Silica-alumina catalyst support, an efficient catalyst for synthesis of halogen substituted 2,6-bis(imino)pyridines

Article abstract of DOI:10.1055/s-2003-40850

Silica-alumina catalyst support was found to be an efficient catalyst for the condensation reaction of 2,6-, 2,5-, and 2,4-difluoroaniline and ortho-halogen-aniline with 2,6-diacetylpyridine to afford corresponding 2,6-bis(imino)pyridines in 56-75% isolat

Full text of DOI:10.1055/s-2003-40850

LETTER
1419
Silica-Alumina Catalyst Support, an Efficient Catalyst for Synthesis of
Halogen Substituted 2,6-Bis(imino)pyridines
Silica-Alumina
C
h
atalyst
S
upp
a
ort ngtao Qian,* Feifeng Gao, Yaofeng Chen, Lijun Gao
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
354 Fenglin Road, Shanghai 200032, China
Fax +86(21)64166148; E-mail: qianct@mail.sioc.ac.cn
Received 3 March 2003
in refluxing chlorobenzene, toluene, xylene, or 1,2,3,4-
tetrahydronnaphthalene with removal of water,13 and pro-
moted by TiCl4 in refluxing solvents,14 often with low to
moderate yield. It promotes us to find a new method to
Abstract: Silica-alumina catalyst support was found to be an effi-
cient catalyst for the condensation reaction of 2,6-, 2,5-, and 2,4-di-
fluoroaniline and ortho-halogen-aniline with 2,6-diacetylpyridine
to afford corresponding 2,6-bis(imino)pyridines in 56–75% isolated
yields under extremely mild reaction conditions. The catalyst can be synthesize di-fluoro- and ortho-halogen-substituted 2,6-
recovered and reused
bis(imino)pyridines.
Key words: silica-alumina catalyst support, halogen substituted
2,6-bis(imino)pyridine, condensation reaction
The condensation reaction of 2,6-dihalogenaniline with
2,6-diacetylpyridine, catalyzed by p-TsOH in fluxing tol-
uene, won’t go on without removing water by azeotropic
distillation.6 Because the halogen substituted 2,6-bis(imi-
Recently, a class of iron and cobalt complexes bearing
bis(imino)pyridines were reported by Brookhart1–3 and
Gibson.4,5 These complexes are highly active catalysts for
ethylene polymerization and oligomerization in the pres-
ence of MAO(methylaluminoxane). All reported bis(imi-
no)pyridines at high temperature are not stable in air, the
condensation reactions were sensitive to temperature.
Synthesis of di-fluoro-substituted 2,6-bis(imino)pyridine
shown the same property. At a higher temperature the re-
action produced complicated mixture and the yield de-
creased steeply (entries 1, 2, Table 1). It must be noted
that the product should be purified by recrystallization,
Attempted separation of the product by flash column led
to a sharp decrease of yield.15
no)pyridines
are
exclusively
alkyl-substituted
compounds. To our knowledge, there is no report about
synthesis of halogen substituted bis(imino)pyridines in
literature. Due to electronic and steric effects of halogen,
it is interesting to study the relationship between catalyst
efficiency and halogen substituents. In our previous work,
we synthesized a series of di-chloro- and di-bromo-substi-
tuted 2,6-bis(imino)pyridines and their iron and cobalt
complexes.6 The investigation of their catalytic activities
in ethylene polymerization has shown that these iron and
cobalt complexes are very active.7 Also we found the
iron(II) complex bearing 2,6-di-fluoro-substituted
bis(imino)pyridine(1a) oligomerized ethylene to a-olefins
with very high activity and selectivity.8 In addition, halo-
gen-substituted ketimines are important intermediates or
precursors for preparing pyrimidine with polyhaloalkyl
group,9 which are of great interest because of their herbi-
cidal, fungicidal, antibiotic, antiviral or antineoplastic
properities,10 electron transport materials in positive
charge electrophtography,13c spiro-heterocycles of indole
derivatives.13b Also these ketimines can be used as adhe-
sive, crosslinking agent, and curing agent in resin.11
A number of reactions have been found to proceed
smoothly by the catalysis of rare earth(III) triflates.16 Sev-
eral Ln(OTf)3 (Ln = La, Gd, Yb) were examined to cata-
lyze this condensation reaction. Gd(OTf)3 provided the
best result of 44% yield (entry 7, Table 1). In the case of
La(OTf)3, a sluggish reaction was observed in THF and
CH2Cl2 (entries 4–6, Table 1). A stronger Lewis acid
Gd(OPf)3 (Pf = perfluorooctanesulfonate)17 was also test-
ed with a dramatic decrease of yield (entry 9, Table 1).
Fortunately, we found silica-alumina catalyst support
(Grade 135) combination with 4 Å molecular sieves18
could catalyze this condensation reaction at 30 °C with
satisfied 65% yield, after simple filtering and vacuum-
ing.19 The mixture of Si-Al-135 and 4 Å MS powder re-
covered could be reactivated by heating at 200 °C in
vacuo without reducing its reactivity (entry 10, Table 1).
Increasing the calcination temperature from 200 °C to
500 °C, the yield was decreased from 65% to 31%. In sol-
vents other than toluene, it gave much lower yield (entries
10–12, Table 1). Especially, when THF was used, only
half condensation product 2 was obtained in 41% yield
(Figure 1). Compound 2a may be an excellent ligand, be-
cause it was reported the half condensed 2,6-di-i-Pr-
aniline analogous exhibited high activity for ethylene
polymerization.20
However, in most case those halogen substituted 2,6-
bis(imino)pyridines cannot be prepared in the same man-
ner as reported alkyl substituted ones.2,3,5 Moreover, in the
case of the reaction of halogen-substituted aniline with ar-
omatic ketone, it needs much stronger reaction conditions
such as at 210 °C,12 catalyzed by AlCl3, ZnCl2, or p-TsOH
Synlett 2003, No. 10, Print: 05 08 2003.
Art Id.1437-2096,E;2003,0,10,1419,1422,ftx,en;U04103ST.pdf.
© Georg Thieme Verlag Stuttgart · New York

