Synthesis of Quinolines via Iron-Catalyzed Redox Condensation of Alcohols with 2-Nitrobenzyl Methyl Ether/2-Nitrobenzyl Alcohols

Article abstract of DOI:10.1055/s-0035-1562496

An iron-catalyzed redox condensation of 2-nitrobenzyl alcohols, formic acid, and alcohols has been developed, which affords substituted quinolines with carbon dioxide and water as the only side products. With the use of formic acid as a redox moderator to fill the electron gap of the global redox condensation process, the reaction goes smoothly with a smaller amount of alcohol in comparison to previous reports (i.e. 1.2 equiv versus 3.3-4 equiv). The reaction goes equally well when 2-nitrobenzyl methyl ether was used instead of 2-nitrobenzyl alcohol under otherwise identical conditions, shedding a new light on the study of this quinoline synthetic method.

Full text of DOI:10.1055/s-0035-1562496

SYNTHESIS
0
0
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9
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7
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8
1
1
4
3
7
-
2
1
0
X
© Georg Thieme Verlag Stuttgart · New York
2016, 48, A–K
paper
A
Q. Wang et al.
Paper
Synthesis
Synthesis of Quinolines via Iron-Catalyzed Redox Condensation of
Alcohols with 2-Nitrobenzyl Methyl Ether/2-Nitrobenzyl Alcohols
Qi Wanga
R1
R2
R1
OH
dppf (5 mol%)
DIPEA (1.5 equiv)
Meirong Wangb
Hui-Jing Lia
Shuai Zhua
R3
OH
R2
R3
H
H
H
O
X
X
H
H
PhMe, 150 °C, 1 d
4 H2O + CO2
O
NO2
N
Ying Liu*a
H
Yan-Chao Wu*a
R2 = H, Ph
R3 = H, n-Pr, Ar
X = H, F, Cl, MeO
R1 = H, Me, CF3
18 examples
39–79% yield
a School of Marine Science and Technology, Harbin
Institute of Technology, No. 2 Wenhuaxi Road,
Weihai 264209, P. R. of China
liuying@iccas.ac.cn
ycwu@iccas.ac.cn
b School of Materials Science and Engineering, Harbin
Institute of Technology, No. 2 Wenhuaxi Road,
Weihai 264209, P. R. of China
Received: 22.04.2016
Accepted after revision: 20.05.2016
Published online: 30.06.2016
aminobenzyl alcohols and aldehydes,9 and potential nucle-
ophilic substitution of the benzyl alcohol moiety with the
amino moiety of 2-aminobenzyl alcohols in the presence of
various Lewis acids.10 Another solution is the redox con-
densation of 2-nitrobenzaldehydes with alcohols in the
presence of Ru(PPh3)3Cl2, which offered an alternative ac-
cess to quinolines using easily available and stable starting
materials (Scheme 1).11a However, no less than three equiv-
alents of alcohol were required in this reaction, and the for-
mation of side products, aldehydes/ketones, is obviously
unavoidable.11a This is because the oxidation of an alcohol
to an aldehyde/ketone can transfer only two electrons
while the reduction of a 2-nitrobenzaldehyde to the corre-
DOI: 10.1055/s-0035-1562496; Art ID: ss-2016-h0276-op
Abstract An iron-catalyzed redox condensation of 2-nitrobenzyl alco-
hols, formic acid, and alcohols has been developed, which affords sub-
stituted quinolines with carbon dioxide and water as the only side prod-
ucts. With the use of formic acid as a redox moderator to fill the
electron gap of the global redox condensation process, the reaction
goes smoothly with a smaller amount of alcohol in comparison to previ-
ous reports (i.e. 1.2 equiv versus 3.3–4 equiv). The reaction goes equal-
ly well when 2-nitrobenzyl methyl ether was used instead of 2-nitroben-
zyl alcohol under otherwise identical conditions, shedding a new light
on the study of this quinoline synthetic method.
sponding 2-aminobenzaldehyde requires six electrons.12
A
Key words quinolines, 2-nitrobenzyl alcohols, iron catalysis, redox
condensation, Friedländer annulation
large amount of alcohol (3.3–4 equiv) was still required
when 2-nitrobenzyl alcohols were used instead of 2-nitro-
benzaldehydes (Scheme 1),11 which is not in agreement
with the principles of green and sustainable chemistry.
Considering the dehydrogenation of formic acid and its
salts is substantially irreversible due to the evolution of
CO2,13 we envisioned that they might be better suited hy-
drogen donors than alcohols to fill the electron gap for this
unbalanced electron-transfer process. Notably, formic acid
as the hydrogen donor is abundant, inexpensive, and easy
to handle.13 In this context, we wish to describe here a new
quinoline synthesis via iron-catalyzed redox condensation
of 2-nitrobenzyl alcohols, formic acid, and alcohols
(Scheme 1).14
Quinolines are important building blocks for the con-
struction of a large number of pharmaceuticals,1 natural
products,2 and functional materials.3 Accordingly, various
synthetic methods have been developed for the construc-
tion of quinolines,4–6 amongst which the Friedländer quino-
line synthesis is still one of the simplest and most straight-
forward methods.6,7 2-Aminobenzaldehydes, as the typical
starting materials for a Friedländer annulation, can readily
undergo self-condensation reactions and this, thereby, lim-
its the scope and generality of the quinoline synthesis.6 To
overcome this inherent problem, 2-aminobenzyl alcohols
were used instead of 2-aminobenzaldehydes in some modi-
fied Friedländer quinoline syntheses, which underwent ox-
idation to produce reactive 2-aminobenzaldehydes and the
latter were condensed with aldehydes/ketones for conver-
sion in situ into quinolines.8 This approach indeed provided
a shortcut for quinoline synthesis, but still has some draw-
backs, such as the potential formation of oxazines from 2-
Initially, the reaction of 2-nitrobenzyl alcohol (1a) with
1-phenylethanol (2a) was used as a probe for evaluating the
reaction conditions, and representative results are summa-
rized in Table 1. Reaction of 1a (1.0 equiv) with 2a (3.3
equiv) in the presence of Ru(PPh3)3Cl2 (5 mol%) and K2CO3
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–K

B
Q. Wang et al.
Paper
Synthesis
R1
Thus, the ferrocene/Ph3P catalytic system was investigated
for this reaction, which afforded quinoline 3a in 17% yield
(entries 8 and 9). Quinoline 3a was not obtained in the ab-
sence of ferrocene under otherwise identical conditions
(entries 9 and 10). An increased yield was also observed
with the use of FeSO4/Ph3P in comparison to FeSO4 (entries
5 and 11). These results indicated that the iron/phosphine
couple might be responsible for transfer reduction of the
nitro group with an alcohol group, which agrees well with
Beller’s observation that the in situ combination of
Fe(BF4)2·6H2O and P(CH2CH2PPh2)3 is an excellent catalytic
system for the transfer reduction of nitroarenes.16 Solvent
played an important role in this transformation. The reac-
tion did not work in tert-amyl alcohol or DMF (entries 12
and 13). With the use of 1-methylpyrrolidin-2-one (NMP)
in comparison to PhCl, a lower yield was observed (entries
2 and 14). To our delight, the yield of quinoline 3a increased
to 55% when this reaction was performed in toluene (en-
tries 2 and 15). The reaction went equally well when the
loading of dppf was greater than 5 mol% (entries 15–17).
