Synthesis method of nitrogen heterocyclic compound tetrazole

Abstract

The invention discloses a synthetic method of nitrogen heterocyclic compound tetrazole. The method comprises the following steps: S1, reacting metal sulfate cyanate with halogenated hydrocarbon in a first solvent under the action of a catalyst to generate thiocyanate organic ester; s2, carrying out a reaction on the organic thiocyanate, sodium azide and ammonium chloride in a second solvent to generate 5-R thiotetrazole; s3, 5-R sulfenyl tetrazole is subjected to hydrogenation to remove R sulfenyl in a third solvent under the catalysis of Reranai nickel, and nitrogen heterocyclic compound tetrazole is synthesized; the metal sulfate cyanate in S1 is potassium sulfate cyanate or sodium sulfate cyanate; r in the halogenated hydrocarbon R-X is a linear chain of 25 carbon atoms or aliphatic hydrocarbon with a branched chain, or benzyl aromatic hydrocarbon with different substituent groups, and X is chlorine or bromine; the catalyst is one or more of tetrabutylammonium chloride, tetrabutylammonium bromide, benzyltriethylammonium bromide and benzyltriethylammonium chloride. The synthesis method provided by the invention has the advantages of simple process, easily available raw materials, easy operation, high comprehensive product yield and the like.

Description

Technical Field

[0001] The invention relates to the technical field of chemical engineering, and in particular to a method for synthesizing tetrazole, a nitrogen heterocyclic compound. Background Art

[0002] At present, the production of tetrazole is mainly produced by reacting hydrazoic acid with hydrocyanic acid at 100°C for a long time or under high pressure. The process is complicated, the raw materials are highly toxic and explosive, and the product is expensive. Therefore, it is urgent to develop a new synthesis method of tetrazole to solve the above technical problems. Summary of the invention

[0003] Based on the technical problems existing in the background technology, the present invention proposes a method for synthesizing tetrazolyl nitrogen heterocyclic compound, which has simple process, easy raw materials, easy operation and high comprehensive yield of the product.

[0004] The synthesis method of the nitrogen heterocyclic compound tetrazole proposed by the present invention comprises the following steps:

[0005] S1: reacting a metal sulfate cyanate with a halogenated hydrocarbon in a first solvent under the action of a catalyst to generate an organic thiocyanate;

[0006]

[0007] S2: reacting an organic thiocyanate, sodium azide and ammonium chloride in a second solvent to generate 5-R-thiotetrazolyl;

[0008]

[0009] S3: 5-R-thio tetrazole is subjected to hydrogenation in a third solvent under the catalysis of Rarely Nickel to remove the R-thio group to synthesize a nitrogen heterocyclic compound tetrazole.

[0010]

[0011] Preferably, the metal sulfate cyanate in S1 is potassium sulfate cyanate or sodium sulfate cyanate; R in the halogenated hydrocarbon RX is a straight-chain or branched aliphatic hydrocarbon with 25 carbon atoms, a benzyl aromatic hydrocarbon with different substituents, and X is chlorine or bromine; the first solvent is one or more of anhydrous ethanol, 95% ethanol, methanol, isopropanol, acetonitrile, benzene, toluene and xylene; the catalyst is one or more of tetrabutylammonium chloride, tetrabutylammonium bromide, benzyltriethylammonium bromide and benzyltriethylammonium chloride.

[0012] Preferably, the molar ratio of metal sulfate cyanate, halogenated hydrocarbon and catalyst in S1 is 1-1.3:1:0.001-0.01.

[0013] Preferably, the reaction temperature in S1 is 40-80° C., and the reaction time is 5-10 h.

[0014] Preferably, the molar ratio of ammonium chloride, sodium azide and ethyl thiocyanate in S2 is 1-1.3:1-1.2:1.

[0015] Preferably, the second solvent in S2 is composed of water and ethanol in a volume ratio of 1-10:1.

[0016] Preferably, the reaction temperature in S2 is 60-100° C., and the reaction time is 5-10 h.

[0017] Preferably, the third solvent in S3 is one or more of water, methanol, ethanol and acetonitrile.

[0018] Preferably, the molar ratio of 5-ethylthiotetrazolyl to erythritol nickel in S3 is 1:0.1-0.3.

[0019] Preferably, the reaction condition in S3 is heating to reflux reaction for 5-12 h.

