CN102675234B - Synthetic method of sym-triazine derivative - Google Patents

Abstract

The invention relates to a synthetic method of a sym-triazine derivative. The method comprises the following step of: performing a coupling reaction on chlorinated sym-triazine and Negishi of an organic zinc reagent by taking a chlorinated sym-triazine solution and the organic zinc reagent as substrates and taking a palladium salt catalyst, a palladium composition catalyst and a palladium-phosphine ligand mixed catalyst with high catalyzing activities as catalysts to synthesize a polysubstitution sym-triazine derivative. In a reaction process, the using amounts of the catalysts are small, and the reaction yield is high; a zinc alkyl reagent, a zinc aryl reagent and a zinc heteroaryl reagent with appropriate reaction activities used in the reaction process have high functional group compatibility and wide substrate application ranges, and have high reaction selectivity in synthesis of an asymmetric sym-triazine derivative; and moreover, cheap and readily-available chlorinated sym-triazine is taken as an active ingredient in the reaction, so that the method has general applicability to synthesis of sym-triazine derivatives, and is relatively low in cost.

Description

The synthetic method of s-triazine derivative

technical field

The invention belongs to the technical field of chemical synthesis of s-triazine derivatives, in particular to a method for synthesizing s-triazine derivatives using palladium salts, palladium complexes and mixtures of palladium salts, palladium complexes and phosphine ligands as catalysts.

Background technique

At present, the traditional synthesis method for triazine derivatives is mainly through the polymerization reaction of cyano compounds, but this method takes a long time to react, the substrate functional group compatibility is poor, and the yield of the product is low. The triazine derivatives that can be prepared There are fewer types of compounds, and the difficulty is relatively large, especially for asymmetric triazine derivatives, it is almost difficult to use this method.

In addition, some people have prepared triazine derivatives through coupling reactions, but there are only a few reports. Menicagli et al. tried to prepare tertiary alkyl bulky triazine derivatives by coupling Grignard reagents with chlorotriazines. In addition, Knochel et al. converted chlorotriazines to iodotriazines with higher reactivity, obtained triazine Grignard reagents by exchange with alkyl Grignard reagents, and metal exchanged triazine Grignard reagents with zinc chloride to obtain The triazine zinc reagent, the triazine zinc reagent and brominated arene coupling reaction to prepare aryl triazine derivatives.

The inventor finds that the above-mentioned method all has the following problems in the test and research process:

1. The functional group compatibility of the reaction substrate is poor, the scope of application is small, and the selectivity of the reaction product is poor;

2. The process steps are cumbersome, the reaction time is long, the amount of catalyst is large, and the reaction yield is relatively low.

In view of the existence of the above-mentioned defects, the synthesis of existing triazine derivatives is limited to a certain extent in industrial applications, so further research on this aspect is needed.

Contents of the invention

In order to solve the problems of large amount of catalyst, low reaction yield, small scope of substrate application and poor reaction selectivity in the preparation process of multi-substituted s-triazine derivatives in the prior art, the present invention provides a highly efficient, high regioselective Synthetic method of s-triazine derivatives.

The technical solution for solving technical problems is: a synthetic method of s-triazine derivatives, comprising the following steps:

1) From -30°C to 75°C, replace the dry reactor with _N2 and add chloro-s-triazine, organic zinc reagent and catalyst in sequence. The molar ratio of chloro-s-triazine to organic zinc reagent and catalyst is 1:1.00 ～2.50: 0.0025～0.20, the reaction time is 1.5～4.5 hours;

2) adding a hydrochloric acid solution with a concentration of 1 mol/L to the reacted solution until the quenching reaction is complete, extracting the generated aqueous phase three times, combining the organic layers, drying, and concentrating to obtain a crude s-triazine derivative;

3) The crude s-triazine derivatives are purified by silica gel column chromatography to obtain s-triazine derivatives;

The above-mentioned catalyst is any one of palladium salt catalyst, palladium complex catalyst, mixed catalyst of palladium salt and phosphine ligand, mixed catalyst of palladium complex and phosphine ligand, palladium salt in the mixed catalyst of palladium salt and phosphine ligand The molar ratio of the palladium complex to the phosphine ligand is 1:0.05~8, and the molar ratio of the mixed catalyst between the palladium complex and the phosphine ligand is 1:0.05~8;

The above organic zinc reagent is one of alkyl zinc reagents, aryl zinc reagents and heteroaryl zinc reagents.

