Environmentally Friendly Nafion-Mediated Friedl?nder Quinoline Synthesis under Microwave Irradiation: Application to One-Pot Synthesis of Substituted Quinolinyl Chalcones

SYNTHESIS

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C.-K. Chan et al.

Paper

Synthesis

Environmentally Friendly Nafion-Mediated Friedländer Quinoline

Synthesis under Microwave Irradiation: Application to One-Pot

Synthesis of Substituted Quinolinyl Chalcones

Chieh-Kai Chan

Chien-Yu Lai

Friedländer

reaction

R

R²

R¹

R²

R¹

Nafion NR50

EtOH, MW

O

Cheng-Chung Wang*

+

Ar

NH₂

O

N

Institute of Chemistry, Academia Sinica, Taipei 11529,

Taiwan, R.O.C.

wangcc@gate.sinica.edu.tw

· 56 examples · good FG tolerance · high yields

· atom-economic · environmentally friendly

Received: 06.02.2020

Accepted after revision: 25.02.2020

Published online: 19.03.2020

-methylene group, followed by cyclodehydration, belongs

to the simplest and most straightforward approaches for

the synthesis of polysubstituted quinolines.^17b–dAlthough

the Friedländer synthesis using 2-aminobenzaldehyde and

acetaldehyde was already reported in 1882 in the presence

of sodium hydroxide,^17bthere are some problems due to the

basic reaction conditions, causing less generality and more

operational complexity because of the occurrence of side

reactions. Moreover, base-catalyzed annulations of 2-ami-

nobenzophenone with uncomplicated ketones, including

cyclohexanone or -keto esters, fail to occur,²¹which is why

acid-catalyzed Friedländer annulations have been broadly

developed.

DOI: 10.1055/s-0039-1690088; Art ID: ss-2020-f0074-op

Abstract An efficient and eco-friendly synthetic route for Friedländer

quinoline synthesis of polysubstituted quinolines is described. This

green chemical method starts from various 2-aminobenzophenones

and mono- or dicarbonyl synthons and uses reusable Nafion NR50 ma-

terial as a solid catalyst in ethanol under microwave irradiation. The pro-

tocol has a high generality of functional groups and provides the de-

sired quinolines in good to excellent yields. Some structures were

confirmed by single-crystal X-ray diffraction analysis.

Key words Friedländer reaction, Nafion catalyst, quinolines, chalcone,

microwave irradiation

Numerous Friedländer-type quinoline synthetic meth-

ods have been developed with the involvement of various

Brønsted or Lewis acid catalysts for the preparation of sub-

stituted quinoline skeletons.²²Among them, sulfonic acid

and its analogues have been widely applied to the synthesis

of substituted quinolines, especially p-toluenesulfonic acid.

For example, Wang’s group developed a p-toluenesulfonic

acid catalyzed synthesis of quinoline derivatives under sol-

vent-free and microwave irradiation conditions.^18gHeydari

and co-workers presented a facile protocol for quinoline

synthesis in an aqueous medium by the use of a sulfonic

acid functionalized ionic liquid as a water-tolerant acidic

catalyst.²³Javanshir’s group reported an innovative ball-

milling technique for the synthesis of quinoline deriva-

tives.²⁴In 2018, Wang described a p-toluenesulfonic acid

catalyzed annulation to obtain quinolines in ethanol at re-

flux.^18mIn the past two years, Pastor published imidazolium

salt mediated quinoline syntheses.^18n,oRecently, some het-

erogeneous catalysts, alumina or acid-supported and met-

al-organic framework (MOF) materials, have been devel-

oped.²⁵Hasaninejad developed a reusable sulfonic acid

modified polyethylene glycol (PEG) to prepare substituted

quinolines under microwave irradiation conditions.²⁶

Therefore, the development of a facile, simple, low-cost, and

eco-benign protocol for preparing quinolines is desirable in

organic synthesis.

Quinoline is a ubiquitous skeleton in privileged hetero-

cyclic scaffold systems. It is found in numerous natural

products,¹and is widely used as synthons²and as ligands

for the preparation of metal complexes.³Its usefulness to

drug discovery and remarkably broad pharmacological and

biological activities, such as antimalarial (chloroquinine

and quinine),⁴antifungal and analgesic,⁵anticancer,⁶anti-

bacterial,⁷anti-inflammatory,⁸anti-platelet aggregation,⁹

anti-asthmatic,¹⁰anti-hypertensive,¹¹and anti-tuberculosis

properties,¹²as tyrosine kinase PDGF-RTK inhibiting

agents,^5e,10a,13as multifunctional agents for Alzheimer’s dis-

ease,¹⁴and applications as other therapeutic agents,¹⁵have

been widely explored. Nevertheless, substituted quinoline

derivatives are valuable precursors to hierarchically under-

go self-assembly processes for the preparation of various

nano- and mesostructures with enhanced electronic and

photonic functions.¹⁶

The traditional protocols for the construction of quino-

lines include Skraup, Doebner, Doebner–von Miller, Gould–

Jacobs, Combes, Pfitzinger, and Friedländer quinoline syn-

theses.¹⁷Most of these reactions require drastic reaction

conditions or unsatisfactory yields. Among these,

Friedländer annulation, an acid-,¹⁸base-,¹⁹or metal-pro-

moted²⁰intermolecular condensation of substituted 2-ami-

nobenzaldehyde, 2′-aminoacetophenone, or 2-aminoben-

zophenone with a carbonyl compound possessing a reactive

Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

B

C.-K. Chan et al.

Paper

Synthesis

Nafion is a commercially available acidic material, and

belongs to a type of synthetic polymer possessing ionic

properties named ionomers.²⁷Its unique ionic properties

result from copolymerization incorporating perfluorovinyl

ether groups terminated with sulfonate groups onto a

tetrafluoroethylene (PTFE) backbone.²⁸Therefore, the de-

velopment of new synthetic routes for the preparation of

substituted quinoline derivatives is of relevant interest in

organic synthesis.²⁹Continuing our research on synthetic

applications of microwave irradiation³⁰and the preparation

of quinoline derivatives,³¹in this work, we aim to provide a

facile, efficient, eco-benign, and greener protocol for the

preparation of substituted quinolines by using reusable,

commercially available Nafion NR50 as a sulfonic acid func-

tionalized material catalyst under microwave irradiation

conditions (Scheme 1).³²

Friedländer

reaction

R

R²

R¹

R²

R¹

Nafion NR50

O

+

Ar

EtOH, MW

NH₂

O

N

Scheme 1 Nafion NR50 mediated synthesis of substituted quinolines

Table 1 Synthesis of Substituted Quinolines 1a–q^a,b

R

O

R

O

Nafion NR50

O

+

Ar

EtOH, 1 h

MW, 200 °C

NH₂

O

N

2

3a

1a–q

O

Br

O₂N

Cl

N

1a (95%)

1b (91%)

1c (83%)

O

MeO

N

1d (93%)

1e (92%)

1f (95%)

F

MeO

O

N

1g (91%)

1h (94%)

1i (91%)

Cl

Br

O

N

1j (90%)

1k (93%)

1l (92%)

OMe

R

N

O

Cl

O

Cl

N

1p R = Me (94%)

1q R = H (95%)

1m (95%)

1n (92%)

1o (86%)

^aReaction conditions: 2 (1.0 mmol), 3a (1.1 mmol), Nafion NR50 (20 mol%), EtOH (10 mL), MW.

^bIsolated yields given in parentheses.

C

C.-K. Chan et al.

Paper

Synthesis

To examine this transformation of compounds 2 and 3

to quinoline 1, 2-amino-5-chlorobenzophenone (2a) and

acetylacetone (3a) were selected as the model substrates;

the optimization of the reaction conditions and the plausi-

ble mechanism are shown in Table S1 and Scheme S1, re-

spectively (Supporting Information, SI). With an effective

Friedländer cyclization procedure established, the substrate

scope of the Nafion-catalyzed quinoline synthesis was

probed, as shown in Table 1. Initially, numerous 2-amino-

benzophenones 2 were examined individually by reacting

them with acetylacetone (3a) under the optimized reaction

conditions. Compounds 2 with halogens (2a,b), nitro (2c),

electron-donating (2d–g), and naphthalene (2h) groups on

the Ar ring gave the desired products 1a–h in high yields.

Other substituents on Ar such as electron-withdrawing

halophenyl groups (2i–k), electron-donating p-tolyl (2l),

methoxyphenyl (2m), and unsubstituted phenyl (2n) gave

corresponding quinolines 1i–n in good to excellent yields.

Chlorophenyl-substituted 2o was also suitable to provide

1o in an 86% yield. Non-aryl R substituents, as in 2′-amino-

acetophenone 2p and 2′-aminobenzaldehyde 2q, reacted

with 3a to afford the corresponding 1p and 1q in excellent

yields. The structures of 1a,b and 1i–l were confirmed by

single-crystal X-ray crystallography.³³

Next, other 1,3-diketone synthons 3b–l were investigat-

ed in reactions with compound 2a in the presence of Nafion

NR50 under the optimized reaction conditions (Table 2).

The reaction of 2a and unsymmetrical diketone 3b provid-

ed two isomers 1r and 1s in 43% and 41% yield, respectively.

Benzoylacetone 3c and dibenzoylmethane 3d reacted with

2a to provide products 1t,u in high yields. The reactions be-

tween cyclic 1,3-diketones 3e–g and 2a afforded the de-

sired tricyclic quinolines 1v–x in 88–93% yield. Additional-

ly, functionalized -keto esters 3h–l were also suitable for

this transformation to provide products 1y–ac in good to

excellent yields. The structures of 1t, 1x, 1ab, and 1ac were

confirmed by single-crystal X-ray crystallography.³³

On the basis of the above-mentioned results in Tables 1

and 2, we set out to survey monocarbonyl-containing -

methylene group substrates. As shown in Scheme 2,

Friedländer quinoline cyclization of substituted 2-amino-

benzophenones 2 with acetone (4a) proceeded smoothly,

leading to the desired 4-aryl-2-methylquinolines 5a–k in

good to excellent yields. The structure of 5a was confirmed

by single-crystal X-ray crystallography.³³

We further examined various monocarbonyl synthons

4b–q with 2a under the optimized reaction conditions (Ta-

Table 2 Synthesis of Substituted Quinolines 1r–ac^a,b

Ph

O

Ph

N

O

Cl

R²

Nafion NR50

O

+

R¹

EtOH, 1 h

MW, 200 °C

NH₂

O

2a

3b–l

1r–ac

O

Cl

N

1r (43%)^c

1s (41%)^c

1t (92%)

1u (89%)

O

Cl

OMe

N

1v (89%)

1w (88%)

1x (93%)

1y (95%)

O

Cl

OEt

Cl

OEt

N

NO₂

OMe

1z (94%)

1aa (89%)

1ab (92%)

1ac (92%)

^aReaction conditions: 2a (1.0 mmol), 3b–l (1.1 mmol), Nafion NR50 (20 mol%), EtOH (10 mL), MW.

^bIsolated yields given in parentheses.

^cTwo products 1r and 1s were obtained from the reaction between 2a and 3b.

D

C.-K. Chan et al.

Paper

Synthesis

ble 3), based on the successful preparation of 2-meth-

ylquinolines 5a–k in Scheme 2. The reactions between 2a

and acetophenone (4b) and 4-nitroacetophenone (4c) took

place as expected to afford the desired 2,4-diarylquinolines

6a,b in high yields. Interestingly, the reactions with medi-

um-sized cyclic ketones 4d–f, 4-tert-butylcyclohexanone

(4g), tetralones 4h–j, and benzo-fused cycloketone 4k pro-

ceeded smoothly to provide tri- or tetracyclic quinolines

6c–j in good to excellent yields.

Moreover, functionalized deoxybenzoins 4l,m were ap-

propriate reagents in this transformation to give products

6k,l in excellent yields (Table 3). Hydroxy-substituted ace-

tophenone 4n and substituted 4-chromanones 4o,p were

suitable precursors to give 6m–o in moderate to good

yields. Compound 6p was formed in 87% yield from 2a and

-keto nitrile 4q. The structures of 6a, 6c–f, 6h–k, and 6n,o

were confirmed by single-crystal X-ray crystallography.³³

To understand the catalytic activity of recovered Nafion

NR50 particles, recycling experiments were conducted (SI,

Figure S1).

Chalcone is regarded as a privileged and ubiquitous

scaffold found in many naturally occurring compounds and

is used as an effective template in medicinal chemistry for

drug discovery. Additionally, substituted chalcones are also

versatile building blocks in organic chemistry because of

their ,-unsaturated ketone functional group, which is a

potential Michael acceptor.³⁴Because of the significant

properties of substituted chalcones in organic and medici-

Table 3 Synthesis of Substituted Quinolines 6^a,b

Ph

R⁴

R³

Cl

R⁴

R³

Nafion NR50

O

+

EtOH, 1 h

MW, 200 °C

O

NH₂

N

2a

4b–q

6

Cl

N

NO₂

6a (91%)

6b (92%)

6c (88%)

6d (94%)

Cl

N

OMe

6e (94%)

6f (86%)

6g (86%)

6h (90%)

Cl

N

OMe

F

OMe

6i (92%)

6j (92%)

6k (93%)

6l (95%)

Cl

OH

Cl

CN

Cl

O

N

OMe

6m (77%)

6n (92%)

6o (93%)

6p (87%)

^aReaction conditions: 2a (1.0 mmol), 4b–q (1.1 mmol), Nafion NR50 (20 mol%), EtOH (10 mL), MW.

