CN102976951A - Preparation method of 2-methyl-1,2-propane diamine - Google Patents
Preparation method of 2-methyl-1,2-propane diamine Download PDFInfo
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- CN102976951A CN102976951A CN2012105054738A CN201210505473A CN102976951A CN 102976951 A CN102976951 A CN 102976951A CN 2012105054738 A CN2012105054738 A CN 2012105054738A CN 201210505473 A CN201210505473 A CN 201210505473A CN 102976951 A CN102976951 A CN 102976951A
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Abstract
The invention discloses a preparation method of 2-methyl-1,2-propane diamine. The method comprises the following preparation steps of: 1) preparing alpha-amino isobutyronitrile (I); 2) preparing alpha-acetamido isobutyronitrile (II); 3) preparing 2,4,4-trimethyl-2-imidazoline (III); and 4) preparing 2-methyl-1,2-propane diamine (IV). The preparation method disclosed by the invention has the advantages of stable raw materials, low cost, mild reaction conditions and high reaction yield and is easy to industrialize. The solvent in the reaction process can be recycled by distilling.
Description
Technical field
The invention belongs to the organic synthesis field, be specifically related to a kind of 2-methyl isophthalic acid, the preparation method of 2-propylene diamine.
Background technology
2-methyl isophthalic acid, 2-propylene diamine are the important intermediate H of preparation anti-malaria medicaments OZ277 of new generation (Arterolane)].02277 has overcome the resistance of protozoon to traditional antimalarial agent, and oral effectively, toxicity is low, be beneficial to absorptions, duration of efficacy is long, market outlook are wide, corresponding intermediate 2-methyl isophthalic acid, the demand of 2-propylene diamine is also at increase year after year.Other 2-methyl isophthalic acid, the 2-propylene diamine still prepares the desirable feedstock of battery, metal chelating, refrigerant, gel retardant, polymeric amide etc.
Although the 2-methyl isophthalic acid, the 2-propylene diamine is of many uses, and there are the shortcomings such as raw material is unstable, preparation time long, many, the more difficult industrialization yields of side reaction are low in its preparation method at present, is unfavorable for industrialization.
Summary of the invention
Technical problem to be solved by this invention is: provide that a kind of raw material is stable, cost is low, reaction conditions is gentle, reaction yield is high, is easy to industrialized 2-methyl isophthalic acid, 2-propylene diamine preparation method.
For solving the problems of the technologies described above, the technical solution used in the present invention is: a kind of 2-methyl isophthalic acid, and the preparation method of 2-propylene diamine, its preparation process is:
1) preparation of alpha-amino group isopropyl cyanide (I)
Add ammoniacal liquor and ammonium chloride in the reactor, stirring and dissolving, 0～5 ℃ adds liquefied ammonia in reactor, drip simultaneously acetone cyanohydrin, 28～30 ℃ of reaction 3 ~ 3.5h, it is complete that GC detects raw material reaction, reaction finishes, add tetrahydrofuran (THF) and tell organic layer, water layer extracts with tetrahydrofuran (THF), merges organic layer, anhydrous sodium sulfate drying, filter, 60 ℃/267kPa cut is collected in the filtrate decompression distillation, obtains alpha-amino group isopropyl cyanide (I);
2) preparation of alpha-acetamido-isopropyl cyanide (II)
Add aceticanhydride in the reactor, be cooled to 0～5 ℃, stir the lower alpha-amino group isopropyl cyanide (I) that drips, be warming up to 45 ~ 50 ℃ of insulation reaction 1.5 ~ 2h after dripping off, add DMAP (DMAP), 45 ~ 50 ℃ of continuation are reacted and are detected alpha-amino group isopropyl cyanide (I) to GC and react completely, and reaction finishes; The underpressure distillation desolventizing gets consubstantiality, is cooled to 0 ~ 5 ℃ and adds the ether stirring, and the ether drip washing of suction filtration, filter cake obtains alpha-acetamido-isopropyl cyanide (II);
