CN106380418A - Method for efficiently rearranging ketoxime Beckmann by N-methyl pyrrolidone/SOC12 (thionyl chloride) - Google Patents

Method for efficiently rearranging ketoxime Beckmann by N-methyl pyrrolidone/SOC12 (thionyl chloride) Download PDF

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CN106380418A
CN106380418A CN201610808075.1A CN201610808075A CN106380418A CN 106380418 A CN106380418 A CN 106380418A CN 201610808075 A CN201610808075 A CN 201610808075A CN 106380418 A CN106380418 A CN 106380418A
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ketoxime
methyl pyrrolidone
reaction
ethyl acetate
thionyl chloride
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CN106380418B (en
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周安西
郑大贵
祝显虹
罗年华
胡鹏辉
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Shangrao Normal University
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Shangrao Normal University
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C231/00—Preparation of carboxylic acid amides
    • C07C231/10—Preparation of carboxylic acid amides from compounds not provided for in groups C07C231/02 - C07C231/08
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D201/00—Preparation, separation, purification or stabilisation of unsubstituted lactams
    • C07D201/02—Preparation of lactams
    • C07D201/04—Preparation of lactams from or via oximes by Beckmann rearrangement
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
    • C07D223/02—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings
    • C07D223/06—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D223/08—Oxygen atoms
    • C07D223/10—Oxygen atoms attached in position 2
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D225/00—Heterocyclic compounds containing rings of more than seven members having one nitrogen atom as the only ring hetero atom
    • C07D225/02—Heterocyclic compounds containing rings of more than seven members having one nitrogen atom as the only ring hetero atom not condensed with other rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D227/00—Heterocyclic compounds containing rings having one nitrogen atom as the only ring hetero atom, according to more than one of groups C07D203/00 - C07D225/00
    • C07D227/02—Heterocyclic compounds containing rings having one nitrogen atom as the only ring hetero atom, according to more than one of groups C07D203/00 - C07D225/00 with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D227/06—Heterocyclic compounds containing rings having one nitrogen atom as the only ring hetero atom, according to more than one of groups C07D203/00 - C07D225/00 with only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D227/08—Oxygen atoms
    • C07D227/087—One doubly-bound oxygen atom in position 2, e.g. lactams

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Other In-Based Heterocyclic Compounds (AREA)

Abstract

The invention provides a method for efficiently rearranging ketoxime Beckmann by N-methyl pyrrolidone/SOC12 (thionyl chloride). The method comprises the following steps of at room temperature, reacting the N-methyl pyrrolidone and the SOC12 for 20min, adding ketoxime, continuing to react for 15min, slowly adding water, adding ethyl acetate extraction separating liquid, washing an organic layer by saturated salt water, drying by anhydrous sodium sulfate, evaporating solvent, and separating and purifying by silica-gel column chromatography, so as to obtain amide. The method has the characteristics that the technology process is simple, the reaction time is short, the reaction yield is high, and the like.

