CN111302962A - Rapid method for reducing nitro in aliphatic nitro compound into amino - Google Patents
Rapid method for reducing nitro in aliphatic nitro compound into amino Download PDFInfo
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- CN111302962A CN111302962A CN202010197661.3A CN202010197661A CN111302962A CN 111302962 A CN111302962 A CN 111302962A CN 202010197661 A CN202010197661 A CN 202010197661A CN 111302962 A CN111302962 A CN 111302962A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/04—Formation of amino groups in compounds containing carboxyl groups
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/12—Preparation of carboxylic acid amides by reactions not involving the formation of carboxamide groups
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Abstract
The invention discloses a rapid method for reducing nitro in an aliphatic nitro compound into amino. The invention adopts Raney nickel as a catalyst, hydrazine hydrate as a reducing agent, ethanol or methanol as a solvent, and the reaction is carried out at the reaction temperature of 60-70 ℃, so that the whole reaction of reducing the aliphatic nitro compound into the aliphatic amino compound can be rapidly completed, and the reaction time is not more than 2 hours. The reaction is rapid, no pressurization or sealing is needed, no inert gas protection is needed, the yield is high, and the method is suitable for mass production.
Description
Technical Field
The invention relates to the technical field of organic synthesis, in particular to a rapid method for reducing nitro in an aliphatic nitro compound into amino.
Background
The reduction of nitro compounds to amino compounds is an important reaction in organic synthesis and has important application in various organic synthesis intermediates, medicines, materials and chemical industry. The aromatic nitro compound is cheap and easy to obtain, and the corresponding aromatic amine can be synthesized by using the corresponding aromatic nitro compound as a substrate through simple conversion. Various methods for directly reducing aromatic nitro compounds into aromatic amines have been reported in the literature so far, such as catalytic hydrogenation, metal reduction, alkali sulfide reduction, electrochemical reduction, catalytic hydrogen transfer, glucose reduction, photochemical reduction and enzyme reduction, wherein the metal reduction is simple, low in cost and most widely applied. The reduction of the aromatic nitro compound is relatively simple, the research is more, and the method is mature.
However, the reduction of the aliphatic nitro group into the amino group is more difficult than the reduction of the aromatic nitro group, and the currently widely adopted method is to stir for 24 hours at normal temperature in a hydrogen atmosphere of 304-405 kPa by taking Raney nickel or Pd/C as a catalyst and ethanol as a solvent. This method has some significant disadvantages: firstly, a pressure reaction kettle is used, the reaction can not be carried out under the condition of no pressure reaction kettle, and the requirements on laboratory equipment are strict; secondly, flammable and explosive hydrogen is used, and gaseous hydrogen is difficult to control and operate, is easy to leak and is easy to corrode metal to form hydrogen embrittlement; thirdly, the reaction time is long, generally up to 24 hours, and stirring is needed to be carried out overnight; fourthly, the solubility of the general aliphatic nitro compound in ethanol at normal temperature is very limited, so that the dosage of each time cannot be too much, and the large-scale production of the reaction is limited. If the reaction is heated, the solubility of hydrogen in ethanol is sharply reduced, the reaction is slowed, and the pressure bearing capacity of the pressure kettle is also considered during the heating, and if the reaction is carried out at room temperature, the solubility of the aliphatic nitro compound in ethanol at room temperature is limited, so that the mass production cannot be realized.
Accordingly, the prior art is yet to be improved and developed.
Disclosure of Invention
In view of the defects of the prior art, the invention aims to provide a rapid method for reducing nitro in an aliphatic nitro compound into amino, and aims to solve the problems of flammable and explosive hydrogen and long reaction time in the prior art.
The technical scheme of the invention is as follows:
a rapid method for reducing nitro in aliphatic nitro compound into amino, wherein, aliphatic nitro compound is added into solvent containing catalyst and reducer, and reaction is carried out at 60-70 ℃; the catalyst is Raney nickel, the reducing agent is hydrazine hydrate, hydroxyamine, sodium borohydride or lithium aluminum hydride, and the solvent is a polar solvent with high stability.
Further, the polar solvent is ethanol, methanol, tetrahydrofuran, acetonitrile or acetone.
Further, the reducing agent is hydrazine hydrate, and the solvent is ethanol or methanol.
Further, the amount of the catalyst used was 10 mol%, that is, 5.8g of the catalyst was used per mole of the reactant (aliphatic nitro compound).
Further, the amount of the reducing agent is 150-200 mol%, that is, the amount of the reducing agent used per mol of the reactant is 1.5-2.0 mol.
Furthermore, the reaction time is 30 minutes to 2 hours, and the reaction is basically finished after the titration of the reducing agent is finished according to the using amount of the reducing agent.
Has the advantages that: the invention adopts Raney nickel as a catalyst, uses hydrazine hydrate, hydroxylamine, sodium borohydride or lithium aluminum hydride as a reducing agent, and can rapidly complete the whole reaction of reducing the aliphatic nitro compound into the aliphatic amino compound in a water-soluble solvent at the reaction temperature of 60-70 ℃, and the reaction time is not more than 2 hours. The reaction is rapid, no pressurization or sealing is needed, no inert gas protection is needed, the yield is high, and the method is suitable for mass production.