3) 2,4, the preparation of 4-trimethylammonium-2-tetrahydroglyoxaline (III)
Ammoniacal liquor and the Raney's nickel of alpha-acetamido-isopropyl cyanide (II), anhydrous methanol, 26 ~ 30Wt.% (massfraction) are added reactor, nitrogen replacement passes into hydrogen and is warming up to 95～100 ℃, and keeping reactor pressure is 0.9～1.0MPa reaction, 9 ~ 10h, react complete and be cooled to 20 ~ 25 ℃, migrate out reaction solution, add activated carbon filtration, filtrate decompression rectifying, collect 112～116 ℃ cut, obtain 2,4,4-trimethylammonium-2-tetrahydroglyoxaline (III);
4) 2-methyl isophthalic acid, the preparation of 2-propylene diamine (IV)
Add 2,4,4-trimethylammonium-2-tetrahydroglyoxaline (III), water and KOH solid successively in reactor, temperature rising reflux reaction 10 ~ 11h is cooled to 0 ~ 5 ℃, standing demix; Isolate the upper strata organic layer, add KOH, regulate 40 ~ 42 ℃ of temperature and keep 2 ~ 2.5h, leave standstill and tell supernatant liquid, anhydrous sodium sulfate drying, 65 ~ 70 ℃ of constant temperature 1.5 ~ 2h, atmospheric distillation obtains the 2-methyl isophthalic acid, the 2-propylene diamine.
Described 2-methyl isophthalic acid, the preparation process of 2-propylene diamine, its reaction equation is:
The mol ratio of the ammonium chloride step 1), liquefied ammonia and acetone cyanohydrin is 0.6 ~ 0.8:3.5 ~ 4:1.
The mol ratio of alpha-amino group isopropyl cyanide, aceticanhydride and the DMAP step 2) is 1:2.5 ~ 3:0.02 ~ 0.05.
Step 3) Raney's nickel described in and alpha-acetamido-isopropyl cyanide mass ratio are 1:1.5 ~ 2.0.
Step 4) 2,4 described in, the mass ratio of 4-trimethylammonium-2-tetrahydroglyoxaline and KOH is 1:3.5 ~ 4.
Step 2) underpressure distillation described in, pressure are 0.67kPa, and temperature is 60 ~ 62 ℃ and reclaims solvent.
Beneficial effect of the present invention: raw material disclosed by the invention is stable, cost is low, reaction conditions is gentle, reaction yield is high, is easy to industrialization.Solvent in the reaction process is through the distillation recoverable.
Embodiment
Embodiment
1) preparation of alpha-amino group isopropyl cyanide (I)
Add 68g ammoniacal liquor and 32.1g (0.6mol) ammonium chloride in the reactor, stirring and dissolving, 0～5 ℃ adds 59.5g (3.5mol) liquefied ammonia in reactor, drip simultaneously 85g (1mol) acetone cyanohydrin, 28～30 ℃ of reaction 3h, it is complete that GC detects raw material reaction, and reaction finishes, and adds tetrahydrofuran (THF) and tell organic layer, water layer extracts with tetrahydrofuran (THF), merge organic layer, anhydrous sodium sulfate drying filters, 60 ℃/267kPa cut is collected in the filtrate decompression distillation, obtain alpha-amino group isopropyl cyanide (I) (colourless liquid 76.7g, yield 86.9%, content 99.9% (GC area normalization method mensuration));
2) preparation of alpha-acetamido-isopropyl cyanide (II)
Add 76.5g (0.75mol) aceticanhydride in the reactor, be cooled to 0～5 ℃, stir lower 25.2g (0.3mol) the alpha-amino group isopropyl cyanide (I) that drips, be warming up to 45 ~ 50 ℃ of insulation reaction 1.5 ~ 2h after dripping off, add 7.4g (0.06mol) DMAP (DMAP), 45 ~ 50 ℃ of continuation are reacted and are detected alpha-amino group isopropyl cyanide (I) to GC and react completely, and reaction finishes; The underpressure distillation desolventizing gets loose white consubstantiality, and be cooled to 0 ~ 5 ℃ and add the stirring of 100mL ether, suction filtration, filter cake obtains alpha-acetamido-isopropyl cyanide (II) oven dry 36.8g with 100mL * 2 ether drip washing, and yield 97.3% is surveyed 104～105 ℃ of fusing points;
3) 2,4, the preparation of 4-trimethylammonium-2-tetrahydroglyoxaline (III)
