A kind of preparation method of salicylamide

Abstract

The present invention belongs to the field of fine chemical synthesis, and in particular to a preparation method of salicylic amide. The present invention innovatively adopts an organic solvent to replace part of phenol, and Ca-Mg-Al hydrotalcite is used as a catalyst to catalyze phenol and urea to synthesize salicylic amide. The preparation method significantly reduces the usage of phenol, can effectively alleviate the problems such as excessive wastewater caused by excessive phenol, high energy consumption, etc. The addition of an organic solvent can also dilute the reactant, improve the contact of the reaction raw materials with the active sites on the Ca-Mg-Al hydrotalcite catalyst, thereby significantly reducing the temperature and time of the reaction, that is, the present invention can prepare salicylic amide with a purity of 99.5% under mild conditions. The present invention prepares raw materials cheap and easy to obtain, and organic solvent and phenol can be recycled and reused, has good economic benefit, simple preparation process, and broad application prospects.

Description

Technical Field

[0001] The invention belongs to the field of fine chemical synthesis, and particularly relates to a method for preparing salicylamide. Background Art

[0002] Salicylamide (SA), also known as 2-hydroxybenzamide, is an important fine chemical intermediate. It can be used as a raw material for the synthesis of chemical products such as nitrosamide and o-ethoxybenzamide. It can also be used to make antipyretic and analgesic drugs for fever, headache, neuralgia, arthralgia, and active rheumatism. Therefore, it is widely used in many fields such as medicine, fragrances, dyes, and rubber additives.

[0003] Currently, the main methods for synthesizing salicylamide include ammoniation, urea and phenol synthesis, phosgene and salicylic acid solution synthesis, salicylic acid amine method, and o-hydroxybenzonitrile and D-phenylglycinol synthesis. Chinese patents CN 105503640A, CN 106518704A, and CN 102304061A disclose a method for synthesizing salicylamide using the ammoniation method. This method has a low reaction temperature (40-60°C), a short reaction time (5-6 hours), and a reaction pressure of 0.25-0.35 MPa. However, this method also has a complex product purification process and a low yield. Chinese patents CN 105646269B, CN 110183342A and CN 114225768A disclose a method for synthesizing salicylamide using urea and phenol as raw materials in the presence of a catalyst. The method uses cheap and readily available raw materials, has a simple process, and the ammonia generated by the reaction can be recycled and coupled with CO to generate urea. However, phenol serves as both a reactant and a solvent, resulting in excessive phenol consumption. After the reaction is complete, a large amount of phenol-containing wastewater is produced, polluting the environment. Furthermore, the method is carried out in a reactor filled with N2 inert gas, with a high reaction temperature (210-240°C), a long reaction time (6-24h), and a low product yield (41.2-54.3%). Chinese patent CN 113754553A discloses a continuous method for synthesizing salicylamide. This method involves reacting phosgene, an acyl chlorination reagent, with a salicylic acid solution in a continuous reactor to produce salicyl chloride. This salicyl chloride is then esterified with methanol to produce methyl salicylate. Finally, the methyl salicylate is aminated with a methanolic ammonia solution to produce salicylamide. The yield of the resulting product is greater than 98% and the purity can reach 99.1%. However, the production process is complex and industrial production is difficult. Chinese patent CN 101891645A discloses a method using salicylamide as a raw material, adding an acidic catalyst to produce a salicylamide solution with an 80% saturation. After dehydration and separation, salicylamide is obtained. The process is simple and uses a single raw material, but the product requires a reaction temperature of 145-160°C and a reaction time of 6-11 hours to obtain the product. Chinese patent CN 105017053B discloses a method for producing salicylamide using o-hydroxybenzonitrile and D-phenylglycinol as raw materials under PtCl4 catalysis. However, the method requires reflux under anaerobic conditions for 72 hours, and the product must be purified through multiple steps after the reaction. The process is complex and difficult to produce on a large scale.

[0004] Therefore, the production process of salicylamide is plagued by problems such as low product yield and purity, complex preparation process, tedious crude product purification steps, excessive phenol dosage, high reaction temperature, and long reaction time. In view of this, it is urgent to develop a new, green, and low-energy preparation method for salicylamide. Summary of the Invention

[0005] One of the purposes of the present invention is to provide a method for preparing salicylamide, which is simple, easy to operate and has low energy consumption.

