desired product at room temperature. However,
when the reaction mixture was warmed to 50 °C, a clean
formation of 2a was noted. The formation of the desired
product 3a was achieved with a further rise in the reaction
temperature to 80 °C, albeit with a low conversion of 10%.
When the iron–ammonium chloride quantity was doubled,
a complete conversion of 1a into 3a was observed with a
yield of 74% of the desired product (Table 1, see the Sup-
porting Information for optimization details).
DOI: 10.1055/s-0036-1588751; Art ID: st-2017-d0026-l
Abstract A novel synthetic route for the synthesis of quinolines start-
ing from Δ2-isoxazolines under reductive conditions is reported. The
reductive cyclization to quinolines is achieved under both metal and
metal-free conditions. The reaction proceeds via an intramolecular
N–H···O hydrogen bond intermediate, accelerating the reductive cleav-
age 1000-fold (DFT calculations) in comparison with non-hydrogen
bonded system.
Key words heterocycles, cyclization, reduction, isoxazoline, quino-
lines
Δ2-Isoxazolines and quinolines constitute classes of het-
erocycles having diverse applications, including agrochemi-
cals, drugs, dyes, rubber chemicals, flavoring agents, and in
materials science.1–12 Δ2-Isoxazolines can be accessed by a
variety of methods, notably the [3+2] cycloaddition be-
tween nitrile oxides and unsaturated systems.13,14 Their
ease of synthesis, stability and ability to undergo an array
of further transformations render them valuable interme-
diates in organic synthesis15,16 and prompted us to investi-
gate the potential application of these substrates to access
quinolines via a reductive O–N bond cleavage.17,18 It was hy-
pothesized that a suitably placed nitro group in the sub-
strates would not only be reduced to an amine but also ac-
celerate the cyclization into a quinoline with concomitant
O–N bond cleavage (Figure 1).19
O2N
R
N
O
N
R
NH OH NH2
R
N
R
OH
Figure 1 Conversion of 2′-nitroaryl-∆2-isoxazolines into 2-arylquino-
lines
To assess the postulated route, a range of 2′-nitroaryl-
Δ2-isoxazolines 1a–m were synthesized in good to excellent
yields (70–90%) via the [3+2] cycloaddition route using the
corresponding nitrile oxide and the requisite styrene (Table
1).20–23
The reductive cyclization, when carried out with iron as
reductant in acetic acid, resulted in complete conversion of
the starting material within one hour without compromis-
ing the yield.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–E

B
P. Kamath et al.
Letter
Synlett
N
O
N
O
Reductant,
Solvent
+
N
Δ
NO2
NH2
1a
2a
3a
Scheme 1 Conversion of 1a into 2a and 3a in the presence of various reducing agents
Replacement of the reductant with zinc in acetic acid or
tin(II) chloride in ethanol gave similar conversions of 1a
into 3a. Reductive cyclization with freshly prepared nickel
boride gave 2a as the sole product, despite attempts to force
the reaction further by increasing the concentration of the
reductant or the reaction temperature.
In order to test the generality of the reaction, a variety
of 3,5-disubstituted Δ2-isoxazoline derivatives25 1a–m were
subjected to iron (8.0 equiv) and ammonium chloride (8.0
equiv) in a 1:1 ethanol–water mixture as the solvent at 80
°C (Table 1). Irrespective of the substitution pattern, a con-
sistently good yield of the corresponding quinoline 3 was
obtained (72–82% yield),26 suggesting little or no influence
of the substituent in position 3 of the isoxazolines on the
overall reaction outcome.
nitro group reductions with sodium dithionite is well docu-
mented, there is no precedent for the reductive cleavage of
an O–N bond in isoxazolines.29,30 To test this, 1a was initial-
ly treated with sodium dithionite (4.0 equiv) in ethanol as
the solvent at 80 °C. No conversion was observed, but this
appeared to be due to the heterogeneous reaction condi-
tions. To circumvent this, a 50% aqueous solution of ethanol
in water was used as the solvent. This resulted in complete
conversion of 1a into 2a. When the reaction was extended
by an additional 6 hours, 10% formation of 3a was observed.
