CN101863833A - Preparation method of 3-carboxymethyl-5,5-diphenylhydantoin - Google Patents
Preparation method of 3-carboxymethyl-5,5-diphenylhydantoin Download PDFInfo
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- ISTMZIFNQQCIIZ-UHFFFAOYSA-N 2-(2,5-dioxo-4,4-diphenylimidazolidin-1-yl)acetic acid Chemical compound O=C1N(CC(=O)O)C(=O)NC1(C=1C=CC=CC=1)C1=CC=CC=C1 ISTMZIFNQQCIIZ-UHFFFAOYSA-N 0.000 title claims abstract description 24
- 238000002360 preparation method Methods 0.000 title abstract description 3
- 238000000034 method Methods 0.000 claims abstract description 25
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 21
- 238000006243 chemical reaction Methods 0.000 claims abstract description 17
- 238000010992 reflux Methods 0.000 claims abstract description 15
- CXOFVDLJLONNDW-UHFFFAOYSA-N Phenytoin Chemical compound N1C(=O)NC(=O)C1(C=1C=CC=CC=1)C1=CC=CC=C1 CXOFVDLJLONNDW-UHFFFAOYSA-N 0.000 claims abstract description 12
- 239000000047 product Substances 0.000 claims abstract description 10
- FOCAUTSVDIKZOP-UHFFFAOYSA-N chloroacetic acid Chemical compound OC(=O)CCl FOCAUTSVDIKZOP-UHFFFAOYSA-N 0.000 claims abstract description 9
- 229940106681 chloroacetic acid Drugs 0.000 claims abstract description 9
- 238000003756 stirring Methods 0.000 claims abstract description 9
- WBJINCZRORDGAQ-UHFFFAOYSA-N ethyl formate Chemical compound CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 claims abstract description 8
- 239000000706 filtrate Substances 0.000 claims abstract description 6
- 230000035484 reaction time Effects 0.000 claims abstract description 6
- 238000010438 heat treatment Methods 0.000 claims abstract description 3
- 238000000926 separation method Methods 0.000 claims abstract description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Substances [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 30
- 239000000243 solution Substances 0.000 claims description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 13
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 8
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- 239000003513 alkali Substances 0.000 claims description 4
- 239000007864 aqueous solution Substances 0.000 claims description 4
- 239000000203 mixture Substances 0.000 claims description 4
- 230000020477 pH reduction Effects 0.000 claims description 4
- 239000002904 solvent Substances 0.000 claims description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims description 2
- 238000010790 dilution Methods 0.000 claims description 2
- 239000012895 dilution Substances 0.000 claims description 2
- 239000012065 filter cake Substances 0.000 claims description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 claims description 2
- 239000012046 mixed solvent Substances 0.000 claims description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- 239000002585 base Substances 0.000 claims 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 1
- 230000007935 neutral effect Effects 0.000 claims 1
- 239000002994 raw material Substances 0.000 abstract description 4
- 230000002194 synthesizing effect Effects 0.000 abstract description 3
- 238000001035 drying Methods 0.000 abstract description 2
- 150000002391 heterocyclic compounds Chemical class 0.000 abstract description 2
- 238000004519 manufacturing process Methods 0.000 abstract description 2
- 238000001953 recrystallisation Methods 0.000 abstract description 2
- 239000007858 starting material Substances 0.000 abstract description 2
- -1 5,5-diphenylacetylhydantoin Chemical compound 0.000 abstract 1
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 4
