CN104529815B - The method of synthesis 2,4-2,4-dinitrophenoxy amine - Google Patents
The method of synthesis 2,4-2,4-dinitrophenoxy amine Download PDFInfo
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- CN104529815B CN104529815B CN201410729653.3A CN201410729653A CN104529815B CN 104529815 B CN104529815 B CN 104529815B CN 201410729653 A CN201410729653 A CN 201410729653A CN 104529815 B CN104529815 B CN 104529815B
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- hydroxylamine salt
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- dinitrophenoxy
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Abstract
The present invention open one synthesis 2, the method of 4 2,4-dinitrophenoxy amine, hydroxylamine salt is added in reaction vessel, water and acetas, n (acetas): n (hydroxylamine salt)=1.0 2.0:1, at a temperature of 15 40 DEG C, drip 30% alkali metal hydroxide aqueous solution and continue to react 1 hour, n (alkali metal hydroxide): n (hydroxylamine salt)=1.5 3；Reaction is warming up to 50 DEG C after terminating, the acetate solution (concentration 50%) of dropping 2,4 dinitrochlorobenzene, and n (2,4 dinitrochlorobenzene): n (hydroxylamine salt)=0.5 1.0, drip complete follow-up continuous reaction 2 hours；Cooling filtration alkali liquor making beating washing refilters；Adding filter cake in reaction vessel, after addition equimolar hydrochloric acid, temperature reaction 13 hours, filters after cooling；Product is obtained after filter cake recrystallizing methanol.Reactions steps of the present invention is short, and raw material is cheap and easy to get, easy and simple to handle, easy industrialized production.
Description
Technical field
The present invention relates to compou nd synthesis method and technology field, particularly to a kind of method of synthesis.
Background technology
2,4-dinitrophenoxy amine (2,4-2,4-dinitrophenoxy amine, O-(dinitrophenyl group) azanol) is in organic synthesis one
Excellent aminating agent, can be used for all kinds of containing secondary nitrogen and the aminating reaction of carbanion compound.Amine is carried out with 2,4-dinitrophenoxy amine
Change the most easy and simple to handle, and be applicable to its molecule, there are other influential compound when nitrosation or reduction subsequently is drawn
Enter amino.
The method being currently used for synthesizing 2,4-2,4-dinitrophenoxy amine has:
1) Eidem (J Heterocyel Chem 1967,4,413) describes with nitrogen in tertiary fourth oxygen formyl chloride protection azanol
After atom, then react introducing aryl on oxygen atom with DNFB, finally by the technique of trifluoroacetic acid hydrolysis.This work
Skill uses tertiary fourth oxygen formyl chloride and trifluoroacetic acid to make raw material, expensive.
2) Japan Kokai 87-70344 discloses and forms N-hydroxyl phthalyl with phthalic anhydride with azanol
Imines, then react with DNFB, then hydrazinolysis or the technique of azanol solution.Though this processing step is short, but hydrazinolysis or hydroxyl
Amine solution troublesome poeration, by-product is not easily recycled, relatively costly.
3) Xin's great waves etc. (Chinese Journal of Pharmaceuticals 1993,03,134-135) describe in the mixed liquor of second cyanogen and ethanol
It is passed through dry hydrogen chloride and prepares ethyl acetimidate hydrochlorate, then react generation acethydroximic acid ethyl ester, oxygen atom with oxammonium hydrochloride.
On carry out virtueization, then by the technique of perchloric acid hydrolysis.This processing step is longer, complex process and troublesome poeration, is unfavorable for big
Produce.
Summary of the invention
The present invention is directed to the above-mentioned deficiency of prior art, it is provided that a kind of raw material is cheap and easy to get, and step is short, easy and simple to handle, holds
The easily method of the synthesis 2,4-2,4-dinitrophenoxy amine of industrialized production.
