Preparation of 3-hydroxyquinolines from direct oxidation of dihydroquinolinium salts

Article abstract of DOI:10.1039/c8ra07940d

A series of functionalized 3,4-dihydroquinolinium salts were prepared from the reaction of aryldiazonium salt with alkene in a nitrile solution. Further oxidation yielding either 3-hydroxyquinoline or quinoline products was investigated. A one-pot process from aryldiazonium salts, alkenes and nitriles leading to 3-hydroxyquinolines was also developed. Furthermore, an intramolecular trapping of an N-arylnitrilium ion with a vinyl group at the ortho position leading to 2-substituted quinolines was revealed.

Full text of DOI:10.1039/c8ra07940d

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Preparation of 3-hydroxyquinolines from direct
oxidation of dihydroquinolinium salts†
Cite this: RSC Adv., 2018, 8, 38166
*
Mani Ramanathan,‡ Jing Wan‡ and Shiuh-Tzung Liu
A series of functionalized 3,4-dihydroquinolinium salts were prepared from the reaction of aryldiazonium
salt with alkene in a nitrile solution. Further oxidation yielding either 3-hydroxyquinoline or quinoline
products was investigated. A one-pot process from aryldiazonium salts, alkenes and nitriles leading to 3-
hydroxyquinolines was also developed. Furthermore, an intramolecular trapping of an N-arylnitrilium ion
with a vinyl group at the ortho position leading to 2-substituted quinolines was revealed.
Received 25th September 2018
Accepted 5th November 2018
DOI: 10.1039/c8ra07940d
rsc.li/rsc-advances
Despite the excellent signicance, synthetic efforts towards
this ubiquitous core remain largely underdeveloped. Classical
Introduction
routes leading to 3-hydroxyquinoline derivatives are Fried-
lander type condensations,9 Ptzinger synthesis,10 Danheiser
type annulation of 2-iodostyrenes with acetylenes,11 Knoevena-
gel condensation followed by decyanative epoxide-arene cycli-
zation,12 and Cromwell's approach of epoxide opening/
condensation of o-aminobenazalacetophenone oxides.13 In
Functionalized quinolines are highly privileged structural units
due to their widespread occurrence in various natural products
and functional materials.1 The quinoline core is known to be
a versatile building block in the preparation of small molecules
with diverse therapeutic properties.2 Among the various quin-
oline derivatives, 3-hydroxyquinolines (quinoline-3-ols) are
privileged (Fig. 1).3 Typically, Talnetant is a potential neuro-
kinin 3 receptor antagonist primarily used in irritable bowel
syndrome and psychotic disorders,3a whereas PSI-697 is utilized
as an orally active effective P-selectin inhibitor.3b These ubiq-
uitous cores have also been studied as selective inhibitors HIV-1
reverse transcriptase,4 antiallergic agents (TA-270),5 anti-
oxidant3c and D-amino acid oxidase inhibitors (DAAO).6 In
addition, these frameworks have been used as building blocks
in functional materials.7 Notably, naturally occurring anti-HIV
fungal metabolites such as viridicatol, viridication and 3-O-
methylviridicatin are derivatives of 3-hydroxyquinolin-2(1H)-
ones.8
recent years, Jamison et al. demonstrated
a convenient
synthesis of 3-hydroxyquinolines via aerobic oxidation of cor-
responding aryl Grignard reagents under a continuous ow
method.14 In 2017, Yadav's group described a NBS mediated
deacylative formation of 3-hydroxyquinolines from 3-acetylqui-
nolines via an epoxide intermediate.15 More recently, Mamedov
et al. developed an in situ Meinwald rearrangement-
intramolecular
reductive
cyclization
of
o-nitro-
arylacetophenone oxides under mild conditions.16 Nevertheless,
the above-mentioned routes require pre-functionalized
Fig. 1 Selected 3-hydroxyquinoline derivatives.
Department of Chemistry, National Taiwan University, Taipei, Taiwan 106. E-mail:
stliu@ntu.edu.tw
† Electronic supplementary information (ESI) available: Spectral data of all
compounds and spectra. See DOI: 10.1039/c8ra07940d
‡ Equal contribution.
Scheme 1 Strategies leading to quinolone derivatives.
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substrates, metal catalysts and/or multistep synthetic protocol
with a limited functionality presented in the molecule. Thus,
there is still a need for the development of a convenient method
from easily available precursors with a diversity of functionality.
In early this year, Youn's group reported the reaction of
aryldiazonium salts with nitrile followed by the cyclization with
alkenes to achieve 3,4-dihydroquinolines, which was subse-
quently either oxidized or reduced to yield the corresponding
quinolines or tetrahydroquinolines, respectively (Scheme 1a).17
In this work, we adopted the similar method to prepare 3,4-
dihydroquinolines followed by a further oxidation at C-3 posi-
tion leading to 3-hydroxyquinolines (Scheme 1b).
Scheme 2 Reactions of 1a with benzonitrile.
Results and discussion
Preparation of dihydroquinolinium salts
According to Youn's procedure, we have prepared a series of 4-
aryl-dihydroquinolines by reaction of aryldiazonium tetra-
uoroborate with styrenes in a nitrile solution (Table 1). Inter-
estingly, when arylnitrile was employed, the corresponding 2,4-
diaryl substituted quinolinium salt (3h) was obtained as the
major products, but accompanied with quinazolines (4) as the
side product (Scheme 2).18c Similarly, when a-methylstyrene was
used as the substrate, a 4,4-disubstituted dihydroquinoline 3m
was isolated in 49% yield. However, reaction of a-bromostyrene
with 1a in acetonitrile gave quinoline 5 as the single product
presumably due the elimination of HBr (Scheme 3). Instead of
styrene, norbornylene smoothly participated in the reaction
leading to fused-tricyclic quinolinium salts 3n in 62% yield
(eqn. (1)).
Scheme 3 Reactions of 1a with 1,1-disubstituted styrenes.
(1)
Oxidization of 3,4-dihydroquinolinium salts
Table 1 Isolation of dihydroquinolinesa
During the chromatographic purication of dihydroquinoline,
we learned that both quinoline and 3-hydroxyquinoline,
resulting from the oxidation, were obtained. This observation
raised our attention of the preparation of 3-hydroxyquinolines
from dihydroquinoline via oxidation. Thus, further studies
focused on this issue with the use of 3a as a model. Basically, we
proposed that the allylic oxidation giving 6a0 followed by tau-
tomerization should render the desired product (Scheme 4).
Table 2 summarizes the results of the oxidation of 3a under
various conditions.
