N-vinyl benzyl carbamate and preparation method thereof
By reacting benzyl carbamate with acetaldehyde or paracetaldehyde under alkaline conditions, and recrystallization with ethyl acetate and petroleum ether, the safety hazards and purification difficulties of the N-vinyl carbamate synthesis route are solved, and high purity and high yield preparation is achieved, which is suitable for industrial applications.
Patent Information
- Application Number
- CN202510431519.3
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-04-08
- Publication Date
- 2025-07-11
AI Technical Summary
The existing synthesis route of benzyl N-vinyl carbamate has problems such as high safety hazards, difficult raw materials to obtain and difficult purification, making it difficult to adapt to industrial production.
Benzyl carbamate, acetaldehyde or paracetaldehyde, acetic anhydride and alkaline substances were used to react at a specific temperature, and then the N-vinyl benzyl carbamate was prepared by recrystallization of ethyl acetate and petroleum ether.
It has achieved a low-cost and safe preparation process, with a product purity of up to 99.5%, and a yield of up to 78%, making it suitable for industrial production.
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Abstract
Description
Technical Field
[0001] The present invention relates to the technical field of the synthesis of pharmaceutical intermediates, and particularly relates to N-vinyl carbamic acid benzyl ester and a preparation method thereof. Background Art
[0002] The nitrogen atom of N-vinyl carbamic acid benzyl ester is connected with a vinyl group. As a monomer, it can homopolymerize or copolymerize with other unsaturated compounds to form high-polymer compounds. Such high-polymer compounds have special uses. For example, they can be made into emulsifiers to improve the photosensitivity of silver halide. Its homopolymer or copolymers with acrylonitrile, acrylic acid, acrylamide, etc. can be used as adhesives, molded bodies and surface coatings, and the product copolymerized with vinylamine can be used as a colorant for acid dyes, etc.
[0003] N-vinyl carbamic acid benzyl ester is also a very crucial pharmaceutical intermediate.
[0004] At present, there are literature reports on the synthesis route of this compound as follows:
[0005]
[0006] This route first uses acrylic acid as a raw material to react with sodium azide or other azide compounds to generate acryloyl azide, and then obtains vinyl isocyanate through high-temperature rearrangement, and then reacts with benzyl alcohol to obtain N-vinyl carbamic acid benzyl ester. However, this route requires the use of azide compounds and high-temperature rearrangement, which has relatively large potential safety hazards. At the same time, the residual benzyl alcohol makes the purification of the product difficult, which is not conducive to scale-up.
[0007] In addition, there are also literature reports on the synthesis route for preparing the above intermediate 2:
[0008]
[0009] This route uses ethylamine as a raw material, makes isocyanate through phosgene, then chlorinates with chlorine, eliminates hydrogen chloride to form a double bond to obtain intermediate 2, and then reacts with benzyl alcohol to obtain N-vinyl carbamic acid benzyl ester. However, this route requires the use of phosgene and chlorine, which is very unfriendly to the environment, and there are also relatively large potential safety hazards after scale-up, which is not conducive to scale-up. Summary of the Invention
[0010] Based on the problems of harsh reaction conditions and relatively high potential safety hazards in the current synthesis route of N-vinyl carbamic acid benzyl ester, the purpose of the present invention is to provide N-vinyl carbamic acid benzyl ester and a preparation method thereof. The synthesis route is simple, the raw materials are easy to obtain and the cost is relatively low, the reaction conditions are mild, the post-treatment is convenient, it can be well used for industrial production, and at the same time, the purity and yield of N-vinyl carbamic acid benzyl ester produced by this preparation method are both very high.
[0011] The present invention is achieved through the following technical solutions:
[0012] In a first aspect, the present application provides a method for preparing N-vinyl carbamic acid benzyl ester, comprising the following steps:
[0013] Add benzyl carbamate, a reaction reagent, and a solvent into a reaction vessel, cool down, and then add a base. First, heat to 25°C to 30°C for reaction, and then heat to 55°C to 80°C for reaction;
[0014] After the benzyl carbamate is less than 1%, filter the system, concentrate the filtrate to obtain a crude product, and then recrystallize with ethyl acetate and petroleum ether to obtain the N-vinyl carbamic acid benzyl ester product.
[0015] In a specific embodiment, the reaction reagent used in the reaction includes any one of acetaldehyde, paraldehyde, and vinyl acetate, preferably acetaldehyde.
[0016] In a specific embodiment, the solvent used in the reaction includes acetic anhydride or acetic acid, preferably acetic anhydride.