In order to solve above-mentioned technical problem, the technical solution adopted in the present invention is: first carry out with hydroxylamine salt with acetas
N is protected by oximation reaction, and its reaction equation is shown below:
In formula, R is methyl or ethyl, and HX is hydrochloric acid or sulphuric acid；
Then the product of gained reacts with DNFB, and its reaction equation is shown below:
Then adding hydrochloric acid to be hydrolyzed, its reaction equation is shown below:
Concrete synthesis step is as follows:
(1) in reaction vessel add hydroxylamine salt, water and acetas, then at a temperature of 15-40 DEG C, in reaction vessel
Dropping mass percent is the alkali metal hydroxide aqueous solution of 25-35% and is incubated 1-2 hour；The consumption of water is hydroxylamine salt weight
0.5-2 times of amount, acetas is 1.0-2.0:1 with the mol ratio of hydroxylamine salt, alkali metal hydroxide and the mol ratio of hydroxylamine salt
For 1.5-3.0:1；
(2) insulation is warming up to 40-50 DEG C after terminating, acetate solution (2, the 4-dinitros of dropping DNFB
Chlorobenzene mass percent in the acetate solution configured is 40-50%), after dropping, 40-50 DEG C of insulation 1-2 is little
Time；The mol ratio of added hydroxylamine salt is 0.5-1.0:1 to 1-CHLORO-2,4-DINITROBENZENE with step (1)；
(3) filtering after the material that step (2) synthesizes is down to room temperature, gained filter cake mass percent is 3-5% alkali gold
Belonging to hydroxide aqueous solution making beating washing, filter cake and mass percent are weight between 3-5% alkali metal hydroxide aqueous solution
Ratio is 1:1-2, is the most again filtrated to get filter cake；
(4) in reaction vessel, add step (3) be again filtrated to get filter cake, be subsequently adding with step (2) in 2,4-
The equimolar mass percent of dinitrochlorobenzene be 10-20% hydrochloric acid (equimolar be 1-CHLORO-2,4-DINITROBENZENE with hydrochloric acid mole
Than), then heat to 50-70 DEG C react 1-3 hour, reaction terminate after be down to room temperature (according to room temperature environment at that time, general 15-
30 degree) it is filtrated to get filtrate；
(5) methanol of the 5-6 times of weight of filtrate obtained by step (4) filtrate is heated to reflux, cool down realization heavily tie
Crystalline substance, refilter the crystallization of acquisition 50-60 DEG C, be vacuum dried 3-4 hour under 0.5-0.8MPa, obtain 2,4-2,4-dinitrophenoxy amine
Product.
In above-mentioned steps (1), the consumption of water is preferably 0.8-1.5 times of hydroxylamine salt weight, and very few hydroxylamine salt cannot be dissolved completely and led
Cause the generation of side reaction, too high, cause productivity ratio to decline, energy consumption increases.
In above-mentioned steps (1), alkali metal hydroxide is sodium hydroxide or potassium hydroxide, preferably sodium hydroxide, because of both
Performance is more or less the same, but price differs greatly, and sodium hydroxide can significantly reduce cost.
In above-mentioned steps (1), alkali metal hydroxide is preferably 1.6-2.2:1 with the mol ratio of hydroxylamine salt, crosses low reaction not
Completely, too high, it is easily caused side reaction.
In above-mentioned steps (1), acetas is preferably 1.1-1.5:1 with the mol ratio of hydroxylamine salt, crosses low reaction incomplete, mistake
High wastage of material.
In above-mentioned steps (1), reaction temperature is preferably 20-30 DEG C, crosses low reaction incomplete, too high, is easily caused side reaction.
In above-mentioned steps (2), the mol ratio of added hydroxylamine salt is preferably 0.6-to 1-CHLORO-2,4-DINITROBENZENE with step (1)
0.8:1, too low then consumption of raw materials increases, and too high alkylation is incomplete, is easily generated side reaction.
In above-mentioned steps (4), the response time is 1-2 hour, crosses hydrolysis the most at least not exclusively, long causes side reaction to increase；Instead
Answering temperature to be 50-60 DEG C, too low then hydrolysis not exclusively, too high causes side reaction to increase.
Compared with prior art, it is an advantage of the current invention that:
1. the present invention does not use tertiary fourth oxygen formyl chloride and trifluoroacetic acid of equal value in synthesizing the method for 2,4-2,4-dinitrophenoxy amine
The raw material that lattice are expensive, raw material is cheap and easy to get.
2. the present invention synthesizes 2, in the method for 4-2,4-dinitrophenoxy amine, uses hydrochloric acid hydrolysis, no in hydrolysis reaction
Only raw material is cheap and easy to get, and processes simple.
3. the present invention synthesizes 2, the method for 4-2,4-dinitrophenoxy amine and original acethydroximic acid ethyl ester technics comparing, it is to avoid step
Rapid longer, complex process and troublesome poeration are unfavorable for the problems such as big production, easy industrialized production.
Detailed description of the invention
Below in conjunction with embodiment, the present invention is described in further detail, but the present invention is not limited solely to following enforcement
Example.
