CN108503612B - A kind of method of phenylpropyl alcohol ketone class compound and dimethyl sulfoxide building furane derivative derivative - Google Patents
A kind of method of phenylpropyl alcohol ketone class compound and dimethyl sulfoxide building furane derivative derivative Download PDFInfo
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- 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
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Abstract
The invention discloses a kind of methods of phenylpropyl alcohol ketone class compound and dimethyl sulfoxide building furane derivative derivative, furane derivative derivative includes furyl neighbour diketone precursor structure, it simultaneously include aryl, thioether group etc. is multiple can modification group, it is a kind of newtype drug intermediate, its synthetic method be phenylpropyl alcohol ketone class compound containing potassium peroxydisulfate with carry out cyclization in the dimethyl sulphoxide solution system of halogen simple substance and/or haloid, to obtain the final product, this method is using cheap phenylpropyl alcohol ketone class and dimethyl sulfoxide as raw material, reaction condition is mild, it is completed under without a huge sum of money or precious metal catalyst effect by one kettle way, and reaction yield is high, be conducive to industrialized production.
Description
Technical field
The present invention relates to a kind of synthetic methods of furane derivative derivative, in particular to by phenylpropyl alcohol ketone class compound with
Dimethyl sulfoxide constructs furan using furyl neighbour diketone as the method for the furan derivatives of parent, belongs to pharmaceutical intermediate synthetic technology
Field.
Background technique
Oxygen helerocyclics be in organic compound in important component, be many biologically active natural
In product important structural unit ([1] Atul G, Amit K.Ashutosh, R.Synthesis, Stereochemistry,
Structural Classification,and Chemical Reactivity of Natural
Pterocarpans.Chem.Rev.,2013,113,1614-1640；[2]Gu Z,Zakarian A.Studies toward
the Synthesis of Maoecrystal V.Org.Lett.,2011,13:1080-1082).Therefore, oxygen heterocycle chemical combination
The synthesis of object is always the research hotspot in organic synthesis.The study found that Oxygenic heterocyclic compounds have good pharmaceutical activity
([3]Ye O Z,Xie S X,Huang M,et al.Metalloform-Selective Inhibitors of
Escherichia coli Methionine Aminopeptidase and X-ray Structure of a Mn(II)-
Form Enzyme Complexed with an Inhibitor.J.Am.Chem.Soc.,2004,126:13940；[4]
Carlsson B,Singh B N,Temciuc M,et al.Synthesis and Preliminary
Characterization of a Novel Antiarrhythmic Compound(KB130015)with an Improved
Toxicity Profile Compared with Amiodarone.J.Med.Chem., 2002,45:623-630), to some
Disease has good curative effect.In recent years, oxa- cyclics are widely used in the industries such as medical treatment, agricultural, material.Cause
This, synthesizing oxa- cyclics by simple method is just particularly important.
Furan nucleus is a kind of structural unit being widely present in natural and unnatural products.Furane derivative analog derivative
As important organic and medicine intermediate ([5] Frederic T, Yohann B, Dirr R, et al.Synthetic
Analogue of Rocaglaol Displays a Potent and Selective Cytotoxicity in Cancer
Cells:Involvement of Apoptosis Inducing Factor and Caspase-12.J.Med.Chem.,
2009,52:5176-5187；[6]Gu Z,Zakarian A.Studies toward the Synthesis of
Maoecrystal V.Org.Lett., 2011,13:1080-1082), the exploration of synthetic method is research work all the time
The research hotspot of person.Traditional synthetic method is mainly paal-knorr reaction and Feist-B é nary reaction.paal-knorr
Reaction is dehydrated under anhydrous acid condition using Isosorbide-5-Nitrae-dicarbonyl compound, and Furan and its derivatives are generated.The reaction
Mechanism is under p-methyl benzenesulfonic acid effect, wherein forming enol-type structure with carbonyl, another carbonyl of attack forms dihydro to hydroxyl again
Furans reoxidizes to form furan structure.Feist-B é nary reaction is α-halogenatedketone and beta-dicarbonyl compound under base catalysis
Nucleophilic displacement of fluorine occurs and cyclization generates dihydrofuran derivative, it is derivative that the latter is further dehydrated generation polysubstituted furan
Object.
Nineteen eighty-three, Utimoto et al. form furan from coupling under Pd (II) catalysis using aliphatic alkynyl acetone for the first time
It mutters ring, provides new synthetic route ([7] Utimoto K.palladium catalyzed for the construction of furan nucleus
Synthesis of heterocycles.Pure Appl.Chem., 1983,55:1845-1852) reaction condition is mild, behaviour
Make simple.And alkynyl ethyl alcohol and alkynyl ethamine can synthesize corresponding dihydrofuran ring structure and pyrroles's ring structure at the standard conditions,
New route is provided for the synthesis of five-membered heterocycles.Later, huang seminar is using aromatic alkynyl acetone in Pd
(0) catalysis is lower forms corresponding furan ring structure ([8] Sheng H, Lin S, et al.Palladium catalyzed from coupling
synthesis of heterocycles.Synthesis,1987,1022-1023).Utimoto is compared as shown in reaction equation 1
Et al. method, it is wider that this method substrate expands range, and has done to reaction mechanism and has compared in-depth study, has proposed in Pd (0)
It is catalyzed the intermediate that lower alkynyl acetone conversion is connection ketenes and is further constructing corresponding furan ring structure from coupling.Grinding later
Study carefully and shows other transition metal ([9] Gulevich A V, Dudnik A S, Chernyak N, et al.Transition
Metal-Mediated Synthesis of Monocyclic Aromatic Heterocycles.Chem.Rev.,2013,
113:3084-3213) (such as copper, zinc, gold, silver, platinum) can also be catalyzed the compound of propanone structure containing alkynyl and form corresponding furans
Ring structure, but the disadvantages of generally existing raw material is not easy to obtain, and reaction cost is higher.
2012, Cui et al. reported the Terminal Acetylenes and α-diazonium second ketone compounds building furan nucleus of Co (II) catalysis
React ([10] Xin C, Xue X, Wojtas L, et al.Regioselective Synthesis of
Multisubstituted Furans via Metalloradical Cyclization of Alkynes withα-
Diazocarbonyls:Construction of Functionalized α-Oligofurans.J.Am.Chem.Soc.,
2012,134:19981-19984).As shown in reaction equation 2, mild condition is easy to operate.Substrate expansion range is wide, to formyl
Base, the stronger acetylene compound of hydroxyl phenylacetylene isoreactivity and pyridine acetylene class relatively inert acetylene compound all have good simultaneous
Capacitive, but non-end acetylene compound and it is not suitable for the reaction system.Raw material α-diazonium second ketone compounds need to synthesize and react
It need to be in N2Protection is lower to be carried out, and operation difficulty is increased.
