Combinatorial synthesis and evaluation of α-iminocarboxamide- nickel(II) catalysts for the copolymerization of ethylene and a polar monomer

Article abstract of DOI:10.1021/co200081j

Late-transition metal catalysts used for olefin polymerization, the so-called postmetallocenes, which includes α-iminocarboxamide-nickel(II) catalysts have attracted a great deal of attention because of many valuable features such as the copolymerization of α-olefins with polar monomers. In this paper, the combinatorial synthesis and evaluation of α- iminocarboxamide-nickel(II) catalysts are discussed for their roles in the discovery of a highly active catalyst and elucidation of its structure-activity relationship. The combinatorial optimization of each reaction condition was performed, then a combinatorial library of α-iminocarboxamides with systematically modified substituents was constructed by amidation of α-keto acid chlorides and subsequent imination of α-keto carboxamides in parallel fashion. As a result, 87 analytically pure α-iminocarboxamide ligands were successfully synthesized. α-Iminocarboxamide-nickel(II) catalysts were prepared from the synthesized α-iminocarboxamide ligands. The catalysts' activities for polymerization of ethylene and copolymerization of ethylene and 5-norbornen-2-ol were evaluated. Results of the present study revealed 9 novel active catalysts for ethylene polymerization and 7 novel active catalysts for copolymerization of ethylene and 5-norbornen-2-ol. It should be noted that the best catalysts for ethylene polymerization and for copolymerization in the present study showed higher activities compared to the known active catalyst. Polymerization activities of the catalysts varied dramatically according to the combination of substituents on the α-iminocarboxamides.

Full text of DOI:10.1021/co200081j

Research Article
pubs.acs.org/acscombsci
Combinatorial Synthesis and Evaluation of
α-Iminocarboxamide-Nickel(II) Catalysts for the Copolymerization
of Ethylene and a Polar Monomer
Shinichiro Fuse,† Hisashi Masui,† Akio Tannna,‡ Fumihiko Shimizu,‡ and Takashi Takahashi*,†
†Department of Applied Chemistry, Tokyo Institute of Technology, 2-12-1 Ookayama, Meguro, Tokyo 152-8552, Japan
‡Mitsubishi Chemical Group, Science and Technology Research Center, Inc., 1000 Kamoshida-cho, Aoba-ku, Yokohama 227-8502,
Japan
S
* Supporting Information
ABSTRACT: Late-transition metal catalysts used for olefin
polymerization, the so-called postmetallocenes, which includes
α-iminocarboxamide-nickel(II) catalysts have attracted a great
deal of attention because of many valuable features such as
the copolymerization of α-olefins with polar monomers. In this
paper, the combinatorial synthesis and evaluation of
α-iminocarboxamide-nickel(II) catalysts are discussed for their
roles in the discovery of a highly active catalyst and elucidation of
its structure−activity relationship. The combinatorial optimiza-
tion of each reaction condition was performed, then a
combinatorial library of α-iminocarboxamides with systematically
modified substituents was constructed by amidation of α-keto acid chlorides and subsequent imination of α-keto carboxamides in
parallel fashion. As a result, 87 analytically pure α-iminocarboxamide ligands were successfully synthesized. α-Iminocarboxamide-
nickel(II) catalysts were prepared from the synthesized α-iminocarboxamide ligands. The catalysts’ activities for polymerization
of ethylene and copolymerization of ethylene and 5-norbornen-2-ol were evaluated. Results of the present study revealed 9 novel
active catalysts for ethylene polymerization and 7 novel active catalysts for copolymerization of ethylene and 5-norbornen-2-ol. It
should be noted that the best catalysts for ethylene polymerization and for copolymerization in the present study showed higher
activities compared to the known active catalyst. Polymerization activities of the catalysts varied dramatically according to the
combination of substituents on the α-iminocarboxamides.
KEYWORDS: olefin polymerization, α-iminocarboxamide-nickel(II) catalysts
substituent R′. As the bulk of the substituent R′ increases, the
N,O-binding mode tends to prevail (Figure 1). However,
reduction of the steric bulk gives rise to complexes that take
advantage of the electronically preferred N,N-binding mode
(Figure 1).4 It is known that ethylene polymerization upon
activation of Ni(COD)2, is observed only with the N,O-bound
species. As the bulk of the substituent R increases, monomer
consumption activity increases. When R is an electron
withdrawing group, the catalyst becomes more active.11
Although the structure−activity information described above
is available and much progress has been made in theoretical
calculations,12−14 it remains difficult to estimate the copoly-
merization activity of the catalysts based on their structures.
It seems to be difficult to optimize each substituent as an
independent factor for the activity, because a change in one
substituent influences the steric and electric environment of the
other substituents.
