Process for synthesizing enamine from 2-methyl-4-amino-5-formylaminomethylpyrimidine mother liquor and application of enamine

Abstract

The invention provides a process for synthesizing enamine from 2-methyl-4-amino-5-formylaminomethylpyrimidine mother liquor and application of the process, and relates to the technical field of enamine condensation. Comprising the following steps: carrying out enamine condensation reaction on the 2-methyl-4-amino-5-formylaminomethylpyrimidine mother liquor and alpha-sodium formyl-beta-formylaminopropionitrile under an acidic condition, so as to obtain enamine; the 2-methyl-4-amino-5-formylaminomethylpyrimidine mother liquor is a mother liquor obtained by a reaction of alpha-(o-chloroaniline)-based methine-beta-formylaminopropionitrile and an acetamidine solution. The method solves the technical problems that in the prior art, the energy consumption for recovering o-chloroaniline from the 2-methyl-4-amino-5-formylaminomethylpyrimidine mother liquor is large, the recovery is not thorough, and enamine contained in the mother liquor cannot be recycled, and achieves the purposes of reducing the recovery energy consumption, thoroughly recovering o-chloroaniline, improving the recovery efficiency and the like. The enamine contained in the mother liquor is subjected to resource utilization; and the product yield is improved.

Description

Technical Field

[0001] The invention relates to the technical field of enamine condensation, in particular to a process for synthesizing enamine from 2-methyl-4-amino-5-formylaminomethylpyrimidine mother liquor and application thereof. Background Art

[0002] In the cyclization reaction, α-(o-chloroaniline)-methyl-β-formylaminopropionitrile, referred to as enamine, obtained from the upstream enamine condensation process reacts with acetamidine solution to generate 2-methyl-4-amino-5-formylaminomethylpyrimidine and by-product o-chloroaniline mother liquor. The main problems are as follows: the by-product o-chloroaniline mother liquor is distilled by steam heating kettle distillation to recover o-chloroaniline, and the recovered o-chloroaniline is used in the upstream enamine condensation process, and the remaining kettle residue is treated as a high-boiling treatment, which not only uses a large amount of steam and has a high recovery cost, but also has a recovery rate of less than 90% of the obtained o-chloroaniline; at the same time, according to detection, the mother liquor still contains 5%-6% of unreacted enamine, which cannot be recycled because it is treated as a high-boiling treatment after the mother liquor distillation is completed.

[0003] In view of this, the present invention is proposed. Summary of the invention

[0004] One of the purposes of the present invention is to provide a process for synthesizing enamine from 2-methyl-4-amino-5-formylaminomethylpyrimidine mother liquor, which can solve the technical problems of high energy consumption and incomplete recovery of o-chloroaniline from 2-methyl-4-amino-5-formylaminomethylpyrimidine mother liquor, and failure to recycle enamine contained in the mother liquor.

[0005] The second object of the present invention is to provide an application of a process for synthesizing enamines from a 2-methyl-4-amino-5-formylaminomethylpyrimidine mother liquor, which is beneficial to reducing recovery energy consumption, completely recovering o-chloroaniline, and resourcefully utilizing the enamines contained in the mother liquor, thereby improving product yield.

[0006] In order to achieve the above-mentioned purpose of the present invention, the following technical solutions are particularly adopted:

[0007] In a first aspect, a process for synthesizing enamine from a 2-methyl-4-amino-5-formylaminomethylpyrimidine mother liquor comprises the following steps:

[0008] Carrying out an enamine condensation reaction of 2-methyl-4-amino-5-formylaminomethylpyrimidine mother liquor and α-sodium formyl-β-formylaminopropionitrile under acidic conditions to obtain the enamine;

[0009] The 2-methyl-4-amino-5-formylaminomethylpyrimidine mother liquor is the mother liquor obtained by the reaction of α-(o-chloroaniline)methyl-β-formylaminopropionitrile and acetamidine solution.

[0010] Furthermore, the mass proportion of o-chloroaniline in the 2-methyl-4-amino-5-formylaminomethylpyrimidine mother liquor is greater than 50%.

[0011] Furthermore, the mass proportion of enamine in the 2-methyl-4-amino-5-formylaminomethylpyrimidine mother liquor is 5%-6%.

[0012] Furthermore, the acid used in the acidic condition includes hydrochloric acid.