2012, Lei seminar reported Ag2CO3It is reacted with Terminal Acetylenes under KOAc catalytic action with 1,3- cyclohexadione compounds
It constructs furan ring structure and reacts ([11] He C, Guo S, Ke J, et al.Silver-Mediated OxidaKve C-H/C-H
Functionalization:A Strategy to Construct Polysubstituted
Furans.J.Am.Chem.Soc.,2012,134:5766-5769).As shown in reaction equation 3, reaction condition is mild, operation letter
It is single.The system has good compatibility to reaction system, and it is anti-to be applicable in this for aliphatic Terminal Acetylenes and aromatic series Terminal Acetylenes
Answer system.The α that N- replaces, beta-unsaturated ketone compound can synthesize corresponding pyrroles's ring structure in the reaction system, and
This method can be with the biologically active furans of one-step synthesis/pyrroles's ring structure, to contain furan nucleus/pyrrole ring with bioactivity
The synthesis of structural material provides preferable experimental basis.Ag in reaction system2CO3Still have after can recycling again good
Catalytic activity.But non-end acetylene compound is simultaneously not suitable for the reaction system, Ag2CO32 equivalents are required with KOAc, increase reaction
Cost.
2013, Kuram et al. utilized phenol and 1, and the synthesis two under Pd (0)/Cu (II) catalysis of bis- replaced acetylene of 2- takes
Benzofuran structure ([12] Kuram M R, Bhanuchandra M, Sahoo A.Direct Access to Benzo in generation
[b]furans through Palladium-Catalyzed Oxidative Annulation of Phenols and
Unactivated Internal Alkynes.Angew.Chem.Int.Ed.,2013,52:4607–4612.).Such as reaction equation 4
Shown, raw material is simple and easy to get, and substrate expansion range is wide, and atom utilization is high, and aliphatic and aromatic acetylene compound all have
There is good applicability.And biologically active phenolic compound and tolans are also at the corresponding benzofuran ring knot of synthesis
Structure provides preferable experimental basis for the synthesis with bioactivity substance containing furan ring structure.But the reaction needs use compared with
The Cu (OAc) measured greatly2·H2O and NaOAc, economic serviceability is poor, and the reaction time is longer (for 24 hours~72h), the reaction time
Control is stringenter, increases operation difficulty, reacts opposite end acetylene compound and is simultaneously not suitable for.
2013, Yang seminar, which reports, synthesized the new of furan nucleus in the case where Cu (II) is catalyzed using acetophenone and cinnamic acid
Method ([13] Yang Y Z, Yao J Z, Zhang Y H.Synthesis of Polysubstituted Furansvia
Copper-Mediated Annulation ofAlkyl Ketones with r,β-Unsaturated Carboxylic
acids.Org.Lett.,2013,15(13):3206-3209).The operation as shown in reaction equation 5 is simple, and raw material is easy to get,
And corresponding furan ring structure can be also obtained with styrene reaction using acetophenone.But reaction need to use two kinds of Cu (II) salt, have
The effect of two kinds of mantoquitas of body is not clear enough, and requires 1 equivalent, lacks economic serviceability.
2013, Maiti seminar was using phenol and alkene at Pd (OAc)2/Cu(OAc)2The lower synthesis 2- of catalysis replaces
Furan structure ([14] Upendra S, Togati N, Maji A, et al.Palladium-Catalyzed Synthesis of
Benzofurans and Coumarins from Phenols and Olefin.Angew.Chem.Int.Ed.,2013,52:
12669–12673).As shown in reaction equation 6, centre of the reaction in the case where Pd (II) is catalyzed Jing Guo 1,2- disubstituted ethylene structure
Body, then five-membered ring structure is formed from coupling.The reaction raw materials are easy to get, easy to operate, and atom utilization is high, for aliphatic olefin
And aromatic olefin all has good yield (53%~92%), wide application range of substrates；And phenol and methyl acrylate are in standard
Under the conditions of can synthesize Benzofurantone compound.But it uses larger amount of metal salt as catalyst, has lacked economical suitable
The property used.
Later, Maiti seminar is using phenol and cinnamic acid at Pd (OAc)2/Cu(OAc)2Three are unexpectedly synthesized under catalysis
Substituted furan ring structure ([15] Agasti S, Sharma U, Naveen T, et al.Orthogonal selectivity
with cinnamic acids in 3-substituted benzofuran synthesis through C–H
olefination of phenols.Chem.Commun.,2015,51:5375-5378).As shown in reaction equation 7, react in Pd
(II) the lower intermediate Jing Guo 1,1- diphenylethlene structure of catalysis, then cyclization form five-membered ring structure.This method is for fat
The acrylic compounds of race can also synthesize corresponding furan ring structure with phenol.
Ghosh in 2015 et al. using Cu (I) be catalyzed acetophenone and nitrostyrolene generate furan nucleus ([16] Ghosh M,
Mishra S,Hajra A.Regioselective Synthesis of Multisubstituted Furans via
Copper-Mediated Coupling between Ketones andβ-Nitrostyrenes.J.Org.Chem.,2015,
80:5364-5368).As shown in reaction equation 8, the reaction is with CuBrSMe2For catalyst, TBHP is oxidant, DMF solvent,
Reaction is for 24 hours.Either fragrant ketone, alkanones or ring ketone compounds can be realized and nitrostyrolene class compound
Corresponding furan ring structure is synthesized, but the yield of obtained furane derivative is universal lower (48%~67%), and reaction makes
Catalyst is made with the mantoquita of 1 equivalent, lacks economic serviceability.
2015, tang seminar was using oxobutyrate and Terminal Acetylenes in alkaline condition and I2Furan is synthesized under catalytic condition
Mutter ring ([17] Tang S, Liu K, Long Y, et al.Tuning radical reactivity using iodine in
oxidativeC(sp3)–H/C(sp)–H cross-coupling:an easy way toward the synthesis of
furans and indolizines.Chem.Commun.,2015,51:8769-8772).As shown in reaction equation 9, the reaction is first
Secondary proposition is with I2As radical initiator, 2- iodo oxobutyrate intermediate is formed, then is coupled cyclization, synthesis with Terminal Acetylenes
Corresponding furan ring structure.This method mild condition, it is easy to operate, and 2- pyridylacetic acid ester can also close at the standard conditions with Terminal Acetylenes
At corresponding pyrrole structure.Either aliphatic Terminal Acetylenes and aromatic series Terminal Acetylenes can realize furan corresponding with oxobutyrate synthesis
It mutters ring structure, but the yield of obtained furane derivative is universal lower (46%~60%).Due to 1,3- diketone chemical property
It is relatively active, it can not furan ring structure corresponding to Terminal Acetylenes synthesis at the standard conditions.
