Method for preparing carbon isotope labeled urea by taking divalent carbonate as raw material

Abstract

The invention provides a method for preparing carbon isotope labeled urea by taking divalent carbonate as a raw material, and belongs to the technical field of helicobacter pylori detection. The method comprises the following steps: S1, mixing acid with divalent carbonate powder, and collecting generated carbon dioxide; s2, drying the carbon dioxide, and introducing a nitrogen source solution until the carbon dioxide is saturated to obtain a reaction solution; s3, sequentially carrying out heating reflux, cooling, filtering, solvent removal and vacuum concentration on the reaction liquid to obtain carbon-labeled C (NTMS) 2; s4, dissolving the carbon-labeled C (NTMS) 2 in 1, 4-dioxane, then adding a hydrogen fluoride aqueous solution and oxalic acid, carrying out a reflux reaction, collecting a solid, and drying to obtain carbon isotope labeled urea; the divalent carbonate in the S1 is marked by carbon 13 or carbon 14. The high-purity carbon isotope labeled urea is prepared by adopting the carbon labeled divalent carbonate as the raw material, the preparation condition is mild, the synthesis process is convenient, green and environment-friendly, and the method is suitable for industrial production.

Description

Technical Field

[0001] The invention belongs to the technical field of Helicobacter pylori detection, and specifically relates to a method for preparing carbon isotope labeled urea by taking divalent carbonate as a raw material. Background Art

[0002] The carbon-14 breath test is a safe and simple method to detect Helicobacter pylori infection and determine whether the Helicobacter pylori elimination treatment is successful. Helicobacter pylori produces highly active urease. When taking urea labeled with carbon-14, if Helicobacter pylori is present in the stomach, the urease produced by Helicobacter pylori will decompose the urea into carbon-14 labeled carbon dioxide and ammonia. The carbon-14 labeled carbon dioxide is then exhaled through the blood. By analyzing the content of carbon-14 labeled carbon dioxide in the exhaled breath, it can be determined whether the patient is infected with Helicobacter pylori.

[0003] The existing method for synthesizing carbon-14 labeled urea mainly uses carbon-14 labeled barium carbonate or carbon-14 labeled potassium cyanide as the starting material. The reaction of carbon-14 labeled barium carbonate with barium amide or ammonia at high temperature is not only dangerous, but also the raw materials are both in solid phase, and the reaction contact is not sufficient, resulting in low reaction yield. Carbon-14 labeled potassium cyanide is more expensive than carbon-14 labeled barium carbonate, and is also highly toxic, has higher requirements for operation, and has a great impact on personal safety and the environment.

[0004] Therefore, a simple and non-toxic method for synthesizing carbon isotope-labeled urea is urgently needed. Summary of the invention

[0005] In view of this, the purpose of the present invention is to provide a method for preparing carbon isotope labeled urea using divalent carbonate as raw material. The present invention uses carbon-labeled divalent carbonate as raw material to prepare high-purity carbon isotope labeled urea. The preparation conditions are mild, the synthesis process is convenient and green and environmentally friendly, and it is suitable for industrial production.

[0006] In order to achieve the above object, the present invention provides the following technical solutions:

[0007] The present invention provides a method for preparing carbon isotope labeled urea using divalent carbonate as a raw material, comprising the following steps:

[0008] S1. mixing the acid with divalent carbonate powder and collecting the generated carbon dioxide;

[0009] S2. The carbon dioxide is dried and then introduced into a nitrogen source solution until saturated to obtain a reaction solution;

[0010] S3. The reaction solution is heated to reflux, cooled, filtered, the solvent is removed, and concentrated under reduced pressure to obtain carbon-labeled C (NTMS) 2 ;

[0011] S4. Carbon labeled C(NTMS) 2 Dissolved in 1,4-dioxane and then added with aqueous hydrogen fluoride solution and oxalic acid for reflux reaction, then collected and dried to obtain carbon isotope labeled urea;

[0012] The divalent carbonate in S1 is labeled with carbon 13 or carbon 14.

[0013] Preferably, the volume mass ratio of the acid to the divalent carbonate powder in S1 is (10-100) mL: (1-20) g.