Further parameter optimization identified 150 °C as the
most effective reaction temperature (entries 15, 18, and
19). The choice of base was also important for this reaction,
and an inappropriate base might promote the conversion of
an in situ generated 2-aminobenzaldehyde intermediate
R1
N
O
X
R2
R3
previous work
NO2
R1
OH
X
Ru cat.
R2
or
+
R3
– 4 H2O
+
O
R2
3.3–4.0 equiv
OH
R3
X
NO2
R1
1.0 equiv
this work
Fe cat.
R1
N
R2
R3
OH
OH
R2
X
X
+
R3
HCO2H
NO2
1.0 equiv
+ CO2 + 4 H2O
2.0 equiv
1.2 equiv
Scheme 1 Synthesis of quinolines via redox condensation of alcohols
with 2-nitrobenzaldehydes/2-nitrobenzyl alcohols
(1.0 equiv) at 150 °C for 1 day afforded quinoline 3a in only
25% yield (entry 1), in which Ru(PPh3)3Cl2 appeared to serve
the role of not only a Friedländer annulation catalyst but
also a hydrogen-transfer catalyst.11a Accordingly, a series of
other hydrogen-transfer catalysts were investigated, in
which dppf was found to be a relatively effective catalyst.15
By treating 1a (1.0 equiv) with 2a (2.0 equiv) in the pres-
ence of dppf (5 mol%) at 150 °C for 1 day, quinoline 3a was
obtained in 37% yield (entry 2). Subsequently, various iron
salts were tested for this reaction, in which dppf showed
the best efficiency (entries 2–8). Quinoline 3a was not ob-
tained at all when ferrocene was used instead of dppf under
otherwise the same conditions, reflecting the phosphine
moiety of dppf effect on this reaction (entries 2 and 8).
into the corresponding 2-aminobenzoic acid via
a
Cannizzaro reaction.17 With the addition of Li2CO3 or Na2CO3
under otherwise identical conditions, quinoline 3a was ob-
tained in 61% and 62% yields, respectively (entries 20 and
21). However, quinoline 3a was obtained in relatively lower
yields when K2CO3, Cs2CO3, KOH, K3PO4, t-BuOK, NaHCO3, or
NaOH was used as the base (entries 15 and 22–28). With
the use of Pd(PPh3)3Cl2, Ir(PPh3)2(CO)Cl, CuH(PPh3), and
Ru(PPh3)3Cl2 in comparison to dppf, there was no improve-
ment in the results obtained (entries 28–32). Two equiva-
lents of alcohol 2a were used in these transformations (en-
tries 2–31), in which one equivalent of 2a served as a reduc-
ing agent (hydrogen donor). Considering HCO2Na could
serve a dual role as the base and hydrogen donor, it was
used instead of Na2CO3 to save nearly one equivalent of al-
cohol 2a (entry 33). However, the reaction afforded quino-
line 3a in only a moderate yield even with excess HCO2Na.
Thus, the combination of HCO2H with an organic base was
next investigated. Fortuitously, the combination of HCO2H
(2.0 equiv) with DIPEA (1.5 equiv) was found to be a good
choice in the formation of quinoline 3a (entry 34). Addition
of NiCl (5 mol%), CoCl2 (5 mol%), PtCl2 (5 mol%), PdCl2 (5
mol%), or RuCl3 (5 mol%) to the above reaction system did
not provide any better results (entries 34–39). Unsurpris-
ingly, the reaction did not work in the absence of dppf (en-
try 40). Decreased yields of quinoline 3a were observed in
the absence of either DIPEA or HCO2H (cf. entries 34 with
41 and 42). Furthermore, scaling up 1a to 1.53 g the reac-
tion provided the yield at an excellent level (entry 43).
(a)
x
NO2
NH2
dppf, HCO2H
5
4
+
DIPEA, PhMe
150 °C, 1 d
OH
O
(b)
(c)
6a
2a
1a
dppf, DIPEA
OH
NO2
O
PhMe, 150 °C
4 h, 60%
NO2
7a
Cl
Cl
Cl
dppf, HCO2H
O
O
(d)
(e)
DIPEA, PhMe
150 °C, 4 h, 46%
NO2
NH2
7c
8c
3c
Cl
6a, dppf, HCO2H
O
DIPEA, PhMe
N
Ph
NH2
140 °C, 1 d, 37%
8c
Scheme 2 Verification experiments
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–K

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Synthesis
Table 1 (continued)
Table 1 Survey of Conditions for the Synthesis of Quinoline 3a from 2-
Nitrobenzyl Alcohol (1a) with 1-Phenylethanol (2a)a
Entry
Catalyst
Base
Solvent
Temp
(°C)
Yield
(%)
OH
OH
NO2
conditions
+
39e,f
40e,f
41e,g
42e,h
43e,f,i
dppf/RuCl3
–
DIPEA
PhMe
PhMe
PhMe
PhMe
PhMe
150
150
150
150
150
8
0
Ph
N
Ph
DIPEA
–
1a
2a
3a
dppf
52
23
72
dppf
DIPEA
DIPEA
Entry
Catalyst
Base
Solvent
Temp
(°C)
Yield
(%)
dppf
1b
2
Ru(PPh3)3Cl2
dppf
K2CO3
PhCl
150
150
150
150
150
150
150
150
150
150
150
150
150
150
150
150
150
140
160
150
150
150
150
150
150
150
150
150
150
150
150
150
150
150
150
150
150
150
25
37
13
10
9
a General conditions: 1a (0.5 mmol), 2a (1.0 mmol), catalyst (5 mol%),
base (0. 5 mmol), solvent (1.0 mL), under argon, 1 d.
b 1.65 mmol of 2a was used.
–
PhCl
c 3 mol% of dppf was used.