Description

A kind of N-Methyl pyrrolidone/SOCl2Efficiently realize ketoxime Beckmann rearrangement Method
Technical field
The present invention relates to a kind of N-Methyl pyrrolidone/SOCl2The method efficiently realizing ketoxime Beckmann rearrangement, tool Body belongs to technical field of organic synthesis.
Background technology
Amide is the Organic substance of a class generally existing, is usually used in industry, agricultural and pharmacy industry.Ketoxime is reset through Beckmann Obtain amide, be the common method (J.Am.Chem.Soc.2005,127,11240-11241) preparing amide.Realize ketoxime The reagent that Beckmann resets is from initially use PCl5, development is finally using other mineral acids, organic acid, organic chloro-containing reagent Deng.For example, " metaboric acid " (Tetrahedron Lett.2002,43,2455), " sulfamic acid " (Tetrahedron are used Lett.2004,45,3369), " chlorosulfonic acid " (Tetrahedron Lett.2005,46,671), " chloral hydrate " (Tetrahedron Lett.2003,44,755), " ethyl chloroformate/boron trifluoride ether solution " (Tetrahedron Lett.2000,41,5427) etc..These reagent enrich the method realizing ketoxime Beckmann rearrangement, but deposit in varying degrees In some shortcomings：Higher reaction temperature, longer response time, indivedual reagent toxicity are larger or expensive, with other The generation of side reaction or post processing complexity, reaction yield not high (Tetrahedron Lett.2011,52,4888 4891).
In recent years, chemist is still devoted to developing the new method realizing ketoxime Beckmann rearrangement.
A kind of method is to utilize 1,2- bis- substituted cyclopropane ketenes and oxalyl chloride in-situ generation 1,2- bis- replacement -3,3- dichloro Cyclopropylene, 1, the 2- bis- replacement -3- chlorine cyclopropylene cation catalysis ketoxime that the latter's dissociation generates occurs Beckmann rearrangement to obtain Amide (Chem.Commun., 2010,46,5808 5810；Chem.Sci.,2010,1,705–708).This kind of reaction is in room temperature Under carry out, most of ketoximes complete rearrangement reaction in several tens minutes and obtain amide, good yields, but reagent used is more special Very.
Another kind of method is that the Vilsmeier salt using " dialkyl group substituted amide-chloro-containing reagent " in-situ generation is catalyzed ketone Oxime occurs Beckmann rearrangement to obtain amide.At present, this kind of composite reagent of document report has：" dimethylformamide (DMF)- Cyanuric trichloride " (J.Org.Chem.2002,67,6272-6274), " DMF- pivaloyl chloride " (Tetrahedron Lett.2011, 52,4888 4891) and " DMF- carbon tetrabromide " (Synlett 2014,25,665 670).The feature of this kind of method is reaction bar Part relatively gentle (reacting under room temperature), reaction yield higher (generally more than 80%), but more special (for example, the tetrabromo of portion of reagent Change carbon, pivaloyl chloride), the response time longer (a few hours to tens of hours).
Content of the invention
The present invention utilizes N-Methyl pyrrolidone (NMP) and thionyl chloride to react the Vilsmeier salt promotion ketoxime generating Beckmann rearrangement reaction, one kind gently efficient amide preparation method is provided.
Its reaction principle can be described as follows：
First, NMP and thionyl chloride effect generate Vilsmeier salt (I)；And then, ketoxime and Vilsmeier salt (I) Effect generates intermediate (II), and dischargesDue to the generation of (II), N-O key polarity is remarkably reinforced, and leads to N-O key easily Fracture, thus the molecule NMP that leaves away, and R1Tropic rearrangement is occurred to obtain (III)；Finally (III) and water effect obtain amide.
Technical scheme is as follows：
A kind of N-Methyl pyrrolidone/SOCl of the present invention2The method efficiently realizing ketoxime Beckmann rearrangement is in N- Methyl pyrrolidone and thionyl chloride react and add ketoxime in the Vilsmeier salt generating, and the Beckmann realizing ketoxime resets, Obtain corresponding amide；Specifically include following steps：
Step 1：Under room temperature, thionyl chloride is added in N-Methyl pyrrolidone, after reaction 20min, adds ketoxime Continue reaction 15min, obtain product；Ketoxime is 1.0 with the mol ratio of thionyl chloride:1.0～2.0, the quality of ketoxime with The volume ratio of N-Methyl pyrrolidone is 1.0:5～30, in terms of g, described volume is in terms of ml for described quality.
Step 2：After step 1 reaction terminates, it is slowly added to water in product, adds ethyl acetate, be sufficiently stirred for Stratification afterwards；The aqueous layer with ethyl acetate extraction separating, divides after the extract of ethyl acetate is merged with the organic layer separating Yong not saturated common salt water washing, anhydrous sodium sulfate drying；Crude product is obtained, through silica gel column layer after it after ethyl acetate solvent is evaporated off Analysis isolates and purifies and obtains amide；Or after above-mentioned steps 1 reaction terminates, product is dissolved in the system of water, produces to reaction Add water in thing after reaction is quenched, then amide is obtained by vacuum distillation.
Described ketoxime is fragrant ketoxime or alicyclic ring ketoxime.
Advantages of the present invention：Reagent used is cheap and easy to get, reaction condition is gentle, technological operation is simple, the response time is short, Reaction yield is high.Contrasted with the existing close document that associates, advantages of the present invention is as shown in the table：
Remarks：Ref 1:Chem.Commun.,2010,46,5808–5810；Ref 2:Chem.Sci.,2010,1,705– 708；Ref 3:Tetrahedron Lett.2011,52,4888–4891；Ref 4:J.Org.Chem.2002,67,6272- 6274；Ref 5:Synlett 2014,25,665–670.
Specific embodiment
Further describe the present invention by following examples, but the scope of the present invention is not appointed by these embodiments What limits.
Embodiment 1
Acetanilide is prepared by acetophenone oxime.
Representational implementation process：Under room temperature, sequentially add in reaction bulb 20ml N-Methyl pyrrolidone (NMP) and 0.55ml (7.5mmol) thionyl chloride, after reaction 20min, adds acetophenone oxime 0.68g (5mmol), continues reaction at room temperature 15min.After being slowly added to 50ml water, add 50ml ethyl acetate, divide liquid with separatory funnel after being sufficiently mixed, water layer is used again The extraction of 50ml ethyl acetate, the organic layer water of merging and saturated common salt water washing, anhydrous sodium sulfate drying, are evaporated off ethyl acetate Obtain crude product, obtain white solid 0.64g, 114～116 DEG C of fusing point, reaction yield 94% with column chromatography further.
Embodiment 2
N- phenylbenzamaide is prepared by diphenyl-ketoxime.
Under room temperature, in reaction bulb, sequentially add 20ml NMP and 0.55ml (7.5mmol) thionyl chloride, after reaction 20min, Add diphenyl-ketoxime 0.68g (5mmol), continue reaction 15min at room temperature.After being slowly added to 50ml water, add 50ml Ethyl acetate, divides liquid with separatory funnel after being sufficiently mixed, water layer again use 50ml ethyl acetate extract, the organic layer water of merging and Saturated common salt water washing, anhydrous sodium sulfate drying, ethyl acetate is evaporated off and obtains crude product, obtain white with column chromatography further solid Body 0.95g, 162～164 DEG C of fusing point, reaction yield 96%.
Embodiment 3
N- benzyl phenyl acetamide is prepared by dibenzyl ketoxime.
Under room temperature, in reaction bulb, sequentially add 20ml NMP and 0.55ml (7.5mmol) thionyl chloride, after reaction 20min, Add dibenzyl ketoxime 1.13g (5mmol), continue reaction 15min at room temperature.After being slowly added to 50ml water, add 50ml Ethyl acetate, divides liquid with separatory funnel after being sufficiently mixed, water layer again use 50ml ethyl acetate extract, the organic layer water of merging and Saturated common salt water washing, anhydrous sodium sulfate drying, ethyl acetate is evaporated off and obtains crude product, obtain white with column chromatography further solid Body 1.04g, 67～69 DEG C of fusing point, reaction yield 92%.
Embodiment 4
Ring lauramide is prepared by cyclododecanone oxime.
Under room temperature, in reaction bulb, sequentially add 20ml NMP and 0.55ml (7.5mmol) thionyl chloride, after reaction 20min, Add cyclododecanone oxime 0.99g (5mmol), continue reaction 15min at room temperature.After being slowly added to 50ml water, add 50ml Ethyl acetate, divides liquid with separatory funnel after being sufficiently mixed, water layer again use 50ml ethyl acetate extract, the organic layer water of merging and Saturated common salt water washing, anhydrous sodium sulfate drying, ethyl acetate is evaporated off and obtains crude product, obtain white with column chromatography further solid Body 0.88g, 150～152 DEG C of fusing point, reaction yield 89%.
Embodiment 5
By preparing caprolactam with cyclohexanone-oxime.
Under room temperature, in reaction bulb, sequentially add 20ml NMP and 0.55ml (7.5mmol) thionyl chloride, after reaction 20min, Add cyclohexanone-oxime 0.57g (5mmol), continue reaction 15min at room temperature.Add water and reaction is quenched, vacuum distillation obtains white Solid 0.50g, 69～71 DEG C of fusing point, reaction yield 88%.

