Synthesis of pyrazinyl compounds from glycerol and 1,2-propanediamine over Cu-TiO2 catalysts supported on γ-Al2O3

Article abstract of DOI:10.1016/j.cclet.2013.04.010

Cu-TiO₂ catalysts supported on γ-Al₂O ₃ are prepared and used in glycerol cyclization with 1,2-propanediamine to produce pyrazinyl compounds including 6-hydroxymethyl-2- methylpyrazine, 5-hydroxymethyl-2-methylpyrazine, 2,6-dimethylpyrazine and 2,5-dimethylpyrazine in a fixed-bed system. It is found that glycerol cylclization with 1,2-propanediamine gave a high total yield of pyrazinyl compounds (>80%) over Cu-TiO₂/γ-Al₂O₃ catalyst, and cyclization was through the reactions between activated 1,2-propanediamine and the intermediates from glycerol dehydration and oxidation. In addition, the regioselectivity of the pyrazinyl compounds was mainly controlled by the steric hindrance of the substrates during the cyclization process.

Full text of DOI:10.1016/j.cclet.2013.04.010

Chinese Chemical Letters 24 (2013) 751–754
Contents lists available at SciVerse ScienceDirect
Chinese Chemical Letters
journal homepage: www.elsevier.com/locate/cclet
Original article
Synthesis of pyrazinyl compounds from glycerol and 1,2-propanediamine over
Cu–TiO2 catalysts supported on g-Al2O3
Xue Li a, Cheng-Hua Xu a, , Chuan-Qi Liu a,b, Yu Chen a, Jian-Ying Liu a
*
a Air Environmental Modeling and Pollution Controlling Key Laboratory of Sichuan Higher Education Institutes, Chengdu University of Information Technology, Chengdu 610225, China
b College of Optoelectronic Technology, Chengdu University of Information Technology, Chengdu 610225, China
A R T I C L E I N F O
A B S T R A C T
Article history:
Cu–TiO2 catalysts supported on
g-Al2O3 are prepared and used in glycerol cyclization with 1,2-
Received 26 February 2013
Received in revised form 2 April 2013
Accepted 3 April 2013
propanediamine to produce pyrazinyl compounds including 6-hydroxymethyl-2-methylpyrazine, 5-
hydroxymethyl-2-methylpyrazine, 2,6-dimethylpyrazine and 2,5-dimethylpyrazine in a fixed-bed
system. It is found that glycerol cylclization with 1,2-propanediamine gave a high total yield of pyrazinyl
Available online 10 May 2013
compounds (>80%) over Cu–TiO2/g-Al2O3 catalyst, and cyclization was through the reactions between
activated 1,2-propanediamine and the intermediates from glycerol dehydration and oxidation. In
addition, the regioselectivity of the pyrazinyl compounds was mainly controlled by the steric hindrance
of the substrates during the cyclization process.
Keywords:
Catalytic cyclization
Glycerol
ß 2013 Cheng-Hua Xu. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights
reserved.
Alkyl-substituted pyrazines
Steric effect
1. Introduction
2. Experimental
Pyrazinyl compounds such as pyrazine and alkyl-substituted
pyrazines are widely used as intermediates for the production of
perfumes, medicines and agricultural chemicals. 2-Methylpyra-
Cu–TiO2/
g
-Al2O3 (CxTyA, where x and y represented the weight
-Al2O3
content of the introduced TiO2 and metal Cu relative to the
g
support, respectively) catalysts were prepared through fractional
impregnation by using tetrabutyltitanate and Cu(NO3)2Á3H2O as
precursors, respectively. After calcination at 400 8C in air, the
obtained catalysts were characterized by X-ray powder diffraction
(XRD) on a DX-2700 powder diffractometer with Cu K
NH3-temperature programmed desorption (NH3-TPD) and H2-
temperature programmed reduction (H2-TPR) on TP-5080
adsorption instrument, respectively. GL cyclization with PDA
was carried out at 380 8C with a feeding rate of liquid reactant with
a GL:PDA:H2O molar ratio of 1:1:8.84 being 1.5 hÀ1 in a fixed-bed
quartz tubular reactor. Prior to catalyst testing, the catalysts were
on-line pretreated by H2. The collected liquid mixture were
analyzed by a GC-2000 gas chromatograph (GC) equipped with a
zine as
a key intermediate for pyrazineamide, an effective
antitubercular drug, has been successfully synthesized by a
cyclization reaction between ethylenediamine (EDA) and propa-
nediol [1–3]. Recently, it has been found that glycerol (GL) can also
be used as a raw material providing two –OH groups to react with
EDA through a cyclization reaction to form a 2-hydroxymethyl
pyrazine intermediate, which is easily converted to 2-MP through
a hydrodehydration reaction of one of the –CH2OH groups along
with the production of H2 [4,5]. Similarly, 1,2-propanediamine
(PDA) containing two –NH2 groups can also react with GL to form
6- or 5-hydroxymethyl-2-methylpyrazine (6-HMP or 5-HMP) and
even 2,6- or 2,5-dimethylpyrazine (2,6-DMP or 2,5-DMP). Of
course, it is important to choose a catalyst capable of activating
both the –NH2 group in PDA and the –OH group in GL
simultaneously. Along this line of reasoning, the present work
a radiation,
a
DB-WAXETR (50 m  0.32 mm  1.00
mm, Agilent, USA) capillary
column and a flame ionization detector. The produced pyrazinyl
compounds and unconverted raw materials were identified by the
GC retention time of the corresponding standard reagents, and
their contents were quantified using the corresponding GC peak
areas and correction factors.
introduces Cu0 and an acidic species TiO2 to the
g-Al2O3 support to
produce bifunctional catalysts that catalyze the GL vapor-phase
cyclization reactions with PDA in a fixed-bed system.
3. Results and discussion
From Table 1, it can be clearly observed that PDA cyclization
with GL over typical catalysts certainly produces four important
* Corresponding author.
E-mail address: xch@cuit.edu.cn (C.-H. Xu).
1001-8417/$ – see front matter ß 2013 Cheng-Hua Xu. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
http://dx.doi.org/10.1016/j.cclet.2013.04.010