[0017] In a specific embodiment, the base used in the reaction includes any one of potassium carbonate, sodium carbonate, potassium tert-butoxide, sodium tert-butoxide, and sodium acetate, preferably potassium carbonate.
[0018] In a specific embodiment, the molar ratio of the reaction reagent to the benzyl carbamate is (3 to 6):1, preferably 5:1.
[0019] In a specific embodiment, the molar ratio of the base to the benzyl carbamate is (0.1 to 0.5):1, preferably 0.2:1.
[0020] In a specific embodiment, after adding benzyl carbamate, a reaction reagent, and a solvent into the reaction vessel, cool down to 10°C to 15°C. Among them, the cooling method can use ice-water cooling.
[0021] In a specific embodiment, the reaction time after heating to 25°C to 30°C is 0.5 h to 4 h, and the reaction time after heating to 55°C to 80°C is 6 h to 14 h.
[0022] In a specific embodiment, the volume ratio of ethyl acetate to petroleum ether used is (1 to 5):10, preferably 1:3.
[0023] In a second aspect, the present application provides an N-vinyl carbamic acid benzyl ester, which is prepared by the above preparation method.
[0024] Compared with the prior art, the present invention has the following advantages and beneficial effects:
[0025] In the preparation method of N-vinyl carbamic acid benzyl ester in the present invention, the raw materials used are simple and easy to obtain, the reaction conditions are mild, the use of highly dangerous raw materials such as flammable and explosive substances is avoided, which is more conducive to the scale-up of production and industrial production. At the same time, the purity of N-vinyl carbamic acid benzyl ester prepared by the preparation method of the present invention is as high as 99.5%, and the yield is as high as 78%. Specific Embodiments
[0026] In order to make the objectives, technical solutions and advantages of the present invention clearer and more understandable, the present invention will be further described in detail below with reference to the embodiments. The illustrative embodiments and descriptions of the present invention are only used to explain the present invention and are not intended to limit the present invention.
[0027] In the following description, numerous specific details are set forth in order to provide a thorough understanding of the present invention. However, it is obvious to those of ordinary skill in the art that the present invention does not have to employ these specific details. In other embodiments, well-known materials or methods have not been described in detail in order to avoid obscuring the present invention.
[0028] Throughout the specification, the reference to "one embodiment", "embodiment", "one example" or "example" means that the specific features, structures or characteristics described in connection with the embodiment or example are included in at least one embodiment of the present invention. Thus, the phrases "one embodiment", "embodiment", "one example" or "example" appearing throughout the specification do not necessarily all refer to the same embodiment or example. In addition, the specific features, structures or characteristics can be combined in any appropriate combination and / or sub-combination in one or more embodiments or examples. The term "and / or" used herein includes any and all combinations of one or more of the related listed items. In addition, without contradiction, those skilled in the art can combine and combine the different embodiments or examples described in this specification and the features of different embodiments or examples.
[0029] The "range" disclosed in this application is defined in the form of a lower limit and an upper limit. A given range is defined by selecting a lower limit and an upper limit, and the selected lower limit and upper limit define the boundaries of a particular range. The ranges defined in this way can include or exclude the end values, and can be combined arbitrarily, that is, any lower limit can be combined with any upper limit to form a range. For example, if ranges of 60 - 120 and 80 - 110 are listed for a specific parameter, ranges of 60 - 110 and 80 - 120 are also contemplated. In addition, if the minimum range values 1 and 2 are listed, and if the maximum range values 3, 4, and 5 are listed, then the following ranges are all contemplated: 1 - 3, 1 - 4, 1 - 5, 2 - 3, 2 - 4, and 2 - 5. In this application, unless otherwise specified, the numerical range "a - b" represents an abbreviated representation of any real number combination between a and b, where a and b are both real numbers. For example, the numerical range "0 - 5" means that all real numbers between "0 - 5" are fully listed herein, and "0 - 5" is only an abbreviated representation of these numerical combinations. Additionally, when stating that a certain parameter is an integer ≥2, it is equivalent to disclosing that the parameter is, for example, the integers 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, etc.
[0030] If there is no special instruction, all steps of this application can be carried out sequentially or randomly, and preferably sequentially. For example, the method includes steps (a) and (b), which means that the method can include steps (a) and (b) carried out sequentially, or can also include steps (b) and (a) carried out sequentially. For example, when it is mentioned that the method may further include step (c), it means that step (c) can be added to the method in any order. For example, the method can include steps (a), (b), and (c), or can also include steps (a), (c), and (b), or can also include steps (c), (a), and (b), etc.
