Central control detection method for preparing urotropine through formaldehyde condensation

Abstract

The invention is applicable to the field of experimental equipment, and provides a central control detection method for preparing urotropine by formaldehyde condensation, which comprises the following steps: preparing a to-be-detected test solution and a plurality of contrast solutions in which the concentrations of urotropine and ammonia water are in the same order of magnitude, and the formaldehyde content in the contrast solutions is known; and dropwise adding the silver nitrate standard solution into the control solution and the to-be-detected test solution until formed white precipitates disappear, standing, dropwise adding the silver nitrate solution prepared by ammonia, shaking while adding until the color and the silver mirror state do not change any more, and determining the residual content range of formaldehyde in the to-be-detected test solution according to the formaldehyde content in the control solution. Through limit colorimetry, detection personnel can clearly, rapidly and accurately judge the content range of formaldehyde in a reaction solution of urotropine, and the method has good specificity and sensitivity, can be effectively used for quality monitoring in the production reaction process of urotropine, ensures that paraformaldehyde remaining in a urotropine finished product is within the limit range, and has high detection accuracy. Therefore, the preparation efficiency, the preparation precision and the preparation quality of the urotropine are effectively improved.

Description

Technical Field

[0001] The present invention belongs to the technical field of chemical analysis, and particularly relates to a method for on-line monitoring and detection of the preparation of hexamethylenetetramine by the condensation of formaldehyde. Background Art

[0002] Hexamethylenetetramine, also known as methenamine, is a colorless, shiny crystal or white crystalline powder, and can be widely used in industries such as resins, plastics, rubbers, and pharmaceuticals.

[0003] In actual industrial production, hexamethylenetetramine is usually prepared by using formaldehyde and ammonia water as starting materials, and condensing them at 50-80 °C to obtain an aqueous solution containing hexamethylenetetramine, and then concentrating, crystallizing, centrifuging, and drying to obtain the finished product of hexamethylenetetramine. However, when hexamethylenetetramine is used as the raw material drug of a medicine, the requirement for the residual paraformaldehyde in hexamethylenetetramine is more stringent than that for chemical products. If the reaction process of the condensation of formaldehyde and ammonia to prepare hexamethylenetetramine is not monitored, it is easy to cause the detection result of paraformaldehyde in the finished product of hexamethylenetetramine to exceed the standard.

[0004] The European Pharmacopoeia 11.0 can detect the free formaldehyde (maximum 50 ppm) in the finished product of hexamethylenetetramine by using the silver mirror reaction. The method is as follows: Take 0.8 g of hexamethylenetetramine, dissolve it with ultrapure water and dilute it to 8 mL, add 2 mL of ammoniacal silver nitrate solution, shake well, and let it stand for 5 min. The color of the solution shall not be darker than that of the control solution (take 8 mL of freshly prepared 5 ppm formaldehyde standard solution, add 2 mL of ammoniacal silver nitrate solution, and mix well). However, there is residual ammonia water in the reaction solution of the condensation of formaldehyde and ammonia to prepare hexamethylenetetramine, and the ammonia water will interfere with the silver mirror reaction of the ammoniacal silver nitrate solution and the aldehyde group, which is not conducive to the analysis and monitoring of the formaldehyde content in the reaction solution. It is difficult to realize the on-line monitoring of the reaction of the condensation of formaldehyde and ammonia to prepare hexamethylenetetramine by this pharmacopoeia method. And, after searching domestic and foreign literatures, it is found that there is currently no effective method for monitoring the formaldehyde content in the reaction of the condensation of formaldehyde and ammonia to prepare hexamethylenetetramine.

[0005] Therefore, in order to ensure that the residual paraformaldehyde in the finished product of hexamethylenetetramine is within the limit range, it is particularly important to seek a method for on-line monitoring and detection of the condensation of formaldehyde and ammonia to prepare hexamethylenetetramine. Summary of the Invention

[0006] The present invention provides a method for on-line monitoring and detection of the preparation of hexamethylenetetramine by the condensation of formaldehyde, aiming to solve the problem of how to monitor the formaldehyde content in the reaction of the condensation of formaldehyde and ammonia to prepare hexamethylenetetramine, so as to ensure that the residual paraformaldehyde in the finished product of hexamethylenetetramine is within the limit range.