752
X. Li et al. / Chinese Chemical Letters 24 (2013) 751–754
e
Table 1
Catalytic properties of typical catalysts in cyclization.a
Catalyst
Conversion
(mol%)
Yield of target products (mol%)
PDA
GL
2,6-DMP
2,5-DMP
6-HMP
5-HMP
g
T7A
-Al2O3
96.4
85.6
87.5
86.9
83.1
94.1
94.9
92.1
94.8
93.5
21.4
33.2
34.5
37.6
31.8
10.5
45.2
44.2
41.3
39.8
6.2
5.5
4.6
4.5
8.8
8.4
0.4
1.2
1.4
1.2
C5A
C5T7A
C5T21
A
Scheme 1. Formation of pyrazinyl compounds from GL and PDA.
a
20%H2–N2 mixture as carrier gas (SV 1200 hÀ1).
[(Fig._1)TD$FIG]
studied first. The results show that all catalysts with a variety of
different Cu contents (from 1 wt% to 6 wt%) give high PDA and GL
conversions of about 85% and 95%, respectively. However, an
increase of 6-Pys formation and a decrease of 5-Pys formation are
found as shown in Fig. 1 when Cu content increases from 0 to
2 wt%, but a reverse trend is observed as the Cu content further
increases. XRD patterns (Fig. 2) indicate that the supported Cu
species are highly dispersed and TiO2 is in the form of anatase
phase. H2-TPR results show that Cu species can be converted to Cu0
during the catalyst pretreatment with H2 at 420 8C. According to
our previous studies [6], Cu0 sites can catalyze the hydrodehydra-
tion reactions of alcohols. GL dehydration possibly leads to acetol
formation [7], which can be improved by H2 in carrier gas. Of
course, the acidic sites are also known catalytic centers for the
dehydration of alcohols [8]. Thus, GL cyclization with PDA is
conceivably through the pathway as shown in Scheme 1(a).
The carbonyl group in acetol easily reacts with the terminal –
NH2 group in PDA to form selectively 2,5-DMP due to steric effect.
But the terminal –NH2 can be adsorbed on the acidic sites of
catalysts, leading to a facile reaction between acetol and the 2-NH2
group in PDA to form 2,6-DMP. The increase on Cu content will
accelerate the acetol formation, which is helpful to the 2,6-DMP
formation. However, increase of Cu species will reduce acidic sites
(Fig. 3a), thus favors the 2,5-DMP formation. Clearly, GL can also be
converted to dihydroxylpropanal (DHP) over Cu0 or other active
sites through dehydrogenation [9], which will result in the
formation of 6- and 5-HMP as shown in Scheme 1(b). Incidentally,
DMP can also be derived from HMP hydrodehydration.
46
44
42
40
38
36
6-Pys yield
5-Pys yield
6-HMP yield
5-HMP yield
8
6
4
2
0
0
1
2
3
4
5
6
Cu content in CTA /wt%
Fig. 1. Effect of Cu content on property of CxT7A catalysts in cyclization in 20%H2–N2
mixture. 6-Pys: 6-HMP and 2,6-DMP; 5-Pys: 5-HMP and 2,5-DMP.
pyrazinyl compounds, namely 2,6-DMP, 2,5-DMP, 6-HMP and
5-HMP. However,
compounds (only 46.5%) is obtained, although conversions of
both GL and PDA are very high over -Al2O3.The total yield of the
four products reaches up to 81.6% over Cu, TiO2 or Cu–TiO2
catalysts supported on -Al2O3. -Al2O3 gives some side-products,
but the presence of Cu and/or TiO2 species can improve the PDA
cyclization with GL. Moreover, it can be found that the total yield of
four products over four catalysts except
conversion, indicating that the side reactions over these catalysts
are mainly derived from GL molecules.
In order to investigate the role of Cu and TiO2 species, the effect
of Cu content on the catalytic properties of CTA catalysts (TiO2
content = 7 wt%) in the cyclization reaction between GL and PDA is
a low total yield for the four pyrazinyl
g
g
g
The effects of TiO2 content in the C2TyA catalyst (2 wt% Cu) on
the condensation between GL and PDA (Fig. 4) to produce of 5- or
6-HMP are negligible, but the formation of 5- and 6-DMP strongly
depends on the TiO2 content. This is possibly a result ofthe
production of more acid sites due to the presence of TiO2 species,
which is consistent with the NH3-TPD results (Fig. 3b). Acidic sites
provide catalytic centers for GL hydration to form acetol, also
g-Al2O3 is near PDA
[(Fig._2)TD$FIG]
anatase TiO2
CuO
(a)
(b)
Anatase TiO2
r-Al2O3
r-Al2O3
C6T7A
C4T7A
C2T17A
C2T12A
C2T7A
C1T7A
C0T7A
C2T7A
C2T2A
20
30
40
50
60
70
80
20
30
40
50
60
70
80
/(o)
2
/(o)
2
Fig. 2. XRD patterns of CxT7A catalysts (a) and C2TyA catalysts (b).

