NZ247594A

NZ247594A - Preparation of iminostilbene by high temperature dehydrogenation of iminodibenzyl on a catalyst

Info

Publication number: NZ247594A
Application number: NZ247594A
Authority: NZ
Inventors: Beat Michael Aebli; Daniel Monti; Milos Rusek
Original assignee: Ciba Geigy Ag
Priority date: 1992-05-13
Filing date: 1993-05-11
Publication date: 1996-02-27
Also published as: KR940005559A; NO931727L; FI932116A; AU3711193A; KR100364041B1; CN1080285A; EP0570336A2; RU2126795C1; MX9302768A; ZA933303B; HUT68568A; GR3035480T3; MY109264A; IL105678A0; AU663580B2; JP3645279B2; DK0570336T3; NO304737B1; HU214775B; EP0570336A3

Abstract

The invention relates to a novel process for the production of iminostilbene by high temperature dehydration of iminodibenzyl on an iron oxide/potassium salt contact catalyst in the vapour phase, characterised in that an iron oxide/potassium salt contact catalyst is used containing 35 to 90% by weight of an iron compound, calculated as Fe2O3, and 7 to 35% by weight of a potassium compound, calculated as K2O, as well as 0.0 to 3.5% by weight of a chromium compound, calculated as Cr2O3, and with or without conventional promoters.