Further, step a) is also included between step 1) and step 2) to add an organic zinc reagent to the solution after the reaction in step 1), and the molar ratio of chloro-s-triazine to the organic zinc reagent added again is 1: 1 to 2.5, the reaction time is 1.5 to 4.5 hours.

The molar ratio of the above-mentioned chloro-s-triazine to the first organic zinc reagent and the catalyst is preferably in the range of 1:1.50-2.00:0.03-0.15.

The above-mentioned chloro-s-triazine is 2-chloro-4,6-dimethoxy-1,3,5-triazine or 2,4-dichloro-6-methoxy-1,3,5-triazine .

In the above mixed catalyst of palladium salt and phosphine ligand, the molar ratio of palladium salt to phosphine ligand is preferably in the range of 1:1-4, and the molar ratio of the mixed catalyst of palladium complex and phosphine ligand is in the range of 1:1-4 better.

The above-mentioned palladium salt is palladium acetate or palladium dichloride or a combination thereof.

The above-mentioned palladium complex is any one of tetrakis(triphenylphosphine)palladium, bis(triphenylphosphine)palladium dichloride, tris(dibenzylideneacetone)dipalladium, bis(acetylacetonate)palladium, or at least Any combination of the two.

The above-mentioned phosphine ligand is triphenylphosphine or 1,2-bis(diphenylphosphine)ethane.

The above-mentioned alkyl zinc reagent is isopropyl zinc chloride or n-butyl zinc chloride or benzyl zinc chloride;

The aryl zinc reagents mentioned above are phenyl zinc chloride, 4-methylphenyl zinc chloride, 4-methoxyphenyl zinc chloride, 4-bromophenyl zinc chloride, 4-cyanophenyl zinc chloride any of zinc;

The aforementioned heteroaryl zinc reagent is 2-thienyl zinc chloride or 2-pyridine zinc chloride.

The present invention uses chloro-s-triazine solution and organozinc reagent as substrate, palladium salt catalyst with high catalytic activity, palladium complex catalyst, palladium-phosphine ligand mixed catalyst as catalyst, through chlorinated-s-triazine and organozinc reagent The multi-substituted s-triazine derivatives were synthesized by the Negishi coupling reaction, and the reaction process used less catalysts and high reaction yields, and the reaction process used moderately reactive alkyl zinc reagents, aryl zinc reagents and hetero The aryl zinc reagent has good functional group compatibility, a wide range of substrate applications, and high reaction selectivity in the synthesis of asymmetric triazine derivatives; in addition, the reaction uses cheap and easy-to-obtain chlorotriazine as an active ingredient, making This method has universal applicability in the synthesis of s-triazine derivatives, and the cost is relatively low.

Detailed ways

The present invention will be described in further detail below in conjunction with the examples, but the present invention is not limited to these examples.

Example 1

The synthetic method of the s-triazine derivative of the present embodiment is realized by the following steps:

Step 1: At 0°C, a 50 mL dry reaction tube equipped with a stirring bar and a rubber stopper was replaced with nitrogen three times, and 1.25 mL of phenylmagnesium bromide with a concentration of 1.20 mol/L and 1.50 mL with a concentration of 1.0 mol/L zinc chloride tetrahydrofuran solution, stirred for 15 minutes, raised to room temperature to prepare 1.25ml of phenyl zinc chloride with a concentration of 1.2mol/L; then add 175.6mg of 2-Chloro-4,6-dimethoxy-1,3,5-triazine and 35.1 mg bis(triphenylphosphine) palladium dichloride and 26.2 mg triphenylphosphine mixed catalyst, 2-chloro - The molar ratio of 4,6-dimethoxy-1,3,5-triazine to phenylzinc chloride to the mixed catalyst is 1:1.5:0.15, bis(triphenylphosphine) dichloride in the catalyst The molar ratio of palladium chloride and triphenylphosphine is 1:2, and react at room temperature for 3 hours;

