Method for synthesizing p-toluenesulfonyl isocyanate by sodium cyanate method

Abstract

The invention discloses a method for synthesizing paratoluensulfonyl isocyanate by a sodium cyanate method. The method comprises the following steps: S1, performing anhydrous treatment on raw materials including sodium cyanate, paratoluensulfonyl chloride and a solvent; s2, adding a certain amount of sodium cyanate, paratoluensulfonyl chloride, a phase transfer catalyst and a solvent into the reaction kettle, and stirring and reacting at 25-30 DEG C for 2-3 hours; s3, filtering out solids from a reaction product in S2, and extracting an organic phase; and S4, distilling the organic phase in S3 to recover the solvent, and performing reduced pressure distillation to obtain p-toluenesulfonyl isocyanate. According to the method for synthesizing the p-toluenesulfonyl isocyanate by the sodium cyanate method, provided by the invention, a high-yield and high-purity product can be obtained by optimizing reaction conditions and purifying steps.

Description

Technical Field

[0001] The invention relates to the technical field of organic synthesis, in particular to a method for synthesizing p-toluenesulfonyl isocyanate using a sodium cyanate method. Background Art

[0002] p-Toluenesulfonyl isocyanate (TsNCO) is an important organic synthesis intermediate widely used in pharmaceuticals, pesticides, polymer materials, and fine chemicals. Its molecular structure contains both sulfonyl and isocyanate groups, endowing it with high reactivity. It is commonly used for amino protection, heterocyclic compound synthesis, polyurethane modification, and as an electrophilic reagent in various addition reactions. For example, in pharmaceutical synthesis, TsNCO can be used to construct amide bonds or as an isocyanate group donor. In the polymer industry, it can be used as a crosslinker or functional monomer to enhance material properties. Therefore, developing efficient, safe, and environmentally friendly processes for the preparation of TsNCO has significant application value.

[0003] The commonly used synthesis methods of substituted benzoyl isocyanate are mainly the following: Method 1: Benzoyl isocyanate is synthesized by using substituted phenylformamide and oxalyl chloride. Considering the relatively high price of oxalyl chloride, the cost is not advantageous in commercial production. Method 2: Benzoyl isocyanate is synthesized by using substituted phenylformamide and phosgene. Phosgene is a highly toxic gas, and its production and use are strictly regulated in my country and some other countries. In addition, the reaction requires high airtightness of the equipment, strict safety precautions, high investment, and strict regulations for the treatment of waste gas. It is not suitable for the production needs of ordinary enterprises. Method 3: Benzoyl isocyanate is synthesized by using substituted phenylformamide and cyanate. In this method, the yield is not high and the reproducibility is poor due to the formation of by-product benzonitrile.

[0004] The Chinese invention patent with the authorization announcement number CN111004150B discloses a method for synthesizing substituted benzoyl isocyanate, which comprises the following steps: reacting substituted benzoyl chloride with cyanate in an organic solvent in the presence of a composite catalyst composed of Lewis acid and p-toluenesulfonic acid to produce substituted benzoyl isocyanate. In this invention patent, relatively cheap sodium cyanate and substituted benzoyl chloride are first reacted, and the composite catalyst is simultaneously used to achieve the purpose of improving yield. However, the synthesis method provided by this invention has a long reaction time (6.5-9.0h), and the boiling points of the catalysts p-toluenesulfonic acid (140°C) and chlorobenzene (132°C) used in this invention are relatively close, which makes it difficult to separate the catalysts in the subsequent separation process. In addition, the control of side reactions in this synthesis method also needs to be improved. Summary of the Invention

[0005] In view of the shortcomings of the prior art, the object of the present invention is to provide a method for synthesizing p-toluenesulfonyl isocyanate by the sodium cyanate method, which can achieve high yield and high purity products by optimizing the reaction conditions and purification steps.

[0006] The technical solution adopted by the present invention to solve the technical problem is: a method for synthesizing p-toluenesulfonyl isocyanate by a sodium cyanate method, the method comprising the following steps: S1, subjecting raw materials sodium cyanate, p-toluenesulfonyl chloride and solvent to anhydrous treatment; S2. Add a certain amount of sodium cyanate, p-toluenesulfonyl chloride, a phase transfer catalyst, and a solvent to the reactor, and stir the reaction at 25-30° C. for 2-3 hours; S3, filtering the reaction product in S2 to remove the solid, and extracting the organic phase; S4. After distilling the organic phase in S3 to recover the solvent, distill under reduced pressure to obtain p-toluenesulfonyl isocyanate.

