CN107903177A - The preparation method of 4 methoxyl group, 2,3 Dinitrobenzenecarbonitrile - Google Patents
The preparation method of 4 methoxyl group, 2,3 Dinitrobenzenecarbonitrile Download PDFInfo
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- CN107903177A CN107903177A CN201711257751.1A CN201711257751A CN107903177A CN 107903177 A CN107903177 A CN 107903177A CN 201711257751 A CN201711257751 A CN 201711257751A CN 107903177 A CN107903177 A CN 107903177A
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- methoxyl groups
- dinitrobenzenecarbonitrile
- bromo
- preparation
- methoxyl group
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
- C07C201/06—Preparation of nitro compounds
- C07C201/08—Preparation of nitro compounds by substitution of hydrogen atoms by nitro groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
- C07C201/06—Preparation of nitro compounds
- C07C201/12—Preparation of nitro compounds by reactions not involving the formation of nitro groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
- C07C253/14—Preparation of carboxylic acid nitriles by reaction of cyanides with halogen-containing compounds with replacement of halogen atoms by cyano groups
Abstract
The present invention relates to the preparation method of 4 methoxyl group, 2,3 Dinitrobenzenecarbonitrile.Mainly solve the technical problem that the compound lacks Industrialized synthesis method.The method of the present invention is divided into 2 steps：The first step, reacts to obtain 1 bromine, 4 methoxyl group, 2,3 dinitro benzene by 1 bromine, 4 methoxyl group, 2 nitrobenzene is added dropwise under the concentrated sulfuric acid and concentrated nitric acid priority low temperature；Second step, 1 bromine, 4 methoxyl group, 2,3 dinitro benzene, which is dissolved in N methyl pyrrolidones, adds cuprous cyanide pyroreaction generation 4 methoxyl group, 2,3 Dinitrobenzenecarbonitrile.
Description
Technical field
4- methoxyl group -2,3- Dinitrobenzenecarbonitriles are synthesized by the bromo- 4- methoxyl groups -2- nitrobenzenes of 1- the present invention relates to a kind of
Method.
Background technology
Molecular perspectives：Molecule and its derivative involved in the present invention are the important centres for having synthesized CHROMATOGRAPHIC FRACTIONATION AND MASS antibody drug
Body.Research shows, antibody drug conjugates（antibody drug conjugates, ADC）Realize large biological molecule and small
The combination among the strong ones of molecule toxin advantage, is considered as the important means of future tumors treatment.Maytansine and its derivative are at this stage
One of toxin that ADC is most widely used, using ADC medicine Ah mores' Herceptins of the toxoid according to ester（ATE）Listing,
The indication leukemia of ADC is successfully expanded into other entity tumors.
The content of the invention
The object of the present invention is to provide a kind of preparation method by 4- methoxyl group -2,3- Dinitrobenzenecarbonitriles.Mainly solve
The compound lacks the technical problem of Industrialized synthesis method.
Technical scheme：A kind of preparation method of 4- methoxyl groups -2,3- Dinitrobenzenecarbonitrile, including following step
Suddenly, the method for the present invention is divided into 2 steps：The first step, will be added dropwise to the bromo- 4- methoxyl groups -2- of 1- under the concentrated sulfuric acid and concentrated nitric acid priority low temperature
Nitrobenzene reacts to obtain the bromo- 4- methoxyl groups -2,3- dinitro benzenes of 1-；Second step, bromo- 4- methoxyl groups -2, the 3- dinitro benzene dissolvings of 1-
The method that cuprous cyanide pyroreaction generation 4- methoxyl group -2,3- Dinitrobenzenecarbonitriles are added in 1-methyl-2-pyrrolidinone；Instead
Answer formula as follows：
。
Low temperature described in the first step is 0 DEG C, and reaction temperature is 0 DEG C-room temperature（20-30℃）, the bromo- 4- methoxyl groups -2- nitros of 1-
Benzene and concentrated nitric acid, the molar ratio of the concentrated sulfuric acid are 1:(2~3):(2~3)；High temperature described in second step is 150 DEG C, the bromo- 4- methoxyl groups of 1--
The molar ratio of 2,3- dinitro benzenes and cuprous cyanide is 1:3~5.
The beneficial effects of the invention are as follows：Route is short, easy to operate, and cost is low, and purifying is simple, is a kind of efficient, energy saving
The method for synthesizing 4- methoxyl group -2,3- Dinitrobenzenecarbonitriles.The invention belongs to initiate, pertinent literature is had no before this and reports this molecule
Synthetic method.
Embodiment
Embodiment 1,
Step 1：
The bromo- 4- methoxyl groups -2- nitrobenzenes of 1- are first added into three-necked flask and are cooled to 0 DEG C, keep temperature that dense nitre is slowly added dropwise successively
Acid and the concentrated sulfuric acid, be warmed to room temperature reaction 1 it is small when obtain bromo- 4- methoxyl groups -2, the 3- dinitro benzenes of intermediate 1-, the bromo- 4- methoxyl groups of 1- -
2- nitrobenzenes and concentrated nitric acid, the molar ratio of the concentrated sulfuric acid are 1:2:3, reaction solution is diluted with water, and is then extracted with ethyl acetate, concentration
After add petroleum ether：Ethyl acetate=3:1 mixed solvent, is stirred 20 minutes at room temperature.Filter residue is collected by filtration and is dried to obtain
The bromo- 4- methoxyl groups -2,3- dinitro benzenes of intermediate 1-.1H NMR (400 MHz, CDCl3) δ 7.79 (d, J = 4.8 Hz
1H), 7.16 (d, J = 9.2 Hz 1H), 4.00 (s, 3H).
