A method for synthesizing glycine anhydride from glycine

Abstract

The present invention provides a simple method for preparing glycine anhydride from glycine. Glycine is added to a solvent and stirred, followed by the addition of a phosphorus-containing additive. After the reaction is complete, the reaction is cooled to precipitate a large amount of solid, which is then filtered, washed, and dried to obtain the product. The phosphorus-containing additive is any one of phosphoric acid, phosphorus pentoxide, dibenzyl phosphite, diphenylphosphinyl chloride, phosphorus oxychloride, or phosphorus trichloride. Compared with existing technologies, this method has the advantages of simple operation, high reaction selectivity, reduced reaction temperature, low wastewater content, and solvent recyclability, thus having potential industrial application value.

Description

Technical Field

[0001] The invention belongs to the technical field of fine organic synthesis and relates to a simple method for synthesizing glycine anhydride from glycine. Background Art

[0002] Glycine anhydride is a very important chemical raw material, obtained by the condensation of glycine. Due to its unique six-membered heterocyclic ring structure, it is a versatile compound with a wide range of applications. Its main applications include the following: Glycine anhydride serves as a drug intermediate and plays an important role in pharmaceutical chemistry. It is used to synthesize a variety of drug molecules, including antiviral and anticancer drugs. Glycine anhydride can be used as a biochemical reagent. Hydrolysis with alkali, acid, or hot water can produce glycylglycine. In the food industry, glycine anhydride is used as a food additive to increase the nutritional value or improve the sensory properties of foods.

[0003] Li Hongyu and others disclosed a catalytic system that can synthesize cyclic dipeptides in one step. Specifically, a high-activity titanium salt catalytic system synthesized by a double decomposition reaction using a metal titanium compound and an organic superacid as raw materials is used for catalysis. However, the catalyst powder is easily deliquescent, and the metal titanium salt is expensive and difficult to recycle. U.S. Patent US0024180 provides a method for synthesizing 2,5-diketopiperazine by cyclization of glycine, wherein the glycine organic solvent is heated at a temperature between about 50-200°C, particularly between about 80°C and about 150°C, wherein the solvent is preferably a solvent that can form a low-boiling azeotrope with water, such as acetonitrile, allyl alcohol, benzene, benzyl alcohol, and n-butanol. However, the synthesis efficiency is low and high temperature is required. Summary of the Invention

[0004] To overcome the shortcomings of the prior art, the present invention provides a simple method for synthesizing glycine anhydride from glycine. By utilizing the additive of the present invention during the ring condensation reaction, the method achieves higher yields and higher purity of glycine anhydride in a shorter reaction time compared to conventional methods. The entire reaction process offers advantages such as simple operation, low wastewater production, and solvent recyclability.

[0005] To achieve the above-mentioned purpose, the technical solution of the present invention is as follows:

[0006] A simple method for synthesizing glycine anhydride from glycine, comprising the following steps:

[0007] Glycine is stirred in a solvent, and a phosphorus-containing additive is added. After the reaction is completed, the solid is cooled to precipitate, and then filtered, washed, and dried to obtain glycine anhydride.

[0008] In the steps, the solvent includes any one of ethanol, ethylene glycol, glycerol, 1,3-propylene glycol, N,N-dimethylformamide, pentaerythritol, and m-cresol.

[0009] In the steps, the additive includes any one of phosphoric acid, phosphorus pentoxide, dibenzyl phosphite, diphenylphosphinyl chloride, phosphorus oxychloride or phosphorus trichloride, and the molar equivalent of the additive is 1-6 times that of glycine.

[0010] In the steps, the molar concentration of glycine in the solvent is in the range of 0.1-10 M, preferably 1.0-8.0 M.

[0011] In the steps, the reaction time is 0.5-10 h, and the reaction temperature is 25-220°C, preferably 80°C-150°C.

[0012] In the steps, the temperature range of cooling and precipitation is -10-10°C, and the cooling time is 4-12 hours.

[0013] In the above steps, the filter cake obtained by filtration is washed with any one of petroleum ether, methanol, ethanol, ethyl acetate and cold water.

[0014] In the above steps, the filtrate obtained by filtration is dried with anhydrous sodium sulfate, calcium chloride, silica gel, montmorillonite, etc., and the filtrate can be recovered and reused.

[0015] The steps can be used to open a large number of reactions, and the amplification effect is not obvious. When the reaction volume is amplified to 1 mol, the yield is more than 90%.

[0016] The beneficial effects of the present invention are as follows:

[0017] 1. The present invention discloses a simple method for synthesizing glycine anhydride from glycine. Compared with the methods reported by other scholars, the reaction temperature can be lowered by adding cheap and readily available phosphorus pentoxide, making the reaction conditions milder.

[0018] 2. In the method of the present invention, the recovered mother liquor can be reused, and the yield decreases little, which can greatly reduce production costs.

[0019] 3. The method of the present invention can be used for large-scale experiments, and the amplification effect is not obvious, it is easy to produce on a large scale, and has good industrial prospects.

[0020] 4. The technical solution of the present invention can achieve a glycine anhydride yield of more than 80%, more preferably more than 85%, and even more preferably more than 90%. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 For example 1 of the present invention, glycine anhydride is prepared 1 H NMR spectrum.