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 3
- 238000004566 IR spectroscopy Methods 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 238000004811 liquid chromatography Methods 0.000 description 3
- 238000004949 mass spectrometry Methods 0.000 description 3
- 239000012265 solid product Substances 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- BJLAIBYNFMQGOT-UHFFFAOYSA-N ethyl 2-(2,5-dioxo-4,4-diphenylimidazolidin-1-yl)acetate Chemical compound O=C1N(CC(=O)OCC)C(=O)NC1(C=1C=CC=CC=1)C1=CC=CC=C1 BJLAIBYNFMQGOT-UHFFFAOYSA-N 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- IZLFUDHPNDYYHS-UHFFFAOYSA-M potassium;2-bromoacetate Chemical compound [K+].[O-]C(=O)CBr IZLFUDHPNDYYHS-UHFFFAOYSA-M 0.000 description 2
- KPFSGNRRZMYZPH-UHFFFAOYSA-M potassium;2-chloroacetate Chemical compound [K+].[O-]C(=O)CCl KPFSGNRRZMYZPH-UHFFFAOYSA-M 0.000 description 2
- 239000001632 sodium acetate Substances 0.000 description 2
- FDRCDNZGSXJAFP-UHFFFAOYSA-M sodium chloroacetate Chemical compound [Na+].[O-]C(=O)CCl FDRCDNZGSXJAFP-UHFFFAOYSA-M 0.000 description 2
- UYBPMPGSEWRTLG-UHFFFAOYSA-N 2-(2,5-dioxoimidazolidin-1-yl)acetic acid Chemical class OC(=O)CN1C(=O)CNC1=O UYBPMPGSEWRTLG-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000002082 anti-convulsion Effects 0.000 description 1
- 230000002921 anti-spasmodic effect Effects 0.000 description 1
- 229940124575 antispasmodic agent Drugs 0.000 description 1
- 239000002934 diuretic Substances 0.000 description 1
- 229940030606 diuretics Drugs 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- VEUUMBGHMNQHGO-UHFFFAOYSA-N ethyl chloroacetate Chemical compound CCOC(=O)CCl VEUUMBGHMNQHGO-UHFFFAOYSA-N 0.000 description 1
- 238000004880 explosion Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000007127 saponification reaction Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
本发明属杂环化合物制备方法领域，尤其涉及一种以5，5-二苯基乙酰内脲为起始原料，合成3-羧甲基-5，5-二苯基海因的方法。可按如下步骤依次进行：(1)将氯乙酸或溴乙酸与碱液在室温搅拌条件下进行反应，所得溶液待用；(2)将5，5-二苯基乙内酰脲与碱液混和，于搅拌条件下，加热至回流；(3)将步骤(1)所得溶液，滴加到(2)中，滴加完毕，继续回流反应，停止加热；反应液经稀释、过滤、酸化滤液、分离、干燥、乙醇重结晶，即得目标产物。纯产品纯度＞98％。本发明方法所需的原料简单易得，操作过程简便、安全，反应时间短，成本低，产率高，适于工业规模化生产，具有较强的实用性。The invention belongs to the field of preparation methods of heterocyclic compounds, and in particular relates to a method for synthesizing 3-carboxymethyl-5,5-diphenylhydantoin by using 5,5-diphenylacetylhydantoin as a starting material. It can be carried out in sequence as follows: (1) react chloroacetic acid or bromoacetic acid with lye under stirring conditions at room temperature, and the resulting solution is ready for use; (2) mix 5,5-diphenylhydantoin with lye Mix and heat to reflux under stirring; (3) Add the solution obtained in step (1) dropwise to (2), after the dropwise addition is complete, continue the reflux reaction and stop heating; the reaction solution is diluted, filtered, and the filtrate acidified , separation, drying, and ethanol recrystallization to obtain the target product. Pure product purity > 98%. The raw materials required by the method of the invention are simple and easy to obtain, the operation process is simple and safe, the reaction time is short, the cost is low, the yield is high, the method is suitable for industrial scale production, and has strong practicability.
Description
技术领域technical field
本发明属杂环化合物制备方法领域，尤其涉及一种以5，5-二苯基乙内酰脲为起始原料，合成3-羧甲基-5，5-二苯基海因的方法。The invention belongs to the field of preparation methods of heterocyclic compounds, and in particular relates to a method for synthesizing 3-carboxymethyl-5,5-diphenylhydantoin by using 5,5-diphenylhydantoin as a starting material.