3
Fe(NO3)3
FeCl3
–
PhCl
d 10 mol% of dppf was used.
e 0.6 mmol of 2a was used.
4
–
PhCl
f 1.0 mmol of HCO2H and 0.75 mmol of DIPEA were used.
g 1.0 mmol of HCO2H was used.
5
FeSO4
–
PhCl
h 0.75 mmol of DIPEA was used.
6
Fe(OTf)3
Fe(OH)3
ferrocene
–
PhCl
0
i 1.53 g of 1a was used.
7
–
PhCl
0
8
–
PhCl
0
With the optimized reaction conditions in hand, the
scope of the reaction was subsequently investigated (Table
2). With the aromatic rings of 2-nitrobenzyl alcohols bear-
ing hydrogen atoms (entry 1), electron-withdrawing groups
(entries 2 and 3), and electron-donating groups (entry 4),
2-nitrobenzyl alcohols 1a–d reacted smoothly with 1-
phenylethanol (2a) and formic acid in the presence of
DIPEA at 150 °C to afford quinolines 3a–d in 53–73% yields
within 1 day. 1-(2-Nitrophenyl)ethanol (1e) reacted with
alcohol 2a and formic acid uneventfully to afford 2,4-sub-
stituted quinoline 3e under standard conditions, albeit at a
relatively higher reaction temperature (entry 5). An obvious
increase yield was observed with 2,2,2-trifluoro-1-(2-nitro-
phenyl)ethanol (1f) in comparison to 2-nitrobenzyl alcohol
1e (entries 5 and 6). 1-(4-Fluorophenyl)ethanol (2b) and 1-
(4-methoxyphenyl)ethanol (2c) reacted equally well with
2-nitrobenzyl alcohol 1f and formic acid under standard
conditions to give quinolines 3g,h in 79% and 67% yields, re-
spectively (entries 7 and 8). With the para position of the
aromatic rings bearing electron-withdrawing groups such
as fluoro, chloro, and bromo, benzyl alcohols 2b,d,e reacted
smoothly with 2-nitrobenzyl alcohol 1a and formic acid to
afford quinolines 3i–k in good yields (entries 9–11). With
an electron-donating group such as a methoxy group at the
para position of the aromatic ring, benzyl alcohol 2c react-
ed with 2-nitrobenzyl alcohol 1a and formic acid to afford
quinoline 3l with decreased yield (cf. entries 1 and 12). or-
tho-Substituted benzyl alcohols 2f,g and a meta-substituted
benzyl alcohol 2h were also investigated, which reacted
with 2-nitrobenzyl alcohol (1a) and formic acid under stan-
dard conditions to afford quinolines 3m–o in moderate
yields (entries 13–15). By treatment of 1-(4-tolyl)propan-1-
ol (2i) with 2-nitrobenzyl alcohol (1a) and formic acid un-
der standard conditions, 2-substituted quinoline 3p was
obtained in 60% yield (entry 16). Primary aliphatic alcohol
9
ferrocene/Ph3P
Ph3P
–
PhCl
17
0
10
11
12
13
14
15
16c
17d
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33e
34e,f
35e,f
36e,f
37e,f
38e,f
–
PhCl
FeSO4/Ph3P
dppf
–
PhCl
11
0
–
Me2EtCOH
DMF
dppf
–
0
dppf
–
NMP
10
55
33
55
48
29
61
62
33
33
10
27
22
51
29
0
dppf
–
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
dppf
–
dppf
–
dppf
–
dppf
–
dppf
Li2CO3
Na2CO3
K2CO3
Cs2CO3
KOH
K3PO4
t-BuOK
NaHCO3
NaOH
Na2CO3
Na2CO3
Na2CO3
Na2CO3
HCO2Na
DIPEA
DIPEA
DIPEA
DIPEA
DIPEA
dppf
dppf
dppf
dppf
dppf
dppf
dppf
dppf
Pd(PPh3)Cl2
Ir(PPh3)2(CO)Cl
CuH(PPh3)
Ru(PPh3)3Cl2
dppf
21
10
22
43
73
28
18
24
15
dppf
dppf/NiCl
dppf/CoCl2
dppf/PtCl2
dppf/PdCl2
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–K

D
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Synthesis
2j reacted smoothly with 2-nitrobenzyl alcohol 1a and for-
mic acid under standard conditions to afford 3-substituted
quinoline 3q in 68% yield (entry 17). Only one quinoline re-
gioisomer 3r was obtained (62% yield) when a non-sym-
metric secondary aliphatic alcohol (2j) was used (entry 18),
demonstrating excellent regioselectivity.
Table 2 Synthesis of Various Quinolines a
R1
R1
R2
R3
OH
dppf, HCO2H
DIPEA, PhMe
R2
OH
+
X
R3
X
N
NO2
1
2
3
Entry
1
1
2
Product 3: yield
OH
OH
NO2
Ph
N
Ph
2a
1a
3a: 73%
F
F
OH
NO2
2
3
4
2a
2a
2a
N
Ph
3b: 61%
1b
Cl
Cl
OH
NO2
N
Ph
1c
3c: 53%
MeO
MeO
OH
NO2
MeO
MeO
N
Ph
1d
3d: 70%
OH
NO2
5b
2a
2a
N
Ph
1e
3e: 39%
CF3
OH
NO2
CF3
6
N
Ph
1f
1f
3f: 73%
CF3
N
OH
7
8
F
2b
F
3g: 79%
CF3
OH
1f
N
OMe
OMe
2c
3h: 67%
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–K

E
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Synthesis
Table 2 (continued)
Entry
1
2
Product 3: yield
N
9
10
11
12
1a
1a
1a
1a
2b
F
3i: 66%
OH
N
Cl
Cl
2d
3j: 59%
OH
N
Br
Br
2e
2c
3k: 70%
N
OMe
3l: 41%
OH
OH
Cl
Cl
N
13
14
15
16
1a
1a
1a
1a
2f
3m: 55%
OMe
OMe
N
2g
3n: 40%
OH
Cl
Cl
N
2h
3o: 44%
OH
N
2i
3p: 60%
Ph
HO
17
18
1a
1a
Ph
N
2j
3q: 68%
OH
N
2k
3r: 62%
a General conditions: 1 (0.5 mmol), 2 (0.6 mmol), HCO2H (1.0 mmol), DIPEA (0.75 mmol), dppf (5 mol%), toluene (1.0 mL), under argon, 150 °C, 1 d.