[0007] The present invention is implemented as follows. The present application provides a method for on-line detection in the preparation of hexamine by formaldehyde condensation, which is used to detect the residual formaldehyde content in the reaction solution for preparing hexamine by the condensation of formaldehyde and ammonia. The on-line detection method includes:

[0008] Step S1, preparing a test solution to be measured and multiple control solutions; wherein, the concentrations of hexamine and ammonia water in the control solutions are of the same order of magnitude as those in the test solution to be measured (for example, the concentrations of hexamine and ammonia water in the control solutions are the same as those in the test solution to be measured), and the formaldehyde content in the control solutions is known;

[0009] Step S2, respectively dropping the same amount of silver nitrate standard solution into each control solution and the test solution to be measured until the formed white precipitate disappears. After standing, then respectively drop the same amount of ammoniacal silver nitrate solution while shaking. After dropping until the color and silver mirror state in each control solution and the test solution to be measured no longer change, then appropriately drop an excessive amount of the same amount of ammoniacal silver nitrate solution;

[0010] Step S3, comparing the test solution to be measured with each control solution, and obtaining the range of the residual formaldehyde content in the test solution to be measured according to the comparison of the chromaticity of the test solution to be measured with that of each control solution, that is, the range of the residual formaldehyde content in the reaction solution.

[0011] Optionally, step S1 includes: sampling from the reaction solution for preparing hexamine by the condensation of formaldehyde and ammonia to obtain the test solution to be measured, wherein the concentration range of hexamine in the test solution to be measured is 10% - 30%, and the concentration range of ammonia water is 1% - 5%.

[0012] Optionally, step S1 further includes: simulating the composition of the reaction solution for preparing hexamine by the condensation of formaldehyde and ammonia, weighing a certain amount of hexamine, and adding ammonia water solution and formaldehyde solution to prepare multiple control solutions with different formaldehyde contents of 0.01% - 5%; wherein, the concentrations of hexamine and ammonia water in each control solution are of the same order of magnitude as those in the test solution to be measured.

[0013] Optionally, the standard for passing the on-line reaction in the on-line detection method is that the formaldehyde content in the reaction solution ≤ 0.05%.

[0014] Optionally, the formaldehyde content of the control solution in step S1 is 0.05% - 5%.

[0015] Optionally, the test solution to be measured is from the reaction solution in the synthesis process of preparing hexamine by the condensation of formaldehyde and ammonia, wherein the synthesis process of preparing hexamine by the condensation of formaldehyde and ammonia includes:

[0016] Add 1.0 eq of formaldehyde solution to the reaction kettle. After stirring, add 0.67 - 0.95 eq of ammonia water dropwise. After the addition of ammonia water is complete, heat up to 40 - 80 °C and react for 1 - 2 h. The relevant reaction formula is:

[0017]

[0018] Optionally, in step S2, the concentration of the silver nitrate standard solution is 0.1 mol / L and the volume is 1 - 5 mL.

[0019] Optionally, in step S2, the concentration of the silver ammonia nitrate solution is 0.1 mol / L and the volume is 50 - 500 μL.

[0020] Optionally, in step S2, the volumes of each control solution and the test sample solution to be measured are equal.

[0021] Optionally, there are at least four control solutions, and the formaldehyde contents of the four control solutions are 0.05%, 0.5%, 1%, and 5% respectively.

[0022] Optionally, the standing time in step S2 is 5 min.

[0023] The beneficial effects achieved by the present invention: A method for in - process control detection of preparing hexamine by formaldehyde condensation provided by the present invention includes: Step S1, prepare a test sample solution to be measured and multiple control solutions; wherein, the concentrations of hexamine and ammonia water in the control solution are of the same order of magnitude as those in the test sample solution to be measured, and the formaldehyde content in the control solution is known; Step S2, drop the same amount of silver nitrate standard solution into each control solution and the test sample solution to be measured until the formed white precipitate disappears. After standing, then drop the same amount of silver ammonia nitrate solution respectively, shake while adding, and continue to drop the silver ammonia nitrate solution in an appropriate excess amount after the color and silver mirror state in each control solution and the test sample solution to be measured no longer change; Step S3, compare the test sample solution to be measured with each control solution. The final color and the silver mirror produced in the test sample solution to be measured shall not be darker than those in the control solution. Based on the comparison of the chromaticity of the test sample solution to be measured with that of each control solution, obtain the residual content range of formaldehyde in the test sample solution to be measured, that is, the residual content of formaldehyde in the reaction solution. By setting control solutions with the same order of magnitude of hexamine and ammonia water concentrations as those in the test sample solution to be measured and with known formaldehyde contents in the control solutions, the silver nitrate standard solution can be dropped into the test sample solution to be measured and the control solutions to carry out the corresponding silver mirror reaction. After the reaction of the test sample solution to be measured and the control solutions is completed, compare the chromaticity of the test sample solution to be measured with that of each control solution. Since the formaldehyde content in the control solution is known, the formaldehyde content range of the test sample solution to be measured can be directly obtained, which is the residual content range of formaldehyde in the reaction solution for the condensation of formaldehyde and ammonia to prepare hexamine.

