CN1382686A - Process for preparing 3-aminobenzoylamine - Google Patents
Process for preparing 3-aminobenzoylamine Download PDFInfo
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- CN1382686A CN1382686A CN 01115402 CN01115402A CN1382686A CN 1382686 A CN1382686 A CN 1382686A CN 01115402 CN01115402 CN 01115402 CN 01115402 A CN01115402 A CN 01115402A CN 1382686 A CN1382686 A CN 1382686A
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- aminobenzoate
- aminobenzamide
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Abstract
A process for preparing 3-aminobenzoylamin (3-AB) features that ammonolysis reaction of 30-aminobenzoate at 150 deg.C. The said 3-aminobenzoate may be 3-methyl (or ethyl, or propyl) aminobenzoate. Its advantages are only one-step reaction, high output rate u pto 60%, and easy post-treating.
Description
The present invention relates to the field of chemical synthesis, be specifically related to a kind of preparation method of the 3-aminobenzamide as the ADPRT inhibitor.
In recent years, study effect and the inhibitor itself of this enzyme in the dna damage reparation with the ADPRT inhibitor and caused extensive interest as radiation, chemotherapeutic sensitizer.As the 3-aminobenzamide (3-AB) of this ADPRT inhibitor, have the report of synthetic method abroad, and the domestic finished product that does not still have this compound at present.
In the synthetic bibliographical information of relevant 3-aminobenzamide, (1949) such as Jacobs etc. (1917) and Macovski are successively with FeSO
4+ NH
4OH and CaCl
2+ Zn nitro compound reducing becomes in the report of amine, comprises the m-nitro methane amide and is reduced to m-aminophenyl methane amide (3-AB).Its reaction formula is:
Nineteen eighty-two, Japanese Patent 8221320 reported a series of hypoglycemic agentss, general formula such as I (wherein comprising 3-AB).With 3-aminobenzoyl Isopropylamine is example.Its synthetic route is as follows:
Aforesaid method is to obtain 3-aminobenzamide (3-AB) by the 3-nitrobenzoyl chloride through benzamide and nitroreduction, and synthetic route is long, and step is numerous and diverse, and the aftertreatment of the oily mater that obtains is difficulty comparatively.
In order to overcome above-mentioned shortcoming, the object of the present invention is to provide a kind of more easy synthetic method, and make yield higher, aftertreatment is more or less freely.
For achieving the above object, the present invention utilizes the raw material 3-Aminobenzoate of easy acquisition, separates a step through ammonia and makes 3-aminobenzamide (3-AB).Reaction formula is as follows:
The method for preparing the 3-aminobenzamide recited above, described ammonolysis reaction reacts under room temperature to 150 degree.
The method for preparing the 3-aminobenzamide as mentioned above, used 3-Aminobenzoate can be 3-Methyl anthranilate, 3-subcutin and 3-propyl aminobenzoate.
Particularly, the method for the described 3-of preparation aminobenzamide comprises the steps:
1) the 3-Aminobenzoate is dissolved in alcohol and forms solution, places in the withstand voltage device of refrigerative, to wherein adding strong aqua, and feeds ammonia and makes solution saturated;
2) with behind the container covered and enclosed, in≤150 ℃ of heating 5 to 10 hours;
3) cooling back opening, with TLC detection reaction liquid, raw material point disappears, and behind the superfluous ammonia that volatilizees, material is to oily matter in the concentrating under reduced pressure container;
4) soluble impurity in the adding dissolution with solvents oily matter is born solid, solid collected by filtration;
5) the above-mentioned solid of water recrystallization obtains product.
Wherein, the described 3-Aminobenzoate of step 1) is 3-Methyl anthranilate, 3-subcutin and 3-propyl aminobenzoate, and used correspondent alcohol is methyl alcohol, ethanol and propyl alcohol; Step 2) temperature is preferably room temperature to 120 degree; The step 4) solvent for use is benzene and ethyl acetate.
Aforesaid method shortened for two steps than foreign literature synthesis method.Method is easy, and yield can reach about 60%.Simultaneously, the improvement of aftertreatment makes isolating oily product more easily become crystallization, thereby obtains effect preferably.
Prove reliable in quality with the inventive method synthetic 3-aminobenzamide (3-AB) through chemical analysis (element, mass spectrum and Infrared spectroscopy) among the embodiment.