[0007] Furthermore, in step S1, the sodium cyanate is dried in an oven at 100° C. for 1 to 2 hours, the p-toluenesulfonyl chloride is dried, and the solvent is dehydrated by molecular sieves.

[0008] Furthermore, in step S1, the solvent is acetonitrile, tetrahydrofuran or dichloromethane.

[0009] Furthermore, in step S2, the molar ratio of sodium cyanate to p-toluenesulfonyl chloride is 1.03-1.08:1; the phase transfer catalyst is tetrabutylammonium bromide, and the amount of the phase transfer catalyst accounts for 0.5-1 mol% of the amount of p-toluenesulfonyl chloride; and the mass of the solvent is 4-6 times the mass of p-toluenesulfonyl chloride.

[0010] Furthermore, in step S2, high-speed mechanical stirring is used with a rotation speed of ≥500 rpm to ensure that the two phases are fully mixed.

[0011] Furthermore, in step S2, a polymerization inhibitor is added to the reactor to inhibit the polymerization of isocyanate; the polymerization inhibitor is hydroquinone, and the mass of the polymerization inhibitor is 0.1-0.3% of the mass of p-toluenesulfonyl chloride.

[0012] Furthermore, in step S2, in order to ensure an anhydrous system, molecular sieves can be added together with the raw materials during the reaction process, and the mass of the added molecular sieves is 10-20% of the mass of p-toluenesulfonyl chloride.

[0013] Furthermore, in step S3, the reaction product is filtered to remove unreacted NaOCN and generated NaCl solid; the filtrate is extracted several times with petroleum ether or n-hexane, and the organic phases are combined.

[0014] Furthermore, in step S4, distillation is performed under reduced pressure at 130-135° C. and 5 mmHg to collect the p-toluenesulfonyl isocyanate fraction.

[0015] Furthermore, the p-toluenesulfonyl isocyanate fraction obtained after reduced pressure distillation is purified by recrystallization, and the p-toluenesulfonyl isocyanate is dissolved in a hot solvent, slowly cooled to -20°C, white crystals precipitated, filtered and vacuum dried; the solvent is n-hexane, dichloromethane, chloroform, dimethyl sulfoxide, chlorobenzene, dichlorobenzene or trichlorobenzene.

[0016] In the present invention, the raw materials p-toluenesulfonyl chloride (TsCl) and sodium cyanate (NaOCN) react in a solvent and a phase transfer catalyst to generate p-toluenesulfonyl isocyanate (TsNCO) and sodium chloride (NaCl). This reaction is a nucleophilic substitution reaction, specifically the cyanate ion (OCN - ) acts as a nucleophile, attacking the sulfur atom in the sulfonyl chloride, replacing the chloride ion to form TsNCO. By optimizing a series of conditions, including anhydrous treatment, room temperature reaction, and the addition of a phase transfer catalyst and inhibitor, the reaction time was shortened, side reactions were suppressed, and the reaction yield was increased.

[0017] The beneficial effects of the present invention are as follows: compared with the prior art, the method for synthesizing p-toluenesulfonyl isocyanate using a sodium cyanate method provided by the present invention has the following advantages: 1) The reaction process is strictly controlled to avoid side reactions (such as TsCl hydrolysis) to the greatest extent possible; 2) Since sodium cyanate in the raw material is insoluble in the solvent, a phase transfer catalyst is added during the reaction to accelerate the full reaction of the two phases and reduce the occurrence of side reactions; 3) The reaction process is carried out at room temperature (25-30°C) with strong stirring and a phase transfer catalyst, shortening the reaction time to 2-3 hours (more than 50% shorter than conventional methods), with fewer side reactions and a yield of 85%-90%; 4) Adding polymerization inhibitors during the reaction to inhibit isocyanate polymerization and increase the reaction yield; 5) The preparation method of the present invention uses sodium cyanate as a raw material, has low production cost, avoids the use of highly toxic phosgene, and the by-product NaCl can be recycled, thus having high production value. DETAILED DESCRIPTION

[0018] The present invention will be further described below by way of specific examples, which are only intended to illustrate the present invention and are not intended to limit the scope of the present invention.