[0031] Example 1
[0032] This example provides a method for preparing N - vinyl carbamate benzyl ester, which adopts the following steps:
[0033] S1. Add 7.56 g of benzyl carbamate, 11 g of acetaldehyde, and 37.8 ml of acetic anhydride into a reaction vessel, and cool it to 12 °C using ice water;
[0034] S2. Add 1.38 g of potassium carbonate into the reaction vessel, first heat it to 27 °C and react for 2 hours, and then continue to heat it to 77 °C and react for 10 hours;
[0035] S3. After detecting that benzyl carbamate is less than 1% by high-performance liquid chromatography, filter the system, concentrate the filtrate to obtain the crude product, and then crystallize it with ethyl acetate and petroleum ether in a ratio of 1:3 to obtain 6.65 g of a white product with a yield of 75.0% and a purity of 99.1%.
[0036] The synthetic route of benzyl N-vinylcarbamate in this example is as follows:
[0037]
[0038] Example 2
[0039] This example provides a method for preparing benzyl N-vinylcarbamate. Different from Example 1, paraldehyde is used to replace acetaldehyde in this example, and other process conditions are the same as those in Example 1. The preparation is specifically carried out by the following steps:
[0040] S1. Add 7.56 g of benzyl carbamate, 11 g of paraldehyde, and 37.8 ml of acetic anhydride to the reaction vessel, and cool it to 12 °C using ice water.
[0041] S2. Add 1.38 g of potassium carbonate to the reaction vessel, first heat it to 27 °C and react for 2 hours, and then continue to heat it to 77 °C and react for 10 hours.
[0042] S3. After detecting that benzyl carbamate is less than 1% by high-performance liquid chromatography, filter the system, concentrate the filtrate to obtain the crude product, and then crystallize it with ethyl acetate and petroleum ether in a ratio of 1:3 to obtain 6.87 g of a white product with a yield of 77.5% and a purity of 99.5%.
[0043] The synthetic route of benzyl N-vinylcarbamate in this example is as follows:
[0044]
[0045] Example 3
[0046] This example provides a method for preparing benzyl N-vinylcarbamate. Different from Example 1, vinyl acetate is used to replace acetaldehyde in this example, and other process conditions are the same as those in Example 1. The preparation is specifically carried out by the following steps:
[0047] S1. Add 7.56 g of benzyl carbamate, 11 g of vinyl acetate, and 37.8 ml of acetic anhydride to the reaction vessel, and cool it to 12 °C using ice water.
[0048] S2. Add 1.38 g of potassium carbonate to the reaction vessel, first heat it to 27 °C and react for 2 hours, and then continue to heat it to 77 °C and react for 10 hours.
[0049] S3. After detecting that the benzyl carbamate is less than 1% by high performance liquid chromatography, filter the system, concentrate the filtrate to obtain the crude product, and then crystallize it with ethyl acetate and petroleum ether in a ratio of 1:3 to obtain 6.48 g of a white product with a yield of 73.0% and a purity of 99.2%.
[0050] The synthetic route of benzyl N-vinylcarbamate in this example is as follows:
[0051]
[0052] Example 4
[0053] This example provides a method for preparing benzyl N-vinylcarbamate. Different from Example 1, the amount of raw materials used in this example was increased by 10 times, and other process conditions were the same as those in Example 1. The following steps were adopted:
[0054] S1. Add 75.6 g of benzyl carbamate, 110 g of acetaldehyde, and 378 ml of acetic anhydride to the reaction vessel, and cool it to 12 °C with ice water;
[0055] S2. Add 13.8 g of potassium carbonate to the reaction vessel, first heat it to 27 °C and react for 2 hours, and then continue to heat it to 77 °C and react for 10 hours;
[0056] S3. After detecting that the benzyl carbamate is less than 1% by high performance liquid chromatography, filter the system, concentrate the filtrate to obtain the crude product, and then crystallize it with ethyl acetate and petroleum ether in a ratio of 1:3 to obtain 69.1 g of a white product with a yield of 78.0% and a purity of 99.4%.