INTRODUCTION
■
Late-transition metal catalysts for olefin polymerization, the
so-called postmetallocenes, have attracted a great deal of
attention in both academia and industry, because these catalysts
have many unique and practical features such as the
copolymerization of α-olefins with certain comonomers
possessing polar functionalities, chain-walking reactions to
give hyper-branched polyolefins, and polymerization in polar
solvents such as water.1,2
In 2001, Bazan, et al. disclosed α-iminocarboxamide-
nickel(II) catalyst 1 for ethylene polymerization (Figure 1).3
Upon activation with bis(1,5-cyclooctadiene)nickel (Ni-
(COD)2), the catalysts promoted quasi-living copolymerization
of ethylene and functionalized norbornenes to generate
a variety of polyethylene-based materials, such as random
copolymers,4,5 block copolymers,6−8 and polyolefins grafted
with polar chains.9,10
The steric and electric effects of the substituents on the
α-iminocarboxamide ligands were investigated by independ-
ently changing substituents R and R′.4,11 It was reported that
the binding mode of the catalysts is altered according to the
Received: May 6, 2011
Revised: October 6, 2011
Published: October 23, 2011
© 2011 American Chemical Society
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ACS Combinatorial Science
Research Article
Figure 1. Structure of α-iminocarboxamide-nickel(II) catalyst 1.
Figure 2. Combinatorial synthesis of α-imino carboxamides 6.
Combinatorial chemistry, which revolutionized drug discov-
ery, is very powerful when the rational design of molecules is
difficult. We have reported the construction of combinatorial
libraries based on biologically active natural products15−36 and
liquid crystals.37−43 Combinatorial chemistry has recently
become increasingly important in catalyst development as
well.44,45
We anticipated that the best combination of substituents for
copolymerization activity could be found, and the structure−
activity relationship could be elucidated by constructing a
combinatorial library consisting of α-iminocarboxamides with
systematically modified substituents R and R′. Independent
optimization of each substituent without changing the other
substituents has been reported.4,11 However, combinatorial
optimization of substituents has not been reported. This
paper is the first report of the construction of a combinatorial
library of α-iminocarboxamides and the evaluation of the
ethylene polymerization and copolymerization activities of
α-iminocarboxamide-nickel(II) catalysts prepared from synthe-
sized α-iminocarboxamides.
RESULTS AND DISCUSSION
■
The synthetic plan for the construction of a library of
α-iminocarboxamides is shown in Figure 2. The aim was to
synthesize 12 α-ketocarboxamides by the amidation of
α-ketoacidchlorides 3{1−3}, which can be easily derived from
corresponding α-ketoacids 2{1−3}, with substituted anilines
4{1−4}. The desired α-iminocarboxamides 6{1−3,1−4,1−9}
were obtained by imination of the 12 α-ketocarboxamides with
substituted anilines 5{1−9}. This synthetic route consists of
simple and reliable reactions, amidation and imination, and
requires no special equipment such as a glovebox.11
Scheme 2. Combinatorial Optimization of Acid-Promoted
Imination Reaction
Scheme 1. Synthesis of α-Ketocarboxamide 7{1,1−4}
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Research Article
Table 2. Acylation of Anilines 4{1−4} with α-
Ketoacidchloride 3{1−3}
a
a
b
entry products yield entry products yield entry products yield
1
2
3
4
7{1,1} quant.
7{1,2} quant.
7{1,3} 91%
5
6
7
8
7{2,1} quant.
7{2,2} 94%
9
7{3,1} 98%
10
7{3,2} quant.
7{3,3} 88%
7{3,4} 94%
7{2,3} quant. 11
7{2,4} quant. 12
7{1,4} 89%
a
b
Isolated yield. Isolated yield in 2 steps from 2{3}
Figure 4. Preparation of α-iminocarboxamide-nickel(II) catalysts 8
from α-imino carboxamides 6.
Figure 3. Combinatorial optimization of acid-promoted imination
reaction.
Initially, we optimized the amidation conditions using
α-ketoacidchloride 3{1} and the substituted anilines 4{1−4}
(Scheme 1).46 The α-ketoacidchloride 3{1} was easily prepared
from the corresponding α-ketoacid 2{1} using α,α-dichloro-
methy methyl ether.47 The optimized combination of base and
solvent varied according to the substituents in the anilines. For
example, the combination of Et3N and toluene was suitable in
the case of 4{1−3}, whereas the combination of pyridine and
CH2Cl2 was suitable in the case of 4{4}.46
Figure 5. Ethylene polymerization and copolymerization of ethylene
and 5-norbornen-2-ol.
The pKa of the protonic acids varies among solvents;
therefore, the combinatorial optimization of protonic acids and
solvents in an acid-mediated imination of α-ketocarboxamide 7′
with aniline was performed (Scheme 2). For this process, 10
acids and 10 solvents were examined for a total of 100
conditions. It is well-known that the rate of the imination
reaction is highest around pKa 4. Therefore, 8 weak acids
including PPTS, aniline hydrochloride, 3-phenyl butylic acid,
AcOH, BzOH, HCO2H, 4-nitrobenzoic acid, and CSA were
selected as candidates. Two strong acids, frequently used in
imination reactions, TFA and p-TsOH·H2O were also
examined. Various solvents with different polarities were
examined.