Step 2: After step 1 is completed, add a hydrochloric acid solution with a concentration of 1mol/L to the reaction tube until the quenching reaction is complete, extract the generated aqueous phase with 5ml ether for 3 times, combine the organic layers, add 0.5g anhydrous sodium sulfate to dry, Concentrate to obtain the crude product s-triazine derivative;

Step 3: Purify by silica gel column chromatography to obtain 215.1 mg of 2,4-dimethoxy-6-phenyl-1,3,5-triazine with a yield of 99%.

For the above product, the H NMR spectrum and the C NMR spectrum of the compound were measured by a nuclear magnetic resonance instrument (300 MHz, deuterated chloroform as a solvent, and tetramethylchlorosilane as an internal standard), and the carbon in the compound was determined by an elemental analyzer. , hydrogen, and nitrogen content, the melting point of the compound was measured by a micro melting point apparatus, and the specific results are as follows:

Proton NMR spectrum (δ refers to the chemical shift, the unit is one millionth): δ 8.50 (d, J= 7.5 Hz, 2H), 7.65 - 7.36 (m, 3H), 4.13 (s, 6H).

Carbon NMR spectrum (δ refers to the chemical shift, the unit is one millionth): δ 174.92, 172.90, 135.03, 132.82, 129.01, 128.48, 55.20.

Elemental analysis (compound molecular formula is C ₁₁ H ₁₁ N ₃ O ₂ ): theoretical value C 60.82, H 5.10, N 19.34; measured value C 60.88, H 5.13, N 19.29.

Melting point: the measured value is 88-89°C, and the literature value is 89-90°C.

From the above experimental data, it can be seen that 8.50 and 7.65 -7.36 in the NMR spectrum are five hydrogen chemical shifts on the benzene ring, and 4.13 is the chemical shift of six hydrogens in the methoxy group on the triazine ring; 174.92 and 7.36 in the NMR carbon spectrum 172.90 is the chemical shift of the carbon atom connected to the methoxy group and chlorine on the triazine ring, respectively; 135.03, 132.82, 129.01, and 128.48 are the carbon shifts of the benzene ring connected to the triazine ring; 55.20 is the methoxy group connected to the triazine ring The chemical shift of the carbon atoms in the group. The above-mentioned elemental analysis results show that the measured values of the percentages of carbon, hydrogen and nitrogen elements in the compound are consistent with the theoretical values. The observed melting point of this compound is consistent with that reported in the literature. Thus it can be concluded that the compound is the target compound 2,4-dimethoxy-6-phenyl-1,3,5-triazine.

Example 2

The synthetic method of the s-triazine derivative of the present embodiment is realized by the following steps:

Step 1: Add 175.6mg of 2-chloro-4,6-dimethoxy-1,3,5-triazine and 1.67ml of phenyl with a concentration of 1.2mol/L to the dry reactor at -10°C Zinc chloride and a mixed catalyst consisting of 10.5 mg of bis(triphenylphosphine)palladium dichloride and 3.9 mg of triphenylphosphine, 2-chloro-4,6-dimethoxy-1,3,5- The molar ratio of triazine to phenylzinc chloride and the mixed catalyst is 1:2:0.03, and the molar ratio of bis(triphenylphosphine) palladium dichloride to triphenylphosphine in the mixed catalyst is 1:1. Reaction 4 Hour, other steps are identical with embodiment 1 in this step.

Other steps were the same as in Example 1 to obtain 212.9 mg of 2,4-dimethoxy-6-phenyl-1,3,5-triazine with a yield of 98%.

