Nickel-catalyzed synthesis of diarylsulfides and sulfones via C-H bond functionalization of arylamides

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Nickel-catalyzed synthesis of diarylsulfides and

sulfones via C–H bond functionalization of

Cite this: DOI: 10.1039/x0xx00000x

arylamides†

Vutukuri Prakash Reddy, Renhua Qiu, Takanori Iwasaki and Nobuaki Kambe*

Received 00th January 2012,

Accepted 00th January 2012

The direct sulfenylation and sulfonylation of (sp²)C−H bonds of benzamide derivatives were

achieved using a Ni catalyst with the aid of an 8-aminoquinoline moiety as a bidentate

directing group. These protocols represent a convenient route to the formation of valuable

diaryl sulfides and sulfones in moderate to excellent yields.

DOI: 10.1039/x0xx00000x

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Since the first example of the Pd-catalyzed C–C bond

formation of benzamide derivatives with the aid of an 8-

Introduction

aminoquinoline moiety as a bidentate directing group was

reported by Daugulis,^10,11various groups have successfully

developed carbon-carbon and carbon-heteroatom bond forming

reactions by the use of the bidentate directing group using

different transition metal catalysts such as Ni,¹²Pd,^8b,c,e,10,13

Cu,^6c,d,14Ru,¹⁵and Fe¹⁶. In recent years, Ni complexes have

been shown to be powerful catalysts for inert (sp²)C–H and

(sp³)C–H bond functionalization with the advantages of high

catalytic efficiency and good functional group tolerance.

However, Ni-catalyzed C–H bond functionalizations have been

limited to C–C bond formation reactions. To date, only the

cross-coupling reactions of azoles with aryl esters,¹⁷

alkylation,^12a,dand arylation^12gof (sp²)C–H bonds of aromatic

amides, and alkylation^12cand arylation^12b,e,fof (sp³)C−H bonds

of aliphatic amides have been achieved. With this background

in mind, we investigated direct C–H sulfenylation and

sulfonylation with diaryl disulfides and sulfonyl chlorides. In a

continuation of our studies in the area of C–H bond

functionalization and carbon-chalcogen bond forming

reactions,^8d,18we herein report the first examples of C–H bond

sulfenylation and sulfonylation of aromatic rings catalyzed by

Ni using an 8-aminoquinoline as a removable bidentate

directing group (Scheme 1).^14c,19

Diaryl sulfides and derivatives thereof are ubiquitous structural

motifs that are found in numerous biologically active natural

products, pharmaceuticals, functional materials, and metal

complexes.¹Among the various synthetic routes to the diaryl

sulfides, the transition metal mediated cross-coupling of Ar−X

(X = Cl, Br, I, OTf) or Ar−B(OH)₂with aryl thiols or their

metal salts (ArSM) is one of the most useful methods and is a

powerful tool for preparing diaryl sulfides.²Diaryl sulfones, an

oxidized family of sulfides, can also be prepared by metal

catalyzed coupling reactions between arylsulfonyl chlorides or

arylsulfinic acid salts and an appropriate aryl halide or boronic

acid.³Although these traditional coupling reactions are

effective for constructing various C−S bonds, prefunctionalized

substrates such as aryl halides and aryl metal reagents are

required, and this can often restrict potential applications of

these reactions.

In recent years, transition metal catalyzed C–H

functionalization reactions have received considerable attention

as straightforward transformations for the synthesis of valuable

products from simple starting materials in an inherently benign

fashion, minimizing wastes in atom-economic ways.⁴However,

the formation of C–S bonds through transition metal catalyzed

C–H bond cleavage^5-9has been less studied than the formation

of the corresponding C–C, C–N, and C–O bonds.^10-18a,b

The direct sulfenylation of C−H bonds of arenes to give the

corresponding C−S bonds has been achieved via the use of Cu,⁶

Rh,⁷or Pd⁸catalytic systems. Most recently, the Cu-catalyzed

sulfenylation of benzamides by thiols using a stoichiometric

amount of a Ag salt as the oxidant^6dand the Pd-catalyzed

sulfenylation^8b-dof C–H bonds have been reported. In these

reactions, various sulfur-containing sources, including diaryl

disulfides, thiols, and 1-(phenylthio)pyrrolidine-2,5-dione have

been studied, in efforts to achieve C–H bond sulfenylation.^8a

For the synthesis of sulfones via C–H bond cleavage, Dong^9a

and Frost^9bindependently reported on the sulfonylation of the

C-2 and C-3 position of phenylpyridines by sulfonyl chlorides

using Pd and Ru catalysts, respectively. Very recently, Wu and

coworkers reported on the use of a Cu catalytic system in the

C2-sulfonylation of quinoline N-oxides.^9c

Scheme 1 C–H bond sulfenylation and sulfonylation reactions

Results and discussion

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Initially, the reaction of N-(2-methylbenzoyl)-8-aminoquinoline

1a) with diphenyl disulfide (2a) was chosen as a model

(

reaction to optimize the reaction conditions, and results are

summarized in Table 1. With the combination of NiCl₂and

PPh₃(20 mol%), we examined the effects of bases and solvents.

In the absence of base, only 10% yield of desired sulfenylated

product 3aa was obtained by NiCl₂and PPh₃catalytic system

(entry 1). Among the bases employed, Cs₂CO₃gave the best

results (entries 2-6), giving rise to desired product 3aa in 85%

yield. The structure of 3aa was confirmed by an X-ray

crystallographic analysis (Fig 1a).²⁰1,4-Dioxane was found to

be the best solvent and DMF, DMSO, and DCE resulted in

somewhat lower yields (entries 7-9). In the absence of the PPh₃,

yield of the product slightly dropped to 68% (entry 10) but the

use of 3 equiv of PPh₃did not improve the yield (entry 11).

This may suggests that Ni intermediates are ligated by the

aminoquinoline directing group. Indeed, bidentate ligands, 2,2’-

bipyridine, dppe, and dppp, affected the sulfenylation reaction

(entries 12-14). In the absence of Ni catalyst, no reaction took

place at all (entry 15).

Scheme 2. Yield of 3aa from various sulfur sources for C–H bond

sulfenylation of 1a.

Fig. 1. ORTEP drawing of 3aa (a) and 3ah (b) with thermal ellipsoids at the 50%

probability level. H atoms are omitted for clarity

As shown in Table 2, the reaction of 1a with diaryl

disulfides carrying an electron-donating or -withdrawing

group(s) gave the desired coupling products in excellent yields

Table 1. Optimization of nickel-catalyzed sulfenylation of C–H bond of

benzamide^a

(

3ab-3ag). The reaction of 1a with dimethyl disulfide (2h) gave

the desired product 3ah²⁰in 36% yield (Fig 1b).

Table 2 Ni-catalyzed C–H sulfenylation of a 2-methylbenzamide

Entry

Catalyst

Ligand

Base

Solvent

Yield^b

(%)

10

59

65

61

75

85

70

74

69

68

79

7

13

40

N.D.

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

NiCl₂

PPh₃

–

PPh₃

bpy

–

Dioxane

DMF

K₃PO₄

Na₂CO₃

NaOMe

K₂CO₃

Cs₂CO₃

DMSO

DCE

NiCl₂

Dioxane

NiCl₂(PPh₃)₂

NiCl₂

NiCl₂(dppe)

NiCl₂(dppp)

–

The unsubstituted benzamide 1b and p-substituted

benzamides 1c

underwent sulfenylation to give an approximately 1:1 mixture

of mono- and disulfenylated products ( and ) in good overall

yields under the same conditions (Table 3). m-

Methylbenzamide was predominantly sulfenylated at the

relatively less hindered position to afford a mixture of mono-

and disulfenylated products, 3fa and 4fa, in a 5:1 ratio. The

reaction of naphthamide 1g gave only the 2-sulfenylated

product 3ga in 86% yield.

-e, which contains two ortho-C–H bonds,

^aReaction conditions: 1a (0.25 mmol), 2a (0.5 mmol), Ni catalyst (20

mol%), PPh₃(20 mol%), base (1.0 mmol), and solvent (1.0 mL), 21 h, 140

°C. ^bIsolated yields.

3

4

Then, we tested several sulfur sources having PhS moiety

under the optimized conditions as indicated in Table 1, entry 6

(Scheme 2). Among these sulfur sources, diphenyl disulfide and

S,S’-diphenyl carbonodithioate gave the desired products in

85% and 68% yields, respectively. On the other hand,

benzenethiol as well as phenylsulfenyl chloride were not

effective for the present catalytic system. The reaction

employing N-(phenylthio)phthalimide gave no desired product.

Due to easy accessibility of diaryl disulfides, we chose diaryl

disulfides as the best sulfenylating reagents.

When N-(2-fluorobenzoyl)-8-aminoquinoline

(

1h)

was

reacted with various diphenyl disulfide derivatives,

sulfenylation took place at the both the ortho-position via

concomitant C–H and C–F bond cleavage to give the

disulfenylated products

4 in excellent yields (eq 1). Although

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the mechanism of the C–F bond sulfenylation is not clear at this desired cross-coupling products (entries 12-14). The structures

moment, it may proceed via S_NAr reaction.

of the products 6aa and 7aa were confirmed by X-ray

crystallographic analyses (Fig 2).²⁰

Table 3 Ni-catalyzed C–H sulfenylation of m- or p-substituted benzamides

Table 4. Sulfonylation of C–H bond of benzamide 1a^a

and 1-naphthamide

Entry

1

2

3

4

5

6

7

8

Catalyst (mol%)

NiCl₂(50)

NiCl₂(30)

NiCl₂(100)

NiCl₂/PPh₃(20)

NiCl₂(50)

Base

Cs₂CO₃

K₃PO₄

K₂CO₃

Na₂CO₃

–

Na₂CO₃

K₂CO₃

Yield^b(%)

N.D.

Trace

N.D.

61

44

56

19

N.D.

31

N.D.

Trace

N.D.

9

–

10

11

12^c

13^d

14^e

PdCl₂(PhCN) (10)

PdCl₂(10)

PdCl₂(CH₃CN)₂(50)

CuI (10)

^aAn inseparable mixture of 3 and 4 was obtained. Ratio was determined by

¹H NMR.