Description

<div class="application article clearfix" id="description"> New Zealand Paient Spedficaiion for Paient Number £47594 247594 Priority Date(s): ; Complete Specification Filed: Class: (.?). ZilH®— Publication Date: P.O. Journal No: W/JWG* Patents Form No. 5 N-Z. PATENT OFFKS5 3\J1 MAV1993 RECEIVE NEW ZEALAND PATENTS ACT 1953 COMPLETE SPECIFICATION NOVEL HIGH-TEMPERATURE DEHYDROGENATION PROCESS WE, CIBA-GEIGY AG, a Swiss corporation of Klybeckstrasse 141, 4002 Basle, Switzerland hereby declare the invention, for which We pray that a patent may be granted to us, and the method by which it is to be performed, to be particularly described in and by the following statement: - 1 - (followed by Page la) 247594 4-19088/A Novel high-temperature dehydrogenation process The invention relates to a novel process for the preparation of iminostilbene by high-temperature dehydrogenation of iminodibenzyl on an iron oxide/potassium salt contact catalyst in the vapour phase. Iminostilbene, 5H-dibenz[b,f]azepine, is an important intermediate for the preparation of 5-carbamoyl-dibenz[b,f]azepine which under the generic name carbamazepine has gained great importance as an anti-convulsive active ingredient in medicaments. A number of processes are known for the conversion of iminostilbene into carbamazepine, which processes are based on the direct or stepwise introduction of the carbamoyl group in the 5-position of the azepine ring. Numerous processes are available for the preparation of iminostilbene, amongst which high-temperature dehydrogenation of iminodibenzyl in the vapour phase on iron oxide contacts has achieved particular importance. According to the variant of that process having the greatest technical importance at present, the variant according to US-3,449,324 there is used a contact catalyst comprising "in addition to iron(III) oxide, which is best used in amounts of from 30 to 70 %, preferably also additions of, for example, from 1.5 to 3 % by weight Cr203, from 10 to 15 % by weight CaO and the remainder K2C03" and the operation is carried out "at temperatures of from 300° to 500°C, preferably from 400° to 450°C". As expressly pointed out, and supported by numerical data for reaction temperatures of from 550° and 600°C, in US-3,449,324, temperatures higher than 500°C r "to an unacceptable extent or even predominantly" in undesired acridine secondary products. Furthermore, the known process has the serious disadvantage expressly mentioned in US-3,449,324 that the activity of the catalyst gradually declines, so that according to US-3,449,324 Example 2, it would have to be regenerated after only about 30 minutes' use. This can be attributed to the fact that a not inconsiderable proportion of the iminodibenzyl used becomes resinated and is precipitated in the form of tar- or carbon-like deposits which have to be removed periodically by burning out the catalyst. The yields (followed by page 2 247! -2- given in US-3,449,324 therefore cannot be obtained in practice, as shown especially by Example 21 in comparison with Comparison Examples 1 and 2. The resination of considerable proportions of the iminodibenzyl used not only reduces the yield of iminostilbene but also involves ecological and industrial safety risks resulting from the oxidative secondary reactions which are difficult to control. In particular, it is necessary to interrupt the process periodically, which renders continuous operation impossible. The problem underlying the invention is, therefore, to provide an improved process for the preparation of iminostilbene by catalytic high-temperature dehydrogenation of iminodibenzyl in the vapour phase that avoids the above-described disadvantages and other shortcomings of the known process. The solution to this problem proposed according to the invention is based on the surprising finding that the periodic regeneration of the catalyst is unnecessary when there is used an iron oxide/potassium salt contact catalyst containing from 35 to 90 % by weight of an iron compound, calculated as Fe203, from 7 to 35 % by weight of a potassium compound, calculated as K20, and from 0.0 to 9.0 % by weight of a calcium compound, calculated as CaO, in addition to from 0.0 to 3.5 % by weight of a chromium compound, calculated as CrjC^, and optionally additional customary promoters. It is also surprising that the catalyst used according to the invention in the high-temperature dehydrogenation of a heterocyclic compound of such a high molecular weight as iminodibenzyl works autoregeneratively and exhibits excellent activity and selectivity. It is especially surprising that, as will be seen from Examples 12 to 15, contrary to the prejudice arising from US-3,449,324 according to the invention it is precisely at a reaction temperature of 550°C and above that the best conversion and the highest yield of iminostilbene are achieved. As will be seen from Example 2, the contact catalyst used according to the invention advantageously achieves a service life of more than 1100 hours without significant amounts of iminodibenzyl being lost as a result of undesired oxidative secondary reactions. As a consequence, the invention opens up the possibility of continuous operation. The process according to the invention for the preparation of iminostilbene by high-1 ° ' . temperature dehydrogenation of iminodibenzyl on an iron oxide/potassium salt contact -3- 2*7594 catalyst in the vapour phase is accordingly carried out by using an iron oxide/potassium salt contact catalyst containing from 35 to 90 % by weight of an iron compound, calculated as Fe203, from 7 to 35 % by weight of a potassium compound, calculated as K20, and from 0.0 to 9.0 % by weight of a calcium compound, calculated as CaO, in addition to from 0.0 to 3.5 % by weight of a chromium compound, calculated as Cr2C>3 and optionally additional customary pronators Suitable additional promoters are, for example, magnesium, cerium, molybdenum, cobalt, vanadium and tungsten compounds, for example in the form of oxides of the said metals, especially tungsten, cerium, vanadium and cobalt oxides. Although promoters of the mentioned or similar type can