[0057] The synthetic route of benzyl N-vinylcarbamate in this example is as follows:
[0058]
[0059] Example 5
[0060] This example provides a method for preparing benzyl N-vinylcarbamate. Different from Example 1, acetic acid was used to replace acetic anhydride in this example, and other process conditions were the same as those in Example 1. The following steps were specifically adopted for preparation:
[0061] S1. Add 7.56 g of benzyl carbamate, 11 g of acetaldehyde, and 37.8 ml of acetic acid to the reaction vessel, and cool it to 12 °C with ice water;
[0062] S2. Add 1.38 g of potassium carbonate to the reaction vessel, first heat it to 27 °C and react for 2 hours, and then continue to heat it to 77 °C and react for 10 hours;
[0063] S3. After detecting that benzyl carbamate is less than 1% by high performance liquid chromatography, filter the system. Concentrate the filtrate to obtain the crude product, and then crystallize it with ethyl acetate and petroleum ether in a ratio of 1:3 to obtain 6.33 g of white product with a yield of 71.4% and a purity of 99.0%.
[0064] The synthetic route of benzyl N-vinylcarbamate in this example is as follows:
[0065]
[0066] Example 6
[0067] This example provides a preparation method of benzyl N-vinylcarbamate. Different from Example 1, sodium carbonate is used to replace potassium carbonate in this example, and other process conditions are the same as those in Example 1. The specific preparation steps are as follows:
[0068] S1. Add 7.56 g of benzyl carbamate, 11 g of acetaldehyde, and 37.8 ml of acetic anhydride into the reaction vessel, and cool it to 12 °C with ice water;
[0069] S2. Add 1.38 g of sodium carbonate into the reaction vessel, first heat it to 27 °C and react for 2 hours, and then continue to heat it to 77 °C and react for 10 hours;
[0070] S3. After detecting that benzyl carbamate is less than 1% by high performance liquid chromatography, filter the system. Concentrate the filtrate to obtain the crude product, and then crystallize it with ethyl acetate and petroleum ether in a ratio of 1:3 to obtain 6.39 g of white product with a yield of 72.1% and a purity of 99.2%.
[0071] The synthetic route of benzyl N-vinylcarbamate in this example is as follows:
[0072]
[0073] Example 7
[0074] This example provides a preparation method of benzyl N-vinylcarbamate. Different from Example 1, potassium tert-butoxide is used to replace potassium carbonate in this example, and other process conditions are the same as those in Example 1. The specific preparation steps are as follows:
[0075] S1. Add 7.56 g of benzyl carbamate, 11 g of acetaldehyde, and 37.8 ml of acetic anhydride into the reaction vessel, and cool it to 12 °C with ice water;
[0076] S2. Add 1.38 g of potassium tert-butoxide into the reaction vessel, first heat it to 27 °C and react for 2 hours, and then continue to heat it to 77 °C and react for 10 hours;
[0077] S3. After detecting that the benzyl carbamate is less than 1% by high performance liquid chromatography, filter the system, concentrate the filtrate to obtain the crude product, and then crystallize it with ethyl acetate and petroleum ether in a ratio of 1:3 to obtain 6.41 g of a white product with a yield of 72.4% and a purity of 99.1%.
[0078] The synthetic route of benzyl N-vinylcarbamate in this example is as follows:
[0079]
[0080] Example 8
[0081] This example provides a preparation method of benzyl N-vinylcarbamate. Different from Example 1, sodium tert-butoxide is used to replace potassium carbonate in this example, and other process conditions are the same as those in Example 1. The specific preparation steps are as follows:
[0082] S1. Add 7.56 g of benzyl carbamate, 11 g of acetaldehyde, and 37.8 ml of acetic anhydride to the reaction vessel, and cool it to 12 °C with ice water;
[0083] S2. Add 1.38 g of sodium tert-butoxide to the reaction vessel, first heat it to 27 °C and react for 2 hours, and then continue to heat it to 77 °C and react for 10 hours;
[0084] S3. After detecting that the benzyl carbamate is less than 1% by high performance liquid chromatography, filter the system, concentrate the filtrate to obtain the crude product, and then crystallize it with ethyl acetate and petroleum ether in a ratio of 1:3 to obtain 6.37 g of a white product with a yield of 71.9% and a purity of 98.7%.
[0085] The synthetic route of benzyl N-vinylcarbamate in this example is as follows:
[0086]
[0087] Example 9
[0088] This example provides a preparation method of benzyl N-vinylcarbamate. Different from Example 1, sodium acetate is used to replace potassium carbonate in this example, and other process conditions are the same as those in Example 1. The specific preparation steps are as follows:
[0089] S1. Add 7.56 g of benzyl carbamate, 11 g of acetaldehyde, and 37.8 ml of acetic anhydride to the reaction vessel, and cool it to 12 °C with ice water;
[0090] S2. Add 1.38 g of sodium acetate to the reaction vessel, first heat it to 27 °C and react for 2 hours, and then continue to heat it to 77 °C and react for 10 hours;
[0091] S3. After detecting that the benzyl carbamate is less than 1% by high-performance liquid chromatography, filter the system, concentrate the filtrate to obtain the crude product, and then crystallize it with ethyl acetate and petroleum ether in a ratio of 1:3 to obtain 6.3 g of a white product with a yield of 71.1% and a purity of 98.5%.