[Ru(p-cymene)Cl₂]₂(5)

^aReaction conditions: 1a (0.25 mmol), sulfonyl chloride 5a (0.75

mmol), catalyst, base (2.0 mmol), solvent (1.0 mL), 24 h, 140 °C. ^b

Isolated yields. ^cIn toluene. ^dIn dichloroethane. ^eIn acetonitrile.

After the successful C–H bond sulfenylation of amide

derivatives, we next turned our attention to aromatic C–H bond

sulfonylation using sulfonyl chlorides as the coupling partner.

During course of the revision of the manuscript, a similar

catalytic system has been reported.²¹Initially, the reaction of 2-

methyl-N-(quinolin-8-yl)benzamide (1a) with tosyl chloride

(

5a) was chosen as a model reaction and conducted under the

Fig. 2. ORTEP drawing of 6aa (a) and 7aa (b) with thermal ellipsoids at the 50%

optimized conditions of the sulfenylation reaction; however, the

reaction did not take place. We thus optimized the reaction

conditions and results are shown in Table 4. The desired

sulfonylated product 6aa was obtained in 61% yield

accompanied by a trace amount of the disulfonylated product

7aa, when the reaction was conducted at 140 °C for 24 h using

50 mol% NiCl₂in the presence of Na₂CO₃(2.0 equiv) as a base

(entry 4). Replacement of Na₂CO₃with Cs₂CO₃or K₂CO₃

resulted in no reaction (entries 1 and 3) and K₃PO₄gave the

corresponding product in only a trace amount (entry 2).

Lowering catalyst loading led decreasing of the yield of 6aa

(entry 5); however, 100 mol% of NiCl₂did not improve the

yield (entry 6). The addition of PPh₃dropped the yield of

sulfonylated product (entry 7). Both Ni catalyst and base were

essential to attain the sulfonylation and no reaction took place

without either catalyst or base (entries 8-9). Among various

solvents tested, dioxane gave the best results. PdCl₂(PhCN)₂

showed unsatisfactory catalytic activity and simple Pd chloride

was completely ineffective (entries 10-11). Catalytic

procedures in recent reports for C–H bond sulfonylation by

using Pd,^9aCu,^9cand Ru^9bwere ineffective to provide the

probability level. H atoms are omitted for clarity

Under these optimized conditions, we investigated various

benzamides and aryl sulfonyl chlorides in the reaction, as

shown in Table 5. In all cases, the mono sulfonylated products

6

were obtained as the major products, accompanied by the

formation of a trace amount of disulfonylation products . The

reaction of an ortho-methylbenzamide 1a with sulfonyl

chlorides possessing an electron-donating or an electron-

7

withdrawing group afforded the desired products 6ab

42% to 61% yields. para-Substituted benzamide derivatives

1c gave the desired products 6ca da ia ie in moderate yields.

-6af in

,

d,i

,

, ,

In either cases, no disulfonylation at their ortho-positions took

place, even when 5 equiv of the sulfonyl chloride was used.

When a meta-substituted benzamide derivative was reacted

with TsCl (5a), the reaction took place selectively at the less

hindered position to give the coupling product 6fa in 36%

yield. The reaction of 1- and 2-naphthamides proceeded at the

2- and 3-positions, respectively, to give the desired products

6gb,ja

,jb in 33% to 45% yields. MsCl (5g) did not afford the

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coupling product 6ag under the same conditions, probably due undergoes reductive elimination followed by protonation to

to the thermal decomposition of 5g ^9a

.

afford the desired products with the regeneration of Ni(II) to

complete the catalytic cycle.

Table 5 Ni-mediated C–H bond sulfonylation

Conclusions

In conclusion, we report herein the first example of the Ni-

catalyzed C(sp²)–H bond sulfenylation and sulfonylation of

benzamide derivatives. The present Ni-catalyzed system would

be useful as an alternative or a supplementary method to the

currently used methods for preparing diaryl sulfides and diaryl

sulfones having various substituents from readily available

precursors.

Experimental

General methods

¹H and ¹³C NMR spectra were recorded with a JEOL JNM-

Alice 400 (400 MHz and 100 MHz, respectively) spectrometer.

1

All H NMR chemical shifts were reported in ppm relative to

internal references of tetramethylsilane at  0.00. All ¹³C NMR

chemical shifts were reported in ppm relative to carbon

resonance in chloroform-d₁at  77.00. Conventional mass

spectra were recorded with a JEOL JMS-T100TD spectrometer

(DART) using a time-of-flight mass spectrometer. High

resolution mass spectra were recorded with a JEOL JMS-

DX303HF spectrometer (EI) using a double focusing magnetic

sector mass spectrometer. Melting points were measured using

Stanford Research Systems OptiMelt MPA 100. X-ray

crystallographic analyses were carried out using a Rigaku R-

AXIS RAPID Imaging Plate diffractometer with Cu-K for

3aa

,

6aa, and 7aa and with Mo-K for 3ah. The structures of

3ah 6aa, and 7aa were solved by direct methods

,

^aLess than 2% of 7 was observed in each reaction.

(SHELX97²³). The structure was refined on F²by full-matrix

least-squares method using SHELXL-97.²³Non-hydrogen

atoms were anisotropically refined. Hydrogen atoms were

included in the refinement on calculated positions riding on

their carrier atoms. Catalysts, benzoyl chloride derivatives, 8-

aminoquinoline, and diaryl disulfides were purchased from

Tokyo Chemical Industry Company and Sigma Aldrich

Company. Dehydrated solvents (Wako Pure Chemical

Industries) were purchased and used as received.

A possible catalytic cycle for the reaction is shown in

Scheme 3. The coordination of quinoline to the Ni center and

subsequent deprotonation of the amide N–H leads to the

formation of intermediate

intermediate

via cyclometalation by the aid of Cs₂CO₃.¹²The

oxidative addition of intermediate

to diaryl disulfides²²

affords the Ni(IV) intermediate , which simultaneously

A, which gives rise to the

B

C

General procedure for the preparation of amide substrates

8-Aminoquinoline (3.0 g, 21 mmol) and N,N-dimethyl-4-

aminopyridine (80 mg, 0.65 mmol) were placed in a 100 mL

two-necked flask, and the flask was flushed with nitrogen.

Dichloromethane (20 mL) and Et₃N (3.3 mL, 24 mmol) were

added and the resulting solution was cooled to 0 °C. To this

solution benzoyl chloride derivatives (20 mmol) was added

drop wise. The resulting mixture was stirred at room

temperature for 15 h. The mixture was quenched with water

and the products were extracted with dichloromethane. The

combined organic layer was dried over sodium sulfate and

concentrated to give benzamide derivatives.

2-Methyl-N

-(quinolin-8-yl)benzamide (1a).^{14c 1}H NMR

(400 MHz, CDCl₃): δ = 10.22 (br s, 1H), 8.95 (d, J = 7.2 Hz,

1H), 8.78 (dd, J = 4.0, 1.2 Hz, 1H), 8.18 (dd, J = 8.4, 1.6 Hz,

Scheme 3. A possible catalytic cycle

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1H), 7.69 (d, J = 7.6 Hz, 1H), 7.62-7.54 (m, 2H), 7.47-7.38 (m, 7.31 (m, 1H), 7.26-7.22 (m, 1H); ¹³C NMR (100 MHz, CDCl₃):

2H), 7.34-7.26 (m, 2H), 2.60 (s, 3H); ¹³C NMR (100 MHz, δ = 161.8, 161.64, 161.60, 159.3, 148.5, 138.8, 136.3, 134.8,

CDCl₃): δ = 168.2, 148.2, 138.6, 136.7, 136.6, 136.3, 134.7, 133.6, 133.5, 132.02, 132.00, 128.0, 127.4, 124.9, 124.8, 122.1,

131.3, 130.3, 128.0, 127.4, 127.2, 126.0, 121.7, 121.6, 116.5, 122.04, 122.00, 121.7, 117.2, 116.4, 116.2; MS (DART): m/z

20.2; MS (DART): m/z 263 [M+H]⁺.

-(Quinolin-8-yl)benzamide (1b).^{16c 1}H NMR (400 MHz,

267 [M+H]⁺.

4-Trifluoromethyl-N

-(quinolin-8-yl)benzamide (1i). ¹H

N

CDCl₃): δ = 10.76 (br s, 1H), 8.95 (dd, J = 7.2, 1.2 Hz, 1H), NMR (400 MHz, CDCl₃): δ = 10.79 (br s, 1H), 8.92 (dd, J =

8.86 (dd, J = 8.4, 1.6 Hz, 1H), 8.20 (dd, J = 8.0, 2.0 Hz, 1H), 7.6, 1.6 Hz, 1H), 8.85 (dd, J = 4.0, 1.6 Hz, 1H), 8.22-8.18 (m,

8.11-8.08 (m, 2H), 7.62-7.53 (m, 5H), 7.49 (dd, J = 8.4, 2.0 Hz, 3H), 7.82 (d, J = 8.4 Hz, 2H), 7.63-7.56 (m, 2H), 7.50 (dd, J =

1H); ¹³C NMR (100 MHz, CDCl₃): δ = 165.5, 148.3, 138.8, 8.0, 4.0 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃): δ = 164.0,

136.4, 134.6, 131.8, 128.8, 128.0, 127.5, 127.3, 121.7, 116.5; 148.4, 138.7, 138.4, 136.5, 134.1, 133.6, 133.3, 128.0, 127.7,

MS (DART): m/z 249 [M+H]⁺.

4-Methyl-

-(quinolin-8-yl)benzamide (1c).^{16c 1}H NMR

127.4, 125.90, 125.87, 125.83, 125.80, 122.2, 121.8, 116.7.

