CN104402752A - Preparation method of 1,1'-cyclohexyl monoamide - Google Patents
Preparation method of 1,1'-cyclohexyl monoamide Download PDFInfo
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- CN104402752A CN104402752A CN201410708935.5A CN201410708935A CN104402752A CN 104402752 A CN104402752 A CN 104402752A CN 201410708935 A CN201410708935 A CN 201410708935A CN 104402752 A CN104402752 A CN 104402752A
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Abstract
The invention relates to a preparation method of 1,1'-cyclohexyl monoamide, which comprises the following steps: (1) carrying out ammoniation reaction: adding 1,1'-cyclohexane diacetic anhydride, ammonia water and an acid-binding agent into an inert solvent respectively for reaction for 2-3h at room temperature to form an intermediate product, and (2) carrying out acidification reaction on the intermediate product to form 1,1'-cyclohexyl monoamide, wherein a mole ratio of 1,1'-cyclohexane diacetic anhydride to ammonia water is 1:(1.5-2), and a ratio of 1,1'-cyclohexane diacetic anhydride to the acid-binding agent is 1mol:(10-20)mol. According to the preparation method, the acid-binding agent is added, can absorb acid generated in the reaction and reacts with acid to form salt, acid is prevented from influencing the reaction and reaction balance, and the productivity and purity of 1,1'-cyclohexyl monoamide are further facilitated.
Description
Technical field
The present invention relates to a kind of preparation method of 1,1'-cyclohexyl monoamide, belong to the field of chemical synthesis.
Background technology
1,1'-cyclohexyl monoamide is a kind of important intermediate of synthesis antiepileptic drug gabapentin.In prior art, 1,1'-cyclohexyl monoamide is prepared mainly through following synthetic route:
In addition, prior art adopts 1,1'-cyclohexanediacetic acid acid anhydride as raw material usually, after it carries out aminating reaction and acidification reaction successively, and obtained 1,1'-cyclohexyl monoamide.But after acidification reaction, can produce acid, the existence of acid can affect reaction or molecular balance, thus affects the productive rate of final product.
Summary of the invention
Technical problem to be solved by this invention is the preparation method of 1, the 1'-cyclohexyl monoamide providing a kind of productive rate high for the state of the art.
The present invention solves the problems of the technologies described above adopted technical scheme: a kind of preparation method of 1,1'-cyclohexyl monoamide, comprises the steps:
(1) aminating reaction, adds 1,1'-cyclohexanediacetic acid acid anhydride, ammoniacal liquor and acid binding agent respectively, at room temperature reacts 2 ~ 3h in inert solvent, obtained intermediate product; The mol ratio of described 1,1'-cyclohexanediacetic acid acid anhydride and ammoniacal liquor is 1:1.5 ~ 2, and the ratio of described 1,1'-cyclohexanediacetic acid acid anhydride and acid binding agent is 1mol:10 ~ 20ml;
(2) gained intermediate product is after acidification reaction, obtained 1,1'-cyclohexyl monoamide.
In step (1), described inert solvent is toluene dichloride and/or tetrahydrofuran (THF).
In step (1), described acid binding agent is triethylamine or pyridine.
In step (1), the volume ratio of described inert solvent and acid binding agent is 5 ~ 10:1.
In step (2), the acid used of described acidification reaction is mineral acid.
Wherein, described mineral acid is technical hydrochloric acid.
Wherein, in step (1), the massfraction of described ammoniacal liquor is 10% ~ 25%.
Described mineral acid to be massfraction be 50 ~ 70% sulfuric acid.
Step (1a) was also comprised, by 1,1'-cyclohexanediacetic acid and obtained 1, the 1'-cyclohexanediacetic acid acid anhydride of aceticanhydride before step (1).
Wherein, the weight ratio of described 1,1'-cyclohexanediacetic acid and aceticanhydride is 1:1 ~ 2.
Compared with prior art, the invention has the advantages that: this preparation method with the addition of acid binding agent in preparation process, its acid that can produce in absorption reaction, thus with acid-respons salify, avoid acid impact reaction and molecular balance, and then be conducive to productive rate and the purity of 1,1'-cyclohexyl monoamide.After tested, yield of the present invention reaches as high as 99%, and in product, the content of 1,1'-cyclohexyl monoamide is greater than 99.9%, and its purity is high.
Embodiment
Below in conjunction with embodiment, the present invention is described in further detail.
Embodiment 1
The preparation method of 1, the 1'-cyclohexyl monoamide of the present embodiment comprises the steps:
(1a) 1,1'-cyclohexanediacetic acid acid anhydride is prepared:
350 kilogram 1 is added in the reaction vessel that reflux distillation condenser is housed, 1'-cyclohexanediacetic acid and 350 kilograms of aceticanhydrides, be heated to 125 ~ 140 DEG C, reflux 2 ~ 5 hours, make water distilling apparatus into afterwards, the aceticanhydride in underpressure distillation removing reactive system and acetic acid, obtain 1 of molten state, 1'-cyclohexanediacetic acid acid anhydride, for next step reaction.