The mixtures of α-ketocarboxamide 7′, aniline and acid in a
solvent were stirred at 100 °C for 10 h utilizing a parallel
synthesizer, Zodiac.48 The obtained reaction mixtures were
analyzed by LCUV/MS and the amount of the desired product
was calculated by comparison of the product’s UV intensity
to that of an internal standard. The scores of all reaction
conditions are shown in Figure 3 and Table 1. The best result
was obtained from the combination of 4-nitrobenzoic acid and
DMSO, and the observed relative UV intensity of the desired
a
Table 1. Combinatorial Optimization of Acid-Promoted Imination Reaction
dioxane
toluene
o-xylene
chloro benzene
diglyme
2-t-butyl phenol
n-butanol
NMP
DMA
DMSO
PPTS
0
14
22
33
12
9
44
58
76
92
75
69
74
38
13
65
36
22
19
26
18
13
27
17
24
51
34
34
44
20
24
21
32
29
6
9
11
5
19
13
18
19
20
24
25
19
16
3
27
38
31
37
47
29
38
24
28
18
3
3
18
12
13
11
12
12
20
16
20
13
30
52
aniline hydrochloride
3-phenyl butylic acid
AcOH
4
90
10
12
8
3
29
BzOH
3
29
HCO2H
4
50
4-nitro benzoic acid
CSA
16
16
16
25
11
15
5
7
100
84
3
TFA
3
23
p-TsOH·H2O
52
0
13
33
a
The observed relative UV intensity of the desired product by the best combination of 4-nitrobenzoic acid and DMSO was assigned a score of 100.
The relative UV intensities of the desired product obtained from other reaction conditions were assigned scores from 0 to 100.
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Table 3. Construction of a Combinatorial Library of α-Iminocarboxamides 6
a
a
a
entry
products
yield (%)
entry
products
yield (%)
entry
products
yield (%)
1
6{1,1,1}
6{1,1,2}
6{1,1,3}
6{1,1,4}
6{1,1,5}
6{1,1,6}
6{1,1,7}
6{1,1,8}
6{1,1,9}
6{1,2,1}
6{1,2,2}
6{1,2,3}
6{1,2,4}
6{1,2,5}
6{1,2,6}
6{1,2,7}
6{1,2,8}
6{1,2,9}
6{1,3,1}
6{1,3,2}
6{1,3,3}
6{1,3,4}
6{1,3,5}
6{1,3,6}
6{1,3,7}
6{1,3,8}
6{1,3,9}
6{1,4,1}
6{1,4,2}
6{1,4,3}
6{1,4,4}
6{1,4,5}
6{1,4,6}
6{1,4,7}
6{1,4,8}
35
87
37
24
17
45
45
23
18
55
92
54
27
85
31
65
69
23
53
quant.
20
98
47
24
78
74
b
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
6{2,1,1}
6{2,1,2}
6{2,1,3}
6{2,1,4}
6{2,1,5}
6{2,1,6}
6{2,1,7}
6{2,1,8}
6{2,1,9}
6{2,2,1}
6{2,2,2}
6{2,2,3}
6{2,2,4}
6{2,2,5}
6{2,2,6}
6{2,2,7}
6{2,2,8}
6{2,2,9}
6{2,3,1}
6{2,3,2}
6{2,3,3}
6{2,3,4}
6{2,3,5}
6{2,3,6}
6{2,3,7}
6{2,3,8}
6{2,3,9}
6{2,4,1}
6{2,4,2}
6{2,4,3}
6{2,4,4}
6{2,4,5}
6{2,4,6}
6{2,4,7}
6{2,4,8}
6{2,4,9}
30
82
60
57
23
9
73
6{3,1,1}
6{3,1,2}
6{3,1,3}
6{3,1,4}
6{3,1,5}
6{3,1,6}
6{3,1,7}
6{3,1,8}
6{3,1,9}
6{3,2,1}
6{3,2,2}
6{3,2,3}
6{3,2,4}
6{3,2,5}
6{3,2,6}
6{3,2,7}
6{3,2,8}
6{3,2,9}
6{3,3,1}
6{3,3,2}
6{3,3,3}
6{3,3,4}
6{3,3,5}
6{3,3,6}
6{3,3,7}
6{3,3,8}
6{3,3,9}
6{3,4,1}
6{3,4,2}
6{3,4,3}
6{3,4,4}
6{3,4,5}
6{3,4,6}
6{3,4,7}
6{3,4,8}
6{3,4,9}
18
33
21
10
28
9
2
74
3
75
4
76
5
77
6
78
7
48
5
79
3
8
80
12
b
9
b
81
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
88
20
32
62
37
42
11
73
b
82
18
29
18
8
83
84
85
86
14
12
14
26
b
87
88
89
90
41
38
15
7
91
21
15
23
16
45
10
12
19
b
92
93
94
8
95
69
59
quant.
b
96
97
98
99
92
77
27
37
quant.
53
23
12
b
9
100
101
102
103
104
105
106
107
108
b
10
34
2
12
b
b
b
b
b
b
b
b
b
b
6{1,4,9}
b
b
a
b
Isolated yield. Imination did not proceed.
product was assigned a score of 100. The relative UV intensities
of the desired product obtained from other reaction conditions
were then assigned scores from 0 to 100 (Figure 3 and
Table 1). The combination of AcOH and toluene also afforded
a result comparable to the best combination (score = 92). It is
sometimes difficult to find the best combination by optimizing
each factor (acid and solvent) independently. For example, if
10 solvents were examined using TFA, which is a frequently
used acid in imination reactions, the optimal solvent was
n-butanol (Table 1). All 10 acids were then examined in
n-butanol solvent. The optimal acid was BzOH (Table 1).