[0013] Furthermore, the process comprises the following steps:

[0014] First, the mother liquor of 2-methyl-4-amino-5-formylaminomethylpyrimidine and part of hydrochloric acid are mixed, and then α-sodium formyl-β-formylaminopropionitrile is added and mixed, and the remaining hydrochloric acid is added and mixed, and then the mixture is kept warm for enamine condensation reaction to obtain the enamine.

[0015] Furthermore, the temperature of the enamine condensation reaction is 20°C-40°C.

[0016] Furthermore, the temperature of the enamine condensation reaction is 20°C-30°C.

[0017] Furthermore, the temperature of the enamine condensation reaction is 20°C-25°C.

[0018] Furthermore, the enamine condensation reaction time is at least 10 hours.

[0019] In a second aspect, a process as described in any one of the above items is used for recovering 2-methyl-4-amino-5-formylaminomethylpyrimidine mother liquor.

[0020] Compared with the prior art, the present invention has at least the following beneficial effects:

[0021] The process for synthesizing enamines from a 2-methyl-4-amino-5-formylaminomethylpyrimidine mother liquor provided by the present invention is compared with an existing recovery method in which a 2-methyl-4-amino-5-formylaminomethylpyrimidine mother liquor (containing by-product o-chloroaniline) is subjected to steam heating to recover o-chloroaniline and then the o-chloroaniline is applied to an upstream enamine condensation process. The process directly applies the 2-methyl-4-amino-5-formylaminomethylpyrimidine mother liquor to an upstream enamine condensation process, which can not only significantly reduce the energy consumption of recovering o-chloroaniline, but also solve the problem of incomplete recovery of o-chloroaniline, and also can make resource utilization of unreacted enamines in the mother liquor, thereby improving the product yield of the enamine condensation.

[0022] The application of the process for synthesizing enamine from 2-methyl-4-amino-5-formylaminomethylpyrimidine mother liquor provided by the present invention is beneficial to reducing recovery energy consumption, completely recovering o-chloroaniline, and resourcefully utilizing the enamine contained in the mother liquor, which is beneficial to improving the product yield. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] In order to more clearly illustrate the specific implementation methods of the present invention or the technical solutions in the prior art, the drawings required for use in the specific implementation methods or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are some implementation methods of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0024] Figure 1 A schematic diagram of an enamine condensation reaction provided in one embodiment of the present invention;

[0025] Figure 2 A schematic diagram of a cyclization reaction provided in one embodiment of the present invention;

[0026] Figure 3 A process flow chart for synthesizing enamine from 2-methyl-4-amino-5-formylaminomethylpyrimidine mother liquor is provided in one embodiment of the present invention. DETAILED DESCRIPTION

[0027] The technical solution of the present invention will be clearly and completely described below in conjunction with the embodiments. Obviously, the described embodiments are part of the embodiments of the present invention, rather than all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0028] In the cyclization reaction, α-(o-chloroaniline)-methyl-β-formylaminopropionitrile, referred to as enamine, obtained from the upstream enamine condensation step reacts with acetamidine solution to produce 2-methyl-4-amino-5-formylaminomethylpyrimidine (referred to as formylpyrimidine) and by-product o-chloroaniline, see Figure 1 and Figure 2 In the mother liquor recovery process, there are technical problems such as large energy consumption for recovery of o-chloroaniline, incomplete recovery, and failure to recycle the enamine contained in the mother liquor. In order to solve the above problems, the technical solution of the present invention is proposed.

[0029] According to a first aspect of the present invention, there is provided a process for synthesizing enamine from a 2-methyl-4-amino-5-formylaminomethylpyrimidine mother liquor, comprising the following steps:

[0030] The mother liquor of 2-methyl-4-amino-5-formylaminomethylpyrimidine is subjected to an enamine condensation reaction with α-sodium formyl-β-formylaminopropionitrile under acidic conditions to obtain an enamine;

[0031] The 2-methyl-4-amino-5-formylaminomethylpyrimidine mother liquor is a mother liquor obtained by reacting α-(o-chloroaniline)methyl-β-formylaminopropionitrile with acetamidine solution.