Entry
Substituents
Product 3 (yield)
Quite a lot of procedures were attempted in the oxidation of
3a, but in the most cases leading the quinoline 5, to be a fav-
oured process. Fortunately, the desired hydroxyquinoline 6a
1
2
3
4
5
6
7
8
R1 ¼ H, Ar ¼ Ph, R ¼ Me
3a, (81%)
R1 ¼ 4-Me, Ar ¼ Ph, R ¼ Me
R1 ¼ 4-Me, Ar ¼ Ph, R ¼ Ph
R1 ¼ 4-(t-Bu), Ar ¼ Ph, R ¼ Me
R1 ¼ H, Ar ¼ Ph, R ¼ Pr
3b, R1 ¼ 6-Me (72%)
3c, R1 ¼ 6-Me (54%)
3d, R1 ¼ 6 t-Bu (68%)
3e, (63%)
R1 ¼ H, Ar ¼ Ph, R ¼ i-Pr
3f, (57%)
R1 ¼ H, Ar ¼ Ph, R ¼ c-C3H5
3g, (66%)
R1 ¼ H, Ar ¼ Ph, R ¼ Ph
3h, (67%)b
9
R1 ¼ H, Ar ¼ p-BrC6H4, R ¼ Me
R1 ¼ H, Ar ¼ p-ClC6H4, R ¼ Me
R1 ¼ H, Ar ¼ p-ClCH2C6H4, R ¼ Me
R1 ¼ H, Ar ¼ 2,5-Me2C6H3, R ¼ i-Pr
3i, (80%)
3j, (62%)
3k, (76%)
3l, (39%)
10
11
12
a
Reaction conditions: a mixture of 1a (0.52 mmol), 2a (1.04 mmol) and
b
Scheme
4 Oxidation of dihydroquinoline 3a leading to 3-
solvent (2 mL) in reaction tube. Quinazoline 4 as the side product
(18%).
hydroxyquinoline.
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Table 2 Optimization for oxidation of 3a into 6a and 5a
Entry Conditions
6a
5
1
H2O2 (2 eq.)/CH3CN
—
—
Scheme 6 Oxidation of dihydroquinlines to give 3-hydroxyquinolines
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
H2O2 (2 eq.)/Na2CO3/CH3CN
Oxone (1 eq.)/CH3CN
Oxone (1 eq.)/Na2CO3 (1 eq.)/CH3CN
Silica gel/NaHCO3/CH3CN
I2 (1 eq.)/Na2CO3 (1 eq.)/CH3CN
O2 (1 atm)/Na2CO3 (1 eq.)/CH3CN/50 ꢀ
TBHP (2 eq.)/O2 (1 atm)/CH3CN
S8 (1 eq.)/N2 (1 atm)/CH3CN
Cu2O (1 eq.)/O2 (1 atm)/CH3CN
Cu(OAc)2 (1 eq.)/O2 (1 atm)/CH3CN
Na2WO4 (0.1 mmol)/H2O2 (1.2 eq.)/CH3CN/2 h
TBHP(1.2 eq.)/VO(acac)2(0.1 mmol)/CH3CN/2h
AIBN (1 eq.)/CH3CN/N2/reux
30% 55%
10% 58%
30% 43%
15% 42%
15% 77%
14% 30%
22% 33%
(NMR yields).
same procedure (Scheme 6). In case of 3m, the oxidation gave 4-
methyl-4-phenylquinolin-3(4H)-one (7) (eqn (2)),19 which is in
agreement of the proposed pathway of this oxidation in
Scheme 4.
C
—
76%
26% 37%
8%
6%
56%
36%
(2)
30% 70%
—
6%
93%
61%
KOH (2 eq.)/O2 (1 atm)/CH3CN
Na2CO3 (1 eq.)/O2 (1 atm)/CH3CN
Na2CO3 (10 eq.)/O2 (1 atm)/CH2Cl2/72 h
Na2CO3 (10 eq.)/O2 (1 atm)/MeOH/72 h
Na2CO3 (10 eq.)/TEMPO/O2 (1 atm)/CH2Cl2/72 h 18% 11%
11% 51%
73% 25%
12% 60%
One-pot fashion of preparation of 3-hydoxyquinolines
a
Reaction conditions: a mixture of 3a (0.16 mmol) in solvent (2 mL) was
We attempted to carry out the two step reactions in a one-pot
fashion (Table 3). Various aryldiazonium salts, nitriles and
alkenes participated well in this oxidative transformation to
afford structurally multi-substituted 3-hydroxyquinoline
frameworks. Typically, phenyldiazonium tetrauoroborate was
treated with styrene in anhydrous MeCN under conditions
identical to those employed previously (Table 1), followed by
treatment of Na2CO3 and prolonged exposure to O2 furnished
treated with oxidant as indicated in each entry.
was obtained in 73% yield upon treating with O2 in the presence
of excess of Na2CO3 accompanied with 25% of 5 (Table 2, entry
17). By addition of an equimolar amount of (2,2,6,6-
tetramethylpiperidin-1-yl)oxyl (TEMPO), the reaction was
inhibited dramatically, indicating that a possible radical
pathway is involved in this oxidation (Table 2, entry 19). Thus,
a rationalization of formation of 5 versus 6a is summarized in
Scheme 5. The abstraction of hydrogen atoms from benzylic or
allylic positions would lead to the products. In particular, the
reaction of O2 with intermediate 3a00 yields the desired
product 6a.
Table 3 Preparation of 3-hydroxyquinolines in one-pot fashiona
Few dihydroquinolines were then transformed into the cor-
responding 3-hydroxyquinolines smoothly by adopting the
Entry
Substituents in 6
Product (yield)
1
2
3
4
5
6
7
8
9
R ¼ Me, R1 ¼ H, R2 ¼ C6H5
R ¼ Me, R1 ¼ H, R2 ¼ p-(ClCH2)C6H4
R ¼ Me, R1 ¼ Me, R2 ¼ C6H5,
R ¼ Me, R1 ¼ t-Bu, R2 ¼ C6H5
R ¼ n-Pr, R1 ¼ H, R2 ¼ C6H5,
R ¼ i-Pr, R1 ¼ H, R2 ¼ C6H5
R ¼ c-Pr, R1 ¼ H, R2 ¼ C6H5
R ¼ Me, R1 ¼ H, R2 ¼ CH3(CH2)5
R ¼ C6H5, R1 ¼ H, R2 ¼ C6H5
6a (36%)
6b (34%)
6d (47%)
6e (44%)
6f (32%)
6g (39%)
6h (42%)
6i (56%)
6j (46%)
a
Reaction conditions: a mixture of arenediazonium salt (0.52 mmol),
alkene (1.04 mmol) and nitrile (2 mL) in reaction tube at 80 ꢀC for
2 h; followed by an aqueous workup with saturated aq. NaHCO3 and
stirred in O2 (1 atm) with 5 g of Na2CO3 for 3 days.
Scheme
5 Abstraction of hydrogen from benzylic versus allylic
positions.
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out from diazonium salts in a one-pot fashion. Intramolecular
trapping of in situ generated N-arylnitrilium intermediate with
an alkene could generate 2-substituted quinolines in good
yields. Preparation of functionalized 3-hydroxyquinoline deriv-
atives through other known synthetic avenues generally
requires a multistep synthesis.
Experimental
1H and 13C NMR were recorded in a 400 MHz Bruker spec-
trometer. Chemical shis were given relative to CDCl3, CD3CN
and DMSO-d6. Acetonitrile and other liquid nitriles were dried
over activated molecular sieves, respectively, whereas solid
nitriles were dried under vacuum. All the anilines were
commercially purchased and used for diazotization without
further purication. Other chemicals were used as purchased.