However, the combination of BzOH and n-butanol was not
an optimal combination. Thus, combinatorial optimization of
reaction conditions is a very powerful and reliable method. For
convenience during the workup process, we employed the
second-best combination, AcOH and toluene, for construction
of the α-iminocarboxamide library.
α-ketoacid 2{3} with oxalyl chloride and NEt3 in toluene,
which was then used for the amidation reaction without further
purification.46 Twelve α-ketocarboxamides were prepared by
amidation of the α-ketoacidchlorides 3{1−3} with the
substituted anilines 4{1−4} (Table 2). For amidation with
the anilines 4{1−3}, the combination of NEt3 and toluene was
employed (entries 1−3, 5−7, and 9−11). On the other hand,
for amidation with the aniline 4{4}, the combination of
pyridine and CH2Cl2 was employed (entries 4, 8, 12). All 12
α-ketocarboxamides were obtained in good to excellent yields.
Subsequent imination of the 12 α-ketocarboxamides with
anilines 5{1−9} was carried out using AcOH and toluene. In
the case of R1 = Me group, all the intended products were
obtained (entries 1−36) except for 6{1,3,9} and 6{1,4,9}
(Table 3 entries 27, 36) with a combined steric bulk of aryl
substituents that was the largest. In the case of R1 = Ph and i-Bu
group, imination with the largest aniline 5{9} did not proceed
(Table 3 entries 45, 54, 63, 72, 81, 90, 99, and 108). In
addition, imination of the bulky α-ketocarboxamides, 7{2,4}
and 7{3,4} afforded unsatisfactory results (Table 3 entries 64−
72, and 100−108). The combined steric bulk of substituents
R1−R7 (Figure 2) largely influenced the results of imination.
The combinatorial library of α-iminocarboxamide was
constructed by the procedure developed. α-Ketoacid chloride
3{2} was easily prepared from the corresponding α-ketoacid
2{2}, using the same reaction condition for the synthesis
of 3{1}. α-Ketoacid chloride 3{3} was prepared by treating
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Table 4. Polymerization Activities of α-Iminocarboxamide-nickel(II) Catalysts 8{1,1−4,1−9}
a
b
a
b
entry
1
catalysts
activity
activity
entry
18
catalysts
activity
0
activity
8{1,1,1} (R1 = Me, R2 = Et, R3 = Me, R4 = H,
0
0
8{1,2,9} (R1 = Me, R2 = Et, R3 = Et, R4 = H,
0
R5 = H, R6 = H, R7 =H)
R5 = t-Bu, R6 = t-Bu, R7 = t-Bu)
2
8{1,1,2} (R1 = Me, R2 = Et, R3 = Me, R4 = H,
0
c
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
8{1,3,1} (R1 = Me, R2 = i-Pr, R3 = i-Pr, R4 =
0
0
0
R5 = H, R6 = H, R7 = OMe)
H, R5 = H, R6 = H, R7 =H)
3
8{1,1,3} (R1 = Me, R2 = Et, R3 = Me, R4 = H,
0
0
8{1,3,2} (R1 = Me, R2 = i-Pr, R3 = i-Pr, R4 =
0
R5 = Me, R6 = H, R7 = H)
H, R5 = H, R6 = H, R7 = OMe)
4
8{1,1,4} (R1 = Me, R2 = Et, R3 = Me, R4 = H,
0
c
8{1,3,3} (R1 = Me, R2 = i-Pr, R3 = i-Pr, R4 =
1300
5300
6700
0
0
R5 = Me, R6 = Me, R7 = H)
H, R5 = Me, R6 = H, R7 = H)
5
8{1,1,5} (R1 = Me, R2 = Et, R3 = Me, R4 = H,
0
c
8{1,3,4} (R1 = Me, R2 = i-Pr, R3 = i-Pr, R4 =
0
R5 = Et, R6 = Me, R7 = H)
H, R5 = Me, R6 = Me, R7 = H)
6
8{1,1,6} (R1 = Me, R2 = Et, R3 = Me, R4 = H,
0
21800
0
c
8{1,3,5} (R1 = Me, R2 = i-Pr, R3 = i-Pr, R4 =
0
R5 = Et, R6 = Et, R7 = H)
H, R5 = Et, R6 = Me, R7 = H)
7
8{1,1,7} (R1 = Me, R2 = Et, R3 = Me, R4 = H,
11900
8{1,3,6} (R1 = Me, R2 = i-Pr, R3 = i-Pr, R4 =
0
R5 = i-Pr, R6 = i-Pr, R7 = H)
H, R5 = Et, R6 = Et, R7 = H)
8
8{1,1,8} (R1 = Me, R2 = Et, R3 = Me, R4 = H,
c
8{1,3,7} (R1 = Me, R2 = i-Pr, R3 = i-Pr, R4 =
42000
6000
3000
0
15000
R5 = Me, R6 = Me, R7 = Me)
H, R5 = i-Pr, R6 = i-Pr, R7 = H)
9
8{1,1,9} (R1 = Me, R2 = Et, R3 = Me, R4 = H,
0
c