b The reaction was performed at 170 °C for 1 d.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–K

F
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Synthesis
The reaction mechanism of this quinoline synthetic
method was next studied, and representative results are il-
lustrated in Scheme 2. Reduction of nitrobenzene (4a) to
aniline (5a) with 1-phenylethanol (2a, 1.2 equiv) and for-
mic acid (2 equiv) did not take place in the presence of dppf
(5 mol%) and DIPEA (1.5 equiv) in toluene at 150 °C, and ni-
trobenzene (4a) was recovered [Scheme 2 (a)], indicating
that reduction of simple nitrobenzenes is a difficult process
under these conditions. Instead, acetophenone (6a) could
be detected in this reaction, even in the absence of nitro-
benzene 4a [Scheme 2 (b)], indicating that dehydrogenation
of benzyl alcohols is a relatively easy process compared to
the reduction of simple nitrobenzenes under these condi-
tions. By treating 2-nitrobenzyl alcohol (1a) in the presence
of dppf (5 mol%) and DIPEA (1.5 equiv) in toluene at 150 °C
for 4 hours, 2-nitrobenzaldehyde (7a) was obtained in 60%
yield [Scheme 2 (c)]. As the redox reaction of 2-nitrobenzal-
dehyde with alcohols could take place to afford quino-
lines,11a reduction of 2-nitrobenzaldehyde (7a) to the po-
tential 2-aminobenzaldehyde intermediate should take
place. Considering the 2-aminobenzaldehyde intermediate
might be unstable and degraded under the above condi-
tions and thus was not isolated, various 2-nitrobenzalde-
hyde substrates were next screened to obtain a relatively
stable 2-aminobenzaldehyde. In one case, for example, 2-
amino-5-chlorobenzaldehyde (8c) was obtained in 46%
yield by treating 2-nitro-5-chlorobenzaldehyde (7c) with
formic acid (6 equiv) in the presence of dppf (5 mol%) and
DIPEA (4.5 equiv) in toluene at 150 °C for 4 hours [Scheme 2
(d)].
2-Amino-5-chlorobenzaldehyde (8c) reacted with ace-
tophenone (6a) at 140 °C for 1 day under otherwise the
same conditions to afford quinoline 3c in 37% yield [Scheme
2 (e)]. There was a decrease in the yield with the direct use
of unstable 2-amino-5-chlorobenzaldehyde (8c) in compar-
ison to the use of in situ generated 8c [Scheme 2 (e), and
Table 2, entry 3], reflecting the importance of the in situ
generated 2-aminobenzaldehyde strategy to this reaction.
Based on the above results, a possible reaction mecha-
nism is illustrated in Scheme 3. Dehydrogenation of alco-
hols 2 [Scheme 3 (a)] and formic acid [Scheme 3 (b)] in the
presence of the [Fe] catalyst, dppf, provides carbonyl com-
pounds 6 and two equivalents of [Fe]H2. Dehydrogenation
of the alcohol moiety of 2-nitrobenzyl alcohols 1 gives an-
other equivalent of [Fe]H2 [Scheme 3 (c)]. The above three
equivalents of [Fe]H2 together facilitate the reduction of the
nitro moiety of 2-nitrobenzyl alcohols 1 and thereby form
2-aminobenzaldehydes 8, in which [Fe]H2 is converted back
into [Fe] [Scheme 3 (c)]. Finally, annulation of 2-amino-
benzaldehydes 8 with compounds 6 in the presence of the
[Fe] catalyst affords quinolines 3 [Scheme 3 (c)]. On the oth-
er hand, the aldol reaction between compounds 7 and car-
bonyl compounds 6 might also take place to give com-
pounds 9, which undergo nitro reduction and subsequent
annulation to afford quinolines 3 [Scheme 3 (d)]. It was re-
ported that 2-nitrobenzyl alcohols 1 could be converted
into 2-nitrosobenzaldehydes 11 via a dehydrating self-
redox rearrangement under photochemical or non-photo-
chemical reaction conditions [Scheme 3 (e)].18 Reduction of
2-nitrosobenzaldehydes 11 to 2-aminobenzaldehydes 8
with two equivalents of [Fe]H2, which are generated from
the dehydrogenation of alcohols 2 [Scheme 3 (a)] and for-
mic acid [Scheme 3 (b)], followed by Friedländer annulation
with carbonyl compounds 6 might be also possible to afford
quinolines 3 [Scheme 3 (e)]. The failure detection of the po-
tential 2-nitrosobenzaldehyde intermediates 11 might be
due to their much slower formation than their conversion
into 2-aminobenzaldehydes 8. It was reported that 2-nitro-
benzyl methyl ethers could also be converted into 2-nitro-
sobenzaldehydes via a methanol-releasing self-redox rear-
rangement.19 If 2-nitrosobenzaldehydes 11 were indeed in-
OH
O
[Fe]
R2
R2
(a)
(b)
R3
R3
– [Fe]H2
2
6
[Fe]
– [Fe]H2
R1
CO2
HCO2H
R1
3 [Fe]H2
– 3 [Fe]
[Fe]
OH
NO2
O
X
X
X
– [Fe]H2
NO2
R1
7
3
1
8
R1
R2
O
6, [Fe]
X
X
(c)
N
R3
O
NH2
– 2 H2O
R1
R1
3 [Fe]H2
– 3 [Fe]
O
R3
6, [Fe]
X
R2
– H2O
NO2
NO2
R1
9
3
7
R1
O
R2
R3
R3
[Fe]
X
X
R2
(d)
– H2O
NH2
R1
N
10
R1
2 [Fe]H2
– 2 [Fe]
– H2O
OH
O
X
X
X
X
self-redox
NO2
R1
NO
R1
1
8
11
R2
O
6, [Fe]
(e)
N
R3
NH2
– 2 H2O
3
Scheme 3 Proposed mechanism
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–K

G
Q. Wang et al.
Paper
Synthesis
volved the intermediates, quinolines 3 could be also formed
when 2-nitrobenzyl methyl ethers 12 were used instead of
2-nitrobenzyl alcohols 1 under otherwise identical condi-
tions. Accordingly, the condensation of 2-nitrobenzyl meth-
yl ether (12a), formic acid and 1-phenylethanol (2a) was
performed under standard conditions as shown in Table 2,
which afford quinoline 3a in 72% yield (Scheme 4).
(screw-capped vial) for 1 d under argon, cooled to r.t., then water (5
mL) was added. The two layers were separated, and the aqueous
phase was extracted with EtOAc (3 × 10 mL). The combined organic
extracts were washed by brine, dried (anhyd Na2SO4), filtered, and
concentrated. The residue was purified by flash chromatography on
silica gel (100–200 mesh) to afford the desired quinoline 3a–r.