Flash chromatography was performed using silica gel 230–400
mesh. Analytical thin layer chromatography (TLC) was per-
formed using Merck-60 F-254 plates. In cases of known
compounds, their 1H and 13C NMR values were compared with
the literature values. Melting points were determined on a Fargo
MP-1D instrument. All spectral data are deposited in the ESI.†
Scheme 7 Intra- versus inter-molecular reactions.
the 3-hydroxyquinoline derivative 6a in 36% isolated yield
(Table 3, entry 1). Aryldiazonium salts bearing electron-
donating substituents (Me-, t-Bu-) afforded the corresponding
3-hydroxyquinolines in acceptable yields (Table 3, entries 3–4).
It should be noted that minor amount of 2,4-disubstituted
quinoline derivatives were also isolated from the reaction
mixture. Several aliphatic nitriles such as, primary, secondary,
cyclic nitriles involved in the reaction and smoothly delivered
the corresponding products (Table 3, entries 5–7). Unfortu-
nately, benzylnitrile and chloroacetonitrile failed to produce the
corresponding adducts. To our delight, aliphatic alkene was
also a viable substrate for this oxidative transformation and
provided the corresponding 2,4-dialkyl-3-hydroxyquinoline in
good yield (Table 3, entry 8). As expected, benzonitrile furnished
the expected adduct (6j) together with 21% of 2,4-
phenylquinazoline.
General procedure for preparation of 3,4-dihydroquinolines
In a dry 10 mL glass sealed tube, phenyldiazonium salt (100 mg,
0.52 mmol, 1.0 eq.) and styrene (108 mg, 1.04 mmol, 2.0 eq.)
were suspended in 2 mL of anhydrous nitrile. The tube was
sealed with a Teon screw cap and heated in an oil bath (80 ꢀC)
for 2 h. Aer cooling to room temperature, reaction mixture
with diethyl ether (20 mL). Corresponding 3,4-dihy-
droquinolinium tetrauoroborate salt was formed as a solid
which was washed with 2 ꢁ 10 mL of diethyl ether and dried
under vacuum.
When aryldiazonium salt bearing adjacent phenyl or meth-
ylthio moiety was employed, N-arylnitrilium intermediate
expeditiously underwent the intramolecular cyclization to
deliver 6-methyl-phenanthridine18 (8) and 2-substituted benzo-
thiazole (9) (Scheme 7). Presumably, the intra-molecular
pathway is superior to the inter-molecular one.
2-Methyl-4-phenyl-3,4-dihydroquinolinium tetrauoroborate
(3a)17
Besides the intermolecular reaction with styrenes, we also
examined the reaction via an intramolecular fashion. Thus, o-
1
ethenylbenzenediazonium salt 11 was used for investigation. Off-white solid (130 mg, 81%); mp 193–194 ꢀC: H NMR (400
MHz, CDCl3) d 12.4 (brs, 1H), 7.52 (dd, J ¼ 7.6, 1.6 Hz, 1H), 7.48–
Reaction of 11 with various nitriles gave the corresponding 2-
7.44 (m, 1H), 7.44–7.40 (m, 2H), 7.39–7.32 (m, 2H), 7.23–7.20
(m, 2H), 7.03–7.00 (m, 1H), 4.49 (t, J ¼ 8.8 Hz, 1H), 3.48–3.32 (m,
2H), 2.66 (s, 3H); 13C NMR (100 MHz, CDCl3) d 189.2, 141.8,
133.2, 132.6, 131.3, 130.5, 130.3, 130.1, 129.2, 129.1, 121.8, 38.7,
38.6, 25.7. HRMS (ESI-TOF) calcd for C16H16N (M-BF4)+ m/z ¼
222.1277, found 222.1274. These data are in agreement with the
reported data.
substituted quinolines 12a–d in good yields (eqn (3)). Obviously,
the nucleophilic attack of C]C toward nitrilium ion followed by
elimination took place immediately to deliver the nal product.
(3)
2,6-Dimethyl-4-phenyl-3,4-dihydroquinolinium tetrauoro-
borate (3b)
1
Pale yellow solid (121 mg, 72%). Mp 191–192 ꢀC. H NMR (400
MHz, CD3CN): d ¼ 12.41 (brs, 1H), 7.41–7.37 (m, 3H), 7.35–7.31
(m, 1H), 7.27 (d, J ¼ 8.0 Hz, 1H), 7.20 (d, J ¼ 7.2 Hz, 2H), 6.85 (s,
1H), 4.43 (t, J ¼ 8.8 Hz, 1H), 3.44–3.28 (m, 2H), 2.63 (s, 3H), 2.27
Conclusions
In summary, we have demonstrated a synthetic useful approach (s, 3H) ppm. 13C NMR (100 MHz, CD3CN): d ¼ 187.3, 143.3,
for the preparation of 3-hydroxyquinolines from dihy- 141.8, 130.9, 130.8, 130.6, 130.2, 129.0 (2C), 128.9, 121.4, 38.5,
droquinolines under atmospheric pressure of oxygen in the 38.4, 25.3, 21.5 ppm. HRMS (ESI-TOF) calcd for C17H18N (M-
presence of sodium carbonate. This preparation can be carried BF4)+ m/z ¼ 236.1434, found 236.1443.
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129.9, 128.9 (2C), 120.8, 38.4, 32.1, 21.1, 14.6, 14.1 ppm. HRMS
(ESI-TOF) calcd for C18H18N (M-BF4)+ m/z ¼ 248.1434, found
248.1455.
6-Methyl-2,4-diphenyl-3,4-dihydroquinolinium
tetrauoroborate (3c)
Bright yellow solid (98 mg, 54%). Mp 110–111 ꢀC. 1H NMR (400
MHz, CD3CN): d ¼ 12.28 (brs, 1H), 8.07–8.05 (m, 2H), 7.88–7.84
(m, 1H), 7.72–7.65 (m, 3H), 7.41–7.31 (m, 4H), 7.27–7.24 (m,
2H), 4.61 (t, J ¼ 8.4 Hz, 1H), 3.92–3.79 (m, 2H), 2.33 (s, 3H) ppm.
13C NMR (100 MHz, CD3CN): d ¼ 177.5, 143.8, 141.3, 137.7,
131.8, 131.5, 131.0, 130.9 (2C), 130.5, 130.4, 130.2, 128.9 (2C),
122.5, 38.8, 36.0, 21.6 ppm. HRMS (ESI-TOF) calcd for C22H20N
(M-BF4)+ m/z ¼ 298.1590, found 298.1571.
2,4-Diphenyl-3,4-dihydroquinolinium tetrauoroborate (3h)
Orange solid (129 mg, 67%). Mp 101–102 ꢀC. 1H NMR (400 MHz,
CD3CN): d ¼ 12.32 (brs, 1H), 8.10–8.08 (m, 2H), 7.90–7.86 (m,
1H), 7.77 (dd, J ¼ 8.0, 1.6 Hz, 1H), 7.74–7.70 (m, 2H), 7.56–7.47
(m, 2H), 7.42–7.32 (m, 3H), 7.28–7.26 (m, 2H), 7.12 (d, J ¼
7.6 Hz, 1H), 4.67 (t, J ¼ 8.4 Hz, 1H), 3.97–3.83 (m, 2H) ppm. 13
C
NMR (100 MHz, CD3CN): d ¼ 179.0, 141.1, 138.0, 133.9, 132.7,
131.7, 130.9 (2C), 130.6 (2C), 130.3, 130.0, 129.1, 129.0, 122.6,
38.8, 36.0 ppm. HRMS (ESI-TOF) calcd for C21H18N (M-BF4)+ m/z
¼ 284.1434, found 284.1439.
