10/10/2020 CN101386595 Chemical synthesis method of 10-methoxyl-5H-dibenz[b,f]azapine

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1. CN101386595-CHEMICAL SYNTHESIS METHOD OF

10-METHOXYL-5H-DIBENZ[B,F]AZAPINE
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Chemical synthesis method of 10-methoxy-5H-

dibenzo[b,f]azepine

Technical field
The present invention relates to the technical field of 10-methoxy-5H-dibenzo[b,f]azepine, and more
specifically to the technical field of 10-methoxy-5H-dibenzo[b,f]azepine The technical field of chemical
synthesis, in particular, refers to a chemical synthesis method of 10-methoxy-5H-dibenzo[b,f]azepine.
Background technique
10-methoxy-5H-dibenz[b,f]azepine (10-methoxy-5H-dibenz[b,f]azepine), molecular formula: C 15 H 13
NO, molecular weight: 223.27, appearance is bright yellow crystalline powder, its structural formula is as
follows:

It is a chemical intermediate and has a wide range of uses in the chemical and pharmaceutical synthesis
fields. At present, there are two main routes for the chemical synthesis of 10-methoxy-5H-
dibenzo[b,f]azepine:
A. British Patent GB943277, the announcement date: December 4, 1963, the name: Dibenz[b,f]azepines
and their preparation process (Dibenz[b,f]azepines and process for their preparation), describes a synthetic
method of 10-methoxy-5H-dibenzo[b,f]azepine, the route is as follows:

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10/10/2020 CN101386595 Chemical synthesis method of 10-methoxyl-5H-dibenz[b,f]azapine

In this method, raw material III is reacted with alkali metal hydroxide to obtain product II, and then
excess alkali metal alkanoate is refluxed to obtain product I. The reaction process of this method is relatively
long, and those skilled in the art operate according to the examples in this patent (Examples 1 and 2, where R
is a methyl group) to obtain 10-methoxy-5H-dibenzo[ b, f] The yield of crude azazepines is low, only 64.1%.
B. PCT patent WO 2005096709, the announcement date is: October 20, 2005, the name is: a 10,11-
dihydro-10-oxo-5H-dibenzo[b,f]azepine-5 -The preparation method of carboxamide (A process for the
preparation of 10,11-dihydro-10-oxo-5H-dibenz[b,f]azepine-5-carboxamide), describing 10-methoxy-5H-
diphenyl And [b, f] Azepine another synthetic method, the route is as follows:

The synthesis method uses sodium methoxide to react with raw material IV to obtain product I through
three stages. In this route, only the yield of the final product oxcarbazepine is published, and those skilled in
the art follow the example of synthesis of 10-methoxy-5H-dibenzo[b,f]azepine (Example 2 ) Operation, the
yield of crude product obtained is only 65.6%.
In this way, the use of sodium methoxide in the above two routes A and B, especially in route B, has the
disadvantage of low reaction yield.
Summary of the invention
The main purpose of the present invention is to solve the above problems and shortcomings, improve the
prior art, and provide a chemical synthesis method of 10-methoxy-5H-dibenzo[b,f]azepine, which The process
is reasonable, the reaction yield is high, and it is suitable for large-scale industrial production.
In order to achieve the above objectives, the technical solutions adopted by the present invention are as
follows:
The 10-methoxy-5H-dibenzo[b,f]azepine chemical synthesis method is characterized by using 10,11-
dibromoiminodibenzyl as a raw material, and potassium hydroxide or potassium methoxide The reaction in
methanol produces the 10-methoxy-5H-dibenzo[b,f]azepine.
The reaction equation can be expressed as:

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10/10/2020 CN101386595 Chemical synthesis method of 10-methoxyl-5H-dibenz[b,f]azapine

Preferably, the reaction process is as follows: first add the methanol into the reaction vessel, then add the
potassium hydroxide or potassium methoxide, heat to reflux until dissolved, add the 10,11-
dibromoiminodibenzyl, and heat to reflux Thereby, the 10-methoxy-5H-dibenzo[b,f]azepine is produced.
After heating and refluxing for a period of time, the methanol is distilled off under reduced pressure,
water is added, stirred, and filtered and dried to obtain the crude 10-methoxy-5H-dibenzo[b,f]azepine.
Preferably, after obtaining the crude 10-methoxy-5H-dibenzo[b,f]azepine, a refining step is also included.
More preferably, the refining step includes: adding a solvent to the crude product, heating and dissolving,
cooling, crystallization, filtering and drying, so as to obtain the 10-methoxy-5H-dibenzo[b,f]azepine product.
Because the present invention uses 10,11-dibromoiminodibenzyl as a raw material, it reacts with
potassium hydroxide or potassium methoxide in methanol to generate the 10-methoxy-5H-dibenzo[b,f]aza The
beneficial effect is that the use of potassium hydroxide or potassium methoxide in the methanol solvent in the
reaction process significantly improves the yield (increased by 22 to 26 percentage points over the prior art),
which is significantly higher than the use of sodium methoxide as The reactant method is suitable for
industrialized production and has greater implementation value and social and economic benefits.
detailed description
In order to better understand the content of the present invention, further description will be given below
in conjunction with specific embodiments.
Example 1
Add 500ml of methanol to a 1000ml flask, then add 175g of KOH, and reflux until dissolved. Put in 100g
of 10,11-dibromoiminodibenzyl, heat and reflux for 24 hours; distill the methanol to dryness under reduced
pressure, add 300ml of water, stir, filter, and dry to obtain 10-methoxy-5H-dibenzo[b,f ] 48.4g of crude
azazepines, yield 90.1%;
Add 48.4g of the above crude 10-methoxy-5H-dibenzo[b,f]azepine into 200ml methanol, heat to dissolve,
cool, crystallize, filter and dry to obtain 10-methoxy-5H-dibenzo [b, f] 41.9g of refined azazepines, with a
refined yield of 78.0%.
Example 2
Add 500ml of methanol to a 1000ml flask, and then add 219g of CH3OK (supplier: Zibo Fuxier Chemical
Co., Ltd.), and reflux until dissolved. Put in 100g of 10,11-dibromoiminodibenzyl, heat and reflux for 24
hours; distill methanol to dryness under reduced pressure, add 300ml of water, stir, filter, and dry to obtain 10-
methoxy-5H-dibenzo[b,f ] 47.1 g of crude azepine, yield 87.6%;
Add 47.1g of the above crude 10-methoxy-5H-dibenzo[b,f]azepine to 200ml of methanol, heat to
dissolve, cool, crystallize, filter and dry to obtain 10-methoxy-5H-dibenzo [b, f] 40.7g of fine azepine
products, with a refined yield of 75.7%.
In summary, the chemical synthesis method of 10-methoxy-5H-dibenzo[b,f]azepine of the present
invention has reasonable technology, high reaction yield, and is suitable for large-scale industrial production.
It should be noted that all the documents mentioned in the present invention are cited as references in this
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10/10/2020 CN101386595 Chemical synthesis method of 10-methoxyl-5H-dibenz[b,f]azapine

application, as if each document is individually cited as a reference. In addition, it should be understood that
the above are the specific embodiments of the present invention and the technical principles used. After
reading the above content of the present invention, those skilled in the art can make various changes or
modifications to the present invention without departing from the present invention. The spirit and scope of
these equivalent forms also fall within the scope of the present invention.

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