[0024] Through limit colorimetry, this application enables testers to clearly, quickly, and accurately determine the content range of formaldehyde in the reaction solution of hexamine, with good specificity and sensitivity. It can be effectively used for quality monitoring during the production reaction process of hexamine to ensure that the residual paraformaldehyde in the hexamine finished product is within the limit range, thereby effectively improving the preparation efficiency, preparation accuracy, and quality of hexamine. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] The accompanying drawings here are incorporated into the specification and form a part of this specification, showing embodiments consistent with the present invention and, together with the specification, used to explain the principles of the present invention.

[0026] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the following will briefly introduce the accompanying drawings required for use in the description of the embodiments or the prior art. Obviously, for those of ordinary skill in the art, without creative efforts, other drawings can also be obtained based on these drawings.

[0027] Figure 1 It is the test colorimetric diagram of the test solution to be measured and each control solution in Example 1;

[0028] Figure 2 It is the test colorimetric diagram of the test solution to be measured and each control solution in Example 2;

[0029] Figure 3 It is the test colorimetric diagram of the test solution to be measured and each control solution in Example 3;

[0030] Figure 4 It is the test colorimetric diagram of the test solution to be measured and each control solution in Example 4;

[0031] Figure 5 It is the test colorimetric diagram of the test solution 2 to be measured in Comparative Example 1. DETAILED DESCRIPTION OF THE EMBODIMENTS

[0032] In order to make the objectives, technical solutions, and advantages of the present invention clearer, the following further details the present invention in combination with the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not used to limit the present invention.

[0033] For effective illustration of the embodiments of the present invention, the following elaborates on the embodiments of this application with reference to the accompanying drawings.

[0034] The processes, conditions, reagents, experimental methods, etc. for implementing the present invention, except for the specifically mentioned content below, are all common knowledge and well-known common sense in the art, and the present invention has no particularly restricted content. And in the present invention, unless otherwise stated, the percentages are mass percentages.

[0035] In the embodiments of the present invention, the starting materials for the preparation of hexamine by the condensation of formaldehyde and ammonia, namely formaldehyde solution (mass fraction of 10%) and ammonia water (mass fraction of 36% - 38%), are common items in the market and will not be elaborated in detail here. The reaction formula involved in the preparation of hexamine by the condensation of formaldehyde and ammonia is as follows:

[0036]

[0037] Among them, the basic process flow in the synthesis of hexamine by the condensation of formaldehyde and ammonia is as follows: Add 1.0 eq of formaldehyde solution to the reaction kettle, stir and then dropwise add 0.67 - 0.95 eq of ammonia water solution. After the addition of ammonia water is completed, heat up to 40 - 80 °C and react for 1 - 2 h. The liquid during this reaction period is called the reaction solution. In the embodiments of the present invention, the hexamine test sample used to prepare the control solution is purchased from Sigma Company with a content of ≥99.5%. The following will be elaborated in detail according to the relevant content and will not be elaborated in detail here.

[0038] Example 1

[0039] The embodiments of the present invention provide a method for on - line detection in the preparation of hexamine by the condensation of formaldehyde. This on - line detection method is used to detect the residual content of formaldehyde in the reaction solution of the preparation of hexamine by the condensation of formaldehyde and ammonia, so as to ensure the quality of the hexamine production process. Specifically, this on - line detection method includes the following steps:

[0040] Step S1, prepare the test solution to be measured and the control solution;

[0041] Preparation of the test solution to be measured: Weigh 100.0 g of formaldehyde solution (1.23 mol, 1.0 eq) into a reaction flask, slowly dropwise add 67.1 g of ammonia water (0.99 mol, 0.8 eq). After the addition is completed, heat up to 50 °C and keep the reaction for 2 h, then take 10 mL of the reaction solution as the test solution to be measured. Among them, the ammonia water concentration in the obtained test solution to be measured is 1.7%, and the hexamine concentration is 17.2%;

[0042] Preparation of the control solution:

[0043] 0.05% formaldehyde control solution: Weigh about 1.8 g of the hexamine test sample, accurately weigh it, add 3.5 mL of 5% ammonia water solution and 0.05 mL of 10% formaldehyde solution, and dilute it to 10 mL with water to obtain a 0.05% formaldehyde control solution;

[0044] 0.5% formaldehyde control solution: Weigh about 1.8 g of the hexamine test sample, accurately weigh it, add 3.5 mL of 5% ammonia water solution and 0.5 mL of 10% formaldehyde solution, and dilute it to 10 mL with water to obtain a 0.5% formaldehyde control solution;

[0045] 1% formaldehyde control solution: Weigh about 1.8 g of hexamine test sample, accurately weigh it, add 3.5 mL of 5% ammonia water solution and 1 mL of 10% formaldehyde solution, and dilute it with water to 10 mL to obtain a 1% formaldehyde control solution;

[0046] 5% formaldehyde control solution: Weigh about 1.8 g of hexamine test sample, accurately weigh it, add 3.5 mL of 5% ammonia water solution and 5 mL of 10% formaldehyde solution, and dilute it with water to 10 mL to obtain a 5% formaldehyde control solution.

