FI105027B - A novel high temperature dehydrogenation process for the preparation of iminostilbene - Google Patents

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

105027

A novel high temperature dehydrogenation process for the preparation of iminostilbene

The present invention relates to a novel process for the preparation of iminostilbene ΟφΟ 10 of formula I by high temperature dehydrogenation from iminodibenzyl 15 of formula II (||)

B

with a contact catalyst containing iron, chromium and potassium compounds in the vapor phase at a temperature of 500-600 ° C.

20

Iminostilbene, 5H-dibenz [b, f] azepine, is an important intermediate in the preparation of 5-carbamoyl-dibenz [b, f] azepine, which under the generic name carbamazepine plays an important role as an anti-convulsive active drug. Several methods are known for converting Iminostil-25 be to carbamazepine based on the direct or stepwise attachment of the carbamoyl group to the 5-position of the azepine ring.

Many processes can be used to prepare iminostilbene, of which high temperature dehydrogenation of iminodibenzyl in the vapor phase by iron oxide contacts has been of particular importance. According to the currently technically most important modification of this process according to CH-442,319, a contact catalyst is used which contains f 35 "not only of iron III oxide, which is most preferably used in an amount of 30-70%, preferably also e.g. 3% by weight of Cr 2 O 3, 10-15% by weight of CaO and additionally K 2 CO 3 "and working at" temperatures of 300-500 ° C, preferably 400-450 ° C 2 105027 ". Temperatures higher than 500 ° C, as explicitly emphasized in CH-442,319 and calculated for the reaction temperature of 550 ° C and 600 ° C, lead to "unacceptable amounts or even to a large extent" of unwanted acridine by-products.

In addition, this known method has the distinct disadvantage explicitly mentioned in CH-442,319 that the catalyst activity is gradually lost, requiring regeneration after about 30 minutes, according to CH-10,442,319, Example 2. This is due to the fact that quite a large proportion of the iminodibenzyl used is resinous and precipitates into a tar and carbonaceous layer which must be removed from time to time by burning the catalyst. Therefore, the yields reported in CH-442,319 cannot be practically achieved, as shown in particular in Example 21 as compared to Comparative Examples 1 and 2. However, a considerable proportion of the iminodibenzyl used in the resin itself not only reduces the yield of iminostilbene, but also contains ecological and safety risks due to difficult to control oxidative side reactions. The process must be interrupted at regular intervals, which prevents continuous operation.

It was therefore an object of the invention to provide an improved process for the preparation of an iminostilbene of formula I by catalytic high temperature dehydrogenation of an iminodibenzyl of formula II in a vapor phase which avoids the above and other drawbacks of the known process. The proposal for solving this problem according to the invention is based on the surprising finding that the catalyst does not need to be regenerated at regular intervals if a catalyst containing 44-85% by weight of iron compound Femina, 7-35% by weight of potassium compound-35 calculated as K20 and not more than 3.5% by weight of chromium compound calculated as Cr 2 O 3 and, if necessary, at least one promoter serving 2-3% by weight of magnesium 105027 3 calcium compounds calculated as MgO, 1 to 3% by weight of calcium compound calculated as CaOt, 0,5- 5.0% by weight of the cerium compound calculated as Ce2O3, 0.05-2.5% by weight of the no-lybdenum compound calculated as MoO3, 0.02-1.0% by weight of the co-5 bolt compound calculated as Co2O3 , 0.02-2.5% by weight of vanadium compound calculated as V205 or 0.02-2.0% by weight of tungsten compound calculated as WO03.

Further, it is surprising that the catalyst used in accordance with the invention operates autoregeneratively in the high temperature dehydrogenation of a very high molecular weight heterocyclic compound such as iminodibenzyl and has excellent activity and selectivity properties.

It is particularly surprising that, as exemplified in Examples 12-15, contrary to the expectations generated by CH-442,319, the best reaction and maximum yield of iminostilbene is obtained specifically at and above the reaction temperature of 550 ° C.

20

As exemplified in Example 2, the invention provides the advantage that the contact catalyst of the invention has a lifetime of more than 1100 hours, without wasting said iminodibenzyl moieties in undesired oxidative side reactions. Hereby, according to the invention, there is the possibility of a continuous method.

Suitable promoters are, for example, magnesium, calcium, cerium, molybdenum, cobalt, vanadium and tungsten compounds, for example, as oxides of these metals, in particular tungsten, cerium, vanadium and cobalt oxide.

While the foregoing and similar promoters may further improve catalyst efficiency, they are not necessary, as shown in Examples 17-20. The proportions of the components, by the way, are not a critical factor, as long as the iron and potassium contents remain within the definition given above 4105027.