[0092] The synthesis route of benzyl N-vinylcarbamate in this example is as follows:
[0093]
[0094] Example 10
[0095] This example provides a method for preparing benzyl N-vinylcarbamate. Different from Example 1, in step S1 of this example, ice water is used to cool the temperature to 10 °C, and other process conditions are the same as those in Example 1. The preparation is specifically carried out by the following steps:
[0096] S1. Add 7.56 g of benzyl carbamate, 11 g of acetaldehyde, and 37.8 ml of acetic anhydride to the reaction vessel, and use ice water to cool the temperature to 10 °C;
[0097] S2. Add 1.38 g of potassium carbonate to the reaction vessel, first raise the temperature to 27 °C and react for 2 hours, and then continue to raise the temperature to 77 °C and react for 10 hours;
[0098] S3. After detecting that the benzyl carbamate is less than 1% by high-performance liquid chromatography, filter the system, concentrate the filtrate to obtain the crude product, and then crystallize it with ethyl acetate and petroleum ether in a ratio of 1:3 to obtain 6.55 g of a white product with a yield of 73.9% and a purity of 99.3%.
[0099] The synthesis route of benzyl N-vinylcarbamate in this example is as follows:
[0100]
[0101] Example 11
[0102] This example provides a method for preparing benzyl N-vinylcarbamate. Different from Example 1, in step S1 of this example, ice water is used to cool the temperature to 15 °C, and other process conditions are the same as those in Example 1. The preparation is specifically carried out by the following steps:
[0103] S1. Add 7.56 g of benzyl carbamate, 11 g of acetaldehyde, and 37.8 ml of acetic anhydride to the reaction vessel, and use ice water to cool the temperature to 15 °C;
[0104] S2. Add 1.38 g of potassium carbonate to the reaction vessel, first raise the temperature to 27 °C and react for 2 hours, and then continue to raise the temperature to 77 °C and react for 10 hours;
[0105] S3. After detecting that the benzyl carbamate is less than 1% by high performance liquid chromatography, filter the system, concentrate the filtrate to obtain the crude product, and then crystallize it with ethyl acetate and petroleum ether in a ratio of 1:3 to obtain 6.61 g of a white product with a yield of 74.6% and a purity of 99.2%.
[0106] The synthetic route of benzyl N-vinylcarbamate in this example is as follows:
[0107]
[0108] Example 12
[0109] This example provides a method for preparing benzyl N-vinylcarbamate. Different from Example 1, in step S2 of this example, the temperature is first raised to 25 °C, and other process conditions are the same as those in Example 1. The preparation is specifically carried out using the following steps:
[0110] S1. Add 7.56 g of benzyl carbamate, 11 g of acetaldehyde, and 37.8 ml of acetic anhydride to the reaction vessel, and cool it to 12 °C using ice water;
[0111] S2. Add 1.38 g of potassium carbonate to the reaction vessel, first raise the temperature to 25 °C and react for 2 hours, and then continue to raise the temperature to 77 °C and react for 10 hours;
[0112] S3. After detecting that the benzyl carbamate is less than 1% by high performance liquid chromatography, filter the system, concentrate the filtrate to obtain the crude product, and then crystallize it with ethyl acetate and petroleum ether in a ratio of 1:3 to obtain 6.56 g of a white product with a yield of 74.0% and a purity of 99.2%.
[0113] The synthetic route of benzyl N-vinylcarbamate in this example is as follows:
[0114]
[0115] Example 13
[0116] This example provides a method for preparing benzyl N-vinylcarbamate. Different from Example 1, in step S2 of this example, the temperature is first raised to 30 °C, and other process conditions are the same as those in Example 1. The preparation is specifically carried out using the following steps:
[0117] S1. Add 7.56 g of benzyl carbamate, 11 g of acetaldehyde, and 37.8 ml of acetic anhydride to the reaction vessel, and cool it to 12 °C using ice water;
[0118] S2. Add 1.38 g of potassium carbonate to the reaction vessel, first raise the temperature to 30 °C and react for 2 hours, and then continue to raise the temperature to 77 °C and react for 10 hours;
[0119] S3. After detecting that the benzyl carbamate is less than 1% by high performance liquid chromatography, filter the system, concentrate the filtrate to obtain the crude product, and then crystallize it with ethyl acetate and petroleum ether in a ratio of 1:3 to obtain 6.63 g of a white product with a yield of 74.8% and a purity of 99.3%.