[0032] The process for synthesizing enamines from a 2-methyl-4-amino-5-formylaminomethylpyrimidine mother liquor provided by the present invention is compared with an existing recovery method in which a 2-methyl-4-amino-5-formylaminomethylpyrimidine mother liquor (containing by-product o-chloroaniline) is subjected to steam heating to recover o-chloroaniline and then the o-chloroaniline is applied to an upstream enamine condensation process. The process directly applies the 2-methyl-4-amino-5-formylaminomethylpyrimidine mother liquor to an upstream enamine condensation process, which can not only significantly reduce the energy consumption of recovering o-chloroaniline, but also solve the problem of incomplete recovery of o-chloroaniline, and also can make resource utilization of unreacted enamines in the mother liquor, thereby improving the product yield of the enamine condensation.

[0033] In the present invention, the mass proportion of o-chloroaniline in the mother liquor of 2-methyl-4-amino-5-formylaminomethylpyrimidine can be more than 50%, for example, it can be 52%, 54%, 56%, 58%, 60%, 65%, 70%, 75%, 80%, but not limited to this; the mass proportion of enamine in the mother liquor of 2-methyl-4-amino-5-formylaminomethylpyrimidine can be 5%-6%, for example, it can be 5%, 5.1%, 5.2%, 5.3%, 5.4%, 5.5%, 5.6%, 5.7%, 5.8%, 5.9%, 6%, but not limited to this.

[0034] In a preferred embodiment, the acid used in the acidic condition includes but is not limited to hydrochloric acid, which is more conducive to ensuring the smooth progress of the enamine condensation reaction and improving the effect of the enamine condensation reaction.

[0035] In a preferred embodiment, the process for synthesizing enamine from 2-methyl-4-amino-5-formylaminomethylpyrimidine mother liquor of the present invention comprises the following steps:

[0036] First, the mother liquor of 2-methyl-4-amino-5-formylaminomethylpyrimidine and part of hydrochloric acid are mixed, and then α-sodium formyl-β-formylaminopropionitrile is added and mixed, and the remaining hydrochloric acid is added and mixed, and then the mixture is kept warm for enamine condensation reaction to obtain enamine.

[0037] A typical process for synthesizing enamine from 2-methyl-4-amino-5-formylaminomethylpyrimidine mother liquor, see Figure 3 , comprising the following steps:

[0038] First, add 130g of 2-methyl-4-amino-5-formylaminomethylpyrimidine mother liquor (the mass proportion of o-chloroaniline in the mother liquor is 55.4%, and the mass proportion of enamine is 5.4%) into the reaction equipment, then add 68g of 25% hydrochloric acid for mixing, control the temperature at 20°C-40°C, add 100g of α-sodium formyl-β-formylaminopropionitrile, i.e. sodium formyl (content 83%), and dropwise add 35g of 25% hydrochloric acid, after the addition is completed, keep warm for 10h to carry out enamine condensation reaction, filter and dry after the reaction is completed to obtain the enamine product;

[0039] It should be noted that enamine refers to α-(o-chloroaniline)methyl-β-formylaminopropionitrile;

[0040] Meanwhile, the 2-methyl-4-amino-5-formylaminomethylpyrimidine mother liquor refers to the mother liquor obtained by the reaction of α-(o-chloroaniline)-methyl-β-formylaminopropionitrile and acetamidine solution, which contains by-product o-chloroaniline and unreacted enamine.

[0041] In a preferred embodiment, the temperature of the enamine condensation reaction can be 20°C-30°C, and typical but non-limiting temperatures are, for example, 20°C, 21°C, 22°C, 23°C, 24°C, 25°C, 26°C, 27°C, 28°C, 29°C, and 30°C, and can be further preferably 20°C-25°C, which is more conducive to further improving the product yield of the enamine.

[0042] In a preferred embodiment, the enamine condensation reaction time is at least 10 hours, which is more conducive to ensuring the full progress of the enamine condensation reaction and further conducive to further improving the product yield of the enamine.

[0043] According to a second aspect of the present invention, there is provided an application of any of the above-mentioned processes in the recovery of 2-methyl-4-amino-5-formylaminomethylpyrimidine mother liquor.

[0044] The application of the process for synthesizing enamine from 2-methyl-4-amino-5-formylaminomethylpyrimidine mother liquor provided by the present invention is beneficial to reducing recovery energy consumption, completely recovering o-chloroaniline, and resourcefully utilizing the enamine contained in the mother liquor, which is beneficial to improving the product yield.

[0045] The present invention is further described below by way of examples. Unless otherwise specified, the materials in the examples are prepared according to existing methods or directly purchased from the market.