The conversion was improved to 50% by further increasing
the reductant quantity from 4.0 to 6.0 equivalents.
Table 1 Substrate Scope for the Synthesis of Isoxazolines 1a and Quin-
olines 3b
While the methodology worked as anticipated, the for-
mation of 2a suggested that intramolecular N–H···O hydro-
gen bonding might exist and that it could influence the re-
ductive cyclization described in Scheme 1. To establish this,
solution studies of 2a, such as dilution and solvent-depen-
N
O
R
NO2
N
R1
NO2
1a–m
1
dence experiments, were performed using H NMR spec-
1-nitro-2-vinylbenzene
3a–m
troscopy. Interestingly, in 2a, a single peak was observed for
the NH2 protons, despite variations in the solvent polarity
from non-polar (toluene) to aprotic polar (DMSO).27 As an-
ticipated, a downfield shift in the 1H NMR for the NH2 pro-
tons was observed with an increasing solvent polarity pa-
rameter (EN/T) suggesting an enhanced interaction of the
amine protons with the solvent and thereby a weakening of
the intramolecular hydrogen bonding.
Entry
R
Yield (%) R1
of 1
Yield (%)
of 3c
a
b
c
d
e
f
C6H5
81
88
84
79
70
90
77
82
85
70
82
90
89
C6H5
74 (70)
80
4-BrC6H4
4-BrC6H4
4-Cl-2-FC6H3
4-MeOC6H4
2-thienyl
4-Cl-2-FC6H3
4-MeOC6H4
2-thienyl
80
80 (55)
77
A 1H NMR dilution experiment with 2a had no influence
on the NH2 protons over a concentration range of 0.210 M
to 0.002 M, demonstrating strong N–H···O type intramolec-
ular hydrogen bonding at room temperature. In contrast, a
dilution experiment with 2n, a para-substituted aryl amine
(control), showed a complete disappearance of NH2 protons
under similar concentrations.
Having established the presence of intramolecular N–
H···O hydrogen bonding in solution for intermediate 2a, it
was hypothesized that the reductive cyclization from 1a
into 3a could be carried out under milder conditions to take
advantage of potential activation and, additionally, develop
metal-free conditions for the reductive cyclization.
2-bromopyridyl
2-O2NC6H4
3-Me-4-t-BuO2CC6H3
2-Cl-5-O2NC6H3
3-pyridyl
2-bromopyridyl
2-H2NC6H4
78 (69)
72 (66)
82
g
h
i
3-Me-4-t-BuO2CC6H3
2-Cl-5-H2NC6H3
3-pyridyl
74
j
72 (65)
82
k
l
2-Br-4-ClC6H3
2,4,6-F3C6H2
4-FC6H4
2-Br-4-ClC6H3
2,4,6-F3C6H2
4-FC6H4
81 (83)
81 (76)
m
a Reaction conditions: 1-Nitro-2-vinylbenzene (1.10 mmol), oxime (1.00
mmol), NCS (1.10 mmol), Et3N (1.00 mmol) in DMF (3.0 mL).
b Reaction condition: Method 1: 1(1.00 mmol), Fe (8.00 mmol), EtOH (7.0
mL), NH4Cl (8.00 mmol) in H2O (7.0 mL) at 80 °C for 6 h. Method 2: 1 (1.00
mmol), Na2S2O4 6.00 mmol) in DMSO (7.0 mL) at 100 °C for 3–5 h.
c Yields in parentheses correspond to the yield of 3 using method 2.
Dithionite is a known reductant and forms the sulfur di-
oxide radical anion during the process of reduction, acting
as a source of electrons.28 While literature precedence for
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–E

C
P. Kamath et al.
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Synlett
Further examination of the literature indicated the for-
mation of N-substituted sulfamic acid type intermediates
during the reduction processes using dithionite.31 The for-
mation of such intermediates could impact the overall re-
duction process; therefore addition of base was anticipated
to circumvent this. Hence, addition of a base such as potas-
sium carbonate in equimolar concentration was attempted
and to our satisfaction led to complete conversion into the
desired product 3a.