Example 3

The synthetic method of the s-triazine derivative of the present embodiment is realized by the following steps:

Step 1: Add 175.6mg of 2-chloro-4,6-dimethoxy-1,3,5-triazine and 1.46ml of phenyl chloride with a concentration of 1.2mol/L to the dry reactor at 45°C Zinc chloride and a mixed catalyst consisting of 12.6 mg of bis(triphenylphosphine)palladium dichloride and 18.9 mg of triphenylphosphine, 2-chloro-4,6-dimethoxy-1,3,5-tri The molar ratio of oxazine to phenylzinc chloride and the mixed catalyst is 1:1.75:0.09, and the molar ratio of bis(triphenylphosphine)palladium dichloride to triphenylphosphine in the mixed catalyst is 1:4, and the reaction takes 2 hours , other steps in this step are the same as in Example 1.

Other steps were the same as in Example 1 to obtain 206.4 mg of 2,4-dimethoxy-6-phenyl-1,3,5-triazine with a yield of 95%.

Example 4

The synthetic method of the s-triazine derivative of the present embodiment is realized by the following steps:

Step 1: Add 175.6mg of 2-chloro-4,6-dimethoxy-1,3,5-triazine and 0.84ml of phenyl with a concentration of 1.2mol/L to the dry reactor at -30°C Zinc chloride and a mixed catalyst consisting of 1.7 mg of bis(triphenylphosphine)palladium dichloride and 0.1 mg of triphenylphosphine, 2-chloro-4,6-dimethoxy-1,3,5- The molar ratio of triazine to phenyl zinc chloride and the mixed catalyst is 1:1:0.0025, the molar ratio of bis(triphenylphosphine) palladium dichloride to triphenylphosphine in the mixed catalyst is 1:0.05, and the reaction is 4.5 Hour, other steps are identical with embodiment 1 in this step.

Other steps were the same as in Example 1 to obtain 197.7 mg of 2,4-dimethoxy-6-phenyl-1,3,5-triazine with a yield of 91%.

Example 5

The synthetic method of the s-triazine derivative of the present embodiment is realized by the following steps:

Step 1: Add 175.6mg of 2-chloro-4,6-dimethoxy-1,3,5-triazine and 2.08ml of phenyl chloride with a concentration of 1.2mol/L to the reaction tube at 75°C Zinc chloride and a mixed catalyst consisting of 19.5 mg of bis(triphenylphosphine)palladium dichloride and 46.6 mg of triphenylphosphine, 2-chloro-4,6-dimethoxy-1,3,5-triazine The molar ratio of phenyl zinc chloride and mixed catalyst is 1:2.5:0.2, the molar ratio of bis(triphenylphosphine) palladium dichloride and triphenylphosphine in the catalyst is 1:8, and the reaction takes 1.5 hours. Other steps are identical with embodiment 1 in the step.

Other steps were the same as in Example 1 to obtain 212.9 mg of 2,4-dimethoxy-6-phenyl-1,3,5-triazine with a yield of 98%.

Example 6

In the step 1 of the above-mentioned embodiments 1~5, the active ingredient 2-chloro-4,6-dimethoxy-1,3,5-triazine uses an equimolar amount of 2,4-dichloro-6-methoxy The base-1,3,5-triazine is replaced, and other steps in this step are the same as those in the corresponding examples.

Other steps are the same as the corresponding embodiment.

Example 7

In the step 1 of above-mentioned embodiment 1～6, two (triphenylphosphine) palladium dichlorides in the mixed catalyst use four (triphenylphosphine) palladium, three (dibenzylidene acetone) dipalladium 1. Replace any one of palladium di(acetylacetonate), and other steps in this step are the same as those in the corresponding embodiment.

Other steps are the same as the corresponding embodiment.

Example 8

In the step 1 of above-mentioned embodiment 1～6, two (triphenylphosphine) palladium dichlorides in the mixed catalyst are replaced with palladium acetate or palladium dichloride of equimolar amount or these two kinds of compositions, in this step Other steps are the same as the corresponding embodiment.