[0014] Preferably, the acid in S1 is any one of hydrochloric acid, sulfuric acid and nitric acid.

[0015] Preferably, the divalent carbonate in S1 is any one of calcium carbonate, magnesium carbonate, barium carbonate and zinc carbonate.

[0016] Preferably, the nitrogen source solution in S2 is LiN(TMS) 2 Solution, NaN(TMS) 2 Solution, KN(TMS) 2 Any one of the solutions.

[0017] Preferably, the temperature of the nitrogen source solution in S2 is -30 to 0°C.

[0018] Preferably, the heating reflux temperature in S3 is 60-100° C. and the time is 1-5 h.

[0019] Preferably, the carbon-labeled C(NTMS) in S4 2 The mass volume ratio of 1,4-dioxane, hydrogen fluoride aqueous solution, and oxalic acid is (0.5~2)g:(5~50)mL:(0.1~2)mL:(0.05~2)g.

[0020] Preferably, the reflux temperature in S4 is 100-200° C. and the time is 1-5 h.

[0021] Contains at least the following beneficial technical effects:

[0022] The invention adopts carbon-labeled divalent carbonate as a raw material to prepare high-purity carbon isotope-labeled urea, has mild preparation conditions, convenient synthesis process, is green and environmentally friendly, and is suitable for industrial production. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 This is a schematic diagram of the synthesis route of carbon isotope labeled urea in Example 1. DETAILED DESCRIPTION

[0024] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as limiting the present invention, but should be understood as a more detailed description of certain aspects, features, and embodiments of the present invention.

[0025] It should be understood that the terms described in the present invention are only for describing special embodiments and are not intended to limit the present invention. In addition, for the numerical range in the present invention, it should be understood that each intermediate value between the upper and lower limits of the scope is also specifically disclosed. Each smaller range between the intermediate value in any stated value or stated range and any other stated value or intermediate value in the described range is also included in the present invention. The upper and lower limits of these smaller ranges can be independently included or excluded in the scope.

[0026] Unless otherwise indicated, all technical and scientific terms used herein have the same meanings as those generally understood by those skilled in the art. Although the present invention describes only preferred methods and materials, any methods and materials similar or equivalent to those described herein may also be used in the implementation or testing of the present invention. All documents mentioned in this specification are incorporated by reference to disclose and describe the methods and / or materials associated with the documents. In the event of a conflict with any incorporated document, the content of this specification shall prevail.

[0027] It will be apparent to those skilled in the art that various modifications and variations may be made to the specific embodiments of the present invention description without departing from the scope or spirit of the present invention. Other embodiments derived from the present invention description will be apparent to those skilled in the art. The present application description and examples are exemplary only.

[0028] The words “include,” “including,” “have,” “contain,” etc. used in this document are open-ended terms, meaning including but not limited to.

[0029] The "room temperature" and "normal temperature" mentioned in the present invention are all calculated as 25±2°C unless otherwise specified.

[0030] The raw materials and instruments used in the following examples of the present invention are commercially available unless otherwise specified.

[0031] Example 1

[0032] This embodiment provides a method for synthesizing urea from calcium carbonate, comprising the following steps:

[0033] S1. Add 50 mL of hydrochloric acid to 20 g of carbon 14 labeled calcium carbonate powder and collect the generated carbon dioxide gas;

[0034] S2. Dried carbon dioxide gas is passed into LiN (TMS) at -30 degrees Celsius 2In the solution, saturation was achieved after 2 h to obtain a reaction solution;

[0035] S3. The reaction solution was heated to 80°C and refluxed for 1 h, then cooled to room temperature, filtered through diatomaceous earth, the solvent was removed, and concentrated under reduced pressure to obtain 2 g C(NTMS) 2 ;

[0036] S4. 1.86 g C(NTMS) 2 Dissolve in 10 mL of 1,4-dioxane, then add 0.5 mL of aqueous hydrogen fluoride solution and 450 mg of oxalic acid, reflux at 120°C for 3 h, collect the precipitated solid, and dry to obtain 500 mg of carbon-14 labeled urea with 99% chromatographic purity.