8{1,3,8} (R1 = Me, R2 = i-Pr, R3 = i-Pr, R4 =
2700
R5 = t-Bu, R6 = t-Bu, R7 = t-Bu)
H, R5 = Me, R6 = Me, R7 = Me)
10
11
12
13
14
15
16
17
8{1,2,1} (R1 = Me, R2 = Et, R3 = Et, R4 = H,
0
0
8{1,4,1} (R1 = Me, R2 = t-Bu, R3 = t-Bu, R4 =
0
R5 = H, R6 = H, R7 =H)
t-Bu, R5 = H, R6 = H, R7 =H)
8{1,2,2} (R1 = Me, R2 = Et, R3 = Et, R4 = H,
0
0
8{1,4,2} (R1 = Me, R2 = t-Bu, R3 = t-Bu, R4 =
t-Bu, R5 = H, R6 = H, R7 = OMe)
0
R5 = H, R6 = H, R7 = OMe)
8{1,2,3} (R1 = Me, R2 = Et, R3 = Et, R4 = H,
0
0
8{1,4,3} (R1 = Me, R2 = t-Bu, R3 = t-Bu, R4 =
4600
0
0
0
R5 = Me, R6 = H, R7 = H)
t-Bu, R5 = Me, R6 = H, R7 = H)
8{1,2,4} (R1 = Me, R2 = Et, R3 = Et, R4 = H,
2400
7300
1600
25000
0
0
0
8{1,4,4} (R1 = Me, R2 = t-Bu, R3 = t-Bu, R4 =
t-Bu, R5 = Me, R6 = Me, R7 = H)
R5 = Me, R6 = Me, R7 = H)
8{1,2,5} (R1 = Me, R2 = Et, R3 = Et, R4 = H,
8{1,4,5} (R1 = Me, R2 = t-Bu, R3 = t-Bu, R4 =
19400
2500
12900
0
5000
0
R5 = Et, R6 = Me, R7 = H)
t-Bu, R5 = Et, R6 = Me, R7 = H)
8{1,2,6} (R1 = Me, R2 = Et, R3 = Et, R4 = H,
1300
17300
c
8{1,4,6} (R1 = Me, R2 = t-Bu, R3 = t-Bu, R4 =
t-Bu, R5 = Et, R6 = Et, R7 = H)
R5 = Et, R6 = Et, R7 = H)
8{1,2,7} (R1 = Me, R2 = Et, R3 = Et, R4 = H,
8{1,4,7} (R1 = Me, R2 = t-Bu, R3 = t-Bu, R4 =
5900
0
R5 = i-Pr, R6 = i-Pr, R7 = H)
t-Bu, R5 = i-Pr, R6 = i-Pr, R7 = H)
8{1,2,8} (R1 = Me, R2 = Et, R3 = Et, R4 = H,
8{1,4,8} (R1 = Me, R2 = t-Bu, R3 = t-Bu, R4 =
t-Bu, R5 = Me, R6 = Me, R7 = Me)
R5 = Me, R6 = Me, R7 = Me)
Table 4. continued
a
b
Reactivity of catalysts 8 in the homopolymerization of ethylene (g-polymer/mol-6/h). Reactivity of catalysts 8 in the copolymerization of ethylene
c
with 5-norbornen-2-ol (g-polymer/mol-6/h). Reactivity of catalysts 8 was not evaluated because ethylene polymerization activity of the catalysts
was very low.
Synthesized α-iminocarboxamides were purified by silica gel
column chromatography, and 87 analytically pure products were
obtained from 108 trials. The structures of those products were
determined based on the amount of ethylene consumption
and the resulting polymer weight.
In the present study, 9 novel active catalysts, 8{1,1,7}, 8{1,2,7},
8{1,4,5}, 8{1,4,7}, 8{2,3,6}, 8{2,3,7}, 8{3,1,6}, 8{3,3,6}, and
8{3,3,7}51 (Tables 4−6, entries 7, 16, 31, 33, 56, 57, 68, 84, and
85) showed high activity for ethylene polymerization (>10000
g-polymer/mol-6/h). The high-throughput evaluation method
used in the present study proved to be reliable, as an active
catalyst, 8{1,3,7}49 (Table 4, entry 25), also showed high
ethylene polymerization activity. It should be noted that the
activities of catalysts 8{2,3,7}, and 8{3,3,7} were higher than
that of known active catalyst 8{1,3,7}. The catalysts that had
bulky substituents R2−R7 on their α-iminocarboxamide ligands
tended to have high ethylene polymerization activity. This
observation is consistent with a previous report.4 The Me and
i-Bu groups were more suitable than the Ph group as an R1
substituent for ethylene polymerization (Tables 4−6). The
combination of R2 = R3 = R5 = R6 = i-Pr, R4 = R7 = H afforded
the best results regardless of substitutent R1 (Tables 4−6,
entries 25, 57 and 85). It is interesting that the optimal
substituents R2−R4 differed from substituents R5−R7. For
instance, in the case of R1 = Me group, the optimal
combination of substituents R2−R4 was R2 = R3 = i-Pr, R4 =
H when the combination of substituents R5−R7 was R5 = R6 =
Me, R7 = H, or R5 = R6 = i-Pr, R7 = H, or R5 = R6 = R7 = Me
(Table 4, entries 22, 25 and 26), whereas the optimal
combination of substituents R2−R4 was R2 = R3 = R4 = t-Bu
1
confirmed by H NMR, 13C NMR, IR, and HRMS.