[0006] To achieve the above object, the present invention adopts the following technical solutions:

[0007] A method for preparing salicylamide comprises the following steps:

[0008] (1) Phenol, urea, an organic solvent, and Ca-Mg-Al hydrotalcite are mixed uniformly, and heated to 90°C to 110°C for 2 to 5 hours;

[0009] (2) After the reaction is completed, centrifugation is performed to separate and recover the Ca-Mg-Al hydrotalcite-like substance, and the supernatant after centrifugation is taken; cold water is added to the supernatant to wash and remove residual urea, and then the organic phase is subjected to reduced pressure distillation to recover the solvent to obtain a crude salicylamide;

[0010] (3) subjecting the crude salicylic acid amide obtained in step (2) to melt crystallization to obtain salicylic acid amide.

[0011] Furthermore, the organic solvent in step (1) is one of toluene, o-xylene, and p-xylene; and the ratio of the volume of the organic solvent to the total mass of urea and phenol is 1 mL: (0.5-2) g.

[0012] Furthermore, in step (1), the molar ratio of urea to phenol is 1:(1.5-5).

[0013] Furthermore, in step (1), the mass ratio of the Ca-Mg-Al hydrotalcite to urea is 1:(10-20).

[0014] Furthermore, the preparation method of the Ca-Mg-Al hydrotalcite comprises the following steps:

[0015] (a) preparing a mixed salt solution: stirring and dissolving calcium nitrate tetrahydrate, magnesium nitrate hexahydrate, and aluminum nitrate nonahydrate in deionized water to prepare a mixed salt solution;

[0016] (b) preparing a mixed alkali solution: dissolving sodium hydroxide and sodium carbonate in deionized water to prepare a mixed alkali solution;

[0017] (c) Preparation of Ca-Mg-Al hydrotalcite: The mixed salt solution prepared in step (a) is added dropwise to deionized water, and the pH of the solution is controlled to 7.5-8.5 using the mixed alkali solution prepared in step (b); after the addition of the mixed salt solution prepared in step (a), the reaction product is kept at 55° C.-65° C. for 14-16 hours; cooled, filtered, washed to neutrality, dried, and calcined at 500° C.-600° C. for 5.5-6.5 hours to obtain Ca-Mg-Al hydrotalcite.

[0018] Furthermore, in step (a), the molar ratio of calcium nitrate tetrahydrate, magnesium nitrate hexahydrate, and aluminum nitrate nonahydrate is 2:2:1; and the mass ratio of the total mass of calcium nitrate tetrahydrate, magnesium nitrate hexahydrate, and aluminum nitrate nonahydrate to deionized water is 1:(10-12).

[0019] Furthermore, in step (b), the molar ratio of sodium hydroxide to sodium carbonate is 4:1; and the mass ratio of the total mass of sodium hydroxide and sodium carbonate to deionized water is 1:(3-6).

[0020] Furthermore, in step (c), the volume ratio of the mixed salt solution and deionized water is 1:1.

[0021] Furthermore, the temperature of the cold water in step (2) is 20°C to 25°C.

[0022] Furthermore, the melt crystallization in step (3) is to heat the crude salicylic amide to 150° C. to 160° C. to make it reach a molten state, and then cool it from liquid to solid by cooling.

[0023] Compared with the prior art, the present invention has the following beneficial effects:

[0024] (1) The present invention uses an organic solvent to replace part of the phenol, significantly reducing the amount of phenol used; and the addition of the organic solvent dilutes the reactants, improving the contact between the reaction raw materials and the active sites on the Ca-Mg-Al hydrotalcite catalyst, significantly reducing the reaction temperature and time;

[0025] (2) The raw materials for the preparation of the present invention are cheap and readily available, and the organic solvent and phenol can be recycled and reused, thus achieving good economic benefits;

[0026] (3) The process of the present invention is simple, and the crude salicylic amide can be melt-crystallized to obtain salicylic amide with a purity of 99.5%, which has application prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] Figure 1 This is the infrared spectrum of salicylamide prepared in Example 1. DETAILED DESCRIPTION

[0028] The technical solution of the present invention is further explained below with reference to specific embodiments, comparative examples, test examples and accompanying drawings.