背景技术Background technique
5，5-二取代海因-3-乙酸衍生物具有广泛的药理活性，如抗球虫病、抗惊厥、抗痉挛、作为利尿剂等，并且对神经系统有影响，市场需求广泛。目前，已报道的合成3-羧甲基-5，5-二苯基海因的方法，采用两步法进行。首先，由5，5-二苯基海因与氯乙酸乙酯反应，在乙醇和钠存在的条件下，回流24h，烷基化反应生成5，5-二苯基海因-3-乙酸乙酯。然后，乙基5，5-二苯基海因-3-乙酸酯在氢氧化钠的乙醇溶液中，回流发生皂化反应，经过滤、洗涤、干燥得到5，5-二苯基海因-3-乙酸钠；5，5-二苯基海因-3-乙酸钠经酸化、重结晶得到3-羧甲基-5，5-二苯基海因，总产率为64％(J.Med.Chem.，1965，vol 8：120-122)。该方法原料价格昂贵、操作条件苛刻、反应时间长、产率低，反应过程中产生氢气，易爆炸。操作工艺存在一定的局限性。5,5-disubstituted hydantoin-3-acetic acid derivatives have a wide range of pharmacological activities, such as anticoccidiosis, anticonvulsions, antispasmodics, as diuretics, etc., and have effects on the nervous system, and the market demand is extensive. Currently, the reported method for synthesizing 3-carboxymethyl-5,5-diphenylhydantoin uses a two-step method. First, react 5,5-diphenylhydantoin with ethyl chloroacetate, in the presence of ethanol and sodium, reflux for 24 hours, and generate 5,5-diphenylhydantoin-3-acetic acid ethyl ester. Then, ethyl 5,5-diphenylhydantoin-3-acetate was refluxed in ethanol solution of sodium hydroxide to undergo saponification reaction, and 5,5-diphenylhydantoin-3-acetate was obtained by filtering, washing and drying. 3-sodium acetate; 5,5-diphenylhydantoin-3-sodium acetate obtained 3-carboxymethyl-5,5-diphenylhydantoin through acidification and recrystallization, and the total yield was 64% (J. Med. Chem., 1965, vol 8:120-122). The method has expensive raw materials, harsh operating conditions, long reaction time, low yield, hydrogen gas is generated during the reaction process, and is prone to explosion. There are certain limitations in the operation process.
发明内容Contents of the invention
本发明的目的在于提供一种3-羧甲基-5，5-二苯基海因的合成方法，该方法原料简单易得，操作过程简便、安全，反应时间短，成本低，产率高。The object of the present invention is to provide a kind of synthetic method of 3-carboxymethyl-5,5-diphenylhydantoin, the raw material of this method is simple and easy to get, the operation process is simple and safe, the reaction time is short, the cost is low, and the yield is high .
为达到上述目的，本发明是这样实现的：To achieve the above object, the present invention is achieved in that:
一种制备3-羧甲基-5，5-二苯基海因的方法，可按如下步骤依次进行：A method for preparing 3-carboxymethyl-5,5-diphenylhydantoin, which can be carried out sequentially according to the following steps:
(1)将氯乙酸或溴乙酸与碱液在室温搅拌条件下进行反应，所得溶液待用；(1) reacting chloroacetic acid or bromoacetic acid and lye under stirring conditions at room temperature, and the resulting solution is for use;
(2)将5，5-二苯基乙内酰脲与碱液混和，于搅拌条件下，加热至回流；(2) Mix 5,5-diphenylhydantoin with lye, and heat to reflux under stirring;
(3)将步骤(1)所得溶液，滴加到(2)中，滴加完毕，继续回流反应，停止加热；反应液经稀释、过滤、酸化滤液、分离、干燥、乙醇重结晶，即得目标产物。(3) Add the solution obtained in step (1) dropwise to (2), after the dropwise addition, continue the reflux reaction and stop heating; the reaction solution is diluted, filtered, acidified filtrate, separated, dried, and ethanol recrystallized to obtain target product.