α-Iminocarboxamide-nickel(II) catalysts 8 were prepared from
synthesized α-iminocarboxamides 6 according to a previously
reported procedure,49 after some modifications (Figure 4). The
α-iminocarboxamide was deprotonated with an excess amount of
KH and treated with a mixture of Ni(COD)2, BnCl and 2,6-
lutidine in THF. The resulting solution was concentrated in
vacuo, and diluted with benzene. Insoluble salts were removed by
filtration to give a crude solution of α-iminocarboxamide-
nickel(II) catalysts 8. The crude solutions were used for the
evaluation of polymerization activities of alkenes, without further
purification for the sake of throughput improvement.
Activities of the prepared catalysts 8 for ethylene polymer-
ization and copolymerization of ethylene and 5-norbornen-2-ol
were evaluated (Tables 4−6) by using the Endeavor Catalyst
Screening System50 based on Bazan’s procedure.49 Ethylene
homopolymerization was initiated by introducing ethylene gas
(7.0 bar) to a solution of 8 (10 μmol) in C6D6 (1 mL) and dry
toluene (4 mL) at 40 °C. Copolymerization of ethylene and
5-norbornen-2-ol was carried out in the same manner, except
that 5-norbornen-2-ol (375 μmol) was added to the catalyst
solution prior to heating and ethylene introduction. Polymer-
ization activity (shown in g-polymer/mol-6/hour) was
21
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ACS Combinatorial Science
Research Article
Table 5. Polymerization Activities of α-Iminocarboxamide-nickel(II) Catalysts 8{2,1−4,1−8}
a
b
a
b
entry
35
catalysts
activity
activity
0
entry
49
catalysts
activity
0
activity
0
8{2,1,1} (R1 = Ph, R2 = Et, R3 = Me, R4 = H,
0
8{2,2,7} (R1 = Ph, R2 = Et, R3 = Et, R4 = H,
R5 = H, R6 = H, R7 =H)
R5 = i-Pr, R6 = i-Pr, R7 = H)
36
37
38
39
40
41
42
43
44
45
46
47
48
8{2,1,2} (R1 = Ph, R2 = Et, R3 = Me, R4 = H,
0
c
c
50
51
52
53
54
55
56
57
58
59
60
61
62
8{2,2,8} (R1 = Ph, R2 = Et, R3 = Et, R4 = H,
0
c
R5 = H, R6 = H, R7 = OMe)
R5 = Me, R6 = Me, R7 = Me)
8{2,1,3} (R1 = Ph, R2 = Et, R3 = Me, R4 = H,
0
8{2,3,1} (R1 = Ph, R2 = i-Pr, R3 = i-Pr, R4 =
0
0
R5 = Me, R6 = H, R7 = H)
H, R5 = H, R6 = H, R7 =H)
8{2,1,4} (R1 = Ph, R2 = Et, R3 = Me, R4 = H,
0
0
0
0
c
8{2,3,2} (R1 = Ph, R2 = i-Pr, R3 = i-Pr, R4 =
0
0
R5 = Me, R6 = Me, R7 = H)
H, R5 = H, R6 = H, R7 = OMe)
8{2,1,5} (R1 = Ph, R2 = Et, R3 = Me, R4 = H,
0
8{2,3,3} (R1 = Ph, R2 = i-Pr, R3 = i-Pr, R4 =
0
c
R5 = Et, R6 = Me, R7 = H)
H, R5 = Me, R6 = H, R7 = H)
8{2,1,6} (R1 = Ph, R2 = Et, R3 = Me, R4 = H,
0
8{2,3,4} (R1 = Ph, R2 = i-Pr, R3 = i-Pr, R4 =
0
0
R5 = Et, R6 = Et, R7 = H)
H, R5 = Me, R6 = Me, R7 = H)
8{2,1,7} (R1 = Ph, R2 = Et, R3 = Me, R4 = H,
0
8{2,3,5} (R1 = Ph, R2 = i-Pr, R3 = i-Pr, R4 =
5700
0
R5 = i-Pr, R6 = i-Pr, R7 = H)
H, R5 = Et, R6 = Me, R7 = H)
8{2,1,8} (R1 = Ph, R2 = Et, R3 = Me, R4 = H,
0
0
0
c
8{2,3,6} (R1 = Ph, R2 = i-Pr, R3 = i-Pr, R4 =
13000
3000
R5 = Me, R6 = Me, R7 = Me)
H, R5 = Et, R6 = Et, R7 = H)
8{2,2,1} (R1 = Ph, R2 = Et, R3 = Et, R4 = H,
8{2,3,7} (R1 = Ph, R2 = i-Pr, R3 = i-Pr, R4 =
50900
7800
R5 = H, R6 = H, R7 =H)
H, R5 = i-Pr, R6 = i-Pr, R7 = H)
8{2,2,2} (R1 = Ph, R2 = Et, R3 = Et, R4 = H,
0
0
0
0
0
0
8{2,3,8} (R1 = Ph, R2 = i-Pr, R3 = i-Pr, R4 =
0
0
0
0
d
0
0
0
0
d
R5 = H, R6 = H, R7 = OMe)
H, R5 = Me, R6 = Me, R7 = Me)
8{2,2,3} (R1 = Ph, R2 = Et, R3 = Et, R4 = H,
0
8{2,4,1} (R1 = Ph, R2 = t-Bu, R3 = t-Bu, R4 =
R5 = Me, R6 = H, R7 = H)
t-Bu, R5 = H, R6 = H, R7 =H)
8{2,2,4} (R1 = Ph, R2 = Et, R3 = Et, R4 = H,
