CN101372473B - Preparation of N-hydroxy diimide - Google Patents
Preparation of N-hydroxy diimide Download PDFInfo
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- CN101372473B CN101372473B CN200810201278XA CN200810201278A CN101372473B CN 101372473 B CN101372473 B CN 101372473B CN 200810201278X A CN200810201278X A CN 200810201278XA CN 200810201278 A CN200810201278 A CN 200810201278A CN 101372473 B CN101372473 B CN 101372473B
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Abstract
The invention belongs to the technical field of chemical plating auxiliary agent and fine chemical intermediate, and more particularly relates to a method for preparing N-hydroxide radical diimide. The preparation method uses a novel catalyst system which is acetic anhydride/trifluoroacetic acid/organic base, so as to lead the conditions of the reaction for substituting dicarboxylic anhydride andhydroxylamine compound salt to be more mild; the reaction yield coefficient and product purity are improved, thus greatly reducing the production cost and being applicable to mass production and application.
Description
Technical field
The invention belongs to electroless plating auxiliary agent and fine-chemical intermediate field, be specifically related to a kind of preparation method of N-hydroxy diimide.
Background technology
The sodium salt of N-hydroxy diimide or sylvite can strengthen the stability of plating bath as the electroless plating auxiliary agent, improve the luminance brightness of metal plating, reduce the content of impurity element in the coating, thereby improve the quality of metallic membrane greatly.But, require the sodium salt of N-hydroxy diimide or sylvite to have and surpass 99% purity as the electroless plating auxiliary agent.
The N-hydroxy diimide has obtained using widely as organic synthesis intermediate, and for example, N-maloyl imines is the important reagent of synthetic polypeptide blocking group N-(9-fluorenylmethyloxycarbonyl) butanediamine (FCS); N-maloyl imines also is used to prepare active ester, suppresses the generation of its racemic modification when the peptide coupling, and it can not influence its biological activity with the protein covalent attachment, in antigen separation and immunoassay important application is arranged.(De Leon-Rodriguez, Luis M.Tetrahedron Lett., 2006,47 (39), 6937; Harris J M.US6432397,2002.) the N-hydroxyphthalimide is as the N of azanol, and N-two protection forms are usually used in preparing the azanol that O-replaces.(Ace?K?W，HussainN，Lathbury?D?C?et?al.Tetrahedron?Lett.，1995，36，8141；Bonaccorsi?F，GiorgiR.Synthetic?Commun.，1997，27，1143.)
The N-hydroxy diimide has two kinds of preparation methods usually: (1) will replace dicarboxylic anhydride and oxammonium hydrochloride is water-soluble, and heating together makes reactive system keep negative pressure to extract the volatile matter of generation, is heated to rapidly more than 125 ℃, slowly rises to 160 ℃ behind the 1h.Stop heating, when temperature is reduced to 125 ℃, with in the reactant impouring ethyl acetate and high degree of agitation.Gained crude product re-crystallizing in ethyl acetate, yield 40～75% are filtered in cooling.The shortcoming of this method is that temperature of reaction is higher, the easy charing of product, and the N-hydroxy diimide purity of preparation is lower, is usually less than 95%; Must use enamel reaction still in producing besides, and the thermal conduction of this class still is relatively poor, breaks easily during high temperature, makes that continuity production can not get ensureing.(2) be raw material with unsubstituted imide, reaction earlier generates N-(tertbutyloxycarbonyl) derivative of (being called for short N-Boc), with the aqueous hydroxylamine reaction, obtains corresponding azanol composite salt again, and acidifying gets product again.The advantage of this method is that reaction conditions is relatively gentle, product purity higher (surpassing 98%), and shortcoming is the hydroxylamine solution instability, decomposes easily and explodes; The cost of producing the N-Boc derivative besides is high, can't promote (Einhorn C, Einhorn J, Marcadal-Abbadi C.Synthetic Communications, 2001,31 (5), 741.) equally.
Summary of the invention
The objective of the invention is to propose the new preparation method of a kind of N-hydroxy diimide.
The preparation method that the present invention proposes is: under nitrogen protection; in three-necked bottle, add the azanol composite salt, replace dicarboxylic anhydride, acetic anhydride, trifluoracetic acid, organic bases and solvent; be heated to 60～100 ℃ of reactions 2～6 hours; after reaction finishes; cooling removes solvent under reduced pressure, the resistates ethyl acetate extraction; concentrate the crude product recrystallization purifying.