Thus, the reduction of 1a was carried out in an ethanol–
water mixture (1:1) with sodium dithionite (6.0 equiv) and
potassium carbonate (6.0 equiv) resulting in the clean con-
version of 1a into 3a within 12 hours (70% yield).
placed (p-NH2), and 4a (Scheme 2) which was devoid of any
hydrogen bond donor group. In both cases starting material
was recovered (90–95%) with little decomposition, indicat-
ing the importance of the hydrogen bond for activating the
O–N bond toward reduction. Heating 2a in DMSO at elevat-
ed temperatures up to 130 °C without dithionite did not
lead to the formation of 3a, showing that dithionite was re-
quired for the reductive ring opening of the isoxazoline O–
N bond. To check the generality of the reaction, ∆2-isoxazo-
lines (1a, 1d, 1f, 1g, 1j, 1i and 1m) were treated under the
optimized conditions to give the desired substituted quino-
lines (3a, 3d, 3f, 3g, 3j, 3i and 3m) in reasonable yields (50–
70%).32
As previously stated, under certain reaction conditions
2a was converted cleanly into 3a, whereas under the same
conditions the p-amino compound 2n was unreactive. This
suggests that the o-amino group in 2a is facilitating the re-
ductive cleavage of the ∆2-isoxazoline ring. To gain further
insight we carried out DFT calculations (B3LYP/6-31G** lev-
el of theory) with full geometry optimization (see the Sup-
porting Information) of 2a as well as 2n (a molecule with a
p-amino group). Indeed, the optimized structure of 2a sug-
gests the existence of an intramolecular N–H···O hydrogen
bond. The o-amino group was found to stabilize the radical
anion by 17.2 kJ/mol (compared to a p-amino group) equat-
ing to an acceleration in the rate of reaction by a factor of
approximately 1000. This is consistent with the experimen-
tal observation that the o-amino group is required for the
reductive cleavage of the ∆2-isoxazoline ring.
O
N
HO
O
Na2S2O4
DMSO
R
R
2n: R = NH2
4a: R = H
2o: R = NH2
4b: R = H
Scheme 2 Control experiments with 2n and 4a using method 2
Furthermore, when the reaction solvent was switched
from the ethanol–water mixture to DMSO, the reaction
time decreased from 12 hours to 3 hours. Interestingly,
when the reductive cyclization of 1a was carried out with
sodium dithionite (6.0 equiv) in DMSO without potassium
carbonate, the quinoline product 3a was still formed with
similar efficacy as before, which could be due to the in-
creased availability and/or stability of the sulfur dioxide
radical anion in DMSO.32 Further control experiments were
performed with 2n (Scheme 2) as a model compound in
which the intermediate hydrogen bond donor is remotely
From the experimental observations and theoretical
calculations, a distinct mechanism appears to be operative
during the reductive cyclization of 2′-nitroaryl-Δ2-isoxazo-
lines into 2-arylquinolines, and is summarized in Scheme 3.
In the presence of a suitable reducing agent, the initial step
is the reduction of the o-nitro group in 1a into the amine
Intramolecular
Hydrogen
Bonded
N
N
H
O
N
O
H
N
O
NO2
NH2
Metal-Mediated
or Dithionite Reduction
Non-Hydrogen
Bonded Form
2a1
1a
2a
Hydrogen Bonded Pathway
Non-Hydrogen Bonded Pathway
+ e+ – e+
N–
C•
HN
H
O
HO
H
N
+ e+, 2 H+
H2N
N
Cyclisation
Elimination
O–N Bond
Cleavage
2a1-.