(1) aminating reaction, ammoniacal liquor, inert solvent---toluene dichloride and acid binding agent---triethylamine that 500 kilograms of massfractions are 10% is dropped in ammoniation kettle, after mixing, slowly drip 1 of the molten state that previous step obtains, 1'-cyclohexanediacetic acid acid anhydride, within at room temperature about 3 hours, drip off, then add a small amount of activated carbon filtration.
In this step, the mol ratio of 1,1'-cyclohexanediacetic acid acid anhydride and ammoniacal liquor is the ratio of 1:1.5,1,1'-cyclohexanediacetic acid acid anhydride and acid binding agent is 1mol:10ml; The volume ratio of inert solvent and acid binding agent is 5:1.
(2) acidification reaction, the filtered liquid that above-mentioned steps obtains with 50% sulfuric acid acidation, centrifugal white crystal, dry must 1,1'-cyclohexanediacetic acid monoamide, yield is that to analyze its content be 99.8% to 97%, HPLC.
Embodiment 2
The preparation method of 1, the 1'-cyclohexyl monoamide of the present embodiment comprises the steps:
(1a) 1,1'-cyclohexanediacetic acid acid anhydride is prepared:
350 kilogram 1 is added in the reaction vessel that reflux distillation condenser is housed, 1'-cyclohexanediacetic acid and 450 kilograms of aceticanhydrides, be heated to 125 ~ 140 DEG C, reflux 2 ~ 5 hours, make water distilling apparatus into afterwards, the aceticanhydride in underpressure distillation removing reactive system and acetic acid, obtain 1 of molten state, 1'-cyclohexanediacetic acid acid anhydride, for next step reaction.
(1) aminating reaction, ammoniacal liquor, inert solvent---tetrahydrofuran (THF) and acid binding agent---pyridine that 500 kilograms of massfractions are 10% is dropped in ammoniation kettle, after mixing, slowly drip 1 of the molten state that previous step obtains, 1'-cyclohexanediacetic acid acid anhydride, within at room temperature about 3 hours, drip off, then add a small amount of activated carbon filtration.
In this step, the mol ratio of 1,1'-cyclohexanediacetic acid acid anhydride and ammoniacal liquor is the ratio of 1:1.8,1,1'-cyclohexanediacetic acid acid anhydride and acid binding agent is 1mol:15ml; The volume ratio of inert solvent and acid binding agent is 8:1.
(2) acidification reaction, the industrial hcl acidifying of filtered liquid that above-mentioned steps obtains, centrifugal white crystal, dry 1,1'-cyclohexanediacetic acid monoamide, yield is that to analyze its content be 99.7% to 99%, HPLC.
Embodiment 3
The preparation method of 1, the 1'-cyclohexyl monoamide of the present embodiment comprises the steps:
(1a) 1,1'-cyclohexanediacetic acid acid anhydride is prepared:
350 kilogram 1 is added in the reaction vessel that reflux distillation condenser is housed, 1'-cyclohexanediacetic acid and 700 kilograms of aceticanhydrides, be heated to 125 ~ 140 DEG C, reflux 2 ~ 5 hours, make water distilling apparatus into afterwards, the aceticanhydride in underpressure distillation removing reactive system and acetic acid, obtain 1 of molten state, 1'-cyclohexanediacetic acid acid anhydride, for next step reaction.
(1) aminating reaction, ammoniacal liquor, inert solvent---toluene dichloride and acid binding agent---triethylamine that 500 kilograms of massfractions are 10% is dropped in ammoniation kettle, after mixing, slowly drip 1 of the molten state that previous step obtains, 1'-cyclohexanediacetic acid acid anhydride, within at room temperature about 3 hours, drip off, then add a small amount of activated carbon filtration.
In this step, the mol ratio of 1,1'-cyclohexanediacetic acid acid anhydride and ammoniacal liquor is the ratio of 1:2,1,1'-cyclohexanediacetic acid acid anhydride and acid binding agent is 1mol:20ml; The volume ratio of inert solvent and acid binding agent is 10:1.
(2) acidification reaction, the filtered liquid that above-mentioned steps obtains with 50% sulfuric acid acidation, centrifugal white crystal, dry must 1,1'-cyclohexanediacetic acid monoamide, yield is that to analyze its content be 99.5% to 96%, HPLC.
Above content is only preferred embodiment of the present invention, and for those of ordinary skill in the art, according to thought of the present invention, all will change in specific embodiments and applications, this description should not be construed as limitation of the present invention.
Claims (10)
1. the preparation method of a cyclohexyl monoamide, is characterized in that, comprises the steps:
(1) aminating reaction, adds 1,1'-cyclohexanediacetic acid acid anhydride, ammoniacal liquor and acid binding agent respectively, at room temperature reacts 2 ~ 3h in inert solvent, obtained intermediate product; The mol ratio of described 1,1'-cyclohexanediacetic acid acid anhydride and ammoniacal liquor is 1:1.5 ~ 2, and the ratio of described 1,1'-cyclohexanediacetic acid acid anhydride and acid binding agent is 1mol:10 ~ 20ml;
(2) gained intermediate product is after acidification reaction, obtained 1,1'-cyclohexyl monoamide.
