CN102924371A - Preparation method of 6-oxo-1,6-dihydropyridine-3-carboxylic acid - Google Patents

Abstract

The invention discloses a preparation method of 6-oxo-1,6-dihydropyridine-3-carboxylic acid, adding 0.54g of 2-chloro-5-trifluoromethyl to the liner of a 25ml jacketed hydrothermal reaction kettle Pyridine and 17ml of water were reacted at 100-180°C for 24-72 hours in a sealed sleeve-type hydrothermal reaction kettle. After natural cooling to room temperature, the inner tank was taken out, and the liquid in the inner tank was poured out. White flaky crystals were obtained in the inner tank. 6-oxo-1,6-dihydropyridine-3-carboxylic acid crystal; the method adopts hydrothermal reaction carried out at high temperature, and the synthesized 6-oxo-1,6-dihydropyridine-3-carboxylic acid The crystal has a crystal face, less thermal stress, fewer internal defects, high crystal stability, and can be placed at room temperature for a long time; the method is simple in equipment and easy to operate, using water as the reaction solvent is green and environmentally friendly, and the reaction yield is also high , can reach more than 80%.

Description

The preparation method of 6-oxo-1,6-dihydropyridine-3-carboxylic acid

technical field

The present invention relates to 6-oxo-1,6-dihydropyridine-3-carboxylic acid, in particular to a preparation method of 6-oxo-1,6-dihydropyridine-3-carboxylic acid.

Background technique

6-Hydroxyniacin is a very important chemical and pharmaceutical raw material. It is an intermediate in the synthesis of biologically active drugs and pesticides such as insecticide, bactericide, and herbicide. It has an enol structure and a relatively stable aromatic pyridine ring. , are currently on the market. 6-oxo-1,6-dihydropyridine-3-carboxylic acid is an isomer of 6-hydroxynicotinic acid as reported in Acta Cryst E (2007) E63 for 6-oxo-1,6- The crystal structure of dihydropyridine-3-carboxylic acid is a ketone structure, but its preparation method has not been reported in detail, because it is generally difficult to obtain, and the obtained crystals also have relatively large thermal stress, large internal defects, and high stability. Poor, difficult to preserve for a long time.

Contents of the invention

The technical problem to be solved by the present invention is to provide a 6-oxo-1,6-dihydropyridine-3-carboxylic acid crystal with less thermal stress, less internal defects, better stability, and long-term storage at room temperature method of preparation.

The technical scheme adopted by the present invention to solve the above-mentioned technical problems is: the preparation method of 6-oxo-1,6-dihydropyridine-3-carboxylic acid, in the liner of 25ml sleeve type hydrothermal reaction kettle, add 0.54g 2-Chloro-5-trifluoromethylpyridine and 17ml of water, sealed jacket type hydrothermal reaction kettle, reacted at 100-180°C for 24-72h, naturally cooled to room temperature, took out the inner tank, poured out the liquid in the inner tank, White flaky crystals were obtained in the liner, which were 6-oxo-1,6-dihydropyridine-3-carboxylic acid crystals.

Compared with the prior art, the present invention has the advantage of 6-oxo-1, the preparation method of 6-dihydropyridine-3-carboxylic acid, in the liner of 25ml jacketed hydrothermal reactor, add 0.54g 2- Chloro-5-trifluoromethylpyridine and 17ml of water, sealed sleeve type hydrothermal reaction kettle, react at 100-180°C for 24-72h, cool down to room temperature naturally, take out the inner tank, pour out the liquid in the inner tank, the inner tank Obtain white flaky crystals, be 6-oxo-1,6-dihydropyridine-3-carboxylic acid crystal; This method has adopted the hydrothermal reaction that carries out at high temperature, and the synthetic 6-oxo-1,6- Dihydropyridine-3-carboxylic acid crystals have less thermal stress, fewer internal defects, higher crystal stability, and can be placed at room temperature for a long time; the method is simple in equipment, easy to operate, and uses water as a reaction solvent, which is green and environmentally friendly, and the reaction product The rate is also high, reaching more than 80%.

Detailed ways

Below in conjunction with embodiment the present invention is described in further detail.

Example 1

Add 0.54g of 2-chloro-5-trifluoromethylpyridine and 17ml of water into the liner of a 25ml jacketed hydrothermal reactor, seal the jacketed hydrothermal reactor, react at 140°C for 72h, and cool naturally to room temperature Finally, take out the inner tank, pour out the liquid in the inner tank, scrape out the solid with a spatula, weigh after drying, and obtain 0.4008 g of white flaky crystals, which are 6-oxo-1,6-dihydropyridine-3-carboxylate acid crystals.

Example 2

It is basically the same as Example 1, except that the reaction temperature is 160° C., and 0.372 g of white flaky crystals are obtained.

Example 3

It is basically the same as Example 1, except that the reaction time is 48h, and 0.3444g of white flaky crystals are obtained.

Example 4

It is basically the same as Example 1, except that the reaction temperature is 180° C., and the reaction time is 24 hours, and 0.3868 g of white flaky crystals are obtained.

Example 5

It is basically the same as Example 1, except that the reaction temperature is 120° C., and the reaction time is 48 hours to obtain 0.3927 g of white flaky crystals.

In the present invention, the reaction temperature may also be 100° C., etc., and the reaction time may also be 36 h, etc., which are not listed here.

The above-mentioned white flaky crystals were measured and analyzed by IR spectrum, and the data were as follows: 3080, 2993, 2922, 2490, 1707, 1639, 1607, 1415, 1282, 1260, 1232, 1129, 913, 780, 643, 629, 503 (KBr, cm ⁻¹ ).

α＝82.50(3)°,β=78.32(3)°,γ=75.19(3)°,

Carry out unit cell parameter determination to above-mentioned white flaky crystal: concrete data is as follows:

α＝82.50(3)°, β=78.32(3)°, γ=75.19(3)°,

It shows that the obtained crystal has less thermal stress, fewer internal defects and higher crystal stability.

Claims (1)

1.6-oxo-1, the preparation method of 6-dihydropyridine-3-carboxylic acid, it is characterized in that: in the inner bag of 25 ml shell type hydrothermal reaction kettles, add 0.54g 2-chloro-5-trifluoromethylpyridine and 17 ml water, the sealing-sleeve type hydrothermal reaction kettle, at 100 ~ 180 ℃ of lower reaction 24 ~ 72 h, take out inner bag after naturally cooling to room temperature, inclining liquid in the inner bag, obtains the white plates crystal in the inner bag, be 6-oxo-1,6-dihydropyridine-3-carboxylic acid crystal.