2-Phenylquinoline (3a)
White solid; yield: 74.9 mg (73%); mp 82–84 °C (Lit.5b 81.9–83.6 °C).
OMe
FTIR (film): 2922, 2851, 1598, 1554, 1493, 1446, 1423, 1320, 1285,
OH
dppf, HCO2H
1256, 1177, 1028, 831, 813, 773 cm–1
.
+
Ph
DIPEA, PhMe
150 °C, 1 d, 72%
1H NMR (400 MHz, CDCl3): δ = 8.26–8.16 (m, 4 H), 7.88 (d, J = 8.6 Hz, 1
H), 7.83 (d, J = 8.1 Hz, 1 H), 7.74 (t, J = 7.8 Hz, 1 H), 7.58–7.44 (m, 4 H).
13C NMR (100 MHz, CDCl3): δ = 157.3, 148.1, 139.4, 136.9, 129.7,
NO2
N
Ph
2a
3a
12a
O
O
6a, [Fe]
[Fe]
2 [Fe]H2
– 2 [Fe]
129.6, 129.4, 128.8, 127.6, 127.4, 127.2, 126.3, 119.0.
HRMS (ESI): m/z [M + Na]+ calcd for C15H11NNa: 228.0784; found:
228.0761.
– 2 H2O
self-redox
– MeOH
NO
NH2
11a
8a
6-Fluoro-2-phenylquinoline (3b)
Scheme 4 An additional verification experiment
Pale yellow solid; yield: 68.1 mg (61%); mp 128–130 °C (Lit.20 128–
131 °C).
In conclusion, we have developed an iron-catalyzed re-
dox condensation of alcohols with 2-nitrobenzyl methyl
ether/2-nitrobenzyl alcohols, which provides a shortcut to
quinolines from stable and easily available starting materi-
als. Obviously, this reaction goes smoothly with a smaller
amount of alcohols in comparison to the previous reports
(i.e., 1.2 equiv versus 3.3–4 equiv, Scheme 1),11 and carbon
dioxide and water are the only side products. These charac-
teristics agree well with the principles of green and sus-
tainable chemistry. Moreover, the reaction does not require
an expensive ruthenium catalyst, and thus would facilitate
its practical applications. Further mechanistic investiga-
tions as well as applications of this method are in progress
in our laboratory.
FTIR (film): 2921, 2851, 1606, 1555, 1510, 1493, 1447, 1342, 1280,
1238, 1143, 1114, 1075, 963, 920, 871, 836, 780, 758, 693 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.24–8.13 (m, 4 H), 7.89 (d, J = 8.6 Hz, 1
H), 7.58–7.41 (m, 5 H).
13C NMR (100 MHz, CDCl3): δ = 160.4 (d, 1JC-F = 246.7 Hz, 1 C), 156.7 (d,
4JC-F = 2.7 Hz, 1 C), 145.1, 139.1, 136.3 (d, 4JC-F = 5.0 Hz, 1 C), 132.0 (d,
3
3JC-F = 9.0 Hz, 1 C), 129.5, 128.9, 127.7 (d, JC-F = 10.0 Hz, 1 C), 127.5,
119.9 (d, 2JC-F = 25.6 Hz, 1 C), 119.7, 110.5 (d, 2JC-F = 21.6 Hz, 1 C).
HRMS (ESI): m/z [M + Na]+ calcd for C15H10FNNa: 246.0689; found:
246.0679.
6-Chloro-2-phenylquinoline (3c)
Pale yellow solid; yield: 63.5 mg (53%); mp 133–135 °C (Lit.20 134–
137 °C).
FTIR (film): 2920, 2849, 1646, 1596, 1548, 1485, 1469, 1445, 1420,
1319, 1280, 1130, 1076, 970, 876, 833, 783, 755, 695 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.19–8.11 (m, 4 H), 7.90 (d, J = 8.6 Hz, 1
H), 7.81 (s, 1 H), 7.67 (d, J = 8.6 Hz, 1 H), 7.58–7.45 (m, 3 H).
13C NMR (100 MHz, CDCl3): δ = 157.5, 146.3, 138.9, 136.1, 132.1,
131.1, 130.7, 129.7, 128.9, 127.7, 127.6, 126.1, 119.8.
HRMS (ESI): m/z [M + Na]+ calcd for C15H10ClNNa: 262.0394; found:
Common reagents and materials were purchased from commercial
sources and were used without further purification. Organic solvents
were routinely dried and/or distilled prior to use and stored over mo-
lecular sieves under argon. All experiments were carried out under an
argon atmosphere in flame-dried glassware using standard inert
techniques for introducing reagents and solvents unless otherwise
noted. TLC plates were visualized by exposure to UV light. IR spectra
were recorded by using an Electrothemal Nicolet 380 spectrophotom-
eter. HRMS were recorded by using an Electrothemal LTQ-Orbitrap
mass spectrometer. Elemental analyses were performed on Vario EL
III elementary analyzer. Melting points were measured by using a
Gongyi X-5 microscopy digital melting point apparatus and are un-
corrected. 1H NMR and 13C NMR spectra were obtained by using a
Bruker Avance III 400 MHz NMR spectrometer referenced to solvent
or residual solvent [CHCl3: δ = 7.26 (1H) and CDCl3: δ = 77.0 (13C)].
262.0379.
6,7-Dimethoxy-2-phenylquinoline (3d)
Pale yellow solid; yield: 92.8 mg (70%); mp 132–134 °C (Lit.11a 132–
134 °C).
FTIR (film): 2923, 1623, 1597, 1496, 1463, 1435, 1409, 1390, 1340,
1241, 1211, 1162, 1131, 1054, 1026, 1006, 858, 695 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.17–8.09 (m, 3 H), 7.77–7.42 (m, 5 H),
7.08 (s, 1 H), 4.09 (s, 3 H), 4.37 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 155.0, 152.4, 149.5, 145.1, 139.8,
134.6, 128.61, 128.55, 127.0, 122.5, 116.9, 108.2, 104.8, 55.9, 55.8.
HRMS (ESI): m/z [M + H]+ calcd for C17H16NO2: 266.1176; found:
266.1172.
Quinolines 3; General Procedure
The mixture of 2-nitrobenzyl alcohol 1a–f (0.5 mmol), alcohol 2a–k
(0.6 mmol), HCO2H (53 μL, 1.0 mmol), DIPEA (125 μL, 0.75 mmol), and
dppf (14.1 mg, 0.025 mmol) in toluene (1.0 mL) was stirred at 150 °C
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–K

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Q. Wang et al.