Claims (2)

1. a kind of N-Methyl pyrrolidone/SOCl2Efficiently realize the method for ketoxime Beckmann rearrangement it is characterised in that：Described Method be N-Methyl pyrrolidone and thionyl chloride react generate Vilsmeier salt in add ketoxime, realize ketoxime Beckmann resets, and obtains corresponding amide；Specifically include following steps：
Step 1：Under room temperature, thionyl chloride is added in N-Methyl pyrrolidone, after reaction 20 min, adds ketoxime and continue React 15 min, obtain product；Ketoxime is 1.0 with the mol ratio of thionyl chloride:1.0～2.0, the quality of ketoxime and N- The volume ratio of methyl pyrrolidone is 1.0:5 ~ 30, in terms of g, described volume is in terms of ml for described quality；
Step 2：After step 1 reaction terminates, it is slowly added to water in product, adds ethyl acetate, quiet after being sufficiently stirred for Put layering；The aqueous layer with ethyl acetate extraction separating, uses after the extract of ethyl acetate is merged with the organic layer separating respectively Saturated common salt water washing, anhydrous sodium sulfate drying；Obtain crude product after ethyl acetate solvent is evaporated off, divide through silica gel column chromatography after it Obtain amide from purification；Or after above-mentioned steps 1 reaction terminates, product is dissolved in the system of water, in product Add water after reaction is quenched, then amide is obtained by vacuum distillation.
2. a kind of N-Methyl pyrrolidone/SOCl according to claim 12Efficiently realize ketoxime Beckmann rearrangement Method it is characterised in that：Described ketoxime is fragrant ketoxime or alicyclic ring ketoxime.
CN201610808075.1A 2016-09-07 2016-09-07 It is a kind of to use N-Methyl pyrrolidone/SOCl2The method for efficiently realizing ketoxime Beckmann rearrangement Expired - Fee Related CN106380418B (en)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115304532A (en) * 2022-07-27 2022-11-08 江西盛源新材料有限公司 Purification method of N-methyl pyrrolidone

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EP0515063A1 (en) * 1991-05-21 1992-11-25 Sumitomo Chemical Company Limited Process for producing amide by liquid phase rearrangement of oxime
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JP2011178672A (en) * 2010-02-26 2011-09-15 Yamaguchi Univ Method of producing amide compound

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CN1058391A (en) * 1990-07-20 1992-02-05 赫希斯特人造丝公司 The preparation of acetoamidophenol
EP0515063A1 (en) * 1991-05-21 1992-11-25 Sumitomo Chemical Company Limited Process for producing amide by liquid phase rearrangement of oxime
CN1852898A (en) * 2003-09-18 2006-10-25 住友化学株式会社 Ionic liquid and method of reaction using the same
CN1778796A (en) * 2004-11-17 2006-05-31 中国石油化工股份有限公司 Production of hexyl lactam in ion liquid
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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115304532A (en) * 2022-07-27 2022-11-08 江西盛源新材料有限公司 Purification method of N-methyl pyrrolidone

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