DD294247A5 - IMPROVED PROCESS FOR THE PREPARATION OF 5H-DIBENZ [B, F] AZEPIN - Google Patents

Abstract

The invention relates to an improved process for the preparation of * (iminostilbene) by catalytic dehydrogenation of * (iminodibenzyl) carried out in the liquid phase in the presence of a noble metal catalyst. It is characteristic of the process that the reaction is carried out in the melt or in a high-boiling polar protic solvent or in a mixture of a high-boiling polar protic solvent and an even higher boiling apolar solvent at temperatures below 300 ° C. and to 1 mole * 0. 35-2 mol hydrogen acceptor can be used.

Description

Improved process for the preparation of 5H-dibenz [b, f] azepine

The invention relates to an improved process for preparing the 5H-dibenz [b, f] azepine, generally known by the name iminostilbene, of the formula (I)

(I)

by catalytic dehydrogenation of 10,1-dihydro-5H-dibenz [b, fJazepine (iminodibenzyl) of the formula (II) carried out in the liquid phase

(II).

For the one-step conversion of iminodibenzyl to iminostilbene, methods based on catalytic dehydrogenation are known. According to US 3,074,931 and 3,449,324, DE 1,545,736 and JA 80 17 330, the catalytic dehydrogenation in the gas phase, in the presence of metals or metal oxides as a catalyst, at 350-600 ⁰ C is made; the transformation is incomplete.

According to EP 237 952, the kaxalytisohe dehydrogenation of iminodibenzyl to iminostilbene in the liquid phase is made. The catalyst used are noble metals or metal oxides, diphenyl ether, dimethylaniline as solvent, nitrotoluenes which are acceptable as hydrogen, diethyl maleate and tetra-bromo-benzoquinone. According to the description, the reaction proceeds at 210-250 ⁰ C in 3-5 hours. However, in-house reproducibility of the examples given showed that the reaction was highest under the reaction conditions indicated

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60-65 #ig is and can not be increased duroh much longer reaction times nioht. As the reproduction showed, a reaction time exceeding 2 hours results in decomposition conditions which deteriorate the yield and greatly reduce the quality of the product. On an industrial scale, the product can be produced in this way only in low yield and soley quality. The decomposition occurring during the long reaction time, the large excess of the hydrogen acceptor used and unsuitably selected solvents poison the catalyst, which therefore can not be reused. In summary, it should be noted that this method is not suitable for the economic production of iminostilbene on an industrial scale.

In the preparation of the invention, it was sought in the preparation of the compound (I) from the compound (II) to increase the reaction and the yield, to improve the purity of the product, to shorten the reaction time, to avoid poisoning of the catalyst or limit and to enable the process to be carried out economically on an industrial scale.

The invention is based on the recognition that the decomposition of the product is more influenced by the amount of hydrogen acceptor than by the increase in temperature. It has also been found that decomposition of the product does not occur when the reaction is carried out in the melt or in a liquid phase of particular composition at temperatures lower than 300C and in the presence of a reduced amount of hydrogen acceptor.

The invention is further based on the finding that when working in the melt or in a boiling solvent, the amount of the hydrogen acceptor can be reduced, the poisoning of the catalyst einsonänkbar or avoidable, the reaction better, the reaction time

becomes shorter and the product can be obtained in good yield and excellent quality.

The invention accordingly provides a process for the preparation of 5H-dibenz [b, f] azepine from 10,11-dihydrodibenzo [b, f] azepine by dehydrogenation in the presence of a noble metal catalyst and a vapor acceptor in accordance with the invention the reaction in the melt or in a high-boiling polar protic solvent or in a mixture of a boiling polar protisohen solvent with a nooh higher-boiling apolar solvent at temperatures below 300 ⁰ C made, and to 1 mole of 10,11-dihydrobenz [b , f] azepine are used 0.35-2 mol V / asserstoffakzeptor.