[0037] Example 2

[0038] This embodiment provides a method for synthesizing urea from magnesium carbonate, comprising the following steps:

[0039] S1. 10 mL of sulfuric acid was dropped into 5 g of carbon 14 labeled magnesium carbonate powder to collect the generated carbon dioxide gas;

[0040] S2. Dried carbon dioxide gas is passed into NaN (TMS) at -10 degrees Celsius 2 In the solution, saturation was achieved after 2 h to obtain a reaction solution;

[0041] S3. The reaction solution was heated to 60°C and refluxed for 1 h, then cooled to room temperature, filtered through diatomaceous earth, the solvent was removed, and concentrated under reduced pressure to obtain 0.5 g C(NTMS) 2 ;

[0042] S4. 0.5 g C(NTMS) 2 Dissolve in 10 mL of 1,4-dioxane, then add 0.5 mL of aqueous hydrogen fluoride solution and 200 mg of oxalic acid, reflux at 100°C for 1 hour, collect the precipitated solid, and dry to obtain 120 mg of carbon-14 labeled urea with a chromatographic purity of 99%.

[0043] Example 3

[0044] This embodiment provides a method for synthesizing urea from barium carbonate, comprising the following steps:

[0045] S1. 100 mL of nitric acid was dropped into 20 g of carbon 14 labeled barium carbonate powder to collect the generated carbon dioxide gas;

[0046] S2. Dried carbon dioxide gas is passed into the zero-degree KNN (TMS) 2 The solution reached saturation after 2 h to obtain a reaction solution;

[0047] S3. The reaction solution was heated to 100°C and refluxed for 1 h, then cooled to room temperature, filtered through diatomaceous earth, the solvent was removed, and concentrated under reduced pressure to obtain 2 g C(NTMS) 2 ;

[0048] S4. 1.86 g C(NTMS) 2 Dissolve in 50 mL of 1,4-dioxane, then add 1.5 ml of aqueous hydrogen fluoride solution and 1.5 g of oxalic acid and reflux at 185°C for 5 h. Collect the precipitated solid and dry it to obtain 500 mg of carbon 14 labeled urea with 99% chromatographic purity.

[0049] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A method for preparing carbon isotope labeled urea using divalent carbonate as raw material, characterized in that: The following steps are involved: S1. mixing the acid with divalent carbonate powder and collecting the generated carbon dioxide; S2. The carbon dioxide is dried and then introduced into a nitrogen source solution until saturated to obtain a reaction solution; S3. The reaction solution is heated to reflux, cooled, filtered, the solvent is removed, and concentrated under reduced pressure to obtain carbon-labeled C(NTMS)2; S4. dissolving carbon-labeled C(NTMS)2 in 1,4-dioxane and then adding aqueous hydrogen fluoride solution and oxalic acid to reflux the reaction, collecting the solid and drying it to obtain carbon isotope-labeled urea; The divalent carbonate in S1 is labeled with carbon 13 or carbon 14.

2. The method according to claim 1, characterized in that The volume mass ratio of the acid to the divalent carbonate powder in the S1 is (10-100) mL: (1-20) g.

3. The method according to claim 1, characterized in that The acid in S1 is any one of hydrochloric acid, sulfuric acid and nitric acid.

4. The method according to claim 1, characterized in that: The divalent carbonate in S1 is any one of calcium carbonate, magnesium carbonate, barium carbonate and zinc carbonate.

5. The method according to claim 1, characterized in that The nitrogen source solution in S2 is any one of LiN(TMS)2 solution, NaN(TMS)2 solution, and KN(TMS)2 solution.

6. The method according to claim 1, characterized in that The temperature of the nitrogen source solution in S2 is -30 to 0°C.

7. The method according to claim 1, characterized in that The heating reflux temperature in S3 is 60-100° C. and the time is 1-5 h.

8. The method according to claim 1, characterized in that The mass volume ratio of carbon-labeled C(NTMS)2, 1,4-dioxane, aqueous hydrogen fluoride solution, and oxalic acid in the S4 is (0.5-2) g: (5-50) mL: (0.1-2) mL: (0.05-2) g.

9. The method according to claim 1, characterized in that: The reflux temperature in S4 is 100-200° C. and the time is 1-5 hours.

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