6-(tert-Butyl)-2-methyl-4-phenyl-3,4-dihydroquinolinium
tetrauoroborate (3d)
1
Pale yellow solid (101 mg, 68%). Mp 190–191 ꢀC. H NMR (400
MHz, CD3CN): d ¼ 12.4 (brs, 1H), 7.51 (dd, J ¼ 8.4, 1.6 Hz, 1H),
7.46 (d, J ¼ 8.4 Hz, 1H), 7.40–7.37 (m, 2H), 7.34–7.30 (m, 1H),
7.20 (d, J ¼ 7.2 Hz, 2H), 7.13 (d, J ¼ 1.2 Hz, 1H), 4.50 (t, J ¼
4-(4-Bromophenyl)-2-methyl-3,4-dihydroquinolinium
tetrauoro-borate (3i)
8.4 Hz, 1H), 3.47–3.31 (m, 2H), 2.64 (s, 3H), 1.21 (s, 9H) ppm. 13
C
Orange solid (162 mg, 80%). Mp 145–147 ꢀC. 1H NMR (400 MHz,
CD3CN): d ¼ 12.44 (br, 1H, N–H), 7.56–7.42 (m, 5H, Ar–H), 7.16–
7.13 (m, 2H, Ar–H), 7.02 (d, J ¼ 7.4 Hz, 1H, Ar–H), 4.50, 4.52–4.48
(t, J ¼ 8.8 Hz, 1H, –CH), 3.47–3.29 (m, 2H, –CH2), 2.65 (s, 3H,
–CH3) ppm. 13C NMR (100 MHz, CD3CN): d ¼ 188.7, 140.7,
133.0, 132.7, 132.3, 131.0, 130.3, 129.8(2C), 122.0, 121.4, 38.0,
37.7, 25.3 ppm. HRMS (ESI-TOF) calcd for C16H15N79Br (M-BF4):
m/z ¼ 300.0388, found 300.0379; HRMS (ESI-TOF) calcd for
NMR (100 MHz, CD3CN): d ¼ 187.7, 156.0, 141.9, 130.7, 130.6,
130.2, 128.9, 128.8, 127.3, 126.8, 121.3, 38.7, 38.5, 35.8, 31.2,
25.4 ppm. HRMS (ESI-TOF) calcd for C20H24N (M-BF4)+ m/z ¼
278.1903, found 278.1914.
4-Phenyl-2-propyl-3,4-dihydroquinolinium tetrauoroborate
(3e)
C
16H15N81Br (M-BF4): m/z ¼ 302.0368; found: 302.0359.
1
Pale yellow solid (110 mg, 63%). Mp 132–133 ꢀC. H NMR (400
MHz, CD3CN): d ¼ 12.40 (brs, 1H), 7.59 (d, J ¼ 7.6 Hz, 1H), 7.51–
7.44 (m, 2H), 7.40–7.30 (m, 3H), 7.17 (d, J ¼ 7.2 Hz, 2H), 7.08 (d, J
¼ 7.2 Hz, 1H), 4.52 (t, J ¼ 8.0 Hz, 1H), 3.49–3.36 (m, 2H), 2.93–
4-(4-Chlorophenyl)-2-methyl-3,4-dihydroquinolinium
tetrauoro-borate (3j)
Yellow solid (111 mg, 62%). Mp 161–162 ꢀC. 1H NMR (400 MHz,
2.79 (m, 2H), 1.77–1.58 (m, 2H), 0.92 (t, J ¼ 7.6 Hz, 3H) ppm. 13
C
NMR (100 MHz, CD3CN): d ¼ 191.7, 141.6, 133.3, 132.8, 131.4, CD3CN): d ¼ 7.51–7.39 (m, 5H, Ar–H), 7.22–7.19 (m, 2H, Ar–H),
130.5, 130.4, 130.2, 129.1 (2C), 122.1, 40.9, 38.5, 37.5, 20.2, 7.03 (d, J ¼ 7.2 Hz, 1H, Ar–H), 4.51 4.53–4.49 (t, J ¼ 8.4 Hz, 1H,
14.0 ppm. HRMS (ESI-TOF) calcd for C18H20N (M-BF4)+ m/z ¼ –CH), 3.48–3.29 (m, 2H, –CH2), 2.65 (s, 3H, –CH3) ppm. 13C NMR
250.1590, found 250.1593.
(100 MHz, CD3CN): d ¼ 188.6, 140.3, 134.0, 132.8, 132.3, 130.72,
130.4, 130.0, 129.9, 129.4, 121.4, 38.1, 37.7, 25.3 ppm. HRMS
(ESI-TOF) calcd for C16H15N35Cl (M-BF4) m/z ¼ 256.0893, found
2-Isopropyl-4-phenyl-3,4-dihydroquinolinium
256.0897; HRMS (ESI-TOF) calcd for C16H15N37Cl (M-BF4) m/z ¼
tetrauoroborate (3f)
258.0864; found: 258.0964.
1
Pale yellow solid (101 mg, 57%). Mp 148–149 ꢀC. H NMR (400
MHz, CD3CN): d ¼ 12.20 (brs, 1H), 7.66 (dd, J ¼ 7.2, 1.2 Hz, 1H),
4-(4-(Chloromethyl)phenyl)-2-methyl-3,4-dihydroquinolinium
tetrauoroborate (3k)
7.53–7.45 (m, 2H), 7.39–7.30 (m, 3H), 7.16–7.10 (m, 3H), 4.53 (t, J
¼ 8.0 Hz, 1H), 3.47–3.35 (m, 2H), 3.17 (sept, 6.8 Hz, 1H), 1.27 (d,
J ¼ 6.8 Hz, 3H), 1.15 (d, J ¼ 6.8 Hz, 3H) ppm. 13C NMR (100 MHz, Bright yellow solid (141 mg, 76%). Mp 126–127 ꢀC. 1H NMR (400
CD3CN): d ¼ 194.9, 141.4, 133.4, 132.8, 131.6, 130.4, 130.3, MHz, CD3CN): d ¼ 12.29 (brs, 1H), 7.53–7.49 (m, 2H), 7.47–7.41
130.2, 129.1, 129.0, 122.4, 38.5, 35.2, 18.6, 18.5 ppm. HRMS (m, 3H), 7.22 (d, J ¼ 8.0 Hz, 2H), 7.03 (d, J ¼ 7.6 Hz, 1H), 4.66 (s,
(ESI-TOF) calcd for C18H20N (M-BF4)+ m/z ¼ 250.1590, found 2H), 4.51 (t, J ¼ 8.8 Hz, 1H), 3.48–3.31 (m, 2H), 2.65 (s, 3H) ppm.
250.1597.