[0120] The synthetic route of benzyl N-vinylcarbamate in this example is as follows:
[0121]
[0122] Example 14
[0123] This example provides a method for preparing benzyl N-vinylcarbamate. Different from Example 1, in step S2 of this example, the temperature is further raised to 75 °C, and other process conditions are the same as those in Example 1. The preparation is specifically carried out by the following steps:
[0124] S1. Add 7.56 g of benzyl carbamate, 11 g of acetaldehyde, and 37.8 ml of acetic anhydride to the reaction vessel, and cool it to 12 °C using ice water;
[0125] S2. Add 1.38 g of potassium carbonate to the reaction vessel, first raise the temperature to 27 °C and react for 2 hours, and then further raise the temperature to 75 °C and react for 10 hours;
[0126] S3. After detecting that the benzyl carbamate is less than 1% by high performance liquid chromatography, filter the system, concentrate the filtrate to obtain the crude product, and then crystallize it with ethyl acetate and petroleum ether in a ratio of 1:3 to obtain 6.59 g of a white product with a yield of 74.4% and a purity of 99.0%.
[0127] The synthetic route of benzyl N-vinylcarbamate in this example is as follows:
[0128]
[0129] Example 15
[0130] This example provides a method for preparing benzyl N-vinylcarbamate. Different from Example 1, in step S2 of this example, the temperature is further raised to 80 °C, and other process conditions are the same as those in Example 1. The preparation is specifically carried out by the following steps:
[0131] S1. Add 7.56 g of benzyl carbamate, 11 g of acetaldehyde, and 37.8 ml of acetic anhydride to the reaction vessel, and cool it to 12 °C using ice water;
[0132] S2. Add 1.38 g of potassium carbonate to the reaction vessel, first raise the temperature to 27 °C and react for 2 hours, and then further raise the temperature to 80 °C and react for 10 hours;
[0133] S3. After detecting that the benzyl carbamate is less than 1% by high-performance liquid chromatography, filter the system, concentrate the filtrate to obtain the crude product, and then crystallize it with ethyl acetate and petroleum ether in a ratio of 1:3 to obtain 6.67 g of a white product with a yield of 75.3% and a purity of 99.4%.
[0134] The synthetic route of benzyl N-vinylcarbamate in this example is as follows:
[0135]
[0136] Example 16
[0137] This example provides a method for preparing benzyl N-vinylcarbamate. Different from Example 1, 6.6 g of acetaldehyde is used in this example, and other process conditions are the same as those in Example 1. The preparation is specifically carried out by the following steps:
[0138] S1. Add 7.56 g of benzyl carbamate, 6.6 g of acetaldehyde, and 37.8 ml of acetic anhydride to the reaction vessel, and cool it to 12 °C with ice water;
[0139] S2. Add 1.38 g of potassium carbonate to the reaction vessel, first heat it to 27 °C and react for 2 hours, and then continue to heat it to 77 °C and react for 10 hours;
[0140] S3. After detecting that the benzyl carbamate is less than 1% by high-performance liquid chromatography, filter the system, concentrate the filtrate to obtain the crude product, and then crystallize it with ethyl acetate and petroleum ether in a ratio of 1:3 to obtain 6.31 g of a white product with a yield of 71.2% and a purity of 98.5%.
[0141] The synthetic route of benzyl N-vinylcarbamate in this example is as follows:
[0142]
[0143] Example 17
[0144] This example provides a method for preparing benzyl N-vinylcarbamate. Different from Example 1, 13.2 g of acetaldehyde is used in this example, and other process conditions are the same as those in Example 1. The preparation is specifically carried out by the following steps:
[0145] S1. Add 7.56 g of benzyl carbamate, 13.2 g of acetaldehyde, and 37.8 ml of acetic anhydride to the reaction vessel, and cool it to 12 °C with ice water;
[0146] S2. Add 1.38 g of potassium carbonate to the reaction vessel, first heat it to 27 °C and react for 2 hours, and then continue to heat it to 77 °C and react for 10 hours;
[0147] S3. After detecting that the benzyl carbamate is less than 1% by high performance liquid chromatography, filter the system, concentrate the filtrate to obtain the crude product, and then crystallize it with ethyl acetate and petroleum ether in a ratio of 1:3 to obtain 6.66 g of white product with a yield of 75.2% and a purity of 99.0%.
