CN1091442C

CN1091442C - Method for preparing phenylpyridyl substituted urea

Info

Publication number: CN1091442C
Application number: CN96118798A
Authority: CN
Inventors: 郭立
Original assignee: NORTHWEST INST OF PHYTOLOGY CHINESE ACADEMY OF SCIENCES SHAANXI PROV
Current assignee: NORTHWEST INST OF PHYTOLOGY CHINESE ACADEMY OF SCIENCES SHAANXI PROV
Priority date: 1996-11-15
Filing date: 1996-11-15
Publication date: 2002-09-25
Anticipated expiration: 2016-11-15
Also published as: CN1182736A

Abstract

The present invention discloses a preparation method of N-phenyl-N'-(4-pyridyl) urea. The present invention is mainly characterized in that isoniazid hydrazoate is dissolved into benzole according to the proportion of more than 3 liters for per molar weight, insoluble substances are filtrated, aniline is added, and the mixture is placed into a hot-water bath to be heated until reaction solution is boiled for 4 hours, the mixture is cooled, and products are separated. The present invention has the advantages of simple operation, short manufacturing period, low cost, high yield and high purity. Besides, the method is suitable for the preparation of industrial production, and consequently, the method can be used as a plant growth regulating agent to be widely applied to agricultural production.

Description

A kind of preparation method of phenylpyridyl substituted urea

The invention belongs to improvement, relate to the technical field of crop growth conditioning agent the phenylpyridyl substituted urea preparation method.

The molecular structural formula of phenylpyridyl substituted urea of the present invention is

Its chemical name is N-phenyl-N '-(4-pyridyl) urea, is called for short 4-PU, is a kind of phenylurea derivative.Put down in writing by people such as Soshiro on 1978 Britain " vegetable chemistry ", proof in the experiment of tobacco tissue culture, 4-PU is a kind of highly active phytocytomine, uses the obvious facilitation that is formed with to bud separately.1989 " gardening journal " put down in writing people such as Ogata and 4-PU has been applied in the experiment of apple, Japanese pear, cherry and Kiwifruit, proves that 4-PU can improve the output of apple, Japanese pear and cherry, increases Kiwifruit single fruit weight 50-60%.The inventor was applied to proof in the thin dish experiment such as broccoli, cucumber with 4-PU in 1994 to 1996,4-PU can improve broccoli output 34-40%, improve cucumber yield 50-67%, and 4-PU is applied in the experiment of wheat and paddy rice, obtained tangible effect of increasing production, can effectively increase wheat grains per spike 2.9-5.1 grain, thousand seed weight increases the 2.1-9.0 gram, and yield of wheat improves 15-40%.

4-PU be the earliest nineteen sixty-five by people such as Bruce be synthesized (" life science " 4,461～466).It synthesizes and is divided into two processes, earlier vazadrine and Sodium Nitrite is reacted in hydrochloric acid medium, generates the vazadrine triazo-compound, separation and purification; The reacting by heating in benzole soln with vazadrine triazo-compound and aniline generates 4-PU, separation and purification again.

In people's such as above-mentioned Soshiro work.Concrete grammar to the 4-PU preparation is as follows.Its first step: with the vazadrine (4-H of 0.1mol amount ₂NNHCOC ₅H ₄N) be dissolved in 21.65% hydrochloric acid of 33.6ml, between 0-5 ℃, drip the 30ml aqueous solution of the Sodium Nitrite of 0.2mol amount, stir simultaneously, stirred 30 minutes down at 0 ℃ afterwards, use the extracted with diethyl ether reactant again, extremely neutral with aqueous sodium carbonate washing ether layer, reclaim ether, residue is separated out white crystal after several days, filtration, drying obtain the vazadrine triazo-compound.Since this preparation process numerous and diverse, the cycle is longer, the back by people such as Tohru this step is improved; The vazadrine of 0.1mol amount is dissolved in 24% hydrochloric acid of 30ml, at 2 ℃ of 10ml aqueous solution that drip the Sodium Nitrite of 0.11mol amount down, stir simultaneously, restir is 1 hour afterwards, neutralizes with 20% aqueous sodium carbonate, get reactant with ether benzene again, with sodium bicarbonate washing ether layer, reclaim ether, residue is separated out white crystal in refrigerator overnight, filtration, drying obtain the vazadrine triazo-compound.Though its yield slightly improves, the cycle shortens, that this preparation process still seems is numerous and diverse, the cycle is long, cost is high, yield is low and unstable.Second step of Soshiro is: the vazadrine triazo-compound of equimolar amount and aniline are dissolved in the benzole soln, and heating in water bath refluxed 4 hours, and reaction finishes, reaction solution is passed through silica gel column chromatography, with 1: 1 acetone and chloroform wash-out, separation and purification again obtains the 4-PU xln.This process adopts column chromatography method as can be seen, uses a large amount of organic solvents, makes the cost raising, and trivial operations, yield are low.The inventor repeats that product that said process obtains is separable to go out two kinds of xln in addition, and a kind of is that white needle-like crystals is 4-PU, and biological activity is arranged, fusing point mp162～164 ℃; Another kind is faint yellow tabular crystal, for there not being bioactive by product, and mp173～175 ℃.

From above-mentioned preparation process as can be seen, existing method not only trivial operations, preparation cycle is long, yield is low, cost is high, and purity is low, thereby can not be used for industrial preparation, has limited the application of 4-PU on farm crop produce.

The objective of the invention is existing 4-PU preparation method is improved, overcome above-mentioned defective.