[0019] Example 1 A method for synthesizing p-toluenesulfonyl isocyanate using a sodium cyanate method, comprising the following steps: S1. The raw materials sodium cyanate, p-toluenesulfonyl chloride and acetonitrile are subjected to anhydrous treatment; the sodium cyanate is dried in an oven at 100° C. for 2 hours, the p-toluenesulfonyl chloride is dried, and the acetonitrile is dehydrated by molecular sieve.

[0020] S2. Add a certain amount of sodium cyanate, p-toluenesulfonyl chloride, tetrabutylammonium bromide and acetonitrile to the reactor, stir at 25°C with a high-speed mechanical stirring speed of ≥500 rpm, and the reaction time is 3 hours; wherein, the molar ratio of sodium cyanate to p-toluenesulfonyl chloride is 1.05:1; the amount of tetrabutylammonium bromide accounts for 1 mol% of the amount of p-toluenesulfonyl chloride; the mass of acetonitrile is 5 times the mass of p-toluenesulfonyl chloride.

[0021] S3. After filtering out the solid from the reaction product in S2, the organic phase is extracted; the reaction product is filtered to remove unreacted NaOCN and generated NaCl solid; the filtrate is extracted three times with petroleum ether or n-hexane, and the organic phases are combined.

[0022] S4. After distilling the organic phase in S3 to recover the solvent, distill under reduced pressure at 130-135° C. and 5 mmHg to collect the p-toluenesulfonyl isocyanate fraction to obtain p-toluenesulfonyl isocyanate.

[0023] In this embodiment, the yield of p-toluenesulfonyl isocyanate is 85%, and the product purity is ≥98%.

[0024] Example 2 A method for synthesizing p-toluenesulfonyl isocyanate using a sodium cyanate method, comprising the following steps: S1. The raw materials sodium cyanate, p-toluenesulfonyl chloride and acetonitrile are subjected to anhydrous treatment; the sodium cyanate is dried in an oven at 100° C. for 2 hours, the p-toluenesulfonyl chloride is dried, and the solvent is dehydrated through molecular sieves.

[0025] S2. Add a certain amount of sodium cyanate, p-toluenesulfonyl chloride, tetrabutylammonium bromide, acetonitrile and hydroquinone into the reactor, stir at 25°C with high-speed mechanical stirring, the speed is ≥500 rpm, and the reaction time is 3 hours; wherein, the molar ratio of sodium cyanate to p-toluenesulfonyl chloride is 1.05:1; the amount of tetrabutylammonium bromide accounts for 1 mol% of the amount of p-toluenesulfonyl chloride; the mass of acetonitrile is 5 times the mass of p-toluenesulfonyl chloride; the amount of hydroquinone is 0.1% of the p-toluenesulfonyl chloride.

[0026] S3. After filtering out the solid from the reaction product in S2, the organic phase is extracted; the reaction product is filtered to remove unreacted NaOCN and generated NaCl solid; the filtrate is extracted three times with petroleum ether or n-hexane, and the organic phases are combined.

[0027] S4. After distilling the organic phase in S3 to recover the solvent, distill under reduced pressure at 130-135° C. and 5 mmHg to collect the p-toluenesulfonyl isocyanate fraction to obtain p-toluenesulfonyl isocyanate.

[0028] In this embodiment, the yield of p-toluenesulfonyl isocyanate is 87%, and the product purity is ≥98%.

[0029] Example 3 A method for synthesizing p-toluenesulfonyl isocyanate using a sodium cyanate method, comprising the following steps: S1. The raw materials sodium cyanate, p-toluenesulfonyl chloride and acetonitrile are subjected to anhydrous treatment; the sodium cyanate is dried in an oven at 100° C. for 2 hours, the p-toluenesulfonyl chloride is dried, and the solvent is dehydrated through molecular sieves.