作为一种优选方案，本发明所述步骤(1)或步骤(2)中，碱液中的碱为氢氧化物和碳酸盐中的一种或其混合物；碱液中的溶剂为水、二甲基亚砜、丙酮、四氢呋喃、乙腈、二氧六环、甲醇、乙醇、丙醇、异丙醇、丁醇中的一种或其混合溶剂。As a preferred version, in step (1) or step (2) of the present invention, the alkali in the lye is one or a mixture thereof in hydroxide and carbonate; the solvent in the lye is water, One of dimethyl sulfoxide, acetone, tetrahydrofuran, acetonitrile, dioxane, methanol, ethanol, propanol, isopropanol, butanol or a mixed solvent thereof.
作为另一种优选方案，本发明所述步骤(3)中，回流反应时间为1h～5h。As another preferred solution, in the step (3) of the present invention, the reflux reaction time is 1 h to 5 h.
进一步地，本发明所述步骤(3)中，稀释步骤采用的溶剂为水。Further, in step (3) of the present invention, the solvent used in the dilution step is water.
更进一步地，本发明所述步骤(3)中，酸化步骤采用质量浓度为1％～35％的盐酸或质量浓度为1％～35％的硫酸。Furthermore, in the step (3) of the present invention, the acidification step uses hydrochloric acid with a mass concentration of 1% to 35% or sulfuric acid with a mass concentration of 1% to 35%.
另外，本发明所述步骤(3)中，酸化后溶液的pH值控制在1～3范围内。In addition, in the step (3) of the present invention, the pH value of the acidified solution is controlled within the range of 1-3.
其次，本发明所述步骤(3)中，分离过程采用水或质量浓度为1％～10％的碳酸钠水溶液或质量浓度为1％～10％的碳酸氢钠水溶液洗涤滤饼至中性。Secondly, in the step (3) of the present invention, the separation process uses water or an aqueous sodium carbonate solution with a mass concentration of 1% to 10% or an aqueous sodium bicarbonate solution with a mass concentration of 1% to 10% to wash the filter cake to neutrality.
再次，本发明所述步骤(1)或步骤(2)中，碱液的摩尔浓度为0.1mol/L～5mol/L。Again, in the step (1) or step (2) of the present invention, the molar concentration of the lye is 0.1mol/L˜5mol/L.
本发明所述步骤(1)中，氯乙酸或溴乙酸与碱液中的碱的摩尔比为1∶0.3～2；所述步骤(2)中，5，5-二苯基乙内酰脲与碱液中的碱的摩尔比为1∶0.5～2；所述步骤(2)中的5，5-二苯基乙内酰脲与所述步骤(1)中的氯乙酸或溴乙酸的摩尔比为1∶1～2。In the step (1) of the present invention, the mol ratio of chloroacetic acid or bromoacetic acid to the alkali in the lye is 1: 0.3～2; In the described step (2), 5,5-diphenylhydantoin The mol ratio with the alkali in the lye is 1: 0.5～2; The 5,5-diphenylhydantoin in the described step (2) and the chloroacetic acid or bromoacetic acid in the described step (1) The molar ratio is 1:1-2.
3-羧甲基-5，5-二苯基海因，是一种白色粉末，分子式为C17H14N2O4，结构式为：3-Carboxymethyl-5,5-diphenylhydantoin is a white powder with a molecular formula of C 17 H 14 N 2 O 4 and a structural formula of:
本发明与以往技术相比具有如下显著优点：Compared with the prior art, the present invention has the following significant advantages:
(1)本发明所公开的工艺，反应过程可以不使用有机溶剂，在水相中进行，更符合绿色、环保的要求。(1) In the process disclosed in the present invention, the reaction process can be carried out in the water phase without using an organic solvent, which is more in line with the requirements of green and environmental protection.
(2)本发明采用的原料简单易得，操作过程简便、安全，反应时间短，成本低，产率高，适于工业规模化生产，具有较强的实用性。(2) The raw materials used in the present invention are simple and easy to obtain, the operation process is simple and safe, the reaction time is short, the cost is low, and the yield is high, which is suitable for industrial scale production and has strong practicability.
具体实施方式Detailed ways
下面通过具体实施方式对本发明作进一步描述。本发明的保护范围不仅局限于下列内容的表述。The present invention will be further described below through specific embodiments. The scope of protection of the present invention is not limited to the expression of the following content.