^bIsolated yields given in parentheses.

E

C.-K. Chan et al.

Paper

Synthesis

Cl

Ph

N

Ar²

N

O

Cl

Nafion NR50

O

+

Nafion NR50

Ph

EtOH, 2 h

MW, 200 °C

NH₂

O

Ar¹

+

2a

(1.0 mmol)

3e

(0.5 mmol)

9

EtOH, 1 h

MW, 200 °C

O

NH₂

N

(85%)

2

4a

(5 mL)

5a–k

(1.0 mmol)

Scheme 4 Synthesis of quinoline dimer 9

Ar²= Ph

5a, Ar¹= 4-ClC₆H₃(96%)

5b, Ar¹= 4-BrC₆H₃(92%)

5c, Ar¹= 4-NO₂C₆H₃(88%)

5d, Ar¹= naphthalene-1,2-diyl (98%)

Ar¹= C₆H₄

ment of environmentally friendly Nafion NR50 as an acidic

catalyst. This efficient protocol provides the desired prod-

ucts in good to excellent yields. Nafion NR50 particles are

an environmentally friendly and reusable polymer. A two-

step, one-pot pathway for the high-yield synthesis of func-

tionalized chalcones was also developed.

5a

5e, Ar²= 4-FC₆H₄(96%)

5f, Ar²= 4-ClC₆H₄(97%)

5g, Ar²= 4-BrC₆H₄(95%)

5h, Ar²= 4-MeC₆H₄(94%)

5i, Ar²= 4-MeOC₆H₄(88%)

5j, Ar²= Ph (91%)

5k, Ar¹= 4-ClC₆H₃

Ar²= 2-ClC₆H₄(93%)

All reagents and solvents were commercially available and used with-

out further purification. Reactions were routinely performed using

the Discover SP system (CEM) in sealed reaction vessels in standard

mode with the temperature monitored by using a vertically focused

IR sensor. All reactions were monitored by TLC on silica gel 60 F254

(Merck) with detection by UV light. Column chromatography was

performed by using silica gel (200–300 mesh). Products in organic

solvents were dried with anhydrous magnesium sulfate before con-

centration in vacuo. Melting points were determined with a MP-2D

melting apparatus. ¹H and ¹³C NMR spectra were recorded on a Bruker

AVIII 500 and AV 400 spectrometer operating at 500 or 400 and 125

or 100 MHz, respectively. HRMS measurements were obtained on a

Waters LCT Premier XE (Waters Corp., Manchester, UK) instrument

equipped with an electrospray source. The X-ray intensity data were

measured at low temperature (100 K) using an Mo K radiation dif-

fractometer equipped with a kappa geometry goniometer and were

corrected for absorption effects using the numerical method (SAD-

ABS).

Scheme 2 Synthesis of 4-aryl-2-methylquinolines 5a–k and X-ray crys-

tal structure of 5a

nal chemistry, alternative methods for the preparation of

chalcone scaffolds are necessary.

In Scheme 3, the one-pot synthesis of quinolinyl chal-

cones with biological potential is illustrated.³⁵The quino-

linyl chalcone skeleton was prepared from 2-amino-5-chlo-

robenzophenone (2a) and acetylacetone 3a by the involve-

ment of Nafion NR50 in EtOH under microwave irradiation.

Then NaOH and aromatic benzaldehydes 7a–f were added

directly, to afford functionalized chalcones 8a–f. This two-

step one-pot synthetic route provided the desired products

8a–f in high yields. The structure of 8f was confirmed by

single-crystal X-ray crystallography.³³

On the basis of the results in Tables 1–3 and Scheme 2,

we further investigated a double Friedländer route for the

construction of a quinoline dimers. We selected 2-amino-

benzophenone 2a to react with cyclopentane-1,3-dione

(3e) under the optimized reaction conditions (Scheme 4).

The corresponding quinoline dimer 9 was isolated in good

yield.

Quinoline Derivatives 1, 5, and 6; General Procedure

A mixture of 2-aminobenzophenone 2 (1.0 mmol), ketone 3 or 4 (1.1

mmol), and Nafion NR50 (20 mol%) in ethanol (10 mL) was loaded

into a dried 35 mL microwave vial at 25 °C. The mixture was subject-

ed to microwave irradiation and stirred at 200 °C for 1 h. Consump-

tion of the starting materials was confirmed by TLC. The mixture was

cooled to 25 °C and then transferred to a 100 mL round-bottom flask;

the solvent was concentrated under reduced pressure to afford crude

product. The solid crude product was recrystallized (hexane–EtOAc,

5:1 to 2:1). The oily or gummy crude product was purified by column

chromatography (silica gel, hexanes–EtOAc, 4:1 to 1:1). This afforded

products 1a–ac, 5a–k, and 6a–p.

In summary, we reported a Friedländer synthesis of var-

ious quinolines from the reactions of substituted 2-amino-

acetophenones with mono- or diketones by the involve-

Ph

O

Ph

N

O

(i) Nafion NR50 (20 mol%)

EtOH (10 mL), MW 200 °C, 1 h

Cl

O

Ar

+

NH₂

2a (1.0 mmol)

(ii) NaOH (1.0 mmol)

ArCHO 7 (1.2 mmol)

EtOH (10 mL),

O

8a, Ar = Ph (88%)

8b, Ar = 2-FC₆H₄(82%)

8c, Ar = 4-FC₆H₄(84%)

3a (1.1 mmol)

MW, 200 °C, 1 h

8d, Ar = 3,4-(MeO)₂C₆H₃(86%)

8e, Ar = 3,5-(MeO)₂C₆H₃(85%)

8f, Ar = 3,4,5-(MeO)₃C₆H₂(88%)

Scheme 3 One-pot synthesis of quinolinyl chalcones 8a–f

F

C.-K. Chan et al.

Paper

Synthesis

1-(6-Chloro-2-methyl-4-phenylquinolin-3-yl)ethan-1-one (1a)³⁶

HRMS (ESI): m/z [M + H]⁺calcd for C₁₉H₁₈NO: 276.1833; found:

Yield: 280 mg (95%); colorless crystals; mp 160–161 °C (Lit.³⁶159–

276.1375.

160 °C).

1-(6-Methoxy-2-methyl-4-phenylquinolin-3-yl)ethan-1-one (1e)

¹H NMR (500 MHz, CDCl₃):  = 8.00 (d, J = 9.0 Hz, 1 H), 7.64 (dd, J = 2.0,

9.0 Hz, 1 H), 7.56 (d, J = 2.0 Hz, 1 H), 7.53–7.52 (m, 3 H), 7.34–7.32 (m,

2 H), 2.67 (s, 3 H), 1.99 (s, 3 H).

¹³C NMR (125 MHz, CDCl₃):  = 205.25, 153.92, 145.88, 143.06,

135.45, 134.44, 132.44, 130.95, 130.50, 129.89 (2×), 129.20, 128.91

(2×), 125.83, 124.88, 31.79, 23.80.

Yield: 268 mg (92%); colorless solid; mp 135–136 °C.

¹H NMR (500 MHz, CDCl₃):  = 7.94 (d, J = 9.0 Hz, 1 H), 7.48–7.46 (m, 3

H), 7.34–7.32 (m, 3 H), 6.84 (d, J = 2.5 Hz, 1 H), 3.68 (s, 3 H), 2.62 (s, 3

H), 1.95 (s, 3 H).

¹³C NMR (125 MHz, CDCl₃):  = 205.64, 157.54, 150.49, 143.30,

142.39, 135.17, 134.81, 129.97, 129.64 (2×), 128.66, 128.56 (2×),

125.68, 122.04, 103.88, 55.07, 31.64, 23.18.

HRMS (ESI): m/z [M + H]⁺calcd for C₁₈H₁₅ClNO: 296.0837; found:

296.0829.

HRMS (ESI): m/z [M + H]⁺calcd for C₁₉H₁₈NO₂: 292.1332; found:

292.1327.

Single-crystal X-ray crystallography: A crystal of 1a was grown by

slow diffusion of EtOAc into a solution of 1a in CH₂Cl₂to yield color-

less prisms. The compound crystallizes in the monoclinic crystal sys-

tem, space group P21/n, a = 10.4578(12) Å, b = 7.7868(9) Å, c = 17(7)

Å, V = 17.583(2) Å³, Z = 4, d_calcd= 1.372 Mg/m³, F(000) = 616, 2θ range

2.250–27.101°, R indices (all data) R1 = 0.0375, wR2 = 0.0830. CCDC

number: 1945823.

1-(2-Methyl-4,6-diphenylquinolin-3-yl)ethan-1-one (1f)

Yield: 320 mg (95%); colorless solid; mp 169–170 °C.

¹H NMR (500 MHz, CDCl₃):  = 8.14 (d, J = 8.5 Hz, 1 H), 7.96 (dt, J = 2.0,

8.5 Hz, 1 H), 7.80 (d, J = 2.0 Hz, 1 H), 7.54–7.49 (m, 5 H), 7.40–7.37 (m,

4 H), 7.32–7.30 (m, 1 H), 2.72 (s, 3 H), 2.00 (s, 3 H).

¹³C NMR (125 MHz, CDCl₃):  = 205.47, 153.35, 146.81, 143.87,

140.17, 139.14, 135.08, 135.01, 129.93 (2×), 129.64, 129.24, 128.87,

128.74 (2×), 128.67 (2×), 127.51, 127.20 (2×), 125.07, 123.67, 31.75,

23.76.

1-(6-Bromo-2-methyl-4-phenylquinolin-3-yl)ethan-1-one (1b)³⁷

Yield: 308 mg (91%); white solid; mp 161–162 °C (Lit.³⁷157–158 °C).

¹H NMR (500 MHz, CDCl₃):  = 7.92 (d, J = 8.5 Hz, 1 H), 7.76 (dd, J = 2.0,

9.0 Hz, 1 H), 7.72 (d, J = 2.0 Hz, 1 H), 7.53–7.51 (m, 3 H), 7.33–7.31 (m,

2 H), 2.65 (s, 3 H), 1.98 (s, 3 H).

¹³C NMR (125 MHz, CDCl₃):  = 205.12, 154.06, 146.09, 142.95,

135.43, 134.40, 133.49, 130.61, 129.89 (2×), 129.19, 128.90 (2×),

128.15, 126.31, 120.61, 31.76, 23.81.

HRMS (ESI): m/z [M + H]⁺calcd for C₂₄H₂₀NO: 338.1539; found:

338.1536.

1-[6-(4-Methoxyphenyl)-2-methyl-4-phenylquinolin-3-yl]ethan-

1-one (1g)

HRMS (ESI): m/z [M + H]⁺calcd for C₁₈H₁₅BrNO: 340.0332; found:

340.0323.

Yield: 334 mg (91%); colorless solid; mp 190–191 °C.

Single-crystal X-ray crystallography: A crystal of 1b was grown by

slow diffusion of EtOAc into a solution of 1b in CH₂Cl₂to yield color-

less prisms. The compound crystallizes in the monoclinic crystal sys-

tem, space group P21/n, a = 10.5493(7) Å, b = 7.8437(5) Å, c =

17.5892(11) Å, V = 1455.35(16) Å³, Z = 4, d_calcd= 1.553 Mg/m³,

F(000) = 688, 2θ range 2.241–27.102°, R indices (all data) R1 = 0.0237,

wR2 = 0.0559. CCDC number: 1940422.

¹H NMR (500 MHz, CDCl₃):  = 8.11 (d, J = 8.5 Hz, 1 H), 7.95 (dd, J = 2.0,

9.0 Hz, 1 H), 7.73 (d, J = 2.0 Hz, 1 H), 7.53–7.51 (m, 3 H), 7.48 (d, J = 8.5

Hz, 2 H), 7.40–7.38 (m, 2 H), 6.94 (d, J = 8.5 Hz, 2 H), 3.82 (s, 3 H), 2.70

(s, 3 H), 2.00 (s, 3 H).

¹³C NMR (125 MHz, CDCl₃):  = 205.63, 159.35, 153.02, 146.56,

143.76, 138.75, 135.10, 135.05, 132.60, 129.96 (2×), 129.47, 129.15,

128.86, 128.68 (2×), 128.26 (2×), 125.13, 122.85, 114.23 (2×), 55.20,

31.80, 23.76.

1-(2-Methyl-6-nitro-4-phenylquinolin-3-yl)ethan-1-one (1c)^18m

Yield: 254 mg (83%); yellow solid; mp 152–153 °C (Lit.^18m165–

HRMS (ESI): m/z [M + H]⁺calcd for C₂₅H₂₂NO₂: 368.1645; found:

368.1638.

167 °C).

¹H NMR (500 MHz, CDCl₃):  = 8.57 (d, J = 2.5 Hz, 1 H), 8.48 (ddd, J =

1.5, 2.5, 9.0 Hz, 1 H), 8.19 (d, J = 9.0 Hz, 1 H), 7.59–7.56 (m, 3 H), 7.37–

7.35 (m, 2 H), 2.74 (s, 3 H), 2.01 (s, 3 H).