13C NMR (100 MHz, CD3CN): d ¼ 189.0, 142.1, 138.9, 133.1,
132.7, 131.0, 130.8, 130.3, 130.2, 129.7, 121.8, 46.9, 38.5, 38.4,
25.7 ppm. HRMS (ESI-TOF) calcd for C17H1735ClN (MꢂBF4)+ m/z
¼ 270.1044, found 270.1051; HRMS (ESI-TOF) calcd for
2-Cyclopropyl-4-phenyl-3,4-dihydroquinolinium
tetrauoroborate (3g)
Bright yellow solid (114 mg, 66%). Mp 157–158 ꢀC. 1H NMR (400
MHz, CD3CN): d ¼ 12.3 (brs, 1H), 7.52–7.45 (m, 2H), 7.41–7.31
(m, 4H), 7.17–7.14 (m, 2H), 7.03 (d, J ¼ 7.6 Hz, 1H), 4.42 (t, J ¼
8.0 Hz, 1H), 2.95–2.93 (m, 2H), 2.41–2.34 (m, 1H), 1.68–1.56 (m,
C
17H1737ClN (M-BF4)+ m/z ¼272.1044, found 272.1115.
4-(2,5-Dimethylphenyl)-2-isopropyl-3,4-dihydroquinolinium
tetrauoroborate (3l)
2H), 1.55–1.48 (m, 1H), 1.33–1.27 (m, 1H) ppm. 13C NMR (100 Orange solid (74 mg, 39%). Mp 158–159 ꢀC. 1H NMR (400 MHz,
MHz, CD3CN): d ¼ 191.3, 141.0, 133.6, 131.5, 131.2, 130.2 (2C), CD3CN): d ¼ 12.04 (br, 1H, N–H), 7.64–7.62 (d, J ¼ 7.6 Hz, 1H,
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Ar–H), 7.53–7.44 (m, 2H, Ar–H), 7.19–7.17 (d, J ¼ 8.0 Hz, 1H, Ar–
H), 7.05–7.00 (m, 2H, Ar–H), 6.65 (s, 1H, Ar–H), 4.74–4.70 (t, J ¼
8.4 Hz, 1H, –CH), 3.41–3.24 (m, 2H, –CH2), 3.21–3.11 (septet, J ¼
6.8 Hz, 1H, –CH(CH3) (CH3)), 2.37 (s, 3H, –CH3), 2.19 (s, 3H,
–CH3), 1.29–1.27 (d, J ¼ 6.8 Hz, 3H, –CH3), 1.18–1.16 (d, J ¼
6.8 Hz, 3H, –CH3) ppm. 13C NMR (100 MHz, CD3CN): d ¼ 194.8,
138.6, 137.3, 134.1, 133.4, 132.5, 131.9, 131.6, 129.7 (2C), 129.3,
128.5, 122.0, 38.2, 34.3, 33.7, 20.9, 19.1, 18.5, 18.0 ppm. HRMS
General procedure for the oxidation of 3,4-dihydroquinoline
with oxygen
2-Methyl-4-phenyl-3,4-dihydroquinolinium tetrauoroborate 3a
(0.3 mmol) was extracted with DCM (25 mL), washed with
a saturated aqueous solution of NaHCO3 (5 mL). The organic
layer was dried over MgSO4 and ltered. To this was added
Na2CO3 (10 equiv) and this mixture was stirred at room
temperature for 3 days. Next, the resulting mixture was ltered
through a plug of Celite and concentrated in vacuo. The residue
was puried by ash column chromatography (silica gel, eluent,
30% EtOAc in hexane) to give the desired product.
(ESI-TOF) calcd for C20H24 (M-BF4):
278.1906.
¼
278.1909; found:
2,4-Dimethyl-4-phenyl-3,4-dihydroquinolinium
tetrauoroborate (3m)
General procedure for one-pot preparation of 3-
hydroxyquinoline
1
ꢀ
White solid (60 mg, 49%). Mp 171–172 C. H NMR (400 MHz,
CD3CN): d ¼ 7.55–7.51 (m, 3H, Ar–H), 7.37–7.29 (m, 4H, Ar–H),
7.21–7.19 (m, 2H, Ar–H), 3.71–3.66 (d, J ¼ 18.8 Hz, 1H,
–CHa(Hb)), 3.23–3.19 (d, J ¼ 18.8 Hz, 1H, –C(Ha)Hb), 2.63 (s, 3H,
–CH3), 1.72 (s, 3H, –CH3) ppm. 13C NMR (100 MHz, CD3CN): d ¼
188.3, 144.8, 135.8, 132.5, 132.4, 129.7, 129.6, 128.6, 128.3,
127.3, 121.7, 44.8, 40.0, 27.3, 25.4 ppm. HRMS (ESI-TOF) calcd
for C17H18N (M-BF4): ¼ 236.1439; found 236.1442.
In a dry 10 mL glass sealed tube, phenyldiazonium salt (100 mg,
0.52 mmol, 1.0 eq.) and styrene (108 mg, 1.04 mmol, 2.0 eq.)
were suspended in 2 mL of anhydrous nitrile. The tube was
sealed with a Teon screw cap and heated in an oil bath (80 ꢀC)
for 2 h. Aer cooling to room temperature, reaction mixture was
diluted with DCM (20 mL) and washed with saturated aq.
NaHCO3 solution (10 mL). Combined organic layer was stirred
over anhydrous Na2CO3 (5 g) for 3 days. Solvents removed and
puried by column chromatography (eluent: 20% to 40% EtOAc
in hexane) to obtain the corresponding substituted 3-
hydroxyquinolines.
6-Methyl-6a,7,8,9,10,10a-hexahydro-7,10-
methanophenanthridinum tetrauoroborate (3n)
1
ꢀ
Pale yellow solid (95 mg, 62%). Mp 191–192 C. H NMR (400
MHz, CD3CN): d ¼ 12.0 (brs, 1H), 7.45 (t, J ¼ 7.6 Hz, 1H), 7.40 (d,
J ¼ 7.2 Hz, 1H), 7.34 (t, J ¼ 7.2 Hz, 1H), 7.29 (d, J ¼ 7.6 Hz, 1H),
3.28 (d, J ¼ 10.4 Hz, 1H), 3.20 (d, J ¼ 10.4 Hz, 1H), 2.85 (s, 1H),
2.59 (s, 3H), 2.47 (s, 1H), 1.79–1.62 (m, 4H), 1.35–1.28 (m,
2H) ppm. 13C NMR (100 MHz, CD3CN): d ¼ 186.5, 132.5, 131.3,
131.0, 129.4, 129.1, 121.4, 50.1, 49.5, 47.1, 42.9, 36.3, 31.2, 29.3,
24.3 ppm. HRMS (ESI-TOF) calcd for C15H18N (M-BF4)+ m/z ¼
212.1434, found 212.1445.
2-Methyl-4-phenylquinolin-3-ol (6a)18b
Off-white solid (44 mg, 36%); mp 238–239 ꢀC:1H NMR (400
MHz, DMSO-d6) d 8.86 (brs, 1H), 7.87 (d, J ¼ 8.4 Hz, 1H), 7.54 (t, J
¼ 7.2 Hz, 2H), 7.47 (t, J ¼ 7.2 Hz, 2H), 7.34–7.31 (m, 3H), 7.23 (d,
J ¼ 8.0 Hz, 1H), 2.62 (s, 3H); 13C NMR (100 MHz, DMSO-d6)
d 152.5, 145.4, 142.1, 133.7, 130.3, 128.7, 128.4, 128.2, 127.8,
127.5, 125.8, 125.7, 124.1, 21.2. HRMS (ESI-TOF) calcd for
C
16H14NO (M + H)+ m/z ¼ 236.1075, found 236.1073. These data
are in agreement with the reported data.