With 250g (1.98mol) alpha-acetamido-isopropyl cyanide (II), the 600g anhydrous methanol, the ammoniacal liquor of 450g 30Wt.% (massfraction) and 150g Raney's nickel add reactor, nitrogen replacement, pass into hydrogen and be warming up to 95～100 ℃, keeping reactor pressure is 0.9～1.0MPa reaction, 9 ~ 10h, react complete and be cooled to 20 ~ 25 ℃, migrate out reaction solution, add activated carbon filtration, 112～116 ℃ cut is collected in filtrate decompression rectifying, obtains 2,4,4-trimethylammonium-2-tetrahydroglyoxaline (III) (colourless liquid 212.7g, yield 95.7%, content 98.6% (GC area normalization method mensuration));
4) 2-methyl isophthalic acid, the preparation of 2-propylene diamine (IV)
In reactor, add 346g (3.09mol) 2,4 successively, 4-trimethylammonium-2-tetrahydroglyoxaline (III), 1.5L water and 1287gKOH solid, temperature rising reflux reaction 11h is cooled to 0 ~ 5 ℃, standing demix; Isolate the upper strata organic layer, add 50gKOH, regulate 42 ℃ of temperature and keep 2.5h, leave standstill and tell supernatant liquid, anhydrous sodium sulfate drying, 65 ~ 70 ℃ of constant temperature 1.5 ~ 2h, atmospheric distillation obtains the 2-methyl isophthalic acid, the 2-propylene diamine (is collected 118 ~ 120 ℃ of cuts, get colourless liquid 269.2g, yield 87.3%, content 99.8% (GC area normalization method mensuration)).
Claims (6)
1. 2-methyl isophthalic acid, the preparation method of 2-propylene diamine, its preparation process is as follows:
1) preparation of alpha-amino group isopropyl cyanide (I)
Add ammoniacal liquor and ammonium chloride in the reactor, stirring and dissolving, 0～5 ℃ adds liquefied ammonia in reactor, drip simultaneously acetone cyanohydrin, 28～30 ℃ of reaction 3 ~ 3.5h, it is complete that GC detects raw material reaction, reaction finishes, add tetrahydrofuran (THF) and tell organic layer, water layer extracts with tetrahydrofuran (THF), merges organic layer, anhydrous sodium sulfate drying, filter, 60 ℃/267kPa cut is collected in the filtrate decompression distillation, obtains alpha-amino group isopropyl cyanide (I);
2) preparation of alpha-acetamido-isopropyl cyanide (II)
Add aceticanhydride in the reactor, be cooled to 0～5 ℃, stir the lower alpha-amino group isopropyl cyanide (I) that drips, be warming up to 45 ~ 50 ℃ of insulation reaction 1.5 ~ 2h after dripping off, add DMAP, 45 ~ 50 ℃ of continuation are reacted and are detected alpha-amino group isopropyl cyanide (I) to GC and react completely, and reaction finishes; The underpressure distillation desolventizing gets consubstantiality, is cooled to 0 ~ 5 ℃ and adds the ether stirring, and the ether drip washing of suction filtration, filter cake obtains alpha-acetamido-isopropyl cyanide (II);
3) 2,4, the preparation of 4-trimethylammonium-2-tetrahydroglyoxaline (III)
Ammoniacal liquor and the Raney's nickel of alpha-acetamido-isopropyl cyanide (II), anhydrous methanol, 26 ~ 30Wt.% are added reactor, nitrogen replacement passes into hydrogen and is warming up to 95～100 ℃, and keeping reactor pressure is 0.9～1.0MPa reaction, 9 ~ 10h, react complete and be cooled to 20 ~ 25 ℃, migrate out reaction solution, add activated carbon filtration, filtrate decompression rectifying, collect 112～116 ℃ cut, obtain 2,4,4-trimethylammonium-2-tetrahydroglyoxaline (III);
4) 2-methyl isophthalic acid, the preparation of 2-propylene diamine (IV)
Add 2,4,4-trimethylammonium-2-tetrahydroglyoxaline (III), water and KOH solid successively in reactor, temperature rising reflux reaction 10 ~ 11h is cooled to 0 ~ 5 ℃, standing demix; Isolate the upper strata organic layer, add KOH, regulate 40 ~ 42 ℃ of temperature and keep 2 ~ 2.5h, leave standstill and tell supernatant liquid, anhydrous sodium sulfate drying, 65 ~ 70 ℃ of constant temperature 1.5 ~ 2h, atmospheric distillation obtains the 2-methyl isophthalic acid, the 2-propylene diamine.
