Intermolecular cyclization of diethanolamine and methylamine to N,N′-dimethylpiperazine over zeolites under high pressure

Article abstract of DOI:10.1006/jcat.2001.3291

Synthesis of N,N′-dimethylpiperazine via intermolecular cyclization of diethanolamine and methylamine has been investigated under high pressure conditions using zeolites and montmorillonite K10 for the first time. The HZSM-5(30) is particularly effective

Full text of DOI:10.1006/jcat.2001.3291

Journal of Catalysis 202, 430–433 (2001)
doi:10.1006/jcat.2001.3291, available online at http://www.idealibrary.com on
RESEARCH NOTE
Intermolecular Cyclization of Diethanolamine and Methylamine
to N,N0-Dimethylpiperazine over Zeolites under High Pressure
N. Narender, P. Srinivasu, S. J. Kulkarni,1 and K. V. Raghavan
Catalysis Group, Indian Institute of Chemical Technology, Hyderabad-500 007, India
Received February 22, 2001; accepted May 22, 2001
N-methylpiperazine and N,N0-dimethylpiperazine was
<10% at 300 C. The reaction was carried out using a fixed
bed flow reactor system.
Piperazine and substituted piperazines are important in-
termediates in the synthesis of quinoline-type antibacterial
drugs (13). The substituted piperazines are used in the treat-
ment of intestinal worms, e.g., anthelmintics, chemothera-
peutics.
Synthesis of N,N0-dimethylpiperazine via intermolecular cycli-
zation of diethanolamine and methylamine has been investigated
under high pressure conditions using zeolites and montmorillonite
K10 for the first time. The HZSM-5(30) is particularly effective for
N,N0-dimethylpiperazine formation and the catalyst can be reused
c
many times without significant loss of activity.
2001 Academic Press
Key Words: zeolites; cyclization; autogeneous pressure; N,N0-
dimethylpiperazine; autoclave.
A supercritical fluid has liquid-like density and solvation
strength, and it has the ability to homogenize reaction sub-
strates, while possessingtransport properties, i.e., viscosities
and diffusivities, that are more like gases (14, 15). Methy-
lamine has a critical temperature of 156.9 C and a criti-
cal pressure of 73.6 atmosphere both of which are readily
achievable.
INTRODUCTION
The catalytic formation and cleavage of a carbon–
nitrogen (C–N) single bond is of considerable importance
for numerous areas of chemistry because of the ubiquitous
presence of nitrogen-containing compounds in nature. For
example, the catalytic formation of C–N bonds plays a sig-
nificant role in the synthesis of pharmacologically active
molecules (1–6).
N,N0-Dimethylpiperazine was prepared from piperazine
and methanol over H3PO4–SiO2 at 160 C (16), and over
H3PO4–TiO2 at 280 C/13.8 atm (17). In this process
the yield of N,N0-dimethylpiperazine was >80% . N,N0-
Dimethylpiperazine wasalso prepared bycyclodehydration
of HO(CH2)2NHCH3 over activated alumina at 268 C (18),
and over H3PO4–TiO2 at 250–350 C/34.5–138 atm (19).
In this paper, we report for the first time the cy-
clization of diethanolamine and methylamine to N,N0-
dimethylpiperazine over zeolites under high pressure con-
ditions, similar to supercritical conditions with respect to
methylamine. The reaction was carried out in an autoclave
under high pressure in a batch mode in the liquid phase.
We have reported a number of cyclization reactions of C2
to C7 aliphatics in the presence of formaldehyde and am-
monia over modified zeolites (7–11). McAteer and Scriven
(12) published a review on the synthesis of N-heterocyclics.
In the reaction of ethanol, or acetaldehyde in the pres-
ence of formaldehyde and ammonia over zeolites, pyri-
dine and picolines were formed. Products such as 3,5-
and 2,6-lutidines were formed from propanol, isopropanol,
or propionaldehyde in the presence of formaldehyde and
ammonia. Collidines were obtained from 2-butanol and
methyl ethyl ketone. These heterocyclics are intermedi-
ates in the synthesis of drugs and agrochemicals. In the
reaction of diethanolamine and methylamine over zeolites,
N-methylpiperazine was formed at 30–80 H2 atm pressure
and 250–350 C (11). The yield of N-methylpiperazine was
>90% at 300 C and 30–80 H2 atm pressure over HZSM-5
(SiO2/Al2O3 = 30). At atmospheric pressure the yield of
EXPERIMENTAL
Synthesis of N,N0-Dimethylpiperazine
Catalyst (15 g, 20 wt% ), diethanolamine (71.88 ml,
0.75 mol) and 30% methylamine (129.125 ml, 1.5 mol) were
placed (loaded) in a 500-ml (capacity) stainless steel auto-
clave at room temperature. The autoclave was sealed and
the temperature was increased to 300 C under stirring
(autogeneous pressure 100 atm). Agitation was main-
tained at this temperature for 10 h. After completion
1 To whom correspondence should be addressed. Fax: 0091-40-
7173387/7173757. E-mail: sjkulkarni@iict.ap.nic.in.
430
0021-9517/01 $35.00
c
Copyright
2001 by Academic Press
All rights of reproduction in any form reserved.