2015, Manna et al., which is reported, synthesized furans under Cu (I) catalysis using acetophenone and butine dicarboxylic acid ethyl ester
Reaction ([18] Manna S, Antonchick A P.Copper (the I)-Catalyzed Radical Addition of of ring
Acetophenones to Alkynes in Furan Synthesis.Org.Lett., 2015,17:4300-4303.).Such as
Shown in reaction equation 10, a free radical mechanism is passed through in reaction.The reaction is with CuBrSMe2For catalyst, DTBP is oxidant,
It is carried out under DCE solvent condition.Atom utilization is high, mild condition.But needs carry out under the protection of argon gas, and it is difficult to increase operation
Degree and cost.
2016, Wang et al. was reported in Cu (II) for the first time and is catalyzed lower formaldehyde sodium sulfoxylate as methyl original and two molecules
Acetophenone coupling synthesis furans method ([19] Wang M, Xiang J C, Cheng Y, et al.Synthesis of 2,4,
5-Trisubstituted Furans via a Triple C(sp3)-Functionalization Reaction Using
Rongalite as the C1Unit.Org.Lett.,2016,18,524-527).As shown in reaction equation 11, the pass of the reaction
Key is formaldehyde sodium sulfoxylate in Cu (NO3)2·H2Form formaldehyde under O catalytic condition, then with two molecule dimethyl phenacyl first
Base sulfonium iodide coupling building furan nucleus.The operation is simple, and raw material is easy to get, and yield is higher (35%~85%).
2017, Gouthami et al. utilized adjacent three methanesulfonates of trimethyl silicane phenyl and dimethyl phenacyl bromide
Sulfonium synthesizes furan nucleus ([20] Gouthami P, Chavan L N, et al.Syntheses of under the alkaline condition of cesium fluoride
2-Aroyl Benzofurans through Cascade Annulation on Arynes.).It, should as shown in reaction equation 12
Reaction is that adjacent three methanesulfonates of trimethyl silicane phenyl forms benzyne structure, then addition occurs with DMF and generates with the circle of benzo four first
Ring structure finally synthesizes furan nucleus under cesium fluoride effect with dimethyl phenacyl bromide sulfonium.The reaction is proposed with DMF's
Formoxyl constructs furan nucleus and mild condition as carbon source, and easy to operate, yield is higher (66%~87%).But raw material is more multiple
It is miscellaneous, it is not easy to obtain, limits the reactive applications.
Summary of the invention
For the construction method of existing furan nucleus, that there are costs of material is high, yield is relatively low, need to use heavy metal or your gold
The defects of belonging to as catalyst, another object of the present invention are to be to provide a kind of to utilize cheap phenylpropyl alcohol ketone class and dimethyl
Sulfoxide synthesizes furans by one kettle way high yield in temperate condition and under without a huge sum of money or precious metal catalyst effect as raw material
Furyl neighbour's derovatives of the method for base neighbour's derovatives, this method building have novel furan base neighbour diketone parent knot
Structure, and simultaneously comprising multiple aryl, alkyl thioether etc. can modification group, provide new intermediate structure for pharmaceutical synthesis.
In order to achieve the above technical purposes, the present invention provides a kind of phenylpropyl alcohol ketone class compound and dimethyl sulfoxide building are more
The method of substituted furan derivative, this method are by phenylpropyl alcohol ketone class compound containing potassium peroxydisulfate and halogen simple substance and/or halogen
Cyclization is carried out in the dimethyl sulphoxide solution system of salt to get furane derivative derivative；
The phenylpropyl alcohol ketone class compound has 1 structure of formula:
The furane derivative derivative has 2 structure of formula:
Wherein, Ar is phenyl or substituted-phenyl.
Preferred scheme, the substituted-phenyl include that at least one of halogen, alkyl, trifluoromethyl or alkoxy replace
Base.More preferably halogen is fluorine, chlorine, bromine or iodine.More preferably alkyl is C1~C5Alkyl.More preferably alkoxy is C1~C5Alkane
Oxygroup.More preferably substituted-phenyl includes 1~3 substituent group, and substituent group is non-ortho substituted base.Substituted-phenyl of the invention
The substituent group requirement for including is the relatively good substituent group of stability, for containing stability poor substituent group (such as 4- hydroxyl, carboxylic
Base etc.), corresponding furan nucleus framework can not be synthesized.In addition the substituent group on phenyl ring is preferably not and can press down at the ortho position of propiono
The synthesis of furan nucleus processed reduces the yield of product.Especially when the substituent group at the ortho position of propiono on phenyl ring is hydroxyl, α-hydroxyl
Benzoylformaldoxime is reacted with DMSO has unexpectedly obtained the compound with benzofuranone structure.When there are also it for the alpha-position of propiono
When his substituent group (such as isobutyrophenone), monohydroxy substituent group (such as Alpha-hydroxy easily is inserted into the alpha-position of propiono at the standard conditions
Isobutyrophenone).Stable substituent group includes halogen substituted phenyl, alkyl-substituted phenyl, trifluoromethyl substituted-phenyl or alkoxy
Substituted-phenyl.Halogen substituted phenyl include fluorine, chlorine, bromine or iodine replace phenyl, it can be common that fluorine, chlorine or bromine replace phenyl.
Substituted quantity can be 1~5, and common substituent group quantity is 1~3, and the position of substitution on phenyl ring can be phenyl ring
Upper substitutive any position, preferably meta or para position.Alkyl-substituted phenyl is mainly the phenyl that short-chain alkyl replaces, such as C1
~C5Alkyl-substituted phenyl, the quantity of substituent group is generally 1~3, common for mono-substituted alkyl-substituted phenyl, in benzene
The position of substitution on ring can be substitutive any position, preferably meta or para position on phenyl ring.Alkoxy substituted phenyl master
If the phenyl that lower alkyloxy replaces, such as C1~C5Alkoxy substituted phenyl, the quantity of substituent group is generally 1~2, often
See to be mono-substituted alkoxy substituted phenyl, the position of substitution on phenyl ring can be substitutive any position on phenyl ring,
Preferably meta or para position.The quantity for the substituent group that trifluoromethyl substituted-phenyl includes is generally 1, the substitution position on phenyl ring
Set to be substitutive any position, preferably meta or para position on phenyl ring.Have below to furane derivative derivative
Body illustrates.
Preferred scheme, the halogen simple substance include iodine and/or bromine.It is more preferably iodine.
Preferred scheme, the haloid include tetrabutylammonium iodide, tetrabutylammonium bromide, tetrabutylammonium chloride, iodate
At least one of potassium, potassium bromide, potassium chloride.Preferably tetrabutylammonium iodide.Opposite haloid, halogen simple substance have more preferable promote
The effect of reaction.