[0020] Beneficial technical effects of the present invention:

[0021] (1) The present invention generates an organic thiocyanate by reacting a metal sulfate cyanate with a halogenated hydrocarbon, which reacts with sodium azide and ammonium chloride to generate 5-R-thiotetrazolyl, and finally the 5-R-thiotetrazolyl is subjected to a substitution reaction to obtain tetrazole. The process is simple, the raw materials are easy to obtain, the operation is easy, and the comprehensive yield of the product is as high as 65%-72%.

[0022] (2) The 5-R-thiotetrazolyl synthesized in the present invention can also be used as a raw material for synthesizing different tetrazole substituted 6APA or 7ACA mother cores, thereby saving the time for synthesizing tetrazole derivatives.

[0023] (3) The present invention uses a rotating disk, a tooth groove, a rotating rod and a gear to rotate the rotating disk while driving the rotating rod to rotate. At the same time, the tooth groove and the gear make the rotating rod rotate while rotating, so as to fully stir the inside of the distillation tank, promote the bubbles in the liquid inside the distillation tank to float up, prevent the solution from being heated unevenly, and make the raw materials react more violently, thereby improving the distillation efficiency and product quality, and ensuring the smooth progress of the distillation process. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 This is a schematic diagram of the structure of the atmospheric distillation device proposed by the present invention;

[0025] Figure 2 This is a schematic diagram of the internal structure of the atmospheric distillation device proposed by the present invention;

[0026] Figure 3 This is a schematic diagram of the structure of the stirring assembly proposed by the present invention;

[0027] Figure 4This is a schematic structural diagram of the rotating assembly proposed in the present invention. DETAILED DESCRIPTION

[0028] The present invention will be further explained below in conjunction with specific embodiments.

[0029] Reference Figure 1-4 The atmospheric distillation device proposed by the present invention comprises a distillation tank 1, through which materials are sorted and refined, a fixed cover 2 sealed with the distillation tank 1 is fixed on the top of the distillation tank 1, a motor 3 is fixed on the top of the fixed cover 2, a fixed disk 4 is fixed on the bottom of the motor 3, a rotating disk 5 is fixed on the rotating end of the motor 3, the rotating disk 5 is driven to rotate by the motor 3, a tooth groove 6 is opened inside the fixed cover 2, a plurality of rotating rods 7 connected to the rotating disk 5 are penetrated on the top of the rotating disk 5, the rotating rod 7 is limited by the rotating disk 5 so that the rotating rod 7 can only rotate, a gear 8 meshing with the tooth groove 6 is fixed on the top outer surface of the rotating rod 7, while the rotating rod 7 is driven to rotate by the rotation of the rotating disk 5, the rotating rod 7 is self-rotated by the tooth groove 6 and the gear 8, a plurality of stirring rods 9 are fixed on the surface of the rotating rod 7, a plurality of stirring blades 10 are fixed on the surface of the stirring rod 9, the inside of the distillation tank 1 can be fully stirred by the stirring rod 9 and the stirring blades 10, and the stirring function is mainly to promote the floating of bubbles in the liquid and prevent the solution from being heated unevenly.

[0030] A condenser 11 is fixed to the surface of the distillation tank 1 and is connected thereto. The steam generated inside the distillation tank 1 is condensed through the condenser 11. A feed valve tube 12 is fixed to the top of the distillation tank 1 and is connected thereto. Materials can be added conveniently through the feed valve tube 12. A discharge valve tube 13 is fixed to the bottom of the distillation tank 1 and is connected thereto. It is convenient to take out the distilled raw materials. Several support legs 14 are fixed to the bottom of the distillation tank 1. The support legs 14 support the device, thereby ensuring the stability of the device during operation.

[0031] When the device is used, raw materials are put into the distillation tank 1 through the feed valve tube 12 on the top of the distillation tank 1, and the raw materials are heated by the distillation tank 1. At this time, the motor 3 is started again, and the rotating disk 5 is driven by the motor 3 to rotate. The rotation of the rotating disk 5 drives the rotating rod 7 to rotate, and the rotating rod 7 is rotated while rotating through the tooth groove 6 and the gear 8. The rotation of the rotating rod 7 drives the stirring rod 9 and the stirring blade 10 to rotate and also rotate themselves, thereby promoting the floating of bubbles in the liquid inside the distillation tank 1, preventing the solution from being heated unevenly, and making the raw materials react more violently, thereby improving the distillation efficiency and product quality, ensuring the smooth progress of the distillation process, and condensing the generated steam through the condenser 11 on the left side of the distillation tank 1, and discharging the raw materials after distillation through the discharge valve tube 13 at the bottom of the distillation tank 1.

