S Y N T H E S I S OF P Y R A Z I N E S Cycloamination of Alkanolamines W. K. LANGDON, W. W. LEVIS, JR., D.R. JACKSON, MOSES CENKER, AND G . E. B A X T E R Wjandotte Chemicals Cor@., Wyandotte, Mich. Liquid- and vapor-phase continuous processes for converting isopropanolamine ( 1 -amino-2-propanol) to 2,5-dimethylpyrazine and 2,5-dirnethylpiperazine were investigated. A liquid-phase process employing a supported 65% nickel catalyst resulted in a combined conversion to 2,5-dimethylpiperazine and 2,5dimethylpyrazine of about 7070,but could not b e controlled to give either product consistently as the major product. At low temperatures, while the catalyst was relatively fresh, 2,5-dimethylpiperazine was the major product; a t higher temperatures and/or with older catalyst, 2,5-dimethylpyrazine was the major product. Several commercial fixed-bed catalysts were evaluated for converting isopropanolamine to 2J-dimethylpyrazine. Copper chromite was selected for further study. A commercially feasible vapor-phase process based on copper chromite as the catalyst consistently gave about 65% conversion of isopropanolamine to 2,5-dimethylpyrazine and 10% to 2,5-dimethylpiperazine.
presence of hydrogenation-dehydrogenation catalysts, such as isopropanolamine (1-amino-2propanol) will react in a bimolecular manner to form piperazines and pyrazines under either liquid-phase or vapor-phase conditions, and by batch or continuous processes : N THE
I alkanolamines
H N
/ \
HzC
CHCHs
I
I
f"'
H3CHC
CH2
+ 2 HzO
H
OH 2 CH3CH-CH2NH2 I
/
I/
H3CC
I
CH
+2H20+3HzT
These processes and related cycloamination reactions have resulted in commercially feasible processes for preparing these difunctional products from such readily available raw materials as propylene oxide and ammonia or alkylene amines. Several piperazines became available a few years ago, and new uses are continually being found in such applications as polyurethanes (3, 8 ) : polyamides (5): corrosion inhibitors (70), and intermediates for pyrazines ( 2 ) . In a previous study of the effect of reaction variables in a liquid-phase batch process for making 2,5-dimethylpiperazine from isopropanolamine (7), high yields of predominantly trans isomer were obtained by heating isopropanolamine for several hours at a hydrogen pressure of about 1200 p.s.i.g. a t 220' C. in the presence of Raney nickel. Bain and Pollard 8
I&EC
(7) prepared 2,5-dimethylpiperazine by heating isopropanolamine in dioxane as a solvent in the presence of copper chromite at 270"-5' C. More recently Japanese researchers have been investigating this and other cycloamination reactions (4,9). The results of studies of continuous methods for cycloaminating isopropanolamine over fixed beds of nickel, copper chromite, and other catalysts are reported here. The work has led to a commercially practical method for preparing 2,5dimethylpyrazine (6).
PRODUCT RESEARCH A N D DEVELOPMENT
Figure A. B. C. D. E.
F. G. H. I.
1. K. 1.
M. N. 0.
1.
Reactor
system
Graduated feed reservoir Pump G a s inlet Dowtherm heated reactor Inert packing (preheat) Thermocouple wells To condenser Catalyst section Inert packing Safety valve and g a g e Dawlherm condenser Dowtherm pressure g a g e Safety h e a d Sight glass Buret
CATALYST. HARSHAW'S Nl-0104 T 1/8" FEED RATE: 0.5 g. ISOPROPANOLAMINE/g. CAWHR
60 I
2
8
10
-
1
1
1
'
1
II O'
IO0
300
500 PRESSURE,
I
I I
I
800
,I
k-
,
'0,
I 1 ,
p 1
I
RSIG.