3a
– NH3, – H2O
2a2
Intramolecular
Hydrogen Bonded
Scheme 3 Proposed reaction mechanism for the reductive cyclization of 2′-nitroaryl-∆2-isoxazolines to 2-arylquinolines
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–E

D
P. Kamath et al.
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Synlett
intermediate 2a irrespective of the reducing agent used.
The amine intermediate 2a thus equilibrates to the favored
intramolecular hydrogen bonded form 2a1. The latter, in the
presence of a reducing agent, accepts a further electron to
form the corresponding radical anion 2a1- which can rapid-
ly lead to the formation of 3a via O–N bond cleavage
(Scheme 3). This could be the predominant pathway for the
isoxazoline derivatives of type 2a–m having an o-amino
group. However, isoxazolines devoid of an o-amino group
such as 2n and 4a might undergo non-hydrogen bonded O–
N bond cleavage under iron-mediated reducing conditions
to form β-hydroxy ketones.
In conclusion, the work demonstrates a novel heterocy-
cle–heterocycle interconversion methodology for accessing
quinolines from 2′-nitroaryl-Δ2-isoxazolines. The method-
ology has been exemplified under a variety of conditions,
including transition-metal reagents (iron, zinc and tin(II)
chloride) as well as metal-free conditions (sodium dithion-
ite, with or without potassium carbonate). A variety of 2-
arylquinolines were obtained in good yields (50–80%) using
this methodology. The ease of isolation of the product un-
der dithionite-mediated reducing conditions makes the
methodology attractive compared to traditional methods
involving transition metals. The confirmed presence of an
intramolecular H-bond to the isoxazoline in intermediate
2a appears to activate the O–N bond of Δ2-isoxazolines and
accelerates the rate of the reaction 1000-fold towards re-
ductive cyclization. The methodology also demonstrates
the first use of dithionite in the reductive ring opening of
isoxazolines. The methodology is being extended to the
synthesis of other heterocycles in our laboratory.
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Acknowledgment
(24) Kadam, H. K.; Tilve, S. G. RSC Advances 2015, 5, 83391.
(25) 2′-Nitroaryl-Δ2-isoxazoline Derivatives 1a–m: General Pro-
cedure
The authors would like to thank Syngenta Biosciences Pvt. Ltd. for
providing support in carrying out this work under the PhD program.
To a solution of the oxime (1.00 mmol, 1.0 equiv) in DMF (2.0
mL) at r.t. was added N-chlorosuccinimide (1.10 mmol, 1.10
equiv) and the mixture was stirred for 60 min. To the reaction
mixture was added the alkene in one portion (1.10 mmol, 1.1
equiv) followed by a solution of triethylamine (1.00 mmol, 1.00
equiv) in DMF (1.0 mL). After complete addition, the reaction
mixture was stirred at 23–25 °C until complete conversion of
the in situ formed chlorooxime intermediate (reaction was
monitored by TLC). After complete conversion, the reaction was
poured into cold water (30.0 mL) and stirred for 10 min. The
aqueous phase was extracted with ethyl acetate (3 × 20.0 mL),
the combined organic layers were washed with brine (20.0 mL),
dried over anhydrous sodium sulfate, filtered and concentrated
under reduced pressure to yield the crude product which was
purified by flash chromatography.
Supporting Information
Supporting Information for this article is available online at
http://dx.doi.org/10.1055/s-0036-1588751.
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References and Notes
(1) Pasteris, R. J.; Hanagan, M. A.; Bisaha, J. J.; Finkelstein, B. L.;
Hoffman, L. E.; Gregory, V.; Shepherd, C. P.; Andreassi, J. L.;
Sweigard, J. A.; Klyashchitsky, B. A.; Henry, Y. T.; Berger, A. ACS
Symp. Ser. 2015, 1204, 149.
(2) Zhang, Y.-b. Shijie Nongyao 2015, 37, 4.
(3) Kaur, K.; Kumar, V.; Sharma, A. K.; Gupta, G. K. Eur. J. Med. Chem.
2014, 77, 121.