[0029] In the following examples, comparative examples, and test examples, the raw materials and preparation methods used are conventional materials and techniques in the art unless otherwise specified.

[0030] 1. Implementation

[0031] Example 1

[0032] Example 1 provides a method for preparing salicylamide, the specific steps are as follows:

[0033] (1) To a 100 mL four-necked flask equipped with a magnet, a thermometer, and a condenser, 14.1 g of phenol, 3.0 g of urea, 11.4 mL of toluene, and 0.2 g of Ca-Mg-Al hydrotalcite were added in sequence and reacted at 100 °C for 3 h.

[0034] (2) After the reaction is completed, centrifugation is performed to separate and recover the Ca-Mg-Al hydrotalcite-like substance, and the supernatant after centrifugation is taken; 20° C. cold water is added to the supernatant to wash the residual urea, and the organic phase is subjected to reduced pressure distillation to recover the solvent to obtain a crude salicylamide;

[0035] (3) The crude salicylamide obtained in step (2) is heated to 150° C. to melt the crude salicylamide, and then cooled from liquid to solid to obtain salicylamide.

[0036] Detected by liquid chromatography, the yield of salicylamide was 92% and the purity was 99.5%.

[0037] The preparation process of Ca-Mg-Al hydrotalcite is as follows:

[0038] (a) Preparing a mixed salt solution: 1.89 g of calcium nitrate tetrahydrate, 2.05 g of magnesium nitrate hexahydrate, and 1.5 g of aluminum nitrate nonahydrate were dissolved in 50 mL of deionized water by stirring to prepare a mixed salt solution;

[0039] (b) preparing a mixed alkali solution: dissolving 8 g of sodium hydroxide and 5.3 g of sodium carbonate in 50 mL of deionized water to prepare a mixed alkali solution;

[0040] (c) Preparation of a Ca-Mg-Al hydrotalcite: The mixed salt solution prepared in step (a) was added dropwise to 50 mL of deionized water. The pH of the solution was controlled at 8 using the mixed alkali solution prepared in step (b). After the addition of the mixed salt solution prepared in step (a), the reaction product was kept at 60° C. for 15 h. The product was cooled, filtered, washed to neutrality, dried, and calcined at 550° C. for 6 h to obtain a Ca-Mg-Al hydrotalcite.

[0041] Example 2

[0042] Example 2 provides a method for preparing salicylic acid amide, the specific steps are as follows:

[0043] (1) To a 100 mL four-necked flask equipped with a magnet, thermometer, and condenser, 7.05 g of phenol, 3.0 g of urea, 11.4 mL of toluene, and 0.2 g of Ca-Mg-Al hydrotalcite were added in sequence and reacted at 100 °C for 3 h.

[0044] (2) After the reaction is completed, centrifugation is performed to separate and recover the Ca-Mg-Al hydrotalcite-like substance, and the supernatant after centrifugation is taken; 25° C. cold water is added to the supernatant to wash the residual urea, and the organic phase is subjected to reduced pressure distillation to recover the solvent to obtain a crude salicylamide;

[0045] (3) The crude salicylamide obtained in step (2) is heated to 160° C. to reach a molten state, and then cooled from a liquid state to a solid state to obtain salicylamide.

[0046] Detected by liquid chromatography, the yield of salicylamide was 82% and the purity was 90.5%.

[0047] The preparation process of Ca-Mg-Al hydrotalcite is as follows:

[0048] (a) Preparing a mixed salt solution: 1.89 g of calcium nitrate tetrahydrate, 2.05 g of magnesium nitrate hexahydrate, and 1.5 g of aluminum nitrate nonahydrate were dissolved in 60 mL of deionized water with stirring to prepare a mixed salt solution;

[0049] (b) preparing a mixed alkali solution: dissolving 8 g of sodium hydroxide and 5.3 g of sodium carbonate in 45 mL of deionized water to prepare a mixed alkali solution;

[0050] (c) Preparation of Ca-Mg-Al hydrotalcite: The mixed salt solution prepared in step (a) was added dropwise to 50 mL of deionized water. The pH of the solution was controlled at 7.5 using the mixed alkali solution prepared in step (b). After the addition of the mixed salt solution prepared in step (a), the reaction product was kept at 55° C. for 14 h. The product was cooled, filtered, washed to neutrality, dried, and calcined at 500° C. for 5.5 h to obtain Ca-Mg-Al hydrotalcite.