-(Quinolin-8-yl)-2-naphthamide (1j).^{14c 1}H NMR (400

N

(400 MHz, CDCl₃): δ = 10.73 (br s, 1H), 8.94 (d, J = 8.0 Hz, MHz, CDCl₃): δ = 10.90 (br s, 1H), 9.00 (dd, J = 7.6, 1.2 Hz,

1H), 8.85 (d, J = 4.0 Hz, 1H), 8.18 (d, J = 8.4 Hz, 1H), 7.99 (d, 1H), 8.89 (dd, J = 4.0, 1.6 Hz, 1H), 8.60 (s, 1H), 8.18 (dd, J =

J = 7.6 Hz, 2H), 7.61-7.46 (m, 3H), 7.35 (d, J = 8.0 Hz, 2H), 8.0, 1.2 Hz, 1H), 8.14 (dd, J = 7.6, 1.2 Hz, 1H), 8.05-7.99 (m,

2.46 (s, 3H); ¹³C NMR (100 MHz, CDCl₃): δ = 165.4, 148.2, 2H), 7.92-7.91 (m, 1H), 7.64-7.54 (m, 4H), 7.48 (dd, J = 8.0,

142.3, 138.8, 136.4, 134.7, 132.3, 129.4, 128.0, 127.5, 127.3, 4.4 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃): δ = 165.5, 148.3,

121.6, 121.5, 116.4, 21.5; MS (DART): m/z 263 [M+H]⁺.

4-(tert-Butyl)-

-(quinolin-8-yl)benzamide (1d).^{14c 1}H 127.83, 127.77, 127.5, 126.8, 123.7, 121.7, 116.6; MS (DART):

138.8, 136.4, 134.9, 134.6, 132.7, 132.3, 129.2, 128.7, 128.0,

N

NMR (400 MHz, CDCl₃): δ = 10.74 (br s, 1H), 8.94 (dd, J = m/z 299 [M+H]⁺.

7.6, 1.2 Hz, 1H), 8.84 (dd, J = 4.4, 1.2 Hz, 1H), 8.18 (dd, J =

8.4, 1.2 Hz, 1H), 8.03 (d, J = 8.8 Hz, 2H), 7.61-7.52 (m, 4H),

7.47 (dd, J = 8.0, 4.0 Hz, 1H), 1.38 (s, 9H); ¹³C NMR (100

General procedure for Ni-catalyzed sulfenylation of amides with

diaryl disulfides

MHz, CDCl₃): δ = 165.5, 155.3, 148.2, 138.8, 136.4, 134.7, To an oven-dried

132.3, 128.0, 127.5, 127.1, 125.7, 121.6, 121.5, 116.4, 35.0, derivative (1.0 mmol), diaryl disulfides (2.0 mmol), NiCl₂(20

31.8; MS (DART): m/z 305 [M+H]⁺.

mol %), PPh₃(20 mol%), Cs₂CO₃(1.0 equiv), and dioxane (1

4-Methoxy-

-(quinolin-8-yl)benzamide (1e).^{16c 1}H NMR mL) were added in a glove box. The mixture was stirred for 21

5 mL screw-capped vial, benzamide

N

(400 MHz, CDCl₃): δ = 10.69 (br s, 1H), 8.93 (dd, J = 7.6, 1.2 h at 140 °C followed by cooling. The resulting mixture was

Hz, 1H), 8.85 (dd, J = 4.0, 1.2 Hz, 1H), 8.19 (dd, J = 8.0, 1.6 filtered through a celite pad and concentrated in vacuo. The

Hz, 1H), 8.06 (t, J = 2.4 Hz, 2H), 7.61-7.46 (m, 3H), 7.06-7.02 residue was purified by column chromatography on silica gel to

(m, 2H), 3.90 (s, 3H); ¹³C NMR (100 MHz, CDCl₃): δ = 165.0, afford the desired products.

162.5, 148.2, 138.7, 136.4, 134.7, 129.2, 128.0, 127.5, 127.4,

6-Methyl-2-(phenylsulfanyl)-N-(quinolin-8-yl)benzamide

121.6, 121.4, 116.3, 114.0, 55.5; MS (DART): m/z 279 (3aa).^6cFollowing general procedure, the title compound was

[M+H]⁺.

3-Methyl-

purified by flash column chromatography on silica gel

-(quinolin-8-yl)benzamide (1f).^{16c 1}H NMR (hexane/EtOAc = 20:1) to yield 3aa in 85% yield as a solid.

N

(400 MHz, CDCl₃): δ = 10.72 (br s, 1H), 8.95 (dd, J = 7.2, 1.2 Single crystals of 3aa suitable for X-ray crystallography were

Hz, 1H), 8.86 (dd, J = 4.0, 1.2 Hz, 1H), 8.19 (dd, J = 8.4, 1.2 obtained by recrystallization from toluene: mp 152-153 °C; ¹H

Hz, 1H), 7.89 (d, J = 8.0 Hz, 2H), 7.62-7.53 (m, 2H), 7.50-7.38 NMR (400 MHz, CDCl₃): δ = 9.94 (br s, 1H), 8.97 (d, J = 7.2

(m, 3H), 2.49 (s, 3H); ¹³C NMR (100 MHz, CDCl₃): δ = 165.7, Hz, 1H), 8.68 (dd, J = 4.0, 1.2 Hz, 1H), 8.15 (d, J = 8.4 Hz,

148.3, 138.8, 138.7, 136.4, 135.1, 134.6, 132.6, 128.6, 128.1, 1H), 7.61-7.53 (m, 2H), 7.42 (dd, J = 8.4, 4.0 Hz, 1H), 7.32-

128.0, 127.5, 124.2, 121.7, 121.6, 116.5, 21.5; MS (DART): 7.34 (m, 2H), 7.28-7.12 (m, 6H), 2.48 (s, 3H); ¹³C NMR (100

m/z 263 [M+H]⁺.

-(Quinolin-8-yl)-1-naphthamide (1g). ¹H NMR (400 135.6, 134.3, 133.0, 131.3, 130.4, 129.7, 129.6, 129.1, 127.9,

MHz, CDCl₃): δ = 166.9, 148.1, 140.1, 138.5, 136.2, 136.1,

N

MHz, CDCl₃): δ = 10.43 (br s, 1H), 9.06 (d, J = 7.6 Hz, 1H), 127.4, 127.1, 121.9, 121.6, 116.9, 19.6; MS (DART): m/z 371

8.75 (dd, J = 4.0, 1.2 Hz, 1H), 8.54 (d, J = 8.4 Hz, 1H), 8.20 [M+H]⁺; HRMS (EI): m/z [M]⁺Calcd for C₂₃H₁₈N₂O₂S

(dd, J = 8.4, 1.2 Hz, 1H), 8.01 (d, J = 8.0 Hz, 1H), 7.93 (d, J = 370.1140; Found 370.1141; X-ray data for 3aa (CCDC

7.2 Hz, 2H), 7.67-7.55 (m, 5H), 7.46 (dd, J = 8.4, 4.4 Hz, 1H); 1023625): M = 370.47, colorless, monoclinic, P2₁/n (#14), a =

¹³C NMR (100 MHz, CDCl₃): δ = 167.7, 148.3, 138.6, 136.4, 16.1194(3) Å, b = 8.0643(2) Å, c = 16.6212(3) Å,  =

134.8, 134.6, 133.9, 131.1, 130.3, 128.4, 128.0, 127.4, 127.3, 118.7846(7)°, V = 1893.64(6) Å³, Z = 4, D_calcd= 1.299 g/cm³, T

126.5, 125.6, 125.5, 124.9, 121.9, 121.7, 116.7; MS (DART): = –150(2) °C, R₁(wR₂) = 0.0412 (0.1013).

m/z 299 [M+H]⁺.

2-Fluoro-

-(quinolin-8-yl)benzamide (1h). ¹H NMR (400 yl)benzamide (3ab). Following general procedure, the title

2-(4-Methoxyphenylsulfanyl)-6-methyl-N-(quinolin-8-

N

MHz, CDCl₃): δ = 11.16 (br d, J = 12.0 Hz, 1H), 8.98 (dd, J = compound was purified by flash column chromatography on

7.2, 1.6 Hz, 1H), 8.88 (dd, J = 8.0, 1.6 Hz, 1H), 8.25-8.17 (m, silica gel (hexane/EtOAc = 20:1) to yield 3ab in 96% yield as a

2H), 7.61-7.51 (m, 3H), 7.48 (dd, J = 8.0, 4.0 Hz, 1H), 7.35- white solid: mp 138-139 °C; ¹H NMR (400 MHz, CDCl₃): δ =

This journal is © The Royal Society of Chemistry 2012

J. Name., 2012, 00, 1-3 | 5

Organic & Biomolecular Chemistry

^{View Articl}P^{e O}aⁿg^line^e6 of 11

DOI: 10.1039/C5OB00149H

ARTICLE

Journal Name

9.97 (br s, 1H), 9.00 (dd, J = 7.2, 1.6 Hz, 1H), 8.73 (dd, J = 8.0, white solid: mp 132-133 °C; ¹H NMR (400 MHz, CDCl₃): δ =

1.6 Hz, 1H), 8.17 (d, J = 8.4 Hz, 1H), 7.63-7.55 (m, 2H), 7.45- 9.86 (br s, 1H), 8.91 (dd, J = 7.6, 1.6 Hz, 1H), 8.66 (d, J = 3.2

7.42 (m, 1H), 7.38 (d, J = 8.4 Hz, 2H), 7.19 (t, J = 8.0 Hz, 1H), Hz, 1H), 8.14 (d, J = 7.6 Hz, 1H), 7.59-7.52 (m, 2H), 7.41-7.37

7.11 (d, J = 7.6 Hz, 1H), 7.01 (d, J = 7.6 Hz, 1H), 6.77 (d, J = (m, 4H), 7.08-6.94 (m, 3H), 2.51 (s, 3H); ¹³C NMR (100 MHz,

8.4 Hz, 2H), 3.73 (s, 3H), 2.45 (s, 3H); ¹³C NMR (100 MHz, CDCl₃): δ = 166.4, 148.1, 142.3, 138.7, 138.3, 137.0, 136.2,

CDCl₃): δ = 167.1, 159.7, 148.2, 138.5, 138.2, 136.3, 135.8, 134.0, 133.1, 132.8, 131.6, 131.0, 130.3, 130.2, 129.3, 128.5,

135.7, 135.2, 134.3, 129.5, 128.4, 128.0, 127.4, 124.6, 121.9, 127.8, 127.3, 127.0, 122.0, 121.6, 116.8, 19.7; MS (DART):

121.6, 116.9, 114.8, 55.2, 19.5; MS (DART): m/z 401 [M+H]⁺; m/z 439 [M+H]⁺; HRMS (EI): m/z [M]⁺Calcd for

HRMS (EI): m/z [M]⁺Calcd for C₂₄H₂₀N₂O₂S 400.1245; Found C₂₃H₁₆Cl₂N₂OS 438.0360; Found 438.0358.