Detailed Description
The present invention provides a rapid method for reducing nitro groups in aliphatic nitro compounds to amino groups, and the present invention will be described in further detail below in order to make the objects, technical solutions, and effects of the present invention clearer and clearer. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.
In this embodiment, the aliphatic nitro compound means that the carbon atom connected to the nitro group is an aliphatic carbon atom, and is connected to other carbon atoms through a C-C or C-H single bond, and is not connected to other carbon atoms through a large pi conjugated bond, and other structures are not limited. For example, the aliphatic nitro compound may be nitro tert-butane, benzyl nitrate or nitroethylbenzene.
The embodiment of the invention provides a rapid method for reducing nitro in an aliphatic nitro compound into amino, wherein the aliphatic nitro compound is added into a solvent containing a catalyst and a reducing agent and reacts at 60-70 ℃; the catalyst is Raney nickel, the reducing agent is hydrazine hydrate, hydroxyamine, sodium borohydride or lithium aluminum hydride, and the solvent is a water-soluble solvent.
In the embodiment, Raney nickel is used as a catalyst, hydrazine hydrate, hydroxylamine, sodium borohydride or lithium aluminum hydride is used as a reducing agent, and the whole reaction of reducing the aliphatic nitro compound into the aliphatic amino compound can be rapidly completed in a water-soluble solvent at the reaction temperature of 60-70 ℃, wherein the reaction time is not more than 2 hours. The reaction is rapid, no pressurization or sealing is needed, no inert gas protection is needed, the yield is high, and the method is suitable for mass production.
In one embodiment, the water-soluble solvent may be ethanol, methanol, tetrahydrofuran, acetonitrile, propanol, acetone, or the like, but is not limited thereto.
In a specific embodiment, the reducing agent is hydrazine hydrate, and the solvent is ethanol or methanol. That is, in this example, raney nickel is used as a catalyst, hydrazine hydrate is used as a reducing agent, ethanol or methanol is used as a solvent, and the reaction is performed at a reaction temperature of 60-70 ℃, and the specific reaction formula is shown as the following formula. In this example, the reduction of the whole aliphatic nitro compound to aliphatic amino compound can be completed rapidly under the above conditions, and the reaction time is not more than 2 hours. The reaction is rapid, no pressurization or sealing is needed, no inert gas protection is needed, the yield is high, and the method is suitable for mass production. Further, the amount of the catalyst used was 10 mol%, that is, the amount of the catalyst used was 5.8g per mol of the reactants. The amount of the reducing agent is 150-200 mol%, namely the amount of the reducing agent used per mol of reactants is 1.5-2.0 mol. The reaction time is 30 minutes to 2 hours, and is specifically determined according to the dosage of the reducing agent, the titration of the reducing agent is completed, and the reaction is basically finished.
Compared with the prior art, the embodiment has the following advantages:
1. the catalysts are different, expensive metal palladium is needed for reducing the aliphatic nitro compound at present, and the activated metal palladium is loaded on activated carbon, so that the price is high, the preparation is complex, and the embodiment adopts Raney nickel as the catalyst, so that the price is low, the preparation is easy, and the catalyst can be repeatedly used;
2. the reducing agent is different, the existing aliphatic nitro compound is generally reduced by using hydrogen as the reducing agent, the hydrogen is flammable and explosive, has a corrosion effect (hydrogen brittleness) on metal, and has extremely low solubility in an organic solvent (ethanol or methanol), so that the reaction is slow and generally needs 24 hours;
3. different reaction vessels exist, hydrogen is used as a reducing agent for reducing the aliphatic nitro compound, and a high-pressure reaction vessel (pressure reaction kettle) is generally adopted to increase the solubility of the hydrogen in an organic solvent, but the high-pressure reaction kettle is expensive and complex to operate and has certain dangers. The reaction of the embodiment only needs to be carried out in a three-neck flask, the reaction is carried out under normal pressure, the reaction container is easy to obtain, and the protection of inert gas is not needed.
4. The reaction time is different, the existing aliphatic nitro compound reduction adopts Pd/C as a catalyst, hydrogen is used as a reducing agent, the reaction time is generally required to exceed 24 hours, and an overnight reaction is required, while the existing experiment requires that the overnight reaction must be watched by someone, thereby undoubtedly increasing the labor amount. The reaction time of this example can be controlled within 2 hours basically, and the reaction can be finished after the hydrazine hydrate titration is finished. The reaction time is greatly shortened.
The present invention is described in detail below with reference to specific examples.