Among the present invention, used azanol composite salt is a kind of of oxammonium hydrochloride, oxammonium sulfate.
Among the present invention, used organic bases is a kind of of triethylamine, pyridine.
Among the present invention, used solvent is a kind of of tetrahydrofuran (THF), 2-methyltetrahydrofuran, dioxane.
In aforesaid method, if used replacement dicarboxylic anhydride is a Succinic anhydried, the consumption mol ratio of Succinic anhydried, acetic anhydride, trifluoracetic acid, organic bases and azanol composite salt is respectively 0.95～1.2,0.01～0.05,0.01～0.05,1～1.5, obtain N-maloyl imines, structural formula is as follows:
(A)
In aforesaid method, if used replacement dicarboxylic anhydride is maleic anhydride (MALEIC ANHYDRIDE), the consumption mol ratio of maleic anhydride, acetic anhydride, trifluoracetic acid, organic bases and azanol composite salt is respectively 1.0～1.2,0.05～0.1,0.05～0.1,1～1.25, obtain N-hydroxyl maleimide, structural formula is as follows:
(B)
In aforesaid method, if used replacement dicarboxylic anhydride is a Tetra hydro Phthalic anhydride, the consumption mol ratio of Tetra hydro Phthalic anhydride, acetic anhydride, trifluoracetic acid, organic bases and azanol composite salt is respectively 0.9～1.1,0.1～0.2,0.1～0.2,1～1.5, obtain the N-hydroxyphthalimide, structural formula is as follows:
(C)
In aforesaid method, if used replacement dicarboxylic anhydride is 2, the 3-naphthalic anhydride, 2, the consumption mol ratio of 3-naphthalic anhydride, acetic anhydride, trifluoracetic acid, organic bases and azanol composite salt is respectively 0.9～1.1,0.1～0.2,0.1～0.2,1～1.5, then obtain N-hydroxyl-2, the 3-naphthalimide, structural formula is as follows:
(D)
In aforesaid method, if used replacement dicarboxylic anhydride is 1, the 8-naphthalic anhydride, 1, the consumption mol ratio of 8-naphthalic anhydride, acetic anhydride, trifluoracetic acid, organic bases and azanol composite salt is respectively 0.9～1.1,0.1～0.2,0.1～0.2,1～1.5, then obtain N-hydroxyl-1,8-naphthalimide, structural formula is as follows:
(E)
The present invention has adopted a kind of new catalyst system---acetic anhydride/trifluoracetic acid/organic bases, make that the reaction conditions that replaces dicarboxylic anhydride and azanol composite salt is gentle more, reaction yield and product purity improve, thereby greatly reduce production cost, are suitable for scale operation and application.
Embodiment
The invention is further illustrated by the following examples, but be not limitation of the invention.
Embodiment 1,
In the there-necked flask that agitator, nitrogen ingress pipe, reflux exchanger are housed, add Succinic anhydried (1mol), oxammonium hydrochloride (1mol), acetic anhydride (0.02mol), trifluoracetic acid (0.02mol), pyridine (1mol) and dioxane (400ml) successively.Under nitrogen protection, be warming up to 100 ℃, reaction 6h is to the no Succinic anhydried of thin-layer chromatography detection; be cooled to 60 ℃, be evaporated to driedly, add ethyl acetate 4000ml, stir; leave standstill, topple over the upper strata stillness of night, use ethyl acetate extraction again 4 times, each 2000ml; combined ethyl acetate solution removes solvent under reduced pressure, uses re-crystallizing in ethyl acetate; activated carbon decolorizing gets white solid, i.e. compound (A); productive rate 86%, 97～98 ℃ of fusing points, purity〉99.5%.