1420
C. Qian et al.
LETTER
Table 1 The Optimization of the Condensation Reaction Conditions
Table 2 Screening of Some Acidic Aluminosilicates
Cat. (8 g/mol)
4 Å MS
F
N
F
N
+
Aniline
N
cat.
N
F
N
F
N
N
+
F
F
Ar
Ar
N
Toluene, 24 h
30~40 °C
solvent, 24 h
O
O
NH2
O
O
1
1 equiv
2.4 equiv
1 equiv
2.4 equiv
Entry Aniline
Catalyst
Yield (%)a
56b
46
Entry Catalyst
Amount
Solvent
T (°C)
Reflux
Reflux
Reflux
30
Yield (%)a
1
2
2-fluoroaniline
Si-Al-135
1
2
3
4
p-TsOH
p-TsOH
HOAc
8 g/mol Toluene
8 g/mol Benzene
13
Si-Al(II)
24
3
Zeolite H-Y
Zeolite H-Beta
Si-Al-135
67
Cat.
Ethanol
None
21
4
36
La(OTf)3
4 Å MS
5 mol% Toluene
5
2,6-difluoroaniline
65c
39
6
Si-Al(II)
5
6
La(OTf)3
4 Å MS
5 mol% THF
30
30
30
30
30
30
30
30
4
9
7
Zeolite H-Y
Zeolite H-Beta
Si-Al-135
52
La(OTf)3
4 Å MS
5 mol% CH2Cl2
5 mol% Toluene
5 mol% Toluene
5 mol% Toluene
8
36
9
2-bromoaniline
75
7
Gd(OTf)3
4 Å MS
44
40
9
10
11
12
Si-Al(II)
24d
29d
33d
8
Yb(OTf)3
4 Å MS
Zeolite H-Y
Zeolite H-Beta
9
Gd(OPf)3
4 Å MS
a Isolated yield.
b Data taken from Table 3.
c Data taken from Table 1.
d Calculated from 1H NMR.
10
11
12
Si-Al-135 80 g/mol Toluene
4 Å MS
65 (64,b
59,c 57d)
Si-Al-135 80 g/mol THF
4 Å MS
0 (41)e
Si-Al-135 80 g/mol CH2Cl2
4 Å MS
13
a Isolated yield.
F
N
b The second run.
N
F
O
c The third run.
d The fourth run.
e Yield of half condensation product 2a.
2a
Figure 1
We also tested three other acidic aluminosilicates of zeo-
lite H-Beta,21a zeolite H-Y21b and Si-Al(II)21c which has
smaller specific surface area than Si-Al-135 (Table 2).
For small steric aniline as 2-fluoroaninline and 2,6-diflu-
oroaninline, there is a trend in the aluminosilicates with
similar structure, the yields of Si-Al-135 and Si-Al(II) in-
crease with the increase of the specific surface area, so do
the yields of zeolite H-Beta and zeolite H-Y. Zeolite H-Y
could give comparative results with Si-Al-135. For larger
steric aniline as 2-bromoaniline, Si-Al(II), zeolite H-Beta
and zeolite H-Y all gave a mixture of mono- and di-con-
densation products with the ratio of 1.20, 0.65 and 0.76
(mono- to di-). While Si-Al-135 could give 75% yield.
These results were directly related to their specific surface
area and pore size.18,21 It is possible that catalysts with
larger speific surface area and pore diameter could give
better results.
A series of ortho-halogen substituted anilines were
screened in the condensation reactions catalyzed by Si-
Al-135 in toluene. In all cases, the reactions proceeded
smoothly to give the corresponding condensation prod-
ucts with satisfactory yields (56–75%) under extremely
mild reaction conditions (Table 2). These results clearly
demonstrate the superiority of Si-Al-135 catalyst support
as the catalyst.
In conclusion, we found silica-alumina catalyst support an
efficient catalyst for condensation reaction of 2,6-, 2,5-,
and 2,4-difluoroaniline or ortho-halogen-aniline with 2,6-
diacetylpyridine to afford the corresponding 2,6-bis(imi-
no)pyridine in good yield. This method also offers the ad-
vantages of mild reaction conditions, using of much less
solvent, and recovering and recycling of the catalyst.
Synlett 2003, No. 10, 1419–1422 © Thieme Stuttgart · New York