The contact catalyst used in accordance with the invention is brought into contact with the iminodibenzyl vapor from a recommended but not necessarily adiabatic fixed bed reactor. However, tubular (Rohrbvindel), fluidized bed and vortex reactors as well as other prior art reactor types may also be used. The morphology of the catalyst used in accordance with the invention should provide as little resistance as possible to the vapor flowing through the catalyst layers. Preferably, geometric, e.g. cylindrical bodies having a length of about 1-6 mm, particularly 1-4 mm, and a diameter of about 0.5-5 mm, particularly 1-3 mm, are used, and further granulate having an average granulation (grain size) is used. ) is about 0.5 to 5 mm, especially about 1 to 3 mm.

The working temperature is above 500 ° C-600 ° C, preferably about 550-600 ° C, and the iminodibenzyl vapor is diluted with an iner-20 account with a carrier gas such as nitrogen or especially 50-200 times, e.g. 120-140 times molar amount of water vapor. In this case, work is preferably carried out at normal pressure or at low vacuum, e.g. about 0.2-1.1 bar, especially 0.95-1.05 bar (absolute), and ··; The reaction gas is allowed to cool to room temperature, whereupon the formed iminostilbene and unreacted iminodibenzyl are precipitated in a solid form in condensed transport water. The iminostilbene moiety can then be separated from the condensate, and the unreacted iminodibenzyl 30 can be isolated and recycled. The method used is known and described, for example, in CH-442,319.

The following examples illustrate the invention. Temperatures, expressed in degrees Celsius and pressure values in absolute ba-35 Reina.

Example 1: Dehydrogenation of iminodibenzyl (IDB) to iminostil 105027 5 is (IS) in a gas phase is carried out in a quartz glass tube reactor having a diameter of 31 mm and a length of 1 m. The middle of the reaction tube is filled between 30 g of cores Catalysts 5 having the following characteristics:

Composition: 1.1 wt% chromium oxide, calculated as Cr203 22 wt% potassium compound, calculated as K20, remainder of iron oxide Grain size: 1-2 mm

The upper filler layer acts as a vaporization zone for iminodibenzyl. 27.7 g of water are evaporated in a separate furnace and introduced into the reactor from above. Iminodibentyl is dosed as a melt at 6 g / h at 120 ° C directly into the evaporation zone slurry, mixed with preheated steam and evaporated. By means of the electric heating of the reactor, the vapor mixture is heated to a reaction temperature of 550 ° C. After reaction in a catalyst bed approximately 35 mm high, the product vapor is cooled to room temperature in a vessel whereupon a mixture of iminodibenzyl and iminostilbene precipitates in condensed water as a powder. The condensates taken at various times during the experiment are homogenized with dioxane and analyzed by capillary gas chromatography (without water). During the 860 hour trial period, the following product formulations (without * '25 water) were obtained:

Time IDB IS Page Comb. Yield Select.

[h] p .-% p .-% p. -%%% 2 25.0 51.4 20.9 75 72 25 28.9 49.6 21.5 71 70: 30 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 6 105027

In addition to iminodibenzyl (IDB) and iminostilbene (IS), predominantly by-products are 9-methyl acridine and acridine. The test is conducted continuously for about 100 hours each time and is interrupted for the weekend. After interruption, the catalyst is purged with steam at the reaction temperature for one hour and then cooled to room temperature under nitrogen. When the test is restarted, the procedure is reversed.

Example 1 demonstrates the long life and continuous operation of the catalyst.

Example 2; The quartz glass tubular reactor is filled in accordance with Example 1 with 80 g of catalyst having the following composition:

Composition: 12.3 wt.% Of potassium oxide, calculated as K 2 O, 1.9 wt.% Of chromium oxide, calculated as Cr 2 O 3 1.6 wt.% Of tungsten oxide, calculated as W 3 O 2.4 2.4 wt.% Of cerium oxide, calculated as Ce 2 O 3 1.5 wt% vanadium oxide calculated as V205 0.3 wt% cobalt oxide calculated as Co203 remainder iron oxide Grain size: 1-2 mm 25 t * ·

A stream of 40 g / h iminodibenzyl and 480 g / h water vapor is passed at 590 ° C for 1145 hours with the weekend interruptions of Example 1 through the catalyst. The product which is separated from the water by filtration 30 has the following composition (as a function of reaction time): 105027

Time IDB IS Page Comb. Yield Select.