¹³C NMR (125 MHz, CDCl₃):  = 204.52, 157.93, 149.55, 145.65,

145.60, 136.25, 133.58, 130.76, 129.89 (2×), 129.83, 129.24 (2×),

124.37, 123.58, 123.16, 31.68, 24.24.

1-(3-Methyl-1-phenylbenzo[f]quinolin-2-yl)ethan-1-one (1h)

Yield: 292 mg (94%); colorless crystals; mp 199–200 °C.

¹H NMR (500 MHz, CDCl₃):  = 7.94 (s, 2 H), 7.81 (d, J = 7.5 Hz, 1 H),

7.52–7.47 (m, 3 H), 7.42 (d, J = 7.5 Hz, 1 H), 7.38 (d, J = 9.0 Hz, 1 H),

7.32–7.29 (m, 2 H), 7.08 (t, J = 7.5 Hz, 1 H), 2.68 (s, 3 H), 1.91 (s, 3 H).

¹³C NMR (125 MHz, CDCl₃):  = 206.09, 151.70, 148.73, 143.28,

138.87, 136.54, 132.88, 132.03, 129.74, 129.38 (4×), 128.73, 128.65,

127.85, 127.56, 126.37, 125.69, 121.38, 31.77, 23.10.

HRMS (ESI): m/z [M + H]⁺calcd for C₁₈H₁₅N₂O₃: 307.1077; found:

307.1078.

HRMS (ESI): m/z [M + H]⁺calcd for C₂₂H₁₈NO: 312.1383; found:

312.1380.

1-(2,6-Dimethyl-4-phenylquinolin-3-yl)ethan-1-one (1d)

Yield: 256 mg (93%); colorless solid; mp 117–118 °C.

¹H NMR (500 MHz, CDCl₃):  = 7.95 (d, J = 8.5 Hz, 1 H), 7.53–7.49 (m, 4

H), 7.34–7.32 (m, 3 H), 2.66 (s, 3 H), 2.39 (s, 3 H), 1.97 (s, 3 H).

¹³C NMR (125 MHz, CDCl₃):  = 205.83, 152.35, 146.07, 143.17,

136.37, 135.31, 134.78, 132.26, 129.97 (2×), 128.73, 128.61 (2×),

128.52, 124.86, 124.80, 31.87, 23.68, 21.65.

1-[4-(4-Fluorophenyl)-2-methylquinolin-3-yl]ethan-1-one (1i)^18g

Yield: 254 mg (91%); colorless crystals; mp 149–150 °C (Lit.^18g140–

142 °C).

¹H NMR (500 MHz, CDCl₃):  = 8.07 (d, J = 8.5 Hz, 1 H), 7.74–7.70 (m, 1

H), 7.57 (dd, J = 1.0, 8.5 Hz, 1 H), 7.47–7.43 (m, 1 H), 7.36–7.32 (m, 2

H), 7.23–7.20 (m, 2 H), 2.69 (s, 3 H), 2.03 (s, 3 H).

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Synthesis

¹³C NMR (125 MHz, CDCl₃):  = 205.52, 163.0 (d, J = 247.875 Hz),

153.43, 147.50, 142.70, 135.02, 131.85 (d, J = 8.0 Hz, 2×), 131.00 (d, J =

3.125 Hz), 130.17, 128.95, 126.66, 125.79, 124.99, 115.90 (d, J = 21.5

Hz, 2×), 31.99, 23.80.

¹³C NMR (125 MHz, CDCl₃):  = 205.87, 153.50, 147.49, 144.09,

138.86, 134.81, 132.11, 130.01, 129.91 (2×), 129.37 (2×), 128.79,

126.37, 126.19, 125.18, 31.94, 23.84, 21.32.

HRMS (ESI): m/z [M + H]⁺calcd for C₁₉H₁₈NO: 276.1383; found:

276.1377.

HRMS (ESI): m/z [M + H]⁺calcd for C₁₈H₁₅FNO: 280.1132; found:

280.1127.

1-[4-(4-Methoxyphenyl)-2-methylquinolin-3-yl]ethan-1-one (1m)

Single-crystal X-ray crystallography: A crystal of 1i was grown by

slow diffusion of EtOAc into a solution of 1i in CH₂Cl₂to yield colorless

prisms. The compound crystallizes in the monoclinic crystal system,

space group P21/n, a = 9.6875(5) Å, b = 16.2485(8) Å, c = 18.2756(9)

Å, V = 2798.1(2) Å³, Z = 8, d_calcd= 1.326 Mg/m³, F(000) = 1168, 2θ range

1.698–27.095°, R indices (all data) R1 = 0.0501, wR2 = 0.1132. CCDC

number: 1941657.

Yield: 276 mg (95%); colorless crystals; mp 161–162 °C.

¹H NMR (500 MHz, CDCl₃):  = 8.05 (d, J = 8.5 Hz, 1 H), 7.70 (dd, J = 1.5,

8.5 Hz, 1 H), 7.66 (d, J = 8.5 Hz, 1 H), 7.44–7.41 (m, 1 H), 7.28–7.27 (m,

2 H), 7.03–7.01 (m, 2 H), 3.87 (s, 3 H), 2.67 (s, 3 H), 1.99 (s, 3 H).

¹³C NMR (125 MHz, CDCl₃):  = 205.92, 160.01, 153.48, 147.51,

143.72, 134.86, 131.30 (2×), 129.95, 128.79, 127.09, 126.34, 126.07,

125.26, 114.13 (2×), 55.28, 31.82, 23.80.

1-[4-(4-Chlorophenyl)-2-methylquinolin-3-yl]ethan-1-one (1j)^18m

Yield: 266 mg (90%); white solid; mp 152–153 °C (Lit.^18m157–

HRMS (ESI): m/z [M + H]⁺calcd for C₁₉H₁₈NO₂: 292.1332; found:

292.1333.

159 °C).

¹H NMR (500 MHz, CDCl₃):  = 8.07 (d, J = 8.0 Hz, 1 H), 7.72 (t, J = 7.5

Hz, 1 H), 7.55 (d, J = 8.0 Hz, 1 H), 7.27 (d, J = 8.0 Hz, 2 H), 7.45 (t, J = 7.5

Hz, 1 H), 7.30 (d, J = 8.5 Hz, 2 H), 2.69 (s, 3 H), 2.05 (s, 3 H).

¹³C NMR (125 MHz, CDCl₃):  = 205.36, 153.41, 147.48, 142.45,

135.22, 134.88, 133.52, 131.34 (2×), 130.22, 129.02 (2×), 128.98,

126.72, 125.73, 124.76, 32.10, 23.80.

1-(2-Methyl-4-phenylquinolin-3-yl)ethan-1-one (1n)^20k

Yield: 240 mg (92%); white solid; mp 102–103 °C (Lit.^20k100–103 °C).

¹H NMR (500 MHz, CDCl₃):  = 8.07 (d, J = 8.5 Hz, 1 H), 7.73–7.70 (m, 1

H), 7.61 (dd, J = 1.0, 8.5 Hz, 1 H), 7.52–7.49 (m, 3 H), 7.45–7.42 (m, 1

H), 7.36–7.34 (m, 2 H), 2.69 (s, 3 H), 1.99 (s, 3 H).

¹³C NMR (125 MHz, CDCl₃):  = 205.64, 153.51, 147.52, 143.89,

135.19, 134.80, 130.06, 130.04, 130.01 (2×), 128.86, 128.67 (2×),

126.48, 126.12, 125.01, 31.90, 23.84.

HRMS (ESI): m/z [M + H]⁺calcd for C₁₈H₁₅ClNO: 296.0837; found:

296.0838.

Single-crystal X-ray crystallography: A crystal of 1j was grown by

slow diffusion of EtOAc into a solution of 1j in CH₂Cl₂to yield colorless

prisms. The compound crystallizes in the triclinic crystal system,

space group P–1, a = 7.0661(9) Å, b = 10.0723(13) Å, c = 10.5449(14)

Å, V = 724.96(16) Å³, Z = 2, d_calcd= 1.355 Mg/m³, F(000) = 308, 2θ range

1.998–27.061°, R indices (all data) R1 = 0.0390, wR2 = 0.0926. CCDC

number: 1940035.

HRMS (ESI): m/z [M + H]⁺calcd for C₁₈H₁₆NO: 262.1226; found:

262.1222.

1-[6-Chloro-4-(2-chlorophenyl)-2-methylquinolin-3-yl]ethan-1-

one (1o)^18o

Yield: 283 mg (86%); yellow solid; mp 148–149 °C (Lit.^18o144–

146 °C).

¹H NMR (500 MHz, CDCl₃):  = 8.02 (d, J = 9.0 Hz, 1 H), 7.65 (dd, J = 2.5,

9.0 Hz, 1 H), 7.58 (dd, J = 1.0, 8.0 Hz, 1 H), 7.49 (td, J = 2.0, 7.5 Hz, 1 H),

7.42 (td, J = 1.0, 7.5 Hz, 1 H), 7.264 (d, J = 2.0 Hz, 1 H), 7.23 (dd, J = 2.0,

7.5 Hz, 1 H), 2.70 (s, 3 H), 2.15 (s, 3 H).

¹³C NMR (125 MHz, CDCl₃):  = 204.44, 154.06, 145.63, 140.47,

135.67, 133.38, 133.33, 132.77, 132.02, 131.17, 130.85, 130.62,

130.03, 127.40, 125.41, 124.57, 31.27, 23.82.

1-[4-(4-Bromophenyl)-2-methylquinolin-3-yl]ethan-1-one (1k)

Yield: 315 mg (93%); colorless crystals; mp 185–186 °C.

¹H NMR (500 MHz, CDCl₃):  = 8.06 (d, J = 8.5 Hz, 1 H), 7.71 (t, J = 8.0

Hz, 1 H), 7.65 (d, J = 8.0 Hz, 2 H), 7.54 (d, J = 8.5 Hz, 1 H), 7.44 (t, J = 8.0

Hz, 1 H), 7.23 (d, J = 8.0 Hz, 2 H), 2.68 (s, 3 H), 2.05 (s, 3 H).

¹³C NMR (125 MHz, CDCl₃):  = 205.31, 153.38, 147.45, 142.40,

134.78, 133.98, 131.94 (2×), 131.58 (2×), 130.20, 128.95, 126.71,

125.70, 124.64, 123.38, 32.11, 23.78.

HRMS (ESI): m/z [M + H]⁺calcd for C₁₈H₁₄Cl₂NO: 330.0447; found:

330.0445.

HRMS (ESI): m/z [M + H]⁺calcd for C₁₈H₁₅BrNO: 340.0332; found:

340.0326.

1-(2,4-Dimethylquinolin-3-yl)ethan-1-one (1p)³⁹

Single-crystal X-ray crystallography: A crystal of 1k was grown by

slow diffusion of EtOAc into a solution of 1k in CH₂Cl₂to yield color-

less prisms. The compound crystallizes in the triclinic crystal system,

space group P–1, a = 9.0783(9) Å, b = 9.4367(9) Å, c = 9.7984(10) Å,

V = 738.73(13) Å³, Z = 2, d_calcd= 1.529 Mg/m³, F(000) = 344, 2θ range

2.232–27.103°, R indices (all data) R1 = 0.0249, wR2 = 0.0582. CCDC

number: 1940423.

Yield: 187 mg (94%); yellow gum.

¹H NMR (500 MHz, CDCl₃):  = 8.01 (d, J = 8.5 Hz, 1 H), 7.97 (d, J = 8.5

Hz, 1 H), 7.72–7.69 (m, 1 H), 7.56–7.53 (m, 1 H), 2.63 (s, 3 H), 2.59 (s, 3

H), 2.58 (s, 3 H).

¹³C NMR (125 MHz, CDCl₃):  = 206.65, 152.59, 146.94, 138.57,

135.70, 129.80, 129.26, 126.37, 125.95, 123.64, 32.64, 23.54, 15.22.

HRMS (ESI): m/z [M + H]⁺calcd for C₁₃H₁₄NO: 200.1070; found:

200.1065.

1-[2-Methyl-4-(p-tolyl)quinolin-3-yl]ethan-1-one (1l)³⁸

Yield: 253 mg (92%); white solid; mp 130–131 °C (Lit.³⁸130–131 °C).

¹H NMR (500 MHz, CDCl₃):  = 8.06 (d, J = 8.5 Hz, 1 H), 7.72–7.69 (m, 1

H), 7.64 (dd, J = 1.0, 8.5 Hz, 1 H), 7.45–7.41 (m, 1 H), 7.31 (d, J = 7.5 Hz,

2 H), 7.24 (d, J = 8.0 Hz, 2 H), 2.69 (s, 3 H), 2.45 (s, 3 H), 2.01 (s, 3 H).

1-(2-Methylquinolin-3-yl)ethan-1-one (1q)⁴⁰

Yield: 176 mg (95%); white solid; mp 81–82 °C (Lit.⁴⁰75–76 °C).

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C.-K. Chan et al.

Paper

Synthesis

¹H NMR (500 MHz, CDCl₃):  = 8.46 (s, 1 H), 8.02 (d, J = 8.5 Hz, 1 H),

7.84 (d, J = 8.0 Hz, 1 H), 7.77 (t, J = 7.0 Hz, 1 H), 7.54 (t, J = 7.0 Hz, 1 H),

2.90 (s, 3 H), 2.70 (s, 3 H).