[0030] S2. Add a certain amount of sodium cyanate, p-toluenesulfonyl chloride, tetrabutylammonium bromide, acetonitrile and hydroquinone to the reactor, and add an appropriate amount of molecular sieves to the reactor; stir at a high speed mechanical stirring at 25°C, with a speed of ≥500 rpm, and the reaction time is 3 hours; wherein, the molar ratio of sodium cyanate to p-toluenesulfonyl chloride is 1.05:1; the amount of tetrabutylammonium bromide accounts for 1 mol% of the amount of p-toluenesulfonyl chloride; the mass of acetonitrile is 5 times the mass of p-toluenesulfonyl chloride; the amount of hydroquinone is 0.1% of the p-toluenesulfonyl chloride.

[0031] S3. After filtering out the solid from the reaction product in S2, the organic phase is extracted; the reaction product is filtered to remove unreacted NaOCN and generated NaCl solid; the filtrate is extracted three times with petroleum ether or n-hexane, and the organic phases are combined.

[0032] S4. After distilling the organic phase in S3 to recover the solvent, distill under reduced pressure at 130-135° C. and 5 mmHg to collect the p-toluenesulfonyl isocyanate fraction to obtain p-toluenesulfonyl isocyanate.

[0033] In this embodiment, the yield of p-toluenesulfonyl isocyanate is 90%, and the product purity is ≥98%.

[0034] Example 4 A method for synthesizing p-toluenesulfonyl isocyanate using a sodium cyanate method, comprising the following steps: S1. The raw materials sodium cyanate, p-toluenesulfonyl chloride and acetonitrile are subjected to anhydrous treatment; the sodium cyanate is dried in an oven at 100° C. for 2 hours, the p-toluenesulfonyl chloride is dried, and the acetonitrile is dehydrated by molecular sieve.

[0035] S2. Add a certain amount of sodium cyanate, p-toluenesulfonyl chloride, tetrabutylammonium bromide and acetonitrile to the reactor, stir at 25°C with a high-speed mechanical stirring speed of ≥500 rpm, and the reaction time is 3 hours; wherein, the molar ratio of sodium cyanate to p-toluenesulfonyl chloride is 1.05:1; the amount of tetrabutylammonium bromide accounts for 1 mol% of the amount of p-toluenesulfonyl chloride; the mass of acetonitrile is 5 times the mass of p-toluenesulfonyl chloride.

[0036] S3. After filtering out the solid from the reaction product in S2, the organic phase is extracted; the reaction product is filtered to remove unreacted NaOCN and generated NaCl solid; the filtrate is extracted three times with petroleum ether or n-hexane, and the organic phases are combined.

[0037] S4. After distilling the organic phase in S3 to recover the solvent, distill under reduced pressure at 130-135° C. and 5 mmHg to collect the p-toluenesulfonyl isocyanate fraction to obtain p-toluenesulfonyl isocyanate.

[0038] S5. Purify the p-toluenesulfonyl isocyanate obtained in S4 by recrystallization. Dissolve the p-toluenesulfonyl isocyanate in 60°C hot n-hexane, slowly cool to -20°C, precipitate white crystals, filter and vacuum dry.

[0039] In this embodiment, the yield of p-toluenesulfonyl isocyanate is 84%, and the product purity is ≥99%.

[0040] Comparative Example 1 A method for synthesizing p-toluenesulfonyl isocyanate using a sodium cyanate method, comprising the following steps: S1. Add a certain amount of sodium cyanate, p-toluenesulfonyl chloride, tetrabutylammonium bromide, and acetonitrile to a reactor; stir mechanically at 25°C with a speed ≥500 rpm for 3 hours; wherein the molar ratio of sodium cyanate to p-toluenesulfonyl chloride is 1.05:1; the amount of tetrabutylammonium bromide accounts for 1 mol% of the amount of p-toluenesulfonyl chloride; and the mass of acetonitrile is 5 times the mass of p-toluenesulfonyl chloride.

[0041] S2. After filtering out the solid from the reaction product in S1, extract the organic phase; remove the unreacted NaOCN and generated NaCl solid from the reaction product by suction filtration; extract the filtrate three times with petroleum ether or n-hexane, and combine the organic phases.

[0042] S3. After distilling the organic phase in S2 to recover the solvent, distill under reduced pressure at 130-135° C. and 5 mmHg to collect the p-toluenesulfonyl isocyanate fraction to obtain p-toluenesulfonyl isocyanate.

