CN106243072B - The method that alkali-free, condition of no solvent prepare furane derivative by Feist-Benary reactions - Google Patents

The method that alkali-free, condition of no solvent prepare furane derivative by Feist-Benary reactions Download PDF

Info

Publication number
CN106243072B
CN106243072B CN201610566687.4A CN201610566687A CN106243072B CN 106243072 B CN106243072 B CN 106243072B CN 201610566687 A CN201610566687 A CN 201610566687A CN 106243072 B CN106243072 B CN 106243072B
Authority
CN
China
Prior art keywords
reaction
alkyl
condition
alkali
reactions
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Fee Related
Application number
CN201610566687.4A
Other languages
Chinese (zh)
Other versions
CN106243072A (en
Inventor
唐强
罗娟
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Chongqing Medical University
Original Assignee
Chongqing Medical University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Chongqing Medical University filed Critical Chongqing Medical University
Priority to CN201610566687.4A priority Critical patent/CN106243072B/en
Publication of CN106243072A publication Critical patent/CN106243072A/en
Application granted granted Critical
Publication of CN106243072B publication Critical patent/CN106243072B/en
Expired - Fee Related legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
    • C07D307/82—Benzo [b] furans; Hydrogenated benzo [b] furans 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 carbon atoms of the hetero ring
    • C07D307/84—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members 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
    • C07D307/68—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
  • Furan Compounds (AREA)

Abstract

The present invention provides a kind of method preparing furane derivative, i.e., under alkali-free, condition of no solvent, α halogenated ketones react to obtain polysubstituted furan compounds with beta-dicarbonyl compound.The preparation method of polysubstituted furan compounds of the present invention, raw material is easy to get, of low cost, and reaction condition is mild, it is easy to operate easily-controllable, side reaction is less, and post-processing is simple, and product yield is higher, without any catalysts and solvents, production cost is greatly saved, there is preferable environmental benefit and economic benefit, be suitable for industrialized production.