Embodiment 1
Equipped with electric stirring, thermometer, condensing tube 500mL four-hole boiling flask in add 35g water, 35g (0.50mo1)
Oxammonium hydrochloride., adds 44.4g (0.60mol) methyl acetate, constant temperature 25 DEG C, starts to drip 30% liquid after stirring and dissolving under room temperature
Alkali 120g (0.90mol), joining day 1h, react 1h at 25 DEG C after having added.Then 50 DEG C it are warmed up to, the 2 of dropping 1:1,
Methyl acetate solution 121.5g (0.30mol) of 4-dinitrochlorobenzene, joining day 2h, at 50 DEG C, react 2h after having added,
Then 25 DEG C it are cooled to.Filter, the filter cake 5% liquid caustic soda making beating washing of mass ratio 1:1, again filter；Solid puts into 500mL's
In four-hole boiling flask, add 36.6g water, 36.6g (0.30mo1) 31% hydrochloric acid, be warmed up to 60 DEG C, after reacting 2 hours, be cooled to 25
℃.Filtering, solid refluxes recrystallization with 5 times of weight percent methanol, and 50 DEG C are vacuum dried to obtain product 37.1g, and yield 61.0%, liquid phase contains
Amount is 98.3%.
Embodiment 2
Water consumption changes 50g, the other the same as in Example 1 into, and result is 2,4-2,4-dinitrophenoxy amine 37.6g, yield 62.1%, liquid
Phase content is 98.7%.
Embodiment 3
NaOH changes KOH, the other the same as in Example 1 into, and result is 2,4-2,4-dinitrophenoxy amine 37.4g, yield 61.7%, liquid phase
Content is 98.6%
Embodiment 4
Methyl acetate changes ethyl acetate, the other the same as in Example 1 into, and result is 2,4-2,4-dinitrophenoxy amine 36.8g, yield
60.4%, liquid content is 98.1%
Embodiment 5
NaOH consumption changes 0.8mol, the other the same as in Example 1 into, and result is 2,4-2,4-dinitrophenoxy amine 34.8g, yield
57.6%, liquid content is 98.8%.
Embodiment 6
Methyl acetate consumption changes 0.75mol, the other the same as in Example 1 into, and result is 2,4-2,4-dinitrophenoxy amine 37.4g, receives
Rate 61.3%, liquid content is 97.9%.
Embodiment 7
DNFB consumption changes 0.4mol, the other the same as in Example 1 into, and result is 2,4-2,4-dinitrophenoxy amine
36.2g, yield 43.7%, liquid content is 96.3%.
Embodiment 8
Hydrolysising reacting temperature is 70 DEG C, and the insulation reaction time is 2h, the other the same as in Example 1, and result is 2,4-dinitro benzene
Oxygen amine 37.7g, yield 61.9%, liquid content is 98.1%.
Embodiment 9
Oxammonium hydrochloride. changes oxammonium sulfate., the other the same as in Example 1 into, and result is 2,4-2,4-dinitrophenoxy amine 35.1g, yield
57.8%, liquid content is 98.3%
From knowable to above-mentioned specific embodiment, the preparation process of the present invention is simple, post processing is easy and productivity is high, it is easy to hydrolysis
Separate.
Claims (8)
1. a synthesis 2, the method for 4-2,4-dinitrophenoxy amine, it is characterised in that: first carry out oximate by acetas and hydroxylamine salt anti-
Reply N protection, its reaction equation is shown below:
In formula, R is methyl or ethyl, and HX is hydrochloric acid or sulphuric acid；
Then reacting with DNFB, its reaction equation is shown below:
Adding hydrochloric acid hydrolysis, its reaction equation is shown below:
Concrete synthesis step is as follows:
(1) adding hydroxylamine salt in reaction vessel, water and acetas, then at a temperature of 15-40 DEG C, dropping in reaction vessel
Mass percent is the alkali metal hydroxide aqueous solution of 25-35% and is incubated 1-2 hour；The consumption of water is hydroxylamine salt weight
0.5-2 times, acetas is 1.0-2.0:1 with the mol ratio of hydroxylamine salt, and alkali metal hydroxide with the mol ratio of hydroxylamine salt is
1.5-3.0:1；
(2) insulation is warming up to 40-50 DEG C after terminating, the acetate solution of dropping DNFB, 40-50 after dropping
DEG C insulation 1-2 hour；The mol ratio of added hydroxylamine salt is 0.5-1.0:1 to 1-CHLORO-2,4-DINITROBENZENE with step (1)；
(3) filtering after the material that step (2) synthesizes is down to room temperature, gained filter cake mass percent is 3-5% alkali metal hydrogen-oxygen
The making beating washing of compound aqueous solution, filter cake and mass percent are that between 3-5% alkali metal hydroxide aqueous solution, weight ratio is 1:1-
2, the most again it is filtrated to get filter cake；
(4) in reaction vessel, add step (3) be again filtrated to get filter cake, be subsequently adding with step (2) in 2,4-dinitro
The equimolar mass percent of base chlorobenzene is 10-20% hydrochloric acid, and then intensification 50-70 DEG C is reacted 1-3 hour, and reaction is dropped after terminating
It is filtrated to get filtrate to room temperature；
(5) filtrate is heated to reflux, cools down and realize recrystallization by the methanol of the 5-6 times of weight of filtrate obtained by step (4), then
Filtering for crystallizing 50-60 DEG C, be vacuum dried 3-4 hour under 0.5-0.8MPa, obtain 2,4-2,4-dinitrophenoxy amine product.
