Recyclable palladium catalyst on grapheme oxide for the C-C/C-N cross-coupling reactions of heteroaromatic sulfonates

ACCEPTED MANUSCRIPT

Graphical Abstract

Recyclable palladium catalyst on grapheme

oxide for the C-C/C-N Cross-Coupling

Reactions of Heteroaromatic Sulfonates

Leave this area blank for abstract info.

a, b

a

a, c

a

b

Quanlu Yang, Zhengjun Quan,* Shang Wu, Baoxin Du, Mingming Wang, Peidong Li, Yinpan Zhang,

a

Xicun Wang*

a

Laboratory of Eco-Environment-Related Polymer Materials, Ministry of Education; Key Laboratory of

Polymer Materials, College of Chemistry and Chemical Engineering, Northwest Normal University, Lanzhou,

Gansu 730070, P. R. China

E-mail: wangxicun@nwnu.edu.cn, quanzhengjun@hotmail.com

b

College of Chemical Engineering, Lanzhou University of Arts and Science, Beimiantan 400, Lanzhou, Gansu

7

30000, P. R. China

c

College of Chemical Engineering, Northwest University for Nationalities, Lanzhou, Gansu 730030, P. R.

China

1

ACCEPTED MANUSCRIPT

Tetrahedron

journal homepage: www.elsevier.com

Recyclable palladium catalyst on grapheme oxide for the C-C/C-N Cross-Coupling

Reactions of Heteroaromatic Sulfonates

a, b

a

a, c

a

b

Quanlu Yang,

Xicun Wang*

Zhengjun Quan,* Shang Wu, Baoxin Du, Mingming Wang, Peidong Li, Yinpan Zhang,

a

Laboratory of Eco-Environment-Related Polymer Materials, Ministry of Education; Key Laboratory of Polymer Materials, College of Chemistry and Chemical

Engineering, Northwest Normal University, Lanzhou, Gansu 730070, P. R. China

E-mail: wangxicun@nwnu.edu.cn, quanzhengjun@hotmail.com

b

College of Chemical Engineering, Lanzhou University of Arts and Science, Beimiantan 400, Lanzhou, Gansu 730000, P. R. China

College of Chemical Engineering, Northwest University for Nationalities, Lanzhou, Gansu 730030, P. R. China

c

ARTICLE INFO

ABSTRACT

Article history:

Received

Received in revised form

Accepted

2

A well-defined heterogeneous palladium catalyst, graphene oxide grafted with PdCl , was

prepared and found to be an effective catalyst for the C-C, C-N coupling of hetero aryl

sulfonates with aryl boronic acids, terminal alkynes, amines, respectively, leading to the desired

coupling products in moderate to excellent yields. The catalyst was characterized by XRD, IR,

SEM, TEM, XPS and ICP. It is worthy noting that this catalyst offers a number of advantages

such as high stability and negligible metal leaching. It also retains good activity for at least five

successive runs without any additional activation treatment, showing a better performance than

the well-known commercial Pd/C catalysts. This approach would be very useful from a practical

viewpoint.

Available online

Keywords:

C-C coupling

C-N coupling

Nitrogen heterocycles

GO

2

Heterogeneous catalyst

to a narrow application area since their high cost and the

difficulties to purify and reuse after chemical reactions.

1

. Introduction

31-33

Tedious separation and recycling of the palladium catalyst are

major drawbacks of the homogeneous catalysts.

During the past decades, homogeneous palladium(II) catalysis

3

4

was used as one of the most efficient tactics for carbon–carbon

and carbon–heteroatom bond formations. Coupling reactions like

the Heck-, Suzuki-, and Buchwald- type provided one-step

Immobilization of homogeneous catalysts onto a solid surface

can be a method of reformation, which may facilitate the

separation of the catalyst from the reaction products, and make

the reutilization of the catalyst possible in multiple subsequent

cycles. For decades, enormous efforts in this field were made to

immobilize known catalysts onto various separable organic,

1-7

methods for the assembling of complex structures.

Palladium (Pd) catalyzed C-C and C-N coupling reactions

have been of strategic importance since they offer fast reaction

rates, high turnover frequency, good selectivity, and high

3

5-45

46

8-14

inorganic or hybrid supporters,

such as activated carbon,

production yield in various synthetic protocols.

47-49

50

51

52-

polymers,

glass polymer composites, zeolites, silica,

Heteroaromatic compounds are important constituents of a wide

range of natural products, pharmaceuticals, and fine chemicals,

55

56-58 59-62 63

molecular sieves,

clays,

carbon nano tubes,

zinc

64

65

66

15-

ferrite, graphene, and sulfonated graphene. Unfortunately,

the supported Pd complex catalysts often suffer from reduced

activity, inferior selectivity, and other problems such as metal

leaching and high preparation complexity.

hence methods for their functionalization are of high interest.

20

In the Pd-catalyzed Suzuki coupling reactions, aryl sulfonates

are a class of interesting and practical alternatives to aryl halides,

because they are more easily to handle and usually less

expensive than the corresponding aryl halides. However, aryl

sulfonates are generally less reactive in the metal-catalyzed

coupling reactions than the corresponding aryl chlorides, and

thus, ^m^u^c^h21-30^h^a^r^s^h^e^rreaction conditions were adopted

accordingly.

Recently, for catalysis studies, chemically exfoliated graphene

67-80

oxide (GO)

has attracted extensive attention in

heterocatalysis due to their unique two-dimensional structures,

huge surface areas, tunable electrical properties and other

8

1, 82

83

excellent properties.

Many transition metals, such as Ag,

8

4-88

89, 90

91

Pd,

Pt,

and Au, were surported on GO and prepared as

Despite the remarkable utility of Pd catalysts in organic

synthesis, the use of homogenous Pd catalysts has been limited

heterocatalysts for organic reactions.

2

Tetrahedron

in MA

Heterobiaryl compounds, with prevalent st

A

ruc

C

tu

C

ra

E

l m

P

o

T

tif

E

s

D

o

N

xyg

U

en

S

.

C

Th

R

e

I

peak at 2θ = 39.8°is characteristic for Pd (II) with

P

T

many pharmaceuticals and other biologically active molecules,

have been a focus for all the time in the development of

heterocyclic synthesis. In particular, organic molecules with

face centered cubic structure, suggesting that the Pd is composed

of crystalline nanostructures on graphene.

92

9

3

pyrimidine scaffolds are widely used in medication and also as

9

4-97

important precursors in the synthesis of other derivatives.

990s, derivatives of the dihydropyrimidinthione (DHPM) were

found their potential value as calcium antagonists (Figure 1), α -

In

1

a

94, 98-100

antagonists, hypotensor, anticarcinogen, etc.

Hence

increasing efforts were devoted upon the synthesis of the DHPM

derivatives and their reactivity.

101

Figure 1. (a) Amlodipine, a calcium channel blocker of dihydropyridine

;

98-100

(b) Dihydropyrimidine calcium channel blockers

.

2

Figure 2. The XRD spectra of (a) Graphite, (b) GO, (c) GO-PdCl .

More recently, we have developed an approach to C2-

substituted and functionalized pyrimidines, by cross coupling

reactions of pyrimidin-2-yl sulfonates under mild conditions and

Figure 3 shows the FTIR spectra of graphite, GO, and GO-

PdCl . It can be seen that the obvious change was existed in

2

102-104

rapid procedures

. Nonetheless, this homogenous palladium

graphite and graphite oxide. After being oxidized, the peak at

-

1

catalysis owned numerous drawbacks, especially, like high cost,

and non-reusability. Based on the pioneering works in this area,

herein, we report a facile and efficient method to immobilize Pd

3400cm became broadened, which was the typical stretching

-1 -1

vibration peak of –OH in –COOH. 1720 cm and 1398 cm that

are ascribed to the C=O stretching vibrations of COOH groups

and the O–H deformation vibrations of tertiary C–OH, 1625

(

II) complexes on GO in aqueous suspension. We found that this

−1

catalyst can afford high catalytic activities for the C-C and C-N

cross-coupling reactions of pyrimidin-2-yl sulfonates with

arylboronic acids, terminal alkynes and aniline. The catalyst has

been found to be stable and recyclable in these systems, and the

conversions in the case of a variety of substrates have been

found to be good in its presence.

cm that are related to the O–H deformation vibrations of H O

2

−1 −1

groups, 1049 cm and 868 cm that are indexed to the

1

07-108

characteristic peaks of epoxy groups and peroxide groups.