400.1250.

2-(2-Methoxyphenylsulfanyl)-6-methyl-

2-(4-Chlorophenylsulfanyl)-6-methyl-

yl)benzamide (3ag). Following general procedure, the title

N-(quinolin-8-

N

-(quinolin-8-

yl)benzamide (3ac). Following general procedure, the title compound was purified by flash column chromatography on

compound was purified by flash column chromatography on silica gel (hexane/EtOAc = 20:1) to yield 3ag in 93% yield as a

silica gel (hexane/EtOAc = 20:1) to yield 3ac in 92% yield as a white solid: mp 118-119 °C; ¹H NMR (400 MHz, CDCl₃): δ =

white solid: mp 189-190 °C; ¹H NMR (400 MHz, CDCl₃): δ = 9.84 (br s, 1H), 8.94 (dd, J = 7.2, 1.2 Hz, 1H), 8.65 (dd, J = 4.4,

9.98 (br s, 1H), 8.97 (dd, J = 7.6, 1.2 Hz, 1H), 8.67 (dd, J = 8.0, 1.6 Hz, 1H), 8.14 (dd, J = 8.4, 1.6 Hz, 1H), 7.59-7.52 (m, 2H),

1.2 Hz, 1H), 8.13 (dd, J = 8.0, 1.6 Hz, 1H), 7.59-7.52 (m, 2H), 7.41 (dd, J = 8.0, 4.4 Hz, 1H), 7.31-7.17 (m, 5H), 7.11-7.08 (m,

7.39 (dd, J = 8.0, 4.0 Hz, 1H), 7.26-7.13 (m, 5H), 6.85 (t, J = 2H), 2.47 (s, 3H); ¹³C NMR (100 MHz, CDCl₃): δ = 166.7,

7.2 Hz, 1H), 6.73 (d, J = 8.0 Hz, 1H), 3.66 (s, 3H), 2.47 (s, 3H); 148.2, 140.8, 138.3, 136.4, 136.2, 134.8, 134.1, 132.9, 131.9,

¹³C NMR (100 MHz, CDCl₃): δ = 167.0, 157.4, 148.0, 140.3, 131.8, 131.3, 130.3, 129.8, 129.1, 127.9, 127.3, 122.0, 121.6,

138.4, 136.2, 136.1, 134.4, 132.2, 132.1, 130.5, 129.52, 129.46, 116.8, 19.6; MS (DART): m/z 405[M+H]⁺; HRMS (EI): m/z

128.4, 127.8, 127.3, 124.1, 121.8, 121.5, 121.2, 116.8, 110.8, [M]⁺Calcd for C₂₃H₁₇ClN₂OS 404.0750; Found: 404.0751.

55.6, 19.6; MS (DART): m/z 401 [M+H]⁺; HRMS (EI): m/z

[M]⁺Calcd for C₂₄H₂₀N₂O₂S 400.1245; Found 400.1243.

6-Methyl-2-(methylsulfanyl)-N-(quinolin-8-yl)benzamide

(3ah). Following general procedure, the title compound was

6-Methyl-2-(4-methylphenylsulfanyl)-

N

-(quinolin-8-yl)-

purified by flash column chromatography on silica gel

benzamide (3ad). Following general procedure, the title (hexane/EtOAc = 20:1) to yield 3ah in 36% yield as an orange

compound was purified by flash column chromatography on solid. Single crystals of 3ah suitable for X-ray crystallography

silica gel (hexane/EtOAc = 20:1) to yield 3ad in 89% yield as a were obtained by recrystallization from toluene: mp 96-97 °C;

white solid: mp 133-134 °C; ¹H NMR (400 MHz, CDCl₃): δ = ¹H NMR (400 MHz, CDCl₃): δ = 9.99 (br s, 1H), 9.02 (dd, J =

9.95 (br s, 1H), 8.99 (dd, J = 7.2, 1.2 Hz, 1H), 8.69 (dd, J = 4.0, 8.0, 1.6 Hz, 1H), 8.75 (dd, J = 4.0, 1.6 Hz, 1H), 8.18 (dd, J =

1.2 Hz, 1H), 8.14 (dd, J = 8.4, 1.6 Hz, 1H), 7.60-7.52 (m, 2H), 8.4, 2.0 Hz, 1H), 7.63-7.55 (m, 2H), 7.44 (dd, J = 8.0, 4.0 Hz,

7.41 (dd, J = 8.4, 4.0 Hz, 1H), 7.28-7.19 (m, 3H), 7.13 (t, J = 1H), 7.33-7.24 (m, 2H), 7.11 (d, J = 7.2 Hz, 1H), 2.47 (s, 3H),

8.4 Hz, 2H), 7.01 (d, J = 8.0 Hz, 2H), 2.46 (s, 3H), 2.23 (s, 3H); 2.44 (s, 3H); ¹³C NMR (100 MHz, CDCl₃): δ = 167.2, 148.3,

¹³C NMR (100 MHz, CDCl₃): δ = 167.0, 148.1, 139.1, 138.4, 138.5, 138.2, 136.3, 135.6, 135.5, 134.3, 129.5, 128.0, 127.8,

137.5, 136.2, 135.9, 134.29, 134.26, 132.4, 131.2, 129.9, 129.5, 127.4, 125.5, 122.0, 121.6, 116.9, 19.4, 17.4; MS (DART): m/z

129.2, 128.9, 127.9, 127.4, 121.9, 121.5, 116.8, 21.0, 19.5; MS 309 [M+H]⁺; HRMS (EI): m/z [M]⁺Calcd for C₁₈H₁₆N₂OS

(DART): m/z 385 [M+H]⁺; HRMS (EI): m/z [M]⁺Calcd for 308.0983; Found 308.0985; Anal. Calcd for [C₁₈H₁₆N₂OS]: C,

C₂₄H₂₀N₂OS 384.1296; Found 384.1298.

70.10; H, 5.23; N, 9.08. Found: C, 70.05; H, 5.15; N, 8.99; X-

2-(2,6-Dichlorophenylsulfanyl)-6-methyl-

N

-(quinolin-8-

ray data for 3ah (CCDC 1030338): M = 308.40, colorless,

yl)benzamide (3ae). Following general procedure, the title monoclinic, P2₁/c (#14), a = 7.2995(4) Å, b = 8.9313(4) Å, c =

compound was purified by flash column chromatography on 23.2132(12) Å,  = 90.8321(17)°, V = 1513.20(14) Å³, Z = 4,

silica gel (hexane/EtOAc = 20:1) to yield 3ae in 96% yield as a D_calcd= 1.354 g/cm³, T = –150(2) °C, R₁(wR₂) = 0.0400

white solid: mp 170-171 °C; ¹H NMR (400 MHz, CDCl₃): δ = (0.0889).

10.16 (br s, 1H), 9.00 (d, J = 7.6 Hz, 1H), 8.75 (d, J = 4.0 Hz,

2-(Phenylsulfanyl)-

N

-(quinolin-8-yl)benzamide

(3ba).

1H), 8.17 (d, J = 8.4 Hz, 1H), 7.63-7.55 (m, 2H), 7.45 (dd, J = Following general procedure, the title compound was purified

8.0, 4.0 Hz, 1H), 7.35 (d, J = 8.0 Hz, 2H), 7.20-7.09 (m, 3H), by flash column chromatography on silica gel (hexane/EtOAc =

6.72 (d, J = 7.6 Hz, 1H), 2.47 (s, 3H); ¹³C NMR (100 MHz, 20:1) to give 3ba and 4ba in 38% and 45% yields, respectively:

1

CDCl₃): δ = 166.7, 148.2, 141.6, 138.5, 137.2, 136.3, 136.0, mp 111-112 °C; H NMR (400 MHz, CDCl₃): δ = 10.53 (br s,

134.4, 133.5, 131.7, 130.5, 129.5, 128.8, 128.3, 128.0, 127.4, 1H), 8.93 (d, J = 7.2 Hz, 1H), 8.75 (t, J = 2.0 Hz, 1H), 8.15 (dd,

125.4, 122.0, 121.6, 116.8, 19.6; MS (DART): m/z 439 J = 8.0, 1.2 Hz, 1H), 7.81-7.79 (m, 1H), 7.59-7.41 (m, 5H),

[M+H]⁺; HRMS (EI): m/z [M]⁺Calcd for C₂₃H₁₆Cl₂N₂OS 7.31-7.24 (m, 5H), 7.17-7.15 (m, 1H); ¹³C NMR (100 MHz,

438.0360; Found 438.0359.

CDCl₃): δ = 166.2, 148.2, 138.6, 137.4, 136.3, 135.8, 134.5,

2-(2,5-Dichlorophenylsulfanyl)-6-methyl-

N

-(quinolin-8-

134.1, 133.4, 130.9, 130.6, 129.4, 128.2, 128.0, 127.9, 127.4,

yl)benzamide (3af). Following general procedure, the title 126.2, 121.8, 121.6, 116.7; MS (DART): m/z 357 [M+H]⁺;

compound was purified by flash column chromatography on HRMS (EI): m/z [M]⁺Calcd for C₂₂H₁₆N₂OS 356.0983; Found

silica gel (hexane/EtOAc = 20:1) to yield 3af in 98% yield as a 356.0984.