[0047] Step S2, test process: Drop 3 mL of 0.1 mol / L silver nitrate standard solution into each control solution and the test solution to be measured until the formed white precipitate disappears, let it stand for 5 min, then drop 50 μL of 0.1 mol / L ammoniacal silver nitrate solution while shaking, and observe that the color and silver mirror state in each control solution and the test solution to be measured no longer change.

[0048] Step S3, result determination: Compare the test solution to be measured with each control solution (the colors of each control solution can be as shown in the appendix Figure 1 ), the final solution color and the silver mirror produced in the test solution to be measured are significantly lighter than those of the 0.05% formaldehyde control solution, indicating that the remaining amount of formaldehyde in the reaction solution < 0.05%, and the in-process control result is qualified.

[0049] To verify the accuracy and effectiveness of the in-process control detection method, after sampling the reaction solution, end the reaction of formaldehyde condensation to prepare hexamine, concentrate the remaining reaction solution under reduced pressure. After the concentration is completed, stir and crystallize the reaction solution at room temperature for 1 - 2 h, filter by suction, vacuum-dry the obtained wet product, and collect 25.9 g of white crystalline solid (yield 90%). After testing, the result of paraformaldehyde detected in the obtained hexamine finished product is qualified, indicating that the in-process control detection method in this example can realize the quality monitoring of the reaction process and ensure that the residual paraformaldehyde in the hexamine finished product is within the limit range.

[0050] Example 2

[0051] Another in-process control detection method for the condensation of formaldehyde and ammonia to prepare hexamine disclosed in the embodiments of the present invention includes the following steps:

[0052] Step S1, prepare the test solution to be measured and the control solution:

[0053] Preparation of the test solution to be measured: Weigh 100.0 g of formaldehyde solution (1.23 mol, 1.0 eq) into a reaction flask, slowly drop 75.5 g of ammonia water (1.11 mol, 0.90 eq), after dropping, raise the temperature to 50 °C and keep the reaction for 2 h, then take 10 mL of the reaction solution as the test solution to be measured. The ammonia water concentration of the obtained test solution to be measured is 2.8%, and the hexamine concentration is 17.2%;

[0054] Preparation of control solution: Referring to the control solution in Example 1, prepare 10 mL of each control solution containing 0.01% - 5% formaldehyde.

[0055] 0.05% formaldehyde control solution: Weigh about 1.8 g of hexamine test sample accurately, add 5.5 mL of 5% ammonia water solution and 0.05 mL of 10% formaldehyde solution, and dilute with water to 10 mL to obtain a 0.05% formaldehyde control solution.

[0056] 0.5% formaldehyde control solution: Weigh about 1.8 g of hexamine test sample accurately, add 5.5 mL of 5% ammonia water solution and 0.5 mL of 10% formaldehyde solution, and dilute with water to 10 mL to obtain a 0.5% formaldehyde control solution.

[0057] 1% formaldehyde control solution: Weigh about 1.8 g of hexamine test sample accurately, add 5.5 mL of 5% ammonia water solution and 1 mL of 10% formaldehyde solution, and dilute with water to 10 mL to obtain a 1% formaldehyde control solution.

[0058] 5% formaldehyde control solution: Weigh about 1.8 g of hexamine test sample accurately, add 5.5 mL of 5% ammonia water solution and 5 mL of 10% formaldehyde solution, and dilute with water to 10 mL to obtain a 5% formaldehyde control solution.

[0059] Step S2, test process: Drop 3 mL of 0.1 mol / L silver nitrate standard solution into each control solution and the test solution to be measured until the formed white precipitate disappears, let it stand for 5 min, then drop 100 μL of 0.1 mol / L silver ammonia nitrate solution while shaking, and observe that the color and silver mirror state in each control solution and the test solution to be measured no longer change.

[0060] Step S3, result determination: Comparing the test solution to be measured with the control solution (the colors of each control solution as shown in the appendix Figure 2 ), the final solution color and the silver mirror produced in the test solution to be measured are significantly lighter than those of the 0.05% formaldehyde control solution, indicating that the remaining amount of formaldehyde in the reaction solution < 0.05%, and the in - process control result is qualified.