¹H NMR (500 MHz, CDCl₃):  = 8.24 (d, J = 9.0 Hz, 1 H), 7.73 (dd, J = 2.5,

9.0 Hz, 1 H), 7.64–7.62 (m, 3 H), 7.50 (d, J = 7.5 Hz, 2 H), 7.49–7.06 (m,

11 H).

¹³C NMR (125 MHz, CDCl₃):  = 199.90, 157.56, 148.23, 138.14,

131.67, 131.07, 128.53, 128.29, 126.62, 125.57, 29.18, 25.59.

HRMS (ESI): m/z [M + H]⁺calcd for C₁₂H₁₂NO: 186.0913; found:

186.0911.

¹³C NMR (125 MHz, CDCl₃):  = 196.60, 156.54, 146.28, 139.44,

137.51, 134.17, 133.05 (2×), 133.00, 132.76, 131.39, 131.24, 129.12

(8×), 128.75, 128.47, 128.18 (2×), 128.06 (2×), 126.46, 125.06.

HRMS (ESI): m/z [M + H]⁺calcd for C₂₈H₁₉ClNO: 420.1150; found:

420.1148.

1-(6-Chloro-2-methyl-4-phenylquinolin-3-yl)-3-methylbutan-1-

one (1r)

7-Chloro-9-phenyl-2,3-dihydro-1H-cyclopenta[b]quinolin-1-one

(1v)^20h

Yield: 145 mg (43%); yellow gum.

Yield: 261 mg (89%); white crystals; mp 229–230 °C (Lit.^20h208–

209 °C).

¹H NMR (500 MHz, CDCl₃):  = 7.99 (d, J = 9.0 Hz, 1 H), 7.63 (dd, J = 2.0,

9.0 Hz, 1 H), 7.54 (d, J = 2.0 Hz, 1 H), 7.51–7.49 (m, 3 H), 7.32–7.30 (m,

2 H), 2.65 (s, 3 H), 2.10 (d, J = 6.5 Hz, 2 H), 2.02–1.94 (m, 1 H), 0.64 (d,

J = 6.5 Hz, 6 H).

¹³C NMR (125 MHz, CDCl₃):  = 206.81, 154.13, 145.80, 143.05,

135.44, 134.35, 132.36, 130.81, 130.47, 130.17 (2×), 129.07, 128.77

(2×), 125.95, 124.83, 53.43, 23.65, 23.15, 22.15 (2×).

¹H NMR (500 MHz, CDCl₃):  = 8.09 (d, J = 9.0 Hz, 1 H), 7.75 (dd, J = 2.0,

9.0 Hz, 1 H), 7.72 (s, 1 H), 7.57–7.56 (m, 3 H), 7.34–7.33 (m, 2 H), 3.44

(t, J = 7.0 Hz, 2 H), 2.85 (t, J = 7.0 Hz, 2 H).

¹³C NMR (125 MHz, CDCl₃):  = 203.28, 171.25, 149.67, 148.12,

132.99, 132.68, 132.46, 130.57, 129.28 (2×), 129.16, 128.30 (2×),

127.36, 126.87, 124.33, 36.60, 28.41.

HRMS (ESI): m/z [M + H]⁺calcd for C₂₁H₂₁ClNO: 338.1306; found:

338.1298.

HRMS (ESI): m/z [M + H]⁺calcd for C₁₈H₁₃ClNO: 294.0680; found:

294.0678.

1-(6-Chloro-2-isobutyl-4-phenylquinolin-3-yl)ethan-1-one (1s)

7-Chloro-9-phenyl-3,4-dihydroacridin-1(2H)-one (1w)^18o

Yield: 270 mg (88%); colorless crystals; mp 194–195 °C (Lit.^18o199–

Yield: 138 mg (41%); yellow solid; mp 128–129 °C.

¹H NMR (500 MHz, CDCl₃):  = 8.03 (d, J = 8.5 Hz, 1 H), 7.65 (dd, J = 2.5,

9.0 Hz, 1 H), 7.56 (d, J = 2.0 Hz, 1 H), 7.54–7.52 (m, 3 H), 7.35–7.32 (m,

2 H), 2.78 (d, J = 7.0 Hz, 2 H), 2.36–2.28 (m, 1 H), 1.98 (s, 3 H), 0.98 (d,

J = 7.0 Hz, 6 H).

¹³C NMR (125 MHz, CDCl₃):  = 205.32, 157.11, 145.92, 143.03,

135.88, 134.65, 132.40, 130.82, 130.79, 130.03 (2×), 129.12, 128.87

(2×), 125.74, 124.83, 45.30, 32.42, 28.74, 22.57 (2×).

200 °C).

¹H NMR (500 MHz, CDCl₃):  = 8.00 (d, J = 8.5 Hz, 1 H), 7.69 (dd, J = 2.5,

9.0 Hz, 1 H), 7.52–7.50 (m, 3 H), 7.42 (d, J = 2.0 Hz, 1 H), 7.17–7.15 (m,

2 H), 3.36 (t, J = 6.5 Hz, 2 H), 2.71 (t, J = 6.5 Hz, 2 H), 2.28–2.22 (m, 2

H).

¹³C NMR (125 MHz, CDCl₃):  = 197.68, 162.50, 150.49, 147.02,

136.82, 132.56, 132.40, 130.15, 128.30 (2×), 128.26, 127.96 (2×),

127.88, 126.71, 124.42, 40.56, 34.51, 21.24.

HRMS (ESI): m/z [M + H]⁺calcd for C₂₁H₂₁ClNO: 338.1306; found:

338.1303.

HRMS (ESI): m/z [M + H]⁺calcd for C₁₉H₁₅ClNO: 308.0837; found:

308.0832.

(6-Chloro-2-methyl-4-phenylquinolin-3-yl)(phenyl)methanone

(1t)⁴¹

Yield: 328 mg (92%); colorless crystals; mp 224–225 °C (Lit.⁴¹216–

218 °C).

7-Chloro-3,3-dimethyl-9-phenyl-3,4-dihydroacridin-1(2H)-one

(1x)^20h

Yield: 312 mg (93%); yellow crystals; mp 214–215 °C (Lit.^20h213–

214 °C).

¹H NMR (500 MHz, CDCl₃):  = 8.07 (d, J = 9.0 Hz, 1 H), 7.69 (dd, J = 2.0,

9.0 Hz, 1 H), 7.59–7.57 (m, 2 H), 7.55 (d, J = 2.0 Hz, 1 H), 7.48–7.45 (m,

1 H), 7.32–7.18 (m, 7 H), 2.62 (s, 3 H).

¹³C NMR (125 MHz, CDCl₃):  = 197.40, 155.10, 146.21, 144.80,

136.89, 134.12, 133.71, 133.22, 132.46, 131.01, 130.56, 129.90,

129.22 (2×), 128.59 (2×), 128.52 (2×), 128.25, 126.12, 125.01 (2×),

23.98.

¹H NMR (500 MHz, CDCl₃):  = 8.00 (d, J = 9.0 Hz, 1 H), 7.69 (dd, J = 2.5,

9.0 Hz, 1 H), 7.54–7.47 (m, 3 H), 7.43 (d, J = 2.5 Hz, 1 H), 7.17–7.15 (m,

2 H), 3.25 (s, 2 H), 2.57 (s, 2 H), 1.16 (s, 6 H).

¹³C NMR (125 MHz, CDCl₃):  = 197.70, 161.43, 150.10, 147.36,

136.78, 132.49, 132.43, 130.16, 128.33 (2×), 128.20, 127.98 (2×),

127.87, 126.75, 123.28, 54.16, 48.28, 32.23, 28.31 (2×).

HRMS (ESI): m/z [M + H]⁺calcd for C₂₃H₁₇ClNO: 358.0993; found:

358.0991.

HRMS (ESI): m/z [M + H]⁺calcd for C₂₁H₁₉ClNO: 336.1150; found:

336.1147.

Single-crystal X-ray crystallography: A crystal of 1t was grown by

slow diffusion of EtOAc into a solution of 1t in CH₂Cl₂to yield colorless

prisms. The compound crystallizes in the monoclinic crystal system,

space group P21/c, a = 11.6437(7) Å, b = 14.2645(9) Å, c = 10.6138(7)

Å, V = 1762.67(19) Å³, Z = 4, d_calcd= 1.348 Mg/m³, F(000) = 744, 2θ

range 1.749–27.095°, R indices (all data) R1 = 0.0414, wR2 = 0.0940.

CCDC number: 1940033.

Single-crystal X-ray crystallography: A crystal of 1x was grown by

slow diffusion of EtOAc into a solution of 1x in CH₂Cl₂to yield color-

less prisms. The compound crystallizes in the triclinic crystal system,

space group P–1, a = 9.838(3) Å, b = 10.056(3) Å, c = 10.112(3) Å, V =

844.9(4) Å³, Z = 2, d_calcd= 1.320 Mg/m³, F(000) = 352, 2θ range 2.145–

27.089°, R indices (all data) R1 = 0.0544, wR2 = 0.1033. CCDC number:

1947412.

(6-Chloro-2,4-diphenylquinolin-3-yl)(phenyl)methanone (1u)²⁶

Yield: 373 mg (89%); colorless crystals; mp 161–162 °C (Lit.²⁶170–

172 °C).

I

C.-K. Chan et al.

Paper

Synthesis

Methyl 6-Chloro-2-methyl-4-phenylquinoline-3-carboxylate

(1y)²⁶

Ethyl 6-Chloro-2-(4-nitrophenyl)-4-phenylquinoline-3-carboxyl-

ate (1ac)

Yield: 295 mg (95%); colorless crystals; mp 139–140 °C (Lit.²⁶136–

Yield: 397 mg (92%); yellow solid; mp 148–149 °C.

137 °C).

¹H NMR (500 MHz, CDCl₃):  = 8.33 (d, J = 8.5 Hz, 2 H), 8.15 (d, J = 9.0

Hz, 1 H), 7.93 (d, J = 9.0 Hz, 2 H), 7.74 (dd, J = 2.0, 9.0 Hz, 1 H), 7.61 (d,

J = 2.5 Hz, 1 H), 7.55–7.53 (m, 3 H), 7.40–7.38 (m, 2 H), 3.90 (q, J = 7.5

Hz, 2 H), 0.84 (t, J = 7.5 Hz, 3 H).

¹H NMR (500 MHz, CDCl₃):  = 8.00 (d, J = 8.5 Hz, 1 H), 7.64 (dt, J = 1.5,

8.5 Hz, 1 H), 7.54 (d, J = 7.5 Hz, 1 H), 7.51–7.48 (m, 3 H), 7.34–7.32 (m,

2 H), 3.57 (s, 3 H), 2.75 (s, 3 H).

¹³C NMR (125 MHz, CDCl₃):  = 168.50, 154.79, 146.02, 145.39,

134.85, 132.27, 131.05, 130.45, 129.04 (2×), 128.70, 128.38 (2×),

127.91, 125.73, 125.11, 52.13, 23.65.

HRMS (ESI): m/z [M + H]⁺calcd for C₁₈H₁₅ClNO₂: 312.0786; found:

312.0779.

¹³C NMR (125 MHz, CDCl₃):  = 167.39, 153.67, 148.09, 146.98,

146.12, 145.85, 134.41, 133.92, 131.93, 131.45, 129.64 (2×), 129.15

(2×), 129.04, 128.51 (2×), 127.52, 126.61, 125.35, 123.58 (2×), 61.72,

13.38.

HRMS (ESI): m/z [M + H]⁺calcd for C₂₄H₁₈ClN₂O₄: 433.0950; found:

433.0950.

Ethyl 6-Chloro-2-methyl-4-phenylquinoline-3-carboxylate (1z)⁴²

Yield: 306 mg (94%); white solid; mp 102–103 °C (Lit.⁴²101–103 °C).

Single-crystal X-ray crystallography: A crystal of 1ac was grown by

slow diffusion of EtOAc into a solution of 1ac in CH₂Cl₂to yield color-

less prisms. The compound crystallizes in the triclinic crystal system,

space group P–1, a = 10.4312(6) Å, b = 10.6735(6) Å, c = 18.7880(12)

Å, V = 2012.4(2) Å³, Z = 4, d_calcd= 1.429 Mg/m³, F(000) = 896, 2θ range

1.124–27.143°, R indices (all data) R1 = 0.0437, wR2 = 0.0946. CCDC

number: 1951570.

¹H NMR (500 MHz, CDCl₃):  = 8.00 (d, J = 9.0 Hz, 1 H), 7.64 (dd, J = 2.5,

9.0 Hz, 1 H), 7.53 (d, J = 2.5 Hz, 1 H), 7.51–7.49 (m, 3 H), 7.35–7.33 (m,

2 H), 4.06 (q, J = 7.0 Hz, 2 H), 2.76 (s, 3 H), 0.94 (t, J = 7.0 Hz, 3 H).

¹³C NMR (125 MHz, CDCl₃):  = 168.09, 154.98, 146.04, 145.40,

134.96, 132.32, 131.12, 130.48, 129.25 (2×), 128.75, 128.43 (2×),

128.16, 125.93, 125.20, 61.47, 23.72, 13.60.

6-Chloro-2-methyl-4-phenylquinoline (5a)⁴³

Yield: 243 mg (96%); colorless crystals; mp 94–95 °C (Lit.⁴³85–86 °C).

