2- chloropyridine -N- oxide pharmaceutical grade large cargo small cargo

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Pyridine nitrogen oxides and their derivatives are important intermediates for organic synthesis of pyridine as raw materials. They are very different from their unoxidized parent compounds in their properties, and are obviously different in electrophilic and nucleophilic substitution reactions.Mainly because oxygen atom has an important influence on the reaction, and can be removed by reduction method after the reaction, so it is often used as the positioning group of substitution, rearrangement and other reactions.At the same time, many medicines, dyes, bactericidal preservatives, catalysts and so on are derivatives of pyridine nox, so the study of these compounds has important significance and practical value.2-chloropyridine n-oxide is an important compound in pyridine series of nitrogen oxides, which is an important intermediate of pesticide, medicine and daily chemical products, as well as an important intermediate in the synthesis of skin cleanser, shampoo and pyrithiazine antiseptic fungicides.It is a necessary raw material for the synthesis of phenylurea plant growth regulator important intermediate synthesis-2-chloro-4-nitropyridine, especially in the production of anti-dandruff antipruritic ZPT and water-soluble anti-mildew anti-pruritic ANTI-dandruff antipruritic PC preservatives.There are many synthetic methods to prepare 2-chloropyridine n-oxide, such as hydrogen peroxide oxidation, peroxide acetic acid oxidation, sodium perborate oxidation and so on.In this experiment, tungstic acid and sulfuric acid as catalyst, hydrogen peroxide as oxidant, from the amount of catalyst and oxidant, reaction temperature, reaction time and other aspects of the comparative experiment, from which to find the rule of the best reaction conditions, for the synthesis of 2-chloropyridine nitrogen oxides to provide basic data.1 Materials and Methods 1.1 Experimental instruments and reagents Electric mixer (Shandong Juancheng Xiangyang Instrument Factory, Model D8401), voltage regulator transformer (Tianjin Dongfeng Electric Factory, Model TDGC2-2), water ring vacuum pump (Zhengzhou Great Wall Instrument Factory, model SHB-3), melting point tester (Beijing No. 3 Optical Instrument Factory,Model X-4), spherical condenser, thermometer, four-port flask, water bath, constant pressure drip funnel.2-chloropyridine (98% above), hydrogen peroxide (30% hydrogen peroxide), tungstic acid, concentrated sulfuric acid, distilled water, 4% dilute HCl, CaO.1.2 Synthesis equation, as shown below:Figure 1 reaction formula for 2-chloropyridine n-oxide synthesis 1.3 Experimental Procedure Add 25ml 2-chloropyridine, 28mL distilled water, 1.1ml 98%concentrated sulfuric acid and 2.2g tungstic acid into a 250mL four-end flask equipped with an electric mixer, thermometer, spherical condenser and a constant pressure drop funnel. Start the mixer.Add 30mL hydrogen peroxide to the constant pressure drop funnel.Adjust the water bath temperature, when the reaction liquid temperature reaches 70℃, start to drop hydrogen peroxide, control the temperature at 70 ~ 80℃, about 12h to finish adding, then continue to stir at 75 ~ 80℃ and keep for 24h, take samples every 3h, a total of 8 samples.At the end of the reaction, the solution turned into a light yellow transparent solution and was lowered to room temperature. The sample was analyzed by gas chromatography and the conversion rate of the reaction was calculated.Add 2.5gcao into a small beaker, and then add distilled water to prepare Ca(OH)2 emulsion. Adjust the pH value of the reaction solution to 6 ~ 7 with this emulsion, stir at room temperature for 1h, precipitation is generated, the precipitation is CaWO4, filter and wash the precipitation, dry for later use.Dilute hydrochloric acid with the amount of 2-chloropyridine and other substances is added to the filtrate to make the product into salt, and the water is dried by vacuum distillation with a water pump, and the 2-chloropyridine hydrochloride of nitrogen oxide is a light yellow solid, and its melting point is 141 ~ 143℃, which is consistent with the theoretical