[0046] Example 1

[0047] A process for synthesizing enamine from 2-methyl-4-amino-5-formylaminomethylpyrimidine mother liquor, the process parameters and yield are shown in Table 1, comprising the following steps:

[0048] First, add 130g of 2-methyl-4-amino-5-formylaminomethylpyrimidine mother liquor (the mass proportion of o-chloroaniline in the mother liquor is 55.4%, and the mass proportion of enamine is 5.4%) to the reaction equipment, then add 68g of 25% hydrochloric acid for mixing, control the temperature at 35°C-40°C, add 100g of α-sodium formyl-β-formylaminopropionitrile (referred to as sodium formyl, content 83%), and dropwise add 35g of 25% hydrochloric acid, after the addition is completed, keep the temperature for reaction for 10h, filter and dry after the reaction is completed, and obtain 121g of enamine product, the enamine content is detected to be 93.1%, and the enamine condensation yield is 85.3%;

[0049] It should be noted that enamine refers to α-(o-chloroaniline)methyl-β-formylaminopropionitrile;

[0050] Meanwhile, the 2-methyl-4-amino-5-formylaminomethylpyrimidine mother liquor refers to the mother liquor obtained by the reaction of α-(o-chloroaniline)-methyl-β-formylaminopropionitrile and acetamidine solution, which contains by-product o-chloroaniline and unreacted enamine.

[0051] Example 2

[0052] A process for synthesizing enamine from 2-methyl-4-amino-5-formylaminomethylpyrimidine mother liquor, the process parameters and yield are shown in Table 1, comprising the following steps:

[0053] First, add 130g of 2-methyl-4-amino-5-formylaminomethylpyrimidine mother liquor (the mass proportion of o-chloroaniline in the mother liquor is 55.4%, and the mass proportion of enamine is 5.4%) to the reaction equipment, then add 68g of 25% hydrochloric acid for mixing, control the temperature at 30°C-35°C, add 100g of α-sodium formyl-β-formylaminopropionitrile (referred to as sodium formyl, content 83%), and dropwise add 35g of 25% hydrochloric acid, after the addition is completed, keep the temperature for reaction for 10h, filter and dry after the reaction is completed, and obtain 123g of enamine product, the enamine content is detected to be 93.3%, and the enamine condensation yield is 86.9%;

[0054] It should be noted that enamine refers to α-(o-chloroaniline)methyl-β-formylaminopropionitrile;

[0055] Meanwhile, the 2-methyl-4-amino-5-formylaminomethylpyrimidine mother liquor refers to the mother liquor obtained by the reaction of α-(o-chloroaniline)-methyl-β-formylaminopropionitrile and acetamidine solution, which contains by-product o-chloroaniline and unreacted enamine.

[0056] Example 3

[0057] A process for synthesizing enamine from 2-methyl-4-amino-5-formylaminomethylpyrimidine mother liquor, the process parameters and yield are shown in Table 1, comprising the following steps:

[0058] First, add 130g of 2-methyl-4-amino-5-formylaminomethylpyrimidine mother liquor (the mass proportion of o-chloroaniline in the mother liquor is 55.4%, and the mass proportion of enamine is 5.4%) to the reaction equipment, then add 68g of 25% hydrochloric acid for mixing, control the temperature at 25°C-30°C, add 100g of α-sodium formyl-β-formylaminopropionitrile (referred to as sodium formyl, content 83%), and dropwise add 35g of 25% hydrochloric acid, after the addition is completed, keep the temperature for reaction for 10h, filter and dry after the reaction is completed, and obtain 125.8g of enamine product, the enamine content is detected to be 94.3%, and the enamine condensation yield is 89.9%;

[0059] It should be noted that enamine refers to α-(o-chloroaniline)methyl-β-formylaminopropionitrile;

[0060] Meanwhile, the 2-methyl-4-amino-5-formylaminomethylpyrimidine mother liquor refers to the mother liquor obtained by the reaction of α-(o-chloroaniline)-methyl-β-formylaminopropionitrile and acetamidine solution, which contains by-product o-chloroaniline and unreacted enamine.