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Synthesis
1
4-Methyl-2-phenylquinoline (3e)
Pale yellow solid; yield: 42.7 mg (39%); mp 65–67 °C (Lit.21 65–67 °C).
13C NMR (100 MHz, CDCl3): δ = 163.8 (d, JC-F = 247.4 Hz, 1 C), 156.1,
148.1, 136.9, 135.7 (d, 4JC-F = 2.8 Hz, 1 C), 129.8, 129.5, 129.4 (d, 3JC-F
8.3 Hz, 1 C), 127.4, 127.0, 126.3, 118.5, 115.4 (d, 2JC-F = 22.2 Hz, 1 C).
HRMS (ESI): m/z [M + Na]+ calcd for C15H10FNNa: 246.0689; found:
=
FTIR (film): 2922, 2851, 1597, 1551, 1509, 1495, 1451, 1348, 1079,
1029, 861, 769, 694 cm–1
.
246.0673.
1H NMR (400 MHz, CDCl3): δ = 8.24 (d, J = 8.4 Hz, 1 H), 8.19 (d, J = 7.2
Hz, 2 H), 7.97 (d, J = 8.1 Hz, 1 H), 7.77–7.46 (m, 6 H), 2.73 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 157.0, 148.1, 144.7, 139.8, 130.3,
129.2, 129.1, 128.7, 127.5, 127.2, 125.9, 123.5, 119.6, 18.9.
HRMS (ESI): m/z [M + H]+ calcd for C16H14N: 220.1121; found:
2-(4-Chlorophenyl)quinoline (3j)
White solid; yield: 70.7 mg (59%); mp 113–115 °C (Lit.5b 114.8–116.2
°C).
FTIR (film): 2919, 2849, 1659, 1631, 1593, 1469, 1429, 816, 788, 752,
220.1120.
715 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.24–8.14 (m, 2 H), 8.06 (d, J = 8.1 Hz, 2
H), 7.85–7.79 (m, 2 H), 7.74 (t, J = 7.2 Hz, 1 H), 7.65 (d, J = 8.1 Hz, 2 H),
7.53 (t, J = 7.2 Hz, 1 H).
13C NMR (100 MHz, CDCl3): δ = 156.0, 148.2, 138.4, 137.0, 131.9,
129.8, 129.7, 129.1, 127.5, 127.2, 126.5, 123.9, 118.4.
2-Phenyl-4-(trifluoromethyl)quinoline (3f)
Pale yellow form; yield: 99.7 mg (73%).
FTIR (film): 2926, 2854, 1609, 1439, 1371, 1359, 1137, 1125, 865,
768, 695 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.36–8.17 (m, 5 H), 7.85–7.81 (m, 1 H),
7.68–7.51 (m, 4 H).
13C NMR (100 MHz, CDCl3): δ = 156.6, 148.8, 138.0, 135.1 (q, JC-F
HRMS (ESI): m/z [M + Na]+ calcd for C15H10ClNNa: 262.0394; found:
262.0377.
2
=
30.8 Hz, 1 C), 130.7, 130.4, 130.0, 129.1, 129.0, 127.9, 127.3, 123.9,
2-(4-Bromophenyl)quinoline (3k)
White solid; yield: 99.4 mg (70%); mp 121–123 °C (Lit.23 121–122 °C).
123.2 (q, 1JC-F = 273.6 Hz, 1 C), 115.9 (q, 3JC-F = 7.3 Hz, 1 C).
Anal. Calcd for C16H10F3N: C, 70.33; H, 3.69; N, 5.13. Found: C, 70.49;
H, 3.52; N, 5.30.
FTIR (film): 2920, 2850, 1632, 1594, 1572, 1469, 1429, 1317, 1126,
1073, 1006, 817, 788, 752, 716 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.23 (d, J = 8.4 Hz, 1 H), 8.16 (d, J = 8.4
Hz, 1 H), 8.06 (d, J = 7.1 Hz, 2 H), 7.87–7.81 (m, 2 H), 7.40 (t, J = 7.6 Hz,
1 H), 7.66 (d, J = 7.1 Hz, 2 H), 7.54 (t, J = 7.2 Hz, 1 H).
13C NMR (100 MHz, CDCl3): δ = 156.0, 148.2, 138.4, 137.0, 132.0,
129.9, 129.7, 129.1, 127.5, 127.3, 126.5, 124.0, 118.5.
2-(4-Fluorophenyl)-4-(trifluoromethyl)quinoline (3g)
Pale yellow form; yield: 115.0 mg (79%).
FTIR (film): 2924, 2853, 1601, 1506, 1431, 1373, 1358, 1229, 1136,
1112, 872, 841, 761 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.17–8.02 (m, 5 H), 7.74–7.70 (m, 1 H),
7.58–7.54 (m, 1 H), 7.16–7.12 (m, 2 H).
HRMS (ESI): m/z [M + Na]+ calcd for C15H10BrNNa: 305.9889; found:
305.9875.
1
13C NMR (100 MHz, CDCl3): δ = 164.2 (d, JC-F = 248.9 Hz, 1 C), 155.4,
149.0, 135.2 (q, 2JC-F = 31.3 Hz, 1 C), 134.5 (d, 3JC-F = 3.2 Hz, 1 C), 130.5,
2-(4-Methoxyphenyl)quinoline (3l)
White solid; yield: 48.2 mg (41%); mp 123–125 °C (Lit.5b 123.7–125.6
°C).
1
129.5, 129.4, 127.9, 123.85, 123.83, 123.5 (q, JC-F = 273.2 Hz, 1 C),
116.0 (d, 2JC-F = 21.7 Hz, 1 C), 115.5 (q, 3JC-F = 5.3 Hz, 1 C).
Anal. Calcd for C16H9F4N: C, 65.98; H, 3.11; N, 4.81. Found: C, 66.10; H,
3.07; N, 4.93.
FTIR (film): 2920, 2850, 1645, 1597, 1499, 1431, 1289, 1252, 1176,
1031, 819, 790, 755 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.23–8.13 (m, 4 H), 7.86–7.77 (m, 2 H),
7.72 (t, J = 7.4 Hz, 1 H), 7.50 (t, J = 7.4 Hz, 1 H), 7.05 (d, J = 8.2 Hz, 2 H),
3.89 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 161.0, 156.8, 147.9, 147.2, 136.9,
129.7, 129.3, 129.0, 127.4, 126.9, 126.0, 118.6, 114.3, 55.4.
2-(4-Methoxyphenyl)-4-(trifluoromethyl)quinoline (3h)
Pale yellow form; yield: 101.5 mg (67%).