The results provided direct evidences for the successful

oxidation of graphite. For GO-PdCl , the peak corresponding to

2

oxygen functional groups significantly decreased or disappeared.

2+

This is relatively consistent with the XRD data, where the Pd

2

. Results and discussion

reacts with surface oxygen, and the corresponding XRD peak

intensity was reduced.

.1 Synthesis and characterization of the catalyst

GO was prepared by chemical oxidation and exfoliation of

natural graphite under acidic conditions according to the

105

improved Hummer’s method. Subsequently, 1.0 g the GO and

.2 g PdCl were mixed with 20 mL of de-ionized water, stirred

0

2

at r.t. for 3 h. Despite the low solubility of PdCl in water, cation

2

exchange took place overnight. The suspension was separated by

centrifugation, washed with de-ionized water (3 × 20 mL) and

o

acetone (3 × 20 mL), dried in a vacuum oven at 40 C for 4 h and

gently powdered was obtained. The palladium content in GO-

PdCl was determined by means of inductively coupled plasma

2

equipped with atomic emission spectrometry (ICP-AES) and

amounted to be 2.86 wt % (0.27mmol/g).

In order to understand the structural properties of graphite, GO

and GO-PdCl , XRD measurements were performed (Figure 2).

2

The graphite powder presents a typical sharp diffraction peak at

2

θ = 26.3°, which is characteristic for (002) reflection in

graphite, corresponding d-spacing of 0.33 nm .Upon oxidation,

A broad peak at 2θ = 9.3° was observed with a d-spacing of 0.95

nm, corresponding to the (002) reflection of GO. The increase in

2

Figure 3. The FTIR spectra of (a) Graphite, (b) GO, (c) GO-PdCl .

d-spacing is due to the insertion of H O molecules and various

2

106-

oxygen functional groups in the AB-stacked graphite sheets.

We examined the detailed electronic configurations of GO-

108

In GO-PdCl , the intensity of the peak at 9.3° significantly

2

PdCl complex using X-ray photoelectron spectroscopy (XPS)

2

decreased, and an obvious peak at 2θ = 21.4° appeared. It is

measurements. (Figure 4) The peaks at 342.80 eV and 337.43 eV

were assigned to the binding energy of Pd₃_d₃_/₂and Pd₃_d₅_/₂in

reasonable to consider that the reduced peak intensity in GO

2+

resulted from Pd was conjugated onto the GO with surface

3

ACCEPTED MA

P

N

dC

U

l

2

S

re

C

sp

R

ec

I

tively; it was found to 0.75 eV and 0.87 eV

P

T

decrease in GO-PdCl complex, which are originated from Pd

2

3d3/2

II

and Pd₃_d₅_/₂of Pd . The results show the coordination or ionic

bonds are formed in PdCl with GO.

2

The morphologies of the Graphite, GO and GO-PdCl were

2

found out by scanning electron microscopy (SEM-EDX) and

transmission electron microscopy (TEM). The SEM (Figure 5)

and TEM (Figure 6) image (a, Figure 5; a, Figure 6) indicated

stacking of multilayer in Graphite structure. After being

oxidized, the sheet morphology with typical wrinkle of GO is

clearly observed in the TEM and SEM images of GO (b, Figure

; b, Figure 6). And then in Figure 5 (c) and Figure 6 (c), no

obvious aggregated Pd particle on the surface of GO was

observed. Furthermore, the EDS mapping images (d, Figure 5)

revealed that a homogeneous distribution of Pd on GO, and then

5

(

the EDX of GO and GO-PdCl was texted (e and f, Figure 5); the

2

presence of oxygen elements was confirmed, which indicated the

successful oxidization of the graphite (e, Figure 5), and Figure 5

f) revealed that the presence of Pd on the surface of GO. This is

relatively consistent with the XRD and FTIR data.

2

Figure 4. The XPS spectra of (a) GO, (b) GO-PdCl .

2 2

Figure 5. SEM image of (a) Graphite, (b) GO, (c) GO-PdCl , (d) the corresponding EDS mapping of Pd; and the EDX spectrum of (e) GO, (f) GO-PdCl .

2

Figure 6. TEM image of (a) Graphite, (b) GO, (c) GO-PdCl .

4

Tetrahedron

o

(

2.0 equiv. ), catalyst (Pd 2.86 wt %), solvent (5 mL), 110 C, 18 h.

2

.2 Coupling reactions of pyrimidin-2-yl

A

su

C

lf

C

on

E

at

P

es

TED

w

i

th MANUSCRIPT

[b]

Isolated yield of 3a by column chromatography.

arylboronic acids

The catalytic performance of the prepared catalyst was

systematically examined through Suzuki coupling reactions. As a

model, the coupling reaction of ethyl 4-methyl-6-phenyl-2-

To expand the scope of substrates, we further examined the

GO-Pd catalyst for the Suzuki coupling reactions of various

pyrimidin-2-yl sulfonates (1) with different phenylboronic acids

(2) under the optimized conditions (Table 2). Notably, there

was not any obvious trend or difference in reactivity

between the systems of varied electronic effects.

Arylboronic acids with electron-donating (Me- and MeO-) and

electron-withdrawing groups (Cl-) were well tolerated (entries 2-

6), and satisfactory yields were obtained. Additionally, the

arylboronic acids with either p-substituted (entry 2) or m-

substituted (entry 3) methyl group afforded the cross-coupling

products in 85% and 88% yields, respectively. On the other

hand, sterically hindered substituents on the arylboronic acids

impacted on the reaction. For example, the reactions involving 2-

methylphenylboronic acid (2d) gave the corresponding product

3d only in 72% yield (entry 4). As expected, electron-deficient

1-naphthylboronic acid 2g was also a suitable reaction partner

(entry 7).

In addition to arylboronic acids, several pyrimidin-2-yl

sulfonates were used as starting compounds in the reaction.

These substituted pyrimidin-2-yl sulfonates, bearing fluoro,

chloro, bromation, methyl, and methoxyl groups, were smoothly

converted to the corresponding products in high yields (entries 8-

15). Fortunately, the catalytic system can be used for selective

coupling of sulfonates groups keeping halogen functionalities

intact with only 3j, 3k, 3l produced, respectively (entries 10-12).

To our delight, all reactions took place smoothly with the desired

coupling products 3 isolated in moderate to excellent yields.

Additionally, sulfonates of pyridine derivatives were also tested

under this catalytic system, leading to moderated yields for the

corresponding products 3n and 3o (entry 14, 15).

(tosyloxy)pyrimidine-5-carboxylate (1a) with phenylboronic

acid (2a) was studied (Table 1). Firstly, 1,4-dioxane was chosen

as the solvent, and the ligands as well as the bases were

evaluated, respectively (entries 1-7). It seems that PPh₃and

K PO₄were the suitable ligand and base to give the

3

corresponding coupling product 3a in 87% yield (entry 2). The

yield

declined

when

2,2’-oxybis(2,1-

phenylene)bis(diphenylphosphane) (DPE-Phos) was used as the

ligand (entry 1). However, an increase in the cross coupling

reactivity was observed with CsCO₃as base under similar

conditions (entry 5). Other bases including NaOAc, TBAB,

K CO and NaF provided poor conversion (entries 3-4, 6-8).

2

3

Further optimization of conditions was achieved for the solvent.

Among the different solvents that were studied, low yields were

obtained in toluene, CH CN and CCl (entries 8-10). In the

3

4

controlling experiments, no reaction occurred without ligand or

GO, indicating their indispensible roles in the reaction. (entries

1

4, 15). Tests upon the catalyst amount suggested that 20 mg of

the GO-PdCl catalyst was enough to afford the high yield of the

2

product (compare entry 2 with entry 11, 12). More catalyst added

did not obviously accelerate the reaction in further (entry 13).

Thereby, the appropriate condition is optimized as pyrimidin-2-

yl sulfonate 1a (0.25 mmol), arylboronic acid 2a (0.375 mmol),

K PO (2.0 equiv.), PPh (20 mol %), 20 mg of GO-PdCl

2

3

4

3

o

catalyst (Pd 2.86 wt %), stirred in 5 mL 1,4-dioxane at 110 C

for 18 h.

