JPS5940152B2 - Production method of phthalazinone - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel method for producing 1-phthalazinone. Specifically, the present invention relates to a novel method for producing 1-phthalazinone. This is a novel production method for producing 1-phthalazinone in an extremely good yield by reacting it with hydrazine in the presence of a solvent capable of producing it.

The gist of the present invention is shown by the following reaction formula.

qcNH2N-:/H2O□ZH I ■ 1-phthalazinone (■) is an important compound as a synthetic intermediate for pharmaceuticals, such as antihypertensive agents, and many production methods have been proposed for this.

Its main manufacturing method is (1) using phthalide as a synthetic intermediate;
- Process for producing logenophthalide (Acta,
Pol, Pharm, 25, 105 (1968) [C
, A,'' and, 77198c (1968)]), (Ij)
Oxidizes naphthalene, phthalonic acid, 1-phthalazone-4-
Production method via carboxylic acid (Yakugaku Zasshi 5, 1423
(1955)), Method for Reacting Phthalaldehyde Acid with Hydrazine (Chem, Ber., Z, 521).
(1893)), (IN/)α・α′-polychloro
A method of reacting 0-xylene with hydrazine (Fr,
Patent.

1438827 (1966)), [C, A, 66, 95
069d (1967)]).

Among these methods, methods (1) to 3 have problems such as the long manufacturing process from raw materials, complicated reaction operations, and the use of expensive chemicals, so they are not necessarily satisfactory as industrial manufacturing methods. I can't say this is the right way to do it. In addition, the method (11-l) has difficulty in supplying the raw material compound. With the aim of developing an industrial production method for 1-phthalazinone that can solve these drawbacks, the present inventors focused on using inexpensive and easily available compounds as starting materials, and as a result of their studies,
α・α-Cycloro-0-tolnitrile I (German Patent Publication No. 2207550 (1972)), which is produced in good yield by chlorination of the side chain of 0-tolnitrile, is subjected to one-step ring closure with hydrazine in the presence of a base catalyst. The present invention was successfully completed by successfully developing a method for producing the desired 1-phthalazone in good yield through the following reaction. To describe the present invention in more detail, this reaction is achieved by heating and ring-closing α·α-dichloro-0-tolnitrile and hydrazine in a suitable solvent in the presence of a strong base. In this reaction, the presence of a strong base is essential, and the ring-closing reaction does not proceed, for example, even when I is reacted with excess hydrazine or when these are reacted in the presence of an organic base such as triethylamine. In addition, in this reaction, the production of 1-aminophthalazine, which is generally expected from the condensation ring-closing reaction of a nitrile group and an amino group, may be produced in some cases, but it is only a very small amount, and the target compound is This does not in any way reduce its value as a synthetic intermediate. To describe this reaction in more detail, the solvent used in the reaction is water, lower alcohols, or a mixed solvent thereof. As the base catalyst, inorganic bases, particularly alkali metal hydroxides such as caustic soda and caustic potash, alkaline earth metal hydroxides such as calcium hydroxide, etc. are suitably used, and the amount thereof is usually 1% per raw material compound I. -5 times the mole range. Hydrazine hydrazine, which is an auxiliary raw material, is used as hydrazine hittride, which is available at a low cost, and is usually in a slight excess of the raw material compound (1), with an appropriate amount of 1 to 1.5 molar equivalents. Although the reaction temperature depends on the solvent used in the reaction, it is appropriately selected from the range of 50 to 120°C, and usually 80 to 100°C is suitable for the reaction in an aqueous solution. After carrying out the reaction as described above, the reaction mixture is neutralized, and the resulting compound () is separated from the reaction system by conventional means to obtain 1 phthalazinone (1) in good yield.
) can be obtained.

As described above, according to the method of the present invention, α-α-dichloro-0-tolnitrile (1), which is available at low cost as an industrial raw material, can be produced at low cost through simpler steps and operations compared to conventional methods. It is possible to produce the compound () and provides an excellent industrial production method. Example α・α-dichloro-0-tolnitrile 3.727, 85
% hydrazine hydrogen chloride 1.53 and caustic soda 2
．． 47 with 10 ml of water and reacted at 90-100° C. with stirring for 8 hours.

Claims (1)

[Claims] 1-, characterized in that α・α-dichloro-0-tolnitrile is reacted with hydrazine in the presence of a base catalyst.
Method for producing phthalazinone.