Description

Alkali-free, condition of no solvent prepare furane derivative by Feist-Benary reactions Method
Technical field
The present invention relates to the preparation methods of polysubstituted furan compounds, and in particular to α-halogenatedketone and beta-dicarbonyl compound The method for efficiently synthesizing polysubstituted furan compounds for raw material.
Background technology
Furans is important five member ring heterocyclic compound, plays important role in chemistry, biology and drug research, very More natural products all contain furan nucleus nuclear structure, these furan derivatives usually all have certain bioactivity, such as anti- Bacterium, desinsection, it is antitumor, calm the effects that.
Synthesis about furan compound has many document reports, such as under bronsted acid or Louis acid catalysis, Isosorbide-5-Nitrae-dicarbonyl compound occurs condensation reaction and prepares (Paal-Knorr furans synthetic reaction)；Using alkene, alkynes as substrate, lead to Transition metal-catalyzed cyclization is crossed to prepare；Structural modification is carried out as substrate prepare complicated furan compound etc. using simple furans Deng.Wherein most classical is Feist-B é nary furans synthetic reactions, and this method is directly with α-halogenatedketone or aldehyde and beta-dicarbonyl Compound is substrate, and preparing synthesis by two-step reaction obtains furane derivative.
Being reacted by the Feist-B é nary of raw material of α-halogenatedketone for document report, is usually required for two steps.The first step, alkali Dihydrofuran IV is catalyzed and synthesized, and is needed with excessive alkali come generated acid in neutralization reaction.Used alkali includes：Ammonia Gas, triethylamine, sodium carbonate, potassium carbonate, sodium hydroxide, potassium hydroxide, sodium methoxide, sodium ethoxide, sodium hydride etc..Used solvent Including ether, dichloromethane, toluene, methanol, water, DMF etc. (1. K.Ghosh, R.Karmakar, D.Mal, Eur.J.Org.Chem.2013,2013,4037-4046；2. Stetter, H.；Lauterbach, R., Synthese des Evodons und Menthofurans.Chem.Ber.1960,93,603-607；3. R.Aranda, K.Villalba, E.C.F.Masaguer, J.Brea, F.Areias, E.Dom í nguez, J.Selent, L.L ó pez, F.Sanz, M.Pastor, M.I.Loza, J.Med.Chem.2008,51,6085-6094).Second step needs acid catalysis heating to carry out dihydro The dehydration of furans IV, finally to prepare furane derivative III.Used acid includes hydrochloric acid, acetic acid, sulfuric acid etc..
As it can be seen that although Feist-B é nary furans synthetic reactions are the most classical modes of current synthesis furan compound, but Usually it is required for two steps to synthesize, first step reaction needs that excessive alkali is added to be catalyzed reaction, and is generated during neutralization reaction Acid；The dihydrofuran intermediate of generation needs again acid adding heating that could be dehydrated and wait until corresponding furans product again.The reaction needs A large amount of solvent, and two-step reaction are wanted, cumbersome, yield is relatively low.
Invention content
The purpose of the present invention is to provide one kind not needing alkali or acid, does not need solvent, with good chemical specificity, instead Answer condition simple, post-processing is simple, the preparation method of the much lower substituted furan compound of production cost.
Purpose of the present invention is to what is be achieved through the following technical solutions：
The method that alkali-free, condition of no solvent prepare furane derivative by Feist-B é nary reactions：In alkali-free and without molten Under the conditions of agent, beta-dicarbonyl shown in α-halogenatedketone and general formula (IIa) or (IIb) shown in general formula (Ia), (Ib) or (Ic) Conjunction object, which reacts, respectively obtains polysubstituted furan compounds shown in general formula (IIIa), (IIIb) or (IIIc), and chemistry is anti- Answer formula (A), (B) and (C) as follows：
Wherein, R1For H, C1-C4Alkyl or phenyl；R2For H, C1-C4Alkyl or phenyl；R3For C1-C4Alkyl；R4For C1-C4 Alkyl；R5For C1-C4Alkyl；R6For C1-C4Alkyl；R7For C1-C4Alkyl or C1-C4Alkoxy；Or R6With R7Be connected to each other cyclization, Composition-(CH2)3-；X is bromine or chlorine atom.
Preferably, the R1For H or phenyl；R2For H, methyl or phenyl；R3For C1-C2Alkyl；R4For C1-C2Alkyl；R5For C1-C2Alkyl；R6For C1-C2Alkyl；R7For C1-C2Alkyl or C1-C2Alkoxy；Or R6With R7Be connected to each other cyclization, constitute- (CH2)3-；X is bromine or chlorine atom.
Wherein, the reaction temperature is 0-120 DEG C, and the reaction time is 0.5-100 hours.
Wherein, the molar ratio of both the α-halogenatedketone and described beta-dicarbonyl compound is 1-10: 1.
The method for preparing furane derivative, operating procedure are as follows：Under stiring, the α-halogenatedketone and described Beta-dicarbonyl compound reacts, and reaction process is monitored with TLC, waits for after reaction, through isolating and purifying to obtain described take more For furan compound.
The method for preparing furane derivative, concrete operation step are as follows：Under stiring, the α-halogenatedketone and The beta-dicarbonyl compound is reacted at 0-120 DEG C, until becoming uniform liquid, reaction process is monitored with TLC, after reaction The mixture arrived carries out silica gel column chromatography separation, obtains the polysubstituted furan compounds.
Compared with existing Feist-B é nary furans synthetic reactions, the present invention has the following advantages that：
1) method that the present invention prepares polysubstituted furan compounds is not necessarily to any catalysts and solvents, reduces and be produced into This, reduces environmental pollution.
2) preparation method of the present invention, reaction condition is mild, one pot reaction, easy to operate.
3) synthetic method of the present invention, regioselectivity is good, and side reaction is less, and product is easily separated, and post-processing is simple, And achieve preferable yield (70-85%).