LETTER
Silica-Alumina Catalyst Support
1421
Table 3 Preparation of Halogen Substituted bis(Imino)pyridine Catalyzed by Si-Al Support
Cat. Si-Al-135, 4 Å MS
N
+
Aniline
N
N
N
Toluene, 24 h
30~40 °C
Ar
Ar
O
O
1
1 equiv
2.4 equiv
Product (% yield)a
Br
N
Br
Cl
N
Cl
F
N
N
F
N
N
N
N
N
1d
75%
1c
65%
1b
56%
F
N
F
F
I
N
N
I
F
N
F
N
N
N
N
N
F
F
1e
F
1f
72%
64%
1g
70%
F
N
F
N
F
N
F
1a
65%
a Isolated yield.
bis(imino)pyridyl iron complexes, 2,6-bis-diacetyl-
Acknowledgment
pyridinebis(2,6-dibrom-4-methylanil)FeCl2 and 2,6-bis-
diacetyl pyridinebis(2,6-dichloroanil)FeCl2, appeared, but
there was no characterization of the complexes.
Financial support from the National Natural Sciences Foundation
of China and the State Key Project of Basic Research (Project
973, No. G2000048007) is gratefully acknowledged. Many thanks
are due to Prof. Gao Zi of Fudan Univ. for providing us with help-
ful discussions, the catalysts of zeolite H-Y, zeolite H-Beta and
Si-Al(II) and identifying of them.
(8) Chen, Y. F.; Qian, C. T.; Sun, J. Organometallics 2003, 22,
1231.
(9) Sonovskikh, V. Y.; Usachev, B. I.; Röschenthaler, G. V.
Tetrahedron 2002, 58, 1375.
(10) Sevennard, D.; Khomotutov, O.; Koryakova, O.; Sattarova,
V.; Kodess, M.; Stelten, J.; Loop, I.; Lork, E.; Pashkevich,
K. I.; Röeschenthaler, G. V. Synthesis 2000, 1738.
References
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(7) We applied a China patent (CN1322717A) in January 2001.
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Synlett 2003, No. 10, 1419–1422 © Thieme Stuttgart · New York