6100
0
8{2,4,2} (R1 = Ph, R2 = t-Bu, R3 = t-Bu, R4 =
t-Bu, R5 = H, R6 = H, R7 = OMe)
R5 = Me, R6 = Me, R7 = H)
8{2,2,5} (R1 = Ph, R2 = Et, R3 = Et, R4 = H,
8{2,4,3} (R1 = Ph, R2 = t-Bu, R3 = t-Bu, R4 =
R5 = Et, R6 = Me, R7 = H)
t-Bu, R5 = Me, R6 = H, R7 = H)
8{2,2,6} (R1 = Ph, R2 = Et, R3 = Et, R4 = H,
3000
8{2,4,4} (R1 = Ph, R2 = t-Bu, R3 = t-Bu, R4 =
t-Bu, R5 = Me, R6 = Me, R7 = H)
R5 = Et, R6 = Et, R7 = H)
Table 5. continued
a
b
Reactivity of catalysts 8 in homopolymerization of ethylene (g-polymer/mol-6/h). Reactivity of catalysts 8 in copolymerization of ethylene with
c
5-norbornen-2-ol (g-polymer/mol-6/h). Reactivity of catalysts 8 was not evaluated because ethylene polymerization activity of the catalysts was very
d
low. The amount of the prepared α-iminocarboxamide ligand 6{2,4,4} was not enough to evaluate polymerization activity.
Table 6. Polymerization Activities of α-Iminocarboxamide-nickel(II) Catalysts 8{3,1−4,1−8}
a
b
a
b
entry
63
catalysts
activity
activity
entry
76
catalysts
activity
activity
8{3,1,1} (R1 = i-Bu, R2 = Et, R3 = Me, R4 = H,
0
0
8{3,2,6} (R1 = i-Bu, R2 = Et, R3 = Et, R4 = H,
0
9600
0
0
R5 = H, R6 = H, R7 =H)
R5 = Et, R6 = Et, R7 = H)
64
65
66
67
68
69
70
71
72
73
74
75
8{3,1,2} (R1 = i-Bu, R2 = Et, R3 = Me, R4 = H,
0
c
77
78
79
80
81
82
83
84
85
86
87
8{3,2,7} (R1 = i-Bu, R2 = Et, R3 = Et, R4 = H,
1300
R5 = H, R6 = H, R7 = OMe)
R5 = i-Pr, R6 = i-Pr, R7 = H)
8{3,1,3} (R1 = i-Bu, R2 = Et, R3 = Me, R4 = H,
0
0
0
0
0
0
0
0
c
8{3,2,8} (R1 = i-Bu, R2 = Et, R3 = Et, R4 = H,
0
R5 = Me, R6 = H, R7 = H)
R5 = Me, R6 = Me, R7 = Me)
8{3,1,4} (R1 = i-Bu, R2 = Et, R3 = Me, R4 = H,
2400
8{3,3,1} (R1 = i-Bu, R2 = i-Pr, R3 = i-Pr, R4 =
0
0
R5 = Me, R6 = Me, R7 = H)
H, R5 = H, R6 = H, R7 =H)
8{3,1,5} (R1 = i-Bu, R2 = Et, R3 = Me, R4 = H,
0
8{3,3,2} (R1 = i-Bu, R2 = i-Pr, R3 = i-Pr, R4 =
0
0
R5 = Et, R6 = Me, R7 = H)
H, R5 = H, R6 = H, R7 = OMe)
8{3,1,6} (R1 = i-Bu, R2 = Et, R3 = Me, R4 = H,
23000
8{3,3,3} (R1 = i-Bu, R2 = i-Pr, R3 = i-Pr, R4 =
0
0
R5 = Et, R6 = Et, R7 = H)
H, R5 = Me, R6 = H, R7 = H)
8{3,1,7} (R1 = i-Bu, R2 = Et, R3 = Me, R4 = H,
5400
8{3,3,4} (R1 = i-Bu, R2 = i-Pr, R3 = i-Pr, R4 =
1900
6800
26900
71800
0
0
R5 = i-Pr, R6 = i-Pr, R7 = H)
H, R5 = Me, R6 = Me, R7 = H)
8{3,1,8} (R1 = i-Bu, R2 = Et, R3 = Me, R4 = H,
4200
8{3,3,5} (R1 = i-Bu, R2 = i-Pr, R3 = i-Pr, R4 =
0
6200
11560
0
R5 = Me, R6 = Me, R7 = Me)
H, R5 = Et, R6 = Me, R7 = H)
8{3,2,1} (R1 = i-Bu, R2 = Et, R3 = Et, R4 = H,
0
0
0
0
0
8{3,3,6} (R1 = i-Bu, R2 = i-Pr, R3 = i-Pr, R4 =
R5 = H, R6 = H, R7 =H)
H, R5 = Et, R6 = Et, R7 = H)
8{3,2,2} (R1 = i-Bu, R2 = Et, R3 = Et, R4 = H,
8{3,3,7} (R1 = i-Bu, R2 = i-Pr, R3 = i-Pr, R4 =
R5 = H, R6 = H, R7 = OMe)
H, R5 = i-Pr, R6 = i-Pr, R7 = H)
8{3,2,3} (R1 = i-Bu, R2 = Et, R3 = Et, R4 = H,
0
0
0
8{3,3,8} (R1 = i-Bu, R2 = i-Pr, R3 = i-Pr, R4 =
R5 = Me, R6 = H, R7 = H)
H, R5 = Me, R6 = Me, R7 = Me)
8{3,2,4} (R1 = i-Bu, R2 = Et, R3 = Et, R4 = H,
8{3,4,2} (R1 = i-Bu, R2 = t-Bu, R3 = t-Bu, R4
0
c
R5 = Me, R6 = Me, R7 = H)
= t-Bu, R5 = H, R6 = H, R7 = OMe)
8{3,2,5} (R1 = i-Bu, R2 = Et, R3 = Et, R4 = H,
R5 = Et, R6 = Me, R7 = H)
Table 6. continued
a
b
Reactivity of catalysts 8 in homopolymerization of ethylene (g-polymer/mol-6/h). Reactivity of catalysts 8 in copolymerization of ethylene with
c
5-norbornen-2-ol (g-polymer/mol-6/h). Reactivity of catalysts 8 was not evaluated because ethylene polymerization activity of the catalysts was
very low.