To sum up, synthetic method (one pot reaction) of the present invention, raw material is easy to get, of low cost, reaction condition temperature With easy to operate easily-controllable, side reaction is less, and post-processing is simple, and product yield is higher, is not necessarily to any catalysts and solvents, significantly Production cost has been saved, there is preferable environmental benefit and economic benefit, be suitable for industrialized production.
Specific implementation mode
It is illustrated in detail by way of the following examples the present invention, but the present invention is not only limitted in embodiment.
Embodiment 1：1- chlroacetones and 1, hydroresorcinol reaction
In 50mL round-bottomed flasks, 1- chlorine cyclohexanone (10mmol) and 1, hydroresorcinol (5mmol) is added.In stirring Slowly heating rises to 60 DEG C, and mixture becomes uniform liquid, constantly monitors reaction in reaction with TLC.It obtains after reaction Mixture directly carries out silica gel column chromatography separation, and it is yellow oil, yield 85% to obtain furans IIIa1.
1H NMR (400MHz, CDCl3) δ 7.06 (s, 1H), 2.82 (t, J=6.3Hz, 2H), 2.46 (dd, J=7.2, 5.8Hz, 2H), 2.19 (d, J=1.3Hz, 3H), 2.18-2.10 (m, 2H)；13C NMR (101MHz, CDCl3) δ 195.73, 167.42,138.93,120.44,119.10,38.31,23.64,22.76,9.09；IR (KBr, cm-1) 2952,1667,1462, 1411,1071,573；MS(ESI)calcd for C9H11O2(M+H)+：151.1, Found：151.2.
Embodiment 2：3-BrPA ethyl ester and 1, hydroresorcinol reaction
In 50mL round-bottomed flasks, 3-BrPA ethyl ester (10mmol) and 1, hydroresorcinol (5mmol) is added.It is stirring Slowly heating rises to 80 DEG C of mixtures and becomes uniform liquid in mixing, and constantly monitors reaction in reaction with TLC.It obtains after reaction Mixture directly carry out silica gel column chromatography separation, obtain furans IIIc1 be pale yellow oil, yield 76%.
1H NMR (400MHz, CDCl3) δ 7.85 (s, 1H), 4.31 (q, J=7.1Hz, 2H), 2.88 (t, J=6.3Hz, 2H), 2.61-2.44 (m, 2H), 2.24-2.07 (m, 2H), 1.34 (t, J=7.1Hz, 3H)；13C NMR (101MHz, CDCl3)δ 191.98,168.33,161.91,147.77,118.73,117.48,60.94,38.71,23.60,22.17,14.19；IR (KBr, cm-1)：3451,3120,1736,1554,1455,1300,1183,1002,878,769,586；MS(ESI)calcd for C11H13O4(M+H)+：209.0, Found：209.1
Embodiment 3：3-BrPA ethyl ester and 1, the reaction of 3- pentanediones
In 50mL round-bottomed flasks, 3-BrPA ethyl ester (10mmol) and 1,3- pentanediones (5mmol) is added.It is stirring In slowly heating rise to 100 DEG C of mixtures and become uniform liquid, reaction is constantly monitored in reaction with TLC.It obtains after reaction Mixture directly carry out silica gel column chromatography separation, obtain furans IIIc2 be yellow oil, yield 81%.
Embodiment 4：3-BrPA ethyl ester is reacted with ethyl acetoacetate
In 50mL round-bottomed flasks, 3-BrPA ethyl ester (10mmol) and ethyl acetoacetate (5mmol) is added.It is stirring Slowly heating rises to 100 DEG C of mixtures and becomes uniform liquid in mixing, and constantly monitors reaction in reaction with TLC.After reaction The mixture arrived directly carries out silica gel column chromatography separation, and it is yellow oil, yield 72% to obtain furans IIIc3.
Embodiment 5：2- chloroacetyl acetacetic esters and 1, hydroresorcinol reaction
In 50mL round-bottomed flasks, 2- chloroacetyl acetacetic esters (10mmol) and 1, hydroresorcinol (5mmol) is added. Slowly heating rises to 60 DEG C of mixtures and becomes uniform liquid in stirring, constantly monitors reaction in reaction with TLC.After reaction The mixture arrived directly carries out silica gel column chromatography separation, and it is light colorless oil, yield 75% to obtain furans IIIb1.
1H NMR (400MHz, CDCl3) δ 4.37 (q, J=7.1Hz, 2H), 2.91 (t, J=6.3Hz, 2H), 2.55 (s, 3H), 2.53-2.46 (m, 2H), 2.23-2.09 (m, 2H), 1.38 (t, J=7.1Hz, 3H)；13C NMR (101MHz, CDCl3)δ 195.11,168.69,159.51,140.19,129.70,121.72,60.94,38.41,23.78,22.20,14.37, 10.39；MS(ESI)calcd for C12H15O4(M+H)+：223.1, Found：223.0.
Embodiment 6：Chloro- 1, the 3- diphenyl acetones of 1- and 1, hydroresorcinol reaction
In 50mL round-bottomed flasks, chloro- 1, the 3- diphenyl acetones (10mmol) of 1- and 1, hydroresorcinol is added (5mmol).Slowly heating rises to 100 DEG C of mixtures and becomes uniform liquid in stirring, constantly monitors reaction in reaction with TLC. The mixture obtained after reaction directly carries out silica gel column chromatography separation, and it is red solid, yield to obtain furans IIIa2 73%.
1H NMR (400MHz, CDCl3) δ 7.47-7.38 (m, 4H), 7.38-7.29 (m, 3H), 7.29-7.19 (m, 3H), 4.00 (s, 2H), 2.89 (t, J=6.3Hz, 2H), 2.51 (t, J=6.3Hz, 2H), 2.27-2.10 (m, 2H)；13C NMR (101MHz, CDCl3) δ 194.04,166.48,150.42,138.00,131.52,129.82,128.66,128.45, 128.00,127.41,126.64,120.52,119.78,38.66,32.09,23.78,22.49；IR (KBr, cm-1)：3423, 3414,1670,1574,1428,1073,1009,773,502；MS(ESI)calcd for C21H19O2(M+H)+：303.1 Found：303.0.
Embodiment 7：The chloro- 2- butanone of 3- and 1, hydroresorcinol reaction
In 50mL round-bottomed flasks, the chloro- 2- butanone (10mmol) of 3- and 1, hydroresorcinol (5mmol) is added.It is stirring In slowly heating rise to 80 DEG C of mixtures and become uniform liquid, reaction is constantly monitored in reaction with TLC.It obtains after reaction Mixture directly carries out silica gel column chromatography separation, and it is brown oil, yield 83% to obtain furans IIIa3.
1H NMR (400MHz, CDCl3) δ 2.78 (t, J=6.3Hz, 2H), 2.46-2.39 (m, 2H), 2.17 (s, 3H), 2.14-2.07 (m, 2H), 2.10 (s, 3H)；13C NMR (101MHz, CDCl3) δ 195.84,165.18,147.49,121.03, 112.60,38.28,23.48,22.76,10.85,8.98；IR (KBr, cm-1)：2950,1671,1585,1438,1296, 1193,1009,896,677,560；MS(ESI)calcd for C10H13O2(M+H)+：165.0, Found：165.4.
Embodiment 8：3-BrPA methyl esters is reacted with methyl acetoacetate
In 50mL round-bottomed flasks, 3-BrPA methyl esters (40mmol) and methyl acetoacetate (5mmol) is added.It is stirring Slowly heating rises to 50 DEG C of mixtures and becomes uniform liquid in mixing, and constantly monitors reaction in reaction with TLC.It obtains after reaction Mixture directly carry out silica gel column chromatography separation, obtain furans IIIc3 be yellow oil, yield 72%.