Table 1. Optimized conditions for the coupling of pyrimidin-2-yl

[

a]

sulfonates with arylboronic acids

.

Table 2. Suzuki coupling reactions of pyrimidin-2-yl sulfonates with

[

a]

arylboronic acids

.

[

b]

Entry

Catalyst

GO-PdCl (20 mg)

GO-PdCl

GO (20 mg)

GO-PdCl (20 mg)

Base

Ligand

Solvent

dioxane

toluene

Yield

1

2

3

4

5

6

7

8

9

2

K

3

PO

4

DPE-Phos

72%

87%

10%

trace

52%

---

2

(20 mg)

(10 mg)

(15 mg)

(30 mg)

K

4

PPh

3

Arylboronic

acid

[

b]

2

NaOAc

TBAB

PPh

3

Entry

Sulfonate

Product

Yield

2

PPh

2

Cs

2

CO

NaF

3

PPh

3

2

K

2

3

1

87%

85%

88%

2

3

---

2

a

1

a

3

a

2

K

3

K

3

K

3

K

3

K

3

K

3

K

3

K

3

PO

4

3

8%

2

3

CH

3

CN

trace

---

10

11

12

13

14

15

2

3

CCl

4

2

3

1a

2

3

dioxane

63%

71%

89%

---

2

b

2

3

3b

2

3

DPE-Phos

---

2

---

2

c

[a]

Reaction condition: 1a (0.25 mmol), 2a (1.5 equiv. ), ligands (20 or 6 mol %), base

3

c

5

ACCEPTED MANUSCRIPT

1

3

82%

2

a

4

1a

72%

2

d

1

g

3

m

3

d

1

4

5

68%

2

a

5

6

1a

86%

92%

1h

3

n

2

e

3

e

76%

2

1

i

3

o

[a]

Reaction conditions: 1 (0.25 mmol), 2 (1.5 equiv. ), PPh

Pd 2.1 mol %), K PO (2.0 equiv. ), stirred in 5 mL 1,4-dioxane at 110 C, 18 h.

3 4

3

(20 mol %), GO-PdCl

2

(20 mg,

o

2

f

[b]

Isolated Yield of product 3.

3

f

2

.3 Coupling reactions of pyrimidin-2-yl sulfonates with

terminal alkynes

Subsequently, as a model reaction, the coupling reaction of

pyrimidin-2-yl sulfonate (1a) with phenyl acetylene (4a) was

studied. Firstly, the reaction conditions were studied (Table 3).

7

1a

96%

2

g

a

89

3

g

Our previous optimized conditions

bimetallic catalytic system, using a combination of GO-PdCl₂

20 mg, Pd 2.86 wt %) and CuI (10 mol%), PPh (10 mol%), and

were applied to the

(

3

Et N (2.0 equiv.) in 1.4-dioxane (5 mL) at 110 °C for 48 h.

3

8

83%

Unfortunately, it provided poor yield of product 5a (entry 1).

2

Further study showed that this low yield remained when copper

(

I) thiophenecarboxylate (CuTC) was adopted instead of CuI

1

b

3

h

(entry 2). And then, the choice of ligand was critical to the

success of the reaction, when 2-(dicyclohexylphosphino)-

2

3

’,4’,6’-triisopropylbiphenyl (X-Phos) was screened as ligand,

8% of conversion was detected (entry 3). Finally, to our delight,

9

87%

91%

88%

81%

the yield was dramatically increased to 86 % when K

chosen as a base (entry 5).

3 4

PO was

2a

1

c

Table 3. Optimization of the conditions of pyrimidin-2-yl sulfonates

3

i

[

a]

with terminal alkynes

.

1

0

1

2

1

d

3

j

[

b]

Entry

[Cu]

CuI

Base

Ligands

Yield

7%

1

2

3

4

5

Et

3

Et

3

Et

3

N

PPh

3

CuTC

PPh

8%

1

X-Phos

38%

56%

86%

K

2

CO

PO

3

1

e

3

k

K

3

4

[a]

2

Reaction condition: 1a (0.25 mmol), 4a (0.38 mmol), GO-PdCl (20 mg, Pd 2.1

mol %), CuTC (10 mol %), K PO (2.0 equiv. ), X-Phos (6 mol %), 1,4-dioxane (5 mL),

3

4

o

1

10 C, 48 h.

1

[b]

Isolated yield of 5a by column chromatography.

On the basis of the results described above, we can conclude

1f

3

l

that GO-PdCl can be a fine catalyst for this type of Sonogashira

2

coupling reactions between pyrimidin-2-yl sulfonates and

terminal alkynes. To extend the scope of this reaction system,

more substrates were examined under the optimized conditions

(Table 4). The catalysts displayed nearly 100% selectivity to the

6

Tetrahedron

products. As the similar result with Suz

A

uki

C

r

C

ea

E

ct

P

io

T

n,

E

t

D

he MA

P

N

Ph

U

(

S

as

C

li

R

ga

I

n

P

d) (entry 6) gives the most efficient N-arylation

T

3

Sonogashira reaction is relatively insensitive to the electronic

characteristics of the substituent groups. And all substrates can

be converted into the corresponding products in excellent yields.

product 7a (81% yield in 24 h).

[

a]

Table 5. Optimization of the conditions of the C-N coupling reactions

.

[

a]

Table 4. Sonogashira coupling of pyrimidin-2-yl sulfonates with alkynes

.

[

b]

Entry

Base

Ligands

Yield

0%

1

2

3

4

5

6

DBU

PPh

3

[

b]

Entry

Sulfonate

Alkyne

Product

Yield

Et

CO

PO

K PO

3

N

PPh

0%

K

2

3

PPh

3

0%

Cs

2

3

PPh

3

0%

1

86%

87%

89%

4

a

K

3

4

-

44%

81%

1

a

5

a

3

4

PPh₃

[

a]

Reaction condition: 1a (0.25 mmol), 6a (0.38 mmol), GO-PdCl

2

(20 mg, Pd 2.1

o

mol %), PPh (20 mol %),, K PO (2.0 equiv. ), 1,4-dioxane (5 mL), 110 C, 24 h.

3

4

[b]

2

3

1a

Isolated yield of 7a by column chromatography.

4

b

5

b

To evaluate the scope of C-N catalytic system, we investigated

the coupling reactions by treating various pyrimidin-2-yl

sulfonates with different anilines (Table 6). High catalytic

activities were observed for the pyrimidin-2-yl sulfonates and

both electron-rich and electron-poor anilines, affording the

corresponding N-arylation compounds in good to excellent

yields (entries 2-4). In particular, o-toluidine, which has

discernible steric- encumbrance, afforded the corresponding

product 7c in low yields (entry 3). For all the anilines examined,

the reaction tolerated a variety of anilines containing an electron-

withdrawing group (Cl) (entry 6) as well as an electron-donating

group (OMe) (entry 5) on the phenyl ring, and gave similar

yields.

4

c

5

c

4

1a

84%

4

d

b

5

d

[

a]

Table 6. Scope of the C-N coupling reactions

.

5

66%

4

5

e

1

b

Arylboronic

[

b]

Entry

Sulfonate

Product

Yield

6

89%

4

b

acid

5

f

1

e

[

a]

1

81%

2

Reaction conditions: 1 (0.25 mmol), 4 (1.5 equiv. ), GO-PdCl (20 mg, Pd 2.1 mol %),

o

CuTC (10 mol%), K

h.

3 4

PO (2.0 equiv. ), X-Phos (6 mol %), 1,4-dioxane (5 mL), 110 C, 48

6

a

1

a

[b]

7a

Isolated yield of product 5.

2

.4 C-N Coupling reactions of pyrimidin-2-yl sulfonates with

anilines

In addition to C-C coupling, anilines were used as

2

3

1a

79%

49%

6

b

7

b

nucleophiles in the C-N coupling reactions. The catalytic activity

was investigated in the model reaction of pyrimidin-2-yl

sulfonate (1a) with aniline (6a) (Table 5). The controlling

experiments and the effect of varying base, and ligand on

conversions suggest that the combination of K PO (as base) and

3

4

6

c

7

c

7

ACCEPTED MANUSCRIPT

4

5

1a

82%

6

d

7d

1

00

78%

2.8

2.4

2

6

a

9

8

7

0

1

c

7

e

60

1

.6

1.2

.8

5

4

3

2

0

6

88%

0.4

0

Yield(%)

Pd(wt)%

6

a

10

0

1

2

3

4

5

1

e

7

f

Recycle Times

Figure 7. Recycling test of GO-PdCl for Suzuki reaction.