[0043] In this embodiment, the yield of p-toluenesulfonyl isocyanate is 75%, and the product purity is ≥95%.

[0044] The above embodiments are only used to illustrate the present invention, and are not intended to limit the present invention. Ordinary technicians in the relevant technical field may make various changes and modifications without departing from the spirit and scope of the present invention. Therefore, all equivalent technical solutions also fall within the scope of the present invention. The scope of patent protection of the present invention should be defined by the claims.

Claims

1. A method for synthesizing p-toluenesulfonyl isocyanate by a sodium cyanate method, characterized in that: The method comprises the following steps: S1, subjecting raw materials sodium cyanate, p-toluenesulfonyl chloride and solvent to anhydrous treatment; S2. Add a certain amount of sodium cyanate, p-toluenesulfonyl chloride, a phase transfer catalyst, and a solvent to the reactor, and stir the reaction at 25-30° C. for 2-3 hours; S3, filtering the reaction product in S2 to remove the solid, and extracting the organic phase; S4. After distilling the organic phase in S3 to recover the solvent, distill under reduced pressure to obtain p-toluenesulfonyl isocyanate.

2. The method for synthesizing p-toluenesulfonyl isocyanate by a sodium cyanate method as claimed in claim 1, wherein: In step S1, the sodium cyanate is dried in an oven at 100° C. for 1 to 2 hours, the p-toluenesulfonyl chloride is dried, and the solvent is dehydrated by molecular sieves.

3. A method for synthesizing p-toluenesulfonyl isocyanate by a sodium cyanate method as claimed in claim 1 or 2, characterized in that: In step S1, the solvent is acetonitrile, tetrahydrofuran or dichloromethane.

4. The method for synthesizing p-toluenesulfonyl isocyanate by a sodium cyanate method as claimed in claim 1, wherein: In step S2, the molar ratio of sodium cyanate to p-toluenesulfonyl chloride is 1.03-1.08:1; the phase transfer catalyst is tetrabutylammonium bromide, and the amount of the phase transfer catalyst accounts for 0.5-1 mol% of the amount of p-toluenesulfonyl chloride; and the mass of the solvent is 4-6 times the mass of p-toluenesulfonyl chloride.

5. The method for synthesizing p-toluenesulfonyl isocyanate by a sodium cyanate method as claimed in claim 1, wherein: In step S2, high-speed mechanical stirring is used with a rotation speed of ≥500 rpm to ensure that the two phases are fully mixed.

6. The method for synthesizing p-toluenesulfonyl isocyanate by a sodium cyanate method as claimed in claim 1, wherein: In step S2, a polymerization inhibitor is added to the reactor to inhibit isocyanate polymerization; the polymerization inhibitor is hydroquinone, and the mass of the polymerization inhibitor is 0.1-0.3% of the mass of p-toluenesulfonyl chloride.

7. The method for synthesizing p-toluenesulfonyl isocyanate by a sodium cyanate method as claimed in claim 1, wherein: In step S2, in order to ensure an anhydrous system, molecular sieves can be added together with the raw materials during the reaction process, and the added mass of the molecular sieves is 10-20% of the mass of p-toluenesulfonyl chloride.

8. The method for synthesizing p-toluenesulfonyl isocyanate by a sodium cyanate method as claimed in claim 1, wherein: In step S3, the reaction product is filtered to remove unreacted NaOCN and generated NaCl solid; the filtrate is extracted several times with petroleum ether or n-hexane, and the organic phases are combined.

9. The method for synthesizing p-toluenesulfonyl isocyanate by a sodium cyanate method as claimed in claim 1, wherein: In step S4, the reaction mixture is distilled under reduced pressure at 130-135° C. and 5 mmHg to collect the p-toluenesulfonyl isocyanate fraction.

10. The method for synthesizing p-toluenesulfonyl isocyanate by a sodium cyanate method as claimed in claim 1, wherein: The p-toluenesulfonyl isocyanate fraction obtained after vacuum distillation is purified by recrystallization. The p-toluenesulfonyl isocyanate is dissolved in a hot solvent and slowly cooled to -20°C to precipitate white crystals, which are filtered and then vacuum dried. The solvent is n-hexane, dichloromethane, chloroform, dimethyl sulfoxide, chlorobenzene, dichlorobenzene or trichlorobenzene.