6 | J. Name., 2012, 00, 1-3

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DOI: 10.1039/C5OB00149H

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Journal Name

Organic & Biomolecular Chemistry

ARTICLE

4-Methyl-2-(phenylsulfanyl)-N-(quinolin-8-yl)benzamide 1H), 8.93 (d, J = 7.2 Hz, 1H), 8.77 (dd, J = 4.0, 2.0 Hz, 1H),

(3ca). Following general procedure, the title compound was 8.15 (dd, J = 8.4, 1.2 Hz, 1H), 7.82 (d, J = 8.8 Hz, 2H), 7.58-

purified by flash column chromatography on silica gel 7.7.20 (m, 13H), 6.78-6.82 (m, 1H), 6.60 (s, 2H), 3.68 (s, 3H);

(hexane/EtOAc = 20:1) to give 3ca and 4ca in 45% and 39% ¹³C NMR (100 MHz, CDCl₃): δ = 165.8, 165.2, 161.4, 160.1,

yields, respectively: ¹H NMR (400 MHz, CDCl₃): δ = 10.57 (br 148.1, 148.0, 140.8, 138.6, 138.4, 137.3, 136.3, 136.1, 134.7,

s, 1H), 8.92 (dd, J = 7.2, 1.2 Hz, 1H), 8.76 (dd, J = 4.0, 1.6 Hz, 134.3, 134.1, 133.9, 133.5, 132.7, 132.2, 130.0, 129.5, 139.3,

1H), 8.17 (dd, J = 8.4, 1.6 Hz, 1H), 7.73 (d, J = 7.6 Hz, 1H), 128.4, 127.93, 127.90, 127.9, 127.40, 127.39, 127.3, 121.8,

7.59-7.52 (m, 2H), 7.46-7.42 (m, 3H), 7.32-7.24 (m, 3H), 7.13 121.54, 121.46, 116.8, 116.6, 115.2, 115.0, 111.1, 55.28, 55.22.

(d, J = 8.0 Hz, 1H), 7.02 (s, 1H), 2.29 (s, 3H); ¹³C NMR (100

5-Methyl-2-(phenylsulfanyl)-N-(quinolin-8-yl)benzamide

MHz, CDCl₃): δ = 166.3, 148.2, 141.4, 138.7, 136.8, 136.3, (3fa:4fa). Following general procedure, the title compound was

134.7, 134.5, 133.5, 132.9, 131.6, 129.3, 128.5, 127.9, 127.8, purified by flash column chromatography on silica gel

127.4, 127.3, 121.7, 121.6, 116.7, 21.4; MS (DART): m/z 371 (hexane/EtOAc = 20:1) to give 3fa and 4fa as an inseparable

[M+H]⁺; HRMS (EI): m/z [M]⁺Calcd for C₂₃H₁₈N₂OS mixture in 78% of combined yield with 5:1 ratio (determined

1

370.1140; Found 370.1137.

by H NMR): ¹H NMR (400 MHz, CDCl₃): δ = (major product

4-Methyl-2,6-bis(phenylsulfanyl)-N-(quinolin-8-

3fa) 10.51 (br s, 1H), 8.95-8.89 (m, 1H), 8.72 (dd, J = 4.4, 1.2

1

yl)benzamide (4ca). mp 145-146 °C; H NMR (400 MHz, Hz, 1H), 8.14 (dd, J = 8.4, 1.2 Hz, 1H), 7.62-7.10 (m, 11H),

CDCl₃): δ = 10.00 (br s, 1H), 8.95 (dd, J = 7.6, 1.2 Hz, 1H), 2.40 (s, 3H); ¹³C NMR (100 MHz, CDCl₃): δ = 166.4, 165.7,

8.66 (dd, J = 8.4, 1.2 Hz, 1H), 8.13 (dd, J = 8.0, 1.2 Hz, 1H), 148.1, 147.8, 143.3, 138.6, 138.3, 137.2, 137.1, 136.7, 136.2,

7.58-7.50 (m, 2H), 7.41-7.38 (m, 5H), 7.25-7.16 (m, 6H), 7.00 136.0, 135.4, 135.3, 134.5, 134.2, 133.9, 132.3, 132.1, 132.0,

(s, 2H), 2.19 (s, 3H); ¹³C NMR (100 MHz, CDCl₃): δ = 165.4, 131.8, 131.6, 129.9, 129.20, 129.17, 128.9, 127.9, 127.7, 127.6,

148.0, 140.5, 138.4, 138.2, 136.1, 134.9, 134.8, 134.3, 132.0, 127.37, 127.35, 127.30, 125.6, 121.8, 121.7, 121.5, 121.3,

131.5, 129.2, 127.8, 127.5, 127.4, 121.8, 121.4, 116.9, 21.2; 116.8, 116.7, 21.0, 20.9.

MS (DART): m/z 479 [M+H]⁺.

2-(Phenylsulfanyl)-

N-(quinolin-8-yl)-1-naphthamide

4-(tert-Butyl)-2-(phenylsulfanyl)-N-(quinolin-8-

(3ga). Following general procedure, the title compound was

yl)benzamide (3da). Following general procedure, the title purified by flash column chromatography on silica gel

compound was purified by flash column chromatography on (hexane/EtOAc = 20:1) to give 3ga in 86% yield: mp 180-181

silica gel (hexane/EtOAc = 20:1) to give 3da and 4da in 39% °C; ¹H NMR (400 MHz, CDCl₃): δ = 10.22 (br s, 1H), 9.11 (dd,

1

and 31% yields, respectively: mp 72-73 °C; H NMR (400 J = 7.6, 1.2 Hz, 1H), 8.63 (dd, J = 4.0, 1.2 Hz, 1H), 8.16 (dd, J

MHz, CDCl₃): δ = 10.57 (br s, 1H), 8.92 (dd, J = 7.6, 1.6 Hz, = 8.4, 1.6 Hz, 1H), 8.06-8.04 (m, 1H), 7.87-7.81 (m, 2H), 7.66-

1H), 8.75 (dd, J = 4.0, 1.6 Hz, 1H), 8.15 (dd, J = 8.4, 1.2 Hz, 7.50 (m, 4H), 7.42-7.38 (m, 4H), 7.26-7.17 (m, 3H); ¹³C NMR

1H), 7.78 (d, J = 8.0 Hz, 1H), 7.58-7.50 (m, 2H), 7.45-7.42 (m, (100 MHz, CDCl₃): δ = 166.5, 148.2, 138.4, 137.4, 136.2,

3H), 7.35-7.23 (m, 5H), 1.21 (s, 9H); ¹³C NMR (100 MHz, 135.4, 134.4, 132.4, 131.5, 130.7, 130.6, 130.1, 129.3, 129.2,

CDCl₃): δ = 166.2, 154.3, 148.2, 138.7, 136.5, 136.3, 134.70, 128.1, 127.9, 127.7, 127.4, 127.2, 126.8, 125.2, 122.1, 121.6,

134.67, 133.4, 132.9, 129.2, 128.45, 128.36, 127.9, 127.8, 117.0; MS (DART): m/z 407 [M+H]⁺; HRMS (EI): m/z [M]⁺

127.4, 123.6, 121.7, 121.6, 116.7, 34.9, 30.9; MS (DART): m/z Calcd for C₂₆H₁₈N₂OS 406.1140; Found 406.1143.

413 [M+H]⁺; HRMS (EI): m/z [M]⁺Calcd for C₂₆H₂₄N₂OS

2,6-Bis(phenylsulfanyl)-N-(quinolin-8-yl)benzamide

412.1609; Found 412.1608.

(4ha). Following general procedure, the title compound was

4-(tert-Butyl)-2,6-bis(phenylsulfanyl)-

N

-(quinolin-8-

purified by flash column chromatography on silica gel

1

yl)benzamide (4da). mp 155-156 °C; H NMR (400 MHz, (hexane/EtOAc = 20:1) to yield 4ha in 89% yield as an orange

CDCl₃): δ = 9.97 (br s, 1H), 8.94 (d, J = 7.6 Hz, 1H), 8.65-8.64 solid: ¹H NMR (400 MHz, CDCl₃): δ = 10.06 (br s, 1H), 8.97

(m, 1H), 8.13 (d, J = 8.4 Hz, 1H), 7.58-7.51 (m, 2H), 7.41-7.36 (d, J = 6.8 Hz, 1H), 8.67 (dd, J = 4.4, 1.2 Hz, 1H), 8.12 (dd, J =

(m, 5H), 7.26-7.15 (m, 8H), 1.14 (s, 9H); ¹³C NMR (100 MHz, 8.4, 1.2 Hz, 1H), 7.58-7.50 (m, 2H), 7.41-7.37 (m, 5H), 7.26-

CDCl₃): δ = 165.4, 153.4, 148.0, 138.4, 138.2, 136.1, 134.9, 7.10 (m, 9H); ¹³C NMR (100 MHz, CDCl₃): δ = 165.2, 148.0,

134.5, 134.3, 131.8, 129.1, 128.4, 127.8, 127.40, 127.38, 121.8, 139.8, 138.4, 136.2, 135.6, 134.2, 134.1, 132.5, 130.1, 130.0,

121.4, 116.9, 34.9, 30.8; MS (DART): m/z 521 [M+H]⁺; HRMS 129.3, 127.83, 127.75, 127.4, 122.0, 121.5, 116.9; MS (DART):

(EI): m/z [M]⁺Calcd for C₃₂H₂₈N₂OS₂520.1643; Found m/z 465 [M+H]⁺; HRMS (EI): m/z [M]⁺Calcd for C₂₈H₂₀N₂OS₂

520.1645.

5-Methyl-2-(phenylsulfanyl)-

464.1017; Found 464.1014.