The process according to the invention is therefore carried out in the melt or in a high-boiling liquid phase. As polar protisohes solvent come, for example, ethylene glycol, oligo- and polyethylene glycols or their derivatives in Betraoht. The high boiling polar protic solvent may also be mixed with apolar solvents having a higher boiling point (e.g., diphyl, polychlorinated benzenes).

The high boiling polar protic solvents have two beneficial effects on the catalytic dehydrogenation reaction. On the one hand, they promote the adsorption / desorption processes taking place on the surface of the catalyst, in which the iminodibenzyl, the iminostilbene, the hydrogen acceptor and their reduced products participate. Since the desorption of iminostilbene and hydrogen acceptor proceeds more easily in the process according to the invention than in EP 237 952, the amount of hydrogen acceptor can be reduced (to 0.35-2 mol, based on 1 mol of compound II), thereby reducing the poisoning of the catalyst or off, resulting in an acceleration of the reaction and an increase in conversion.

" ⁴ "

On the other hand, since the reaction is carried out in. Essentially less hydrogen acceptor and solvent or at all without solvent, the concentration of the starting material in the Reaktionsgemisoh much larger. Therefore, the reaction proceeds within 1-2 hours, decomposition of the product hardly occurs, the product can be isolated in good yield and high purity.

Duroh the use of the high-boiling protic solvent and the smaller amount of hydrogen acceptor, the poisoning of the catalyst can be so far zurüokgedrängt that the catalyst can be reused several times <> Another advantage of using the high-boiling polar protic solvent is that the entire amount of ziielproduktes can be separated from the reaction mixture by adding water after completion of the reaction.

The reaction time can be further reduced by adding an apolar solvent whose boiling point is higher to the high-boiling polar protic solvent.

According to a variant of the method according to the invention, the melt of iminodibenzyl at 150-300 ⁰ C, preferably 200-250 ⁰ C, in the presence of a noble metal catalyst (palladium or platinum, optionally on a! Präger) and in the presence of based on 1 mol of iminodibenzyl 0 , 35-2 mol hydrogen acceptor (high-boiling nitro compounds, high-boiling unsaturated compounds) reacted for 1-2 hours. After completion of the reaction, the reaction mixture is dissolved hot in a polar organic solvent (eg aoeton, chloroform, dimethylsulfoxide, dimethylformamide, alcohols), the catalyst is filtered off and the product is crystallized or duroh a solvent in which it dissolves so easily (lower alcohols, Hydrocarbons, water) precipitated.

According to another variant of the process according to the invention, the iminodibenzyl is dissolved in a boiling polar protic solvent in the presence of a noble metal

0.35-2 mol of hydrogen acceptor at temperatures of 180-300 ⁰ C, preferably 200-280 ° C, reacted for 1-2 hours in the presence of 1 mol of iminodibenzyl. After completion of the reaction, the catalyst is filtered off. The product is either precipitated from the filtrate with a solvent in which it dissolves poorly, preferably with water, or the solvent is distilled off from the filtrate and the residue is treated in the manner already described.

Finally, it is also possible according to the invention to carry out the reaction of iminodibenzyl in a mixture of high-boiling polar protic solvents and still higher-boiling nonpolar solvents (eg diphyl, polychlorinated benzenes) under the reaction conditions of the first variant of the process. The isolation of the product is carried out in the manner already described.

The process will be explained in more detail with reference to the following examples.

example 1

A Gemisoh of 60 g (0.308 mol) of iminodibenzyl, 30 ml (0.254 mol) of 2-nitrotoluene and 3.6 g of 10% palladium activated carbon is heated to 100 ⁰ C. After switching on the stirrer, the melt is kept under reflux for 1-2 hours at 200-220 ⁰ C. Then the soymel is dissolved in 400 ml of diethylene glycol, the catalyst is filtered off from the hot solution, the filtrate is mixed with 250 ml of methanol and then allowed to stand overnight at 0-5 ⁰ C. The precipitated product is filtered off, washed with a little methanol and then dried. Yield: 46.5 g (71.3%), m.p .: 194-196 ⁰ C.