2. a kind of 2-methyl isophthalic acid according to claim 1, the preparation method of 2-propylene diamine is characterized in that: step 1) described in the mol ratio of ammonium chloride, liquefied ammonia and acetone cyanohydrin be 0.6 ~ 0.8:3.5 ~ 4:1.
3. a kind of 2-methyl isophthalic acid according to claim 1, the preparation method of 2-propylene diamine is characterized in that: step 2) described in the mol ratio of alpha-amino group isopropyl cyanide, aceticanhydride and DMAP be 1:2.5 ~ 3:0.02 ~ 0.05.
4. a kind of 2-methyl isophthalic acid according to claim 1, the preparation method of 2-propylene diamine is characterized in that: step 3) described in Raney's nickel and alpha-acetamido-isopropyl cyanide mass ratio be 1:1.5 ~ 2.0.
5. a kind of 2-methyl isophthalic acid according to claim 1, the preparation method of 2-propylene diamine is characterized in that: step 4) described in 2,4, the mass ratio of 4-trimethylammonium-2-tetrahydroglyoxaline and KOH is 1:3.5 ~ 4.
6. according to claim 1 to the described a kind of 2-methyl isophthalic acid of 5 any claims, the preparation method of 2-propylene diamine is characterized in that: step 2) described in underpressure distillation, pressure is 0.67kPa, temperature is 60 ~ 62 ℃ and reclaims solvents.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103626664A (en) * | 2013-11-01 | 2014-03-12 | 西安近代化学研究所 | Method for synthesizing 2-methyl-1,2-propane diamine |
| CN105585505A (en) * | 2015-12-25 | 2016-05-18 | 辽宁本源制药有限公司 | Novel preparation method of anagliptin intermediate 1,2-diamido-2-methylpropane |
| CN106316865A (en) * | 2016-08-22 | 2017-01-11 | 岳阳昌德化工实业有限公司 | Synthetic method of 2-(aminomethyl)cyclohexanamine |
| CN113717055A (en) * | 2021-09-02 | 2021-11-30 | 西安近代化学研究所 | Separation and purification method and system of 2-methyl-1, 2-propane diamine |
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103626664A (en) * | 2013-11-01 | 2014-03-12 | 西安近代化学研究所 | Method for synthesizing 2-methyl-1,2-propane diamine |
| CN105585505A (en) * | 2015-12-25 | 2016-05-18 | 辽宁本源制药有限公司 | Novel preparation method of anagliptin intermediate 1,2-diamido-2-methylpropane |
| CN105585505B (en) * | 2015-12-25 | 2017-10-31 | 辽宁本源制药有限公司 | A kind of new preparation method of the methylpropane of 1,2 diaminourea of An Naigelieting intermediates 2 |
| CN106316865A (en) * | 2016-08-22 | 2017-01-11 | 岳阳昌德化工实业有限公司 | Synthetic method of 2-(aminomethyl)cyclohexanamine |
| CN113717055A (en) * | 2021-09-02 | 2021-11-30 | 西安近代化学研究所 | Separation and purification method and system of 2-methyl-1, 2-propane diamine |
| CN113717055B (en) * | 2021-09-02 | 2024-03-26 | 西安近代化学研究所 | Separation and purification method and system for 2-methyl-1, 2-propanediamine |
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Application publication date: 20130320 |