Organic compounds -- part of the class 532-570 series – Organic compounds – Four or more ring nitrogens in the bicyclo ring system
Reexamination Certificate
1999-06-21
2001-02-27
Kifle, Bruck (Department: 1624)
Organic compounds -- part of the class 532-570 series
Organic compounds
Four or more ring nitrogens in the bicyclo ring system
Reexamination Certificate
active
06194577
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to a process for producing alicyclic hydrazine derivatives, tetrahydropyridazine and hexahydropyridazine which are useful as intermediate starting materials such as medicines and agricultural chemicals.
2. Description of Prior Art
The present inventors proposed a method for producing tert-butylhydrazine hydrohalogenic acid salt by reacting hydrazine hydrohalogenic acid salt and tert-butanol which are industrially or economically advantageous starting materials (Japanese Patent Publication No. 48823/1986).
However, it has not yet been known that a difunctional alcohol (diol) or an alicyclic ether compound reacts with a hydrazine hydrohalogenic acid salt to give an alicyclic hydrazine derivative hydrohalogenic acid salt.
As a method for producing an alicyclic hydrazine derivative or its hydrohalogenic acid salt, there are known a method of reacting an alkyl dihalide with hydrazine hydrate [USSR Pat. 87-4337106], [J. Am. Chem. Soc. 88, 3959-3963 (1966)] (prior art 1), and a method of synthesizing alicyclic hydrazine by using an alicyclic amine as a starting material [U.S. Pat. No. 3,317,607] (prior art 2).
However, the prior art 1 relating to a method of producing an alicyclic hydrazine derivative or its hydrohalogenic acid salt has a problem that an economically expensive dihalogenobutane is required as a starting material. Furthermore, the prior art 2 is a general method of synthesizing alicyclic hydrazine, but the stability and toxicity of the nitroso body which is an intermediate pose a problem.
On the other hand, a known conventional method of synthesizing hexahydropyridazine includes reacting a hydrazine dicarboxylic derivative with a dihalogenobutane to obtain hexahydropyridazine-1,2-dicarboxylic derivative, and further decarboxylating the resulting product to give an intended product [Japanese Laid-Open Patent Publication Nos. 224043/1995, 224044/1995 and 198853/1996] (prior art 3).
A method of producing hexahydropyridazine which comprises synthesizing tetrahydropyridazine from 1,4-butanedial and hydrazine and hydrogenating this tetrahydropyridazine is also known [Japanese Laid-Open Patent Publication No. 109170/1996] (prior art 4).
As a method for producing tetrahydropyridazine from 1-aminopyrrolidine, there is known a method comprising carrying out a rearrangement reaction of diazenehydrazone on silica or alumina in, for example, a chloroform-methanol solvent [Tetrahedoron Letters, No. 52, pp. 5025 to 5026] (prior art 5). Furthermore, a method comprising leaving 1-aminopyrrolidine to stand at room temperature in chloroform for 2 weeks is also known [Japanese Laid-Open Patent Publication No. 250388/1989], [Chem. Ber., 109, (11), 3707 (1976)](prior art 6).
However, the prior art 3 relating to a method for producing hexahydropyridazine has a problem that the dihalogenobutane as a starting material is economically expensive, and the synthetic route up to the product is long.
On the other hand, in the prior art 4, 1,4-butanedial used as a starting material is not easily available, and the yield is as low as about 60%.
Furthermore, the prior art 5 relating to a method for producing tetrahydropyridazine conducts a oxidation and rearrangement reaction of the starting material while it is adsorbed on silica or alumina. However, the after-treatment after the reaction is complicated. Furthermore, in the prior art 6, the reaction time is long, and it is inadequate as an industrial method for producing tetrahydropyridazine.
SUMMARY OF THE INVENTION
The present invention dissolves the defects of the conventional techniques, and makes it an object of providing a method of producing an alicyclic hydrazine derivative or its hydrohalogenic acid salt industrially and economically advantageously from an inexpensive starting material which is easy to handle, namely a diol compound or an alicyclic ether compound.