HRMS (ESI): m/z [M + H]⁺calcd for C₁₉H₁₇ClNO₂: 326.0942; found:

326.0936.

¹H NMR (500 MHz, CDCl₃):  = 7.98 (d, J = 9.0 Hz, 1 H), 7.79 (d, J = 2.5

Hz, 1 H), 7.55 (dd, J = 2.5, 9.0 Hz, 1 H), 7.49–7.39 (m, 5 H), 7.19 (s, 1 H),

2.72 (s, 3 H).

¹³C NMR (125 MHz, CDCl₃):  = 158.61, 147.52, 146.59, 137.24,

131.40, 130.49, 129.93, 129.17 (2×), 128.54 (2×), 128.42, 125.60,

124.26, 122.75, 25.11.

Ethyl 6-Chloro-2,4-diphenylquinoline-3-carboxylate (1aa)^20h

Yield: 344 mg (89%); white solid; mp 113–114 °C (Lit.^20h118–119 °C).

¹H NMR (500 MHz, CDCl₃):  = 8.17 (d, J = 9.0 Hz, 1 H), 7.76 (d, J = 8.0

Hz, 2 H), 7.70 (dd, J = 1.0, 9.0 Hz, 1 H), 7.59 (s, 1 H), 7.53–7.40 (m, 8 H),

3.89 (q, J = 7.0 Hz, 2 H), 0.82 (t, J = 7.0 Hz, 3 H).

¹³C NMR (125 MHz, CDCl₃):  = 167.75, 156.14, 146.26, 146.13,

139.72, 134.76, 132.95, 131.35 (2×), 129.23 (2×), 129.00, 128.76,

128.45 (2×), 128.39 (2×), 128.36 (2×), 127.87, 126.25, 125.18, 61.32,

13.32.

HRMS (ESI): m/z [M + H]⁺calcd for C₁₆H₁₃ClN: 254.0731; found:

254.0732.

Single-crystal X-ray crystallography: A crystal of 5a was grown by

slow diffusion of EtOAc into a solution of 5a in CH₂Cl₂to yield color-

less prisms. The compound crystallizes in the monoclinic crystal sys-

tem, space group P21/c, a = 15.6239(8) Å, b = 7.8332(4) Å, c =

20.5290(10) Å, V = 2475.0(2) Å³, Z = 8, d_calcd= 1.362 Mg/m³, F(000) =

1056, 2θ range 2.014–27.107°, R indices (all data) R1 = 0.0409, wR2 =

0.0893. CCDC number: 1954104.

HRMS (ESI): m/z [M + H]⁺calcd for C₂₄H₁₉ClNO₂: 388.1099; found:

388.1105.

Ethyl 6-Chloro-2-(4-methoxyphenyl)-4-phenylquinoline-3-car-

boxylate (1ab)⁴²

Yield: 384 mg (92%); colorless crystals; mp 141–142 °C (Lit.⁴²133–

6-Bromo-2-methyl-4-phenylquinoline (5b)

135 °C).

Yield: 273 mg (92%); yellow solid; mp 89–90 °C.

¹H NMR (500 MHz, CDCl₃):  = 8.13 (d, J = 9.0 Hz, 1 H), 7.73 (d, J = 9.0

Hz, 2 H), 7.68–7.66 (m, 1 H), 7.55 (d, J = 2.0 Hz, 1 H), 7.52–7.50 (m, 3

H), 7.40–7.38 (m, 2 H), 7.00 (d, J = 8.5 Hz, 2 H), 3.92 (q, J = 7.5 Hz, 2 H),

3.85 (s, 3 H), 0.86 (t, J = 7.5 Hz, 3 H).

¹³C NMR (125 MHz, CDCl₃):  = 167.99, 160.39, 155.57, 146.16,

146.13, 134.82, 132.61, 132.20, 131.22 (2×), 129.91 (2×), 129.23 (2×),

128.69, 128.31 (2×), 127.73, 126.03, 125.12, 113.87 (2×), 61.29, 55.24,

13.41.

¹H NMR (500 MHz, CDCl₃):  = 7.98 (d, J = 2.0 Hz, 1 H), 7.94 (d, J = 8.5

Hz, 1 H), 7.73 (d, J = 9.0 Hz, 1 H), 7.54–7.44 (m, 5 H), 7.23 (s, 1 H), 2.74

(s, 3 H).

¹³C NMR (125 MHz, CDCl₃):  = 158.92, 147.62, 146.93, 137.34,

132.66, 130.73, 129.30 (2×), 128.68 (2×), 128.56, 127.69, 126.28,

122.89, 119.70, 25.27.

HRMS (ESI): m/z [M + H]⁺calcd for C₁₆H₁₃BrN: 298.0226; found:

298.0219.

HRMS (ESI): m/z [M + H]⁺calcd for C₂₅H₂₁ClNO₃: 418.1205; found:

418.1209.

2-Methyl-6-nitro-4-phenylquinoline (5c)⁴⁴

Single-crystal X-ray crystallography: A crystal of 1ab was grown by

slow diffusion of EtOAc into a solution of 1ab in CH₂Cl₂to yield color-

less prisms. The compound crystallizes in the orthorhombic crystal

system, space group Pbca, a = 15.2409(18) Å, b = 15.4430(19) Å, c =

17.0445(19) Å, V = 4011.7(8) Å³, Z = 8, d_calcd= 1.384 Mg/m³, F(000) =

1744, 2θ range 2.225–27.125°, R indices (all data) R1 = 0.0497, wR2 =

0.0897. CCDC number: 1951569.

Yield: 232 mg (88%); yellow crystals; mp 195–196 °C (Lit.⁴⁴141 °C).

¹H NMR (500 MHz, CDCl₃):  = 8.81 (d, J = 2.5 Hz, 1 H), 8.44 (dd, J = 1.0,

9.0 Hz, 1 H), 8.17 (d, J = 9.0 Hz, 1 H), 7.61–7.56 (m, 3 H), 7.51–7.49 (m,

2 H), 7.39 (s, 1 H), 2.83 (s, 3 H).

J

C.-K. Chan et al.

Paper

Synthesis

¹³C NMR (125 MHz, CDCl₃):  = 162.65, 150.61, 150.43, 145.11,

136.52, 130.75, 129.36 (2×), 129.22, 129.04 (2×), 124.15, 123.83,

122.86 (2×), 25.68.

HRMS (ESI): m/z [M + H]⁺calcd for C₁₆H₁₃N₂O₂: 265.0972; found:

265.0973.

¹H NMR (500 MHz, CDCl₃):  = 8.10 (d, J = 8.0 Hz, 1 H), 7.87 (d, J = 8.5

Hz, 1 H), 7.65 (t, J = 7.5 Hz, 1 H), 7.38 (t, J = 7.5 Hz, 1 H), 7.36 (d, J = 7.5

Hz, 2 H), 7.28 (d, J = 7.5 Hz, 2 H), 7.19 (s, 1 H), 2.75 (s, 3 H), 2.43 (s, 3

H).

¹³C NMR (125 MHz, CDCl₃):  = 158.25, 148.36, 148.26, 137.98,

135.01, 129.22 (2×), 129.03 (3×), 128.83, 125.51, 125.43, 125.00,

121.95, 25.15, 21.09.

3-Methyl-1-phenylbenzo[f]quinoline (5d)

HRMS (ESI): m/z [M + H]⁺calcd for C₁₇H₁₆N: 234.1277; found:

Yield: 264 mg (98%); white solid; mp 91–92 °C.

234.1274.

¹H NMR (500 MHz, CDCl₃):  = 8.01 (d, J = 9.0 Hz, 1 H), 7.95 (d, J = 9.0

Hz, 1 H), 7.84 (d, J = 8.0 Hz, 1 H), 7.64 (d, J = 8.5 Hz, 1 H), 7.51–7.49 (m,

3 H), 7.43 (t, J = 7.5 Hz, 1 H), 7.42–7.39 (m, 2 H), 7.23 (s, 1 H), 7.14 (t,

J = 8.5 Hz, 1 H), 2.78 (s, 3 H),.

4-(4-Methoxyphenyl)-2-methylquinoline (5i)⁴⁸

Yield: 219 mg (88%); white solid; mp 99–100 °C (Lit.⁴⁸92–93 °C).

¹³C NMR (125 MHz, CDCl₃):  = 156.95, 149.25, 148.48, 142.68,

132.51, 131.19, 129.68, 129.03 (2×), 128.44, 128.23, 128.19 (2×),

127.91, 127.74, 126.06, 125.32, 124.78, 121.73, 24.49.

¹H NMR (500 MHz, CDCl₃):  = 8.08 (d, J = 8.0 Hz, 1 H), 7.90 (dd, J = 1.0,

8.5 Hz, 1 H), 7.69–7.66 (m, 1 H), 7.45–7.41 (m, 1 H), 7.43 (d, J = 8.5 Hz,

2 H), 7.21 (s, 1 H), 7.04 (d, J = 8.5 Hz, 2 H), 3.89 (s, 3 H), 2.76 (s, 3 H).

HRMS (ESI): m/z [M + H]⁺calcd for C₂₀H₁₆N: 270.1277; found:

270.1276.

¹³C NMR (125 MHz, CDCl₃):  = 159.74, 158.44, 148.41, 148.17, 130.69

(2×), 130.38, 129.17, 128.95, 125.63, 125.56, 125.22, 122.11, 113.96

(2×), 55.34, 25.30.

4-(4-Fluorophenyl)-2-methylquinoline (5e)⁴⁵

HRMS (ESI): m/z [M + H]⁺calcd for C₁₇H₁₆NO: 250.1226; found:

250.1219.

Yield: 228 mg (96%); colorless crystals; mp 108–109 °C.

¹H NMR (500 MHz, CDCl₃):  = 8.07 (d, J = 8.5 Hz, 1 H), 7.77 (d, J = 8.5

Hz, 1 H), 7.66 (t, J = 8.5 Hz, 1 H), 7.43–7.38 (m, 3 H), 7.19–7.15 (m, 3

H), 2.74 (s, 3 H).

2-Methyl-4-phenylquinoline (5j)⁴³

Yield: 199 mg (91%); white solid; mp 102–103 °C (Lit.⁴³96–97 °C).

¹³C NMR (125 MHz, CDCl₃):  = 162.72 (d, J = 246.5 Hz), 158.36,

148.31, 147.26, 133.97 (d, J = 3.25 Hz), 131.05 (d, J = 8.125 Hz, 2×),

129.25, 129.02, 125.74, 125.21, 124.90, 122.12, 115.45 (d, J = 21.375

Hz, 2×), 25.20.

HRMS (ESI): m/z [M + H]⁺calcd for C₁₆H₁₃FN: 238.1027; found:

238.1023.

¹H NMR (500 MHz, CDCl₃):  = 8.09 (d, J = 8.5 Hz, 1 H), 7.85 (d, J = 8.5

Hz, 1 H), 7.69–7.66 (m, 1 H), 7.53–7.46 (m, 5 H), 7.44–7.41 (m, 1 H),

7.23 (s, 1 H), 2.77 (s, 3 H).

¹³C NMR (125 MHz, CDCl₃):  = 158.41, 148.47, 148.30, 138.06, 129.42

(2×), 129.24, 128.92, 128.45 (2×), 128.25, 125.66, 125.57, 125.01,

122.15, 25.26.

HRMS (ESI): m/z [M + H]⁺calcd for C₁₆H₁₄N: 220.1121; found:

220.1114.

4-(4-Chlorophenyl)-2-methylquinoline (5f)⁴³

Yield: 245 mg (97%); colorless crystals; mp 116–117 °C (Lit.⁴³109–

110 °C).

6-Chloro-4-(2-chlorophenyl)-2-methylquinoline (5k)

¹H NMR (500 MHz, CDCl₃):  = 8.08 (d, J = 8.5 Hz, 1 H), 7.77 (d, J = 8.0

Hz, 1 H), 7.66 (dd, J = 2.0, 8.0 Hz, 1 H), 7.47–7.45 (m, 2 H), 7.43–7.38

(m, 3 H), 7.17 (s, 1 H), 2.75 (s, 3 H).

¹³C NMR (125 MHz, CDCl₃):  = 158.39, 148.29, 147.07, 136.43,

134.42, 130.69 (2×), 129.35, 129.05, 128.68 (2×), 125.84, 125.13,

124.70, 122.02, 25.25.

Yield: 267 mg (93%); yellow crystals; mp 108–109 °C.

¹H NMR (500 MHz, CDCl₃):  = 8.01 (d, J = 9.0 Hz, 1 H), 7.59 (d, J = 9.0

Hz, 1 H), 7.54 (d, J = 8.0 Hz, 1 H), 7.43–7.36 (m, 3 H), 7.28 (d, J = 7.5 Hz,

1 H), 7.20 (s, 1 H), 2.75 (s, 3 H).

¹³C NMR (125 MHz, CDCl₃):  = 158.73, 146.40, 145.04, 136.01,

133.08, 131.66, 131.12, 130.58, 130.22, 129.92, 129.88, 126.83,

125.79, 124.28, 123.35, 25.24.

HRMS (ESI): m/z [M + H]⁺calcd for C₁₆H₁₃ClN: 254.0731; found:

254.0728.

HRMS (ESI): m/z [M + H]⁺calcd for C₁₆H₁₂Cl₂N: 288.0341; found:

288.0338.