[0051] Example 3

[0052] Example 3 provides a method for preparing salicylic acid amide, the specific steps are as follows:

[0053] (1) To a 100 mL four-necked flask equipped with a magnet, thermometer, and condenser, 23.5 g of phenol, 3.0 g of urea, 11.4 mL of toluene, and 0.2 g of Ca-Mg-Al hydrotalcite were added in sequence and reacted at 100 °C for 3 h.

[0054] (2) After the reaction is completed, centrifugation is performed to separate and recover the Ca-Mg-Al hydrotalcite-like substance, and the supernatant after centrifugation is taken; 22° C. cold water is added to the supernatant to wash the residual urea, and the organic phase is subjected to reduced pressure distillation to recover the solvent to obtain a crude salicylamide;

[0055] (3) The crude salicylamide obtained in step (2) is heated to 155° C. to reach a molten state, and then cooled from a liquid state to a solid state to obtain salicylamide.

[0056] Detected by liquid chromatography, the yield of salicylamide was 89% and the purity was 94.6%.

[0057] The preparation process of Ca-Mg-Al hydrotalcite is as follows:

[0058] (a) Preparing a mixed salt solution: 1.89 g of calcium nitrate tetrahydrate, 2.05 g of magnesium nitrate hexahydrate, and 1.5 g of aluminum nitrate nonahydrate were dissolved in 55 mL of deionized water with stirring to prepare a mixed salt solution;

[0059] (b) preparing a mixed alkali solution: dissolving 8 g of sodium hydroxide and 5.3 g of sodium carbonate in 75 mL of deionized water to prepare a mixed alkali solution;

[0060] (c) Preparation of a Ca-Mg-Al hydrotalcite: The mixed salt solution prepared in step (a) was added dropwise to 50 mL of deionized water. The pH of the solution was controlled at 8.5 using the mixed alkali solution prepared in step (b). After the addition of the mixed salt solution prepared in step (a), the reaction product was kept at 65° C. for 16 h. The product was cooled, filtered, washed to neutrality, dried, and calcined at 600° C. for 6.5 h to obtain a Ca-Mg-Al hydrotalcite.

[0061] Example 4

[0062] Example 4 provides a method for preparing salicylamide, which differs from Example 1 in that: step (1) 14.1 g of phenol, 3.0 g of urea, 34.2 mL of toluene, and 0.2 g of Ca-Mg-Al hydrotalcite are added in sequence to a 100 mL four-necked flask equipped with a magnet, a thermometer, and a condenser, and the mixture is reacted at 100° C. for 3 h; the remaining steps are the same as in Example 1 to obtain salicylamide.

[0063] Detected by liquid chromatography, the yield of salicylamide was 81% and the purity was 90.4%.

[0064] Example 5

[0065] Example 5 provides a method for preparing salicylamide, which differs from Example 1 in that: step (1) 14.1 g of phenol, 3.0 g of urea, 8.55 mL of toluene, and 0.2 g of Ca-Mg-Al hydrotalcite are added in sequence to a 100 mL four-necked flask equipped with a magnet, a thermometer, and a condenser, and the mixture is reacted at 100° C. for 3 h; the remaining steps are the same as in Example 1 to obtain salicylamide.

[0066] Detected by liquid chromatography, the yield of salicylamide was 88% and the purity was 94.8%.

[0067] Example 6

[0068] Example 6 provides a method for preparing salicylamide, which differs from Example 1 in that: step (1) 14.1 g of phenol, 3.0 g of urea, 11.4 mL of p-xylene, and 0.2 g of Ca-Mg-Al hydrotalcite are added in sequence to a 100 mL four-necked flask equipped with a magnet, a thermometer, and a condenser, and the mixture is reacted at 100° C. for 3 h; the remaining steps are the same as in Example 1 to obtain salicylamide.

[0069] Detected by liquid chromatography, the yield of salicylamide was 88.5% and the purity was 92.1%.