It is another object of the present invention to provide a method of producing hexahydropyridazine which is economically and industrially advantageous. In the present invention, in comparison with the prior art, hexahydropyridazine can be obtained with high selectivity from cheap and easily handlable starting materials.
Another object of the present invention is to provide a method of producing tetrahydropyridazine which becomes an intermediate of synthesizing hexahydropyridazine with high selectivity from cheap and easily handlable starting materials.
The present invention provides a method for producing an alicyclic hydrazine derivative or its hydrohalogenic acid salt which comprises reacting a hydrazine.hydromonohalogenic acid salt and a diol compound or an alicyclic ether compound in the presence of an excessive inorganic acid present in a free form or in the form of an acid addition salt.
The present invention also provides a method for producing hexahydropyridazine which comprises hydrogenating tetrahydropyridazine, wherein the tetrahydropyridazine is hydrogenated in the presence of abase.
The present invention further provides a method for producing tetrahydropyridazine from 1-aminopyrrolidine, which comprises oxidizing 1-aminopyrrolidine with an oxidizing agent to form tetrahydropyridazine.
The present invention further provides a method for producing hexahydropyridazine which comprises oxidizing 1-aminopyrrolidine with an oxidizing agent to synthesize tetrahydropyridazine, and then hydrogenating the tetrahydropyridazine in the presence of a base.
According to one embodiment of the present invention, there is provided a method for producing hexahydropyridazine, which comprises reacting hydrazine hydrohalogenic acid salt with butanediol or tetetrahydrofuran to synthesize 1-aminopyrrolidine, and then oxidizing 1-aminopyrrolidine with an oxidizing agent to synthesize tetrahydropyridazine, and thereafter hydrogenating the tetrahydropyridazine in the presence of a base.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENT
In the first embodiment of the present invention, it is desired that
1. the hydrazine hydrohalogenic acid salt is a hydrazine hydromonohalogenic acid salt expressed by the formula (1)
NH
2
NH
2
.HX (1)
wherein X represents a halogen atom;
2. the diol compound is a diol compound expressed by the following formula (2)
HO—(CH
2
)
m
—A—(CH
2
)
n
—OH (2)
wherein A represents an oxygen atom, a methylene group or an ethylidene group, and m and n are integers of 1 to 3;
3. the alicyclic ether compound is an alicyclic ether compound shown by the formula (3)
wherein r is an integer of 4 or 5.
4. the alicyclic hydrazine derivative is an alicyclic hydrazine derivative expressed by the formula (4)
wherein A represents an oxygen atom, a methylene group or an ethylidene group, and m and n are integers of 1 to 3,
or expressed by the formula (5)
wherein p is an integer of 3 or 4;
5. the excessive inorganic acid is a hydrohalogenic acid or its salt.
6. the excessive inorganic acid is present in the form of a hydrazine hydrodihalogenic acid or its salt.
7. the reaction is carried out at a temperature of 100 to 150° C. under an elevated pressure while the mole ratio of the diol compound or the alicyclic ether compound:hydrazine hydromonohalogenic acid salt:excessive inorganic acid is 1:1-10:0.2-3.
The reaction solution obtained by the above method is concentrated, and an alcohol solvent, etc. is added. The unreacted hydrazine hydrohalogenic acid salt precipitated as a crystal is removed in a customary manner. Then, the separated mother liquor is subjected to an ordinary method such as dilution or cooling, whereby an alicyclic hydrazine derivative.hydrohalogenic acid salt precipitated as a crystal can be separated and recovered. Furthermore, the above separated mother liquor is neutralized with a base, and distilled to give an alicyclic hydrazine derivative.
In the present invention, the diol compound or the alicyclic ether compound is reacted with the hydrazine hydrohalogenic acid salt in the presence o
Fujita Hiroyuki
Hasegawa Youichi
Hyoda Shunji
Oki Yasuo
Sawada Hirotoshi
Fulbright & Jaworski L.L.P.
Japan Hydrazine Co. Ltd.
Kifle Bruck
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