2,4-Diphenylquinazoline (4)18c
4-(4-(Chloromethyl)phenyl)-2-methylquinolin-3-ol (6b)15
1
ꢀ
White solid (26 mg, 18%). Mp 110–111 C. H NMR (400 MHz,
CDCl3): d ¼ 8.70 (d, J ¼ 8.0 Hz, 2H), 8.15 (d, J ¼ 8.4 Hz, 1H), 8.12
(d, J ¼ 8.4 Hz, 1H), 7.89–7.85 (m, 3H), 7.59–7.57 (m, 3H), 7.55–
7.47 (m, 4H) ppm. 13C NMR (100 MHz, CDCl3) d 168.3, 160.2,
151.9, 138.1, 137.6, 133.5, 130.5, 130.1, 129.9, 129.1, 128.6, 128.5
(3C), 126.9, 121.6 ppm. HRMS (ESI-TOF) calcd for C20H15N2 (M +
H)+ m/z ¼ 283.1235, found 283.1231. These data are in agree-
ment with the reported data.18c
1
Pale yellow solid (59 mg, 69%). H NMR (400 MHz, DMSO-d6):
d ¼ 8.98 (br, 1H, O–H), 7.88 (d, J ¼ 8.4 Hz, 1H, Ar–H), 7.60 (d, J ¼
8.0 Hz, 2H, Ar–H), 7.50–7.46 (m, 1H, Ar–H), 7.37–7.33 (m, 3H,
Ar–H), 7.23 (d, J ¼ 8.4 Hz, 1H, Ar–H), 4.88 (s, 2H, -CH2Cl), 2.63 (s,
3H, -CH3) ppm. 13C NMR (100 MHz, DMSO-d6): d ¼ 152.6, 145.5,
142.1, 137.1, 133.9, 130.7, 129.0, 128.3, 128.2, 127.4, 125.8(2C),
124.0, 46.0, 21.3 ppm. HRMS (ESI-TOF) calcd for C17H1535ClNO
(M + H+) m/z ¼ 284.0842; found: 284.0840; HRMS (ESI-TOF)
calcd for C17H1537ClNO (M + H+) m/z ¼ 286.0813; found:
286.0807. These data are in agreement with the reported data.
2-Methyl-4-phenylquinoline (5)
Pale yellow solid (33 mg, 77%). 1H NMR (400 MHz, CDCl3): d ¼
4-(4-Chlorophenyl)-2-methylquinolin-3-ol (6c)
8.07 (d, J ¼ 8.8 Hz, 1H), 7.82 (d, J ¼ 8.4 Hz, 1H), 7.66–7.63 (m,
1
ꢀ
1H), 7.49–7.43 (m 5H), 7.38 (t, J ¼ 7.2 Hz, 1H), 7.19 (s, 1H), 2.75 Pale yellow solid (41 mg, 50%). Mp 272–274 C. H NMR (400
(s, 3H). 13C NMR (100 MHz, CDCl3): d ¼ 158.4, 148.4, 148.3, MHz, DMSO-d6): d ¼ 7.87 (d, J ¼ 8.4 Hz, 1H, Ar–H), 7.59 (d, J ¼
138.0, 129.4, 129.2, 128.9, 128.4, 128.2, 125.6, 125.5, 125.0, 8.4 Hz, 2H, Ar–H), 7.50–7.46 (m, 1H, Ar–H), 7.38–7.33 (m, 3H,
122.1, 25.2; HRMS (ESI) calcd for C16H14N (M + H)+ m/z ¼ Ar–H), 7.23 (d, J ¼ 8.0 Hz, 1H, Ar–H), 2.61 (s, 3H, –CH3) ppm. 13
C
220.1126 found 220.1127. These data are in agreement with the NMR (125 MHz, DMSO-d6): d ¼ 152.6, 145.7, 142.0, 132.7, 132.4,
reported data.18b
128.6, 128.3, 127.3, 127.2, 126.0, 125.9(2C), 123.9, 21.2 ppm.
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HRMS (ESI-TOF) calcd for C16H1335ClNO (M + H+) m/z ¼ 1.2 Hz, 1H), 7.51–7.44 (m, 2H), 3.02 (t, J ¼ 8.0 Hz, 2H), 2.67 (s,
270.0680; found: 270.0695; HRMS (ESI-TOF) calcd for 3H), 1.66–1.58 (m, 2H), 1.43–1.36 (m, 2H), 1.28–1.26 (m, 2H),
C
16H1337ClNO (M + H+) m/z ¼ 272.0651; found: 272.0692.
1.25–1.23 (m, 2H), 0.84 (t, J ¼ 6.8 Hz, 3H) ppm. 13C NMR (100
MHz, CDCl3): d ¼ 150.2, 146.1, 141.5, 127.6 (2C), 126.9, 126.3,
122.9 (2C), 31.6, 29.6, 29.3, 25.2, 22.5, 20.0, 14.0 ppm. HRMS
(ESI-TOF) calcd for C16H22NO (M + H)+ m/z ¼ 244.1701, found
244.1696.
2,6-Dimethyl-4-phenylquinolin-3-ol (6d)
1
ꢀ
Pale yellow solid (56 mg, 47%). Mp 205–206 C. H NMR (400
MHz, CDCl3): d ¼ 7.92 (d, J ¼ 8.4 Hz, 1H), 7.57–7.47 (m, 3H),
7.37–7.32 (m, 3H), 7.06 (s, 1H), 4.32 (brs, 1H), 2.71 (s, 3H), 2.35
(s, 3H) ppm. 13C NMR (100 MHz, CDCl3): d ¼ 150.3, 144.8, 141.0,
136.0, 135.8, 132.4, 130.2, 129.4, 128.8, 128.5, 127.9, 127.2,
123.3, 21.6, 20.4 ppm. HRMS (ESI-TOF) calcd for C17H16NO (M +
H)+ m/z ¼ 250.1232, found 250.1239.
2,4-Diphenylquinolin-3-ol (6j)20
Off-white solid (68 mg, 46%). Mp 123–124 ꢀC. 1H NMR (400
MHz, CDCl3): d ¼ 8.15 (d, J ¼ 8.4 Hz, 1H), 8.01–7.93 (m, 2H),
7.62–7.58 (m, 2H), 7.58–7.53 (m, 2H), 7.52–7.48 (m, 2H), 7.48–
7.42 (m, 3H), 7.42–7.37 (m, 2H), 5.45 (brs, 1H). 13C NMR (100
MHz, CDCl3): d ¼ 150.0, 143.9, 143.3, 137.2, 132.2, 130.3 (2C),
129.5 (2C), 129.4 (2C), 129.1, 128.4 (2C), 127.6, 126.8, 124.5.
HRMS (ESI-TOF) calcd for C21H16NO (M + H)+ m/z ¼ 298.1232,
found 298.1242. These data are in agreement with the reported
data.