Preferred scheme, concentration of the phenylpropyl alcohol ketone class compound in dimethyl sulphoxide solution system are 0.1~1mol/L；Compared with
Preferably 0.15~0.4mol/L.
Preferred scheme, the mole of potassium peroxydisulfate are 0.25~2 times of phenylpropyl alcohol ketone class compound mole；More preferably it is
0.75~1.5 times.
The integral molar quantity of preferred scheme, halogen simple substance and haloid be phenylpropyl alcohol ketone class compound mole 10%~
100%；It is more preferably 40~80%.
Preferred scheme, the temperature of the cyclization are 60~140 DEG C, and the time is 4~12h.More preferably scheme, institute
The temperature for stating cyclization is 110~130 DEG C, and the time is 6~10h.
The invention proposes reasonable furane derivative derivative synthesis mechanisms: being constructed with propiophenone and dimethyl sulfoxide coupling
Furan nucleus is illustrated reaction mechanism: by consulting and with reference to pertinent literature, devising a series of mechanism study experiment,
Shown in following reaction equation (1) and equation (2).Firstly, in order to prove whether the reaction passes through the reaction process of free radical,
The DBPC 2,6 ditertiary butyl p cresol (BHT) or 2,2,6,6- tetramethyl piperidine oxides of 2.0 equivalents are added at the standard conditions
(TEMPO), 8h is reacted, as a result, it has been found that fully reacting is suppressed almost without spawn under GC-MS detection, illustrates that this is anti-
It should may have passed through the reaction process of a free radical.In order to prove compound B whether be the reaction intermediate, pass through design
Experiment (2) demonstrates guess, and products collection efficiency is 88% under GC-MS detection.
It is proposed that propiophenone is coupled building oxa- ring with dimethyl sulfoxide and reacts possible reasonable reaction mechanism according to above-mentioned experiment,
As shown in reaction equation (3).Firstly, DMSO provides oxygen source and propiophenone in I2Effect generates benzoyl ethyl ketone.Then exist
K2S2O8It acts on lower acetophenone and reacts synthesis compound D with DMSO, while B is in I2Effect is lower to synthesize compound C, and compound C can be fast
Speed is transformed into e.Compound D and e are in K2S2O8Effect is lower to generate g free radical, and electronics transfer occurs later and forms corresponding cation
h.Intramolecular cyclization and deprotonation occur for cation h, form compound j.Last dehydrogenation oxidation forms target product.
Compared with the prior art, technical solution of the present invention bring advantageous effects:
1) present invention successfully synthesizes a kind of furane derivative radical derivative with furyl neighbour's diketone structure, it includes
Furyl neighbour's diketone precursor group and aryl, alkyl thioether etc. can modification group, completely new parent knot is provided for pharmaceutical synthesis
Structure.
2) it is avoided in furane derivative derivative synthesis process of the invention and uses heavy metal or noble metal as catalysis
Agent, and cost has not only been saved as catalyst using halogen or haloid cheap and easy to get, and avoid the dirt of environment
Dye；
3) it is used as in furane derivative derivative synthesis process of the invention using phenylpropyl alcohol ketone class and dimethyl sulfoxide basic
Raw material is all existing conventional industrial chemicals, low in cost, is conducive to industrialized production.
4) one pot reaction is used in furane derivative derivative synthesis process of the invention, and reaction condition is mild, it can
It is easy to operate to be reacted in air environment, meet demand of industrial production.
5) raw material availability is high in furane derivative derivative synthesis process of the invention, product yield between 63%~
Between 92%.
Detailed description of the invention
Fig. 1 is the nucleus magnetic hydrogen spectrum figure of furane derivative derivative prepared by embodiment 1；
Fig. 2 is the nuclear-magnetism carbon spectrogram of furane derivative derivative prepared by embodiment 1；
Fig. 3 is the nucleus magnetic hydrogen spectrum figure of furane derivative derivative prepared by embodiment 3；
Fig. 4 is that the nuclear-magnetism carbon of furane derivative derivative prepared by embodiment 3 composes spectrogram；
Fig. 5 is the nucleus magnetic hydrogen spectrum figure of furane derivative derivative prepared by embodiment 10；
Fig. 6 is that the nuclear-magnetism carbon of furane derivative derivative prepared by embodiment 10 composes spectrogram.
Specific embodiment
Following embodiment is intended to further illustrate the content of present invention, rather than limits the protection model of the claims in the present invention
It encloses.
Unless otherwise stated, all reactions carry out in Schlenk test tube.
All reaction raw materials solvents are obtained from commercial source, and are used without further purification.
Product separation uses silica gel chromatographic column, silica gel (- 400 mesh of 300 mesh of granularity).
1H NMR (400MHz), 13C NMR (100MHz) and 19F NMR (376MHz) detection use Bruker
ADVANCEIII spectrometer, with CDCl3For solvent, using TMS as internal standard, chemical shift is in terms of parts per million (ppm), with tetramethyl
The 0.0ppm of silane is with reference to displacement.Explain multiplicity using following abbreviation (or combinations thereof): s=is unimodal, and d=is bimodal, t=
Triplet, q=quartet, m=multiplet, br=broad peak.The unit of coupling constant J is hertz (Hz).Chemical shift is with ppm table
Show, in the center line of 77.0ppm triplet or refers to deuterated DMSO in the center line of 39.52ppm septet with reference to deuterated chloroform.
GC-MS is detected using GC-MS QP2010 equipment, and HRMS is measured using electron ionization (EI) method, mass-synchrometer
Type is TOF, and EI is detected using Esquire 3000plus instrument.
Condition optimizing experiment:
By taking the experiment of propiophenone and dimethyl sulfoxide coupling building furan nucleus as an example, seek optimal reaction condition, to catalysis
Agent type and multiple influence factors such as dosage, oxidant and dosage, reaction temperature and time, reaction dissolvent amount are inquired into.
1) selection of additive
The type of additive has a great impact to reaction.Different types of additive has been investigated by a large amount of control experiments
The influence that building furan nucleus reacts is coupled with dimethyl sulfoxide to propiophenone.Experimental result is as shown in table 1.The experimental results showed that when
When doing additive using halogeno salt or halogen simple substance, the conversion ratio of propiophenone can be 95% or more, but only in elemental iodine
(I2) under effect, effect is best, has reached 89% yield.However, when do not use any additive when, reaction yield it is extremely low (<
5%).Therefore, I2It is chosen as the optimum addn of the reaction.
Influence of 1 additive of table to reaction
aReaction condition: propiophenone (0.5mmol), DMSO (2.0mL), oxidant K2S2O8(1.0mmol), 120 DEG C, in sky
8h is reacted under gas.