Embodiment 2,
In the there-necked flask that agitator, nitrogen ingress pipe, reflux exchanger are housed, add Succinic anhydried (1mol), oxammonium hydrochloride (1.05mol), acetic anhydride (0.04mol), trifluoracetic acid (0.03mol), pyridine (1.05mol) and dioxane (400ml) successively.Under nitrogen protection, be warming up to 100 ℃, reaction 6h is to the no Succinic anhydried of thin-layer chromatography detection; be cooled to 60 ℃, be evaporated to driedly, add ethyl acetate 4000ml, stir; leave standstill, topple over the upper strata stillness of night, use ethyl acetate extraction again 4 times, each 2000ml; combined ethyl acetate solution removes solvent under reduced pressure, uses re-crystallizing in ethyl acetate; activated carbon decolorizing gets white solid, i.e. compound (A); productive rate 90%, 97～98 ℃ of fusing points, purity〉99.5%.
Embodiment 3,
In the there-necked flask that agitator, nitrogen ingress pipe, reflux exchanger are housed, add maleic anhydride (1mol), oxammonium sulfate (1.1mol), acetic anhydride (0.05mol), trifluoracetic acid (0.05mol), triethylamine (1.25mol) and 2-methyltetrahydrofuran (400ml) successively.Under nitrogen protection, be warming up to 80 ℃, reaction 6h is to the no maleic anhydride of thin-layer chromatography detection; be cooled to 50 ℃, be evaporated to driedly, add ethyl acetate 4000ml, stir; leave standstill, topple over the upper strata stillness of night, use ethyl acetate extraction 4 times, each 2000ml; combined ethyl acetate solution removes solvent under reduced pressure, uses re-crystallizing in ethyl acetate again; activated carbon decolorizing gets white solid, i.e. compound (B); productive rate 80%, 148～149 ℃ of fusing points (decomposition), purity〉99.5%.
Embodiment 4,
In the there-necked flask that agitator, nitrogen ingress pipe, reflux exchanger are housed, add maleic anhydride (1mol), oxammonium sulfate (1.2mol), acetic anhydride (0.08mol), trifluoracetic acid (0.06mol), triethylamine (1.0mol) and 2-methyltetrahydrofuran (400ml) successively.Under nitrogen protection, be warming up to 80 ℃, reaction 6h is to the no maleic anhydride of thin-layer chromatography detection; be cooled to 50 ℃, be evaporated to driedly, add ethyl acetate 4000ml, stir; leave standstill, topple over the upper strata stillness of night, use ethyl acetate extraction 4 times, each 2000ml; combined ethyl acetate solution removes solvent under reduced pressure, uses re-crystallizing in ethyl acetate again; activated carbon decolorizing gets white solid, i.e. compound (B); productive rate 83%, 148～149 ℃ of fusing points (decomposition), purity〉99.5%.
Embodiment 5,
In the there-necked flask that agitator, nitrogen ingress pipe, reflux exchanger are housed, add Tetra hydro Phthalic anhydride (1mol), oxammonium hydrochloride (1.05mol), acetic anhydride (0.2mol), trifluoracetic acid (0.2mol), pyridine (1.5mol) and tetrahydrofuran (THF) (400ml) successively.Under nitrogen protection, be warming up to 60 ℃, reaction 6h is to the no Tetra hydro Phthalic anhydride of thin-layer chromatography detection; be cooled to 40 ℃, be evaporated to driedly, add ethyl acetate 4000ml, stir; leave standstill, topple over the upper strata stillness of night, use ethyl acetate extraction again 4 times, each 2000ml; combined ethyl acetate solution removes solvent under reduced pressure, uses re-crystallizing in ethyl acetate; activated carbon decolorizing gets white solid, i.e. compound (C); productive rate 90%, 241～242 ℃ of fusing points, purity〉99.5%.
Embodiment 6,
In the there-necked flask that agitator, nitrogen ingress pipe, reflux exchanger are housed, add Tetra hydro Phthalic anhydride (0.95mol), oxammonium hydrochloride (1.05mol), acetic anhydride (0.15mol), trifluoracetic acid (0.15mol), pyridine (1.25mol) and tetrahydrofuran (THF) (400ml) successively.Under nitrogen protection, be warming up to 60 ℃, reaction 6h is to the no Tetra hydro Phthalic anhydride of thin-layer chromatography detection; be cooled to 40 ℃, be evaporated to driedly, add ethyl acetate 4000ml, stir; leave standstill, topple over the upper strata stillness of night, use ethyl acetate extraction again 4 times, each 2000ml; combined ethyl acetate solution removes solvent under reduced pressure, uses re-crystallizing in ethyl acetate; activated carbon decolorizing gets white solid, i.e. compound (C); productive rate 96%, 241～242 ℃ of fusing points, purity〉99.5%.