Fig. 1 is the inventive method synthetics mass spectrum;
Fig. 2 (a) is the inventive method synthetics infrared spectrogram;
Fig. 2 (b) is external commodity infrared spectrogram.
Ultimate analysis:
Analytical procedure: use the automatic microanalyser of CHN (1106 elemental analysers, Italy card Raul Bagong department) to test.
The result:
Ultimate analysis: C
7H
8N
2O.H
2O
Calculated value %:C54.55, H6.49, N18.18
Measured value %:C55.01, H6.46, N18.86
Mass spectroscopy
Analytical procedure: MS MAT771 type instrument.
Result: m/z 137 (M
++ 1), 136 base peaks, 272 (2M
+), 273 (2M
++ 1);
Mass spectrum is referring to Fig. 1.
Infrared spectra
Analytical procedure: Beckman4260 type instrument, pressing potassium bromide troche.
The result: relatively infrared spectra is in full accord for synthetics and known sample (claiming standard substance temporarily).IR(cm
-1)：3390-3190(-NH
2)，1690(C＝O)，1400(C-N)，800-640(N-H)
Collection of illustrative plates is relatively seen Fig. 2.
Biological test results
3-aminobenzamide (3-AB) can suppress the reclosing of Hela S3 dna chain breakage under non-toxic concn, and can reduce Hela S3 cell according to the back current deposit rate.3-A does not separately cause the DNA splitting of chain with the insulation of Hela S3 cell, and the while is not seen the toxic reaction of pair cell.
In addition, observe 3-AB to the inhibition that DNA splitting of chain reclosing is repaired after Zhengguangmycin A5 is handled of Hela S3 cell.Thereby 3-AB can strengthen Zhengguangmycin A5 and thermotherapy uses 3-AB to provide foundation as sensitizer to the lethal effect of Hela S3 cell when clinically tumour being carried out radiotherapy chemotherapy and thermotherapy.
Biological experiment conclusive evidence 3-AB has reached the requirement of base application research as new radiation-sensitizing agents.
Embodiment one:
3-subcutin (Rf 0.83 benzene-acetone 1: 1) 15g, ethanol 30ml and strong aqua (27%) 30ml logical ammonia under the reactor water-cooled is saturated, add a cover, in bathing 120 ℃ of heating of temperature 9h, cold back opening, TLC detects has not had the raw material spot, treat to carry out concentrating under reduced pressure after the ammonia volatilization, residuum is carried decon with benzene and ethyl acetate, and water-cooled oily matter gets solid, through the water recrystallization, obtain product.
After testing, product mp112～115 ℃ (113～114 ℃ of literature values; 79～80 ℃ in hydrate), Rf0.29 (benzene-acetone 1: 1), MS m/z:137 (M
++ 1), base peak 136.Ultimate analysis C
7H
8N
2O-H
2O calculated value %C54.55, H6.49 N18.18; Measured value %C55.0, H6.46, N18.86; Standard substance C55.19, H6.41, N18.86.Infrared spectra IR (cm
-1): 3390-3190 (NH
2), 1690 (C=O), 1400 (C-N), 800-640 (N-H).IR is consistent with standard substance.
Embodiment two:
Identical with the embodiment method, adopt 3-Methyl anthranilate 15g, methyl alcohol 30ml and strong aqua (27%) 30ml logical ammonia under the reactor water-cooled is saturated, adds a cover, react in kept at room temperature overnight, to the no raw material spot of TLC detection, uncap, treat to carry out concentrating under reduced pressure after the ammonia volatilization, residuum is carried decon with benzene and ethyl acetate, water-cooled oily matter gets solid, through the water recrystallization, obtains product.
Embodiment three:
Identical with embodiment one method, use 3-propyl aminobenzoate 15g, propyl alcohol 30ml and strong aqua (27%) 30ml logical ammonia under the reactor water-cooled is saturated, adds a cover, heat a few hours for 120 ℃ to 150 ℃ in bathing temperature, cold back opening, TLC detects has not had the raw material spot, treats to carry out concentrating under reduced pressure after the ammonia volatilization, residuum is carried decon with benzene and ethyl acetate, water-cooled oily matter gets solid, through the water recrystallization, obtains product.