[a]

Reaction conditions: Reaction conditions: 1 (0.25 mmol), 6 (1.5 equiv. ), PPh

mol %), GO-PdCl (20 mg, Pd 2.1 mol %), K PO (2.0 equiv. ), stirred in 5 mL 1,4-

dioxane at 110 C, 24 h.

3

(20

2

3

4

o

[b]

Isolated yield of product 7.

2

.5 Recycling of the catalyst

An important point concerning the use of heterogeneous

catalysts is its lifetime, particularly for industrial and

pharmaceutical applications. The recycling experiments were

performed with the Suzuki coupling reaction between ethyl 4-

methyl-6-phenyl-2-(tosyloxy)pyrimidine-5-carboxylate (1a) and

phenylboronic acid (2a) as the model substrates, under the same

reaction conditions as described above. After completion of each

running, the mixture was cooled to room temperature, and then

the catalyst was separated by centrifugation, and was washed,

dried and replaced in the reaction vessel to be used in the

sequential running. The reaction progress was monitored by TLC,

and the conversion and product selectivity were observed by GC

analysis (Figure 7).

The catalyst was used repeatedly for 5 times and then was

examined by ICP-AES analysis within very narrow scope

(

2.86% to 2.75%) to observe its palladium content. Only 128

parts per billion palladium was detected in the reaction phase,

ICP-MS) indicating quite a slender metal leaching of the

catalyst during the reactions. (Figure 7).

(

Figure 8. XPS spectra of the reused wool-Pd complex catalyst.

Figure 9. (a) SEM image of the reused catalyst (after the Suzuki reaction), (b) the corresponding EDS mapping of Pd, (c) the corresponding EDX spectrum.

8

Tetrahedron

ACCEPTED MANUSCRIPT

To further investigate the reused catalyst, XPS was employed

photocatalyst was conducted by an energy-dispersive X-ray

spectrometer (EDX) attached to the scanning electron

microscope. Column chromatography was generally performed

on silica gel (200–300 mesh) and TLC analyses were conducted

on silica gel GF254 plates.

to characterize. Figure 8 showed the Pd 3d spectrum of the

reused catalyst. It can be seen that a doublet for two chemically

different Pd entities, with peak binding energies of 335.22 eV

(Pd 3d ₅_/₂) and 340.60 eV (Pd 3d ₃_/₂), which confirmed the

0

presence of Pd in the reused catalyst. The XPS results indicated

that Pd (0) was formed during the catalytic reaction. This was in

an agreement with the previous report.

Subsequently, the reused catalyst was again examined by

SEM-EDX, and the image indicated that the surface morphology

of the recycled catalyst did not show any significant change even

after 5 reaction cycles (Figure 9), showing a good stability of the

4.3 General procedures for the Suzuki coupling reactions of

pyrimidin-2-yl sulfonates with arylboronic acids

Pyrimidin-2-yl sulfonate 1 (0.25 mmol), arylboronic Acid 2

(0.375 mmol), K PO (2.0 equiv.), PPh (20 mol %), 20 mg of

40

3

4

3

GO-PdCl catalyst (Pd 2.86 wt %) were added to a 15 mL

2

Schlenk tube, and was then evacuated and purged with nitrogen

gas for four times sequentially; then 5 mL 1,4-dioxane in was

added by a syringe under nitrogen atomosphere; the mixture was

GO-PdCl catalyst during the Suzuki coupling reaction.

2

o

2

.6 Hot filtration test

then stirred at 110 C for 18 h. After completion, the catalyst was

In order to further evaluate the palladium leaching of the GO-

separated by centrifugation, and the mixture was cooled to room

PdCl₂catalyst as well as the catalytic contributions of the

leached palladium, we carried out the hot filtration tests upon the

C-C coupling reaction. The test was operated between the

coupling reaction of 1a and 2a under standard conditions. The

reaction mixture was stirred for 6 hours and filtered in order to

remove the heterogeneous catalyst (the conversion is 37%); then

the mixture was stirred for another 18 hours. However, no

further reaction was detected. This result indicated that any

leaching of active species into solution was insignificant.

temperature, quenched by addition of saturated aqueous NH Cl

4

(3 mL), and extracted with diethyl ether (3 × 5 mL). The organic

solvents were combined and washed with aqueous NaOH (2

mmol/ mL, 2 mL), brine, and then dried with anhydrous

magnesium sulfate, filtered and concentrated under reduced

pressure. The residue was purified by silica gel column

chromatography with a mixture of ethyl acetate and petroleum

ether as eluent. The product was analyzed by GC-MS or NMR

analysis. The conversion and selectivity were determined using

GC analysis. All the prepared compounds are known and were

3

. Conclusion

89

compared with authentic samples.

We have achieved the preparation of a reactive, selective, and

4.3.1 Ethyl 4-methyl-2,6-diphenylpyrimidine-5-carboxylate (3a).

1

recyclable GO-PdCl₂catalyst. This catalyst exhibited high

enrichment towards the reactants as well as excellent activity for

a wide scope of C-C/C-N cross-coupling reactions. In addition,

White solid; m.p. 66-67 °C. H NMR (400 MHz, CDCl

3

): δ =

8.62- 8.59 (dd, J = 2.8 Hz, 6.4 Hz, 2H), 7.81-7.79 (m, 2H), 7.54-

7

1

.52 (m, 6H), 4.28-4.22 (q, J = 7.2 Hz, 2H), 2.75 (s, 3H), 1.14-

13

.10 (t, J= 7.2 Hz, 3H) ppm. C NMR (100 MHz, CDCl ): δ=

3

the GO-PdCl showed an improved stability in the coupling

2

68.52, 165.40, 163.72, 163.69, 138.22, 137.1, 131.12, 130.01,

28.73, 128.58, 128.52, 128.49, 123.41, 61.8, 22.90, 13.68 ppm.

reactions of pyrimidin-2-yl sulfonates with arylboronic acids,

terminal alkynes and aryl amines. Further exploration of the

heterogeneous catalyst developed by the organic reaction in

other useful catalytic transformations is actively undergoing in

our laboratory.

4

.3.2 Ethyl 4-methyl-6-phenyl-2-p-tolylpyrimidine-5-carboxylate

1

(

3b). White solid; m.p. 61-63 °C. H NMR (400 MHz, CDCl ): δ

3

=

8.49-8.47 (d, J = 8.2 Hz, 2H), 7.79-7.77 (m, 2H), 7.54-7.46 (m,

3

2

H), 7.33-7.31 (d, J = 8.1 Hz, 3H), 4.26-4.21 (q, J = 7.2 Hz, 2H),

1

3

.72 (s, 3H), 2.46 (s, 3H), 1.12-1.10 (t, J = 7.2 Hz, 3H) ppm.

C

4

. Experimental section

NMR (100 MHz, CDCl ): δ = 168.52, 165.34, 163.68, 163.61,

3

1

41.49, 138.33, 134.42, 130.01, 129.33, 128.72, 128.54, 128.48,

23.12, 61.83, 22.72, 21.61, 13.70 ppm.

.1 Chemicals

All starting materials and reagents were commercially

available and used without further purification unless otherwise

noted. Solvents were purified and dried by standard methods

prior to use. All products have been previously reported and

characterized. All known products gave satisfactory analytical

data corresponding to the reported literature values.