Example 2

6 g (0.03 mol) of iminodibenzyl, 3 ml (0.025 mol) of 2-nitrotoluene and 0.2 g of platinum black are boiled at 200-220 ° C for 1-2 hours. Then the melt is cooled, dissolved hot in 100 ml of acetone, the catalyst removed by filtration

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and concentrated the Piltrat. After cooling, the product is filtered off and dried. Yield: 5.05 g (85.0 #) Sohmp .: 190-192 ⁰ C.

Example 3

A Gemisoh of 30 g (0.154 KoI) iminodibenzyl, 200 ml of diethylene glycol and 20 g (0.146 mol) of 2-nitrotoluene is treated with 1.8 g of 10% palladium activated carbon and then at Rüokfluß 1.5 hours at 220-240 ⁰ C. gekooht. The catalyst is filtered off from the hot solution and the iminostilbene is precipitated by addition of 200 ml of water, filtered off, washed with water and then dried. Yield: 28.1 g (94.6%), Sohmp .: 194-196 ⁰ C.

Example 4

A mixture of 30 g (0.154 mol) of iminodibenzyl, 150 ml of triethylene glycol and 10 g (0.06 mol) of 1,3-dinitrobenzene is treated with 1.9 g of 10 '/ fig palladium activated carbon and then at 240-270 ⁰ C for one hour stirred for a long time. Then, the catalyst is filtered off from the hot solution, the filtrate mixed with 100 ml of methanol and cooled. The precipitated iminostilbene is filtered off, washed with 30 ml of methanol and then tocrown. Yield: 26.3 g (88.6 #), m.p .: 198 to 199.5 ⁰ C.

Example 5

12 g (0.06 mol) of iminodibenzyl and 7.4 g (0.06 mol) of nitrobenzene are boiled in the presence of 0.75 g of 10% palladium activated carbon in a mixture of 30 ml of diphyl and 30 ml of diethylene for one hour on Rüokfluß , The catalyst is filtered off while hot and the cooled solution is mixed with 60 ml of methanol. The product is filtered off, washed with 20 ml of methanol and then tocrown. Yield: 9.94 g (85.0 %), mp. I96-I98 ° C.

Example 6

A mixture of 19.5 g (0.1 mol) of iminciibonzyl, 1 g of 10% palladium activated carbon, 21.9 g (0.15 mol) of benzalacetone, 50 ml of di-ethyleneglycol and 50 ml of diphyl is boiled at reflux for 2 hours with stirring , The catalyst is filtered off while hot and the filtrate is mixed with 100 ml of methanol. After cooling, the product is filtered off, washed with methanol and then dried. Yield: 14.51 g (75.2%), Sch-ηρ «: 196-19Θ ⁰ C.

Claims (5)

claims 1. Process for the preparation of 5H-dibenz [b, f] azepine of the formula (i) by catalytic dehydrogenation of 10, 11-dihydrodibenzCb, f] azepine of the formula (II), carried out in the presence of a hydrogen acceptor, (II) daduroh characterized in that the reaction is carried out in the soymilk or in a high-boiling polar protic solvent or in a mixture of a high-boiling polar protic solvent and a still higher-boiling apolar solvent at temperatures below 300 ⁰ C and to 1 mol lO, ll DihydrodibenzD?, F] azepine 0.35-2 mol hydrogen acceptor can be used. 2. The method according to Anspruoh 1, characterized in that are used as hydrogen acceptor high-boiling nitro compounds or high-boiling unsaturated compounds « 3. The method according to claim 1, characterized that are used as polar protic solvents Athylenglycol, oligo- or polyethylene glycols and their derivatives, as apolar solvent component Diphyl or polychlorinated benzenes * 4. The method according to claim 1, characterized gekennzeiohnot that the catalyst from the Reaktionsgetnisoh optionally NaOH addition of a solvent filtered off and crystallized the product or with a solvent in which it is schleoht soluble, or preferably precipitated with water. 5. The method according to claim 1, characterized in that the noble metal catalyst used is used several times.