2. the preparation method of 1,1'-cyclohexyl monoamide according to claim 1, it is characterized in that: in step (1), described inert solvent is toluene dichloride and/or tetrahydrofuran (THF).
3. the preparation method of 1,1'-cyclohexyl monoamide according to claim 1, it is characterized in that: in step (1), described acid binding agent is triethylamine or pyridine.
4. the preparation method of 1,1'-cyclohexyl monoamide according to claim 1, is characterized in that: in step (1), the volume ratio of described inert solvent and acid binding agent is 5 ~ 10:1.
5. the preparation method of 1,1'-cyclohexyl monoamide according to claim 1, is characterized in that: in step (2), and the acid used of described acidification reaction is mineral acid.
6. the preparation method of 1,1'-cyclohexyl monoamide according to claim 4, is characterized in that: described mineral acid is technical hydrochloric acid.
7. the preparation method of 1,1'-cyclohexyl monoamide according to claim 4, is characterized in that: described mineral acid to be massfraction be 50 ~ 70% sulfuric acid.
8. the preparation method of 1,1'-cyclohexyl monoamide according to claim 1, is characterized in that: before step (1), also comprise step (1a), by 1,1'-cyclohexanediacetic acid and obtained 1, the 1'-cyclohexanediacetic acid acid anhydride of aceticanhydride.
9. the preparation method of 1,1'-cyclohexyl monoamide according to claim 8, is characterized in that: the weight ratio of described 1,1'-cyclohexanediacetic acid and aceticanhydride is 1:1 ~ 2.
10. the preparation method of 1,1'-cyclohexyl monoamide according to claim 1, is characterized in that: in step (1), the massfraction of described ammoniacal liquor is 10% ~ 25%.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109232295A (en) * | 2018-10-24 | 2019-01-18 | 河北三川化工有限公司 | A kind of method for crystallising of 1,1- cyclohexanediacetic acid monoamides |
| CN115850109A (en) * | 2022-09-14 | 2023-03-28 | 河北三川化工有限公司 | CAM preparation process and application thereof |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1297885A (en) * | 2000-12-01 | 2001-06-06 | 杭州手心精细化工有限公司 | Preparation of 1.1-cyclohexyl oxalic amide |
| WO2003002517A1 (en) * | 2001-06-28 | 2003-01-09 | Bromine Compounds Ltd. | Process for the preparation of 1.1-cyclohexane diacetic acid monoamide |
| CN101037395A (en) * | 2006-12-20 | 2007-09-19 | 杭州手心医药化学品有限公司 | Preparation method of 1,1-Cyclohexane diethyl acid mono amide |
| US20080103334A1 (en) * | 2006-10-26 | 2008-05-01 | Ipca Laboratories Ltd | Process For Synthesis Of Gabapentin |
| CN101417960A (en) * | 2008-12-01 | 2009-04-29 | 太仓市运通化工厂 | Method for preparing 1,1-cyclohexanediacetic acid mono amide |
| CN103333081A (en) * | 2013-06-27 | 2013-10-02 | 南通泰通化学科技有限公司 | Preparation method of 1,1-cyclohexanediacetic acid mono amide |
-
2014
- 2014-11-28 CN CN201410708935.5A patent/CN104402752A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1297885A (en) * | 2000-12-01 | 2001-06-06 | 杭州手心精细化工有限公司 | Preparation of 1.1-cyclohexyl oxalic amide |
| WO2003002517A1 (en) * | 2001-06-28 | 2003-01-09 | Bromine Compounds Ltd. | Process for the preparation of 1.1-cyclohexane diacetic acid monoamide |
| US20080103334A1 (en) * | 2006-10-26 | 2008-05-01 | Ipca Laboratories Ltd | Process For Synthesis Of Gabapentin |
| CN101037395A (en) * | 2006-12-20 | 2007-09-19 | 杭州手心医药化学品有限公司 | Preparation method of 1,1-Cyclohexane diethyl acid mono amide |
| CN101417960A (en) * | 2008-12-01 | 2009-04-29 | 太仓市运通化工厂 | Method for preparing 1,1-cyclohexanediacetic acid mono amide |
| CN103333081A (en) * | 2013-06-27 | 2013-10-02 | 南通泰通化学科技有限公司 | Preparation method of 1,1-cyclohexanediacetic acid mono amide |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109232295A (en) * | 2018-10-24 | 2019-01-18 | 河北三川化工有限公司 | A kind of method for crystallising of 1,1- cyclohexanediacetic acid monoamides |
| CN115850109A (en) * | 2022-09-14 | 2023-03-28 | 河北三川化工有限公司 | CAM preparation process and application thereof |
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Application publication date: 20150311 |