Figure 2. Effects of temperatures and pressures in liquid-phase cycloarnination
Apparatus
The reactor system (Figure 1) consists of a metering pump for delivering reactant continuously at a fixed measurable rate, a preheater section, a heated catalyst chamber, and a condenser system. The reactor, D,consists of a 1-inch steel pipe 72 inches long surrounded by a 60-inch Dowtherm jacket. Heat is supplied by Chromel-ribbon heating elements and the reactor is insulated with magnesia lagging. The level of the Dowtherm used as the heat transfer medium is adjusted to be above the catalyst bed, H. The electrical heating elements located below the Dowtherm level are used to boil the Dowtherm, the corresponding pressure being measured on the pressure gage, L. Dowtherm vapor is condensed by the condenser, K , and returned to the jacket through the sight glass, IV. Emergency protection against excessive pressure is provided by the safety head, M . The temperatures of the Dowtherm liquid and vapor, and the temperatures throughout the reactor section are measured by thermocouples at three sites, F. I n addition to the inlet for liquid feed at the top of the reactor, a second inlet for gases, C, is provided. The feed system consists essentially of a graduated feed reservoir, A , and a proportioning pump, B, for delivering the liquid feed to the top of the reactor. The buret, 0 , is used to calibrate the feed rate. By closing the valve at the bottom of the reservoir and feeding from the buret, 0, accurate volume readings can be obtained. A mercury manometer, J , attached to the feed line measures the back pressure in the system and also serves as a safety head. Several accessory pieces of equipment are: a wet-test meter used to measure noncondensable off-gases, a potentiometer for reading temperature, a Variac (1.5 kv.-amp.) to control the heat input to the reactor, a pressure-release valve in the line between the pump and the reactor, and flowmeters and gas cylinders (hydrogen and nitrogen) used in the reduction of the catalyst. Although the Dowthem-heated reactor described above was the preferred form finally developed, in some of the experiments an electrically heated core furnace was used.
An aliqdot of the crude furnace effluent was charged to a distilling flask along with sufficient water to remove 2,5dimethylpyrazine completely as a water azeotrope that contains about 35y0 of dimethylpyrazine and boils at 98' C. The products were distilled through a 0.9- X 120-cm. column containing a 9-mm. spiral of No. 14 wire at a reflux ratio between 2 : l and 5 : l . The remaining water was removed by distillation up to a head temperature of 115' C. The dimethylpiperazine fraction, which also contained any unconverted isopropanolamine, was then collected over the range of 155' to 170' C. 2,5-Dimethylpyrazine was determined by ultraviolet absorption analysis. 2,5-Dimethylpiperazine and isopropanolamine were determined by potentiometric titration. 2?5-Dimethylpiperazines have break points in the potentiometric curve a t p H 7.5 and 3.5. The isopropanolamine content was calculated on the basis of the total acid required, and acid required to titrate to the first break point in pH. liquid-Phase Continuous Cycloamination
Conversion and yields to 2,5-dimethylpiperazine and 2,5dimethylpyrazine as used in this discussion, have the following meanings :
yo conversion
=
moles product X 2 X 100 moles isopropanolamine charged
yo yield
=
moles product X 2 X 100 moles isopropanolamine charged - moles of recoverable isopropanolamine
Data on a series of runs made to determine the gross effects of temperature and pressure on the liquid phase conversion of isopropanolamine to cyclic products are shown in Figure 2. Isopropanolamine was fed over a 1- X 18-inch bed of pelletized l/8- X ',&inch nickel-on-kieselguhr catalyst (obtained from
Table I.
Analysis of Products
The boiling and melting points of isopropanolamine and reaction products are given in Table I. Since the boiling points of the raw material and products are so close, simple fractional distillation was not a practical method of separation. An azeotropic method was developed for separating dimethylpyrazine from other products.
a
Boiling and Melting Points
Boilinga Point, O C.
M e l t inga Point, C.
trans-2,5-Dimethylpiperazine cis-2,5-Dimethylpiperazine
160 162
2,5-Dimethylpyrazine Isopropanolamine
153 159
118 18 15 1
Uncorrected.