[0061] To verify the accuracy and effectiveness of the in - process control detection method, after sampling the reaction solution, end the reaction of formaldehyde condensation to prepare hexamine, concentrate the remaining reaction solution under reduced pressure. After the concentration is completed, stir and crystallize the reaction solution at room temperature for 1 - 2 h, filter by suction, vacuum - dry the obtained wet product, and collect 25.9 g of white crystalline solid (yield 90%). After testing, the result of the trimethanal detected in the obtained hexamine finished product is qualified, indicating that the in - process control detection method in this example can realize the quality monitoring of the reaction process and ensure that the residual paraformaldehyde in the hexamine finished product is within the limit range.

[0062] Example 3

[0063] A central control detection method for preparing hexamethylenetetramine by the condensation of formaldehyde and ammonia disclosed in an embodiment of the present invention includes the following steps:

[0064] Step S1, prepare a test solution and a control solution;

[0065] Test solution: Weigh 100.0 g of formaldehyde solution (1.23 mol, 1.0 eq) into a reaction flask, slowly add dropwise 58.8 g of ammonia water (0.86 mol, 0.7 eq). After the addition is complete, heat up to 50 °C and keep the reaction for 2 h. Then take 10 mL of the reaction solution as the test solution to be measured. The ammonia water concentration of the obtained test solution to be measured is 0.4%, and the hexamethylenetetramine concentration is 17.2%;

[0066] Control solution: Refer to the control solution in Example 1 and prepare 10 mL of control solutions containing 0.01% - 5% formaldehyde each.

[0067] 0.05% formaldehyde control solution: Weigh about 1.8 g of the hexamethylenetetramine test sample, accurately weigh it, add 0.8 mL of 5% ammonia water solution and 0.05 mL of 10% formaldehyde solution, and dilute with water to 10 mL to obtain a 0.05% formaldehyde control solution;

[0068] 0.5% formaldehyde control solution: Weigh about 1.8 g of the hexamethylenetetramine test sample, accurately weigh it, add 0.8 mL of 5% ammonia water solution and 0.5 mL of 10% formaldehyde solution, and dilute with water to 10 mL to obtain a 0.5% formaldehyde control solution;

[0069] 1% formaldehyde control solution: Weigh about 1.8 g of the hexamethylenetetramine test sample, accurately weigh it, add 0.8 mL of 5% ammonia water solution and 1 mL of 10% formaldehyde solution, and dilute with water to 10 mL to obtain a 1% formaldehyde control solution;

[0070] 5% formaldehyde control solution: Weigh about 1.8 g of the hexamethylenetetramine test sample, accurately weigh it, add 0.8 mL of 5% ammonia water solution and 5 mL of 10% formaldehyde solution, and dilute with water to 10 mL to obtain a 5% formaldehyde control solution.

[0071] Step S2, test process: Drop 2 mL of 0.1 mol / L silver nitrate standard solution into each control solution and the test solution to be measured until the formed white precipitate disappears. Let it stand for 5 min, then drop 50 μL of 0.1 mol / L ammoniacal silver nitrate solution drop by drop while shaking. Observe that the color and silver mirror state in each control solution and the test solution to be measured no longer change.

[0072] Step S3, result determination: Compare the test solution to be measured with the control solution (as shown in the appendix Figure 3(for each of the control solutions shown), the color of the final solution and the silver mirror produced in the test sample solution were significantly darker than those of the 0.05% formaldehyde control solution and lighter than those of the 0.5% formaldehyde control solution, indicating that the remaining amount of formaldehyde in the reaction solution was between 0.05% and 0.5%, and the in-process control result was unqualified.

[0073] To verify the accuracy and effectiveness of the in-process control detection method, after sampling the reaction solution, the reaction of formaldehyde condensation to prepare hexamine was terminated. The remaining reaction solution was concentrated under reduced pressure. After the concentration was completed, the reaction solution was stirred and crystallized at room temperature for 1 - 2 h, filtered by suction, and the obtained wet product was dried in vacuo. 25.3 g of white crystalline solid was obtained (yield 88%). After testing, the result of the detected paraformaldehyde in the final hexamine product was unqualified, indicating that the in-process control detection method in this example could achieve the quality control of the reaction process and ensure that the residual paraformaldehyde in the hexamine product was within the limit range.

[0074] Example 4

[0075] An in-process control detection method for the condensation of formaldehyde and ammonia to prepare hexamine disclosed in the embodiments of the present invention includes the following steps:

[0076] Step S1, prepare the test sample solution and the control solution;

[0077] Test sample solution: Weigh 100.0 g (1.23 mol, 1.0 eq) of formaldehyde solution into a reaction flask, slowly add 50.4 g of ammonia water (0.74 mol, 0.6 eq) dropwise. After the addition is complete, heat up to 50 °C and keep the reaction for 2 h. Then, take 10 mL of the reaction solution as the test sample solution to be measured. The ammonia water concentration in the obtained test sample solution to be measured is 0%, and the hexamine concentration is 17.2%;

[0078] Control solution: Referring to the control solution in Example 1, prepare 10 mL of control solutions containing 0.01% - 5% formaldehyde each.