increase the performance of the catalyst, they are not absolutely necessary, as will be seen from Examples 17 to 20. In general the quantitative ratios of the components are not critical provided that the proportions of iron and potassium remain within the scope of the definition given above. The contact catalyst used according to the invention is preferably, but not necessarily, brought into contact with iminodibenzyl vapours in an adiabatic fixed bed reactor. It is also possible, however, to use tube bundle, fluid bed and fluidised bed reactors, as well as other types of reactor in accordance with the prior art. The morphology of the catalyst used according to the invention should offer as little resistance as possible to the vapours flowing through the catalyst bed. It is preferable to use geometric, for example cylindrical, moulded bodies about 1 to 6 mm, especially 1 to 4 mm, in length and about 0.5 to 5 mm, especially 1 to 3 mm, in diameter, and also granules having an average particle size of about from 0.5 to 5 mm, especially about from 1 to 3 mm. It is advantageous to carry out the operation in a temperature range above 500°C, preferably at from about 550° to about 600°C, and to dilute the iminodibenzyl vapours with an inert carrier gas, such as with nitrogen or especially an approximately 50- to 200-fold, for example approximately 120- to 140-fold, molar amount of water vapour. It is advantageous to operate at normal pressure or at slightly reduced pressure, for example at about from 0.2 to 1.1 bar, especially about from 0.95 to 1.05 bar, (absolute) and to allow the reaction gases to cool to room temperature, the resulting iminostilbene and unreacted iminodibenzyl being obtained in a solid form suspended in the condensed transport water. The iminostilbene component can then be separated from the condensate and the unreacted iminodibenzyl can be isolated and recycled. The procedure to be usedsS,pffiwn and can be found, for example, in US-3,449,324. ^ 24 7 5 9 4 -4- The following Examples serve to illustrate the invention; temperatures are given in degrees Celsius and pressures in bar absolute. Example 1: The dehydrogenation of iminodibenzyl (DDB) to iminostilbene (IS) in the gaseous phase is carried out in a quartz glass tube reactor 31 mm in diameter and 1 m in length. 30 g of a catalyst having the following properties Composition: 1.1 % by weight chromium oxide, calculated as Cr203 22 % by weight potassium compound, calculated as K20 remainder iron oxide particle size: 1-2 mm are introduced between two filler layers (corundum; particle size: 1-2 mm) in the centre of the reaction tube. The upper filler layer acts as a vaporisation zone for the iminodibenzyl. 27.7 g/h of water are vaporised in a separate oven and passed into the reactor from above. 6 g/h of iminodibenzyl at 120°C in molten form are metered directly into the vaporisation zone, mixed with the pre-heated vapour and vaporised. By electrically heating the reactor, the vapour mixture is heated to the reaction temperature of 550°C. After the reaction in the approximately 35 mm high catalyst layer, the product vapours are cooled to room temperature in a vessel, so that the mixture of iminodibenzyl and iminostilbene is obtained in the form of powder in condensed water. The condensates taken at different times during the experiment are homogenised with dioxane and analysed by capillary gas chromatography (without water). During the 860-hour duration of the experiment, the following product composition (without water) is obtained: 24 75 94 -5- time [h] IDB % by wt. IS % by wt. sec. comp. % by wl conversion % selectivity % 2 25.0 51.4 20.9 75 72 25 28.9 49.6 21.5 71 70 92 27.4 48.4 24.2 73 67 554 30.9 47.5 21.6 68 69 630 26.7 49.9 21.6 73 69 860 29.9 47.2 22.9 70 67 In addition to iminodibenzyl (IDB) and iminostilbene (IS), mainly 9-methylacridine and acridine are detected as secondary compounds. The experiment is carried out continuously for about 100 hours each time with interruptions at weekends. After an interruption the catalyst is scavenged for one hour with water vapour at the reaction temperature and then cooled to room tempetrature under nitrogen. When the experiment is started up again, that procedure is followed in reverse order. Example ! demonstrates the long service life and the continuous operation of the catalyst. Example 2:80 g of a catalyst having the following composition is introduced into a quartz glass tube reactor according to Example 1: Composition: 12.3 % by weight of potassium oxide, calculated as K20 1.9 % by weight of chromium oxide, calculated as Cr203 1.6 % by weight of tungsten oxide, calculated as WO3 2.4 % by weight of cerium oxide, calculated as Ce2C>3 1.5 % by weight of vanadium oxide, calculated as V2C>5 0.3 % by weight of cobalt oxide, calculated as C02O3 remainder iron oxide particle size: 1-2 mm A stream of 40 g/h of iminodibenzyl and 480 g/h of water vapour at 590° is passed over the catalyst for 1145 hours with the interruptions at weekends described in Example 1. 247 594 The product, which is separated from water by filtration, has the following composition (as a function of the reaction time): time IDB IS byproducts conversion selectivity [h] % by wt. % by wt. % by wt. % % 39 13.5 76.2 10.3 87 88 148 13.5 74.7 11.8 87 87 250 12.6 76.9 10.5 86 88 367 13.1 76.8 10.1 87 88 460 13.7 76.1 10.2 87 88 550 14.6 75.3 10.1 86 88 685 12.7 76.2 11.1 87 87 914 11.6 77.4 11.0 89 88 1028 13.0 75.8 11.2 87 87 1145 14.6 74.4 11.0 86 87 Example 2 demonstrates the good selectivity, the long service life of more than 1100 hours and the continuous operation of a catalyst comprising tungsten oxide, cerium oxide, vanadium oxide and cobalt oxide as promotors. Examples 3 to 6: Using the same experimental procedure and the same conditions as in Example i, the amount of water in relation to the metered amount of IDB is varied within a wide range: Example water [g/h] IDB % by wt. IS ■% by wt. sec. comp. % by wt. conversion % selectivity % 3 11.7 38.6 32.0 29.4 61 52 4 27.7 26.7 49.9 23.4 73 68 5 55.4 20.6 60.2 19.2 79 76 6 110.8 1.7 60.1 38.2 98 61 ^ A* tsl :■ . fl 24 7 51 -7- Examples 3 to 