2) optimization of additive amount
Determining I2After optimum addn, influence of the additive to the reaction of different amounts is explored.Experimental result is such as
Shown in table 2.The experimental results showed that when there is the dosage of additive between 0%~50%, with the increase of additive capacity,
The yield of product also increases with it.And when the amount of additive > 50%, yield is basicly stable.Therefore, I2Amount reach 50%
When, it is best to the effect of the reaction.
Influence of 2 additive amount of table to reaction
aReaction condition: propiophenone (0.5mmol), DMSO (2.0mL), I2(X mol%), K2S2O8(1.0mmol),120
DEG C, 8h is reacted under air conditions.
3) optimization of oxidant
After additive and its dosage has been determined, then different oxidants is screened, experimental result is as shown in table 3.
Use potassium persulfate (K2S2O8) be used as oxidant when reaction effect it is best, yield has reached 89%.When use tert-butyl mistake
Hydrogen oxide (TBHP) or hydrogen peroxide (H2O2) reaction yield sharply declines (< 5%) when being used as oxidant, when being passed through oxygen or not
It does not react when oxidizer.Therefore, K is selected2S2O8As optimal oxidant.
Influence of 3 oxidant of table to reaction
aReaction condition: propiophenone (0.5mmol), DMSO (2.0mL), I2(50mol%), K2S2O8, 120 DEG C, air conditions
Lower reaction 8h.
4) optimization of oxidizer
Determining K2S2O8After best oxidant, influence of the oxidant to reaction of different amounts is explored.Experimental result is such as
Shown in table 4.When the dosage of oxidant is between 0~2 equivalent, with the increase of oxidant content, the conversion ratio of raw material and production
The yield of object also increases with it.And when oxidant > 2 equivalent when, yield is declined and basicly stable.Therefore, 2 equivalents
K2S2O8The optimum amount of the reaction.
Influence of 4 oxidizer of table to reaction
aReaction condition: propiophenone (0.5mmol), DMSO (2.0mL), I2(50mol%), K2S2O8(X mmol), 120 DEG C,
8h is reacted under air conditions.
5) optimization of reaction temperature
Reaction temperature is to influence a key factor of chemical reaction process, and optimal reaction temperature, has studied in order to obtain
The yield of the reaction, experimental result are as shown in table 5 at different temperatures.When between 60~120 DEG C, as the temperature increases,
The yield of its product also increases with it, and reaction yield reaches maximum (83%) when temperature is raised to 120 DEG C.Continue to increase the temperature to
140 DEG C, reaction yield decreases.Therefore, 120 DEG C of optimum temperatures for the reaction.
Influence of 5 reaction temperature of table to reaction
aReaction condition: propiophenone (0.5mmol), DMSO (2.0mL), I2(50mol%), K2S2O8(1mmol), air item
8h is reacted under part.
6) optimization of reaction dissolvent amount
Better reaction effect in order to obtain is optimizing additive, additive amount, oxidant, oxidizer, temperature
After the reaction conditions such as degree, influence of the additional amount of solvent (DMSO) to reaction is further also investigated, experimental result is as shown in table 6.
When between 0.5~2mL, with the increase of DMSO amount, the yield of product is also increased with it, the reaction yield when being added to 2mL
Reach maximum (89%).The metering of DMSO is continued growing, reaction yield decreases.Therefore, 2mL is the optimum solvent of the reaction
Amount.
Influence of the 6 reaction dissolvent amount of table to reaction
aReaction condition: propiophenone (0.5mmol), DMSO (X mL), I2(50mol%), K2S2O8(X mmol), 120 DEG C,
8h is reacted under air conditions.
7) optimization in reaction time
In chemical reaction, reaction time length be influence target product yield an important factor for one of, too short reaction
Time may make feed stock conversion lower, and the too long reaction time may cause the increase of by-product.For this purpose, investigating not
Influence of the same reaction time to the reaction.Experimental result is as shown in table 7.When between 4~8h, with the increasing in reaction time
Add, the yield of product also increases with it, and is increased to 83% by 53%.When continue extend reaction time yield reaction yield almost
It is constant.Therefore, select 8h as the best duration of reaction.
Influence of 4.7 reaction time of table to reaction
aReaction condition: propiophenone (0.5mmol), DMSO (2.0mL), I2(50mol%), K2S2O8(1mmol), 120 DEG C,
It is reacted under air conditions.
It can determine that propiophenone is coupled the optimal conditions that building oxa- ring reacts with dimethyl sulfoxide by above-mentioned optimization experiment:
The propiophenone of 60mg (0.5mmol), 55.3mg (50mol%) iodine, the potassium persulfate (K of 270mg (2.0equiv)2S2O8), two
First sulfoxide (DMSO) 2mL reaction is stirred to react 8h under conditions of 120 DEG C.
8) range of choice of reaction substrate:
After being determined that α-ethyl ketone is coupled the optimal conditions reacted for constructing furan nucleus with dimethyl sulfoxide, to the bottom of reaction
Object range and applicability are probed into, and experimental result is as shown in table 8.As can be seen from Table 8, different substituents are had on phenyl ring
Phenylpropyl alcohol ketone class compound corresponding furane derivative ring structure, and target can be effectively synthesized under the reaction condition of standard
The yield of product is between 63%~92%.And (such as 4- hydroxypropiophenonepreparation) containing the poor substituent group of stability is in standard conditions
Under can not synthesize corresponding furan nucleus framework.By comparing 7b, 7i, 7p in table 8 it can be found that when fluoro substituents ortho position,
When meta position and contraposition, it is respectively 67%, 88% and 91% that reaction, which obtains the yield of target product,；This illustrates the substituent group on phenyl ring
The propiophenone replaced in contraposition or meta position is all more advantageous to the conversion of product；It, may be due to and when substituent group is in ortho position
Space steric effect, it is suppressed that the conversion of product reacts obtain at the standard conditions so as to cause the propiophenone of ortho-substituent
Target product yield it is relatively low.It is noted that 2- propiono thiophene (1q) can equally synthesize correspondence under the same conditions
Furan ring structure, obtain the yield 85% of target product.
8 α of table-ethyl ketone compounds substrate range
The substrate scope of application of other phenylpropyl alcohol ketone class compounds:
In addition to this, other different types of phenylpropyl alcohol ketone class compounds under the reaction conditions anti-further has also been attempted
Performance is answered, as shown in table 9.(a) the interior coupling of reaction molecular synthesizes Benzopyranone kind to o-hydroxy acetone at the standard conditions
Close object.(b) DMSO provides oxygen source and isobutyrophenone synthesizes Alpha-hydroxy isobutyrophenone at the standard conditions.
Other the different types of phenylpropyl alcohol ketone class compounds substrate ranges of table 9
Following example 1~17 are reacted under optimum condition of the invention, to the response situations of different substrates into
Row illustrates.
