2,5-dimethylpyrazine. Both catalysts are in the form of l / g inch tablets. The Ni 0104 catalyst contains 6570 nickel on a kieselguhr support and the C u 0203 catalyst contains copper and chromium oxides in a ratio of 80 to 20. The copper chromite was slightly superior under the conditions tested, and additional work showed it to have even better activity a t higher temperatures, and a much longer life than the nickel catalyst. Therefore, the performance of this copper chromite was studied more extensively. Additional data on the activity of copper chromite, plotted in Figure 4, show the effect of temperature over the range of 200'-275' C. upon the ratio of dimethylpyrazine and dimethylpiperazine produced. The highest conversion to dimethylpyrazine (66%) and the highest total conversion to cyclic products were obtained a t 275' C. This would indicate that still higher temperatures might be desirable, but further study showed that 275' C. was approximately the optimum temperature for this reaction. At 300' C. and higher, the catalyst had good initial activity, but a relatively short life. T h e excellent life of this catalyst when used a t 275' C. is illustrated in Figure 5. During 214 hours of operation, the conversion to 2,5-dimethylpyrazine averaged 65% and the conversion to 2,5-dimethylpiperazine was fairly constant a t about 10%. Toward the end of the run conversion to 2,5-
dimethylpyrazine decreased slightly, but because of increased recovery of isopropanolamine the yield remained constant. Actually this catalyst has a much longer life than is shown, since it can be repeatedly regenerated by air oxidation followed by hydrogen reduction (2). literature Cited
(1) Bain, J. P., Pollard, C. B., J . Am. Chem. Sod. 61, 532 (1939). (2) Cenker, M., Jackson, D. R., Langdon, \Y. K., Levis, W. W., Tarailo, s., Baxter, G., IND.ENG.CHEM. PROD.RES.DEVELOP. 3, 11 (1964). 13) Hill. R., Walker, E. E., J . Polymer Sci.3, 609 (1948). iro, T., Kitamura, E., Matsumura, M., Yakugaku Zasshi 1-4 (1957). M. (to E. I. du Pont de Nemours & Co.), U. S. Patent 2,949,440 (1960). (6) Langdon, I Y . K. (to Wyandotte Chemicals Corp.), Zbid., 2,813,869 (Nov. 19, 1957) ; 3,067,199 (Dec. 4, 1962). (7) Langdon, \Y. K., Levis, JY. FY., Jackson, D. R., Znd. Eng. Chem. Proc. Design Deoelop. 1, 153 (1962). (8) Lyman, D. J., Jung, S. L., J . Polymer Sci. 40, 407 (1959). (9) Sasaki, T., Yuki Gosei Kagaku KyokaiShi 16,614-20 (1958). (10) Schwoeder. E. J., Berman, L. U., Corrosion 15. No. 3, 128 ' (March 1939):
RECEIVED for review September 27, 1963 ACCEPTEDJanuary 8, 1964 Division of Industrial and Engineering Chemistry, 144th Meeting, ACS, Los Angeles, Calif., April 1963.
SYNTHESIS OF PYRAZINES Vapor-Phase De/ydrogenation of Piperaz$aes M O S E S C E N K E R , D . R. J A C K S O N , W . K . L A N G D O N , W . W . L E V I S , J R . , S. D . T A R A I L O , A N D G . E . B A X T E R Wyandotte Chemicals Corp., Wyandotte, Mich.
2-Methylpiperazine i s dehydrogenated to methylpyrazine in 89% yield in a continuous vapor-phase process using a prereduced 80% Cu0:20% C r z 0 3catalyst a t 350" C. The conversion to methylpyrazine initially i s 85 to 87% and drops to approximately 50% after 100 hours' operation. Activity of the catalyst can be restored b y air oxidation and hydrogen reduction. Incorporation of alkaline or acidic materials in the catalyst results in a less effective catalyst. Increased feed rates depress the conversion. Operation a t moderate pressure allows the use of higher feed rates with high conversion. Piperazine, 2-ethylpiperazine, 2,6-dimethylpiperazine, and 2,3,5,6-tetramethylpiperazine are dehydrogenated to the corresponding pyrazines in conversions of 7 9 to 89% b y the same process. PROCESS for the bimolecular cycloamination of a,P-alkanolamines to give symmetrically substituted pyrazines (Equation l ) has been described ( 6 ) . An alternative procedure, which also permits the preparation of unsymrnecrically substituted pyrazines, is the vapor-phase dehydrogenation of piperazines (Equation 2 ) .