Claims (3)

1. the method that alkali-free, condition of no solvent prepare furane derivative by Feist-B é nary reactions, it is characterised in that：In nothing Under alkali and condition of no solvent, β-shown in α-halogenatedketone and general formula (IIa) or (IIb) shown in general formula (Ia), (Ib) or (Ic) Dicarbonyl compound, which reacts, respectively obtains polysubstituted furan compounds shown in general formula (IIIa), (IIIb) or (IIIc), Its chemical equation (A), (B) and (C) is as follows：
Wherein, the R1For H or phenyl；R2For H, methyl or phenyl；R3For C1-C2Alkyl；R4For C1-C2Alkyl；R5For C1-C2Alkane Base；R6For C1-C2Alkyl；R7For C1-C2Alkyl or C1-C2Alkoxy；Or R6With R7Be connected to each other cyclization, composition-(CH2)3-；X is Bromine or chlorine atom；Its concrete operation step is as follows：Under stiring, the α-halogenatedketone and the beta-dicarbonyl compound are in 0- 120 DEG C of reactions monitor reaction process, the mixture obtained after reaction carries out silica gel column layer until becoming uniform liquid with TLC Analysis separation, obtains the polysubstituted furan compounds.
2. the method according to claim 1 for preparing furane derivative, wherein the reaction temperature is 0-120 DEG C, reaction Time is 0.5-100 hours.
3. the method according to claim 1 for preparing furane derivative, wherein the α-halogenatedketone and the beta-dicarbonyl The molar ratio of both compounds is 1-10: 1.
CN201610566687.4A 2016-07-18 2016-07-18 The method that alkali-free, condition of no solvent prepare furane derivative by Feist-Benary reactions Expired - Fee Related CN106243072B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201610566687.4A CN106243072B (en) 2016-07-18 2016-07-18 The method that alkali-free, condition of no solvent prepare furane derivative by Feist-Benary reactions