Specific operation process: the aryl or aromatic heterocyclic acetone of 67mg (0.5mmol), 64mg (50mol%) iodine list are weighed
Matter (I2), the potassium persulfate (K of 270mg (2.0equiv)2S2O8) in the reaction tube of 25mL, the dimethyl sulfoxide of 2mL is added
(DMSO) it is used as solvent, mixed liquor stirs 8h at 120 DEG C of air atmosphere.Reaction solution is cooled to room temperature, using ethyl acetate
(10mL) is diluted reaction solution, washes (5mL), ethyl acetate (5mL × 3) extracts reaction solution, extracted to have
Machine is mutually dried using anhydrous sodium sulfate, then solvent is spin-dried for by filtering with Rotary Evaporators.Matter utilization silicon after concentration
Plastic column chromatography carries out separating-purifying (eluant, eluent is petrol ether/ethyl acetate).
Embodiment 1
Propiophenone reacts (7a) with DMSO's
Obtain yellow solid 77.9mg, yield 89%.
Characterize data: 1H NMR (400MHz, CDCl3): δ 8.17 (d, J=7.6Hz, 1H), 8.05 (d, J=7.7Hz,
1H), 7.70 (t, J=7.3Hz, 1H), 7.63-7.52 (m, 2H), 7.48 (t, J=7.5Hz, 1H), 7.44 (s, 1H), 2.51
(s,2H).13C NMR(100MHz,CDCl3):δ190.6,181.6,180.6,149.2,148.2,137.6,135.6,
135.3,133.2,132.1,130.3,129.7,129.1,128.6,119.8,15.9.HRMS(EI)m/z calcd for
C20H14O4S[M+]:350.0613；found,350.0617.
Embodiment 2
2- fluorobenzene acetone reacts (7b) with DMSO's
Obtain yellow solid 61.6mg, yield 67%.
Characterize data:1H NMR(400MHz,CDCl3): δ 7.95 (td, J=7.9,1.7Hz, 1H), 7.73-7.60 (m,
2H), 7.53-7.47 (m, 1H), 7.44 (s, 1H), 7.35 (t, J=7.6Hz, 1H), 7.20 (dt, J=10.0,8.1Hz, 2H),
7.09–7.01(m,1H),2.56(s,3H).13C NMR(100MHz,CDCl3):δ188.9,180.4,180.1,162.8(d,J
=246.3Hz), 160.3 (d, J=243.6Hz), 148.9 (d, J=2.2Hz), 147.7,137.1 (d, J=9.2Hz),
136.8,133.9 (d, J=8.7Hz), 130.9,130.5 (d, J=2.4Hz), 125.2 (d, J=13.8Hz), 125.0 (d, J
=3.3Hz), 124.2 (d, J=3.6Hz), 121.6 (d, J=11.0Hz), 119.0 (s), 116.6 (d, J=21.5Hz),
116.3 (d, J=21.8Hz), 15.7.HRMS (EI) m/z calcdfor C20H12F2O4S[M+]:386.0424；found,
386.0426.
Embodiment 3
3,4- difluoro propiophenone reacts (7c) with DMSO's
Obtain yellow solid 66.4mg, yield 63%.
Characterize data:1H NMR(400MHz,CDCl3): δ 8.07 (t, J=9.2Hz, 1H), 7.98 (t, J=8.8Hz,
1H), 7.91 (d, J=4.4Hz, 1H), 7.48 (s, 1H), 7.41-7.28 (m, 2H), 2.54 (s, 3H)13C NMR(100MHz,
CDCl3): δ 187.20,178.73,178.61,149.15,147.79,138.62,132.43 (dd, J=4.6,3.3Hz),
129.16 (dd, J=5.0,3.5Hz), 128.07 (dd, J=7.9,3.7Hz), 127.03 (dd, J=7.4,3.7Hz),
120.35,119.54 (d, J=2.0Hz), 119.42-119.30 (m), 119.14 (d, J=1.6Hz), 118.28 (d, J=
18.1Hz), 117.71 (d, J=17.8Hz), 15.89.HRMS (EI) m/z calcd for C20H10F4O4S[M+]:
422.0236；found,422.033.
Embodiment 4
3,4- dichloropropiophenone reacts (7d) with DMSO's
Obtain yellow solid 86.2mg, yield 71%.
Characterize data:1H NMR(400MHz,CDCl3): δ 8.32 (s, 1H), 8.22 (s, 1H), 8.10 (d, J=8.4Hz,
1H), 7.96 (d, J=8.4Hz, 1H), 7.65 (dd, J=10.8,8.6Hz, 2H), 7.51 (s, 1H), 2.57 (s, 3H)13C
NMR(101MHz,CDCl3):δ187.5,178.8,178.7,149.1,147.7,140.4,138.8,138.0,135.0,
134.0,133.3,132.0,131.7,131.6,131.3,130.8,129.2,128.7,120.1,15.9.HRMS(EI)m/z
calcd for C20H10Cl4O4S[M+]:485.9054；found,485.9058.
Embodiment 5
3,5- difluoro propiophenone reacts (7e) with DMSO's
Obtain yellow solid 79.1mg, yield 75%.
Characterize data:1H NMR(400MHz,CDCl3): δ 7.72 (d, J=6.5Hz, 1H), 7.62 (d, J=5.4Hz,
2H), 7.49 (s, 1H), 7.15 (t, J=7.8Hz, 1H), 7.05 (t, J=7.9Hz, 1H), 2.54 (s, 3H)13C NMR
(100MHz,CDCl3): δ 187.19 (dd, J=4.5,2.2Hz), 178.47 (t, J=2.7Hz), 178.27,164.25 (dd, J
=25.3,11.8Hz), 161.75 (dd, J=23.1,11.8Hz), 149.12,147.53,139.15,138.06 (t, J=
8.3Hz) ,-112.60 (m), 110.73 (t, J of 134.65 (t, J=8.1Hz), 120.22,113.46-113.12 (m), 112.94
=25.4Hz), 108.65 (t, J=25.3Hz), 15.86.HRMS (EI) m/z calcd for C20H10F4O4S[M+]:
422.0236；found,422.0237.
Embodiment 6
3- brom-acetophenone reacts (7f) with DMSO's
Obtain yellow solid 105.0mg, yield 83%.
Characterize data:1H NMR(400MHz,CDCl3): δ 8.32 (t, J=1.6Hz, 1H), 8.25 (t, J=1.6Hz,
1H), 8.15 (d, J=7.9Hz, 1H), 8.02 (d, J=7.8Hz, 1H), 7.87-7.82 (m, 1H), 7.78-7.72 (m, 1H),
7.49 (s, 1H), 7.46 (d, J=7.9Hz, 1H), 7.41 (d, J=7.9Hz, 1H), 2.56 (s, 3H)13C NMR(100MHz,
CDCl3):δ188.7,179.9,179.4,149.2,147.8,138.4,138.1,137.2,136.1,133.8,132.9,
132.6,130.6,130.2,128.9,128.2,123.4,122.8,119.8,15.9.HRMS(EI)m/z calcd for
C20H12Br2O4S[M+]:505.8823；found,505.8827.