Embodiment 7,
In the there-necked flask that agitator, nitrogen ingress pipe, reflux exchanger are housed, add 2 successively, 3-naphthalic anhydride (1mol), oxammonium hydrochloride (1.05mol), acetic anhydride (0.2mol), trifluoracetic acid (0.2mol), pyridine (1.5mol) and dioxane (400ml).Under nitrogen protection, be warming up to 100 ℃, reaction 6h is to thin-layer chromatography detection nothing 2; the 3-naphthalic anhydride is cooled to 60 ℃, is evaporated to driedly, adds ethyl acetate 4000ml; stir, leave standstill, topple over the upper strata stillness of night, use ethyl acetate extraction again 4 times; each 2000ml, combined ethyl acetate solution removes solvent under reduced pressure, uses re-crystallizing in ethyl acetate; activated carbon decolorizing gets white solid, i.e. compound (D); productive rate 92%, 260～261 ℃ of fusing points, purity〉99.5%.
Embodiment 8,
In the there-necked flask that agitator, nitrogen ingress pipe, reflux exchanger are housed, add 2 successively, 3-naphthalic anhydride (0.95mol), oxammonium hydrochloride (1.1mol), acetic anhydride (0.16mol), trifluoracetic acid (0.18mol), pyridine (1.3mol) and dioxane (400ml).Under nitrogen protection, be warming up to 100 ℃, reaction 6h is to thin-layer chromatography detection nothing 2; the 3-naphthalic anhydride is cooled to 60 ℃, is evaporated to driedly, adds ethyl acetate 4000ml; stir, leave standstill, topple over the upper strata stillness of night, use ethyl acetate extraction again 4 times; each 2000ml, combined ethyl acetate solution removes solvent under reduced pressure, uses re-crystallizing in ethyl acetate; activated carbon decolorizing gets white solid, i.e. compound (D); productive rate 86%, 260～261 ℃ of fusing points, purity〉99.5%.
Embodiment 9,
In the there-necked flask that agitator, nitrogen ingress pipe, reflux exchanger are housed, add 1 successively, 8-naphthalic anhydride (1mol), oxammonium hydrochloride (1.05mol), acetic anhydride (0.2mol), trifluoracetic acid (0.2mol), pyridine (1.5mol) and dioxane (400ml).Under nitrogen protection, be warming up to 100 ℃, reaction 6h is to thin-layer chromatography detection nothing 1; the 8-naphthalic anhydride is cooled to 60 ℃, is evaporated to driedly, adds ethyl acetate 4000ml; stir, leave standstill, topple over the upper strata stillness of night, use ethyl acetate extraction again 4 times; each 2000ml, combined ethyl acetate solution removes solvent under reduced pressure, uses re-crystallizing in ethyl acetate; activated carbon decolorizing gets white solid, i.e. compound (E); productive rate 88%, 282～283 ℃ of fusing points, purity〉99.5%.
Embodiment 9,
In the there-necked flask that agitator, nitrogen ingress pipe, reflux exchanger are housed, add 1 successively, 8-naphthalic anhydride (0.95mol), oxammonium hydrochloride (1.1mol), acetic anhydride (0.14mol), trifluoracetic acid (0.16mol), pyridine (1.2mol) and dioxane (400ml).Under nitrogen protection, be warming up to 100 ℃, reaction 6h is to thin-layer chromatography detection nothing 1; the 8-naphthalic anhydride is cooled to 60 ℃, is evaporated to driedly, adds ethyl acetate 4000ml; stir, leave standstill, topple over the upper strata stillness of night, use ethyl acetate extraction again 4 times; each 2000ml, combined ethyl acetate solution removes solvent under reduced pressure, uses re-crystallizing in ethyl acetate; activated carbon decolorizing gets white solid, i.e. compound (E); productive rate 80%, 282～283 ℃ of fusing points, purity〉99.5%.