[0079] 0.05% formaldehyde control solution: Weigh about 1.8 g of the hexamine test sample, accurately weigh it, add 0.05 mL of 10% formaldehyde solution, and dilute it to 10 mL with water to obtain a 0.05% formaldehyde control solution;

[0080] 0.5% formaldehyde control solution: Weigh about 1.8 g of the hexamine test sample, accurately weigh it, add 0.5 mL of 10% formaldehyde solution, and dilute it to 10 mL with water to obtain a 0.5% formaldehyde control solution;

[0081] 1% formaldehyde control solution: Weigh about 1.8 g of the hexamine test sample, accurately weigh it, add 1 mL of 10% formaldehyde solution, and dilute it to 10 mL with water to obtain a 1% formaldehyde control solution;

[0082] 5% Formaldehyde Control Solution: Weigh approximately 1.8 g of the hexamine test sample accurately, add 5 mL of 10% formaldehyde solution, and dilute with water to 10 mL to obtain a 5% formaldehyde control solution.

[0083] Step S2, Test Procedure: Drop 2 mL of 0.1 mol / L silver nitrate standard solution into each control solution and the test solution to be measured until the formed white precipitate disappears. Let it stand for 5 min, then drop 50 μL of 0.1 mol / L ammoniacal silver nitrate solution while shaking. Observe that the color and silver mirror state in each control solution and the test solution to be measured no longer change.

[0084] Step S3, Result Judgment: When comparing the test solution to be measured with the control solution (the colors of the control solutions as shown in the appendix Figure 4 ), the final solution color and the formed silver mirror in the test solution to be measured are significantly darker than those in the 0.5% formaldehyde control solution, indicating that the remaining amount of formaldehyde in the reaction solution > 0.5%, and the in-process control result is unqualified.

[0085] To verify the accuracy and effectiveness of the in-process control detection method, after sampling the reaction solution, the reaction of formaldehyde condensation to prepare hexamine is terminated. The remaining reaction solution is concentrated under reduced pressure. After the concentration is completed, the reaction solution is stirred and crystallized at room temperature for 1 - 2 h, then filtered by suction. The obtained wet product is dried in vacuo, and 24.7 g of white crystalline solid is obtained (yield 86%). After testing, the result of the paraformaldehyde detected in the obtained hexamine finished product is unqualified, indicating that the in-process control detection method in this example can realize the quality monitoring of the reaction process to ensure that the residual paraformaldehyde in the hexamine finished product is within the limit range.

[0086] In the actual experimental process, the purposes of Examples 1 - 3 are to prove that under the condition of different ammonia water residual amounts, this method can still detect the content of free formaldehyde. In Example 4, formaldehyde is in excess, and the remaining amount of formaldehyde will be greater than 0.05%. Therefore, through this detection method, a more obvious silver mirror phenomenon can be found. Thus, it is proved that when there is formaldehyde residue, the content range of formaldehyde can be detected, thereby effectively verifying the feasibility and accuracy of this detection method.

[0087] Of course, in the specific implementation process, the preparation process of this control solution is not limited to the four control solutions of 0.05% formaldehyde control solution, 0.10% formaldehyde control solution, 1% formaldehyde control solution, and 5% formaldehyde control solution provided in the above examples. Control solutions with multiple formaldehyde concentrations can also be set. Specifically, the preparation process of this control solution can also include the following several types:

[0088] 0.10% Formaldehyde Control Solution: Weigh approximately 1.8 g of the hexamine test sample accurately, add 0 - 2 mL of 5% ammonia water solution and 0.10 mL of 10% formaldehyde solution, and dilute with water to 10 mL to obtain a 0.10% formaldehyde control solution;

[0089] 0.25% formaldehyde control solution: Weigh about 1.8 g of hexamine test sample accurately, add 0 - 2 mL of 5% ammonia water solution and 0.25 mL of 10% formaldehyde solution, then dilute to 10 mL with water to obtain 0.25% formaldehyde control solution;

[0090] 0.75% formaldehyde control solution: Weigh about 1.8 g of hexamine test sample accurately, add 0 - 2 mL of 5% ammonia water solution and 0.75 mL of 10% formaldehyde solution, then dilute to 10 mL with water to obtain 0.75% formaldehyde control solution;

[0091] 3% formaldehyde control solution: Weigh about 1.8 g of hexamine test sample accurately, add 0 - 2 mL of 5% ammonia water solution and 3 mL of 10% formaldehyde solution, then dilute to 10 mL with water to obtain 3% formaldehyde control solution.