4-PU preparation method's proposed by the invention technical scheme is, the vazadrine is dissolved in concentration greater than in 25% the hydrochloric acid, below 5 ℃, agitation and dropping is gone into and the aqueous solution of vazadrine with the Sodium Nitrite of molar weight, keep temperature of reaction stirring 1 hour below 10 ℃ afterwards, again with saturated aqueous sodium carbonate alkalization, separate out white crystal, after filtration, obtain the vazadrine triazo-compound after the drying in the reaction solution; In the ratio of 1 molar weight the vazadrine triazo-compound is dissolved in the benzene greater than 3 liters, the elimination insolubles, add aniline again with vazadrine triazo-compound equimolar amount, placing hot water bath to be heated to the reaction solution boiling kept 4 hours, naturally cooling, separate out white crystal, after filtration, obtain 4-PU after the drying.

From above-mentioned technology as can be seen, 4-PU preparation method of the present invention not only operates greatly, and simplification, preparation cycle obviously shorten, cost reduces significantly, face and yield and purity are all high, are convenient to industrial preparation, thereby make the 4-PU can widespread use on farm crop produce.The present invention has strengthened concentration of hydrochloric acid in the first step process, make reaction more thorough, use the saturated sodium carbonate alkalization that moisture content has been reduced to lower-most point, make the vazadrine compound that dissolves directly from reaction solution, separate out, do not use silica gel column chromatography, saved a large amount of organic solvents; In the present invention's second step process, strengthened the usage quantity of reaction medium benzene, and elimination insolubles, reacting by heating to the boiling, make reaction more thorough, thereby 4-PU directly separated out from reaction solution, saved a large amount of organic solvents.Thereby the production preparation that makes 4-PU more levels off to suitability for industrialized production.

Embodiment 1-1: the vazadrine (13.7 gram) that takes by weighing 0.1 molar weight is dissolved among 25.7% the hydrochloric acid 35ml, is stirred to dissolving.At 0 ℃ of aqueous solution that drips about 0.11 molar weight (7.5 gram) Sodium Nitrite, stir in the dropping process and maintain the temperature at below 5 ℃, add the back and keep temperature of reaction, restir 1 hour below 10 ℃.The saturated aqueous sodium carbonate stirring is added in the reaction solution, separate out the white crystals body in the solution.After the filtration, use vitriol oil drying, obtain vazadrine triazo-compound 13 grams, yield is 90%, its mp29-35 ℃.

Embodiment 1-2: the vazadrine (137 gram) that takes by weighing 1 molar weight is dissolved among 28.8% the hydrochloric acid 500ml, is stirred to dissolving, and is at 0 ℃ of aqueous solution that drips about 1.2 molar weights (84 gram) Sodium Nitrite, identical among operation thereafter and the routine 1-1.Obtain vazadrine triazo-compound 143 gram, yield is 97%, its mp29～35 ℃.

Embodiment 1-3: the vazadrine (13.7 gram) that takes by weighing 0.1 molar weight is dissolved among 31.5% the hydrochloric acid 40ml, is stirred to dissolving.At 0 ℃ of aqueous solution that drips about 0.1 molar weight (7 gram) Sodium Nitrite, identical among operation thereafter and the routine 1-1.Obtain vazadrine triazo-compound 13.3 grams, yield is 92%, its mp29-35 ℃.

Embodiment 2-1: place the dry benzene of 100ml to dissolve the vazadrine triazo-compound of about 0.01 molar weight (1.5 gram), a spot of insolubles of elimination adds the heavily steaming aniline (1 gram) of about 0.011 molar weight again.Insert back flow reaction in the hot water bath, be heated to reaction solution boiling and kept 4 hours, afterwards with the reaction solution naturally cooling, after filtration, after the drying white crystals body 4-PU1.8 gram, yield is 84%, its mp159～162 ℃.

Embodiment 2-2: the vazadrine triazo-compound of about 0.37 molar weight (55 gram) inserted in 2 liters the dry benzene and dissolve, a spot of insolubles of elimination adds the heavily steaming aniline (32 gram) of about 0.36 molar weight again, and is identical among operation thereafter and the routine 2-1.Obtain 4-PU71 gram, yield is 90%, its mp158～160 ℃.

Embodiment 2-3: the vazadrine triazo-compound of about 0.03 molar weight (4.4 gram) is inserted in the dry benzene of 100ml and dissolve, a spot of insolubles of elimination adds the heavily steaming aniline (2.8 gram) of about 0.03 molar weight again, and is identical among operation thereafter and the routine 2-1.Obtain the 4-PU5.4 gram, yield is 84%, its mp158-160 ℃.

Claims

1. the preparation method of N-phenyl-N '-(4-pyridyl) urea, its step is, the vazadrine is dissolved in the hydrochloric acid, stirring the adding and the aqueous solution of vazadrine below 5 ℃ with the Sodium Nitrite of molar weight, restir reaction 1 hour obtains the vazadrine triazo-compound behind separation and purification, filtration drying; Second step be with the vazadrine triazo-compound of molar weight and aniline in benzene solvent, behind reacting by heating, filtration drying, promptly obtain the purpose product; It is characterized in that: the concentration of hydrochloric acid of described dissolving vazadrine should be greater than 25%, and stirring reaction needs below 10 ℃, and the separation and purification after reaction finishes is to use saturated aqueous sodium carbonate that reaction solution is alkalized, and obtains the vazadrine triazo-compound after filtration after the drying; Second step was in the ratio of 1 molar weight greater than 3 liters the vazadrine triazo-compound to be dissolved in the benzene, and the elimination insolubles adds aniline again, through the reacting by heating postcooling, is drying to obtain the purpose product more after filtration.

2. preparation method according to claim 1 is characterized in that, employed benzene is dry benzene in second step, the aniline steaming aniline of attaching most importance to.