Claims (1)
1. the preparation method of a N-hydroxy diimide; it is characterized in that: under nitrogen protection; in three-necked bottle, add the azanol composite salt, replace dicarboxylic anhydride, acetic anhydride, trifluoracetic acid, organic bases and solvent, be heated to 60～100 ℃ of reactions 2～6 hours, after reaction finishes; cooling; remove solvent under reduced pressure, the resistates ethyl acetate extraction concentrates; the crude product recrystallization purifying
Wherein, used organic bases is a kind of of triethylamine, pyridine;
Used solvent is a kind of of tetrahydrofuran (THF), 2-methyltetrahydrofuran, dioxane;
Used azanol composite salt is a kind of of oxammonium hydrochloride, oxammonium sulfate;
Used replacement dicarboxylic anhydride is Succinic anhydried, maleic anhydride, Tetra hydro Phthalic anhydride, 2,3-naphthalic anhydride, 1, and a kind of in the 8-naphthalic anhydride, and:
(1) replacing dicarboxylic anhydride is Succinic anhydried, the consumption mol ratio of Succinic anhydried, acetic anhydride, trifluoracetic acid, organic bases and azanol composite salt is respectively 0.95～1.2,0.01～0.05,0.01～0.05,1～1.5, obtain N-maloyl imines, structural formula is as follows:
(2) replacing dicarboxylic anhydride is maleic anhydride, the consumption mol ratio of maleic anhydride, acetic anhydride, trifluoracetic acid, organic bases and azanol composite salt is respectively 1.0～1.2,0.05～0.1,0.05～0.1,1～1.25, obtain N-hydroxyl maleimide, structural formula is as follows:
(3) replacing dicarboxylic anhydride is Tetra hydro Phthalic anhydride, the consumption mol ratio of Tetra hydro Phthalic anhydride, acetic anhydride, trifluoracetic acid, organic bases and azanol composite salt is respectively 0.9～1.1,0.1～0.2,0.1～0.2,1～1.5, obtain the N-hydroxyphthalimide, structural formula is as follows:
(4) replacing dicarboxylic anhydride is 2, the 3-naphthalic anhydride, 2, the consumption mol ratio of 3-naphthalic anhydride, acetic anhydride, trifluoracetic acid, organic bases and azanol composite salt is respectively 0.9～1.1,0.1～0.2,0.1～0.2,1～1.5, obtain N-hydroxyl-2, the 3-naphthalimide, structural formula is as follows:
(5) replacing dicarboxylic anhydride is 1, the 8-naphthalic anhydride, 1, the consumption mol ratio of 8-naphthalic anhydride, acetic anhydride, trifluoracetic acid, organic bases and azanol composite salt is respectively 0.9～1.1,0.1～0.2,0.1～0.2,1～1.5, obtain N-hydroxyl-1, the 8-naphthalimide, structural formula is as follows:
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101845012B (en) * | 2010-02-10 | 2012-03-21 | 李瑞菊 | Method for synthesizing N-hydroxy phthalimide with solid-phase process |
| CN103145601B (en) * | 2013-03-22 | 2015-08-19 | 上海其新生物科技有限公司 | The preparation method of N-hydroxysuccinimide |
| CN103351324A (en) * | 2013-07-01 | 2013-10-16 | 太仓市恒益医药化工原料厂 | Preparation method for 9-fluorenylmethoxycarbonyl succinimide |
| CN103575727B (en) * | 2013-10-18 | 2015-07-29 | 山西大学 | A kind of reagent and method detecting mercaptan |
| CN105111128B (en) * | 2015-09-14 | 2017-09-05 | 南京红宝丽醇胺化学有限公司 | A kind of preparation method of N hydroxyphthalimides |
| CN107903227B (en) * | 2017-11-22 | 2021-03-30 | 云南大学 | Succinic anhydride compound, gene and protein related to succinic anhydride compound and preparation method of succinic anhydride compound |
| CN108558728B (en) * | 2018-03-21 | 2021-10-15 | 泰安科赛尔化学科技有限公司 | Preparation method of N-hydroxysuccinimide |
| CN109053533A (en) * | 2018-09-14 | 2018-12-21 | 南京化学试剂股份有限公司 | A kind of refining methd of N- hydroxysuccinimide |
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| CN1953963A (en) * | 2004-05-17 | 2007-04-25 | 大赛璐化学工业株式会社 | Process for producing cyclic N-hydroxyimide compound |
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| CN1953963A (en) * | 2004-05-17 | 2007-04-25 | 大赛璐化学工业株式会社 | Process for producing cyclic N-hydroxyimide compound |
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