A
From Alkanolamines:
From Piperazines:
Dixon (2) has described processes for dehydrogenation of piperazine to pyrazine using various supported metal and/or metal oxide catalysts a t temperatures ranging from 350' to 500° C. A dilute solution of piperazine in a n inert diluent (usually 4% in benzene) was used and a 35 to 457, conversion to pyrazine was obtained. Kitchen and Hanson (4) used the Dixon process to dehydrogenate 2-methylpiperazine in 37 to 46% conversion, and more recently ( 3 ) , Japanese workers applied the process to a number of alkylpiperazines to obtain the corresponding pyrazines in 33 to 63% yield. A similar process was disclosed in 1948 ( g ) , in which a cadmium oxidecopper oxide catalyst on a magnesia-potassium carbonatecement support was used for the dehydrogenation of piperazine. In common with other prior reports, a low feed rate was used and a moderate to low conversion to pyrazine (30 to 41%) was obtained. The present paper describes the first commercially practical process developed for the dehydrogenation of piperazines (7, 70). VOL. 3
NO. 1 M A R C H 1 9 6 4
11
Experimental
The reactor used has been described in detail ( 6 ) . The alkylpiperazines dehydrogenated were prepared by the cycloamination of appropriately substituted alkanolamines (5, 7, 8 ) . Piperazine was obtained from the Union Carbide Chemical Co. The copper-chromium oxide catalysts were supplied by the Harshaw Chemical Co. in the form of '/*-inch tablets. Catalyst Reduction. Before these catalysts are used for dehydrogenation, they are reduced with hydrogen under controlled conditions. Without this prereduction, the highly exothermic reaction between the catalyst and the hydrogen resulting from initial dehydrogenation often raises the temperature of the catalyst bed to a point where the reaction and temperature become uncontrollable. After the catalyst is placed in the reactor, the catalyst bed is heated in a stream of nitrogen a t a high flow rate to approximately 225' C. Hydrogen is introduced into the gas stream to give a mixture containing about 20% of hydrogen. A hot zone (275' to 300' C.) develops a t the top of the bed and travels down through the catalyst. When the hot zone has traveled the length of the catalyst bed, hydrogen alone is passed over the catalyst a t 250' to 275' C. for 2 hours longer to ensure reduction of the catalyst. Catalyst Regeneration. Spent catalyst is regenerated by ?rst passing water vapor through the catalyst bed a t 210' to 220' C. for 2 to 3 hours until the condensate is clear and colorless. The catalyst is then oxidized by a procedure identical to that used for reduction, except that air is substituted for hydrogen. As in the case of reduction, a hot zone, which develops a t the top of the catalyst bed, is maintained at 275" to 300" C. while it moves down through the bed. When the oxidation is completed, the catalyst is reduced as described above. Dehydrogenation a n d Product Work-up. After the catalyst bed is reduced and the reactor temperature is adjusted, the hydrogen flow through the reactor is stopped and the piperazine solution is pumped into the reactor a t the desired rate. The solution is vaporized and the vapor heated to the desired temperature in the preheater section of the reactor. Dehydrogenation, which is a n endothermic reaction, depresses the temperature of the upper section of the catalyst bed, but the lower portion of the catalyst bed can be maintained a t the desired temperature. The magnitude of this endotherm is a measure of the catalyst activity and becomes smaller as the catalyst becomes less active. The condensable products are removed from the eWuent gas stream and collected. The noncondensable gas (essentially hydrogen) passes through a meter and is vented. The amount of gas is indicative of the amount of dehydrogenation and is used to estimate the need for regenerating the catalyst. The condensed furnace eWuent is diluted with additional water and fractionated by distilling off the pyrazine-water azeotrope, followed by continued distillation to recover unreacted piperazine. The azeotrope is treated with sodium hydroxide to salt out the pyrazine, which is then redistilled.
