CN106380418B - It is a kind of to use N-Methyl pyrrolidone/SOCl2The method for efficiently realizing ketoxime Beckmann rearrangement - Google Patents

It is a kind of to use N-Methyl pyrrolidone/SOCl2The method for efficiently realizing ketoxime Beckmann rearrangement Download PDF

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Publication number
CN106380418B
CN106380418B CN201610808075.1A CN201610808075A CN106380418B CN 106380418 B CN106380418 B CN 106380418B CN 201610808075 A CN201610808075 A CN 201610808075A CN 106380418 B CN106380418 B CN 106380418B
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ketoxime
reaction
ethyl acetate
added
methyl pyrrolidone
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CN106380418A (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 present invention provides a kind of with N methyl pyrrolidones/SOCl2The method for efficiently realizing ketoxime Beckmann rearrangement.This approach includes the following steps：At room temperature, N methyl pyrrolidones react 20 min with thionyl chloride, ketoxime is added, after the reaction was continued 15 min, it is slowly added to water, ethyl acetate extraction liquid separation is added, organic layer obtains amide after saturated common salt water washing, anhydrous sodium sulfate drying and solvent being evaporated off with silica gel column chromatography separating purification.The present invention has the characteristics that technical process is simple, the reaction time is short, reaction yield is high.