[0092] In the specific implementation process, the selected control solutions can be the control solutions with four formaldehyde concentrations of 0.05% formaldehyde control solution, 0.10% formaldehyde control solution, 1% formaldehyde control solution, and 5% formaldehyde control solution, or the control solutions with seven formaldehyde concentrations of 0.05% formaldehyde control solution, 0.25% formaldehyde control solution, 0.50% formaldehyde control solution, 0.75% formaldehyde control solution, 0.10% formaldehyde control solution, 1% formaldehyde control solution, and 5% formaldehyde control solution. Since the reaction rate may be slower when the formaldehyde concentration is lower during the silver mirror reaction by adding silver nitrate standard solution, it is necessary to provide multiple control solutions with smaller intervals such as 0.05% formaldehyde control solution, 0.25% formaldehyde control solution, and 0.75% formaldehyde control solution for the test sample solution to be compared, and at the same time, it can also ensure the controllability of the time for the condensation of formaldehyde and ammonia to prepare hexamine during the actual production process, so as to ensure the quality of hexamine. Of course, in order to be able to grasp the reaction progress of the condensation of formaldehyde and ammonia to prepare hexamine in real time during the actual production process, other formaldehyde concentration control solutions can also be set. Of course, it can also be like the Figure 1 eight control solutions of 0.05% formaldehyde control solution, 0.25% formaldehyde control solution, 0.50% formaldehyde control solution, 0.75% formaldehyde control solution, 0.10% formaldehyde control solution, 1% formaldehyde control solution, 3% formaldehyde control solution, and 5% formaldehyde control solution provided in the application for experiments, which will not be elaborated in detail here.

[0093] By using the above central control detection method, a control solution with the same order of magnitude as the concentrations of hexamine and ammonia in the test solution to be measured is set, and the formaldehyde content in the control solution is known. Thus, the silver nitrate standard solution can be added dropwise to the test solution to be measured and the control solution to cause the corresponding silver mirror reaction. After the reactions of the test solution to be measured and the control solution are completed, by comparing the color degrees of the test solution to be measured with those of each control solution, a control solution with a color degree extremely similar to or the same as that of the test solution to be measured is obtained. Since the formaldehyde content in the control solution is known, the formaldehyde content corresponding to this control solution can be directly obtained, and thus the formaldehyde content of the test solution to be measured can be obtained, which is the residual formaldehyde content in the reaction solution for preparing hexamine by the condensation of formaldehyde and ammonia.

[0094] Through limit colorimetry in this application, the detection personnel can clearly, quickly, and accurately determine the content range of formaldehyde in the reaction solution of hexamine, which has good specificity and sensitivity, and can be effectively used for quality control during the production reaction process of hexamine to ensure that the residual paraformaldehyde in the finished product of hexamine is within the limit range, thereby effectively improving the preparation efficiency, preparation precision, and quality of hexamine.

[0095] In addition, in the actual production line for preparing hexamine by the condensation of formaldehyde and ammonia, since this method can pre-obtain the colors of control solutions with different formaldehyde contents, samples can be taken at any time during the production process of the production line for experiments, so as to obtain the color of a test solution to be measured (taken from the reaction solution). Furthermore, by comparing with the control solution, the residual formaldehyde content in the current reaction solution can be quickly known. When the residual formaldehyde content is lower than 0.05%, it can be known that the reaction for preparing hexamine is about to end. Since this experimental process is relatively fast, about ten minutes before and after, the preparation efficiency, preparation precision, and quality of hexamine can be effectively improved through this central control detection method.

[0096] Comparative Example 1

[0097] Referring to the central control detection method for preparing hexamine by the condensation of formaldehyde and ammonia in the European Pharmacopoeia 11.0, it includes the following steps:

[0098] Step S1, prepare the test solution and the control solution;

[0099] Test solution 1: The sampled reaction solution is the same as that in Example 1. 8 mL of the sampled solution is used as the test solution to be measured, and the reaction and sampling processes are not elaborated in detail here;

[0100] Test solution 2: The sampled reaction solution is the same as that in Example 4. 8 mL of the sampled solution is used as the test solution to be measured, and the reaction and sampling processes are not elaborated in detail here;

[0101] Control solution: 8 mL of freshly prepared 5 ppm formaldehyde standard solution.