Embodiment 7
3- trifluoromethyl propiophenone reacts (7g) with DMSO
Obtain yellow solid 103.2mg, yield 85%.
Characterize data:1H NMR(400MHz,CDCl3): δ 8.49 (s, 1H), 8.42 (d, J=7.9Hz, 1H), 8.38 (s,
1H), 8.30 (d, J=8.0Hz, 1H), 7.98 (d, J=7.8Hz, 1H), 7.88 (d, J=7.8Hz, 1H), 7.76-7.65 (m,
2H),7.55(s,1H),2.58(s,4H).13C NMR(100MHz,CDCl3):δ188.4,179.9,179.0,149.3,
(147.7,138.7,136.1,133.4,132.8,132.6,131.8 d, J=33.4Hz), 131.5 (dd, J=6.9,
3.3Hz), 131.2 (d, J=33.0Hz), 129.8,129.6 (q, J=3.5Hz), 129.3,127.0 (dd, J=7.5,
3.7Hz), 126.7 (dd, J=7.8,3.8Hz), 120.0,15.8.HRMS (EI) m/z calcd for C22H12F6O4S[M+]:
486.0360；found,486.0358.
Embodiment 8
(7h) is reacted to methoxybenzene acetone and NHPI
Obtain yellow solid 86.7mg, yield 83%.
Characterize data:1H NMR(400MHz,CDCl3): δ 8.14 (s, 1H), 8.08 (d, J=11.2Hz, 2H), 7.95 (d,
J=7.8Hz, 1H), 7.67 (d, J=8.0Hz, 1H), 7.57 (d, J=7.9Hz, 1H), 7.53-7.42 (m, 3H), 2.54 (s,
3H).13C NMR(100MHz,CDCl3):δ188.9,180.0,179.4,149.2,147.9,138.4,137.0,135.5,
135.2,134.9,133.6,133.2,130.4,130.0,129.9,129.7,128.5,127.8,119.9,15.8.HRMS
(EI)m/z calcd for C20H12Cl2O4S[M+]:417.9833；found,417.9837.
Embodiment 9
3- chloro-acetophenone reacts (7i) with DMSO's
Obtain yellow solid 84.9mg, yield 88%.
Characterize data:1H NMR(400MHz,CDCl3): δ 8.02 (d, J=7.7Hz, 1H), 7.86 (d, J=8.3Hz,
2H), 7.79 (d, J=8.9Hz, 1H), 7.58-7.45 (m, 3H), 7.41 (t, J=8.1Hz, 1H), 7.31 (t, J=8.2Hz,
1H),2.54(s,3H).13C NMR(100MHz,CDCl3): δ 188.96,180.10,179.47,164.00 (d, J=
20.5Hz), 161.53 (d, J=18.5Hz), 149.21,147.95,138.36,137.48 (d, J=6.9Hz), 134.06 (d,
), J=6.6Hz 130.91 (d, J=7.6Hz), 130.33 (d, J=7.7Hz), 126.39 (d, J=3.0Hz), 125.59 (d, J
=3.0Hz), 122.53 (d, J=21.5Hz), 120.36 (d, J=21.5Hz), 120.06,116.71 (d, J=8.8Hz),
116.48 (d, J=9.1Hz), 15.90.HRMS (EI) m/z calcdfor C20H12F2O4S[M+]:386.0424；found,
386.0427.
Embodiment 10
3- methoxybenzene acetone reacts (7j) with DMSO's
Obtain yellow solid 81.0mg, yield 79%.
Characterize data:1H NMR(400MHz,CDCl3): δ 7.80 (d, J=7.7Hz, 1H), 7.72 (s, 1H), 7.59 (d, J
=8.8Hz, 2H), 7.49-7.34 (m, 3H), 7.25 (d, J=10.8Hz, 2H), 7.15 (d, J=8.2Hz, 1H), 3.88 (s,
6H),2.52(s,3H).13C NMR(100MHz,CDCl3):δ190.5,181.2,180.6,160.1,159.6,149.3,
148.2,137.7,136.8,133.3,130.1,129.6,123.4,122.5,122.3,120.4,119.5,113.5,
113.3,55.5,55.4,15.9.HRMS(EI)m/z calcd for C22H18O6S[M+]:410.0824；found,
410.0827.
Embodiment 11
4- brom-acetophenone reacts (7k) with DMSO's
Obtain yellow solid 113.8mg, yield 90%.
Characterize data:1H NMR(400MHz,CDCl3): δ 8.10 (d, J=8.4Hz, 1H), 7.97 (d, J=8.4Hz,
1H), 7.71 (dd, J=17.9,8.4Hz, 2H), 7.48 (s, 1H), 2.56 (s, 1H)13C NMR(100MHz,CDCl3):δ
189.0,179.4,176.2,149.1,148.0,146.8,142.4,138.1,134.3,132.5,132.0,131.6,
131.2,128.6,120.1,15.9.HRMS(EI)m/z calcd for C20H12Br2O4S[M+]:505.8823；found,
505.8827.
Embodiment 12
4- trifluoromethyl propiophenone reacts (7l) with DMSO's
Obtain yellow solid 110.5mg, yield 91%.
Characterize data:1H NMR(400MHz,CDCl3): δ 8.30 (d, J=8.0Hz, 2H), 8.21 (d, J=8.0Hz,
2H), 7.81 (dd, J=12.4,8.4Hz, 4H), 7.52 (s, 1H), 2.56 (s, 3H)13C NMR(100MHz,CDCl3):δ
149.24,147.90,138.75,138.43,136.48,136.15,134.79,130.74 130.06,126.11 (q, J=
3.7Hz), 125.66 (q, J=3.5Hz), 120.43,15.89.HRMS (EI) m/z calcd for C22H12F6O4S[M+]:
486.0360；found,486.0363.
Embodiment 13
4- ethyl propiophenone reacts (7m) with DMSO's
Matter utilization silica gel column chromatography after concentration carries out separating-purifying (eluant, eluent is petrol ether/ethyl acetate), obtains
Yellow solid 87.2mg, yield 86%.