value, so as to calculate the yield.2 Results and Discussion 2.1 Influence of Different catalyst Dosage on reaction Yield In 2-chloropyridine n-oxidation reaction, the use of catalyst is very important, the yield of the reaction is closely related to the amount of catalyst, and the conversion rate of the reaction is calculated by measuring the remaining amount of unreacted 2-chloropyridine by gas chromatography.Other conditions: 25ml 2-chloropyridine, 2.2g tungstic acid, 30mL hydrogen peroxide, 28mL distilled water, the reaction temperature is 70-80 ℃, the reaction time is 12h.When the volume fraction of concentrated sulfuric acid and 2-chloropyridine was 0.2∶1.0 ~ 0.3∶1.0, the side reaction increased rapidly and the yield of the reaction decreased obviously when it was higher than 0.3∶1.0.In this experiment, another catalyst tungstic acid was used, and the effect of tungstic acid dosage on the yield was investigated. N1 was N-oxidation-2-chloropyridine, n2 was 2-chloropyridine, similarly below.Other conditions: 25mL

2-chloropyridine, 30mL hydrogen peroxide, 28mL distilled water, 1.1ml 98% concentrated sulfuric acid, the reaction temperature was 70-80 ℃, the reaction time was 12h.Under these conditions, the reaction yield is the highest when the amount of tungstic acid is 2.2 ~ 3.0g, that is, the molar ratio of 2-chloropyridine to tungstic acid is 18.5∶1 ~ 20.8∶1.If tungstic acid is not used or the amount of tungstic acid is too small, the conversion rate of the reaction will be significantly reduced.On the contrary, excessive use of tungstic acid will also interfere with the reaction, so that the selectivity of the reaction is reduced, and tungstic acid is expensive, the cost of large use is too high, the best reaction will be recycled tungstic acid, so as to reduce the cost, but also reduce the pollution of heavy metals to the environment.2.2 Influence of dosage of hydrogen peroxide on reaction Hydrogen peroxide is the oxidant of the reaction, and its dosage is also a key factor affecting the reaction.Theoretically, if the reaction can occur completely, the required raw material hydrogen peroxide and 2-chloropyridine is equal to the molar ratio, but in practice, in order to convert 2-chloropyridine to a greater extent, n-oxidation-2-chloropyridine, it is usually necessary to add excessive oxidants.In this experiment, different experiments were carried out under certain conditions by changing the dosage of hydrogen peroxide, other conditions: 25ml 2-chloropyridine, 2.2g tungstate acid, 28mL distilled water, 1.1ml 98% concentrated sulfuric acid, the reaction temperature was 70 ~ 80℃, the reaction time was 12h.When the molar ratio of hydrogen peroxide to 2-chloropyridine was between 1.3∶1 and 1.5∶1, the yield of the reaction was higher, but the excessive amount of hydrogen peroxide did not contribute significantly to the increase of the yield of the reaction.2.3 Influence of Temperature on reaction the nitride oxidation reaction of 2-chloropyridine is special, which is particularly sensitive to temperature. When the reaction temperature is too high, the color of the reaction solution will be deepened, so that the final product will be darker.And the temperature is too low, and will slow down the reaction or even no reaction.This experiment confirms that the optimum temperature is 70 ~ 80℃.2.4 Effect of Holding Time on reaction yield In the 2-chloropyridine n-oxidation reaction, the yield of the reaction is significantly related to the temperature and the length of holding time, and the experimental results are shown in Table 4.In a certain range, the length of holding time is proportional to the reaction yield;But when the holding time is more than 30h, the reaction yield basically remains unchanged.Samples were taken at different holding times and then determined by gas chromatography.Other conditions: 25ml 2-chloropyridine, 30mL hydrogen peroxide, 2.2g tungstic acid, 28mL distilled water, 1.1ml 98% concentrated sulfuric acid, reaction temperature 70-80 ℃, reaction time 12h.[1] Wang Chang-shou, HUANG Jian-liang, Zhang Zhi-jie.Preparation of 2-chloropyridine n-oxide by catalytic oxidation [J]. Shaanxi Chemical Industry, 1999, 28:26-30. (in Chinese