[0070] Example 7

[0071] Example 7 provides a method for preparing salicylamide, which differs from Example 1 in that: step (1) 14.1 g of phenol, 3.0 g of urea, 11.4 mL of o-xylene, and 0.2 g of Ca-Mg-Al hydrotalcite are added in sequence to a 100 mL four-necked flask equipped with a magnet, a thermometer, and a condenser, and the mixture is reacted at 100° C. for 3 h; the remaining steps are the same as in Example 1 to obtain salicylamide.

[0072] Detected by liquid chromatography, the yield of salicylamide was 86% and the purity was 92.7%.

[0073] Example 8

[0074] Example 8 provides a method for preparing salicylamide, which differs from Example 1 in that: step (1) 14.1 g of phenol, 3.0 g of urea, 11.4 mL of toluene, and 0.2 g of Ca-Mg-Al hydrotalcite are added in sequence to a 100 mL four-necked flask equipped with a magnet, a thermometer, and a condenser, and the mixture is reacted at 90° C. for 3 h; the remaining steps are the same as in Example 1 to obtain salicylamide.

[0075] Detected by liquid chromatography, the yield of salicylamide was 80% and the purity was 89.4%.

[0076] Example 9

[0077] Example 9 provides a method for preparing salicylamide, which differs from Example 1 in that: step (1) 14.1 g of phenol, 3.0 g of urea, 11.4 mL of toluene, and 0.2 g of Ca-Mg-Al hydrotalcite are added in sequence to a 100 mL four-necked flask equipped with a magnet, a thermometer, and a condenser, and the mixture is reacted at 110° C. for 3 h; the remaining steps are the same as in Example 1 to obtain salicylamide.

[0078] Detected by liquid chromatography, the yield of salicylamide was 91.5% and the purity was 99.3%.

[0079] Example 10

[0080] Example 10 provides a method for preparing salicylamide, which differs from Example 1 in that: step (1) 14.1 g of phenol, 3.0 g of urea, 11.4 mL of toluene, and 0.2 g of Ca-Mg-Al hydrotalcite are added in sequence to a 100 mL four-necked flask equipped with a magnet, a thermometer, and a condenser, and the mixture is reacted at 100° C. for 2 h; the remaining steps are the same as in Example 1 to obtain salicylamide.

[0081] Detected by liquid chromatography, the yield of salicylamide was 83% and the purity was 91%.

[0082] Example 11

[0083] Example 11 provides a method for preparing salicylamide, which differs from Example 1 in that: step (1) 14.1 g of phenol, 3.0 g of urea, 11.4 mL of toluene, and 0.2 g of Ca-Mg-Al hydrotalcite are added in sequence to a 100 mL four-necked flask equipped with a magnet, a thermometer, and a condenser, and the mixture is reacted at 100° C. for 5 h; the remaining steps are the same as in Example 1 to obtain salicylamide.

[0084] Detected by liquid chromatography, the yield of salicylamide was 89.5% and the purity was 94.6%.

[0085] 2. Comparative Example

[0086] Comparative Example 1

[0087] Comparative Example 1 provides a method for preparing salicylamide, which differs from Example 1 in that the organic solvent is m-xylene, and the other conditions are the same as those in Example 1 to prepare salicylamide.

[0088] Detected by liquid chromatography, the yield of salicylamide was 68% and the purity was 81%.

[0089] 3. Test Examples

[0090] Test Example 1

[0091] Test Example 1: Infrared spectroscopy was used to analyze the structure of salicylamide obtained in Example 1. Figure 1 shown.

[0092] Depend on Figure 1 It can be seen that 3400cm -1 The NH vibration of amide is at 3000 cm -1 , 1600cm -1 The characteristic absorption peak of benzene ring is 1250cm -1 The vibration of phenolic hydroxyl group is consistent with the characteristic peak of salicylic acid amide. Therefore, the preparation method of the present invention can successfully prepare salicylic acid amide.

[0093] As can be seen from the above, compared with Example 1, Comparative Example 1 uses m-xylene as the organic solvent to replace part of the phenol. Liquid chromatography analysis shows that the salicylamide produced in Comparative Example 1 has a yield of 68% and a purity of 81%. It can be seen that replacing the organic solvent of the present invention with other organic solvents cannot effectively improve the yield and purity of salicylamide. This shows that the organic solvent provided by the present invention can not only prepare salicylamide, but also improve the yield and purity of salicylamide.