3,5-Bis(2-nitrophenyl)-4,5-dihydroisoxazole (1g)
White solid; yield: 241 mg (77%); mp 120–121 °C. 1H NMR
(CDCl3, 400 MHz): δ = 8.18 (dd, J = 8.3, 1.3 Hz, 2 H), 8.07 (dd, J =
8.0, 1.3 Hz, 2 H), 7.91 (dd, J = 7.9, 1.4 Hz, 2 H), 7.69–7.80 (m, 4
(4) Imran, M.; Khan, S. A.; Siddiqui, N. Indian J. Pharm. Sci. 2004, 66,
377.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–E

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P. Kamath et al.
Letter
Synlett
H), 7.52–7.65 (m, 6 H), 6.42 (d, J = 6.3 Hz, 1 H), 6.39 (d, J = 6.3 Hz,
1 H), 4.04 (d, J = 6.0 Hz, 1 H), 3.27 (d, J = 6.3 Hz, 1 H), 3.22 (d, J =
6.3 Hz, 1 H). 13C NMR (CDCl3, 101 MHz): δ = 154.1, 145.4, 142.2,
136.3, 133.5, 132.6, 130.0, 129.9, 128.0, 127.0, 124.1, 124.0,
123.9, 78.7, 45.2. HRMS (ESI-TOF): m/z [M + H]+ calcd for
4-Chloro-3-(2-quinolyl)aniline (3i)
Off-white gum; yield: 188 mg (74%). 1H NMR (CDCl3, 400 MHz):
δ = 8.18–8.23 (m, J = 8.5 Hz, 2 H), 7.86 (dd, J = 8.0, 1.3 Hz, 1 H),
7.69–7.78 (m, 2 H), 7.57 (ddd, J = 8.2, 7.0, 1.1 Hz, 1 H), 7.20–7.28
(m, 1 H), 7.02 (d, J = 3.0 Hz, 1 H), 6.68 (dd, J = 8.5, 2.8 Hz, 1 H).
13C NMR (CDCl3, 101 MHz): δ = 157.5, 147.6, 145.6, 139.6, 136.0,
130.8, 129.9, 129.3, 127.6, 127.2, 126.9, 123.0, 121.2, 118.0,
116.9. HRMS (ESI-TOF): m/z [M + H]+ calcd for C15H11ClN2:
254.0610; found: 254.0611.
C15H11N3O5: 313.0698; found: 313.0698.
tert-Butyl 2-methyl-4-[5-(2-nitrophenyl)-4,5-dihydroisox-
azol-3-yl]benzoate (1h)
White solid; yield: 313 mg (82%); mp 167–168 °C. 1H NMR
(CDCl3, 400 MHz): δ = 8.18 (dd, J = 8.3, 1.3 Hz, 1 H), 7.83–7.87
(m, 2 H), 7.71 (t, J = 7.6 Hz, 1 H), 7.49–7.54 (m, 3 H), 4.15 (dd, J =
17.3, 11.3 Hz, 1 H), 3.26 (dd, J = 17.3, 6.8 Hz, 1 H), 2.58 (s, 3 H),
1.57–1.62 (s, 9 H). 13C NMR (CDCl3, 101 MHz): δ = 166.5, 155.7,
139.8, 137.7, 134.5, 133.4, 131.4, 130.7, 129.7, 128.8, 127.6,
125.2, 123.9, 81.6, 79.3, 43.9, 28.2, 21.7. HRMS (ESI-TOF): m/z
[M + H]+ calcd for C21H22N2O5: 382.1528; found: 382.1525.
2-Arylquinoline Derivatives 3; General Procedure 1
(26) Reichardt, C.; Welton, T. Solvents and Solvent Effects in Organic
Chemistry, 4th. ed.; Wiley-VCH: Weinheim, 2010.
(27) Vellanki, B. P.; Batchelor, B.; Abdel-Wahab, A. Environ. Eng. Sci.
2013, 30, 264.
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Takeuchi, Y. Org. Process Res. Dev. 2012, 16, 96.