4-(4-Bromophenyl)-2-methylquinoline (5g)⁴⁶

Yield: 282 mg (95%); yellow crystals; mp 116–117 °C (Lit.⁴⁶135–

6-Chloro-2,4-diphenylquinoline (6a)⁴⁹

137 °C).

Yield: 287 mg (91%); yellow solid; mp 117–118 °C (Lit.⁴⁹120–121 °C).

¹H NMR (500 MHz, CDCl₃):  = 8.20–8.17 (m, 3 H), 7.87 (d, J = 2.5 Hz, 1

H), 7.84 (s, 1 H), 7.67 (dd, J = 2.5, 9.0 Hz, 1 H), 7.58–7.48 (m, 8 H).

¹³C NMR (125 MHz, CDCl₃):  = 157.06, 148.42, 147.20, 139.18,

137.72, 132.17, 131.70, 130.42, 129.57, 129.42 (2×), 128.88 (2×),

128.79 (2×), 128.69, 127.51 (2×), 126.46, 124.46, 120.02.

¹H NMR (500 MHz, CDCl₃):  = 8.09 (d, J = 8.0 Hz, 1 H), 7.79 (d, J = 8.5

Hz, 1 H), 7.70 (t, J = 8.0 Hz, 1 H), 7.66 (d, J = 8.0 Hz, 2 H), 7.44 (t, J = 8.0

Hz, 1 H), 7.37 (d, J = 8.0 Hz, 2 H), 7.20 (s, 1 H), 2.78 (s, 3 H).

¹³C NMR (125 MHz, CDCl₃):  = 158.51, 148.39, 147.23, 137.04, 131.75

(2×), 131.08 (2×), 129.47, 129.14, 125.96, 125.23, 124.75, 122.70,

122.06, 25.33.

HRMS (ESI): m/z [M + H]⁺calcd for C₂₁H₁₅ClN: 316.0888; found:

316.0887.

HRMS (ESI): m/z [M + H]⁺calcd for C₁₆H₁₃BrN: 298.0226; found:

298.0219.

Single-crystal X-ray crystallography: A crystal of 6a was grown by

slow diffusion of EtOAc into a solution of 6a in CH₂Cl₂to yield color-

less prisms. The compound crystallizes in the orthorhombic crystal

system, space group Pca21, a = 7.6512(4) Å, b = 10.1449(5) Å, c =

2-Methyl-4-(p-tolyl)quinoline (5h)⁴⁷

Yield: 219 mg (94%); yellow solid; mp 60–61 °C (Lit.⁴⁷60–61 °C).

K

C.-K. Chan et al.

Paper

Synthesis

19.8333(10) Å, V = 1539.47(14) Å³, Z = 4, d_calcd= 1.362 Mg/m³,

F(000) = 656, 2θ range 2.007–27.104°, R indices (all data) R1 = 0.0259,

wR2 = 0.0659. CCDC number: 1957108.

¹H NMR (500 MHz, CDCl₃):  = 7.95 (d, J = 9.0 Hz, 1 H), 7.52–7.46 (m, 4

H), 7.24 (d, J = 2.0 Hz, 1 H), 7.21–7.19 (m, 2 H), 3.30–3.22 (m, 2 H),

2.72–2.64 (m, 2 H), 1.88–1.78 (m, 4 H), 1.64–1.55 (m, 2 H).

¹³C NMR (125 MHz, CDCl₃):  = 165.03, 144.62, 144.16, 136.81,

134.76, 131.28, 130.19, 129.26 (2×), 128.94, 128.57 (2×), 127.88,

127.66, 125.08, 40.05, 31.78, 30.66, 28.30, 26.87.

6-Chloro-2-(4-nitrophenyl)-4-phenylquinoline (6b)⁵⁰

Yield: 331 mg (92%); white solid; mp 225–226 °C (Lit.⁵⁰219–220 °C).

HRMS (ESI): m/z [M + H]⁺calcd for C₂₀H₁₉ClN: 308.1201; found:

308.1197.

¹H NMR (500 MHz, CDCl₃):  = 8.38 (br s, 4 H), 8.19 (d, J = 9.0 Hz, 1 H),

7.90 (d, J = 2.5 Hz, 1 H), 7.88 (s, 1 H), 7.71 (dd, J = 2.5, 9.0 Hz, 1 H),

7.61–7.54 (m, 5 H).

¹³C NMR (125 MHz, CDCl₃):  = 154.25, 149.15, 148.46, 147.19,

144.96, 137.25, 133.31, 131.91, 131.03, 129.37 (2×), 129.01, 128.94

(2×), 128.29 (2×), 126.87, 124.60, 124.06 (2×), 119.79.

Single-crystal X-ray crystallography: A crystal of 6e was grown by

slow diffusion of EtOAc into a solution of 6e in CH₂Cl₂to yield color-

less prisms. The compound crystallizes in the triclinic crystal system,

space group P–1, a = 9.3909(12) Å, b = 9.5008(12) Å, c = 10.1043(13)

Å, V = 764.86(17) Å³, Z = 2, d_calcd= 1.337 Mg/m³, F(000) = 324, 2θ range

2.172–27.103°, R indices (all data) R1 = 0.0391, wR2 = 0.0872. CCDC

number: 1951568.

HRMS (ESI): m/z [M + H]⁺calcd for C₂₁H₁₄ClN₂O₂: 361.0738; found:

361.0747.

7-Chloro-9-phenyl-2,3-dihydro-1H-cyclopenta[b]quinoline (6c)⁴²

Yield: 246 mg (88%); colorless crystals; mp 92–93 °C (Lit.⁴²96–98 °C).

2-(tert-Butyl)-7-chloro-9-phenyl-1,2,3,4-tetrahydroacridine (6f)⁵²

Yield: 300 mg (86%); white solid; mp 150–151 °C (Lit.⁵²146–148 °C).

¹H NMR (500 MHz, CDCl₃):  = 7.98 (d, J = 9.0 Hz, 1 H), 7.57 (d, J = 2.5

Hz, 1 H), 7.54–7.50 (m, 3 H), 7.48–7.45 (m, 1 H), 7.32 (d, J = 8.0 Hz, 2

H), 3.20 (t, J = 7.5 Hz, 2 H), 2.88 (t, J = 7.5 Hz, 2 H), 2.18–2.12 (m, 2 H).

¹³C NMR (125 MHz, CDCl₃):  = 167.77, 146.29, 141.83, 135.96,

134.61, 131.24, 130.30, 129.09 (2×), 128.92, 128.65 (2×), 128.22,

126.96, 124.43, 35.05, 30.30, 23.36.

¹H NMR (500 MHz, CDCl₃):  = 7.93 (d, J = 8.5 Hz, 1 H), 7.54–7.45 (m, 4

H), 7.27 (d, J = 2.0 Hz, 1 H), 7.21–7.19 (m, 2 H), 3.31–3.26 (m, 1 H),

3.12–3.05 (m, 1 H), 2.67–2.62 (m, 1 H), 2.31–2.26 (m, 1 H), 2.14–2.10

(m, 1 H), 1.56–1.43 (m, 2 H), 0.83 (s, 9 H).

¹³C NMR (125 MHz, CDCl₃):  = 159.64, 145.79, 144.60, 136.21,

131.03, 129.98, 129.70, 129.11, 129.01, 128.78, 128.75 (2×), 128.01,

127.31, 124.48, 44.55, 34.75, 32.49, 29.33, 27.05 (3×), 24.00.

HRMS (ESI): m/z [M + H]⁺calcd for C₁₈H₁₅ClN: 280.0888; found:

280.0880.

HRMS (ESI): m/z [M + H]⁺calcd for C₂₃H₂₅ClN: 350.1670; found:

Single-crystal X-ray crystallography: A crystal of 6c was grown by

slow diffusion of EtOAc into a solution of 6c in CH₂Cl₂to yield color-

less prisms. The compound crystallizes in the monoclinic crystal sys-

tem, space group C2/c, a = 23.676(5) Å, b = 9.3719(17) Å, c = 13.351(3)

Å, V = 2743.2(9) Å³, Z = 8, d_calcd= 1.355 Mg/m³, F(000) = 1168, 2θ range

1.858–27.096°, R indices (all data) R1 = 0.0366, wR2 = 0.0924. CCDC

number: 1951572.

350.1665.

Single-crystal X-ray crystallography: A crystal of 6f was grown by

slow diffusion of EtOAc into a solution of 6f in CH₂Cl₂to yield colorless

prisms. The compound crystallizes in the orthorhombic crystal sys-

tem, space group Pbca, a = 11.0458(14) Å, b = 18.128(2) Å, c =

18.878(2) Å, V = 3780.2(8) Å³, Z = 8, d_calcd= 1.230 Mg/m³, F(000) =

1488, 2θ range 2.158–27.114°, R indices (all data) R1 = 0.0704, wR2 =

0.1298. CCDC number: 1948414.

7-Chloro-9-phenyl-1,2,3,4-tetrahydroacridine (6d)⁴¹

Yield: 275 mg (94%); colorless crystals; mp 172–173 °C (Lit.⁴¹163–

165 °C).

9-Chloro-7-phenyl-5,6-dihydrobenzo[c]acridine (6g)⁴²

Yield: 293 mg (86%); colorless crystals; mp 154–155 °C (Lit.⁴²146–

¹H NMR (500 MHz, CDCl₃):  = 7.93 (d, J = 9.0 Hz, 1 H), 7.52–7.49 (m, 3

H), 7.47–7.44 (m, 1 H), 7.27 (d, J = 2.0 Hz, 1 H), 7.19 (d, J = 7.0 Hz, 2 H),

3.16 (t, J = 6.5 Hz, 2 H), 2.57 (t, J = 6.5 Hz, 2 H), 1.96–1.91 (m, 2 H),

1.78–1.73 (m, 2 H).

¹³C NMR (125 MHz, CDCl₃):  = 159.36, 145.59, 144.57, 136.27,

131.03, 129.97, 129.32, 129.11, 128.90 (2×), 128.71 (2×), 127.94,

127.27, 124.41, 34.09, 27.99, 22.78, 22.68.

148 °C).

¹H NMR (500 MHz, CDCl₃):  = 8.59 (d, J = 8.0 Hz, 1 H), 8.11 (d, J = 9.0

Hz, 1 H), 7.59–7.51 (m, 4 H), 7.44 (t, J = 8.0 Hz, 1 H), 7.40–7.38 (m, 2

H), 7.30 (d, J = 7.0 Hz, 2 H), 7.25 (d, J = 9.0 Hz, 1 H), 2.93–2.87 (m, 2 H),

2.86–2.81 (m, 2 H).

¹³C NMR (125 MHz, CDCl₃):  = 153.39, 145.57, 144.66, 139.26,

136.20, 134.76, 131.69, 131.19, 129.86, 129.39 (2×), 129.35, 129.06,

128.77 (2×), 128.21, 127.98, 127.73, 127.31, 126.31, 124.82, 28.10,

26.51.

HRMS (ESI): m/z [M + H]⁺calcd for C₁₉H₁₇ClN: 294.1044; found:

294.1042.

Single-crystal X-ray crystallography: A crystal of 6d was grown by

slow diffusion of EtOAc into a solution of 6d in CH₂Cl₂to yield color-

less prisms. The compound crystallizes in the Monoclinic crystal sys-

tem, space group C2/c, a = 24.1033(16) Å, b = 8.9412(6) Å, c =

14.6847(10) Å, V = 2864.6(3) Å³, Z = 8, d_calcd= 1.362 Mg/m³, F(000) =

1232, 2θ range 1.867–27.118°, R indices (all data) R1 = 0.0331, wR2 =

0.0849. CCDC number: 1948413.

HRMS (ESI): m/z [M + H]⁺calcd for C₂₃H₁₇ClN: 342.1044; found:

342.1044.

9-Chloro-2-methoxy-7-phenyl-5,6-dihydrobenzo[c]acridine (6h)

Yield: 334 mg (90%); colorless crystals; mp 164–165 °C.

¹H NMR (500 MHz, CDCl₃):  = 8.17 (d, J = 2.5 Hz, 1 H), 8.12 (d, J = 9.0

Hz, 1 H), 7.58–7.52 (m, 4 H), 7.38 (d, J = 2.0 Hz, 1 H), 7.30 (d, J = 7.0 Hz,

2 H), 7.15 (d, J = 8.5 Hz, 1 H), 6.96 (dd, J = 2.5, 8.5 Hz, 1 H), 3.97 (s, 3 H),

2.81 (s, 4 H).

2-Chloro-11-phenyl-7,8,9,10-tetrahydro-6H-cyclohepta[b]quino-

line (6e)⁵¹

Yield: 289 mg (94%); colorless crystals; mp 203–204 °C (Lit.⁵¹193–

195 °C).

L

C.-K. Chan et al.

Paper

Synthesis

¹³C NMR (125 MHz, CDCl₃):  = 159.02, 153.22, 145.43, 144.59,

136.21, 135.65, 131.69, 131.15, 129.36 (2×), 129.28, 129.26, 129.10,

128.76, 128.73 (2×), 128.16, 128.00, 124.78, 117.05, 109.94, 55.53,

27.20, 26.74.