6 demonstrate the large amount of influence exerted by the ratio of water to IDB on the conversion and on the selectivity of the reaction. Examples 7 to 11: Using the same experimental procedure and 30 g of the same catalyst as in Example I, the dehydrogenation is carried out at 570°C. The metered amounts of IDB and water are altered in such a manner that the ratio of water to IDB remains constant. Example water [g/h] IDB [g/h] IDB %bywt ' IS 7o by wt. sec. comp. conversion selectivity % by wt. % % 7 276.9 30 34.0 55.4 10.6 66 84 8 138.5 15 16.4 67.3 16.3 84 81 9 92.3 10 9.6 70.9 19.5 90 78 10 55.4 6 8.1 64.7 27.2 92 70 11 27.7 3 5.5 57.5 37.0 95 61 Examples 7 to H demonstrate the influence exerted by the contact time (contact time factor = 1-10 h per hour) on the conversion or the selectivity of the reaction, (contact time factor - ^catalyst> ) o(iminodibenzyl) with a constant ratio of water to iminodibenzyl (IDB). Examples 12 to 15: Using the same experimental procedure and 30 g of the same catalyst and the same metered amounts of water and IDB as in Example i, the dehydrogenation reaction is carried out at various temperatures. The Table below shows the product composition. -8- 24 75 94 Example temperature C°C] IDB % by wt. IS %by wt sec. comp. % by wt. conversion selectivity % % 12 510 55.1 32,7 12.2 45 73 13 530 39.5 43.4 17.1 61 72 14 550 26.7 49.9 23.4 73 68 15 570 25.5 45.0 29.5 75 60 Examples 12 to 15 demonstrate the strong influence exerted by the temperature on the rate of reaction and the selectivity of the reaction. Example 16: 30 g of a catalyst having the following properties are introduced into the reactor of Example 1,: Composition: 9.0 % by weight of a potassium compound, calculated as K20 0.04 % by weight of chromium oxide, calculated as Cr203 2.7 % by weight of a calcium compound, calculated as CaO 4.8 % by weight of cerium oxide, calculated as Ce203 2.5 % by weight of magnesium oxide, calculated as MgO 2.0 % by weight of molybdenum oxide, calculated as M0O3 remainder iron oxide particle size: 1.5 mm At 0.4 bar (absolute) and 570°C, a vaporous stream of 6.0 g/h of IDB and 55.4 g/h of water is passed over the catalyst. The product comprises 2.9 % by weight IDB, 74.0 % by weight IS and 23.1 % by weight secondary compounds (mainly acridine and 9-methyl-acridine) without taking account of the water. The same experiment at normal pressure results in a product composition of 6.2 % by weight IDB, 66.9 % by weight IS and 26.9 % by weight secondary compounds. Example 16 demonstrates the influence exerted by reduced pressure (vacuum) on the conversion and the selectivity of the reaction. -9- 247 594 Examples 17 to 20: In the following Examples the influence of the composition of the catalyst on the conversion and on the selectivity of the reaction under the same test conditions is demonstrated. In the test apparatus of Example I, 30 g of each of the catalysts given below are tested (particle size 1-2 mm). At 550°C, 15 g/h of IDB and 180 g/h of water in vapour form are passed over the catalysts. Example IDB % by wt. IS % by wt. sec. comp. % by wt. conversion % selectivity % 17 28.2 59.0 12.8 72 82 18 18.0 67.7 14.3 82 83 19 20.9 63.2 15.9 79 80 20 27.2 60.0 12.8 73 82 The composition of the catalysts used in Examples 17 to 20 is given in the following Table: Example Fe203 K20 Cr203 CaO Ce203 MgO Mo03 [% by wt.][% by wt.] [% by wt.] [% by wt.] [% by wt.] [% by wt.][% by wt.] 17 61 22 1.1 — — — — 18 85 9 1.9 — — — — 19 77 9 0.04 2.7 4.8 2.5 2.0 20 44 31 2.5 0.5 w__ 0.1 Examples 17 to 20 demonstrate that the reaction can be carried out using various catalysts of very different composition. Example 21: Using the experimental procedure of Example 1, 30 g of a catalyst having the following properties are introduced: Composition: 1.3 % by weight of chromium oxide, calculated as Cr203 13.1 % by weight of a potassium compound, calculated as K2O remainder iron oxide -10- 247594 particle size: 1-2 ram At 550°C and 1 bar absolute, a vaporous stream of 6 g/h of iminodibenzyl and 72 g/h of water is passed over the catalyst. By filtering and drying the condensed products it is possible to recover a mass of 99 %, based on the amount of substance used (iminodibenzyl). The loss in mass of 1 % is attributable to the removal of hydrogen and methane from the reactants. The isolated product has the following composition: 76.2 % by weight iminostilbene, 3.8 % by weight iminodibenzyl and 20 % by weight secondary compounds. The total yield of iminostilbene, taking account of the losses in mass, is therefore 75.4 %. That Example demonstrates the high yields that can be attained and the low losses in mass when the reaction is carried out continuously. Comparison Example 1: (Comparison with the cyclic process) Using the experimental procedure of Example 1_, 50 g of the catalyst described in Example 1 of US-3,449,324 are introduced. In accordance with the data given in the above-mentioned Patent, the reaction is carried out at 430°C, 1 bar absolute and with cyclic operation. The cycle times are as follows: 5 minutes pre-scavenging with water vapour, 18 minutes reaction, 5 minutes post-scavenging with water vapour and 30 minutes regeneration (oxidation of the catalyst with air). The metered amounts are: prescavenging with water vapour: 38.3 g/h, reaction: 8.3 g/h of IDB and 38.3 g/h of water vapour, post-scavenging: 38.3 g/h of water vapour, and regeneration: 100 ml/minute of air and 38.3 g/h of water vapour. The product collected during 20 cycles is filtered off and dried. The amount of substance recovered was 88 % by weight of the amount of IDB used. Since a portion of the product remains on the catalyst after the reaction phase, that adsorbed portion is oxidised with air during the regeneration phase to form unusable products. The product composition is on average: 65 % by weight iminostilbene, 28 % by weight iminodibenzyl and 7 % by weight secondary compounds. The total yield, taking account of the losses in mass, is accordingly 57 %. That Comparison Example demonstrates the significantly poorer yield obtained using the cyclic process in comparison with the continuous process. </div>