Description

It is a kind of to use N-Methyl pyrrolidone/SOCl2Efficiently realize ketoxime Beckmann rearrangement Method
Technical field
N-Methyl pyrrolidone/SOCl is used the present invention relates to a kind of2The method for efficiently realizing ketoxime Beckmann rearrangement, tool Body belongs to technical field of organic synthesis.
Background technology
Amide is the organic matter of a kind of generally existing, is usually used in industry, agricultural and pharmacy industry.Ketoxime is reset through Beckmann Amide is obtained, is the common method (J.Am.Chem.Soc.2005,127,11240-11241) for preparing amide.Realize ketoxime The reagent that Beckmann is reset is from initially use PCl5, development is finally using other inorganic acids, organic acid, organic chloro-containing reagent Deng.For example, using " metaboric acid " (Tetrahedron Lett.2002,43,2455), " sulfamic acid " (Tetrahedron 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 reagents enrich the method for realizing ketoxime Beckmann rearrangement, but deposit in varying degrees In some shortcomings：Higher reaction temperature, longer reaction time, individual reagent toxicities are larger or expensive, adjoint other The generation of side reaction or post-processing complexity, reaction yield be not high (Tetrahedron Lett.2011,52,4888-4891).
In recent years, chemist is still dedicated to the new method that ketoxime Beckmann rearrangement is realized in development.
A kind of method is that 1,2-, bis- substituted cyclopropane ketenes and oxalyl chloride in-situ generation 1,2- bis- is utilized to replace -3,3- dichloros Cyclopropylene, the latter dissociate 1,2-, the bis- substitution -3- chlorine cyclopropylene cations catalysis ketoxime generation Beckmann generated and reset to obtain Amide (Chem. Commun., 2010,46,5808-5810；Chem.Sci.,2010,1,705–708).This kind of reaction is in room temperature Lower progress, most of ketoximes complete rearrangement reaction in dozens of minutes and obtain amide, good yields, but reagent used is more special Very.
Another method is that the Vilsmeier salt of " dialkyl group substituted amide-chloro-containing reagent " in-situ generation is utilized to be catalyzed ketone Oxime occurs Beckmann and resets to obtain amide.Currently, this kind of composite reagent of document report has：" dimethylformamide (DMF)- Cyanuric trichloride " (J.Org.Chem.2002,67,6272-6274), " DMF- pivaloyl chlorides " (Tetrahedron Lett.2011, 52,4888-4891) and " DMF- carbon tetrabromides " (Synlett 2014,25,665-670).The characteristics of such methods is reaction item Part is relatively mild (reacting at room temperature), and reaction yield is higher (generally 80% or more), but portion of reagent is more special (for example, tetrabromo Change carbon, pivaloyl chloride), the reaction time it is longer (a few hours to tens of hours).
Invention content
The present invention is reacted the Vilsmeier salt generated with thionyl chloride using N-Methyl pyrrolidone (NMP) and promotes ketoxime Beckmann rearrangement reactions, a kind of mild efficient amide preparation method is provided.
Its reaction principle can be described as follows：
First, NMP generates Vilsmeier salt (I) with thionyl chloride effect；And then, ketoxime and Vilsmeier salt (I) Effect generates intermediate (II), and releasesDue to the generation of (II), N-O key polarity is remarkably reinforced, and leads to N-O keys pole Easy fracture, to the molecule NMP that leaves away, and R1Tropic rearrangement occurs to obtain (III)；Finally (III) acts on obtaining amide with water.
Technical solution is as follows：
The present invention is a kind of to use N-Methyl pyrrolidone/SOCl2Efficiently realize that the method for ketoxime Beckmann rearrangement is in N- Methyl pyrrolidone, which is reacted with thionyl chloride in the Vilsmeier salt generated, is added ketoxime, realizes that the Beckmann of ketoxime is reset, Obtain corresponding amide；Specifically comprise the following steps：
Step 1：At room temperature, thionyl chloride is added in N-Methyl pyrrolidone, after reacting 20min, adds ketoxime The reaction was continued 15min, obtains reaction product；The molar ratio of ketoxime and thionyl chloride is 1.0:1.0~2.0, the quality of ketoxime with The volume ratio of N- methyl pyrrolidones is 1.0:5~30, the quality is in terms of g, and the volume is in terms of ml.
Step 2：Step 1 after reaction, water is slowly added into reaction product, adds ethyl acetate, is sufficiently stirred Stratification afterwards；The aqueous layer with ethyl acetate extraction separated, divides after the extract of ethyl acetate is merged with the organic layer separated It Yong not saturated common salt water washing, anhydrous sodium sulfate drying；Obtain crude product after ethyl acetate solvent is evaporated off, after through silica gel column layer Analysis isolates and purifies to obtain amide；Or above-mentioned steps 1 are after reaction, and the system of water is dissolved in for reaction product, produced to reaction In object plus water quenching is gone out after reaction, then obtains amide by vacuum distillation.
The ketoxime is fragrant ketoxime or alicyclic ring ketoxime.
Advantages of the present invention：Reagent used is cheap and easy to get, reaction condition is mild, technological operation is simple, the reaction time is short, Reaction yield is high.It is compared with the existing close document that is associated with, 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 implementation mode
By following embodiment, present invention be described in more detail, but the scope of the present invention is not appointed by these embodiments What is limited.
Embodiment 1
Antifebrin is prepared by acetophenone oxime.
Representative implementation process：At room temperature, sequentially added in reaction bulb 20ml N-Methyl pyrrolidones (NMP) and 0.55ml (7.5mmol) thionyl chloride, after reacting 20min, is added acetophenone oxime 0.68g (5mmol), continues at room temperature anti- Answer 15min.After being slowly added to 50ml water, 50ml ethyl acetate is added, separatory funnel liquid separation is used after being sufficiently mixed, water layer is again It is extracted with 50ml ethyl acetate, combined organic layer water and saturated common salt water washing, acetic acid second is evaporated off in anhydrous sodium sulfate drying Ester obtains crude product, further obtains white solid 0.64g, 114~116 DEG C of fusing point, reaction yield 94% with column chromatography.
Embodiment 2
N- phenylbenzamaides are prepared by diphenyl-ketoxime.
At room temperature, 20ml NMP and 0.55ml (7.5mmol) thionyl chloride is sequentially added in reaction bulb, reacts 20min Afterwards, diphenyl-ketoxime 0.68g (5mmol), the reaction was continued at room temperature 15min is added.After being slowly added to 50ml water, add 50ml ethyl acetate uses separatory funnel liquid separation, water layer to use 50ml ethyl acetate to extract again after being sufficiently mixed, combined organic layer is used Water and saturated common salt water washing, anhydrous sodium sulfate drying, are evaporated off ethyl acetate and obtain crude product, further obtained with column chromatography white Color solid 0.95g, 162~164 DEG C of fusing point, reaction yield 96%.
Embodiment 3
N- benzyl phenyl acetamides are prepared by dibenzyl ketoxime.
At room temperature, 20ml NMP and 0.55ml (7.5mmol) thionyl chloride is sequentially added in reaction bulb, reacts 20min Afterwards, dibenzyl ketoxime 1.13g (5mmol), the reaction was continued at room temperature 15min is added.After being slowly added to 50ml water, add 50ml ethyl acetate uses separatory funnel liquid separation, water layer to use 50ml ethyl acetate to extract again after being sufficiently mixed, combined organic layer is used Water and saturated common salt water washing, anhydrous sodium sulfate drying, are evaporated off ethyl acetate and obtain crude product, further obtained with column chromatography white Color solid 1.04g, 67~69 DEG C of fusing point, reaction yield 92%.
Embodiment 4
Ring lauramide is prepared by cyclododecanone oxime.
At room temperature, 20ml NMP and 0.55ml (7.5mmol) thionyl chloride is sequentially added in reaction bulb, reacts 20min Afterwards, cyclododecanone oxime 0.99g (5mmol), the reaction was continued at room temperature 15min is added.After being slowly added to 50ml water, add 50ml ethyl acetate uses separatory funnel liquid separation, water layer to use 50ml ethyl acetate to extract again after being sufficiently mixed, combined organic layer is used Water and saturated common salt water washing, anhydrous sodium sulfate drying, are evaporated off ethyl acetate and obtain crude product, further obtained with column chromatography white Color solid 0.88g, 150~152 DEG C of fusing point, reaction yield 89%.
Embodiment 5
By preparing caprolactam with cyclohexanone-oxime.
At room temperature, 20ml NMP and 0.55ml (7.5mmol) thionyl chloride is sequentially added in reaction bulb, reacts 20min Afterwards, cyclohexanone oxime 0.57g (5mmol), the reaction was continued at room temperature 15min is added.Water quenching is added to go out reaction, vacuum distillation obtains white Color solid 0.50g, 69~71 DEG C of fusing point, reaction yield 88%.