4

.3.3 Ethyl 4-methyl-6-phenyl-2-m-tolylpyrimidine-5-carboxylate

1

(3c). White solid; m.p. 69- 71 °C. H NMR (400 MHz, CDCl ): δ

3

= 8.27-8.29 (d, J = 7.4 Hz, 2H), 7.69-7.67 (dd, J = 6.5 Hz, 3.1

Hz, 2H), 7.42-7.39 (m, 3H), 7.33-7.29(t, J = 7.9 Hz, 1H), 7.25-

7

3

.23(t, J = 7.5 Hz, 1H), 4.16-4.11 (q, J = 7.2 Hz, 2H), 2.62 (s,

13

H), 2.38 (s, 3H), 1.02-0.99 (t, J = 7.2 Hz, 3H) ppm. C NMR

4

.2 Apparatus

(100 MHz, CDCl ): δ = 168.42, 165.31, 163.84, 163.28, 138.22,

3

All reactions were conducted under nitrogen atmosphere with

1

38.14, 137.02, 131.79, 129.91, 129.14, 128.53, 128.42, 125.83,

23.33, 61.67, 22.90, 21.53, 13.59 ppm.

a dual-manifold Schlenk tube and in oven-dried glassware unless

otherwise noted. All NMR spectra are recorded on MERCURY

1

13

4.3.4 Ethyl 4-methyl-6-phenyl-2-o-tolylpyrimidine-5-carboxylate

(

400 MHz for H NMR, 100 MHz for C NMR) spectrometers;

1

(3d). White solid; m.p. 77-78 °C. H NMR (400 MHz, CDCl ): δ

3

chemical shifts are expressed in ppm (δunits) relative to TMS

=

7

3

7.87-7.79 (m, 1H), 7.73-7.57 (m, 2H), 7.46- 7.33 (m, 3H),

signal as internal reference in CDCl . Gas chromatography (GC)

3

.32-7.19 (m, 3H), 4.16 (q, J = 7.2 Hz, 2H), 2.63 (s, 3H), 2.55 (s,

13

analysis was performed on a Shimadezu GC-2010 equipped with

a 15 m × 0.53 mm × 1.5 ꢀm RTX-1 capillary column and a

oxyhydrogen flame detector. ICP-AES were measured on IRIS

Advantage. XPS measurement was recorded on PHI5702

photoelectron spectrometer. Binding energy was referred to C₁_s

H), 1.03 (t, J = 7.2 Hz, 3H) ppm. C NMR (100 MHz, CDCl ):

3

δ = 168.36, 166.75, 165.00, 163.12, 137.93, 137.62, 137.45,

131.31, 130.55, 129.97, 129.65, 128.48, 128.39, 125.93, 122.77,

61.86, 22.78, 21.32, 13.66 ppm.

4

.3.5 Ethyl 2-(4-methoxyphenyl)-4-methyl-6-phenylpyrimidine-5-

1

(284.80 eV). FTIR spectroscopy patterns were obtained on an

carboxylate (3e). White solid; m.p. 57-59 °C. H NMR (400

FT/IR-660 Plus system (Jasco, Tokyo, Japan). The samples were

mixed with KBr powders and pressed into a disk suitable for

FTIR measurement. The morphologies of the catalyst were

examined with field emission scanning electron microscopy (FE-

SEM, Ultra Plus, Carl Zeiss). Elemental analysis of the

MHz, CDCl ): δ = 8.49-8.39 (m, 2H), 7.72-7.60 (m, 2H), 7.46-

3

7.32 (m, 3H), 6.95-6.85 (m, 2H), 4.11 (q, J = 7.2 Hz, 2H), 3.79

1

3

(s, 3H), 2.59 (s, 3H), 0.99 (t, J = 7.2 Hz, 3H) ppm. C NMR

(100 MHz, CDCl ): δ = 168.54, 165.23, 163.53, 163.40, 162.13,

3

9

1

6

41.51, 138.41, 134.4, 130.34, 129.82, 128.39, 122.57, 113.79,

1.63, 55.33, 22.84, 13.63 ppm.

4.3.15 5-nitro-2-phenylpyridine (3o). White solid; m.p. 121-

ACCEPTED MANUSCRIPT

1

122 °C. H NMR (400 MHz, CDCl ): δ = 9.45 (d, J = 2.4 Hz,

3

1

H), 8.47 (dd, J = 8.8, 2.7 Hz, 1H), 8.12-8.02 (m, 2H), 7.87 (d, J

4

.3.6 Ethyl 2-(4-chlorophenyl)-4-methyl-6-phenylpyrimidine-5-

13

1

= 8.8 Hz, 1H), 7.57-7.46 (m, 3H) ppm. C NMR (100 MHz,

carboxylate (3f). White solid; m.p. 84-86 °C. H NMR (400

CDCl ): δ = 162.29, 145.16, 142.82, 136.98, 131.90, 130.88,

1

3

MHz, CDCl ): δ = 8.51-8.36 (m, 2H), 7.80-7.56 (m, 2H), 7.52-

3

29.10, 127.66, 120.00 ppm.

7

1

.29 (m, 5H), 4.13 (q, J = 7.2 Hz, 2H), 2.61 (s, 3H), 1.01 (t, J =

13

.2 Hz, 3H) ppm. C NMR (100 MHz, CDCl ): δ = 168.25,

3

65.48, 163.63, 162.64, 138.04, 137.29, 135.59, 130.00, 129.96,

28.70, 128.44, 128.41, 123.52, 61.80, 22.80, 13.64 ppm.

4

.4 General procedures for the Sonogashira coupling

reactions of pyrimidin-2-yl sulfonates with terminal alkynes

Pyrimidin-2-yl sulfonate 1 (0.25 mmol), terminal alkyne 4

(0.375 mmol), K PO (2.0 equiv.), PPh (20 mol %), 20 mg of

4

.3.7 Ethyl 4-methyl-2-(naphthalen-1-yl)-6-phenylpyrimidine-5-

1

carboxylate (3g). White solid; m.p. 83-85 °C. H NMR (400

3

4

3

MHz, CDCl ): δ = 8.62-8.60 (m, 1H), 8.06 (dd, J = 7.2, 1.2 Hz,

GO-PdCl catalyst (Pd 2.86 wt %) and CuTC (10 mol %) were

3

2

1

2

1

H), 7.89 (d, J = 8.2 Hz, 1H), 7.87-7.80 (m, 1H), 7.77-7.65 (m,

H), 7.59-7.31 (m, 6H), 4.18 (q, J = 7.2 Hz, 2H), 2.69 (s, 3H),

added to a Schlenk tube. The tube containing the mixture of

substrates was evacuated and purged with nitrogen gas for four

times. Then, 5 mL 1,4-dioxane was added by a syringe under

nitrogen atomosphere, and the reaction mixture was stirred at

13

.05 (t, J = 7.2 Hz, 3H) ppm. C NMR (101 MHz, CDCl ): δ =

3

68.26, 166.35, 165.29, 163.53, 137.85, 135.41, 134.05, 130.96,

30.73, 130.06, 129.58, 128.55, 128.42, 126.85, 125.85, 125.70,

25.16, 123.18, 109.69, 61.93, 22.86, 13.67 ppm.

1

10 °C for 48 h. After completion, the catalyst was separated by

centrifugation, the mixture was cooled to room temperature,

quenched by addition of saturated aqueous NH Cl (3 mL), and

4

.3.8 Ethyl 4-methyl-2-phenyl-6-p-tolylpyrimidine-5-carboxylate

1

4

(

3h). White solid; m.p. 66-67 °C. H NMR (400 MHz, CDCl ): δ

3

extracted with diethyl ether (3 × 5 mL). The organic solvents

were combined and washed with aqueous NaOH (2 mmol/mL, 2

mL), brine, and then dried with anhydrous magnesium sulfate,

filtered and concentrated under reduced pressure. The residue

was purified by silica gel column chromatography with a

mixture of ethyl acetate and petroleum ether as eluent. The

product was analyzed by GC-MS or NMR analysis. The

conversion and selectivity were determined using GC analysis.

All the prepared compounds are known and were compared with

=

8.60-8.38 (m, 2H), 7.60 (d, J = 8.1 Hz, 2H), 7.46-7.35 (m, 3H),

7

3

.23-7.17 (m, 2H), 4.16 (q, J = 7.2 Hz, 2H), 2.60 (s, 3H), 2.34 (s,

13

H), 1.06 (t, J = 7.2 Hz, 3H) ppm. C NMR (100 MHz, CDCl₃):

δ = 168.63, 165.14, 163.59, 163.34, 140.23, 137.23, 135.30,

1

2

30.91, 129.17, 128.58, 128.44, 128.41, 123.14, 61.72, 22.81,

1.38, 13.73 ppm.