[0148] The synthetic route of benzyl N-vinylcarbamate in this example is as follows:
[0149]
[0150] Example 18
[0151] This example provides a preparation method of benzyl N-vinylcarbamate. Different from Example 1, 0.69 g of potassium carbonate is used in this example, and other process conditions are the same as those in Example 1. The specific preparation steps are as follows:
[0152] S1. Add 7.56 g of benzyl carbamate, 11 g of acetaldehyde, and 37.8 ml of acetic anhydride into the reaction vessel, and cool it to 12 °C with ice water;
[0153] S2. Add 0.69 g of potassium carbonate into the reaction vessel, first heat it to 27 °C and react for 2 hours, and then continue to heat it to 77 °C and react for 10 hours;
[0154] S3. After detecting that the benzyl carbamate is less than 1% by high performance liquid chromatography, filter the system, concentrate the filtrate to obtain the crude product, and then crystallize it with ethyl acetate and petroleum ether in a ratio of 1:3 to obtain 6.28 g of white product with a yield of 70.9% and a purity of 98.6%.
[0155] The synthetic route of benzyl N-vinylcarbamate in this example is as follows:
[0156]
[0157] Example 19
[0158] This example provides a preparation method of benzyl N-vinylcarbamate. Different from Example 1, 3.45 g of potassium carbonate is used in this example, and other process conditions are the same as those in Example 1. The specific preparation steps are as follows:
[0159] S1. Add 7.56 g of benzyl carbamate, 11 g of acetaldehyde, and 37.8 ml of acetic anhydride into the reaction vessel, and cool it to 12 °C with ice water;
[0160] S2. Add 3.45 g of potassium carbonate into the reaction vessel, first heat it to 27 °C and react for 2 hours, and then continue to heat it to 77 °C and react for 10 hours;
[0161] S3. After detecting that the benzyl carbamate is less than 1% by high performance liquid chromatography, the system is filtered, and the filtrate is concentrated to obtain the crude product, which is then crystallized with ethyl acetate and petroleum ether at a ratio of 1:3 to obtain 6.56 g of a white product, with a yield of 74.0% and a purity of 99.2%.
[0162] The synthetic route of benzyl N-vinylcarbamate in this example is as follows:
[0163]
[0164] Comparative Example 1
[0165] This comparative example provides a method for preparing benzyl N-vinylcarbamate. Different from Example 1, in step S1 of this comparative example, the temperature is directly raised to 77 °C and the reaction is carried out for 12 hours, and the other process steps are the same as those in Example 1. The preparation is specifically carried out by the following steps:
[0166] S1. Add 7.56 g of benzyl carbamate, 11 g of acetaldehyde, and 37.8 ml of acetic anhydride to the reaction vessel, and cool down to 12 °C;
[0167] S2. Add 1.38 g of potassium carbonate to the reaction vessel, and directly raise the temperature to 77 °C and react for 12 hours;
[0168] S3. After detecting that the benzyl carbamate is less than 1% by high performance liquid chromatography, the system is filtered, and the filtrate is concentrated to obtain the crude product, which is then crystallized with ethyl acetate and petroleum ether at a ratio of 1:3 to obtain 5.74 g of a white product, with a yield of 64.8% and a purity of 96.7%.
[0169] The synthetic route of benzyl N-vinylcarbamate in this example is as follows:
[0170]
[0171] Comparative Example 2
[0172] This comparative example provides a synthetic method for benzyl N-vinylcarbamate. This synthetic method is a synthetic method in the prior art and is carried out by the following steps:
[0173] S1. At room temperature, add acrylic acid (71.94 g, 1.0 mol), triethylamine (110.79 g, 1.09 mo1), and toluene (720 ml) to the reaction flask, and dropwise add diphenylphosphoryl azide (274.81 g, 1.0 mo1). After the dropwise addition is completed, stir and react for 30 minutes. After the reaction is completed, add 10 ml of water for washing. After liquid separation, dry the organic layer with magnesium sulfate, and filter to obtain the acrylic acid azide toluene solution.