¹H NMR (500 MHz, CDCl₃):  = 8.19 (d, J = 3.0, 9.0 Hz, 1 H), 7.67 (dd, J =

2.0, 9.0 Hz, 1 H), 7.56–7.55 (m, 1 H), 7.40–7.34 (m, 2 H), 7.33–7.27 (m,

3 H), 7.25–7.18 (m, 3 H), 7.15–7.09 (m, 2 H), 7.06–6.98 (m, 3 H), 6.93–

6.84 (m, 2 H).

HRMS (ESI): m/z [M + H]⁺calcd for C₂₄H₁₉ClNO: 372.1150; found:

372.1146.

¹³C NMR (125 MHz, CDCl₃):  = 159.25, 146.94, 145.71, 140.77,

137.94, 136.24, 133.78, 132.41, 131.34, 131.21 (2×), 130.27, 130.17

(2×), 129.84 (2×), 127.99 (2×), 127.79, 127.77, 127.70 (2×), 127.57,

127.40 (2×), 126.51, 125.33.

HRMS (ESI): m/z [M + H]⁺calcd for C₂₇H₁₉ClN: 392.1201; found:

392.1199.

Single-crystal X-ray crystallography: A crystal of 6h was grown by

slow diffusion of EtOAc into a solution of 6h in CH₂Cl₂to yield color-

less prisms. The compound crystallizes in the monoclinic crystal sys-

tem, space group P21/n, a = 9.5237(7) Å, b = 9.5964(7) Å, c =

20.1366(16) Å, V = 1811.4(2) Å³, Z = 4, d_calcd= 1.364 Mg/m³, F(000) =

776, 2θ range 2.055–27.147°, R indices (all data) R1 = 0.0394, wR2 =

0.0926. CCDC number: 1951571.

Single-crystal X-ray crystallography: A crystal of 6k was grown by

slow diffusion of EtOAc into a solution of 6k in CH₂Cl₂to yield color-

less prisms. The compound crystallizes in the triclinic crystal system,

space group P–1, a = 9.5370(9) Å, b = 10.1602(10) Å, c = 11.5493(12)

Å, V = 996.99(17) Å³, Z = 2, d_calcd= 1.305 Mg/m³, F(000) = 408, 2θ range

1.888–27.103°, R indices (all data) R1 = 0.0417, wR2 = 0.0882. CCDC

number: 1948412.

9-Chloro-2,3-dimethoxy-7-phenyl-5,6-dihydrobenzo[c]acridine

(6i)

Yield: 339 mg (92%); colorless crystals; mp 261–262 °C.

¹H NMR (500 MHz, CDCl₃):  = 8.14 (s, 1 H), 8.08 (d, J = 9.0 Hz, 1 H),

7.57–7.51 (m, 4 H), 7.34 (d, J = 2.0 Hz, 1 H), 7.30–7.28 (m, 2 H), 6.72 (s,

1 H), 4.08 (s, 3 H), 3.94 (s, 3 H), 2.81 (s, 4 H).

6-Chloro-2-(4-fluorophenyl)-3,4-diphenylquinoline (6l)

Yield: 389 mg (95%); colorless crystals; mp 211–212 °C.

¹³C NMR (125 MHz, CDCl₃):  = 153.25, 150.67, 148.40, 145.46,

144.37, 136.30, 132.72, 131.21, 130.83, 129.37 (2×), 129.21, 128.73

(2×), 128.41, 128.13, 127.72, 127.35, 124.81, 110.31, 108.69, 5612,

55.92, 27.67, 26.70.

HRMS (ESI): m/z [M + H]⁺calcd for C₂₅H₂₁ClNO₂: 402.1255; found:

402.1252.

¹H NMR (500 MHz, CDCl₃):  = 8.18 (d, J = 9.0 Hz, 1 H), 7.67 (d, J = 2.0,

9.0 Hz, 1 H), 7.57 (d, J = 2.0 Hz, 1 H), 7.39–7.36 (m, 2 H), 7.32–7.28 (m,

3 H), 7.13–7.11 (m, 2 H), 7.06–7.03 (m, 3 H), 6.93–6.89 (m, 4 H).

¹³C NMR (125 MHz, CDCl₃):  = 162.41 (d, J = 246.375 Hz), 158.03,

147.07, 145.66, 137.79, 136.79 (d, J = 3.125 Hz), 136.08, 133.60,

132.50, 131.72 (d, J = 8.25 Hz, 2×), 131.24, 131.12 (2×), 130.35, 130.08

(2×), 127.99 (2×), 127.60, 127.55 (2×), 127.39, 126.63, 125.32, 114.67

(d, J = 21.375 Hz, 2×).

Single-crystal X-ray crystallography: A crystal of 6i was grown by

slow diffusion of EtOAc into a solution of 6i in CH₂Cl₂to yield colorless

prisms. The compound crystallizes in the monoclinic crystal system,

space group P21/n, a = 11.676(2) Å, b = 10.7728(18) Å, c = 16.079(3)

Å, V = 1938.8(6) Å³, Z = 4, d_calcd= 1.377 Mg/m³, F(000) = 840, 2θ range

1.920–27.103°, R indices (all data) R1 = 0.0397, wR2 = 0.0886. CCDC

number: 1952311.

HRMS (ESI): m/z [M + H]⁺calcd for C₂₇H₁₈ClFN: 410.1106; found:

410.1106.

2-(6-Chloro-4-phenylquinolin-2-yl)-4-methoxyphenol (6m)

Yield: 278 mg (77%); yellow solid; mp 189–190 °C.

¹H NMR (500 MHz, CDCl₃):  = 14.33 (br s, 1 H), 8.03 (d, J = 9.0 Hz, 1

H), 7.92 (s, 1 H), 7.84 (d, J = 2.5 Hz, 1 H), 7.68 (dd, J = 2.0, 9.0 Hz, 1 H),

7.61–7.53 (m, 5 H), 7.43 (d, J = 3.0 Hz, 1 H), 7.04 (d, J = 9.0 Hz, 1 H),

7.00 (dd, J = 2.5, 9.0 Hz, 1 H), 3.83 (s, 3 H).

¹³C NMR (125 MHz, CDCl₃):  = 157.39, 155.07, 152.19, 149.43,

143.88, 137.24, 132.65, 131.21, 129.59, 129.34 (2×), 129.06, 128.94

(2×), 126.05, 124.73, 119.24, 118.89, 118.65, 118.43, 111.64, 56.11.

10-Chloro-8-phenyl-6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-

b]quinoline (6j)

Yield: 327 mg (92%); colorless crystals; mp 174–175 °C.

¹H NMR (500 MHz, CDCl₃):  = 8.15 (d, J = 9.0 Hz, 1 H), 7.92 (d, J = 7.5

Hz, 1 H), 7.60 (d, J = 9.0 Hz, 1 H), 7.57–7.50 (m, 3 H), 7.47 (t, J = 7.5 Hz,

1 H), 7.42 (d, J = 7.5 Hz, 1 H), 7.40 (s, 1 H), 7.33 (d, J = 8.0 Hz, 2 H), 7.25

(d, J = 7.5 Hz, 1 H), 2.65 (t, J = 7.0 Hz, 2 H), 2.42 (t, J = 7.0 Hz, 2 H),

2.09–2.04 (m, 2 H).

¹³C NMR (125 MHz, CDCl₃):  = 160.74, 145.36, 145.15, 140.22,

139.12, 136.42, 131.84, 131.61, 131.19, 129.36 (4×), 128.92, 128.58

(2×), 128.26, 128.16, 127.81, 127.05, 124.98, 31.92, 31.03, 27.32.

HRMS (ESI): m/z [M + H]⁺calcd for C₂₂H₁₇ClNO₂: 362.0942; found:

362.0937.

9-Chloro-7-phenyl-6H-chromeno[4,3-b]quinoline (6n)⁴²

Yield: 316 mg (92%); colorless crystals; mp 184–185 °C (Lit.⁴²181–

HRMS (ESI): m/z [M + H]⁺calcd for C₂₄H₁₉ClN: 356.1201; found:

356.1196.

183 °C).

¹H NMR (500 MHz, CDCl₃):  = 8.50 (d, J = 7.5 Hz, 1 H), 8.10 (d, J = 9.0

Hz, 1 H), 7.61–7.53 (m, 4 H), 7.44 (s, 1 H), 738 (t, J = 7.5 Hz, 1 H), 7.29

(d, J = 7.0 Hz, 2 H), 7.18 (t, J = 7.5 Hz, 1 H), 6.98 (d, J = 7.5 Hz, 1 H), 5.09

(s, 2 H).

¹³C NMR (125 MHz, CDCl₃):  = 157.25, 148.99, 146.43, 142.90,

134.17, 132.06, 131.99, 131.18, 130.19, 129.12 (2×), 128.97 (2×),

128.84, 127.77, 125.71, 124.91, 123.66, 123.17, 122.55, 117.19, 66.61.

Single-crystal X-ray crystallography: A crystal of 6j was grown by

slow diffusion of EtOAc into a solution of 6j in CH₂Cl₂to yield colorless

prisms. The compound crystallizes in the triclinic crystal system,

space group P–1, a = 9.649(3) Å, b = 9.664(3) Å, c = 9.806(3) Å, V =

882.6(4) Å³, Z = 2, d_calcd= 1.339 Mg/m³, F(000) = 372, 2θ range 2.110–

27.142°, R indices (all data) R1 = 0.0542, wR2 = 0.0895. CCDC number:

1952312.

HRMS (ESI): m/z [M + H]⁺calcd for C₂₂H₁₅ClNO: 344.0837; found:

6-Chloro-2,3,4-triphenylquinoline (6k)⁵³

344.0836.

Yield: 364 mg (93%); colorless crystals; mp 166–167 °C (Lit.⁵³191–

193 °C).

Single-crystal X-ray crystallography: A crystal of 6n was grown by

slow diffusion of EtOAc into a solution of 6n in CH₂Cl₂to yield color-

less prisms. The compound crystallizes in the monoclinic crystal sys-

M

C.-K. Chan et al.

Paper

Synthesis

tem, space group C2/c, a = 18.2667(15) Å, b = 7.8037(6) Å, c =

22.7233(18) Å, V = 3229.3(4) Å³, Z = 8, d_calcd= 1.414 Mg/m³, F(000) =

1424, 2θ range 1.798–27.107°, R indices (all data) R1 = 0.0354, wR2 =

0.0858. CCDC number: 1952313.

¹H NMR (400 MHz, CDCl₃):  = 8.06 (d, J = 8.8 Hz, 1 H), 7.69 (dd, J = 2.0,

8.8 Hz, 1 H), 7.59 (d, J = 2.0 Hz, 1 H), 7.41–7.28 (m, 10 H), 7.10 (d, J =

16.0 Hz, 1 H), 6.60 (d, J = 16.0 Hz, 1 H), 2.70 (s, 3 H).

¹³C NMR (100 MHz, CDCl₃):  = 197.12, 155.29, 146.83, 146.13,

144.53, 134.49, 133.92, 133.33, 132.42, 130.97 (2×), 130.54, 129.87

(2×), 128.91 (2×), 128.85, 128.55 (2×), 128.34 (2×), 127.57, 126.09,

125.04, 23.90.

9-Chloro-6,7-diphenyl-6H-chromeno[4,3-b]quinoline (6o)

Yield: 390 mg (93%); colorless crystals; mp 221–222 °C.

HRMS (ESI): m/z [M + H]⁺calcd for C₂₅H₁₉ClNO: 384.1150; found:

384.1140.

¹H NMR (500 MHz, CDCl₃):  = 8.17 (d, J = 8.5 Hz, 1 H), 7.67 (d, J = 2.5

Hz, 1 H), 7.66 (dd, J = 2.5, 9.0 Hz, 1 H), 7.57 (t, J = 7.5 Hz, 1 H), 7.46 (t,

J = 7.5 Hz, 1 H), 7.42–7.40 (m, 2 H), 7.30–7.25 (m, 2 H), 7.18–7.13 (m,

3 H), 7.10 (t, J = 7.5 Hz, 1 H), 7.00 (d, J = 7.5 Hz, 2 H), 6.87 (d, J = 8.0 Hz,

1 H), 6.80 (d, J = 7.5 Hz, 1 H), 6.26 (s, 1 H).

(E)-1-(6-Chloro-2-methyl-4-phenylquinolin-3-yl)-3-(2-fluorophe-

nyl)prop-2-en-1-one (8b)

¹³C NMR (125 MHz, CDCl₃):  = 154.87, 148.70, 146.66, 144.44,

139.35, 134.01, 132.23, 132.03, 131.17, 130.50, 129.44, 128.82 (2×),

128.68, 128.47, 128.31, 128.20 (2×), 127.99 (4×), 125.37, 125.12,

124.77, 123.24, 122.26, 118.12.

Yield: 329 mg (82%); white solid; mp 169–170 °C.

¹H NMR (400 MHz, CDCl₃):  = 8.05 (d, J = 9.2 Hz, 1 H), 7.67 (dd, J = 2.0,

8.8 Hz, 1 H), 7.59 (d, J = 2.0 Hz, 1 H), 7.43–7.37 (m, 3 H), 7.34–7.25 (m,

5 H), 7.08 (t, J = 7.6 Hz, 1 H), 7.01 (t, J = 10.0 Hz, 1 H), 6.63 (d, J = 16.4

Hz, 1 H), 2.69 (s, 3 H).