FTIR (film): 2928, 2839, 1604, 1551, 1509, 1463, 1432, 1376, 1357,
1268, 1252, 1176, 1135, 1115, 1033, 870, 833, 760 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.24–8.11 (m, 5 H), 7.81–7.77 (m, 1 H),
7.64–7.60 (m, 1 H), 7.07 (d, J = 8.8 Hz, 2 H), 3.90 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 161.4, 156.1, 149.1, 134.8 (q, JC-F
31.0 Hz, 1 C), 130.9, 130.4, 130.3, 128.9, 127.4, 123.8, 123.6 (q, 1JC-F
272.9 Hz, 1 C), 115.5 (q, 3JC-F = 5.2 Hz, 1 C), 114.4, 113.6, 55.4.
HRMS (ESI): m/z [M + H]+ calcd for C16H14NO: 236.1070; found:
236.1072.
2
=
=
2-(2-Chlorophenyl)quinoline (3m)
White solid; yield: 65.9 mg (55%); mp 71–72°C (Lit.24 74–78°C).
Anal. Calcd for C17H12F3NO: C, 67.32; H, 3.99; N, 4.62. Found: C, 67.41;
H, 3.84; N, 4.81.
FTIR (film): 2923, 2851, 1618, 1596, 1553, 1505, 1431, 1315, 1283,
1240, 1077, 879, 827, 780, 753 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.25–8.17 (m, 3 H), 8.05–8.02 (m, 1 H),
7.84–7.72 (m, 3 H), 7.57–7.52 (m, 1 H), 7.45–7.43 (m, 2 H).
13C NMR (100 MHz, CDCl3): δ = 155.6, 148.1, 141.2, 137.1, 134.9,
130.0, 129.9, 129.7, 129.3, 127.7, 127.4, 127.3, 126.6, 125.6, 118.6.
2-(4-Fluorophenyl)quinoline (3i)
Pale yellow solid; yield: 73.6 mg (66%); mp 93–95 °C (Lit.22 94–95 °C).
FTIR (film): 2920, 2849, 1592, 1497, 1431, 1124, 1097, 852, 820, 788,
757, 719 cm–1
.
Anal. Calcd for C15H10ClN: C, 75.16; H, 4.21; N, 5.84. Found: C, 75.29;
H, 4.08; N, 5.96.
1H NMR (400 MHz, CDCl3): δ = 8.21–8.13 (m, 4 H), 7.83–7.69 (m, 3 H),
7.52 (t, J = 7.3 Hz, 1 H), 7.25–7.17 (m, 2 H).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–K

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Q. Wang et al.
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Synthesis
2-(2-Methoxyphenyl)quinoline (3n)
13C NMR (100 MHz, CDCl3): δ = 162.8, 147.5, 136.4, 129.4, 128.5,
Pale yellow solid; yield: 47.0 mg (40%); mp 57–59 °C (Lit.25 59 °C).
127.4, 126.7, 125.7, 121.3, 41.0, 23.2, 13.9.
HRMS (ESI): m/z [M + H]+ calcd for C12H14N: 172.1121; found:
172.1113.
FTIR (film): 2920, 2850, 1599, 1581, 1554, 1504, 1491, 1461, 1437,
1421, 1315, 1259, 1232, 1181, 1127, 1063, 1023, 833, 790, 756, 681
cm–1
.
2-Nitrobenzaldehyde (7a)
1H NMR (400 MHz, CDCl3): δ = 8.29 (d, J = 7.5 Hz, 1 H), 8.18 (d, J = 8.0
Hz, 1 H), 7.93–7.82 (m, 3 H), 7.73 (t, J = 7.3 Hz, 1 H), 7.55 (t, J = 7.0 Hz,
1 H), 7.44 (t, J = 7.3 Hz, 1 H), 7.14 (t, J = 7.0 Hz, 1 H), 7.04 (d, J = 8.0 Hz,
1 H), 3.87 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 157.3, 156.8, 135.7, 131.6, 130.6,
129.5, 129.1, 127.4, 127.0, 126.4, 123.5, 121.3, 111.5, 55.7.
A mixture of 2-nitrobenzyl alcohol (1a, 78.1 mg, 0.5 mmol), DIPEA
(125 μL, 0.75 mmol), and dppf (14.1 mg, 5 mol%) in toluene (1.0 mL)
was stirred at 150 °C (screw-capped vial) for 4 h under argon, cooled
to r.t., then water (5 mL) was added. The two layers were separated,
and the aqueous phase was extracted with EtOAc (3 × 10 mL). The
combined organic extracts were washed by brine, dried (anhyd
Na2SO4), filtered, and concentrated. The residue was purified by flash
chromatography (silica gel, 100–200 mesh) to afford 7a (45.8 mg,
60%) as a bright yellow solid; mp 43–44 °C.
HRMS (ESI): m/z [M + H]+ calcd for C16H14NO: 236.1070; found:
236.1066.
2-(3-Chlorophenyl)quinoline (3o)
Pale yellow solid; yield: 52.7 mg (44%); mp 66–68 °C (Lit.23 67–69 °C).
FTIR (film): 3104, 2923, 1697, 1605, 1572, 1524, 1446, 1397, 1344,
1270, 1182, 1141, 1080, 871, 856, 819, 788, 737, 693 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 10.34 (s, 1 H), 8.06 (d, J = 7.6 Hz, 1 H),
7.89 (d, J = 7.6 Hz, 1 H), 7.80–7.72 (m, 2 H).
13C NMR (100 MHz, CDCl3): δ = 188.0, 149.4, 134.0, 133.6, 131.1,
FTIR (film): 2922, 2851, 1659, 1597, 1554, 1506, 1481, 1433, 1315,
1284, 1241, 1078, 875, 828, 796, 781, 755, 694 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.32–8.18 (m, 3 H), 8.10–7.54 (m, 4 H),
7.61–7.44 (m, 3 H).
13C NMR (100 MHz, CDCl3): δ = 155.6, 148.1, 141.3, 136.9, 134.9,
130.0, 129.8, 129.7, 129.2, 127.6, 127.4, 127.3, 126.6, 125.5, 118.6.
129.5, 124.3.
Anal. Calcd for C7H5NO3: C, 55.63; H, 3.33; N, 9.27. Found: C, 55.75; H,
3.19; N, 9.48.
HRMS (ESI): m/z [M + Na]+ calcd for C15H10ClNNa: 262.0394; found:
262.0382.