[0102] Step S2, test process: Quantitatively add 2 mL of 0.1 mol / L silver nitrate solution in ammonia to the control solution and the test sample solution 1-2 to be measured, and let it stand for 5 minutes. The control solution turns gray, and there is no obvious change in the state of the test sample solution 1-2, which is clear and transparent. Continue to add more than 15 mL of 0.1 mol / L silver nitrate solution in ammonia to the control solution and the test sample solution 1-2 to be measured, and it is observed that there is still no obvious change in the control solution and the test sample solution 1-2 to be measured. Among them, the test sample solution 2 is as Figure 5 shown.

[0103] Step S3, result determination: According to the phenomena in the above test process and the results of the trioxymethylene detected in the hexamine finished product verified in Example 1 and Example 4, it shows that the content of free formaldehyde in the test sample solution to be measured cannot be determined by this method. Therefore, this method is not applicable to the in-process detection of the preparation of hexamine by the condensation of formaldehyde and ammonia.

[0104] The above are only the preferred embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent replacements, and improvements made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A central control detection method for preparing urotropine by formaldehyde condensation, which is used to detect the residual formaldehyde content in the reaction solution prepared by condensing formaldehyde and ammonia to prepare urotropine, characterized in that: The central control detection method comprises: Step S1, preparing a test solution to be tested and a plurality of control solutions; wherein the concentrations of urotropine and ammonia in the control solution are kept at the same order of magnitude as those of the test solution to be tested, and the formaldehyde content in the control solution is known; Step S2, dripping the same amount of silver nitrate standard solution into each control solution and the test solution to be tested until the formed white precipitate disappears, and then dripping the same amount of ammoniacal silver nitrate solution into each control solution and the test solution to be tested after standing, shaking while adding, and dripping the same amount of ammoniacal silver nitrate solution into each control solution and the test solution to be tested until the color and the silver mirror state of each control solution and the test solution to be tested no longer change, and then dripping the same amount of ammoniacal silver nitrate solution in excess; Step S3, comparing the test solution to be tested with each control solution, and obtaining the residual formaldehyde content range in the test solution to be tested, that is, the residual formaldehyde content range in the reaction solution, based on the comparison of the chromaticity of the test solution to be tested with the chromaticity of each control solution.

2. The central control detection method for preparing hexamethylenetetramine by formaldehyde condensation as claimed in claim 1, characterized in that: Step S1 comprises: sampling from the reaction solution in which formaldehyde and ammonia are condensed to prepare urotropine to obtain a test solution to be tested, wherein the concentration of urotropine in the test solution to be tested ranges from 10% to 30%, and the concentration of ammonia water ranges from 1% to 5%.

3. The central control detection method for preparing hexamethylenetetramine by formaldehyde condensation as claimed in claim 2, characterized in that: Step S1 also includes: simulating the composition of the reaction solution for preparing urotropine by condensation of formaldehyde and ammonia, weighing urotropine, adding ammonia solution and formaldehyde solution to prepare a plurality of control solutions with different formaldehyde contents ranging from 0.01% to 5%.

4. The central control detection method for preparing hexamethylenetetramine by formaldehyde condensation as claimed in claim 1, characterized in that: The standard for a qualified central control reaction in the central control detection method is that the residual formaldehyde in the reaction solution is ≤0.05%.

5. The central control detection method for preparing hexamethylenetetramine by formaldehyde condensation as claimed in claim 3, characterized in that: The formaldehyde content of the control solution in step S1 is 0.05% to 5%.

6. The central control detection method for preparing hexamethylenetetramine by formaldehyde condensation as claimed in claim 2, characterized in that: The test solution to be tested is a reaction solution from a synthesis process of preparing urotropine by condensation of formaldehyde and ammonia, wherein the synthesis process of preparing urotropine by condensation of formaldehyde and ammonia comprises: Add 1.0eq of formaldehyde solution to the reactor, stir and then drop 0.67-0.95eq of ammonia solution. After the ammonia solution is added, heat to 40-80°C and react for 1-2h. The relevant reaction formula is:

7. The central control detection method for preparing hexamethylenetetramine by formaldehyde condensation as claimed in claim 1, characterized in that: The concentration of the silver nitrate standard solution in step S2 is 0.1 mol / L, and the volume is 1-5 mL.

8. The central control detection method for preparing hexamethylenetetramine by formaldehyde condensation as claimed in claim 1, characterized in that: The concentration of the ammonia-based silver nitrate solution in step S2 is 0.1 mol / L, and the volume is 50-500 μL.

9. The central control detection method for preparing hexamethylenetetramine by formaldehyde condensation as claimed in claim 1, characterized in that: In step S2, the volumes of the control solutions and the test solutions to be tested are equal.

10. The central control detection method for preparing hexamethylenetetramine by formaldehyde condensation as claimed in claim 3, characterized in that: There are at least four control solutions, and the formaldehyde contents of the four control solutions are 0.05%, 0.5%, 1% and 5% respectively.

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