[0032] Example 1

[0033] The synthesis method of the nitrogen heterocyclic compound tetrazole proposed by the present invention has the following steps:

[0034] S1: Add ethyl bromide dropwise to potassium thiocyanate, anhydrous ethanol and tetrabutylammonium chloride catalyst under heating, stirring and reflux, and then react at 60°C for 8 hours. The dosage ratio of the above substances is calculated as potassium thiocyanate: ethyl bromide: catalyst: anhydrous ethanol = 1.1:1:0.005:10. After the reaction is completed, filter out the generated salt and distill the oil layer at normal pressure to obtain ethyl thiocyanate.

[0035] S2: Mix water, ethanol, ammonium chloride, sodium azide, and ethyl thiocyanate evenly, the dosage ratio of the above substances is ammonium chloride: sodium azide: ethyl thiocyanate = 1.2:1.2:1, the volume ratio of water to ethanol is 4:1, stir and heat to 78°C, keep warm and react for 8 hours. After the reaction is completed, add concentrated hydrochloric acid to raise the pH value to 1, cool and precipitate solids, and filter to obtain 5-ethylthiotetrazolyl.

[0036] S3: 5-ethylthiotetrazolyl, Raney nickel, and anhydrous ethanol are heated to reflux reaction for 8 hours, and the usage ratio of the above substances is 5-ethylthiotetrazolyl: Raney nickel: anhydrous ethanol = 1:1.5:30, and then the temperature is naturally lowered to room temperature, the catalyst Raney nickel is recovered, and ethyl mercaptan and solvent ethanol are evaporated to obtain solid tetrazole. The yield of tetrazole is 72.5%.

[0037] Example 2

[0038] The synthesis method of the nitrogen heterocyclic compound tetrazole proposed by the present invention has the following steps:

[0039] S1: Add ethyl bromide dropwise to potassium thiocyanate, anhydrous ethanol and tetrabutylammonium bromide under heating, stirring and reflux, and then react at 40°C for 5 hours. The dosage ratio of the above substances is calculated by the amount of substances: potassium thiocyanate: ethyl bromide: catalyst: anhydrous ethanol = 1.05:1:0.002:8. After the reaction is completed, filter out the generated salt and distill the oil layer at normal pressure to obtain ethyl thiocyanate.

[0040] S2: Mix water, ethanol, ammonium chloride, sodium azide, and ethyl thiocyanate evenly, the dosage ratio of the above substances is ammonium chloride: sodium azide: ethyl thiocyanate = 1.3:1.2:1, the volume ratio of water to ethanol is 1:1, stir and heat to 60°C, keep warm and react for 6 hours. After the reaction is completed, add concentrated hydrochloric acid to raise the pH value to 2, cool and precipitate solids, and filter to obtain 5-ethylthiotetrazolyl.

[0041] S3: 5-ethylthiotetrazolyl, Raney nickel, and anhydrous ethanol are heated to reflux for 6 hours, and the ratio of the above substances is 5-ethylthiotetrazolyl: Raney nickel: anhydrous ethanol = 1:1:20, and then the temperature is naturally lowered to room temperature, the catalyst Raney nickel is recovered, and ethyl mercaptan and solvent ethanol are evaporated to obtain solid tetrazole. The yield of tetrazole is 65.9%.

[0042] Example 3

[0043] The synthesis method of the nitrogen heterocyclic compound tetrazole proposed by the present invention has the following steps:

[0044] S1: Potassium thiocyanate, anhydrous ethanol and benzyltriethylammonium bromide are heated, stirred and refluxed, and ethyl bromide is added dropwise, followed by reaction at 80°C for 10 hours. The dosage ratio of the above substances is calculated based on the amount of substances: potassium thiocyanate: ethyl bromide: catalyst: anhydrous ethanol = 1:1:0.01:6. After the reaction is completed, the generated salt is filtered out and the oil layer is distilled at normal pressure to obtain ethyl thiocyanate.

[0045] S2: Mix water, ethanol, ammonium chloride, sodium azide, and ethyl thiocyanate evenly, with the ratio of ammonium chloride: sodium azide: ethyl thiocyanate = 1.2:1.05:1, and the ratio of water to ethanol is 8:1, stir and heat to 80°C, and keep warm for 10 hours. After the reaction is completed, add concentrated hydrochloric acid to raise the pH to 2, cool and precipitate solids, and filter to obtain 5-ethylthiotetrazolyl.

[0046] S3: 5-ethylthiotetrazolyl, Raney nickel, and anhydrous ethanol are heated to reflux reaction for 10 hours, and the usage ratio (molar ratio) of the above substances is 5-ethylthiotetrazolyl: Raney nickel: anhydrous ethanol = 1:2:30, and then the temperature is naturally lowered to room temperature, the catalyst Raney nickel is recovered, and ethyl mercaptan and solvent ethanol are evaporated to obtain solid tetrazole. The yield of tetrazole is 71.2%.