Example 1: synthesis of Behera amine 1B
To a 250mL three-necked flask equipped with a reflux condenser and a constant pressure dropping funnel, di-tert-butyl 4-nitro-4- (2-tert-butoxycarbonyl-ethyl) -1, 7-heptanedioate (1A) (8.6g), Raney nickel T-1 (3.0g), and methanol (150mL) were added and heated to slight boiling. Hydrazine hydrate (85%, 7.6g) was dissolved in methanol (30mL) and added slowly dropwise to the mixture, boiling vigorously and bubbling out. After the dropwise addition, the reaction is carried out for 30 minutes under the condition of heat preservation, and then the mixture is cooled and filtered by silica gel. The filtrate was collected and the solvent was removed under reduced pressure to obtain a crude product which was purified by column chromatography [ V (petroleum ether): V (ethyl acetate) ═ 2: 1 with a trace amount of ammonium hydroxide ] to obtain a white solid with a yield of 81%. m.p.51-53 deg.C (literature value: 51-52 deg.C); 1H NMR (400MHz, CDCl3) δ:2.23(t, J ═ 7.4Hz,6H),1.67(t, J ═ 8.2Hz,6H),1.43(s, 27H); MS (EI) m/z:415.
Example two: synthesis of second-generation Behera amine 2B of dendrimer
To a 250mL three-necked flask equipped with a reflux condenser and a constant pressure dropping funnel were added di-tert-butyl 4-nitro-4- (2-tert-butoxycarbonyl-ethyl) -1, 7-heptanedioate (2A) (8.6g), Raney nickel T-1 (3.0g), and methanol (150mL), and the mixture was heated to slight boiling. Hydrazine hydrate (85%, 7.6g) was dissolved in methanol (30mL) and added slowly dropwise to the mixture, boiling vigorously and bubbling out. After the dropwise addition, the reaction is carried out for 1 hour under the condition of heat preservation, and then the mixture is cooled and filtered by silica gel. Collecting the filtrate, removing the solvent under reduced pressure to obtain a crude productColumn chromatography purification of [ V (petroleum ether): (ethyl acetate) ═ 2: 1 with trace ammonium hydroxide]White solid was obtained in 81% yield. m.p.191 to 194 ℃ (literature value: 193 to 194 ℃);1H NMR(400MHz,CDCl3)δ:2.19～2.21(m,24H),1.93(t,J＝7.4Hz,18H),1.71(t,J＝8.2Hz,6H),1.41(s,81H)；13C NMR(125MHz,CDCl3)δ:173.1,172.1,82.1,46.4,41.9,29.8,28.8,27.2,18.8,16.3；MS(ESI)m/z:1463.2[M+Na+].
in summary, the invention provides a rapid method for reducing nitro groups in aliphatic nitro compounds into amino groups, which adopts Raney nickel as a catalyst, hydrazine hydrate as a reducing agent, ethanol or methanol as a solvent, and the reaction is carried out at a reaction temperature of 60-70 ℃, so that the whole reaction for reducing the aliphatic nitro compounds into the aliphatic amino compounds can be rapidly completed, and the reaction time is not more than 2 hours. The reaction is rapid, no pressurization or sealing is needed, no inert gas protection is needed, the yield is high, and the method is suitable for mass production.
It is to be understood that the invention is not limited to the examples described above, but that modifications and variations may be effected thereto by those of ordinary skill in the art in light of the foregoing description, and that all such modifications and variations are intended to be within the scope of the invention as defined by the appended claims.
Claims (6)
1. A rapid method for reducing nitro in aliphatic nitro compound into amino is characterized in that the aliphatic nitro compound is added into a solvent containing a catalyst and a reducing agent and reacts at 60-70 ℃; the catalyst is Raney nickel, the reducing agent is hydrazine hydrate, hydroxyamine, sodium borohydride or lithium aluminum hydride, and the solvent is a water-soluble solvent.
2. The rapid method for reducing nitro group in aliphatic nitro compound to amino group according to claim 1, wherein the water-soluble solvent is ethanol, methanol, tetrahydrofuran, acetonitrile, propanol or acetone.
3. The rapid method for reducing nitro group in aliphatic nitro compound to amino group according to claim 1, wherein the reducing agent is hydrazine hydrate, and the solvent is ethanol or methanol.
4. The fast process for reducing nitro groups of aliphatic nitro compounds to amino groups according to claim 3, wherein the amount of the catalyst used is 10 mol%.
5. The fast method for reducing nitro group in aliphatic nitro compound to amino group as claimed in claim 3, wherein the amount of the reducing agent is 150-200 mol%.
6. The fast method for reducing nitro group in aliphatic nitro compound to amino group according to claim 3, wherein the reaction time is 30 minutes to 2 hours.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111672517A (en) * | 2020-07-17 | 2020-09-18 | 浙江海洲制药有限公司 | Preparation method of X-CT contrast agent intermediate |
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2020
- 2020-03-19 CN CN202010197661.3A patent/CN111302962A/en active Pending
Non-Patent Citations (1)
| Title |
|---|
| 马学美等: "一种改进的合成Behera胺方法研究", 《有机化学》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111672517A (en) * | 2020-07-17 | 2020-09-18 | 浙江海洲制药有限公司 | Preparation method of X-CT contrast agent intermediate |
| CN111672517B (en) * | 2020-07-17 | 2023-12-15 | 浙江海洲制药有限公司 | Preparation method of X-CT contrast medium intermediate |
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Application publication date: 20200619 |