Claims (7)
1, a kind of method for preparing the 3-aminobenzamide may further comprise the steps: with the 3-Aminobenzoate is raw material, makes product through one step of ammonolysis reaction.
2, the method for preparing the 3-aminobenzamide according to claim 1 is characterized in that, described ammonolysis reaction reacts under room temperature to 150 degree.
3, the method for preparing the 3-aminobenzamide according to claim 1 is characterized in that, used 3-Aminobenzoate can be 3-Methyl anthranilate, 3-subcutin and 3-propyl aminobenzoate.
4, the method for preparing the 3-aminobenzamide according to claim 1 is characterized in that, the reaction concrete steps comprise:
1) the 3-Aminobenzoate is dissolved in alcohol and forms solution, places in the withstand voltage device of refrigerative, to wherein adding strong aqua, and feeds ammonia and makes solution saturated;
2) with behind the container covered and enclosed, in≤150 ℃ of heating 5 to 10 hours;
3) cooling back opening, with TLC detection reaction liquid, raw material point disappears, and behind the superfluous ammonia that volatilizees, material is to oily matter in the concentrating under reduced pressure container;
4) soluble impurity in the adding dissolution with solvents oily matter is born solid, solid collected by filtration;
5) the above-mentioned solid of water recrystallization obtains product.
5, the method for preparing the 3-aminobenzamide according to claim 4, it is characterized in that, wherein, the described 3-Aminobenzoate of step 1) is 3-Methyl anthranilate, 3-subcutin and 3-propyl aminobenzoate, and correspondent alcohol is methyl alcohol, ethanol and propyl alcohol.
6, the method for preparing the 3-aminobenzamide according to claim 4 is characterized in that, wherein, step 2) temperature is room temperature to 120 degree.
7, the method for preparing the 3-aminobenzamide according to claim 4 is characterized in that, wherein, the step 4) solvent for use is benzene and ethyl acetate.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB011154020A CN1137879C (en) | 2001-04-24 | 2001-04-24 | Process for preparing 3-aminobenzoylamine |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB011154020A CN1137879C (en) | 2001-04-24 | 2001-04-24 | Process for preparing 3-aminobenzoylamine |
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| Publication Number | Publication Date |
|---|---|
| CN1382686A true CN1382686A (en) | 2002-12-04 |
| CN1137879C CN1137879C (en) | 2004-02-11 |
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|---|---|---|---|
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103145580A (en) * | 2013-03-11 | 2013-06-12 | 黄河三角洲京博化工研究院有限公司 | Method for preparing 2-(4-fluorobenzene formyl) benzamide |
| CN104130170A (en) * | 2014-08-11 | 2014-11-05 | 济南大学 | Synthesis method of 4-Hydroxythiobenzamide |
| CN112142614A (en) * | 2020-10-09 | 2020-12-29 | 东莞理工学院 | Preparation method of 3-aminobutanamide and/or 3-hydroxybutyramide |
| CN112745239A (en) * | 2020-12-30 | 2021-05-04 | 王植源 | Preparation method of 4-aminobenzoic acid and derivatives thereof |
-
2001
- 2001-04-24 CN CNB011154020A patent/CN1137879C/en not_active Expired - Fee Related
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103145580A (en) * | 2013-03-11 | 2013-06-12 | 黄河三角洲京博化工研究院有限公司 | Method for preparing 2-(4-fluorobenzene formyl) benzamide |
| CN103145580B (en) * | 2013-03-11 | 2015-04-08 | 黄河三角洲京博化工研究院有限公司 | Method for preparing 2-(4-fluorobenzene formyl) benzamide |
| CN104130170A (en) * | 2014-08-11 | 2014-11-05 | 济南大学 | Synthesis method of 4-Hydroxythiobenzamide |
| CN112142614A (en) * | 2020-10-09 | 2020-12-29 | 东莞理工学院 | Preparation method of 3-aminobutanamide and/or 3-hydroxybutyramide |
| CN112745239A (en) * | 2020-12-30 | 2021-05-04 | 王植源 | Preparation method of 4-aminobenzoic acid and derivatives thereof |
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| Publication number | Publication date |
|---|---|
| CN1137879C (en) | 2004-02-11 |
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