Other steps are the same as the corresponding embodiment.

Example 9

In the step 1 of the above-mentioned examples 1-8, the triphenylphosphine in the mixed catalyst is replaced with an equimolar amount of 1,2-bis(diphenylphosphine)ethane, and other steps in this step are the same as those in the corresponding example.

Other steps are the same as the corresponding embodiment.

Example 10

In step 1 of the above-mentioned embodiments 1 to 9, the mixed catalyst is replaced with an equimolar amount of palladium acetate catalyst or palladium dichloride catalyst, and other steps in this step are the same as in the corresponding embodiment.

Other steps are the same as the corresponding embodiment.

Example 11

In step 1 of the above-mentioned embodiments 1 to 9, the mixed catalyst is replaced with an equimolar mixed catalyst composed of palladium acetate and palladium dichloride, and other steps in this step are the same as those in the corresponding embodiment.

Other steps are the same as the corresponding embodiment.

Example 12

In the step 1 of above-mentioned embodiment 1～9, four (triphenylphosphine) palladium catalysts, two (triphenylphosphine) palladium dichloride catalysts, three (dibenzylidene acetone) dichloride catalysts, three (dibenzylidene acetone) two Any one of the palladium catalyst and bis(acetylacetonate) palladium catalyst is replaced, and other steps in this step are the same as those in the corresponding embodiment.

Other steps are the same as the corresponding embodiment.

Example 13

In the step 1 of above-mentioned embodiment 1～9, four (triphenylphosphine) palladium catalysts, two (triphenylphosphine) palladium dichloride catalysts, three (dibenzylidene acetone) dichloride catalysts, three (dibenzylidene acetone) two The palladium catalyst and the palladium bis(acetylacetonate)palladium catalyst are replaced by a mixture formed by mixing any two or three in any ratio, and other steps in this step are the same as those in the corresponding embodiment.

Other steps are the same as the corresponding embodiment.

Example 14

In the step 1 of above-mentioned embodiment 1～13, the phenyl zinc chloride as organozinc reagent uses equimolar amount 4-methylphenyl zinc chloride, 4-methoxyphenyl zinc chloride, 4-bromo Any one of phenyl zinc chloride, 4-cyanophenyl zinc chloride is replaced, and other steps in this step are the same as the corresponding embodiments.

Other steps are the same as the corresponding embodiment.

Example 15

In the step 1 of above-mentioned embodiment 1～13, any one in isopropyl zinc chloride, n-butyl zinc chloride, benzyl zinc chloride of equimolar amount as the phenyl zinc chloride of organozinc reagent Instead, other steps in this step are the same as those in the corresponding embodiment.

Other steps are the same as the corresponding embodiment.

Example 16

In the step 1 of above-mentioned embodiment 1～13, the phenyl zinc chloride as organozinc reagent is replaced with 2-thienyl zinc chloride or 2-pyridine zinc chloride of equimolar amount, other steps in this step and corresponding implementation Example is the same.

Other steps are the same as the corresponding embodiment.

Example 17

After step 1 of above-mentioned embodiment 1～13, carry out step a, specifically:

In the reaction solution in step 1), add isopropylzinc chloride, n-butylzinc chloride, benzylzinc chloride, 4-methylphenylzinc chloride, 4-methylzinc chloride with a concentration of 1.1mol/l Any one of oxyphenyl zinc chloride, 4-bromophenyl zinc chloride, 4-cyanophenyl zinc chloride, 2-thienyl zinc chloride, and 2-pyridine zinc chloride is used as the second addition The organozinc reagent, the molar ratio of 2,4-dichloro-6-methoxy-1,3,5-triazine to the organozinc reagent added for the second time is 1:1.5, react for 3 hours, after the reaction is complete Proceed to step 2.

Other steps are identical with embodiment 1～13.