INTERMOLECULAR CYCLIZATION OF DIETHANOLAMINE AND METHYLAMINE
431
TABLE 2
of the reaction, the temperature was cooled down to
room temperature, the pressure was released slowly. When
atmospheric pressure was reached, the autoclave was
opened, the reaction mixture was filtered, and the prod-
0
Synthesis of N,N -Dimethylpiperazine over Molecular
Sieves and a Clay
Reactiona
temp.
( C)
Conversion of
Time diethanolamine Yieldb
1
uct N,N0-dimethylpiperazine was identified by H NMR
and GC/mass spectroscopy and quantified by GC.
Entry
Catalyst
(h)
(% )
(% )
RESULTS AND DISCUSSION
1.
2.
3.
4.
5.
6.
HZSM-5(30)
HZSM-5(280)
H-Mordenite
HY
Montmorillonite K10
—
300
300
300
300
300
300
10
10
10
10
10
10
96
84
72
46
88
78
68.0
36.0
33.0
9.3
28.0
8.6
The reaction of diethanolamine and methylamine was
carried out over HZSM-5 (30) in the 200–300 C tempera-
ture range in an autoclave. The results are given in Table 1.
The yields of N,N0-dimethylpiperazine were 40.5, 65.0, and
68% with conversions >90% at 290, 296, and 300 C reac-
tion temperatures and 30–100 atm autogeneous pressure,
respectively in autoclave (batch mode). The highest yield
was obtained at 300 C. On the other hand, the yield of
N,N0-dimethylpiperazine was<10% at 66atm pressure and
285 C, when the reaction was carried out using water as a
solvent and not under supercritical conditions. The stoi-
chiometry of the reaction may be represented by the fol-
lowing equation:
a Autogeneous pressure = 100 atm.
b Yield of N,N0-dimethylpiperazine based on diethanolamine.
Table 2. Thus, HZSM-5 (30) was the best catalyst among
the various zeolites in the cyclization reaction under iden-
tical reaction conditions.
The effect of the molar ratio of diethanolamine and
methylamine was studied over HZSM-5 (30) and the results
are given in Table 3. Best yieldsof N,N0-dimethylpiperazine
were 68.0 and 70.0% for 2.0 and 3.0 molar ratios of di-
ethanolamine and methylamine, over HZSM-5 (30) at
300 C reaction temperature, respectively.
Similarly the weight of the catalyst was varied and the
yields of N,N0-dimethylpiperazine varied from 9–68% for
0 to 20% of the HZSM-5 (30) (Table 4). Thus, HZSM-5 (30)
showed high activity over a wide range of experimental con-
ditions. The Brønsted acidic centers present at the channel
intersections are assumed to be the active centers in this
reaction. Therefore, HZSM-5 (30) showed higher activity
than HZSM-5 (280). A tentative mechanism for the forma-
tion of N,N0-dimethylpiperazine is shown in Scheme 2.
The high yields under high pressure similar to the super-
critical conditions with respect to methylamine are mainly
due to the drastic increase in the reactive collisions and
miscibility. The selectivity is also strongly influenced by the
SCHEME 1
The reaction of diethanolamine and methylamine
(1 : 2 molar ratio) was carried out at 300 C and 100 atm
autogeneous pressure over several solid acid catalysts in au-
toclave (batch mode). The weight ofthe catalyst was20wt%
with respect to the weight of the diethanolamine. The
yields of N,N0-dimethylpiperazine were 68.0, 36.0, 33.0, 9.3,
and 28.0 over HZSM-5 (30), HZSM-5 (280), H-mordenite,
HY, and montmorillonite K10, respectively, as given in
TABLE 1
TABLE 3
0
0
Synthesis of N,N -Dimethylpiperazine over HZSM-5(30):
Synthesis of N,N -Dimethylpiperazine over HZSM-5(30):
Effect of Temperature
Effect of Molar Ratio
Reaction
temp.
( C)
Autogeneous
pressure
Conversion of
diethanolamine
(% )
Reaction
temp.
( C)b
Conversion of
diethanolamine
(% )
Time
(h)
Yielda
(% )
Mol. ratioa
DEA : MA
Time
(h)
Yieldc
(% )
Entry
(Atm.)
Entry
1.
2.
3.
4.
5.
6.
200
250
270
290
296
300
32
59
80
90
95
10
10
10
10
10
10
5
22
41
90
93
96
0.0
0.0
10.3
40.5
65.0
68.0
1.
2.
3.
4.
1 : 1
1 : 1.5
1 : 2
300
300
300
300
10
10
10
10
90
95
96
95
37
45
68
70
1 : 3
a DEA : MA, diethanolamine : methylamine.
100
b Autogeneous pressure = 100 atm.
a Yield of N,N0-dimethylpiperazine based on diethanolamine.
c Yields of N,N0-dimethylpiperazine based on diethanolamine.