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(32) 2-Arylquinoline Derivatives 3; General Procedure 2
To a solution of 2′-nitroaryl-Δ2-isoxazoline 1 (1.00 mmol, 1.0
equiv) in DMSO (7.0 mL) was added sodium dithionite (6.00
mmol, 6.0 equiv) at r.t. The suspension was warmed to 100 °C
and stirred for 3–5 h. The reaction was monitored by TLC and
LC-MS and, after complete conversion, the reaction mixture was
cooled to 25 °C. The reaction mixture was poured into an
icecold solution of sodium hydroxide and stirred for 10 min.
The aqueous phase was extracted with diethyl ether (3 × 10.0
mL) and the combined organic layers were washed with water
(10.0 mL) followed by brine (10.0 mL), dried over anhydrous
sodium sulfate, filtered and the filtrate was concentrated under
reduced pressure to give the crude product which was purified
by flash chromatography.
To a solution of Δ2-isoxazoline derivative 1 (1.00 mmol, 1.0
equiv) in ethanol (7.0 mL) at 25 °C were added iron powder
(8.00 mmol, 8.0 equiv), ammonium chloride (8.00 mmol, 8.0
equiv) and water (7.0 mL). The resulting suspension was stirred
at 80 °C for 6 hours and monitored by TLC and LC-MS. The reac-
tion mixture was allowed to cool to 25 °C, and filtered through a
bed of Celite®. The filtrate was distilled under reduced pressure
and the resulting aqueous phase was extracted with ethyl
acetate (3 × 5.0 mL). The combined organic layers were washed
with water (5.0 mL) followed by brine (5.0 mL), dried over anhy-
drous sodium sulfate, filtered and concentrated under reduced
pressure to yield the crude product which was purified by
column chromatography to yield pure 3.
2-(4-Chloro-2-fluorophenyl)quinoline (3c)
White solid; yield: 206 mg (80%); mp 85–86 °C. 1H NMR (CDCl3,
400 MHz): δ = 8.26 (s, 2 H), 8.20–8.25 (m, 7 H), 8.15 (s, 1 H),
8.13 (s, 2 H), 8.11 (s, 1 H), 7.86–7.90 (m, 9 H), 7.77 (ddd, J = 8.5,
7.0, 1.4 Hz, 5 H), 7.59 (ddd, J = 8.1, 7.0, 1.3 Hz, 5 H), 7.32–7.35
2-(2,4,6-Trifluorophenyl)quinoline (3l)
White solid; yield: 137 mg (53%); mp 97–98 °C. 1H NMR (CDCl3,
400 MHz): δ = 8.26 (d, J = 8.2 Hz, 1 H), 8.19 (d, J = 8.2 Hz, 1 H),
7.88 (d, J = 8.3 Hz, 1 H), 7.77 (ddd, J = 8.5, 7.0, 1.4 Hz, 1 H), 7.60
(t, J = 7.5 Hz, 1 H), 7.54 (d, J = 8.5 Hz, 1 H), 6.83 (t, J = 8.0 Hz, 2 H).
13C NMR (CDCl3, 101 MHz): δ = 164.1–159.5 (m, 3 C), 149.1,
148.2, 136.5, 130.0, 129.7, 127.6, 127.3, 127.1, 123.2, 101.0–
100.4 (m, 2 C). HRMS (ESI-TOF): m/z [M + H]+ calcd for C15H8F3N:
259.0608; found: 259.0608.
(m, 5 H), 7.27 (s, 6 H), 7.24 (d, J = 2.0 Hz, 2 H), 1.72 (br s, 7 H). 13
C
NMR (CDCl3, 101 MHz): δ = 161.8–159.3 (d, J = 254 Hz, 1 C),
132.5, 130.0, 129.5, 128.5, 127.5, 127.3, 127.0, 125.2, 124.3,
122.2, 122.1, 121.5, 117.2, 116.9. HRMS (ESI-TOF): m/z [M + H]+
calcd for C15H9ClFN: 257.0407; found: 257.0401.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–E