Example 18

After step 1 of above-mentioned embodiment 1～13, carry out step a, specifically:

In the reaction solution in step 1), add isopropylzinc chloride, n-butylzinc chloride, benzylzinc chloride, 4-methylphenylzinc chloride, 4-methylzinc chloride with a concentration of 1.1mol/l Any one of oxyphenyl zinc chloride, 4-bromophenyl zinc chloride, 4-cyanophenyl zinc chloride, 2-thienyl zinc chloride, and 2-pyridine zinc chloride is used as the second The added organic zinc reagent, the molar ratio of 2,4-dichloro-6-methoxy-1,3,5-triazine to the second added organic zinc reagent is 1:1, react for 1.5 hours, and the reaction is complete Then proceed to step 2.

Other steps are identical with embodiment 1～13.

Example 19

After step 1 of above-mentioned embodiment 1～13, carry out step a, specifically:

In the reaction solution in step 1), add isopropylzinc chloride, n-butylzinc chloride, benzylzinc chloride, 4-methylphenylzinc chloride, 4-methylzinc chloride with a concentration of 1.1mol/l Any one of oxyphenyl zinc chloride, 4-bromophenyl zinc chloride, 4-cyanophenyl zinc chloride, 2-thienyl zinc chloride, and 2-pyridine zinc chloride is used as the second The added organic zinc reagent, the molar ratio of 2,4-dichloro-6-methoxy-1,3,5-triazine to the second added organic zinc reagent is 1:2.5, reacted for 4.5 hours, and the reaction was complete Then proceed to step 2.

Other steps are identical with embodiment 1～13.

The preparation methods of Menicagli Group and Knochel et al. are compared with the synthesis methods of the s-triazine derivatives of Example 1 and Example 6 of the present invention as Comparative Example 1 and Comparative Example 2 respectively.

Wherein Comparative Example 1 is that the Menicagli group synthesizes s-triazine derivatives by coupling 2-chloro-4,6-dimethoxy-1,3,5-triazine with aryl zinc reagent or benzyl zinc reagent, and the synthetic method as follows:

Step 1: At room temperature, add 1.2g (19mmol) zinc powder, 4.74g (6ml, 115.5mmol, concentration 19.2mol/L) of acetonitrile, 172.2mg (2.25mmol) of allyl chloride in the reaction tube and 21.7mg (0.19mmol) of trifluoroacetic acid, slowly warming up to 80°C, and then adding 392.6mg (2.5mmol) of bromobenzene to the reaction solution, and stirring for 30 minutes. Add 543.1 mg (2.5 mmol) of 2-chloro-4,6-dimethoxy-1,3,5-triazine and 165 mg (0.75 mmol) of cobalt bromide to the above-prepared phenyl zinc bromide , the molar ratio of 2-chloro-4,6-dimethoxy-1,3,5-triazine to phenylzinc bromide and catalyst: 1:1:0.3, reacted at 25°C for 12 hours; step 2 : After step 1 is completed, add the ammonium chloride solution with a concentration of 1.5mol/L to the reaction tube until the quenching reaction is complete, extract the aqueous phase with 5mL dichloromethane for 3 times, combine the organic layers, and add 1g of anhydrous magnesium sulfate Dry and concentrate to obtain the crude product s-triazine derivative; Step 3: Purify 65.2 mg of 2,4-dimethoxy-6-phenyl-1,3,5-triazine through silica gel column chromatography, the yield is 30%.

The method has the advantages that the amount of the catalyst is up to 30%, the reaction time is up to 12 hours, the yield of the product is only 30%, and the reaction substrate is suitable for aryl zinc reagent or benzyl zinc reagent.