[h] p .-% p .-% p .-%% 39 13.5 76.2 10.3 87 88 148 13.5 74.7 11.8 87 87 5 250 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 10 914 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 shows the good selectivity of the catalyst, 15 long lifetime of more than 1100 hours and continuous operation using cobalt oxide tungsten, cerium, vanadium as promoters.

Examples 3-6: Under the same experimental set-up and under the same conditions as in Example 1, the amount of water is varied over a wide range "relative to the IDB dosage:

Ex. Water IDB IS Side Conn. Yield Select.

[g / h] p-% p -% p -%%% 3 11.7 38.6 32.0 29.4 61 52 - 25 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

Examples 3-6 show a high ratio of water to IDB. 30 effect on the selectivity of the reaction.

8 105027

Examples. 7-11: In the same experimental set-ups and 30 g of the same catalyst as in Example 1, dehydrogenation is carried out at 570 ° C. The dosage of IDB and water is then adjusted so that the ratio of water to IDB remains constant.

5 Eg Water IDB IDB IS Side conn. Yield-Se- [g / h] [g / h] p .-% p .-% p .-% to lect.

%% 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 10 11 27.7 3 5.5 57.5 37.0 95 61

Examples 7-11 illustrate the effect of contact time (contact time factor = 1-10 h 9 (catalyst) h (contact time factor = ____) 9 (iminodibenzyl) per hour) on yield or selectivity of the reaction while maintaining the same ratio of water to iminodibenzyl (IDB).

Examples 12-15: In the same experimental set-up and 30 g of the same catalyst and with the same dosing of water and IDB as in Example 1, the dehydrogenation reaction is carried out at different temperatures. The product compositions are shown in the following table.

For example, temperatures. IDB IS Page Comb. Yield Select.

. [° C] p · -% p .-% p .-%% 12,510 55.1 32.7 12.2 45 73 30 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 105027 9

Examples 12-15 show a strong effect of temperature on reaction rate and reaction selectivity.

Example 16: A reactor of Example 1 is charged with 30 g of a cat-5 lyser having the following characteristics:

Composition. 9.0 wt.% Of potassium compound as K 2 O 0.04 wt.% Of chromium oxide as Cr 2 O 3 2.7 wt.% Of calcium compound as CaO 10 4.8 wt.% Of cerium oxide as Ce 2 O 3 2.5 wt. % magnesium oxide calculated as MgOr 2.0 wt% molybdenum oxide calculated as Mo03 remainder iron oxide Grain size 1,5 mm 15

At 0.4 bar (absolute) and 570 ° C, a steam stream of 6.0 g / h IDB and 55.4 g / h water is passed through the catalyst. The product contained 2.9 wt% IDB, 74.0 wt% IS and 23.1 wt% side compounds (mainly acridine and 9-methyl acridine-20) in addition to water. The same experiment under normal pressure gave a product composition of 6.2 wt% IDB, 66.9 wt% IS and 26.9 wt% side compounds.

Example 16 shows the effect of vacuum (vacuum) on the reaction of T. 25 and the selectivity of the reaction.

Examples 17-20: The following examples describe the effect of the catalyst composition on the reaction or on the selectivity of the reaction under the same experimental conditions. In the test apparatus 30 of Example 1, 30 g of the following catalyst (grain size 1-2 mm) are each tested. 15 g / h of IDB and 180 g / h of water are passed through the catalyst at 50 ° C as a vapor.

105027 10

For example, IDB IS Side Conn. Yield Select.

p .-% p .-% p .-%% 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 5 20 27.2 60.0 12.8 73 82

The compositions of the catalysts used in Examples 17-20 are shown in the following table: 10% Fe203 K20 Cr203 CaO Ce2 03 MgO Mo03 [wt%] (wt%] wt%] wt%] [wt%] {p.%] 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 02.5 --- 0.5 --- 0.1 15

Examples 17-20 show that the reaction can be carried out with different catalysts of very different compositions.

7. Example 21: A test apparatus of Example 1 is charged with 30 g of catalyst having the following characteristics:

Composition: 1.3 wt.% Of chromium oxide, calculated as Cr: 03 13.1 wt.% Of potassium compound K, 0, calculated as 25 remainder of iron oxide

Grain size 1-2 mm

A steam stream of 6 g / h iminodibent-30 warts and 72 g / h water is passed through the catalyst at 550 ° C and 5 bar absolute pressure. After filtration and drying of the condensed product, a mass of 99% by weight of the (iminodibenzyl) constituents calculated based on 105027 11 can be recovered. The 1% mass loss is due to hydrogen and methane cleavage from the reaction components. The composition of the isolated product was: 76.2 wt% iminostilbene, 3.8 wt% iminodibenzyl and 20 wt% side compounds. The total yield of iminostilbene, taking into account the weight loss, is thus 75.4%.