[0094] In summary, the direct synthesis of salicylamide from urea and phenol suffers from problems such as excessive phenol usage, the generation of large amounts of phenol-containing wastewater after the reaction, long reaction times, and high reaction temperatures. The present invention innovatively replaces part of the phenol with an organic solvent and uses Ca-Mg-Al hydrotalcite as a catalyst for the synthesis of salicylamide, significantly reducing the amount of phenol used (reducing the molar ratio of urea to phenol to 1:1.5-5). This effectively alleviates the problems of excessive wastewater and high energy consumption caused by excessive phenol. The addition of an organic solvent also dilutes the reactants, improving contact between the reactants and the active sites on the Ca-Mg-Al hydrotalcite catalyst, significantly reducing the reaction temperature and time. Therefore, the present invention can produce salicylamide with a purity of 99.5% under mild conditions, namely, a reaction temperature of 90°C to 110°C and a reaction time of 2-5 hours. The present invention utilizes readily available and inexpensive raw materials, and both the organic solvent and unreacted phenol are recyclable, resulting in low energy consumption, good economic benefits, and a simple preparation process with broad application prospects.

[0095] The above are only preferred embodiments of the present invention and are not limited to the above examples. For those skilled in the art, various changes and modifications are possible under the principles of the present invention. Any modifications and improvements made should be considered within the scope of protection of the present invention.

Claims

1. A method for preparing salicylamide, characterized in that, The following steps are involved: (1) Mix 14.1 g of phenol, 3.0 g of urea, 11.4 mL of toluene, and 0.2 g of Ca-Mg-Al hydrotalcite, and heat to 100 °C or 110 °C for 3 h. (2) After the reaction is completed, centrifugation is performed to separate and recover the Ca-Mg-Al hydrotalcite-like substance, and the supernatant after centrifugation is taken; cold water is added to the supernatant to wash and remove residual urea, and then the organic phase is subjected to reduced pressure distillation to recover the solvent to obtain a crude salicylamide; (3) The crude salicylamide obtained in step (2) is melt-crystallized to obtain salicylamide.

2. The method for preparing salicylamide according to claim 1, wherein The preparation method of the Ca-Mg-Al hydrotalcite comprises the following steps: (a) preparing a mixed salt solution: stirring and dissolving calcium nitrate tetrahydrate, magnesium nitrate hexahydrate, and aluminum nitrate nonahydrate in deionized water to prepare a mixed salt solution; (b) preparing a mixed alkali solution: dissolving sodium hydroxide and sodium carbonate in deionized water to prepare a mixed alkali solution; (c) Preparing a Ca-Mg-Al hydrotalcite: dripping the mixed salt solution prepared in step (a) into deionized water, and controlling the pH of the solution to 7.5-8.5 using the mixed alkali solution prepared in step (b); after the dripping of the mixed salt solution prepared in step (a), keeping the reaction product at 55° C.-65° C. for 14-16 hours; cooling, filtering, washing to neutrality, drying, and calcining at 500° C.-600° C. for 5.5-6.5 hours to prepare a Ca-Mg-Al hydrotalcite.

3. The preparation method of salicylamide according to claim 2, wherein In the step (a), the molar ratio of calcium nitrate tetrahydrate, magnesium nitrate hexahydrate, and aluminum nitrate nonahydrate is 2:2:1; and the mass ratio of the total mass of calcium nitrate tetrahydrate, magnesium nitrate hexahydrate, and aluminum nitrate nonahydrate to deionized water is 1:(10-12).

4. The method for preparing salicylamide according to claim 2, wherein In the step (b), the molar ratio of sodium hydroxide to sodium carbonate is 4:1; and the mass ratio of the total mass of sodium hydroxide and sodium carbonate to deionized water is 1:(3-6).

5. The method for preparing salicylamide according to claim 2, wherein In the step (c), the volume ratio of the mixed salt solution and deionized water is 1:

1.

6. The method for preparing salicylamide according to claim 1, wherein The temperature of the cold water in step (2) is 20°C to 25°C.

7. The method for preparing salicylamide according to claim 1, wherein The step (3) melt crystallization is to heat the crude salicylamide to 150° C. to 160° C. to make it reach a molten state, and then cool it from liquid to solid by cooling.

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