Comparative example 2 is the synthesis of s-triazine derivatives by the Knochel research group through the coupling of 2,4-dichloro-6-methoxy-1,3,5-triazine and alkyl Grignard reagents. The synthesis method is as follows:

Step 1: Add 180.0 mg (1.0 mmol) of 2,4-dichloro-6-methoxy-1,3,5-triazine and 38.1 mg (0.2mmol) cuprous iodide catalyst, after stirring for 30 minutes, slowly add 3.5mL tetrahydrofuran solution of tert-butylmagnesium chloride with a concentration of 1.0mol/L to the above reaction solution, 2,4-dichloro-6 - The molar ratio of methoxy-1,3,5-triazine to tert-butylmagnesium chloride to the catalyst is 1:3.5:0.2, react at 0°C for 12 hours; step 2: after step 1 is completed, add Ammonium chloride solution with a concentration of 1.5 mol/L until the quenching reaction is complete, the resulting aqueous phase is extracted 3 times with 5 mL of ethyl acetate, the organic layers are combined, dried by adding 1.5 g of anhydrous magnesium sulfate, and concentrated to obtain the crude product s-triazine Derivatives; Step 3: 66.5 mg of 2-chloro-4-methoxy-6-phenyl-1,3,5-triazine and 52.7 mg of 2-chloro-4,6 were purified by silica gel column chromatography -Diphenyl-1,3,5-triazine and wherein the molar ratio of mono-substitution and di-substitution is: 60:40, and the total yield is 50%.

In this method, the consumption of catalyzer reaches 20%, and the reaction time reaches 12 hours, and productive rate also only has 50%, and the Grignard reagent used in reaction is limited to alkyl Grignard reagent, and the mol ratio of single substitution and double substitution in the reaction product is : 1.5:1, poor selectivity.

The experimental results are as follows:

The prior art of table 1 compares with the synthetic method of the s-triazine derivative of the present invention

The reaction product of 2-chloro-4,6-dimethoxy-1,3,5-triazine in the above table is 2,4-dimethoxy-6-phenyl-1,3,5-tri Azine; -triazine, the disubstituted product is 2-methoxy-4,6-diphenyl-1,3,5-triazine.

As can be seen from the results of the above table, the amount of catalyst used in the present invention is less, the reaction time is short, and the yield is higher than that of Comparative Examples 1 and 2, and the mono-substituted product of the present invention: the double-substituted product value is 100:0, which is similar to that of the present invention. There are techniques better than its selectivity.

Claims (1)

1. a synthetic method of s-triazine derivatives, characterized in that: comprise the following steps: 1) -30°C ~ 75°C, replace the dry reactor with _N2 and then add 2-chloro-4,6-dimethoxy-1,3,5-triazine, organic zinc reagent and catalyst, 2- The molar ratio of chloro-4,6-dimethoxy-1,3,5-triazine to organic zinc reagent and catalyst is 1:1.50～2.00:0.03～0.15, and the reaction is 1.5～4.5 hours; 2) adding a hydrochloric acid solution having a concentration of 1 mol/L to the reacted solution until the quenching reaction is complete, extracting the generated aqueous phase 3 times, merging the organic layers, drying, and concentrating to obtain a crude s-triazine derivative; 3) The crude product s-triazine derivatives are purified by silica gel column chromatography to obtain s-triazine derivatives; Above-mentioned catalyst is any one in the mixed catalyst of palladium salt and phosphine ligand, the mixed catalyst of palladium complex and phosphine ligand, the molar ratio of palladium salt and phosphine ligand in the mixed catalyst of palladium salt and phosphine ligand is 1 : 1~4, the mixed catalyst molar ratio of palladium complex and phosphine ligand is 1:1~4; Above-mentioned palladium salt is palladium acetate or palladium dichloride or its combination; The above-mentioned palladium complex is any one of bis(triphenylphosphine)palladium dichloride, tetrakis(triphenylphosphine)palladium, tris(dibenzylideneacetone)dipalladium, bis(acetylacetonate)palladium, or at least Any combination of the two; The above-mentioned phosphine ligand is triphenylphosphine or 1,2-bis(diphenylphosphine)ethane; The above organic zinc reagent is any one of isopropylzinc chloride, n-butylzinc chloride, benzylzinc chloride, 2-thienylzinc chloride and 2-pyridinezinc chloride.