This example demonstrates the high yields and small mass losses that can be achieved by continuous reaction.

10

Comparative Example 1: (Comparison to the Periodic Table)

The test apparatus of Example 1 is loaded with 50 g of the catalyst described in Example 1 of CH-442,319. According to the previous patent 15, the reaction is carried out at 430 ° C at an absolute pressure of 1 bar by a periodic procedure. The cycle times were: 5 minutes pre-rinsing with steam, 18 minutes reaction, 5 minutes post-rinsing with steam and 30 minutes regeneration (air oxidation of the catalyst). The dosage was as follows: pre-rinsing with water vapor: 38.3 g / h; reaction: 8.3 g / h IDB and 38.3 g / h water vapor; post-rinsing: 38.3 g / h water vapor; and regeneration: 100 ml / min air and 38.3 g / h water vapor. The product collected over 20 cycles is filtered and dried. The amount of material obtained corresponded to 88% by weight of the ~ 25 IDB used. Since part of the product remained in the catalyst after the reaction step, this adsorbed portion is oxidized during the regeneration step to become unusable with air. The average composition of the product was 65 wt% iminostilbene, 28 wt% iminodibenzyl and 7 wt% side compounds. The total yield, taking into account the mass losses, was thus - 57%.

This comparative example shows a significantly lower yield of the batch method compared to the continuous method 35.

105027 12

Comparative Example 2: (Comparison to my periodic method

5 g / h IDB and 23.3 g / h water vapor are passed through the catalyst in the same test apparatus, at the same cycle times, 5 under the same catalyst and under the same conditions as in Comparative Example 1. After filtration and drying of the reaction mass, 78% can be isolated. The average composition of the product was 72 wt% iminostilbene, 16 wt% iminodibenzyl and 12 wt% side compounds. The size-10 female yield including mass loss was thus 56%.

This comparative example demonstrates that reducing the ratio of metered IDB to catalyst amount can increase yield, but the overall yield is not increased due to higher mass losses resulting from catalyst regeneration.

• ·

Claims (11)

105027 A process for the preparation of an iminostilbene of formula I by high temperature dehydrogenation from an iminodibenzyl of formula II (030 °) H 15 with a contact catalyst containing iron, chromium and potassium compounds in a vapor phase at a temperature of 500-600 ° C. containing from 44 to 85% by weight of iron compound calculated as Fe2O3, from 20 to 35% by weight of potassium compound calculated as K2O and not more than 3.5% by weight of chromium compound calculated as Cr2O3 and, if necessary, at least one promoter serving 2-3 % by weight of magnesium compound, calculated as MgO, 1-3% by weight of calcium compound, calculated as CaO, 0.5-5.0% by weight of ze-25 compound calculated as Ce2O3, 0.05-2.5% by weight molybdenum compound, calculated as MoO3, 0.02-1.0% by weight of cobalt compound, calculated as Co2O3, 0.02-2.5% by weight of vanadium compound, calculated as V205, or 0.02-2, 0 wt% tungsten compound calculated as W03. 30th A process according to claim 1, characterized in that tungsten, cerium, vanadium and cobalt oxide are used as promoters. 3. A process according to claim 1, characterized in that magnesium, cerium and molybdenum oxide are used as promoters. 105027 Process according to one of Claims 1 to 3, characterized in that it comprises a catalyst containing 9 to 31% by weight of the potassium compound calculated as K 2 O. Process according to one of Claims 1 to 4, characterized in that the catalyst is brought into contact with the iminodibenzyl vapor in a tubular reactor. Process according to one of Claims 1 to 5, characterized in that it utilizes a catalyst consisting of a granulate having an average granulation (grain size) of about 0.5 to 5 mm. Process according to one of Claims 1 to 6, characterized in that the process is carried out at about 550-600 ° C. Process according to one of Claims 1 to 7, characterized in that the iminodibenzyl vapor is diluted with an inert carrier gas. 20 Process according to one of Claims 1 to 7, characterized in that the iminodibenzyl vapor is diluted with about 50-200 times the molar amount of water vapor. Method according to one of Claims 1 to 9, characterized in that the process is carried out at a pressure of from about 0.2 to about 1.1 bar (absolute). The process according to any one of claims 1 to 9, characterized in that the process is carried out at a pressure of from about 0.95 to about 0.05 bar (absolute). 9 «105027