Results and Discussion
O n the basis of our experience in the vapor-phase synthesis of 2,5-dimethylpyrazine ( 6 ) ,we chose copper-chromium oxide catalysts for use in dehydrogenation of piperazines to pyrazines. The 80: 20 C u O : C r 2 0 3catalyst (Harshaw Cu 0203) was used to develop a procedure for screening modified copper-chromium oxide catalysts. Initially, molten anhydrous piperazines (2-methyl- and 2,5dimethyl-) were used for dehydrogenation. Although excellent conversions and yields were obtained, feed rate control was difficult. T o facilitate feed rate control for the extended periods desired, aqueous solutions were used in subsequent work. The amount of water used had virtually no effect on the dehydrogenation and solution concentrations were chosen merely to ensure complete solubility. 12
I&EC PRODUCT RESEARCH A N D DEVELOPMENT
Increasing Temperature Dehydrogenation. The first sustained run was made using a n 80% aqueous 2-methylpiperazine (2-MP) solution a t a feed rate of 0.25 gram of 2-MP per gram of catalyst per hour. In Figure 1, conversions (per cent of reactant charged converted to product) and yields (per cent of reactant consumed converted to product) are plotted against cumulative amount of 2-MP reacted. A 65% conversion to methylpyrazine and a n 83% yield were obtained during the first 1.5 hours of operation a t 300' C. However, the conversion level decreased rapidly and the temperature was periodically increased in a n attempt to restore the catalyst activity. Over a period of 200 hours, during which a n amount of 2-MP equal to 50 times the weight of catalyst reacted and the temperature was raised to 415' C., the conversion decreased to 33% although the yield declined to only 72%7:,. This attempt to maintain a n adequate conversion level by increasing the catalyst temperature was not entirely satisfactory. The over-all average conversion for this run was 45% and the average yield was 75%. Constant Temperature Dehydrogenation. The results of a dehydrogenation a t a constant temperature with periodic regeneration of the catalyst are shown in Figure 2. Roughly a 50% conversion level was arbitrarily chosen as the point for regeneration in this experimental work. In production, the minimum conversion level a t which the catalyst would be regenerated would be determined by economics. In this constant temperature run a t 350' C., a 74% aqueous solution of 2-methylpiperazine was fed over 80:20 CuOCrz03 catalyst at a rate of 0.23 gram of 2-MP per gram of catalyst per hour. During the first 66 hours of operation, the conversion decreased from about 82% to 59% while the yield remained almost constant a t 87%. The catalyst was then steamed, oxidized, and reduced by the previously described procedure, which required about 15 hours. I n a second cycle under the same conditions, the conversion decreased from about 87% to 52% over a n 80-hour period, while the yield remained constant a t 89%. In each of the first and second cycles, the average conversion to methylpyrazine was 67%. Similar results were obtained in two more cycles of 100 hours of operation. Thus, for a total reaction time of 345 hours, interrupted by three periods of about 15 hours each for regeneration of the catalyst, an amount of 2-methylpiperazine equal to 80 times the weight of catalyst was fed with a n over-all conversion of 68% to methylpyrazine and a n over-all yield of 89%. This constant temperature procedure was then chosen to evaluate other copperchromium oxide catalysts.
100
r
CATALYST: HARSHAW'S Cu-0203 T 118" FEED RATE: 0 . 2 4 g, 2-MEMYLPIPERAZINE/g. CAT/HR
30IO
"
IO
20 TOTAL
30 2MP
40 50 60 REACTED, g./g. CATALYST
70
80
Figure 1. Dehydrogenation of 2-methylpiperazine (2MP) to methylpyrazine Sustained run activated by periodic temperature increase
Table I. Effect of Catalyst Variation on Efficiency Catalyst Eflciency after Period o f Usea Catalyst Composition, 70 ConOther Yield, version, Time, cu0 Cr203 component % 70 hr. 80 20 ... 87 59 63 50
50
40 72 78.5 49.5 50
75.2 77.6 a
80%
2-1MP/g.