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201610566687.4A CN106243072B (en) 2016-07-18 2016-07-18 The method that alkali-free, condition of no solvent prepare furane derivative by Feist-Benary reactions

Publications (2)

Publication Number Publication Date
CN106243072A CN106243072A (en) 2016-12-21
CN106243072B true CN106243072B (en) 2018-09-28

Family

ID=57613895

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201610566687.4A Expired - Fee Related CN106243072B (en) 2016-07-18 2016-07-18 The method that alkali-free, condition of no solvent prepare furane derivative by Feist-Benary reactions

Country Status (1)

Country Link
CN (1) CN106243072B (en)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113861137B (en) * 2021-09-26 2023-08-15 重庆医科大学 Method for synthesizing furan compound by one-step reaction of ketone and alpha chloroketone

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4025537A (en) * 1975-06-09 1977-05-24 Richard Allan Kretchmer Preparation of 3-carboalkoxy or 3-alkanoyl furans
JPS5419971A (en) * 1977-07-13 1979-02-15 Fujimoto Seiyaku Kk Production of 44 hydroxyindole
JPS6032767A (en) * 1983-08-02 1985-02-19 Sagami Chem Res Center Preparation of 1-substituted-4-oxo-4,5,6,7-tetrahydroindole
CN105198841B (en) * 2015-10-19 2017-04-12 山东大学 Synthetic method for drug intermediate polysubstituted furan compound

Also Published As

Publication number Publication date
CN106243072A (en) 2016-12-21

Similar Documents

Publication Publication Date Title
Luo et al. Chemoenzymatic Synthesis and Application of Bicyclo [2.2. 2] octadiene Ligands: Increased Efficiency in Rhodium-Catalyzed Asymmetric Conjugate Additions by Electronic Tuning We acknowledge Dr. John Whittall for initial inspiration, Dr. Neil Berry for preliminary modeling and the EPSRC for a Dorothy Hodgkin Postgraduate Award to YL
CN111205279B (en) Polysubstituted benzodihydrofuran heterocyclic compound and preparation method and application thereof
Jin et al. A copper-catalyzed tandem reaction for the construction of coumarin fused 9 H-pyrrolo [1, 2-a] indoles
CN106243072B (en) The method that alkali-free, condition of no solvent prepare furane derivative by Feist-Benary reactions
CN103664821B (en) A kind of benzothiazole compound preparation method based near amino thiophenols cyclisation
CN106317001B (en) The method that one pot reaction prepares polycyclic furan compound under no catalyst, condition of no solvent
CN112592306B (en) Pyrrolinones and synthesis method thereof
CN113651788B (en) 3-aminoalkylchromone compound and preparation method thereof
CN107216326B (en) The synthetic method of (1,2,3- triazole) [1,5-f] phenanthridines -10- carboxylic acid ethyl ester compound
CN113173908A (en) Preparation method of thiophene compound
CN104163777B (en) A kind of method synthesizing carbonitrile compounds and the application in Ivabradine synthesizes thereof
CN108440549B (en) Synthesis method of spiro indole compound
CN108727323B (en) Method for catalytically synthesizing trifluoromethyl substituted homoisoflavone compound by using N-heterocyclic carbene
CN106083690A (en) A kind of preparation method of polysubstituted 3 methylene indolones
CN105801333B (en) A kind of preparation method of coronene
CN102791661A (en) Process for producing difluorocyclopropane compound
CN105566202B (en) A kind of 1,2,3,4- tetrahydro cyclopentyl base indole derivatives and its synthetic method
CN109678860A (en) A kind of method of asymmetric synthesis of chirality couroupitine A beta hydroxy acid ester type compound
CN103113323A (en) Preparation method of lasofoxifene tartrate intermediate compound
CN112125843B (en) Preparation method of 3-hydroxymethyl-4-phenyl-3, 4-dihydroquinolinone compound
CN109851548B (en) Preparation method of 2, 3-disubstituted indole compound
CN113004235B (en) Stereoselective synthesis method of (Z) -3-alkenylphthalide derivative
CN110003062B (en) N-phenyl-N-p-toluenesulfonyl difluoroacetamide and application thereof
CN106167478B (en) A kind of preparation method of 2,3-dihydrofuran compound
CN105712851B (en) A kind of preparation method of the two arone compound containing betanaphthyl

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant
CF01 Termination of patent right due to non-payment of annual fee

Granted publication date: 20180928

Termination date: 20190718

CF01 Termination of patent right due to non-payment of annual fee