Synthesize 2 the most according to claim 1, the method for 4-2,4-dinitrophenoxy amine, it is characterised in that: second in described step (1)
Acid esters is methyl acetate or ethyl acetate；Alkali metal hydroxide is sodium hydroxide or potassium hydroxide；Hydroxylamine salt is oxammonium hydrochloride.
Or oxammonium sulfate..
Synthesize 2 the most according to claim 1, the method for 4-2,4-dinitrophenoxy amine, it is characterised in that: the use of water in step (1)
Amount is 0.8-1.5 times of hydroxylamine salt weight.
Synthesize 2 the most according to claim 1, the method for 4-2,4-dinitrophenoxy amine, it is characterised in that: alkali metal in step (1)
Hydroxide is 1.6-2.2:1 with the mol ratio of hydroxylamine salt.
Synthesize 2 the most according to claim 1, the method for 4-2,4-dinitrophenoxy amine, it is characterised in that: acetas in step (1)
It is 1.1-1.5:1 with the mol ratio of hydroxylamine salt.
Synthesize 2 the most according to claim 1, the method for 4-2,4-dinitrophenoxy amine, it is characterised in that: reaction temperature in step (1)
Degree is for 20-30 DEG C.
Synthesize 2 the most according to claim 1, the method for 4-2,4-dinitrophenoxy amine, it is characterised in that: in step (2) 2,4-bis-
The mol ratio of added hydroxylamine salt is 0.6-0.8:1 to chloronitrobenzene with step (1).
Synthesize 2 the most according to claim 1, the method for 4-2,4-dinitrophenoxy amine, it is characterised in that: in step (4) during reaction
Between be 1-2 hour, reaction temperature is 50-60 DEG C.
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| CN113698318A (en) * | 2021-09-14 | 2021-11-26 | 宁波四明化工有限公司 | 2, 4-dinitrophenoxy amine synthesis method and reaction container |
| CN115108891B (en) * | 2022-07-18 | 2024-04-23 | 烟台盛华液晶材料有限公司 | Preparation method of 3, 5-difluorophenol |
Citations (2)
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|---|---|---|---|---|
| WO2010027114A1 (en) * | 2008-09-05 | 2010-03-11 | Choongwae Pharma Corporation | Use of pyrazole-pyridine derivatives and its salts for treating or reventin osteoporosis |
| CN103492384A (en) * | 2011-02-25 | 2014-01-01 | Irm责任有限公司 | Compounds and compositions as trk inhibitors |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010027114A1 (en) * | 2008-09-05 | 2010-03-11 | Choongwae Pharma Corporation | Use of pyrazole-pyridine derivatives and its salts for treating or reventin osteoporosis |
| CN103492384A (en) * | 2011-02-25 | 2014-01-01 | Irm责任有限公司 | Compounds and compositions as trk inhibitors |
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| Iridium-Catalyzed Asymmetric Hydrogenation of Substituted Pyridines;Alban Cadu et al.;《Asian J. Org. Chem.》;20131231(第2期);1061-1065 * |
| 环己烯酮类除草剂-烯草酮的合成;孙光强;《现代农药》;20110228;第10卷(第1期);24-26 * |
| 胺化剂O-（2,4-二硝基苯基）羟胺的合成;忻涛等;《中国医药工业杂志》;19931231;第24卷(第3期);134-135 * |
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