[0061] Example 4

[0062] A process for synthesizing enamine from 2-methyl-4-amino-5-formylaminomethylpyrimidine mother liquor, the process parameters and yield are shown in Table 1, comprising the following steps:

[0063] First, add 130g of 2-methyl-4-amino-5-formylaminomethylpyrimidine mother liquor (the mass proportion of o-chloroaniline in the mother liquor is 55.4%, and the mass proportion of enamine is 5.4%) to the reaction equipment, then add 68g of 25% hydrochloric acid for mixing, control the temperature at 20°C-25°C, add 100g of α-sodium formyl-β-formylaminopropionitrile (referred to as sodium formyl, content 83%), and dropwise add 35g of 25% hydrochloric acid, after the addition is completed, keep warm and react for 10h, filter and dry after the reaction is completed, and obtain 131g of enamine product, the enamine content is detected to be 94.8%, and the enamine condensation yield is 94%;

[0064] It should be noted that enamine refers to α-(o-chloroaniline)methyl-β-formylaminopropionitrile;

[0065] Meanwhile, the 2-methyl-4-amino-5-formylaminomethylpyrimidine mother liquor refers to the mother liquor obtained by the reaction of α-(o-chloroaniline)-methyl-β-formylaminopropionitrile and acetamidine solution, which contains by-product o-chloroaniline and unreacted enamine.

[0066] Comparative Example 1

[0067] A process for synthesizing enamines, the process parameters and yields are shown in Table 1, comprising the following steps:

[0068] First, add 72g of o-chloroaniline to the reaction equipment, and then add 68g of 25% hydrochloric acid to mix, control the temperature at 35°C-40°C, add 100g of α-sodium formyl-β-formylaminopropionitrile (abbreviated as sodium formyl, content 83%), and drop 35g of 25% hydrochloric acid. After the addition is completed, keep the temperature for reaction for 10h. After the reaction is completed, filter and dry to obtain 126g of enamine product, the enamine content is 94.2%, and the enamine condensation yield is 89.9%.

[0069] Table 1

[0070]

[0071] From the results in Table 1, it can be seen that the use of 2-methyl-4-amino-5-formylaminomethylpyrimidine mother liquor instead of o-chloroaniline directly in the enamine synthesis process can not only reduce the recovery energy consumption of o-chloroaniline and solve the problem of incomplete recovery of o-chloroaniline, but also realize the resource utilization of unreacted enamine in the 2-methyl-4-amino-5-formylaminomethylpyrimidine mother liquor, which is beneficial to improve the yield of enamine products.

[0072] 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 it. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or replace some or all of the technical features therein with equivalents. However, these modifications or replacements do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. A process for synthesizing enamine from 2-methyl-4-amino-5-formylaminomethylpyrimidine mother liquor, characterized in that: The following steps are involved: Carrying out an enamine condensation reaction of 2-methyl-4-amino-5-formylaminomethylpyrimidine mother liquor and α-sodium formyl-β-formylaminopropionitrile under acidic conditions to obtain the enamine; The 2-methyl-4-amino-5-formylaminomethylpyrimidine mother liquor is the mother liquor obtained by the reaction of α-(o-chloroaniline)methyl-β-formylaminopropionitrile and acetamidine solution.

2. The process according to claim 1, characterized in that The mass proportion of o-chloroaniline in the 2-methyl-4-amino-5-formylaminomethylpyrimidine mother liquor is more than 50%.

3. The process according to claim 2, characterized in that The mass proportion of enamine in the 2-methyl-4-amino-5-formylaminomethylpyrimidine mother liquor is 5%-6%.

4. The process according to any one of claims 1 to 3, characterized in that The acid used in the acidic condition includes hydrochloric acid.

5. The process according to claim 4, characterized in that The process comprises the following steps: First, the mother liquor of 2-methyl-4-amino-5-formylaminomethylpyrimidine and part of hydrochloric acid are mixed, and then α-sodium formyl-β-formylaminopropionitrile is added and mixed, and the remaining hydrochloric acid is added and mixed, and then the mixture is kept warm for enamine condensation reaction to obtain the enamine.

6. The process according to claim 5, characterized in that The temperature of the enamine condensation reaction is 20°C-40°C.

7. The process according to claim 6, characterized in that The temperature of the enamine condensation reaction is 20°C-30°C.

8. The process according to claim 7, characterized in that The temperature of the enamine condensation reaction is 20°C-25°C.

9. The process according to claim 8, characterized in that The enamine condensation reaction time is at least 10 hours.

10. Use of the process according to any one of claims 1 to 9 in the recovery of 2-methyl-4-amino-5-formylaminomethylpyrimidine mother liquor.

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