实施例1：Example 1:
将60mmol氯乙酸与60mL浓度为1mol/L的氢氧化钠水溶液反应，制得氯乙酸钠溶液，备用。在500mL反应瓶中，加入50mmol 5，5-二苯基乙内酰脲和55mL浓度为1mol/L的氢氧化钠水溶液，搅拌条件下加热至回流；然后于30min内缓慢加入备用的氯乙酸钠溶液，加入结束后，继续回流反应3h。反应结束后，补加80mL水，趁热过滤、分离。待滤液降至室温，滴加质量浓度为5％的盐酸，酸化至PH值为3。分离固体产品，水洗、干燥、乙醇重结晶，得白色晶体3-羧甲基-5，5-二苯基海因。纯产品收率为68％，m.p.：249～252℃。经液相色谱测定，产品纯度为98.5％。3-羧甲基-5，5-二苯基海因经IR，1H NMR，13C NMR，质谱进行表征。分析结果如下：React 60mmol of chloroacetic acid with 60mL of 1mol/L aqueous sodium hydroxide solution to prepare sodium chloroacetate solution for later use. In a 500mL reaction flask, add 50mmol 5,5-diphenylhydantoin and 55mL aqueous sodium hydroxide solution with a concentration of 1mol/L, and heat to reflux under stirring; then slowly add spare sodium chloroacetate within 30min After the solution was added, the reflux reaction was continued for 3h. After the reaction, add 80mL of water, filter while hot, and separate. After the filtrate was cooled to room temperature, hydrochloric acid with a mass concentration of 5% was added dropwise to acidify to a pH value of 3. The solid product was isolated, washed with water, dried, and recrystallized from ethanol to obtain 3-carboxymethyl-5,5-diphenylhydantoin as white crystals. The pure product yield is 68%, mp: 249～252°C. As determined by liquid chromatography, the product purity is 98.5%. 3-Carboxymethyl-5,5-diphenylhydantoin was characterized by IR, 1 H NMR, 13 C NMR and mass spectrometry. The analysis results are as follows:
IR(KBr压片法)：3467，3210，3122，2936，1777，1739，1720，1596，1496，1450，1250，1195，1120，768cm-1。IR (KBr tablet method): 3467, 3210, 3122, 2936, 1777, 1739, 1720, 1596, 1496, 1450, 1250, 1195, 1120, 768 cm -1 .
1H NMR(DMSO-d6，500MHz)δH：11.12(s，1H，COOH)，9.33(s，1H，NH)，7.42-7.32(m，10H，ArH)，4.16(s，2H，CH2)ppm。 1 H NMR (DMSO-d 6 , 500MHz) δ H : 11.12 (s, 1H, COOH), 9.33 (s, 1H, NH), 7.42-7.32 (m, 10H, ArH), 4.16 (s, 2H, CH 2 ) ppm.
13C NMR(DMSO-d6，500MHz)δC：174.7，173.0，168.5，139.9，128.4，127.9，126.8，70.2，31.7ppm。 13 C NMR (DMSO-d 6 , 500 MHz) δ C : 174.7, 173.0, 168.5, 139.9, 128.4, 127.9, 126.8, 70.2, 31.7 ppm.
MS (ESI)：m/z 311(M+H)+。MS (ESI): m/z 311 (M+H) + .