Claims (2)

1. a kind of using N-Methyl pyrrolidone/SOCl2The method for realizing ketoxime Beckmann rearrangement, it is characterised in that：The side Method is to react in the Vilsmeier salt generated that ketoxime is added with thionyl chloride in N-Methyl pyrrolidone, realizes ketoxime Beckmann is reset, and obtains corresponding amide；Specifically comprise the following steps：
Step 1：At room temperature, thionyl chloride is added in N-Methyl pyrrolidone, after reacting 20min, adds ketoxime continuation 15min is reacted, reaction product is obtained；The molar ratio of ketoxime and thionyl chloride is 1.0:1.0~2.0, quality and the N- first of ketoxime The volume ratio of base pyrrolidones is 1.0:5~30, the quality is in terms of g, and the volume is in terms of ml；
Step 2：Step 1 after reaction, water is slowly added into reaction product, adds ethyl acetate, is sufficiently stirred rear quiet Set layering；The aqueous layer with ethyl acetate extraction separated, is used respectively after the extract of ethyl acetate is merged with the organic layer separated Saturated common salt water washing, anhydrous sodium sulfate drying；Obtain crude product after ethyl acetate solvent is evaporated off, after through silica gel column chromatography point Amide is obtained from purifying；Or above-mentioned steps 1 are after reaction, the system of water are dissolved in for reaction product, into reaction product Add water quenching to go out after reaction, then amide is obtained by vacuum distillation.
2. a kind of N-Methyl pyrrolidone/SOCl according to claim 12The method for realizing ketoxime Beckmann rearrangement, It is characterized in that：The 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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Citations (5)

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Publication number Priority date Publication date Assignee Title
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
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
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
JP2011178672A (en) * 2010-02-26 2011-09-15 Yamaguchi Univ Method of producing amide compound

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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
JP2011178672A (en) * 2010-02-26 2011-09-15 Yamaguchi Univ Method of producing amide compound

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Title
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Lactam/MoCl5 interaction in CH2Cl2: synthesis and X-ray characterization of protonated d-valerolactam salts;Fabio Marchetti等;《RSC Adv.》;20131231;第3卷;第10007–10013页 *
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