6-(tert-Butyl)-2-methyl-4-phenylquinolin-3-ol (6e)
Pale yellow solid (52 mg, 44%). Mp 243–244 ꢀC.1H NMR (400
MHz, CDCl3): d ¼ 7.90 (d, J ¼ 9.2 Hz, 1H), 7.59–7.52 (m, 2H),
7.47 (t, J ¼ 7.6 Hz, 2H), 7.38 (d, J ¼ 7.6 Hz, 2H), 7.25–7.24 (m,
1H), 2.68 (s, 3H), 1.24 (s, 9H) ppm. 13C NMR (100 MHz, CDCl3):
d ¼ 150.4, 148.7, 144.6, 141.2, 132.3, 130.2, 129.5, 128.9, 127.9,
127.5, 126.7, 125.1, 119.4, 34.8, 31.0, 20.5 ppm. HRMS (ESI-TOF)
calcd for C20H20NO (M + H)+ m/z ¼ 292.1701, found 292.1702.
2,4-Dimethyl-4-phenylquinolin-3(4H)-one (7)
Yellow oil (52 mg, 70%). 1H NMR (400 MHz, CDCl3): d ¼ 7.60 (d,
J ¼ 7.2 Hz, 1H, Ar–H), 7.46–7.42 (m, 1H, Ar–H), 7.37–7.33 (m, 1H,
Ar–H), 7.29–7.23 (m, 4H, Ar–H), 7.03–7.01 (m, 2H, Ar–H), 2.28 (s,
3H, –CH3), 1.89 (s, 3H, –CH3) ppm. 13C NMR (100 MHz, CDCl3):
d ¼ 196.4, 160.7, 140.7, 140.6, 136.8, 129.4, 128.8, 128.7, 128.4,
127.9, 127.6, 127.2, 53.6, 23.3, 20.0 ppm. HRMS (ESI-TOF) calcd
for C17H16NO (M + H+) m/z ¼ 250.1232; found: 250.1243.
4-Phenyl-2-propylquinolin-3-ol (6f)
Pale yellow solid (43 mg, 32%). Mp 177–178 ꢀC.1H NMR (400
MHz, CDCl3): d ¼ 8.00 (d, J ¼ 8.4 Hz, 1H), 7.57–7.54 (m, 2H),
7.50–7.46 (m, 2H), 7.38 (d, J ¼ 7.2 Hz, 2H), 7.32–7.31 (m, 2H),
5.50 (brs, 1H), 3.02 (t, J ¼ 8.0 Hz, 2H), 1.85 (sextet, J ¼ 7.6 Hz,
2H), 1.05 (t, J ¼ 7.6 Hz, 3H) ppm. 13C NMR (100 MHz, CDCl3)
d 154.7, 144.3, 142.9, 132.2, 130.3, 129.6, 129.0, 128.7, 127.5,
127.1, 126.2, 126.0, 124.3, 36.1, 21.7, 14.2 ppm. HRMS (ESI-TOF)
calcd for C18H18NO (M + H)+ m/z ¼ 264.1388, found 264.1390.
6-Methylphenanthridine (8)18b
1
Pale yellow oil (59 mg, 82%). H NMR (400 MHz, CDCl3): d ¼
8.59 (d, J ¼ 8.0 Hz, 1H), 8.50 (d, J ¼ 8.4 Hz, 1H), 8.18 (d, J ¼
8.4 Hz, 1H), 8.09 (d, J ¼ 8.0 Hz, 1H), 7.81 (t, J ¼ 8.0 Hz, 1H), 7.70–
7.64 (m, 2H), 7.59 (t, J ¼ 7.6 Hz, 1H), 3.02 (s, 3H) ppm. 13C NMR
(100 MHz, CDCl3): d ¼ 158.8, 143.6, 132.5, 130.4, 129.2, 128.6,
127.2, 126.5, 126.3, 125.8, 123.7, 122.2, 121.9, 23.3 ppm.
HRMS(ESI) calcd for C14H12N (M + 1)+ m/z ¼ 194.0970, found
194.0976. These data are in agreement with the reported data.
2-Isopropyl-4-phenylquinolin-3-ol (6g)
Pale yellow solid (53 mg, 39%). Mp 98–99 ꢀC.1H NMR (400 MHz,
CDCl3): d ¼ 8.05 (d, J ¼ 8.4 Hz, 1H), 7.61–7.57 (m, 2H), 7.54–7.47
(m, 2H), 7.40 (d, J ¼ 6.8 Hz, 2H), 7.32–7.31 (m, 2H), 5.25 (brs,
1H), 3.63 (sept, J ¼ 6.8 Hz, 1H), 1.43 (d, J ¼ 6.8 Hz, 6H) ppm. 13
C
NMR (100 MHz, CDCl3): d ¼ 158.5, 143.6, 142.9, 132.2, 130.4,
129.7, 129.1, 129.0, 127.2, 126.9, 126.0, 125.9, 124.2, 31.0,
20.8 ppm. HRMS (ESI-TOF) calcd for C18H18NO (M + H)+ m/z ¼
264.1388, found 264.1394.
2-Phenylbenzo[d]thiazole (9)21b
Off-white solid (45 mg, 52%). Mp 111–112 ꢀC. 1H NMR (400
MHz, CDCl3): d ¼ 8.09–8.05 (m, 3H), 7.88 (dd, J ¼ 8.0, 0.4 Hz,
1H), 7.49–7.45 (m, 4H), 7.36 (t, J ¼ 7.2 Hz, 1H) ppm. 13C NMR
(100 MHz, CDCl3) d 168.0, 154.1, 135.0, 133.5, 130.9, 128.9,
127.5, 126.2, 125.1, 123.0, 121.5 ppm. HRMS(ESI) calcd for
2-Cyclopropyl-4-phenylquinolin-3-ol (6h)
Off-white solid (57 mg, 42%). Mp 127–128 ꢀC. 1H NMR (400
MHz, CDCl3): d ¼ 7.97 (d, J ¼ 8.4 Hz, 1H), 7.58 (t, J ¼ 7.6 Hz, 2H),
7.54–7.44 (m, 2H), 7.41–7.39 (m, 2H), 7.31–7.26 (m, 2H), 5.35
C
13H10NS (M + 1)+ m/z ¼ 212.0534, found 212.0539. These data
are in agreement with the reported data.
(brs, 1H), 2.63 (m, 1H), 1.36–1.35 (m, 2H), 1.10–1.06 (m, 2H). 13
C
NMR (100 MHz, CDCl3): d ¼ 154.5, 144.4, 132.2, 130.3, 129.9 General procedure for preparing 2-substituted quinolines
(2C), 129.6, 129.0, 128.4, 126.6, 126.3, 125.6, 124.3, 11.9, 9.5. from o-vinylaryldiazonium tetrauoroborate
HRMS (ESI-TOF) calcd for C18H16NO (M + H)+ m/z ¼ 262.1232,
In a dry 10 mL glass sealed tube, o-vinylaryldiazonium salt (0.46
found 262.1232.
mmol) is suspended in 2 mL of anhydrous nitrile. The tube was
sealed with a Teon screw cap and heated in an oil bath (60 ꢀC)
4-Hexyl-2-methylquinolin-3-ol (6i)
for 12 h. Aer cooling to room temperature, reaction mixture
Off-white solid (70 mg, 56%). Mp 161–162 ꢀC. 1H NMR (400 was diluted with DCM (20 mL) and washed with saturated aq.