60 18 19.5 49.5 40 18.8 19.4 aqueous 2-MP cat./hr.
...
89
...
90
65 60 10%NazSi03 87 54 .. 45 270 Na2SiOs 1% NazSiOB .. 52 1070 BaO .. 47 6%AlPOi 75 56 3%AlPOa 76 55 reacted at 350"-365' C. at rate of
78 62 18 17 4 17 53 62
0.25 g .
Catalyst Variations. Copper-chromium oxide catalysts of varied copper oxide-chromium oxide ratios and with acidic and basic additives were tested for the dehydrogenation of 2methylpiperazine a t 350 to 365 C. catalyst bed temperature and a n aqueous feed of 0.23 to 0.25 gram of 2-MP per gram of catalyst per hour. All catalysts tested gave high conversions and yields initially. Comparison was therefore made (Table I) on the basis of the effect of prolonged use on conversions, yields, physical stability of the catalyst, and its susceptibility to regeneration. T h e first three catalysts, having varied C u O : C1-203 ratios, gave constant yields of 87 to 90% during initial cycles lasting 66 to 84 hours, and the decline in conversion was about the same for each. With the 50: 50 catalyst, the conversion level decreased to 65% and the average conversion for the run was 74%. With the 40 :60 catalyst, the conversion level decreased to 60% and the average conversion was 65%. However, the 80 :20 C u O : Crz03 catalyst showed good mechanical strength, while the catalysts having the higher Crz03 content exhibited undesirable powdering during the reaction. Because of this, regeneration of these two catalyst was not tested. T h e catalyst obtained by addition of 10% of sodium silicate to the 80 :20 C u O : (21-203gave a constant yield of 87% during a 45-hour run but the conversion level dropped to 5470 after only 18 hours. This catalyst was regenerated after 45 hours' use and the same behavior occurred during the second cycle. Similarly, the conversion obtained with the catalyst containing 2% of sodium silicate rapidly declined to 45% after 17 hours.
CATALYST: HARSHAW'S Cu-0203 T 1/8" FEE0 RATE: 0.23 g. 2-METHYLPIPERPZINE/g. CAT./HR. TEMPERATURE: 35OoC. I
I
Table II.
Dehydrogenation of Various Piperazines5 Concn. of Feed Rate, Length Over-all ConverG./G. of Run, Aqueous Pyrazine Obtained Feed, % Cat./Hr.b Hr. sion, 70
Pyrazine 0.08 22 79 60.5 2-Ethyl0.17 17 89 74 2.6-Dimethvl0.13 40 87 49 2;6-Dimeth$-c 69.5 0.24 132 95 2,3,5,6-Tetramethyl32 0.08 60 85 a Dehydrogenated at 350°-360a C. at atmospheric pressure over Based on piperazine. reduced Harshaw Cu 0203 'ls-inch catalyst. Dehydrogenation at 7.5p.s.i.g. pressure.
The addition of even a small amount of sodium silicate to the 50: 50 C u O : C r z 0 3 catalyst resulted in a conversion level of 52yGafter only 4 hours. T h e standard copper chromite (high pressure hydrogenation) catalyst which contains 10% BaO gave a conversion level of 47% after 17 hours. Thus, when alkaline materials are added to C u O : Cr203 mixtures, catalysts show rapidly declining conversion levels. The catalyst obtained by addition of aluminum phosphate to the 80 :20 C u O : Crz03 mixture gave conversion levels almost equal to those obtained with neutral copper-chromium oxide catalyst, but the yield levels decreased with use. The conversion level was 55 to 56% after 52 to 58 hours with catalysts containing 3 and 6% of AlP04, but the yield levels were only 75 to 76y0-a decrease of about 10% during the run. This increased decomposition of the organic products resulted in undesirably large amounts of tars on the catalyst. Consequently, regeneration of these catalysts was difficult and incomplete. Based on these results, we concluded that neutral copper oxide-chromium oxide catalysts are to be preferred for the dehydrogenation of 2-methylpiperazine to methylpyrazine. Feed Rate Variation and Effect of Pressure. Continuing our investigation of the 80 : 20 C u O : Cr203 catalyst, we next studied the effect of feed rate on conversion. An increased feed rate resulted in a n increased rate of decline in the conversion level. However, a high conversion level could be maintained a t increased feed rates if, a t the same time, the reaction was operated under a slight pressure. In Figure 3, the change in conversion with the amount of 2-methylpiperazine reacted is shown for runs a t varied feed ratks and/or pressures. At atmospheric pressure, increasing the feed rate from 0.19 to 0.24 gram per gram of catalyst per hour decreases the con-
7.