4

.3.9 Ethyl 4-(4-methoxyphenyl)-6-methyl-2-phenylpyrimidine-5-

1

carboxylate (3i). Colorless oil. H NMR (400 MHz, CDCl ): δ =

3

8

.54-8.43 (m, 2H), 7.77-7.62 (m, 2H), 7.45-7.36 (m, 3H), 6.88 (d,

89

J = 8.8 Hz, 2H), 4.15 (q, J = 7.2 Hz, 2H), 3.72 (s, 3H), 2.56 (s,

authentic samples.

1

3

H), 1.05 (t, J = 7.2 Hz, 3H) ppm. C NMR (100 MHz, CDCl₃):

4

.4.1 Ethyl 4-methyl-6-phenyl-2-(phenylethynyl)pyrimidine-5-

1

δ = 168.72, 164.98, 163.36, 162.53, 161.17, 137.14, 130.82,

carboxylate (5a). White solid; m.p. 161-162 °C. H NMR (400

1

2

30.32, 130.01, 128.44, 128.36, 122.68, 113.80, 61.66, 55.24,

2.71, 13.73 ppm.

MHz, CDCl ): δ = 7.70-7.66 (m, 4H), 7.48-7.39 (m, 3H), 7.38-

3

7

.27 (m, 3H), 4.22- 4.17 (q, J = 8.0 Hz,, 2H), 2.67 (s, 3H), 1.06

13

4

.3.10 Ethyl 4-(4-fluorophenyl)-6-methyl-2-phenylpyrimidine-5-

(t, J = 8.0 Hz, 3H) ppm. C NMR (100 MHz, CDCl ) δ = 167.53,

3

1

carboxylate (3j). White solid; m.p. 85- 86 °C. H NMR (400

MHz, CDCl ): δ = 8.46 (dd, J = 6.8, 3.0 Hz, 2H), 7.77-7.62 (m,

165.59, 164.08, 152.38, 137.19, 132.85, 132.54, 130.40, 130.01,

129.91, 129.52, 128.75, 126.53, 128.38, 128.17, 124.19, 121.25,

88.53, 88.09, 61.98, 22.47, 13.48 ppm.

3

2

H), 7.48-7.33 (m, 3H), 7.11-7.06 (m, 2H), 4.16 (q, J = 7.2 Hz,

13

H), 2.61 (s, 3H), 1.06 (t, J = 7.2 Hz, 3H) ppm. C NMR (100

4

.4.2

Ethyl

4-Methyl-2-(oct-1-ynyl)-6-phenylpyrimidine-5-

1

MHz, CDCl ): δ = 168.33, 165.46, 165.20, 163.65, 162.71,

3

carboxylate (5b). Yellow oil. H NMR (400 MHz, CDCl3): δ =

1

62.28, 136.97, 134.28, 131.10, 130.58, 130.50, 128.58, 128.50,

23.16, 115.66, 115.44, 61.84, 22.82, 13.74 ppm.

7

2

.63–7.49 (m, 2H), 7.47–7.28 (m, 3 H), 4.10 (q, J = 7.2 Hz, 2 H),

.54 (s, 3 H), 2.40 (t, J = 7.3 Hz, 2 H), 1.65–1.53 (m, 2 H), 1.43–

4

.3.11 Ethyl 4-(4-chlorophenyl)-6-methyl-2-phenylpyrimidine-5-

1.33 (m, 2 H),1.28–1.19 (m, 4 H), 0.97 (t, J = 7.2 Hz, 3 H), 0.81

1

13

carboxylate (3k). White solid; m.p. 83-84 °C. H NMR (400

(t, J = 6.7 Hz, 3H) ppm. C NMR (100 MHz, CDCl3): δ =

MHz, CDCl ): δ = 8.52-8.41 (m, 2H), 7.69-7.59 (m, 2H), 7.47-

167.58, 165.39, 163.91,152.27, 137.18, 130.06, 128.44, 128.25,

123.95, 91.65, 79.93, 61.87,31.25, 28.70, 27.89, 22.52, 22.43,

19.41, 13.99, 13.53 ppm.

3

7

1

.34 (m, 5H), 4.16 (q, J = 7.2 Hz, 2H), 2.62 (s, 3H), 1.07 (t, J =

13

.2 Hz, 3H) ppm. C NMR (100 MHz, CDCl ): δ = 168.15,

3

65.55, 163.66, 162.31, 136.81, 136.56, 136.36, 131.20, 129.85,

28.73, 128.63, 128.52, 123.19, 61.92, 22.79, 13.74 ppm.

4

.4.3

Ethyl

2-(3,3-Dimethylbut-1-ynyl)-4-methyl-6-

phenylpyrimidine-5-carboxylate (5c). White solid; m.p. 98-99 °C.

1

4

.3.12 Ethyl 4-(4-bromophenyl)-6-methyl-2-phenylpyrimidine-5-

H NMR (400 MHz, CDCl ): δ = 7.57-7.36 (m, 2H), 7.46-7.25

3

1

carboxylate (3l). White solid; m.p. 87-89 °C. H NMR (400

MHz, CDCl ): δ = 8.50 (m, 2H), 7.78 (d, J = 8.4 Hz, 2H), 7.47-

7

1

(m, 3H), 4.10 (q, J = 7.2 Hz, 2H), 2.54 (s, 3H), 1.30 (s, 9H), 0.97

13

3

(t, J = 7.2 Hz, 3H) ppm. C NMR (100 MHz, CDCl ) δ = 167.61,

3

.37 (m, 5H), 4.19 (q, J = 7.2 Hz, 2H), 2.63 (s, 3H), 1.06 (t, J =

165.29, 163.90, 152.51, 137.33, 129.99, 128.43, 128.29, 123.94,

98.45, 78.87, 61.82, 30.38, 27.90, 22.52, 13.54. ppm.

13

.2 Hz, 3H) ppm. C NMR (100 MHz, CDCl ): δ = 168.52,

3

65.39, 163.06, 137.14, 137.00, 131.02, 128.94, 128.87, 128.60,

28.49, 127.78, 127.18, 127.16, 123.22, 61.82, 22.88, 13.72 ppm.

4

.4.4 Ethyl 4-Methyl-6-phenyl-2-(p-tolylethynyl)pyrimidine-5-

1

carboxylate (5d). Yellow oil. H NMR (400 MHz, CDCl ): δ =

3

4

.3.13 Methyl 4-methyl-2,6-diphenylpyrimidine-5-carboxylate

7.65-7.56 (m, 2H), 7.51 (d, J = 8.0 Hz, 2H), 7.45-7.33 (m, 3H),

7.10 (d, J = 7.9 Hz, 2H), 4.12 (q, J = 7.2 Hz,, 2H), 2.58 (s, 3H),

o

1

(

3m). White solid; m.p. 123-125 C. H NMR (400 MHz, CDCl ):

3

13

δ = 8.57-8.55 (m, 2H), 7.77-7.76 (m, 2H), 7.51-7.48 (m, 6H),

2.30 (s, 3H), 0.99 (t, J = 7.2 Hz, 3H) ppm. C NMR (100 MHz,

13

3

1

.72 (s, 3H), 2.68 ppm (s, 3H). C NMR (100 MHz, CDCl ): δ =

CDCl ) δ = 167.57, 165.54, 164.05, 152.47, 140.17, 137.20,

3

69.03, 165.46, 163.77, 163.40, 138.10, 137.10, 131.06, 130.07,

28.63, 128.54, 128.49, 128.35, 123.00, 52.53, 22.89 ppm.

132.65, 130.16, 129.13, 128.54, 128.29, 124.00, 118.09, 89.07,

87.66, 61.96, 22.61, 21.63, 13.58 ppm.

1

4

.3.14 2-Phenylpyridine (3n). Colorless oil. H NMR (400 MHz,

4.4.5

Ethyl

4-Methyl-2-(oct-1-ynyl)-6-p-tolylpyrimidine-5-

1

CDCl ): δ = 8.62 (d, J = 4.6 Hz, 1H), 7.97-7.87 (m, 2H), 7.73-

.59 (m, 2H), 7.42-7.32 (m, 3H), 7.24-7.12 (m, 1H) ppm.