[
X. Li et al. / Chinese Chemical Letters 24 (2013) 751–754
753
(a)
(b)
C2T17A
C2T12A
C2T7A
C2T2A
C1T7A
C2T7A
C4T7A
C6T7A
0
100
200
300
400
500
600
700
800
0
100
200
300
400
500
600
700
800
Heating temperature /oC
Heating temperature /oC
Fig. 3. NH3-TPD profiles of Cu–TiO2/g-Al2O3 catalysts with different Cu content (a) and different TiO2 content (b).
[(Fig._4)TD$FIG]
Table 2
46
44
42
40
38
36
34
32
GL cyclizaion with PDA on C2T7A in different carrier gas.
Carrier gas
Conversion
(mol%)
Yield of target products (mol%)
PDA
GL
2,6-DMP
2,5-DMP
6-HMP
5-HMP
5%O2–N2
N2
64.0
76.5
85.3
84.8
86.8
85.2
82.8
89.5
89.8
94.5
93.2
95.6
92.4
94.7
37.2
40.9
43.6
43.9
43.6
43.6
43.5
17.5
17.9
30.1
36.8
38.2
37.2
37.6
2.8
8.5
8.2
2.2
2.7
2.4
2.6
3.0
7.3
2.1
2.2
1.1
1.0
1.5
5%H2–N2
10%H2–N2
20%H2–N2
30%H2–N2
50%H2–N2
6-DMP yield
5-DMP yield
6-HMP yield
5-HMP yield
30
9
6
3
0
It is possible that it is more difficult for GL to undergo a
hydrodehydration reaction to form acetol in non-reductive gas. In
addition, the yield of 2,6- and 2,5-DMP is also found to increase in
reductive gas. These results suggest that the intermediate from GL
is from a dehydration reaction.
0
3
6
9
12
15
18
21
TiO2 content /wt%
The present work also investigates the catalytic stability of the
Cu–TiO2/g-Al2O3 catalyst (C2T7A) in the cyclization reaction of GL
Fig. 4. Effect of TiO2 content on property of C2TyA catalysts in cyclization using
20%H2–N2 mixture as carrier gas (SV 1200 hÀ1).
and PDA. From the results shown in Fig. 5, it can be observed that the
present catalyst exhibitsaslightdecreaseonPDA conversionandthe
total yield of 2,5- and 2,6-DMP during the 10 h of time-on-stream,
promote the activation of the terminal –NH2 group in PDA through
adsorption. Thus the 6-DMP formation is improved. But too many
acid sites (higher TiO2 content) will lead to the double GL
dehydration to produce acrolein [8,10], which is also detected by
on-line GC analysis. This will be inhibit the 6-DMP formation, but
the formation of 5-DMP can readily occur through the pathway as
shown in Scheme 2. This is because the 2-NH2 group in PDA is more
reactive due to the fact that the terminal –NH2 is adsorbed on
acidic sites.
Table 2 lists the results of the cyclization reaction between GL
and PDA in different reaction gas over the Cu–TiO2/g-Al2O3 catalyst
with Cu and TiO2 content of 2 wt% and 7 wt%, respectively. It can be
clearly seen that the PDA conversion in non-reductive gas is low
(<80%), but is increased when introducing H2 into the reaction gas.
[F(ig._5)TD$FIG]
100
90
80
70
60
50
40
30
20
10
0
GL conversion
PDA conversion
Total yield of 2,6- and 2,5-DMP
Total yield of 6- and 5-HMP
[(Scheme_2)TD$FIG]
0
5
10
15
20
25
30
35
40
Time-on-stream /h
Scheme 2. 2,5-DMP formation through acrolein and PDA on acid sites.
Fig. 5. Effect of time-on-stream on GL cyclization with PDA over C2T7A as catalyst.