[0174] S2. Add benzyl alcohol (256 ml, 2.46 mol), hydroquinone (6.1 g, 0.055 mol), pyridine (6.0 ml, 0.074 mol), potassium carbonate (85.0 g, 0.62 mol) and toluene (250 ml) into the reaction flask, heat up to 100 °C, dropwise add the acrylic acid azide toluene solution obtained in step S1. After adding, stir the reaction until the reaction ends, cool down to room temperature, filter, concentrate the filtrate under reduced pressure to remove toluene and excess benzyl alcohol, rectify the residue to distill out the main product, and purify by column chromatography to obtain 150 g of the product, with a yield of 69% and a purity of 97.4%.
[0175] The synthetic route of benzyl N-vinylcarbamate in this example is as follows:
[0176]
[0177] This comparative example uses acrylic acid as the raw material, reacts with sodium azide or other azide compounds to generate acryloyl azide, then obtains vinyl isocyanate after high-temperature rearrangement, and then reacts with benzyl alcohol to obtain benzyl N-vinylcarbamate. This synthetic method requires the use of azide compounds and high-temperature rearrangement, which poses a relatively large safety hazard. At the same time, the residual benzyl alcohol makes the purification of the product more difficult and is not conducive to scale-up. While using the synthetic methods of Examples 1-19, the raw materials used are simple and easily available, the reaction conditions are mild, avoiding the use of highly flammable, explosive and other high-risk raw materials in the conventional methods, and are more conducive to the scale-up of production and industrial production.
[0178] Detect and calculate the yields and purities of the products in Examples 1-19 and Comparative Examples 1-2, and the results are shown in Table 1 below.
[0179] Table 1
[0180]
[0181]
[0182] It can be seen from the detection data in Table 1 that compared with the benzyl N-vinylcarbamate prepared by the method of the comparative example, the benzyl N-vinylcarbamate prepared by the preparation method of the present application not only has a higher purity, but also has a higher yield. At the same time, the raw materials used in the preparation method of the present application are simple and easily available, and the reaction conditions are also milder.
[0183] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those of ordinary skill in the art should understand that they can still modify the technical solutions described in the foregoing embodiments, or perform equivalent replacements on some or all of the technical features; and these modifications or replacements do not make the essence of the corresponding technical solutions deviate from the scope of the technical solutions of the embodiments of the present invention, and they should all be covered within the scope of the claims and the specification of the present invention.
Claims
1. A method for preparing N-vinyl carbamic acid benzyl ester, characterized in that, It includes the following steps: Add benzyl carbamate, reaction reagent, and solvent into a reaction vessel, cool down, and then add a base. First, heat up to 25°C - 30°C for reaction, and then heat up to 55°C - 80°C for reaction; After the benzyl carbamate is less than 1%, filter the system, concentrate the filtrate to obtain the crude product, and then recrystallize it with ethyl acetate and petroleum ether to obtain the N-vinyl benzyl carbamate product.
2. The preparation method of N-vinyl carbamic acid benzyl ester according to claim 1, characterized in that, The reaction reagent used in the reaction includes any one of acetaldehyde, paraldehyde, and vinyl acetate.
3. The preparation method of N-vinyl carbamic acid benzyl ester according to claim 1, characterized in that, The solvent used in the reaction includes acetic anhydride or acetic acid.
4. The preparation method of N-vinyl carbamic acid benzyl ester according to claim 1, characterized in that, The base used in the reaction includes any one of potassium carbonate, sodium carbonate, potassium tert-butoxide, sodium tert-butoxide, and sodium acetate.
5. The preparation method of N-vinyl carbamic acid benzyl ester according to claim 1, characterized in that, The molar ratio of the reaction reagent to the benzyl carbamate is (3 - 6):
1.
6. The preparation method of N-vinyl carbamic acid benzyl ester according to claim 1, wherein, The molar ratio of the base to the benzyl carbamate is (0.1 - 0.5):
1.
7. A method for preparing N-vinyl carbamic acid benzyl ester according to claim 1, characterized in that, After adding benzyl carbamate, reaction reagent, and solvent into the reaction vessel, cool down to 10°C - 15°C.
8. The preparation method of N-vinyl carbamic acid benzyl ester according to claim 1, characterized in that, The reaction time after heating up to 25°C - 30°C is 0.5 h - 4 h, and the reaction time after heating up to 55°C - 80°C is 6 h - 14 h.
9. The preparation method of N-vinyl carbamic acid benzyl ester according to claim 1, characterized in that, The volume ratio of the ethyl acetate to the petroleum ether is (1 - 5):
10.
10. A benzyl N-vinylcarbamate, characterized in that, It is prepared by using the preparation method described in any one of claims 1 - 9.