432
NARENDER ET AL.
SCHEME 2
reactor design. We also studied the reduction in the
TABLE 4
coke deposit, i.e., deactivation of the catalyst. The strat-
egy is presently being extended to other cyclization reac-
tions.
0
Synthesis of N,N -Dimethylpiperazine over HZSM-5(30):
Effect of Amount of Catalyst
Amount of
catalyst
(wt% )
Reaction
temp.
( C)a
Conversion of
diethanolamine
(% )
Time
(h)
Yieldb
(% )
CONCLUSIONS
Entry
The present study demonstrates the potential of HZSM-
5 (30) catalyst (zeolite) exercising a unique activity in the
synthesisofN,N0-dimethylpiperazine via intermolecular cy-
clization of aliphatic compounds. The catalyst can be reused
without any loss of activity, when the reaction was carried
out in liquid phase, batch mode in an autoclave. It is in-
teresting to note that the selectivity and/or the nature of
1.
2.
3.
4.
5.
—
2.5
5
10
20
300
300
300
300
300
10
10
10
10
10
78
83
85
90
96
9
32
41
46
68
a Autogeneous pressure = 100 atm.
b Yields of N,N0-dimethylpiperazine based on diethanolamine.

INTERMOLECULAR CYCLIZATION OF DIETHANOLAMINE AND METHYLAMINE
433
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ACKNOWLEDGMENTS
We are thankful to Department of Science and Technology, New Delhi
for funding (DST Project No. SP/S1/H07/97). P.S. thanks CSIR, New Delhi,
for the award of a fellowship (IICT Communication No. 4599).
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Heterogeneous Catalysis” (R. A. Sheldon and H. van Bekkum, Eds.),
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University Press, London, 1998.
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