Claims

<div class="application article clearfix printTableText" id="claims"> 24 7594 -11- Comparison Example 2: (Comparison with the cyclic process) Using the same experimental procedure, the same cycle times, the same catalyst and the same conditions as in Comparison Example i, 5 g/h of IDB and 23.3 g/h of water vapour are passed over the catalyst. After filtering and drying the reaction mass it is possible to isolate a further 78 % of the amount of substance used. The product composition is on average: 72 % by weight iminostilbene, 16 % by weight iminodibenzyl and 12 % by weight secondary compounds. The total yield, taking account of the losses in mass, is accordingly 56 %. That Comparison Example shows that although it is possible to increase the conversion by reducing the ratio of the metered amount of IDB to the amount of catalyst, the total yield is not increased, owing to the greater losses in mass occurring on regeneration of the catalyst 247594 1 • -12- WHAT WE CLAIM IS:

1. A process for the preparation of iminostilbene by high-temperature dehydrogenation of iminodibenzyl on an iron oxide/potassium salt contact catalyst in the vapour phase, wherein there is used an iron oxide/potassium salt contact catalyst containing from 35 to 90 % by weight of an iron compound, calculated as Fe203, from 7 to 35 % by weight of a potassium compound, calculated as K20, and from 0.0 to 9.0 % by weight of a calcium compound, calculated as CaO, in addition to from 0.0 to 3.5 % by weight of a chromium compound, calculated as Cr203, and optionally additional customary promotors.

2. A process according to claim 1, wherein there is used an iron oxide/potassium salt contact catalyst containing from 35 to 90 % by weight of an iron compound, calculated as Fe203, and from 7 to 35 % by weight of a potassium compound, calculated as K20, in addition to from 0.0 to 3.5 % by weight of a chromium compound, calculated as Cr203, and optionally additional customary promotors.