1422
C. Qian et al.
LETTER
(19) Typical Experimental Procedure: Under an argon
(14) (a) Denmark, S. E.; Rivera, I. J. Org. Chem. 1994, 59, 6887.
(b) Weingarten, H.; Chupp, J. P.; White, W. A. J. Org.
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(15) The condensation reaction of 2,6-dibromoaniline with 2,6-
diacetylpyridine catalyzed by p-TsOH in refluxing toluene,
with removing water by azeotropic distillation gave
corresponding 2,6-bis(imino)pyridine in 58% yield if
purified by recrystallization, However, it gave 30% yield
when purified by flash column. See ref.6
(16) (a) Kobayashi, S. Chem. Rev. 2002, 102, 2227. (b) Ma, Y.;
Qian, C. T.; Wang, L.; Yang, M. J. Org. Chem. 2000, 65,
3864.
(17) Hanamoto, T.; Sugimoto, Y.; Jin, Y. Z.; Inanaga, J. Bull.
Chem. Soc. Jpn. 1997, 70, 142.
(18) Silica-alumina catalyst support (Grade 135) was purchased
from Aldrich. Si/Al = 5.62, its specific surface area is 421.3
m2/g, average pore size 61.0545 Å. In our study, silica-
alumina catalyst support (Grade 135) combined with 4 Å MS
is found to be excellent catalyst for the condensation reaction
of arylaldehydes with anilines, which gave almost
quantitative yield.
atmosphere, a mixture of 2,6-difluoroaniline (0.77 g, 6.0
mmol), 2,6-diacetylpyridine (0.41 g, 2.5 mmol), silica-
alumina catalyst support (0.2 g) and molecular sieves 4 Å
(0.5 g) in 8 mL toluene was stirred at 30–40 °C for 24 h. The
reaction mixture was filtered and the filtration was
condensed in vacuo. Anhydrous MeOH (5 mL) was added to
the residue. A yellow solid was collected by filtration to
yield 1a in 65% yield. 1H NMR (300 MHz, CDCl3): d = 8.39
(d, 2 H, J = 8.0 Hz), 7.93 (t, 1 H, J = 7.9 Hz), 7.07 (m, 4 H,),
6.99 (t, 2 H, J = 7.6 Hz), 2.46 (s, 6 H). IR (KBr): n = 1636,
1576, 1465, 1369, 1277, 1237, 1215, 1126, 1032, 1002, 827,
789, 759 cm–1. MS (EI): m/z 349 (M+). Anal. Calcd for
C21H15F4N3: C, 72.19; H, 4.90; N, 12.03. Found: C, 71.88; H,
4.96; N, 11.96.
(20) Bellabarba, R. M. et al. 20th International Conference on
Organometallic Chemistry, Book of Abstract; Corfu:
Greece, 2002, 230.
(21) (a) Zeolite H-Beta Si/Al = 19.98, specific surface area 554.4
m2/g, average pore size 6.6–6.7, 5.6–5.6 Å. (b) Zeolite H-Y
Si/Al = 3.35, specific surface area 739.3 m2/g, average pore
size 7.4 Å, cage diameter 12 Å. (c) Si-Al(II) Si/Al = 1.0,
specific surface area 240.4 m2/g.
Synlett 2003, No. 10, 1419–1422 © Thieme Stuttgart · New York