MHz, CDCl3): d ¼ 8.00 (d, J ¼ 8.0 Hz, 1H), 7.83 (dd, J ¼ 8.0, NaHCO3 solution (10 mL). Organic layer was dried over
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anhydrous Na2SO4. Solvents removed and puried by column
chromatography (eluent: 20% EtOAc : hexane) to obtain the title
compound.
Notes and references
1 (a) S. Cretton, S. Dorsaz, A. Azzollini, Q. F. Godal,
L. Marcourt, S. N. Ebrahimi, F. Voinesco, E. Michellod,
D. Sanglard, M. Cuendet and P. Christen, J. Nat. Prod.,
2016, 79, 300; (b) J. P. Michael, Nat. Prod. Rep., 2008, 25,
166; (c) J. P. Michael, Nat. Prod. Rep., 2004, 21, 650.
2 (a) O. Afzal, S. Kumar, M. R. Haider, M. R. Ali, R. Kumar,
M. Jaggi and S. Bawa, Eur. J. Med. Chem., 2015, 97, 871; (b)
S. Kumar, S. Bawa and H. Gupta, Mini-Rev. Med. Chem.,
2009, 9, 1648; (c) D. J. Hazuda, P. Felock and M. Witmer,
Science, 2000, 287, 646; (d) J. Wang, M. W. Chen, Y. Ji,
S. B. Hu and Y. G. Zhou, J. Am. Chem. Soc., 2016, 138,
10413; (e) M. Heitbaum, R. Frchlich and F. Glorius, Adv.
Synth. Catal., 2010, 352, 357, and references therein.
3 (a) L. A. Dawson, K. J. Cato, C. Scott, J. M. Watson,
M. D. Wood, R. Foxton, R. De la Flor, G. A. Jones,
J. N. Kew, J. E. Cluderay, E. Southam, G. S. Murkitt,
J. Gartlon, D. J. Perberton, D. C. Jones, C. H. Davies and
J. Hagen, Neuropsychopharmacology, 2008, 33, 1642; (b)
P. W. Bedard, V. Clerin, N. Sushkova, B. Tchernychev,
T. Antrilli, C. Resmini, J. C. Keith Jr, J. K. Hennan,
N. Kaila, S. Debernardo, K. Janz, Q. Wang, D. L. Crandall,
R. G. Schaub, G. D. Shaw and L. L. Carter, J. Pharmacol.
Exp. Ther., 2008, 324, 497; (c) M. A. Massoud, S. A. El Bialy,
W. A. Bayoumi and W. M. El Husseiny, Heterocycl.
Commun., 2014, 20, 81.
2-Methylquinoline (12a)21c
Brown oil (55 mg, 74%). 1H NMR (400 MHz, CDCl3): d ¼ 7.97 (d,
J ¼ 8.4 Hz, 1H), 7.92 (t, J ¼ 8.0 Hz, 1H), 7.60 (d, J ¼ 8.0 Hz, 1H),
7.61–7.57 (m, 1H), 7.40–7.36 (m, 1H), 7.18–7.15 (m, 1H), 2.66 (s,
3H) ppm. 13C NMR (100 MHz, CDCl3); d ¼ 158.7, 147.6, 135.9,
129.2, 128.3, 127.2, 126.2, 125.4, 121.7, 25.1 ppm. HRMS (ESI-
TOF) calcd for C10H10N (M + H)+ m/z ¼ 144.0813, found
144.0818. These data are in agreement with the reported data.
2-Propylquinoline (12b)21d
1
Pale yellow oil (61 mg, 69%). H NMR (400 MHz, CDCl3): d ¼
8.04 (dd, J ¼ 8.4, 3.2 Hz, 2H), 7.75 (d, J ¼ 8.4 Hz, 1H), 7.68–7.63
(m, 1H), 7.45 (t, J ¼ 8.0 Hz, 1H), 7.27 (d, J ¼ 8.4 Hz, 1H), 2.94 (t, J
¼ 7.6 Hz, 2H), 1.82 (sext, J ¼ 7.6 Hz, 2H), 1.00 (t, J ¼ 7.6 Hz,
3H) ppm. 13C NMR (100 MHz, CDCl3): d ¼ 162.8, 147.7, 136.2,
129.3, 128.6, 127.4, 126.7, 125.6, 121.3, 41.1, 23.2, 13.9 ppm.
HRMS (ESI-TOF) calcd for C12H14N (M + H)+ m/z ¼ 172.1126,
found 172.1126. These data are in agreement with the reported
data.
2-Isopropylquinoline (12c)21e
1
Pale yellow oil (56 mg, 63%). H NMR (400 MHz, CDCl3): d ¼
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8.05 (d, J ¼ 8.4 Hz, 1H), 8.00 (d, J ¼ 8.4 Hz, 1H), 7.70 (d, J ¼
8.0 Hz, 1H), 7.65–7.61 (m, 1H), 7.42 (t, J ¼ 8.4 Hz, 1H), 7.27 (d, J
¼ 8.4 Hz, 1H), 3.24 (sept, J ¼ 6.8 Hz, 1H), 1.37 (d, J ¼ 6.8 Hz,
6H) ppm. 13C NMR (100 MHz, CDCl3): d ¼ 167.4, 147.6, 136.2,
129.0, 128.8, 127.2, 126.7, 125.4, 119.0, 37.1, 22.3. HRMS (ESI-
TOF) calcd for C12H14N (M + H)+ m/z ¼ 172.1126, found
172.1134. These data are in agreement with the reported data.
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2-Phenylquinoline (12d)21c
1
Off-white solid (72 mg, 69%). H NMR (400 MHz, CDCl3): d ¼
8.20–8.14 (m, 4H), 7.85 (d, J ¼ 8.8 Hz, 1H), 7.80 (dd, J ¼ 8.0,
0.8 Hz, 1H), 7.73–7.69 (m, 1H), 7.54–7.49 (m, 3H), 7.47–7.43 (m,
1H) ppm. 13C NMR (100 MHz, CDCl3): d ¼ 157.3, 148.2, 139.6,
136.7, 129.7, 129.6, 129.2, 128.8, 127.5, 127.4, 127.1, 126.2,
118.9 ppm. HRMS (ESI-TOF) calcd for C15H12N (M + H)+ m/z ¼
206.0970, found 206.0965. These data are in agreement with the
reported data.
Conflicts of interest
There are no conicts to declare.
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Chem., 2017, 15, 1080.
16 V. A. Mamedov, V. L. Mamedova, V. V. Sykaev, D. E. Korshin,
G. Z. Khikmatova, E. V. Mironova, O. B. Bazanova,
L. K. Rizvanov and S. K. Latypova, Tetrahedron, 2017, 73,
5082.
Acknowledgements
We thank the Ministry of Science and Technology, Taiwan
(Grant No. MOST106-2113-M-002-018) for the nancial support.
We also thank “National Taiwan University Mass Spectrometry-
based Proteomics Core Facility” for the measurement of ESI
mass data.
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