[0022] Figure 2 For example 1 of the present invention, glycine anhydride is prepared 13 C NMR spectrum. DETAILED DESCRIPTION

[0023] The present invention is further described below with reference to the following examples. However, the scope of protection claimed in the present invention is not limited to the scope described in the examples.

[0024] Instruments and reagents:

[0025] Nuclear magnetic resonance (NMR) spectroscopy was performed using a Bruker AVANCE III 400 MHz Plus NMR spectrometer using D2O as the solvent. A 2YZ-4A rotary vane vacuum pump (Gongyi Yuhua Instrument Co., Ltd.), an EYELA SB-1100 rotary evaporator, an SHZ-E circulating water vacuum pump (Shanghai Rongya Biochemical Instrument Factory), a DZE-6120 vacuum drying oven (Shanghai Hengtian Scientific Instrument Manufacturing Co., Ltd.), an EB2005A electronic balance, and a DFX-5L / 30 low-temperature constant-temperature reaction bath (Wuxi Baichuan Instrument Factory) were used. All reagents were of analytical grade.

[0026] Example 1

[0027] A simple method for synthesizing glycine anhydride from glycine comprises the following experimental steps:

[0028] 7.5 g (100 mmol) of glycine was weighed into a 50 mL two-necked flask, and 20 mL of ethylene glycol was added, followed by 28.4 g of phosphine pentoxide (200 mmol, molar ratio of 1:2). The mixture was heated to 100°C in an oil bath for 2 h. After the reaction, the mixture was cooled to room temperature and then kept at 4°C for 8 h. The mixture was then filtered, and the filter cake was washed several times with ethanol and dried to obtain 5.262 g of the final product with a yield of 92.33%.

[0029] Examples 2-7

[0030] The method and operation are the same as in Example 1, except for the type and equivalent of the additives, as shown in Table 1.

[0031]

[0032] Examples 8-10

[0033] The method and operation are the same as in Example 1, except for the reaction temperature, as shown in Table 2.

[0034]

[0035] Examples 11-14

[0036] The method and operation are the same as in Example 1, except for the reaction solvent, as shown in Table 3.

[0037]

[0038] Examples 15-17

[0039] The method and operation are the same as in Example 1, except that the molar concentration of glycine is different, as shown in Table 4.

[0040]

[0041] Example 18

[0042] The method and operation were the same as those in Example 1, except that the filtrate in Example 1 was dried over anhydrous sodium sulfate and used as the reaction solvent. Finally, 5.095 g of product was obtained with a yield of 89.39%.

[0043] Example 19

[0044] The method and operation were the same as those in Example 18, except that the filtrate in Example 18 was dried over anhydrous sodium sulfate and used as the reaction solvent. Finally, 4.847 g of product was obtained with a yield of 85.04%.

[0045] Example 20

[0046] The method and operation were the same as those in Example 1, except that the amount of glycine in Example 1 was changed to 75 g (1 mol) and the amount of ethylene glycol used was 200 mL. Finally, 51.42 g of the product was obtained with a yield of 90.21%.

[0047] The present invention provides a simple method for synthesizing glycine anhydride from glycine. The method utilizes the additive of the present invention during the ring condensation reaction, resulting in a higher yield and higher purity of glycine anhydride in a shorter reaction time compared to conventional methods. The entire reaction process has the advantages of simple operation, low wastewater production, and solvent recyclability.

[0048] The above embodiments are merely preferred technical solutions of the present invention and should not be construed as limiting the present invention. The embodiments and features in the embodiments of this application may be arbitrarily combined with each other unless they conflict. The scope of protection of the present invention shall be the technical solutions described in the claims, including equivalent replacements of the technical features in the technical solutions described in the claims. Equivalent replacements and improvements within this scope are also within the scope of protection of the present invention.

Claims

1. A method for synthesizing glycine anhydride from glycine, characterized in that: The following steps are involved: Glycine is stirred in a solvent, a phosphorus-containing additive is added, and after the reaction is completed, a large amount of solid is precipitated by cooling, filtering, washing, and drying to obtain glycine anhydride. The solvent is selected from any one or two or more of ethylene glycol, glycerol, and 1,3-propylene glycol, and the additive is selected from any one of phosphoric acid and phosphorus pentoxide, and the molar equivalent of the additive is 2-3 times that of glycine. The mass concentration of glycine in the solvent ranges from 1 to 8 M, the reaction time is 2 hours, and the reaction temperature is 80-100°C.

2. The method for synthesizing glycine anhydride from glycine according to claim 1, wherein The temperature range of cooling precipitation is -10-10 ℃, and the cooling time is 4-12 h.

3. The method for synthesizing glycine anhydride from glycine according to claim 1, wherein The filter cake obtained by filtration is washed with any one solvent selected from petroleum ether, methanol, ethanol, ethyl acetate and cold water.

4. The method for synthesizing glycine anhydride from glycine according to claim 1, wherein The filtrate obtained by filtration is dried over anhydrous sodium sulfate, calcium chloride, silica gel and montmorillonite, and then the filtrate is recovered and reused.

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