N

-(quinolin-8-yl)benzamide

2,6-Bis(4-methoxyphenylsulfanyl)-N-(quinolin-8-

(3ea:4ea). Following general procedure, the title compound yl)benzamide (4hb). Following general procedure, the title

was purified by flash column chromatography on silica gel compound was purified by flash column chromatography on

(hexane/EtOAc = 20:1) to give 3ea and 4ea as an inseparable silica gel (hexane/EtOAc = 20:1) to yield 4hb in 98% yield as

mixture in 82% of combined yield with 2:1 ratio (determined an orange solid: mp 131-132 °C; ¹H NMR (400 MHz, CDCl₃):

1

by H NMR): ¹H NMR (400 MHz, CDCl₃): δ = (major product δ = 10.09 (br s, 1H), 9.04 (dd, J = 7.2, 1.2 Hz, 1H), 8.75 (dd, J

3ea) 10.08 (s, 1H), 8.96 (dd, J = 7.6, 1.2 Hz, 1H), 8.69 (dd, J = = 4.0, 1.2 Hz, 1H), 8.17 (dd, J = 8.4, 1.2 Hz, 1H), 7.62-7.54 (m,

4.4, 1.6 Hz, 1H), 8.13 (dd, J = 8.4, 1.2 Hz, 1H), 7.58-7.7.20 (m, 2H), 7.45-7.40 (m, 5H), 7.07 (t, J = 8.0 Hz, 1H), 6.88 (d, J =

10H), 6.59 (s, 1H), 3.58 (s, 3H): (minor product 4ea) 10.59 (s, 7.6 Hz, 2H), 6.80 (d, J = 8.8 Hz, 4H), 3.73 (s, 6H); ¹³C NMR

This journal is © The Royal Society of Chemistry 2012

J. Name., 2012, 00, 1-3 | 7

Organic & Biomolecular Chemistry

^{View Articl}P^{e O}aⁿg^line^e8 of 11

DOI: 10.1039/C5OB00149H

ARTICLE

Journal Name

(100 MHz, CDCl₃): δ = 165.3, 160.0, 148.1, 138.5, 137.6, 134.3, 129.6, 129.5, 128.2, 128.0, 127.4, 127.0, 122.1, 121.6,

136.6, 136.2, 135.9, 134.3, 129.7, 127.9, 127.5, 127.1, 123.5, 117.0, 21.5, 19.3; MS (DART): m/z 417 [M+H]⁺; HRMS (EI):

122.0, 121.5, 117.0, 114.9, 55.2; MS (DART): m/z 525 m/z [M]⁺Calcd for C₂₄H₂₀N₂O₃S 416.1195; Found 416.1198;

[M+H]⁺; HRMS (EI): m/z [M]⁺Calcd for C₃₀H₂₄N₂O₃S₂X-ray data for 6aa (CCDC 1023627): M = 416.49, colorless,

524.1228; Found 524.1230.

triclinic, P-1 (#2), a = 7.8422(2) Å, b = 10.5048(2) Å, c =

12.7128(3) Å,  = 98.844(1)°,  = 95.249(1)°,  = 107.102(1)°,

2,6-Bis(4-methylphenylsulfanyl)-N-(quinolin-8-

yl)benzamide (4hd). Following general procedure, the title V = 978.68(4) Å³, Z = 2, D_calcd= 1.413 g/cm³, T = –150(2) °C,

compound was purified by flash column chromatography on R₁(wR₂) = 0.0438 (0.1903).

silica gel (hexane/EtOAc = 20:1) to yield 4hd in 95% yield as

6-Methyl-2-tosyl-N-(5-tosylquinolin-8-yl)benzamide

an orange solid: mp 120-121 °C; ¹H NMR (400 MHz, CDCl₃): (7aa). mp 276-277 °C; ¹H NMR (400 MHz, CDCl₃): δ = 10.19

δ = 10.05 (br s, 1H), 9.01 (dd, J = 8.0, 1.6 Hz, 1H), 8.69 (dd, J (br s, 1H), 9.06 (dd, J = 8.4, 2.8 Hz, 2H), 8.74 (dd, J = 4.0, 1.2

= 4.0, 1.2 Hz, 1H), 8.15 (dd, J = 8.4, 1.6 Hz, 1H), 7.59-7.50 (m, Hz, 1H), 8.60 (d, J = 8.4 Hz, 1H), 8.06-7.96 (m, 1H), 7.86-7.82

2H), 7.42 (dd, J = 8.0, 4.0 Hz, 1H), 7.41-7.32 (m, 4H), 7.12- (m, 4H), 7.55-7.48 (m, 3H), 7.29-7.21 (m, 4H), 2.43 (s, 3H),

6.99 (m, 7H), 2.25 (s, 6H); ¹³C NMR (100 MHz, CDCl₃): δ = 2.37 (s, 3H), 2.34 (s, 3H); ¹³C NMR (100 MHz, CDCl₃): δ =

165.3, 148.0, 138.4, 138.3, 138.2, 136.6, 136.2, 134.2, 133.4, 166.2, 148.7, 144.4, 144.2, 139.5, 138.9, 138.18, 138.15, 137.0,

130.1, 129.8, 128.6, 127.9, 127.4, 121.9, 121.5, 117.0, 21.1; 135.6, 135.5, 133.4, 132.0, 129.9, 129.7, 128.1, 127.3, 127.2,

MS (DART): m/z 493 [M+H]⁺; HRMS (EI): m/z [M]⁺Calcd for 124.2, 123.3, 114.8, 21.6, 21.5, 19.3; MS (DART): m/z 571

C₃₀H₂₄N₂OS₂492.1330; Found 492.1327.

2,6-Bis(4-fluorophenylsulfanyl)- -(quinolin-8-

[M+H]⁺; HRMS (EI): m/z [M]⁺Calcd for C₃₁H₂₆N₂O₅S₂

570.1283; Found 570.1286; X-ray data for 7aa (CCDC

N

yl)benzamide (4hi). Following general procedure, the title 1023628): M = 570.68, colorless, triclinic, P-1 (#2), a =

compound was purified by flash column chromatography on 10.2496(2) Å, b = 10.7814(2) Å, c = 13.5184(3) Å,  =

silica gel (hexane/EtOAc = 20:1) to give 4hi in 90% yield as an 65.784(1)°,  = 78.651(1)°,  = 89.847(2)°, V = 1330.66(5) Å³,

orange solid: mp 135-136 °C; ¹H NMR (400 MHz, CDCl₃): δ = Z = 2, D_calcd= 1.424 g/cm³, T = –150(2) °C, R₁(wR₂) = 0.0403

10.00 (br s, 1H), 8.98 (dd, J = 7.6, 1.6 Hz, 1H), 8.71 (dd, J = (0.1212).

4.0, 1.6 Hz, 1H), 8.17 (dd, J = 8.0, 1.6 Hz, 1H), 7.62-7.55 (m,

2-(4-Methoxybenzenesulfonyl)-6-methyl-N-(quinolin-8-

2H), 7.46-7.40 (m, 5H), 7.21-7.17 (m, 1H), 7.07 (d, J = 7.2 Hz, yl)benzamide (6ab). Following general procedure, the title

2H), 6.96-6.92 (m, 4H); ¹³C NMR (100 MHz, CDCl₃): δ = compound was purified by flash column chromatography on

165.0, 163.9, 161.4, 148.1, 139.1, 138.4, 136.3, 136.1, 135.2, silica gel (hexane/EtOAc = 10:3) to yield 6ab in 55% yield as a

135.1, 134.0, 130.1, 129.6, 129.1, 129.0, 127.9, 127.4, 122.2, solid: mp 201-202 °

C; ¹H NMR (400 MHz, CDCl₃): δ = 9.89

121.6, 117.0, 116.6, 116.4; MS (DART): m/z 501 [M+H]⁺; (br s, 1H), 8.96 (dd, J = 7.2, 1.6 Hz, 1H), 8.69 (dd, J = 4.0, 1.6

HRMS (EI): m/z [M]⁺Calcd for C₂₈H₁₈F₂N₂OS₂500.0829; Hz, 1H), 8.17 (dd, J = 8.0, 1.6 Hz, 1H), 8.03-8.00 (m, 1H),

Found 500.0827.

7.90-7.87 (m, 2H), 7.64-7.56 (m, 2H), 7.48-7.47 (m, 2H), 7.43

(dd, J = 8.4, 4.4 Hz, 1H), 6.83-6.79 (m, 2H), 3.73 (s, 3H), 2.44

(s, 3H); ¹³C NMR (100 MHz, CDCl₃): δ = 165.4, 163.2, 148.2,

139.0, 138.3, 137.1, 136.2, 136.1, 135.3, 134.2, 132.7, 130.3,

General procedure for Ni-mediated sulfonylation of amides with

arylsulfonyl chlorides

To an oven-dried

5 mL screw-capped vial, benzamide 129.5, 127.9, 127.3, 126.8, 122.1, 121.6, 116.9, 114.1, 55.4,

derivative (1.0 mmol), aryl sulfonyl chloride (3.0 mmol), NiCl₂19.3; MS (DART): m/z 433 [M+H]⁺; HRMS (EI): m/z [M]⁺

(50 mol %), Na₂CO₃(2.0 equiv), and dioxane (1 mL) were Calcd for C₂₄H₂₀N₂O₄S 432.1144; Found 432.1142.

added in a glove box. The mixture was stirred for 24 h at 140

6-Methyl-2-(3-methylbenzenesulfonyl)-N-(quinolin-8-

°C followed by cooling. The resulting mixture was filtered yl)benzamide (6ac). Following general procedure, the title

through a celite pad and concentrated in vacuo. The residue was compound was purified by flash column chromatography on

purified by column chromatography on silica gel to afford the silica gel (hexane/EtOAc = 10:2) to yield 6ac in 49% yield as a

desired products.

6-Methyl- -(quinolin-8-yl)-2-tosylbenzamide

solid: mp 188-189

(6aa). (br s, 1H), 8.95 (dd, J = 7.2, 1.2 Hz, 1H), 8.67 (dd, J = 8.0, 1.2

°

C; ¹H NMR (400 MHz, CDCl₃): δ = 9.84

N

Following general procedure, the title compound was purified Hz, 1H), 8.17 (dd, J = 8.4, 1.6 Hz, 1H), 8.06-8.03 (m, 1H),

by flash column chromatography on silica gel (hexane/EtOAc = 7.73-7.70 (m, 2H), 7.64-7.57 (m, 2H), 7.51-7.50 (m, 2H), 7.43

10:2) to yield 6aa in 61% yield as a solid accompanied by 7aa

.