when the combination of substituents R5−R7 was R5 = R6 =
R5 = R6 = Et, R7 = H (Table 4, entries 27, 29, 31 and 32).
R7 = H or R5 = Me, R6 = R7 = H or R5 = Et, R6 = Me, R7 = H or
In the case of R1 = i-Bu group, the optimal combination of
22
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ACS Combinatorial Science
Research Article
substituents R2−R4 was R2 = Et, R3 = Me, R4 = H when the
combination of substituents R5−R7 was R5 = R6 = Me, R7 = H,
or R5 = R6 = R7 = Me (Table 6, entries 66 and 70), whereas the
optimal combination of substituents R2−R4 was R2 = R3 = i-Pr,
R4 = H when the combination of substituents R5−R7 was R5 =
Et, R6 = Me, R7 = H or R5 = R6 = Et, R7 = H or R5 = R6 = i-Pr,
R7 = H (Table 6, entries 83−85).
Seven novel catalysts, 8{1,1,7}, 8{1,2,7}, 8{1,4,5}, 8{1,4,7},
8{2,3,7}, 8{3,3,6}, and 8{3,3,7} (Table 4−6, entries 7, 16, 31,
33, 57, 84, and 85), showed high activity for copolymeriza-
tion of ethylene and 5-norbornen-2-ol (>5000 g-polymer/mol-6/h).
A known active catalysts 8{1,3,7}49 (Table 4, entry 25), also
showed high activity. It should be noted that the activity of
catalyst 8{1,2,7} was higher than that of the known active
catalyst 8{1,3,7}. Interestingly, the optimal combination of
substituents R2−R7 differs from substitutent R1. The com-
bination of R2 = R3 = Et, R4 = R7 = H, R5 = R6 = i-Pr afforded
the best result when R1 = Me group (Table 4, entry 16),
whereas the same combination of R2−R7 afforded the
unsatisfactory results when R1 = Ph or i-Bu group (Tables 5
and 6, entries 49 and 77). In the case of R1 = Ph or i-Bu
group, the combination of R2 = R3 = R5 = R6 = i-Pr, R4 =
R7 = H afforded the best result (Tables 5 and 6, entries 57
and 85).
Overall, the novel catalyst 8{3,3,7} showed the highest
activity for ethylene polymerization. It is noteworthy, however,
that it was not the best catalyst for copolymerization of
ethylene and 5-norbornen-2-ol. The novel catalyst 8{1,2,7}
showed the highest activity for copolymerization. To identify
the binding mode of catalyst 8{1,2,7}, purification and NMR
analysis was carried out. The observed NMR spectra was quite
similar to the reported NMR spectra of a known similar catalyst
8{1,3,7}.49 Therefore, the novel catalyst 8{1,2,7} is supposed to
be N,O-binding catalyst.
ASSOCIATED CONTENT
■
S
* Supporting Information
Analytical data (1H, 13C NMR and IR spectra) for the
compounds are provided. This information is available free of
charge via the Internet at http://pubs.acs.org/.
AUTHOR INFORMATION
■
Corresponding Author
*Phone: +81-3-5734-2120. Fax: +81-3-5734-2884. E-mail:
ttak@apc.titech.ac.jp.
ACKNOWLEDGMENTS
■
We thank Dr. Shigekazu Ito, Tokyo Institute of Technology,
and Dr. Naomasa Sato, Mitsubishi Chemical Group, Science
and Technology Research Center, Inc., for assistance in
purification and NMR analysis of 8{1,2,7}.
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CONCLUSION
■
The solution-phase combinatorial synthesis of α-iminocarbox-
amide ligands using an amidation/imination sequence was
successfully demonstrated. In the amidation reaction, the
combination of Et3N and toluene was effective for the less
bulky anilines, while the combination of pyridine and CH2Cl2
was suitable for the bulky anilines. Combinatorial optimization
of the acid-mediated imination conditions disclosed that
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ACS Combinatorial Science
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