NMR (100 MHz, CDCl ): δ = 157.33, 149.50, 139.17, 136.85,

28.97, 128.72, 126.88, 122.08, 120.59 ppm.

carboxylate (5e). Yellow oil. H NMR (400 MHz, CDCl ): δ =

3

13

7

C

7.48 (dd, J = 8.2, 2.0 Hz, 2 H), 7.18–7.14 (m, 2H), 4.13 (dd, J =

7.2, 2.9 Hz, 2H), 2.52 (d, J = 2.5 Hz, 3 H), 2.42–2.37 (m, 2H),

2.31 (d, J = 2.6 Hz, 3H), 1.64–1.54 (m, 2 H), 1.38 (dd, J = 13.1,

3

1

0

Tetrahedron

6

.4 Hz, 2H),1.28–1.16 (m, 4H), 1.05–1.01 (m, 3H), 0.82–0.79

NMR (101 MHz, CDCl ): δ = 168.28, 167.24, 165.70, 158.53,

ACCEPTED MANUSCRIPT

3

13

(m, 3 H) ppm. C NMR (100 MHz, CDCl ): δ = 167.83, 165.15,

138.30, 137.63, 129.75, 128.60, 128.29, 127.95, 127.32, 120.40,

3

1

8

1

63.72, 152.25,140.42, 134.27, 129.17, 128.28, 123.80, 91.41,

0.03, 61.86, 31.27,28.71, 27.92, 22.50, 22.45, 21.35, 19.43,

4.00, 13.64 ppm.

117.25, 61.30, 22.88, 13.52 ppm.

4

.5.5

Ethyl

4-(4-methoxyphenyl)-6-methyl-2-

1

(

phenylamino)pyrimidine-5-carboxylate (7e). Claybank oil, H

4

.4.6

Ethyl

4-(4-Chlorophenyl)-6-methyl-2-(oct-1-

NMR (300 MHz, CDCl ) δ = 7.56 (d, J = 10.1 Hz, 1H), 7.34 (d,

3

1

ynyl)pyrimidine-5-carboxylate (5f). Brown oil. H NMR (400

J = 8.5 Hz, 4H), 7.06-6.95 (m, 2H), 6.72 (t, J = 7.4 Hz, 1H),

6.68-6.61 (m, 2H), 3.88 (q, J = 7.1 Hz, 2H), 3.52 (s, 3H), 2.24 (s,

MHz, CDCl ): δ = 7.58–7.45 (m, 2H), 7.42–7.31 (m, 2H), 4.11–

3

13

4

1

.17 (m, 2H), 2.54 (d, J = 1.2 Hz, 3H), 2.40 (t, J = 7.3 Hz, 2H),

3H), 0.80 (t, J = 7.1 Hz, 3H). C NMR (75 MHz, CDCl ) δ =

3

.65–1.54 (m, 2H), 1.43–1.34 (m, 2H), 1.28–1.19 (m, 4H), 1.07–

168.90, 166.83, 164.88, 161.05, 158.78, 139.26, 130.80, 129.77,

128.75, 122.55, 119.27, 116.67 , 113.75, 61.30, 55.28, 22.83,

13.75 ppm.

13

.03 (m, 3H), 0.85–0.76(m, 3H) ppm. C NMR (100 MHz,

CDCl ): δ = 167.43, 165.64,162.59, 152.33, 136.52, 135.59,

3

1

2

29.73, 128.75, 123.84, 92.04, 79.86,62.07, 31.27, 29.65, 28.72,

7.90, 22.56, 22.45, 19.44, 14.01,13.67 ppm.

4

.5.6

Ethyl

4-(4-chlorophenyl)-6-methyl-2-

(

phenylamino)pyrimidine-5-carboxylate (7f). White solid, m.p.

o

1

7

29-130 C, H NMR (300 MHz, CDCl ) δ = 7.54 (s, 1H), 7.46-

.27 (m, 4H), 7.19-7.14 (m, 2H), 7.09-7.04 (m, 2H), 6.87-6.75

3

4

.5 General procedures for the C-N coupling reactions of

(m, 1H), 3.98-3.86 (m, 2H), 2.42-2.26 (m, 3H), 0.92- 0.74 (m,

pyrimidin-2-yl sulfonates with anilines

Pyrimidin-2-yl sulfonate 1 (0.25 mmol), anilines 6 (0.375

mmol), K PO (2.0 equiv.), PPh (20 mol %), 20 mg of GO-

13

3

1

H). C NMR (75 MHz, CDCl ) δ = 168.38, 167.60, 164.61,

58.92, 139.08, 137.15, 136.02, 129.62, 128.93, 128.65, 122.98,

19.50, 116.97, 61.52, 23.12, 13.78 ppm.

3

4

3

PdCl catalyst (Pd 2.86 wt %) were added to a 15 mL Schlenk

2

tube, and was then evacuated and purged with nitrogen gas for

four times sequentially; then 5 mL 1,4-dioxane in was added by

a syringe under nitrogen atomosphere; the mixture was then

Acknowledgements

o

stirred at 110 C for 24 h until the reaction was completed. After

This work was financially supported by National Natural Science

Foundation of China (Nos. 21362032, 21362031 and 21464013),

the Natural Science Foundation of Gansu Province (No.

1208RJYA083), and the Scientific and Technological Innovation

Engineering program of Northwest Normal University (No.

nwnu-kjcxgc-03-64).

cooling the mixture to room temperature, the catalyst was

separated by centrifugation, and the liquid was quenched with

saturated NH Cl aqueous solution (3 mL), and extracted with

4

ethoxyethane (3 × 5 mL). The organic solvents were combined

and washed with aqueous NaOH (2 mmol/mL, 2 mL), brine, and

then dried with anhydrous magnesium sulfate, filtered and

concentrated under reduced pressure. The crude product was

purified by silica gel column chromatography, eluting with a

mixture of ethyl acetate and petroleum ether. The product was

analyzed by GC-MS or NMR analysis. The conversion and

selectivity were determined using GC analysis. All the prepared

compounds are known and were compared with authentic

References and notes

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Tetrahedron

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1

2

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ACCEPTED MANUSCRIPT

Recyclable palladium catalyst on grapheme oxide for the C-C/C-N

Cross-Coupling Reactions of Heteroaromatic Sulfonates

SUPPORTING INFORMATION

a, b

a

a, c

a

b

Quanlu Yang, Zhengjun Quan,* Shang Wu, Baoxin Du, Mingming Wang, Peidong Li,

b

a

Yinpan Zhang, Xicun Wang*

a Laboratory of Eco-Environment-Related Polymer Materials, Ministry of Education; Key

Laboratory of Polymer Materials, College of Chemistry and Chemical Engineering,

Northwest Normal University, Lanzhou, Gansu 730070, P. R. China

E-mail: wangxicun@nwnu.edu.cn, quanzhengjun@hotmail.com

b College of Chemical Engineering, Lanzhou University of Arts and Science, Beimiantan 400,

Lanzhou, Gansu 730000, P. R. China

c College of Chemical Engineering, Northwest University for Nationalities, Lanzhou, Gansu

7

30030, P. R. China

Contents

Table of contents

General

S1

S2

Experimental details and characterization data for all compounds

Referrence

S3 – S5

S6

Copies of the NMR Spectra for Products

S7 – S33

S1

ACCEPTED MANUSCRIPT

1

. General

All starting materials and reagents were commercially available and used without further

purification unless otherwise noted. Solvents were purified and dried by standard methods

prior to use. All products have been previously reported and characterized. All known

products gave satisfactory analytical data corresponding to the reported literature values.

All reactions were conducted under nitrogen atmosphere with a dual-manifold Schlenk

tube and in oven-dried glassware unless otherwise noted. All NMR spectra are recorded on

1

13

MERCURY (400 MHz for H NMR, 100 MHz for C NMR) spectrometers; chemical shifts

are expressed in ppm (δunits) relative to TMS signal as internal reference in CDCl . Gas

3

chromatography (GC) analysis was performed on a Shimadezu GC-2010 equipped with a 15

m × 0.53 mm × 1.5 ꢀm RTX-1 capillary column and a oxyhydrogen flame detector. ICP-AES

were measured on IRIS Advantage. XPS measurement was recorded on PHI5702

photoelectron spectrometer. Binding energy was referred to C₁_s(284.80 eV). FTIR

spectroscopy patterns were obtained on an FT/IR-660 Plus system (Jasco, Tokyo, Japan). The

samples were mixed with KBr powders and pressed into a disk suitable for FTIR

measurement. The morphologies of the catalyst were examined with field emission scanning

electron microscopy (FE-SEM, Ultra Plus, Carl Zeiss). Elemental analysis of the

photocatalyst was conducted by an energy-dispersive X-ray spectrometer (EDX) attached to

the scanning electron microscope. Column chromatography was generally performed on silica

gel (200–300 mesh) and TLC analyses were conducted on silica gel GF254 plates.