3. A process according to claim 1 wherein there is used as promotor a magnesium, calcium, cerium, molybdenum, cobalt, vanadium or tungsten compound.

4. A process according to claim 2, wherein there is used as promotor a magnesium, cerium, molybdenum, vanadium or tungsten compound.

5. A process according to claim 1, wherein there is used as promotor a calcium oxide, tungsten oxide, cerium oxide, vanadium oxide or cobalt oxide.

6. A process according to claim 2, wherein there is used as promotor a magnesium oxide, cerium oxide or molybdenum oxide.

7. A process according to any one of claims 1 to 6, wherein an iron oxide/potassium salt contact catalyst containing from 44 to 85 % by weight of an iron compound, calculated as Fe203, is used.

8. A process according to any one of claims 1 to 7, wherein an iron oxide/potassium salt contact catalyst containing from 9 to 31 % by weight of a potassium compound, calculated as K20, is used. .#'Xu 11 Cv * //.: // t sp V 24? 594 • 13-

9. A process according to any one of claims 1 to 8, wherein an iron oxide/potassium salt contact catalyst containing from 0.02 to 2.5 % by weight of a chromium compound, calculated as Cr203, is used.

10. A process according to any one of claims 1 to 4 and 7 to 9, wherein an iron oxide/-potassium salt contact catalyst containing from 0.02 to 2.0 % by weight of a tungsten pronotor/ compound, calculated as WC>3, is used.

11. A process according to any one of claims 2 and 7 to 9, wherein an iron oxide/-potassium salt contact catalyst containing from 1.0 to 3.0 % by weight of a calcium pronotor/ compound, calculated as CaO, is used.

12. A process according to any one of claims 1 to 8, wherein an iron oxide/potassium salt contact catalyst containing from 0.5 to 5.0 % by weight of a cerium pronotor /compound, calculated as ^ used-

13. A process according to any one of claims 1 to 5,7 and 8, wherein an iron oxide/- potassium salt contact catalyst containing from 0.02 to 2.5 % by weight of a vanadium pronotor/ compound, calculated as v2o5, is used.

14. A process according to any one of claims 1 to 4,7 and 8, wherein an iron oxide/- potassium salt contact catalyst containing from 2.0 to 3.0 % by weight of a magnesium pronotor/ compound, calculated as MgO,isused.

15. A process according to any one of claims 1 to 4 and 6 to 8, wherein an iron oxide/- potassium salt contact catalyst containing from 0.05 to 2.5 % by weight of a molybdenum prcmotor/ compound, calculated as Mo2o3 f is used.

16. A process according to any one of claims 1 to 3,5,7 and 8, wherein an iron oxide/-potassium salt contact catalyst containing from 0.02 to 1.0% by weight of a cobalt prcmotor/canpound, calculated as Co203;is used.

17. A process according to any one of claims 1 to 16, wherein the contact catalyst is brought into contact with iminodibenzyl vapours in an adiabatic fixed bed i^jptcfrM tube bundle reactor, fluid bed reactor or fluidised bed reactor. 247594 a*"""* ^ j'3 - 14-

18. A process according to any one of claims 1 to 17, wherein the contact catalyst is used in the form of geometric moulded bodies 1 to 6 mm in length and 0.5 to 5 mm in diameter or in the form of granules having an average particle size of from 0.5 to 5 mm.

19. A process according to any one of claims 1 to 18, wherein the operation is carried out in a temperature range above 500°C.

20. A process according to any one of claims 1 to 18, wherein the operation is carried out at from 550° to 600°C.

21. A process according to any one of claims 1 to 20, wherein the iminodibenzyl vapours are diluted with an inert carrier gas.

22. A process according to any one of claims 1 to 20, wherein the iminodibenzyl vapours are diluted with an 50- to 200-fold molar amount of water vapour.

23. A process according to any one of claims 1 to 20, wherein the iminodibenzyl vapours are diluted with an 120- to 140-fold molar amount of water vapour.

24. A process according to any one of claims 1 to 20, wherein the operation is carried out at from 0.2 to 1.1 bar (absolute).

25. A process according to any one of claims 1 to 20, wherein the operation is carried out at from 0.95 to 1.05 bar (absolute). by their attorneys BALDWIN, SON & CAREY c /X. </div>