实施例2：Example 2:
将60mmol溴乙酸与30mL浓度为1mol/L的碳酸钾水溶液反应，制得溴乙酸钾溶液，备用。在500mL反应瓶中，加入50mmol 5，5-二苯基乙内酰脲和27mL浓度为1mol/L的碳酸钾水溶液，搅拌条件下加热至回流；然后于30min内缓慢加入备用的溴乙酸钾溶液，加入结束后，继续回流反应3h。反应结束后，补加80mL水，趁热过滤、分离。待滤液降至室温，滴加质量浓度为5％的硫酸，酸化至PH值为3。分离固体产品，水洗、干燥、乙醇重结晶，得白色晶体3-羧甲基-5，5-二苯基海因。纯产品收率为65％，m.p.：248～250℃。经液相色谱测定，产品纯度为98.5％。3-羧甲基-5，5-二苯基海因经IR，1H NMR，13C NMR，质谱进行表征，表征结果与实施例1一致。React 60mmol of bromoacetic acid with 30mL of 1mol/L potassium carbonate aqueous solution to prepare potassium bromoacetate solution for later use. In a 500mL reaction flask, add 50mmol 5,5-diphenylhydantoin and 27mL aqueous potassium carbonate solution with a concentration of 1mol/L, and heat to reflux under stirring; then slowly add spare potassium bromoacetate solution within 30min , After the addition, the reflux reaction was continued for 3h. After the reaction, add 80mL of water, filter while hot, and separate. After the filtrate was cooled to room temperature, sulfuric acid with a mass concentration of 5% was added dropwise to acidify to a pH value of 3. The solid product was isolated, washed with water, dried, and recrystallized from ethanol to obtain 3-carboxymethyl-5,5-diphenylhydantoin as white crystals. The pure product yield is 65%, mp: 248～250°C. As determined by liquid chromatography, the product purity is 98.5%. 3-carboxymethyl-5,5-diphenylhydantoin was characterized by IR, 1 H NMR, 13 C NMR, and mass spectrometry, and the characterization results were consistent with those in Example 1.
实施例3：Example 3:
将60mmol氯乙酸与60mL浓度为1mol/L的氢氧化钾水溶液反应，制得氯乙酸钾溶液，备用。在500mL反应瓶中，加入50mmol 5，5-二苯基乙内酰脲和55mL浓度为1mol/L的氢氧化钾水溶液，搅拌条件下加热至回流；然后于30min内缓慢加入备用的氯乙酸钾溶液，加入结束后，继续回流反应3h。反应结束后，补加80mL水，趁热过滤、分离，待滤液降至室温，滴加质量浓度为5％的盐酸，酸化至PH值为3。分离固体产品，水洗、干燥、乙醇重结晶，得白色晶体3-羧甲基-5，5-二苯基海因。纯产品收率为72％，m.p.：248～251℃。经液相色谱测定，产品纯度为98.5％。3-羧甲基-5，5-二苯基海因经IR，1H NMR，13C NMR，质谱进行表征，表征结果与实施例1一致。React 60mmol of chloroacetic acid with 60mL of 1mol/L potassium hydroxide aqueous solution to prepare potassium chloroacetate solution for later use. In a 500mL reaction flask, add 50mmol 5,5-diphenylhydantoin and 55mL aqueous potassium hydroxide solution with a concentration of 1mol/L, and heat to reflux under stirring; then slowly add spare potassium chloroacetate within 30min After the solution was added, the reflux reaction was continued for 3h. After the reaction, add 80mL of water, filter and separate while it is hot, wait for the filtrate to cool down to room temperature, add dropwise hydrochloric acid with a mass concentration of 5%, and acidify to a pH of 3. The solid product was isolated, washed with water, dried, and recrystallized from ethanol to obtain 3-carboxymethyl-5,5-diphenylhydantoin as white crystals. The pure product yield is 72%, mp: 248～251°C. As determined by liquid chromatography, the product purity is 98.5%. 3-carboxymethyl-5,5-diphenylhydantoin was characterized by IR, 1 H NMR, 13 C NMR, and mass spectrometry, and the characterization results were consistent with those in Example 1.
可以理解地是，以上关于本发明的具体描述，仅用于说明本发明而并非受限于本发明实施例所描述的技术方案，本领域的普通技术人员应当理解，仍然可以对本发明进行修改或等同替换，以达到相同的技术效果；只要满足使用需要，都在本发明的保护范围之内。It can be understood that the above specific descriptions of the present invention are only used to illustrate the present invention and are not limited to the technical solutions described in the embodiments of the present invention. Those of ordinary skill in the art should understand that the present invention can still be modified or Equivalent replacements to achieve the same technical effect; as long as they meet the needs of use, they are all within the protection scope of the present invention.
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