S2

ACCEPTED MANUSCRIPT

2

. Experimental details and characterization data for all compounds

2

.1 The GO-PdCl was prepared following these procedures: GO was prepared by

2

chemical oxidation and exfoliation of natural graphite under acidic conditions according to

1

the improved Hummer’s method. Subsequently, 1.0 g the GO and 0.2 g PdCl were mixed

2

with 20 mL of de-ionized water, stirred at r.t. for 3 h. Despite the low solubility of PdCl in

2

water, cation exchange took place overnight. The suspension was separated by centrifugation,

washed with de-ionized water(3 × 20 mL) and acetone (3 × 20 mL), dryed in a vacuum oven

o

at 40 C for 4 h and gently powdered was obtained. The palladium content in GO-PdCl was

2

determined by means of inductively coupled plasma equipped with atomic emission

spectrometry (ICP-AES) and amounted to be 2.86 wt %.

2

.2 General procedures for the Suzuki coupling reactions of pyrimidin-2-yl sulfonates

with arylboronic acids (eq S1). Pyrimidin-2-yl sulfonate 1 (0.25 mmol), arylboronic Acid 2

0.375 mmol), K PO (2.0 equiv.), PPh (20 mol %), 20 mg of GO-PdCl catalyst (Pd 2.86

(

3

4

3

2

wt %) were added to a 15 mL Schlenk tube, and was then evacuated and purged with nitrogen

gas for four times sequentially; then 5 mL 1,4-dioxane in was added by a syringe under

o

nitrogen atomosphere; the mixture was then stirred at 110 C for 18 h. After completion, the

catalyst was separated by centrifugation, the mixture was cooled to room temperature,

quenched by addition of saturated aqueous NH Cl (3 mL), and extracted with diethyl ether (3

4

×

2

5 mL). The organic solvents were combined and washed with aqueous NaOH (2 mmol/ mL,

mL), brine, and then dried with anhydrous magnesium sulfate, filtered and concentrated

under reduced pressure. The residue was purified by silica gel column chromatography with a

mixture of ethyl acetate and petroleum ether as eluent. The product was analyzed by GC-MS

or NMR analysis. The conversion and selectivity were determined using GC analysis. All the

prepared compounds are known and were compared with authentic samples.

2

.3 General procedures for the Sonogashira coupling reactions of pyrimidin-2-yl

sulfonates with terminal alkynes (eq S2). Pyrimidin-2-yl sulfonate 1 (0.25 mmol), terminal

alkyne 4 (0.375 mmol), K PO (2.0 equiv.), PPh (20 mol %), 20 mg of GO-PdCl catalyst

3

4

3

2

(Pd 2.86 wt %) and CuTC (10 mol %) were added to a Schlenk tube. The tube containing the

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mixture of substrates was evacuated and purged with nitrogen gas for four times. Then, 5 mL

1

,4-dioxane was added by a syringe under nitrogen atomosphere, and the reaction mixture

was stirred at 110 °C for 48 h. After completion, the catalyst was separated by centrifugation,

the mixture was cooled to room temperature, quenched by addition of saturated aqueous

NH Cl (3 mL), and extracted with diethyl ether (3 × 5 mL). The organic solvents were

4

combined and washed with aqueous NaOH (2 mmol/mL, 2 mL), brine, and then dried with

anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue

was purified by silica gel column chromatography with a mixture of ethyl acetate and

petroleum ether as eluent. The product was analyzed by GC-MS or NMR analysis. The

conversion and selectivity were determined using GC analysis. All the prepared compounds

are known and were compared with authentic samples.

2

.4 General procedures for the C-N coupling reactions of pyrimidin-2-yl sulfonates

with anilines (eq S3). Pyrimidin-2-yl sulfonate 1 (0.25 mmol), anilines 6 (0.375 mmol),

K PO (2.0 equiv.), PPh (20 mol %), 20 mg of GO-PdCl catalyst (Pd 2.86 wt %) were added

3

4

3

2

to a 15 mL Schlenk tube, and was then evacuated and purged with nitrogen gas for four times

sequentially; then 5 mL 1,4-dioxane in was added by a syringe under nitrogen atomosphere;

o

the mixture was then stirred at 110 C for 24 h until the reaction was completed. After cooling

the mixture to room temperature, the catalyst was separated by centrifugation, and the liquid

was quenched with saturated NH Cl aqueous solution (3 mL), and extracted with

4

ethoxyethane (3 × 5 mL). The organic solvents were combined and washed with aqueous

NaOH (2 mmol/mL, 2 mL), brine, and then dried with anhydrous magnesium sulfate, filtered

and concentrated under reduced pressure. The crude product was purified by silica gel column

chromatography, eluting with a mixture of ethyl acetate and petroleum ether. The product was

analyzed by GC-MS or NMR analysis. The conversion and selectivity were determined using

GC analysis. All the prepared compounds are known and were compared with authentic

samples.

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2

.5 Procedures for the hot filtration test. Pyrimidin-2-yl sulfonate 1a (0.25 mmol), phenel

boronic acid 2a (0.375 mmol), K PO (2.0 equiv.), PPh (20 mol %), 20 mg of GO-PdCl

2

3

4

3

catalyst (Pd 2.86 wt %) were added to a 15 mL Schlenk tube, and was then evacuated and

purged with nitrogen gas for four times sequentially; then 5 mL 1,4-dioxane in was added by

o

a syringe under nitrogen atomosphere; the mixture was then stirred at 110 C for 6 h. Sample

was taken from the mixture, and was analyzed by HPLC. The mixture was then filtrated to

o

remove the catalyst, and was stirred at 110 C for another 18 h. Finally the mixture was

analyzed by HPLC. As a result, 37% of product 3a was detected by HPLC, and this

proportion remained after the catalyst was removed, suggesting that no reaction occurred

without the catalyst.

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Referrences

1

2

D. C. Marcano, D. V. Kosynkin, J. M. Berlin, ACS Nano 2010, 4, 4806-4814.

Zheng-Jun Quan, Fu-Qiang Jing, Zhang Zhang, Yu-Xia Da, Xi-Cun Wang, Eur. J. Org.

Chem. 2013, 7175–7183.

3

Zhengjun Quan, Fuqiang Jing, Zhang Zhang, Yuxia Da, and Xicun Wang, Chin. J. Chem.

013, 31, 1495-1502.

2

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Copies of the NMR Spectra for Products

Ethyl 4-methyl-2,6-diphenylpyrimidine-5-carboxylate (3a)

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Ethyl 4-methyl-6-phenyl-2-p-tolylpyrimidine-5-carboxylate (3b)

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Ethyl 4-methyl-6-phenyl-2-m-tolylpyrimidine-5-carboxylate (3c)

S9

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Ethyl 4-methyl-6-phenyl-2-o-tolylpyrimidine-5-carboxylate (3d)

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Ethyl 2-(4-methoxyphenyl)-4-methyl-6-phenylpyrimidine-5-carboxylate (3e)

S11

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Ethyl 2-(4-chlorophenyl)-4-methyl-6-phenylpyrimidine-5-carboxylate (3f)

S12

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Ethyl 4-methyl-2-(naphthalen-1-yl)-6-phenylpyrimidine-5-carboxylate (3g)

S13

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Ethyl 4-methyl-2-phenyl-6-p-tolylpyrimidine-5-carboxylate (3h)

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Ethyl 4-(4-methoxyphenyl)-6-methyl-2-phenylpyrimidine-5-carboxylate (3i)

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Ethyl 4-(4-fluorophenyl)-6-methyl-2-phenylpyrimidine-5-carboxylate (3j)

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Article Doi

Recyclable palladium catalyst on grapheme oxide for the C-C/C-N cross-coupling reactions of heteroaromatic sulfonates

DOI: 10.1016/j.tet.2015.06.103

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Authors:

Article abstract of DOI:10.1016/j.tet.2015.06.103

Full text of DOI:10.1016/j.tet.2015.06.103

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