(dd, J = 8.4, 4.0 Hz, 1H), 7.26-7.41 (m, 2H), 2.45 (s, 3H), 2.16

Single crystals of 6aa and 7aa suitable for X-ray (s, 3H); ¹³C NMR (100 MHz, CDCl₃): δ = 165.1, 148.2, 140.9,

crystallography were obtained by recrystallization from 139.1, 138.4, 138.3, 137.3, 136.3, 136.2, 135.5, 134.2, 133.9,

toluene: mp 232-233 °

C; ¹H NMR (400 MHz, CDCl₃): δ = 9.89 129.5, 128.8, 128.2, 127.9, 127.4, 127.1, 125.2, 122.2, 121.6,

(br s, 1H), 8.95 (dd, J = 7.6, 1.6 Hz, 1H), 8.70 (dd, J = 4.4, 1.6 117.0, 21.1, 19.3; MS (DART): m/z 417 [M+H]⁺; HRMS (EI):

Hz, 1H), 8.18 (dd, J = 8.0, 1.6 Hz, 1H), 8.04-8.00 (m, 1H), 7.83 m/z [M]⁺Calcd for C₂₄H₂₀N₂O₃S 416.1195; Found 416.1197.

(d, J = 8.4 Hz, 2H), 7.65-7.57 (m, 2H), 7.49 (d, J = 5.2 Hz, 2H),

2-(3-Fluorobenzenesulfonyl)-6-methyl-N-(quinolin-8-

7.45 (dd, J = 8.0, 4.0 Hz, 1H), 7.15 (d, J = 8.0 Hz, 2H), 2.45 (s, yl)benzamide (6ad). Following general procedure, the title

3H), 2.30 (s, 3H); ¹³C NMR (100 MHz, CDCl₃): δ = 165.3, compound was purified by flash column chromatography on

148.2, 144.1, 138.7, 138.4, 138.3, 137.2, 136.29, 136.25, 135.5, silica gel (hexane/EtOAc = 10:2) to yield 6ad in 51% yield as a

8 | J. Name., 2012, 00, 1-3

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ARTICLE

solid: mp 165-166 °

C; ¹H NMR (400 MHz, CDCl₃): δ = 9.92 NMR (400 MHz, CDCl₃): δ = 10.03 (br s, 1H), 8.86 (dd, J =

(br s, 1H), 8.95 (dd, J = 7.2, 1.2 Hz, 1H), 8.71 (dd, J = 4.0, 1.6 7.2, 1.6 Hz, 1H), 8.72 (dd, J = 4.0, 1.6 Hz, 1H), 8.25 (d, J = 2.0

Hz, 1H), 8.19 (dd, J = 8.4, 1.6 Hz, 1H), 8.03 (dd, J = 6.8, 2.8 Hz, 1H), 8.17 (dd, J = 8.4, 2.0 Hz, 1H), 7.85 (d, J = 8.4 Hz,

Hz, 1H), 7.79-7.76 (m, 1H), 7.70-7.58 (m, 3H), 7.54-7.52 (m, 2H), 7.69-7.66 (m, 1H), 7.62-7.55 (m, 3H), 7.44 (dd, J = 8.4,

2H), 7.45 (dd, J = 8.4, 4.0 Hz, 1H), 7.40-7.35 (m, 1H), 7.19- 4.0 Hz, 1H), 7.18 (d, J = 8.4 Hz, 2H), 2.29 (s, 3H), 1.39 (s, 9H);

7.14 (m, 1H), 2.47 (s, 3H); ¹³C NMR (100 MHz, CDCl₃): δ = ¹³C NMR (100 MHz, CDCl₃): δ = 165.8, 154.1, 148.2, 144.0,

165.2, 163.5, 160.9, 148.3, 143.4, 143.3, 138.4, 137.8, 137.5, 138.6, 138.4, 138.2, 136.2, 134.43, 134.39, 130.4, 129.5, 128.7,

136.6, 136.3, 136.1, 134.1, 130.83, 130.75, 129.7, 128.0, 127.4, 128.3, 127.9, 127.3, 126.4, 122.1, 121.6 116.9, 35.2, 31.0, 21.5;

127.3, 124.0, 122.3, 121.7, 120.6, 120.4, 117.0, 115.6, 115.4, MS (DART): m/z 459 [M+H]⁺; HRMS (EI): m/z [M]⁺Calcd for

19.3; MS (DART): m/z 421 [M+H]⁺; HRMS (EI): m/z [M]⁺C₂₇H₂₆N₂O₃S 458.1664; Found 458.1666.

Calcd for C₂₃H₁₇FN₂O₃S 420.0944; Found 420.0942.

2-(4-(tert-Butyl)benzenesulfonyl)-6-methyl- -(quinolin-

4-(Trifluoromethyl)-

(6ia). Following general procedure, the title compound was

N-(quinolin-8-yl)-2-tosylbenzamide

N

8-yl)benzamide (6ae). Following general procedure, the title purified by flash column chromatography on silica gel

compound was purified by flash column chromatography on (hexane/EtOAc = 10:2) to yield 6ia in 45% yield as a solid: mp

silica gel (hexane/EtOAc = 10:2) to yield 6ae in 53% yield as a 115-116

solid: mp 215-216

C; ¹H NMR (400 MHz, CDCl₃): δ = 9.93 8.85 (dd, J = 6.0, 2.8 Hz, 1H), 8.74 (dd, J = 4.4, 1.6 Hz, 1H),

°

C; ¹H NMR (400 MHz, CDCl₃): δ = 10.12 (br s, 1H),

°

(br s, 1H), 8.96 (dd, J = 7.6, 1.2 Hz, 1H), 8.72 (d, J = 4.0 Hz, 8.49 (s, 1H), 8.20 (dd, J = 8.4, 2.0 Hz, 1H), 7.92-7.87 (m, 3H),

1H), 8.19 (d, J = 8.0 Hz, 1H), 8.04 (t, J = 4.0 Hz, 1H), 7.91- 7.78 (d, J = 7.6 Hz, 1H), 7.63-7.61 (m, 2H), 7.47 (dd, J = 8.4,

7.88 (m, 2H), 7.66-7.50 (m, 2H), 7.50 (d, J = 4.4 Hz, 2H), 7.46- 4.4 Hz, 1H), 7.23 (d, J = 8.4 Hz, 2H), 2.32 (s, 3H); ¹³C NMR

7.44 (m, 1H), 7.41-7.38 (m, 2H), 2.46 (s, 3H), 1.25 (s, 9H); ¹³

C

(100 MHz, CDCl₃): δ = 164.3, 148.4, 145.0, 140.4, 140.0,

NMR (100 MHz, CDCl₃): δ = 165.5, 157.0, 148.3, 138.9, 138.3, 137.0, 136.3, 134.1, 130.3, 129.8, 129.6, 128.6, 128.0,

138.5, 138.3, 137.2, 136.4, 136.3, 135.5, 134.3, 129.6, 128.1, 127.3, 126.8, 122.6, 121.8, 117.1, 21.6; MS (DART): m/z 471

128.0, 127.4, 127.1, 126.1, 122.2, 121.7, 117.1, 35.1, 31.0, [M+H]⁺; HRMS (EI): m/z [M]⁺Calcd for C₂₄H₁₇F₃N₂O₃S

19.4; MS (DART): m/z 459 [M+H]⁺; HRMS (EI): m/z [M]⁺470.0912; Found 470.0913.

Calcd for C₂₇H₂₆N₂O₃S 458.1664; Found 458.1667.

2-(4-Chlorobenzenesulfonyl)-6-methyl- -(quinolin-8-

2-(4-(tert-Butyl)benzenesulfonyl)-4-(trifluoromethyl)-

(quinolin-8-yl)benzamide (6ie). Following general procedure,

N-

N

yl)benzamide (6af). Following general procedure, the title the title compound was purified by flash column

compound was purified by flash column chromatography on chromatography on silica gel (hexane/EtOAc = 10:2) to yield

1

silica gel (hexane/EtOAc = 10:2) to yield 6af in 42% yield as a 6ie in 54% yield as a solid: mp 203-204

solid: mp 210-211

°

C; H NMR (400

°

C; ¹H NMR (400 MHz, CDCl₃): δ = 10.06 MHz, CDCl₃): δ = 10.15 (br s, 1H), 8.86 (dd, J = 6.0, 3.2 Hz,

(br s, 1H), 8.84 (dd, J = 6.0, 2.8 Hz, 1H), 8.75 (dd, J = 4.4, 1.6 1H), 8.74 (dd, J = 4.0, 1.6 Hz, 1H), 8.49 (s, 1H), 8.20 (dd, J =

Hz, 1H), 8.19 (dd, J = 8.4, 2.0 Hz, 1H), 8.15 (d, J = 8.4 Hz, 8.4, 1.2 Hz, 1H), 7.94 (d, J = 8.0 Hz, 2H), 7.92 (d, J = 9.2 Hz,

1H), 7.85 (d, J = 8.4 Hz, 2H), 7.61-7.58 (m, 4H), 7.47 (dd, J = 1H), 7.78 (d, J = 8.0 Hz, 1H), 7.63-7.61 (m, 2H), 7.48-7.45 (m,

8.4, 4.0 Hz, 1H), 7.20 (d, J = 8.4 Hz, 2H), 2.31 (s, 3H); ¹³

C

3H), 1.26 (s, 9H); ¹³C NMR (100 MHz, CDCl₃): δ = 164.4,

NMR (100 MHz, CDCl₃): δ = 164.1, 148.4, 144.6, 140.0, 157.8, 148.5, 140.5, 140.0, 138.4, 136.9, 136.4, 134.1, 132.8,

138.4, 137.6, 137.5, 136.3, 134.1, 131.2, 130.4, 129.7, 128.9, 130.2, 129.6, 128.5, 128.0, 127.3, 126.93, 126.90, 126.3, 122.7,

128.4, 127.9, 127.3, 122.5, 121.8, 117.1, 21.6; MS (DART): 121.9, 117.2, 35.2, 30.9; MS (DART): m/z 513 [M+H]⁺; HRMS

m/z 437 [M+H]⁺; HRMS (EI): m/z [M]⁺Calcd for (EI): m/z [M]⁺Calcd for C₂₇H₂₃F₃N₂O₃S 512.1381; Found

C₂₃H₁₇ClN₂O₃S 436.0648; Found 436.0647.

4-Methyl- -(quinolin-8-yl)-2-tosylbenzamide

512.1385.

5-Methyl-

N

(6ca).