Step 2：
Bromo- 4- methoxyl groups -2, the 3- dinitro benzenes of 1- are dissolved in 1-methyl-2-pyrrolidinone, add cyaniding Asia ketone, 1- at room temperature
The molar ratio of bromo- 4- methoxyl groups -2,3- dinitro benzenes and cuprous cyanide is 1:4, be warming up to 150 DEG C reaction 3 it is small when generate 4- first
Epoxide -2,3- Dinitrobenzenecarbonitriles.Reaction solution is diluted with water, and is then extracted with ethyl acetate, and after concentration, uses petroleum ether:Acetic acid
Ethyl ester volume ratio=3:1 mixed solvent washing, dry cake obtain 4- methoxyl group -2,3- Dinitrobenzenecarbonitriles.MS, (M-Me
) +: 208.1; 1H NMR (400 MHz, CDCl3) δ 7.95 (d, J = 9.2 Hz 1H), 7.42 (d, J =
9.2 Hz 1H), 4.10 (s, 3H)。
Embodiment 2, the bromo- 4- methoxyl groups -2- nitrobenzenes of 1- and concentrated nitric acid, the molar ratio of the concentrated sulfuric acid are 1:3:2,1- bromo- 4-
The molar ratio of methoxyl group -2,3- dinitro benzenes and cuprous cyanide is 1:3, remaining is the same as embodiment 1.
Embodiment 3, the bromo- 4- methoxyl groups -2- nitrobenzenes of 1- and concentrated nitric acid, the molar ratio of the concentrated sulfuric acid are 1:2.5:2.5,1-
The molar ratio of bromo- 4- methoxyl groups -2,3- dinitro benzenes and cuprous cyanide is 1:5, remaining is the same as embodiment 1.
Claims (7)
1. a kind of preparation method of 4- methoxyl groups -2,3- Dinitrobenzenecarbonitrile, it is characterized in that：Comprise the following steps, the first step, will
The concentrated sulfuric acid reacts to obtain the bromo- 4- methoxyl groups -2,3- of 1- with being added dropwise to the bromo- 4- methoxyl groups -2- nitrobenzenes of 1- under concentrated nitric acid priority low temperature
Dinitro benzene；Second step, bromo- 4- methoxyl groups -2, the 3- dinitro benzenes of 1-, which are dissolved in 1-methyl-2-pyrrolidinone, adds cuprous cyanide
The method that pyroreaction generates 4- methoxyl group -2,3- Dinitrobenzenecarbonitriles；Reaction equation is as follows：
。
2. the preparation method of 4- methoxyl groups -2,3- Dinitrobenzenecarbonitrile according to claim 1, it is characterized in that, the bromo- 4- of 1-
Methoxyl group -2- nitrobenzenes and concentrated nitric acid, the molar ratio of the concentrated sulfuric acid are 1:（2~3）:（2~3）.
3. the preparation method of 4- methoxyl groups -2,3- Dinitrobenzenecarbonitrile according to claim 1, it is characterized in that, the first step
The low temperature is 0 DEG C, and reaction temperature is 0 DEG C-room temperature.
4. the preparation method of 4- methoxyl groups -2,3- Dinitrobenzenecarbonitrile according to claim 1, it is characterized in that, the first step
Specially：First keep 0 DEG C and sequentially add concentrated nitric acid and the concentrated sulfuric acid dropwise into the bromo- 4- methoxyl groups -2- nitrobenzenes of 1-, heat up room temperature
React 1 it is small when obtain bromo- 4- methoxyl groups -2, the 3- dinitro benzenes of intermediate 1-.
5. the preparation method of 4- methoxyl groups -2,3- Dinitrobenzenecarbonitrile according to claim 1, it is characterized in that, the bromo- 4- of 1-
The molar ratio of methoxyl group -2,3- dinitro benzene and cuprous cyanide is 1:3~5.
6. the preparation method of 4- methoxyl groups -2,3- Dinitrobenzenecarbonitrile according to claim 1, it is characterized in that, second step
The high temperature is 150 DEG C.
7. the preparation method of 4- methoxyl groups -2,3- Dinitrobenzenecarbonitrile according to claim 1, it is characterized in that, second step
When reaction 3 is small under conditions of 150 DEG C.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711257751.1A CN107903177A (en) | 2017-12-04 | 2017-12-04 | The preparation method of 4 methoxyl group, 2,3 Dinitrobenzenecarbonitrile |
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|---|---|---|---|
| CN201711257751.1A CN107903177A (en) | 2017-12-04 | 2017-12-04 | The preparation method of 4 methoxyl group, 2,3 Dinitrobenzenecarbonitrile |
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| CN201711257751.1A Pending CN107903177A (en) | 2017-12-04 | 2017-12-04 | The preparation method of 4 methoxyl group, 2,3 Dinitrobenzenecarbonitrile |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101648890A (en) * | 2009-09-16 | 2010-02-17 | 常州工程职业技术学院 | Synthesis method of 2-fluoro-4-nitrobenzonitrile |
| CN102199144A (en) * | 2004-01-14 | 2011-09-28 | 诺瓦提斯公司 | Benzimidazole derivatives |
-
2017
- 2017-12-04 CN CN201711257751.1A patent/CN107903177A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102199144A (en) * | 2004-01-14 | 2011-09-28 | 诺瓦提斯公司 | Benzimidazole derivatives |
| CN101648890A (en) * | 2009-09-16 | 2010-02-17 | 常州工程职业技术学院 | Synthesis method of 2-fluoro-4-nitrobenzonitrile |
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Application publication date: 20180413 |