Characterize data:1H NMR(400MHz,CDCl3): δ 8.15 (d, J=8.0Hz, 1H), 8.00 (d, J=8.0Hz,
1H), 7.43 (s, 1H), 7.39 (d, J=7.9Hz, 1H), 7.34 (d, J=8.0Hz, 1H), 2.75 (dd, J=16.1,7.7Hz,
2H),2.53(s,1H),1.33–1.25(m,4H).13C NMR(100MHz,CDCl3):δ190.3,181.3,180.9,152.8,
150.2,149.2,148.4,137.1,133.3,130.5,130.0,129.9,128.6,128.1,119.8,29.2,29.0,
15.9,15.1,15.0.HRMS(EI)m/zcalcd for C24H22O4S[M+]:406.1239；found,406.1241.
Embodiment 14
4- methyl phenyl ketone reacts (7n) with DMSO's
Obtain yellow solid 87.2mg, yield 88%.
Characterize data:1H NMR(400MHz,CDCl3): δ 8.10 (d, J=7.8Hz, 1H), 7.95 (d, J=7.7Hz,
1H), 7.41 (s, 1H), 7.34 (d, J=7.9Hz, 1H), 7.29 (d, J=7.9Hz, 1H), 2.50 (s, 2H), 2.46 (s, 2H),
2.43(s,2H).13CNMR(100MHz,CDCl3):δ190.3,181.3,180.9,149.2,148.4,146.7,144.1,
137.1,133.1,130.4,129.9,129.8,129.7,129.3,119.7,22.0,21.7,15.8.HRMS(EI)m/z
calcd for C22H18O4S[M+]:378.0926；found,378.0930.
Embodiment 15
4- chlorophenyl acetone reacts (7o) with DMSO's
Obtain yellow solid 96.1mg, yield 92%.
Data characterization:1H NMR(400MHz,CDCl3): δ 8.16 (d, J=7.9Hz, 1H), 8.03 (d, J=7.8Hz,
1H),7.59–7.43(m,3H),2.53(s,1H).13C NMR(100MHz,CDCl3):δ188.8,180.2,179.5,149.2,
148.0,142.2,139.8,138.0,133.9,131.6,131.2,130.5,129.5,129.0,120.1,15.9.HRMS
(EI)m/z calcd forC20H12Cl2O4S[M+]:417.9833；found,417.9836.
Embodiment 16
4- fluorobenzene acetone reacts (7p) with DMSO's
Obtain yellow solid 87.8mg, yield 91%.
Data characterization:1H NMR(400MHz,CDCl3): δ 7.94 (t, J=7.3Hz, 1H), 7.65 (dt, J=25.8,
7.2Hz, 2H), 7.49 (dd, J=13.4,7.4Hz, 1H), 7.42 (s, 1H), 7.33 (t, J=7.6Hz, 1H), 7.24-7.12
(m, 2H), 7.22-7.03 (m, 2H), 7.03 (t, J=9.3Hz, 1H), 2.55 (s, 3H)13C NMR(100MHz,CDCl3):δ
(188.53,179.95,179.81,167.76 d, J=127.0Hz), 165.20 (d, J=123.3Hz), 149.22,148.13,
137.85,133.28 (d, J=9.9Hz), 132.55 (d, J=9.4Hz), 131.99 (d, J=2.9Hz), 128.66 (d, J=
2.7Hz), 120.17,116.54 (d, J=22.2Hz), 115.87 (d, J=21.9Hz), 15.88.HRMS (EI) m/z calcd
for C20H12O4S[M+]:386.0424；found,386.0426.
Embodiment 17
4- hydroxypropiophenonepreparation reacts (7q) with DMSO's
It is 0% that GC, which detects yield,.
Claims (9)
1. a kind of method of phenylpropyl alcohol ketone class compound and dimethyl sulfoxide building furane derivative derivative, it is characterised in that: benzene
Acetones compound carries out being cyclized in the dimethyl sulphoxide solution system containing potassium peroxydisulfate and halogen simple substance and/or haloid anti-
It should be to get furane derivative derivative；
The phenylpropyl alcohol ketone class compound has 1 structure of formula:
The furane derivative derivative has 2 structure of formula:
Wherein, Ar is phenyl or substituted-phenyl；
The substituted-phenyl includes at least one of halogen, alkyl, trifluoromethyl or alkoxy substituent group.
2. a kind of phenylpropyl alcohol ketone class compound according to claim 1 and dimethyl sulfoxide construct furane derivative derivative
Method, it is characterised in that: the halogen is fluorine, chlorine, bromine or iodine；
The alkyl is C1~C5Alkyl；
The alkoxy is C1~C5Alkoxy.
3. a kind of phenylpropyl alcohol ketone class compound according to claim 1 and dimethyl sulfoxide construct furane derivative derivative
Method, it is characterised in that: the substituted-phenyl includes 1~3 substituent group, and substituent group is non-ortho substituted base.
4. a kind of described in any item phenylpropyl alcohol ketone class compounds and dimethyl sulfoxide construct polysubstituted furan according to claim 1~3
It mutters the method for derivative, it is characterised in that: the halogen simple substance includes iodine and/or bromine；The haloid includes tetrabutyl iodate
At least one of ammonium, tetrabutylammonium bromide, tetrabutylammonium chloride, potassium iodide, potassium bromide, potassium chloride.
5. a kind of described in any item phenylpropyl alcohol ketone class compounds and dimethyl sulfoxide construct polysubstituted furan according to claim 1~3
It mutters the method for derivative, it is characterised in that: concentration of the phenylpropyl alcohol ketone class compound in dimethyl sulphoxide solution system is 0.1~
1mol/L。
6. a kind of described in any item phenylpropyl alcohol ketone class compounds and dimethyl sulfoxide construct polysubstituted furan according to claim 1~3
It mutters the method for derivative, it is characterised in that: the mole of potassium peroxydisulfate is 0.25~2 times of phenylpropyl alcohol ketone class compound mole.
7. a kind of described in any item phenylpropyl alcohol ketone class compounds and dimethyl sulfoxide construct polysubstituted furan according to claim 1~3
It mutters the method for derivative, it is characterised in that: the integral molar quantity of halogen simple substance and haloid is phenylpropyl alcohol ketone class compound mole
10%~100%.
8. a kind of described in any item phenylpropyl alcohol ketone class compounds and dimethyl sulfoxide construct polysubstituted furan according to claim 1~3
It mutters the method for derivative, it is characterised in that: the temperature of the cyclization is 60~140 DEG C, and the time is 4~12h.
9. a kind of phenylpropyl alcohol ketone class compound according to claim 8 and dimethyl sulfoxide construct furane derivative derivative
Method, it is characterised in that: the temperature of the cyclization is 110~130 DEG C, and the time is 6~10h.
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| CN107805232A (en) * | 2017-10-31 | 2018-03-16 | 沅江华龙催化科技有限公司 | A kind of synthetic method of the derivative containing thiomethylfuran |
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| CN107805232A (en) * | 2017-10-31 | 2018-03-16 | 沅江华龙催化科技有限公司 | A kind of synthetic method of the derivative containing thiomethylfuran |
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