754
X. Li et al. / Chinese Chemical Letters 24 (2013) 751–754
References
butnoobviousdecreaseisfoundafterthat.Itshowsthatthecatalytic
stability is good under reaction conditions.
[1] J. Basak, N. Hardia, S. Saxena, et al., Vapor-phase catalytic synthesis of 2-methyl-
pyrazine over a nanocrystalline ferrite catalyst, Ind. Eng. Chem. Res. 46 (2007)
7039–7044.
[2] F.L. Jing, W. Chu, Y.Y. Zhang, Y.Q. Chen, S.Z. Luo, Synthesis of 2-methylpyrazine
from cyclocondensation of ethylene diamine and propyele glycol over promoted
copper catalyst, Chin. Chem. Lett. 19 (2008) 752–755.
4. Conclusion
Cu–TiO2/g-Al2O3 catalysts exhibit bifunctional catalytic
[3] I. Park, J.H. Lee, Y.Y. Rhee, Y.H. Han, H.R. Kim, CuO/ZnO/SiO2 catalysts for
cyclization of propyleneglycol with ethylenediamine to 2-methylpyrazine, Appl.
Catal. A 253 (2003) 249–255.
[4] R. Sarkari, C. Anjaneyulu, V. Krishna, et al., Vapor phase synthesis of methylpyr-
azine using aqueous glycerol and ethylenediamine over ZnCr2O4 catalyst: eluci-
dation of reaction mechanism, Catal. Commun. 12 (2011) 1067–1070.
[5] C.Q. Liu, C.H. Xu, T.W. Xia, Y. Guo, J.Y. Liu, Glycerol catalytic cyclocondensation
with ethanediamine to pyrazinyl compounds over the modified SiO2–Al2O3,
Heteroatom Chem. 23 (2012) 377–382.
[6] C.H. Xu, L.K. Zheng, D.F. Deng, J.Y. Liu, S.Y. Liu, Effect of activation temperature on
the surface copper particles and catalytic properties of Cu–Ni–Mg–Al oxides from
hydrotalcite-like precursors, Catal. Commun. 12 (2011) 996–999.
[7] Z.L. Wang, Q.S. Liu, J.F. Yu, T.H. Wu, G.J. Wang, Surface structure and catalytic
behavior of silica-supported copper catalysts prepared by impregnation and sol–
gel methods, Appl. Catal. A 239 (2003) 87–94.
properties in the cyclization reaction of glycerol with 1,2-
propanediamine to produce pyrazinyl compounds. Cu0 centers
catalyze the formation of intermediates from glycerol by
dehydrogenation or hydrodehydration, and acidic sites exhibit
catalytic activity for the 1,2-propanediamine activation and
glycerol dehydration. The cyclization reactions appear to occur
between activated 1,2-propanediamine and the intermediates
from glycerol.
Acknowledgments
This work is supported financially by the Youth Science &
Technology Foundation of Sichuan Province in China (No.
2012JQ0047) and Development foundation from Air Environmen-
tal Modeling and Pollution Controlling Key Laboratory of Sichuan
Higher Education Institutes (No. ZZKT2012003).
[8] A. Ulgen, W.F. Hoelderich, Conversion of glycerol to acrolein in the presence of
WO3/TiO2 catalysts, Appl. Catal. A 400 (2011) 34–38.
[9] M. Campanati, A. Vaccari, O. Piccolo, Environment-friendly synthesis of nitrogen-
containing heterocyclic compounds, Catal. Today 60 (2000) 289–295.
[10] J. Feng, J.B. Wang, Y.F. Zhou, et al., Effect of base additives on the selective hydro-
genolysis of glycerol over Ru/TiO2 catalyst, Chem. Lett. 36 (2007) 1274–1275.