HRMS (ESI): m/z [M + H]⁺calcd for C₂₈H₁₉ClNO: 420.1150; found:

420.1150.

¹³C NMR (100 MHz, CDCl₃):  = 197.15, 161.19 (d, J = 253.2 Hz),

155.25, 145.37 (d, J = 153.8 Hz), 138.92, 134.46, 133.08, 132.45,

132.42, 132.37, 130.99, 130.54, 129.97 (2×), 129.38 (d, J = 5.4 Hz),

128.85, 128.73, 128.55 (2×), 126.01, 125.03, 124.45 (d, J = 3.0 Hz),

122.04 (d, J = 11.5 Hz), 116.12 (d, J = 21.4 Hz), 23.91.

HRMS (ESI): m/z [M + H]⁺calcd for C₂₅H₁₈ClFNO: 402.1056; found:

402.1050.

Single-crystal X-ray crystallography: A crystal of 6o was grown by

slow diffusion of EtOAc into a solution of 6o in CH₂Cl₂to yield color-

less prisms. The compound crystallizes in the triclinic crystal system,

space group P–1, a = 9.6174(7) Å, b = 10.1886(7) Å, c = 11.7888(9) Å,

V = 999.86(13) Å³, Z = 2, d_calcd= 1.395 Mg/m³, F(000) = 436, 2θ range

1.857–27.1125°, R indices (all data) R1 = 0.0401, wR2 = 0.0864. CCDC

number: 1954575.

(E)-1-(6-Chloro-2-methyl-4-phenylquinolin-3-yl)-3-(4-fluorophe-

6-Chloro-2,4-diphenylquinoline-3-carbonitrile (6p)⁵²

Yield: 296 mg (87%); white solid; mp 197–198 °C (Lit.⁵²191–192 °C).

nyl)prop-2-en-1-one (8c)⁴⁹

Yield: 337 mg (84%); yellow gum.

¹H NMR (500 MHz, CDCl₃):  = 8.19 (d, J = 9.0 Hz, 1 H), 8.00 (d, J = 7.5

Hz, 2 H), 7.79 (dd, J = 2.5, 9.0 Hz, 1 H), 7.67–7.63 (m, 4 H), 7.58–7.55

(m, 3 H), 7.53–7.51 (m, 2 H).

¹³C NMR (125 MHz, CDCl₃):  = 158.69, 155.52, 146.88, 137.68,

133.93, 133.86, 133.36, 131.62, 130.12, 130.01, 129.30 (2×), 129.21

(2×), 129.02 (2×), 128.63 (2×), 124.45, 125.41, 116.84, 106.46.

¹H NMR (400 MHz, CDCl₃):  = 8.05 (d, J = 9.2 Hz, 1 H), 7.67 (dd, J = 2.4,

8.8 Hz, 1 H), 7.58 (d, J = 2.4 Hz, 1 H), 7.42–7.38 (m, 3 H), 7.32–7.27 (m,

4 H), 7.06 (d, J = 16.0 Hz, 1 H), 7.00 (t, J = 8.4 Hz, 2 H), 6.50 (d, J = 16.0

Hz, 1 H), 2.69 (s, 3 H).

¹³C NMR (100 MHz, CDCl₃):  = 196.86, 164.26 (d, J = 251.4 Hz),

155.27, 146.13, 145.29, 144.54, 134.50, 133.25, 132.46, 131.01,

130.54, 130.28 (d, J = 8.7 Hz, 2×), 130.16 (d, J = 3.3 Hz), 129.86 (2×),

128.89, 128.57 (2×), 127.23, 126.04, 125.02, 116.15 (d, J = 21.9 Hz, 2×),

23.90.

HRMS (ESI): m/z [M + H]⁺calcd for C₂₂H₁₄ClN₂: 341.0840; found:

341.0840.

HRMS (ESI): m/z [M + H]⁺calcd for C₂₅H₁₈ClFNO: 402.1056; found:

Quinolinyl Chalcones 8; General Procedure

402.1049.

A mixture of 2-aminobenzophenone 2a (1.0 mmol), acetylacetone

(3a; 1.1 mmol), and Nafion NR50 (20 mol%) in ethanol (10 mL) was

placed in a dried 35 mL microwave vial at 25 °C. The mixture was sub-

jected to microwave irradiation and stirred at 200 °C for 1 h. The con-

sumption of the starting materials was confirmed by TLC. The mix-

ture was cooled to 25 °C, the Nafion NR50 particles were removed,

and then NaOH (1.0 mmol) and aromatic benzaldehydes 7 (1.2 mmol)

were added directly, after which the mixture was stirred at 200 °C for

another 1 h. The consumption of the quinolines was confirmed by

TLC. The mixture was cooled to 25 °C and then transferred to a 100

mL round-bottom flask; the solvent was then concentrated under re-

duced pressure to afford the crude product. Solid crude product was

recrystallized (hexane–EtOAc, 5:1 to 2:1). Gummy crude product was

purified by chromatography (silica gel, hexanes–EtOAc, 4:1 to 1:1).

This afforded compounds 8a–f.

(E)-1-(6-Chloro-2-methyl-4-phenylquinolin-3-yl)-3-(3,4-dime-

thoxyphenyl)prop-2-en-1-one (8d)⁵⁴

Yield: 381 mg (86%); yellow solid; mp 195–196 °C.

¹H NMR (400 MHz, CDCl₃):  = 8.05 (d, J = 8.8 Hz, 1 H), 7.67 (dd, J = 2.4,

8.8 Hz, 1 H), 7.57 (d, J = 2.4 Hz, 1 H), 7.44–7.37 (m, 3 H), 7.30 (s, 1 H),

7.29 (dd, J = 2.0, 4.8 Hz, 1 H), 7.02 (d, J = 16.0 Hz, 1 H), 6.91 (dd, J = 2.0,

8.4 Hz, 1 H), 6.84 (d, J = 2.0 Hz, 1 H), 6.79 (d, J = 8.4 Hz, 1 H), 6.49 (d, J =

16.0 Hz, 1 H), 3.88 (s, 3 H), 3.84 (s, 3 H), 2.69 (s, 3 H).

¹³C NMR (100 MHz, CDCl₃):  = 196.96, 155.40, 151.87, 149.25,

147.18, 146.08, 144.46, 134.57, 133.44, 132.36, 130.88, 130.51,

129.84 (2×), 128.76, 128.49 (2×), 126.84, 126.17, 125.71, 125.06,

123.34, 111.01, 109.72, 55.96, 55.83, 23.91.

HRMS (ESI): m/z [M + H]⁺calcd for C₂₇H₂₃ClNO₃: 444.1361; found:

(E)-1-(6-Chloro-2-methyl-4-phenylquinolin-3-yl)-3-phenylprop-

444.1370.

2-en-1-one (8a)⁵⁴

Yield: 337 mg (88%); white solid; mp 164–165 °C (Lit.⁵⁴160–162 °C).

(E)-1-(6-Chloro-2-methyl-4-phenylquinolin-3-yl)-3-(3,5-dime-

thoxyphenyl)prop-2-en-1-one (8e)

Yield: 377 mg (85%); yellow gum.

N

C.-K. Chan et al.

Paper

Synthesis

¹H NMR (400 MHz, CDCl₃):  = 8.06 (d, J = 9.2 Hz, 1 H), 7.68 (dd, J = 2.4,

9.2 Hz, 1 H), 7.58 (d, J = 2.4 Hz, 1 H), 7.44–7.39 (m, 3 H), 7.30–7.28 (m,

2 H), 7.00 (d, J = 16.0 Hz, 1 H), 6.55 (d, J = 16.0 Hz, 1 H), 6.46 (dd, J =

2.4, 8.4 Hz, 1 H), 6.45 (s, 2 H), 3.75 (s, 6 H), 2.69 (s, 3 H).

¹³C NMR (100 MHz, CDCl₃):  = 197.13, 161.01 (2×), 155.31, 146.90,

146.17, 144.61, 135.79, 134.49, 133.29, 132.47, 131.02, 130.57,

129.91 (2×), 128.90, 128.59 (2×), 128.06, 126.13, 125.08, 106.19 (2×),

103.37, 55.41 (2×), 23.93.

Funding Information

The authors thank Academia Sinica (AS-SUMMIT-108) and Ministry

of Science and Technology, Taiwan (MOST 108-3114-Y-001-002 and

MOST 108-2113-M-001-019-) for financial support.

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Supporting Information

HRMS (ESI): m/z [M + H]⁺calcd for C₂₇H₂₃ClNO₃: 444.1361; found:

Supporting information for this article is available online at

https://doi.org/10.1055/s-0039-1690088.

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(E)-1-(6-Chloro-2-methyl-4-phenylquinolin-3-yl)-3-(3,4,5-trime-

References

thoxyphenyl)prop-2-en-1-one (8f)⁵⁴

Yield: 416 mg (88%); yellow crystals; mp 140–141 °C.

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¹H NMR (400 MHz, CDCl₃):  = 8.02 (d, J = 8.8 Hz, 1 H), 7.63 (dd, J = 2.4,

8.8 Hz, 1 H), 7.55 (d, J = 2.4 Hz, 1 H), 7.44–7.34 (m, 3 H), 7.32–7.27 (m,

2 H), 6.99 (d, J = 16.0 Hz, 1 H), 6.54 (s, 2 H), 6.52 (d, J = 16.0 Hz, 1 H),

3.82 (s, 3 H), 3.78 (s, 6 H), 2.67 (s, 3 H).

¹³C NMR (100 MHz, CDCl₃):  = 196.75, 155.19, 153.28 (2×), 146.92,

145.99, 144.42, 140.74, 134.39, 133.20, 132.30, 130.82, 130.41,

129.77 (2×), 129.18, 128.73, 128.43 (2×), 126.91, 126.02, 124.93,

105.50 (2×), 60.79, 56.00 (2×), 23.80.

HRMS (ESI): m/z [M + H]⁺calcd for C₂₈H₂₅ClNO₄: 474.1467; found:

474.1476.

Single-crystal X-ray crystallography: A crystal of 8f was grown by

slow diffusion of EtOAc into a solution of 8f in CH₂Cl₂to yield colorless

prisms. The compound crystallizes in the monoclinic crystal system,

space group P21/n, a = 7.0352(6) Å, b = 28.703(3) Å, c = 11.7018(10)

Å, V = 2328.7(3) Å³, Z = 4, d_calcd= 1.352 Mg/m³, F(000) = 992, 2θ range

1.419–27.103°, R indices (all data) R1 = 0.0328, wR2 = 0.0821. CCDC

number: 1963945.

2,8-Dichloro-6,13-diphenyl-12H-cyclopenta[1,2-b:3,4-b′]diquino-

line (9)

A mixture of 2-aminobenzophenone 2a (1.0 mmol), ketone 3e (0.5

mmol), and Nafion NR50 (20 mol%) in ethanol (10 mL) was placed in a

dried 35 mL microwave vial at 25 °C. The mixture was subjected to

microwave irradiation and stirred at 200 °C for 2 h. The consumption

of the starting materials was confirmed by TLC. The mixture was

cooled to 25 °C and then transferred to a 100 mL round-bottom flask;

then the solvent was concentrated under reduced pressure to afford

crude product. The solid crude product was recrystallized (hexane–

EtOAc, 5:1 to 2:1).

Yield: 207 mg (85%); brown solid; mp 236–237 °C.

Patents

and

Applications;

Thieme:

Stuttgart,

2001.

¹H NMR (500 MHz, CDCl₃):  = 8.07 (d, J = 9.0 Hz, 1 H), 7.79 (s, 1 H),

7.68–7.54 (m, 11 H), 7.48 (d, J = 9.0 Hz, 1 H), 7.43 (d, J = 7.5 Hz, 2 H),

4.13 (s, 2 H).

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¹³C NMR (125 MHz, CDCl₃):  = 165.41, 158.48, 147.15, 146.93,

143.87, 142.70, 135.37, 134.17, 132.40, 132.24 (2×), 131.86, 130.72,

130.57, 130.07 (2×), 129.42, 129.22, 129.07 (2×), 129.01 (2×), 128.73,

128.52, 128.16, 128.11 (2×), 126.97, 125.91, 124.29, 36.13.

HRMS (ESI): m/z [M + H]⁺calcd for C₃₁H₁₉Cl₂N₂: 489.0920; found:

489.0914.

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(33) CCDC 1945823 (1a), 1940422 (1b), 1941657 (1e), 1940035 (1f),

1940423 (1g), 1940033 (1p), 1947412 (1t), 1951569 (1x),

1951570 (1y), 1954104 (5a), 1957108 (6a), 1951572 (6c),

1948413 (6d), 1951568 (6e), 1948414 (6f), 1951571 (6h),

1952311 (6i), 1952312 (6j), 1948412 (6k), 1952313 (6n),

1954575 (6o), and 1963945 (8f) contain the supplementary

crystallographic data for this paper. These data can be obtained

free of charge from The Cambridge Crystallographic Data Centre

via www.ccdc.cam.ac.uk/getstructures.

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Environmentally Friendly Nafion-Mediated Friedl?nder Quinoline Synthesis under Microwave Irradiation: Application to One-Pot Synthesis of Substituted Quinolinyl Chalcones

DOI: 10.1055/s-0039-1690088

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Article abstract of DOI:10.1055/s-0039-1690088

Full text of DOI:10.1055/s-0039-1690088

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