I
CATALYST: HARSHAW'S TEMPERATURE:
90
I
I
1 20
TOTAL
I
30 2MP
I ,
/
40 REACTED,
50 g./g.
60
,
L
50
70
80
40
CATALYST
Figure 2. Dehydrogenation of 2-methylpiperazine MP) to methylpyrazine Sustained run activated b y periodic catalyst regeneration
t
ATMOS. 75 PSIG. 18.5 RSIG.
C D
80C
10
C u - 0 2 0 3 T 1/8"
024 0.37
I
I
I
IO
20
30
I
TOTAL 2MP REACTED, q./q. CATALYST
(2-
Figure 3. Effect of feed rate and pressure on change in conversion Sustained dehydrogenation of 2-rnethylpiperazine (2-MP)
VOL 3
NO. 1
MARCH 1964
13
version level. However, by operating a t 7.5-p.s.i.g. pressure, the conversion level is increased in spite of the higher feed rate. By increasing the pressure to 18.5 p.s.i.g., the feed rate could be increased to 0.37 gram per gram of catalyst per hour while maintaining an even higher conversion level. Thus, a t the point a t which the amount of 2-methylpiperazine rex t e d equaled about 15 times the weight of catalyst in each run, the conversion level in the runs at atmospheric pressure had decreased to 47% using a 0.24 gram per gram of catalyst per hour feed rate and to 58% using a 0.19 gram per gram of catalyst per hour feed rate. T h e conversion level was still 72y0 a t this point in the run a t 7.5-p.s.i.g. pressure and 76% in the run at 18.5-p.s.i.g. pressure. I n terms of pyrazine produced per hour during this same use period, the atmospheric pressure runs yielded 0.13 to 0.16 gram of methylpyrazine per gram of catalyst per hour while the run a t 18.5-p.s.i.g. pressure yielded 0.25 gram-a production rate approximately twice as fast and a t a higher conversion level. Dehydrogenation of Other Piperazines. Other piperazines have been dehydrogenated to the corresponding is, using 80:20 CuOpyrazines by the same process-that Cr-203 catalyst a t 350' to 360' C. As shown in Table 11, piperazine, 2-ethylpiperazine, 2,6-dimethylpiperazine, and 2,3,5,6-tetramethylpiperazinewere dehydrogenated a t atmospheric pressure in runs ranging from 17 to 60 hours in length in over-all conversions of 79 to 89%. 2,6-Dimethylpiper-
azine was also dehydrogenated at 7.5-p.s.i.g. pressure in 95% conversion during a run lasting 132 hours. Thus, the process developed with 2-methylpiperazine is generally applicable to the dehydrogenation of piperazines. literature Cited
(1) Cenker, M., Baxter, G. E. (to IVyandotte Chemicals Corp.), U. S. Patent 3,005,820 (Oct. 24, 1961). (2) Dixon, J. K. (to American Cyanamid Corp.), Ibid., 2,400,398 (May 14, 1946); 2,474,781 (June 28, 1949); 2,474,482 (June 28, 1949); 2,580,221 (Dec. 25, 1951). (3) Isiguro, T., Kitamura, E., Matsumura, M., Yakugaku Zasshi 78. 150 (1959). (4) Kitch