2-Amino-5-chlorobenzaldehyde (8c)
A mixture of 5-chloro-2-nitrobenzaldehyde (7c, 95.6 mg, 0.5 mmol),
HCO2H (159 μL, 3.0 mmol), DIPEA (374 μL, 2.25 mmol), and dppf (14.1
mg, 0.025 mmol) in toluene (1.0 mL) was stirred at 150 °C (screw-
capped vial) for 4 h under argon, cooled to r.t., then water (5 mL) was
added. The two layers were separated, and the aqueous phase was ex-
tracted with EtOAc (3 × 10 mL). The combined organic extracts were
washed by brine, dried (anhyd Na2SO4), filtered, and concentrated.
The residue was purified by flash chromatography (silica gel, 100–
200 mesh) to afford 8c (35.8 mg, 46%) as a yellow solid; mp 72–73 °C.
2-(4-Tolyl)quinoline (3p)
Pale yellow oil; yield: 69.9 mg (60%).
FTIR (film): 2922, 2851, 1659, 1614, 1598, 1489, 1441, 1410, 1373,
1271, 1006, 902, 833, 808, 787, 755, 730, 616 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.23 (d, J = 8.0 Hz, 1 H), 8.04 (s, 1 H),
7.78 (d, J = 7.8 Hz, 1 H), 7.67 (t, J = 7.4 Hz, 1 H), 7.54–7.48 (m, 3 H),
7.31 (d, J = 7.0 Hz, 2 H), 2.48 (s, 3 H), 2.43 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 160.3, 146.2, 138.1, 137.5, 136.9,
129.2 (2 C), 128.9 (2 C), 128.8, 127.4, 126.6, 126.3, 21.2, 20.5.
FTIR (film): 3465, 3352, 1689, 1660, 1617, 1590, 1551, 1474, 1388,
1311, 1186, 1157, 904, 819, 728, 642 cm–1
.
HRMS (ESI): m/z [M + Na]+ calcd for C17H15NNa: 256.1097. Found:
256.1085.
1H NMR (400 MHz, CDCl3): δ = 9.78 (s, 1 H), 7.42 (s, 1 H), 7.23 (d, J =
8.8 Hz, 1 H), 6.60 (d, J = 8.8 Hz, 1 H).
13C NMR (100 MHz, CDCl3): δ = 192.8, 148.3, 135.2, 134.2, 120.7,
119.2, 117.6.
3-Phenylquinoline (3q)
Pale yellow solid; yield: 69.7 mg (68%); mp 49–51 °C (Lit.26 49–50 °C).
Anal. Calcd for C7H6ClNO: C, 54.04; H, 3.89; N, 9.00. Found: C, 54.26;
H, 3.71; N, 9.15.
FTIR (film): 2922, 2851, 1659, 1633, 1493, 1469, 1449, 1412, 1363,
1341, 1125, 1077, 1026, 954, 787, 762, 697 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 9.07 (s, 1 H), 8.18 (s, 1 H), 8.06 (d, J =
7.7 Hz, 1 H), 7.75 (d, J = 7.3 Hz, 1 H), 7.61–7.30 (m, 7 H).
6-Chloro-2-phenylquinoline (3c) from 2-Amino-5-chlorobenzal-
dehyde (8c)
13C NMR (100 MHz, CDCl3): δ = 149.5, 146.9, 137.6, 133.8, 133.4,
129.4, 129.1, 128.9, 128.1, 128.0, 127.9, 127.3, 127.0.
HRMS (ESI): m/z [M + Na]+ calcd for C15H11NNa: 228.0784; found:
228.0776.
A mixture of 2-aminobenzaldehyde 8c (77.8 mg, 0.5 mmol), ace-
tophenone (6a, 71 μL, 0.6 mmol), HCO2H (53 μL, 1.0 mmol), DIPEA
(125 μL, 0.75 mmol), and dppf (14.1 mg, 0.025 mmol) in toluene (1.0
mL) was stirred at 140 °C (screw-capped vial) for 1 d under argon,
cooled to r.t., then water (5 mL) was added. The two layers were sepa-
rated, and the aqueous phase was extracted with EtOAc (3 × 10 mL).
The combined organic extracts were washed by brine, dried (anhyd
Na2SO4), filtered, and concentrated. The residue was purified by flash
chromatography (silica gel, 100–200 mesh) to afford quinoline 3c
(44.3 mg, 37%).
2-Propylquinoline (3r)
Colorless oil; yield: 53.0 mg (62%).
FTIR (film): 2960, 2929, 2871, 1618, 1601, 1561, 1508, 1464, 1426,
1310, 1116, 825, 755 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.08 (d, J = 8.3 Hz, 1 H), 8.06 (d, J = 8.2
Hz, 1 H), 7.78–7.46 (m, 3 H), 7.29 (d, J = 8.4 Hz, 1 H), 2.96 (t, J = 7.8 Hz,
2 H), 1.90–1.79 (m, 2 H), 1.02 (t, J = 7.3 Hz, 3 H).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–K

J
Q. Wang et al.
Paper
Synthesis
2-Phenylquinoline (3a) from 2-Nitrobenzyl Methyl Ether (12a)
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Commun. 2015, 51, 2286. (ab) Liu, G.; Yi, M.; Liu, L.; Wang, J.;
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Alabugin, I. V. Chem. Commun. 2015, 51, 12831. (ae) Sun, K.;
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The mixture of 2-nitrobenzyl methyl ether (12a, 83.6 mg, 0.5 mmol),
1-phenylethanol (2a, 75 μL, 0.6 mmol), HCO2H (53 μL, 1.0 mmol),
DIPEA (125 μL, 0.75 mmol), and dppf (14.1 mg, 0.025 mmol) in tolu-
ene (1.0 mL) was stirred at 150 °C (screw-capped vial) for 1 d under
argon, cooled to r.t., then water (5 mL) was added. The two layers
were separated, and the aqueous phase was extracted with EtOAc (3 ×
10 mL). The combined organic extracts were washed by brine, dried
(Na2SO4), filtered, and concentrated. The residue was purified by flash
chromatography (silica gel, 100–200 mesh) to afford quinoline 3a
(73.9 mg, 72%).
Acknowledgment
This work was supported by the Natural Scientific Research Innova-
tion
Foundation
in
Harbin
Institute
of
Technology
(HIT.NSRIF.201708), the Science and Technology Development Project
of Weihai (2012DXGJ02), the Natural Science Foundation of Shandong
(2015ZRA10064), and the National Natural Science Foundation of
China (21272046).
Supporting Information
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0035-1562496.
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u
p
p
ortioInfgrmoaitn
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p
ortiInfogrmoaitn
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© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–K