[0047] Example 4

[0048] The synthesis method of the nitrogen heterocyclic compound tetrazole proposed by the present invention has the following steps:

[0049] S1: Add ethyl chloride dropwise to potassium thiocyanate, anhydrous ethanol and tetrabutylammonium chloride catalyst under heating, stirring and reflux, and then react at 60°C for 8h. The dosage ratio of the above substances is calculated as potassium thiocyanate: ethyl bromide: catalyst: anhydrous ethanol = 1.1:1:0.005:10. After the reaction is completed, filter out the generated salt and distill the oil layer at normal pressure to obtain ethyl thiocyanate.

[0050] S2: Mix water, ethanol, ammonium chloride, sodium azide, and ethyl thiocyanate evenly, the dosage ratio of the above substances is ammonium chloride: sodium azide: ethyl thiocyanate = 1.2:1.2:1, the volume ratio of water to ethanol is 4:1, stir and heat to 78°C, keep warm and react for 8 hours. After the reaction is completed, add concentrated hydrochloric acid to raise the pH value to 1, cool and precipitate solids, and filter to obtain 5-ethylthiotetrazolyl.

[0051] S3: 5-ethylthiotetrazolyl, Raney nickel, and anhydrous ethanol are heated to reflux reaction for 8 hours, and the usage ratio of the above substances is 5-ethylthiotetrazolyl: Raney nickel: anhydrous ethanol = 1:1.5:30, and then the temperature is naturally lowered to room temperature, the catalyst Raney nickel is recovered, and ethyl mercaptan and solvent ethanol are evaporated to obtain solid tetrazole. The yield of tetrazole is 69.1%.

[0052] Example 5

[0053] The synthesis method of the nitrogen heterocyclic compound tetrazole proposed by the present invention has the following steps:

[0054] S1: Add 2,4-dimethylbenzyl bromide dropwise to potassium thiocyanate, anhydrous ethanol and tetrabutylammonium bromide under heating, stirring and reflux, and then react at 40°C for 5 hours. The dosage ratio of the above substances is calculated by the amount of substances: potassium thiocyanate: ethyl bromide: catalyst: anhydrous ethanol = 1.05:1:0.002:8. After the reaction is completed, filter out the generated salt and distill the oil layer at normal pressure to obtain ethyl thiocyanate.

[0055] S2: Mix water, ethanol, ammonium chloride, sodium azide, and ethyl thiocyanate evenly, the dosage ratio of the above substances is ammonium chloride: sodium azide: ethyl thiocyanate = 1.3:1.2:1, the volume ratio of water to ethanol is 1:1, stir and heat to 60°C, keep warm and react for 6 hours. After the reaction is completed, add concentrated hydrochloric acid to raise the pH value to 2, cool and precipitate solids, and filter to obtain 5-ethylthiotetrazolyl.

[0056] S3: 5-ethylthiotetrazolyl, Raney nickel, and anhydrous ethanol are heated to reflux for 6 hours, and the ratio of the above substances is 5-ethylthiotetrazolyl: Raney nickel: anhydrous ethanol = 1:1:20, and then the temperature is naturally lowered to room temperature, the catalyst Raney nickel is recovered, and ethyl mercaptan and solvent ethanol are evaporated to obtain solid tetrazole. The yield of tetrazole is 66.7%.

[0057] Example 6

[0058] The synthesis method of the nitrogen heterocyclic compound tetrazole proposed by the present invention has the following steps:

[0059] S1: Potassium thiocyanate, anhydrous ethanol and benzyltriethylammonium bromide are heated, stirred and refluxed, and 1-bromobutane is added dropwise, and then reacted at 80°C for 10 hours. The dosage ratio of the above substances is calculated according to the amount of substances: potassium thiocyanate: ethyl bromide: catalyst: anhydrous ethanol = 1:1:0.01:6. After the reaction is completed, the generated salt is filtered out and the oil layer is distilled at normal pressure to obtain ethyl thiocyanate.

[0060] S2: Mix water, ethanol, ammonium chloride, sodium azide, and ethyl thiocyanate evenly, with the ratio of ammonium chloride: sodium azide: ethyl thiocyanate = 1.2:1.05:1, and the ratio of water to ethanol is 8:1, stir and heat to 80°C, and keep warm for 10 hours. After the reaction is completed, add concentrated hydrochloric acid to raise the pH to 2, cool and precipitate solids, and filter to obtain 5-ethylthiotetrazolyl.