N

-(quinolin-8-yl)-2-tosylbenzamide

(6fa).

Following general procedure, the title compound was purified Following general procedure, the title compound was purified

by flash column chromatography on silica gel (hexane/EtOAc = by flash column chromatography on silica gel (hexane/EtOAc =

C; ¹H 10:2) to yield 6fa in 36% yield as a solid: mp 239-240 C; ¹H

10:2) to yield 6ca in 40% yield as a solid: mp 191-192 ° °

NMR (400 MHz, CDCl₃): δ = 10.02 (br s, 1H), 8.86 (dd, J = NMR (400 MHz, CDCl₃): δ = 10.03 (br s, 1H), 8.88 (dd, J =

7.2, 1.6 Hz, 1H), 8.72 (dd, J = 4.0, 1.2 Hz, 1H), 8.17 (dd, J = 7.6, 1.6 Hz, 1H), 8.73 (dd, J = 4.4, 1.6 Hz, 1H), 8.18 (dd, J =

8.4, 1.2 Hz, 1H), 8.03 (s, 1H), 7.88 (d, J = 8.4 Hz, 2H), 7.62- 8.4, 1.6 Hz, 1H), 8.08 (d, J = 7.6 Hz, 1H), 7.85 (d, J = 8.0 Hz,

7.52 (m, 3H), 7.46-7.42 (m, 2H), 7.19 (d, J = 8.0 Hz, 2H), 2.48 2H), 7.63-7.56 (m, 2H), 7.46-7.40 (m, 3H), 7.17 (d, J = 7.6 Hz,

(s, 3H), 2.30 (s, 3H); ¹³C NMR (100 MHz, CDCl₃): δ = 165.8, 2H), 2.44 (s, 3H), 2.30 (s, 3H); ¹³C NMR (100 MHz, CDCl₃): δ

148.2, 144.1, 140.9, 138.7, 138.4, 138.1, 136.2, 134.44, 134.41, = 165.8, 148.3, 144.6, 144.0, 138.4, 138.3, 137.0, 136.3, 136.0,

134.0, 129.9, 129.5, 128.7, 128.3, 127.9, 127.3, 122.1, 121.6, 134.4, 130.8, 129.7, 129.5, 129.3, 128.2, 127.9, 127.3, 122.2,

116.9, 21.5, 21.3; MS (DART): m/z 417 [M+H]⁺; HRMS (EI): 121.6, 117.0, 21.5, 21.4; MS (DART): m/z 417 [M+H]⁺; HRMS

m/z [M]⁺Calcd for C₂₄H₂₀N₂O₃S 416.1195; Found 416.1193.

4-(tert-Butyl)- -(quinolin-8-yl)-2-tosylbenzamide (6da). 416.1194.

Following general procedure, the title compound was purified -(Quinolin-8-yl)-3-tosyl-2-naphthamide

(EI): m/z [M]⁺Calcd for C₂₄H₂₀N₂O₃S 416.1195; Found

N

(6ja).

by flash column chromatography on silica gel (hexane/EtOAc = Following general procedure, the title compound was purified

10:2) to yield 6da in 38% yield as a solid: mp 200-201

°

C; ¹H by flash column chromatography on silica gel (hexane/EtOAc =

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10:2) to yield 6ja in 33% yield as a solid: mp 261-262

°

C; ¹H

1

2

P. Metzner and A. Thuillier, Sulfur Reagents in Organic Synthesis;

A. R.Katritzky, O.Meth-Cohn and C. W. Rees, Eds.; Academic Press:

London, 1994.

NMR (400 MHz, CDCl₃): δ = 10.13 (br s, 1H), 8.90 (dd, J =

7.2, 1.2 Hz, 1H), 8.87 (s, 1H), 8.71 (dd, J = 4.0, 1.2 Hz, 1H),

8.19 (dd, J = 8.0, 1.6 Hz, 1H), 8.13 (s, 1H), 8.08-8.06 (m, 1H),

7.95-7.88 (m, 3H), 7.72-7.68 (m, 2H), 7.65-7.57 (m, 2H), 7.45

(dd, J = 8.4, 4.0 Hz, 1H), 7.17 (d, J = 8.0 Hz, 2H), 2.27 (s, 3H);

¹³C NMR (100 MHz, CDCl₃): δ = 165.6, 148.2, 144.0, 138.4,

138.2, 136.2, 136.1, 134.5, 134.4, 132.8, 132.4, 131.8, 129.9,

129.4, 129.3, 129.0, 128.6, 128.4, 128.2, 127.9, 127.3, 122.1,

121.6, 116.9, 21.5; MS (DART): m/z 453 [M+H]⁺; HRMS (EI):

m/z [M]⁺Calcd for C₂₇H₂₀N₂O₃S 452.1195; Found 452.1197.

For selected reviews, see: (a) T. Kondo and T.-a. Mitsudo, Chem.

Rev., 2000, 100, 3205; (b) J. F. Hartwig, Acc. Chem. Res., 2008, 41

1534; (c) I. P. Beletskaya and V. P. Ananikov, Chem. Rev., 2011,

111, 1596; (d) H. Liu and X. Jiang, Chem. Asian J., 2013, , 2546;

,

8

(e) C.-F. Lee, Y.-C. Liu and S. S. Badsara, Chem. Asian J., 2014, 9,

706.

3

(a) J. M. Baskin and Z. Wang, Org. Lett., 2002,

Cacchi, G. Fabrizi, A. Goggiamani and L. M. Parisi, Org. Lett., 2002,

4, 4719; (c) S. Cacchi, G. Fabrizi, A. Goggoamani, L. M. Parisi and

4, 4423; (b) S.

2-(4-Methoxybenzenesulfonyl)-

N

-(quinolin-8-yl)-1-

naphthamide (6gb). Following general procedure, the title

compound was purified by flash column chromatography on

silica gel (hexane/EtOAc = 10:2) to yield 6gb in 38% yield as a

R. Bernini, J. Org. Chem., 2004, 69, 5608; (d) W. Zhu and D. Ma, J.

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solid: mp 152-153

°

C; ¹H NMR (400 MHz, CDCl₃): δ = 10.16

4

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(s, 1H), 9.13 (dd, J = 7.6, 1.2 Hz, 1H), 8.64-8.63 (m, 1H), 8.18

(d, J = 8.4 Hz, 1H), 8.13-8.07 (m, 2H), 8.03-7.98 (m, 3H), 7.91

(d, J = 7.6 Hz, 1H), 7.70-7.60 (m, 4H), 7.41 (dd, J = 8.0, 4.4

Hz, 1H), 6.86 (d, J = 9.2 Hz, 2H), 3.75 (s, 3H); ¹³C NMR (100

MHz, CDCl₃): δ = 165.2, 163.4, 148.2, 138.4, 136.2, 135.5,

135.4, 135.0, 134.4, 132.8, 130.44, 130.41, 130.1, 129.2, 128.4,

128.1, 128.0, 127.4, 126.7, 123.8, 122.3, 121.7, 117.1, 114.3,

55.5; MS (DART): m/z 469 [M+H]⁺; HRMS (EI): m/z [M]⁺

Calcd for C₂₇H₂₀N₂O₄S 468.1144; Found 468.1141.

3-(4-Methoxybenzenesulfonyl)-N-(quinolin-8-yl)-2-

naphthamide (6jb). Following general procedure, the title

compound was purified by flash column chromatography on

silica gel (hexane/EtOAc = 10:2) to yield 6jb in 45% yield as a

5

6

Metal-free chalcogenations: (a) M. Abdo, Y. Zhang, V. L. Schramm

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D. Mahesh, D. Sar and T. Punniyamurthy, Asian J. Org. Chem.,

solid: mp 217-218 °

C; ¹H NMR (400 MHz, CDCl₃): δ = 10.13

(br s, 1H), 8.92 (dd, J = 7.2, 1.2 Hz, 1H), 8.84 (s, 1H), 8.71 (dd,

J = 4.0, 1.6 Hz, 1H), 8.18 (dd, J = 8.0, 1.6 Hz, 1H), 8.12 (s,

1H), 8.07-8.04 (m, 1H), 7.97-7.92 (m, 3H), 7.72-7.68 (m, 2H),

7.65-7.57 (m, 2H), 7.44 (dd, J = 8.4, 4.0 Hz, 1H), 6.83 (dd, J =

6.8, 2.0 Hz, 2H), 3.71 (s, 3H); ¹³C NMR (100 MHz, CDCl₃): δ

= 165.8, 163.2, 148.3, 138.4, 136.5, 136.2, 134.6, 134.3, 132.8,

132.6, 132.4, 131.6, 130.7, 129.8, 129.3, 129.0, 128.6, 128.2,

127.9, 127.3, 122.1, 121.7, 116.9, 114.0, 55.4; MS (DART):

m/z 469 [M+H]⁺; HRMS (EI): m/z [M]⁺Calcd for C₂₇H₂₀N₂O₄S

468.1144; Found 468.1145.

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7

8

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Acknowledgements

This work was partially supported by Grant-in-Aid for

Scientific Research and Challenging Exploratory Research

from JSPS and a Grant-in-Aid for Scientific Research on

Innovative Area from MEXT. V.P.R and R.Q. thank the JSPS

Postdoctoral Fellowship.

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Notes and references

^aOsaka University, Suita, Osaka 565-0871 Japan.

E-mail: kambe@chem.eng.osaka-u.ac.jp; Fax: +81-6-6879-7390

† Electronic Supplementary Information (ESI) available: Crystallographic

data of CCDC-1023625, -1030338, -1023627, and -1023628 in CIF and

copies of ¹H and ¹³C NMR spectra. See DOI: 10.1039/b000000x/

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10 | J. Name., 2012, 00, 1-3

View Article Online

DOI: 10.1039/C5OB00149H

Page 11 of 11

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20 CCDC-1023625 (3aa), -1030338 (3ah), -1023627 (6aa), and -

1023628 (7aa) 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/data_request/cif.

J. Name., 2012, 00, 1-3 | 11

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Nickel-catalyzed synthesis of diarylsulfides and sulfones via C-H bond functionalization of arylamides

DOI: 10.1039/c5ob00149h

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