VOL. 3
NO. 1 M A R C H 1 9 6 4
9
CATALYST: HARSHAW'S Cu -0203 T 1/8" FEED RATE, 0 5 g ISOPROPANOLAMINE/g
90
m
225
catalyst. This change is very apparent during the periods of longer operation at a fixed temperature-for example, 90 hours of operation a t 180' C. and 50 hours at 185' C. Initially, approximately three times as much 2,5-dimethylpiperazine as 2,5-dimethylpyrazine was produced ; a t The encrofthe run this had changed to 11/2 times as much 2,5-dimethylpyrazine as 2,5-dimethylpiperazine. The change in ratio of products is believed to be due to a loss in ability of the catalyst to function as a hydrogenation catalyst while still maintaining activity as a dehydrogenation catalyst. Regardless of the final product, the first step in the reaction is believed to be dehydrogenation and dehydration to form a cyclic di-Schiff base. This condensation probably proceeds
CAT/HR
275
250
TEMPERATURE, "C.
Figure 4. Effect of temperature in vapor-phase cycloamination
80 -
n
60.
m
0
A
A
\
o 0
A
0
0
A
A/
CONVERSION
TO DIMETHYLPYRAZINE
40-
n.
20 -
CONVERSION
10
0
U
TO Y
DIMETHYLPIPERAZINE
\"
0
n
H
through the formation of aminoacetone by the dehydrogenation of isopropanolamine. If further dehydrogenation occurs, dimethylpyrazine is produced or if hydrogenation takes place, the product is dimethylpiperazine. At lower temperatures with fresh catalyst the favored reaction is hydrogenation; at higher temperatures and/or with aged catalyst, it is dehydrogenation. Harshaw Chemical Co.) a t a rate of 0.5 gram per gram of catalyst per hour. The pressure was varied between 50 and 800 p.s.i.g., and the temperature was varied between 130' and 180' C. At each temperature an increase in pressure suppresses conversion to cyclic products. The best conversion (about 80%) was achieved at a temperature of 165' C. and a pressure of 100 p.s.i.g., the lowest pressure tested at this temperature.
Vapor-Phase Continuous Cycloarnination
Since liquid-phase studies showed that the conversions to 2,5-dimethylpyrazine were highest at low pressures and a t temperatures above the atmospheric boiling points of the reactant and products, developing a vapor-phase process for making 2,5-dimethylpyrazine appeared to be possible. A survey was made of the activity of several types of catalysts for converting isopropanolamine to 2,5dimethylpyrazine under vapor-phase conditions a t varied temperatures. Nickel catalyst, which had been effective in liquid-phase reactions, was tested along with copper chromite and several other metal compounds which might have catalytic activity. Data on the activity of several commercially available copper, nickel, cobalt, zinc, and vanadium catalysts are shown in Table 11. All catalysts except those containing copper were used as received. Copper catalysts were prereduced with hydrogen prior to usc: (2). Under the conditions tested the nickel and copper chromite catalysts, supplied by Harshaw Chemical Co., were both effective in the vapor-phase reaction and gave conversion of more than 60% to cyclics and more than 50% to
The results of a study made to determine the effect of temperature over the range of 165' to 190' C. at the approximate minimum pressure necessary to maintain the reactants in a liquid state, are given in Figure 3. The initial conditions selected for the continuous run of 278 hours' duration were 165' C. a t a hydrogen pressure of 30 p.s.i.g. Periodically, the temperature was raised in 5' C. increments and, the pressure was raised 10 p.s.i.g. to compensate for the increase in vapor pressure. The conversion to cyclics remained fairly constant, a t approximately 70%. The most significant change was the inversion in the ratio of dimethylpiperazine and dimethylpyrazine produced. The proportion of dimethylpyrazine increased with increased temperature and with age of the
Table II.
Catalyst Survey
Copper Chromite, Nickel, Ni 0104
Temperature, C . Conversion to 2,5-dimethylpyrazine, % Conversion to 2,5-dimethylpiperazine, 70 Unreacted isopropanolamine, 70 O
10
200 52 11
3
225
41 15 3
l & E C P R O D U C T RESEARCH A N D D E V E L O P M E N T
Zinc Chromite,
Cu 0203
250
34 3 1
200 35 23 15
225
41 19 19
Zn 0302
250 55
230
300 30
15 2
7 62
10
4
26
Vanadia, Cobalt, 903
0702
230
175