[0061] S3: 5-ethylthiotetrazolyl, Raney nickel, and anhydrous ethanol are heated to reflux reaction for 10 hours, and the usage ratio (molar ratio) of the above substances is 5-ethylthiotetrazolyl: Raney nickel: anhydrous ethanol = 1:2:30, and then the temperature is naturally lowered to room temperature, the catalyst Raney nickel is recovered, and ethyl mercaptan and solvent ethanol are evaporated to obtain solid tetrazole. The yield of tetrazole is 68.3%.

Claims

1. A method for synthesizing a nitrogen heterocyclic compound tetrazole, characterized in that: The steps are as follows: S1: reacting a metal sulfate cyanate with a halogenated hydrocarbon in a first solvent under the action of a catalyst, and obtaining an organic thiocyanate after distillation under normal pressure; S2: reacting an organic thiocyanate, sodium azide and ammonium chloride in a second solvent to generate 5-R-thiotetrazolyl; S3: 5-R-thio tetrazole is subjected to hydrogenation in a third solvent under the catalysis of Rarely Nickel to remove the R-thio group to synthesize a nitrogen heterocyclic compound tetrazole.

2. The method for synthesizing the nitrogen heterocyclic compound tetrazole according to claim 1, characterized in that: The metal sulfate cyanate in S1 is potassium sulfate cyanate or sodium sulfate cyanate; R in the halogenated hydrocarbon RX is a straight-chain or branched aliphatic hydrocarbon with 25 carbon atoms, a benzyl aromatic hydrocarbon with different substituents, and X is chlorine or bromine; the first solvent is one or more of anhydrous ethanol, 95% ethanol, methanol, isopropanol, acetonitrile, benzene, toluene and xylene; the catalyst is one or more of tetrabutylammonium chloride, tetrabutylammonium bromide, benzyltriethylammonium bromide and benzyltriethylammonium chloride.

3. The method for synthesizing the nitrogen heterocyclic compound tetrazole according to claim 1, characterized in that: The molar ratio of metal sulfate cyanate, halogenated hydrocarbon and catalyst in S1 is 1-1.3:1:0.001-0.

01.

4. The method for synthesizing the nitrogen heterocyclic compound tetrazole according to claim 1, characterized in that: The reaction temperature in S1 is 40-80°C and the reaction time is 5-10h.

5. The method for synthesizing the nitrogen heterocyclic compound tetrazole according to claim 1, characterized in that: The molar ratio of ammonium chloride, sodium azide and ethyl thiocyanate in S2 is 1-1.3:1-1.2:

1.

6. The method for synthesizing the nitrogen heterocyclic compound tetrazole according to claim 1, characterized in that: The second solvent in S2 is composed of water and ethanol in a volume ratio of 1-10:

1.

7. The method for synthesizing the nitrogen heterocyclic compound tetrazole according to claim 1, characterized in that: The reaction temperature in S2 is 60-100°C and the reaction time is 5-10h.

8. The method for synthesizing the nitrogen heterocyclic compound tetrazole according to claim 1, characterized in that: The third solvent in S3 is one or more of water, methanol, ethanol and acetonitrile; Preferably, the molar ratio of 5-ethylthiotetrazolyl to erythritol nickel in S3 is 1:0.1-0.3; Preferably, the reaction condition in S3 is heating to reflux reaction for 5-12 h.

9. The method for synthesizing the nitrogen heterocyclic compound tetrazole according to claim 1, characterized in that: The atmospheric distillation device used for atmospheric distillation in S1 includes a distillation tank, a fixed cover is fixed on the top of the distillation tank, a motor is fixed on the top of the fixed cover, a fixed disk is fixed on the bottom of the motor, a rotating disk is fixed on the rotating end of the motor, a tooth groove is opened inside the fixed cover, a plurality of rotating rods rotatably connected to the rotating disk are penetrated through the top of the rotating disk, a gear meshing with the tooth groove is fixed on the top outer surface of the rotating rod, a plurality of stirring rods are fixed on the surface of the rotating rod, and a plurality of stirring blades are fixed on the surface of the stirring rod.

10. The method for synthesizing the nitrogen heterocyclic compound tetrazole according to claim 9, characterized in that: A condenser pipe is fixed to the surface of the distillation tank and is connected therewith; a feed valve pipe is fixed to the top of the distillation tank and is connected therewith; a discharge valve pipe is fixed to the bottom of the distillation tank and is connected therewith; and a plurality of supporting legs are fixed to the bottom of the distillation tank.

Images