CN104910105A - Method for preparation of polysubstituted furan derivative from gem-difluoroolefin - Google Patents

Method for preparation of polysubstituted furan derivative from gem-difluoroolefin Download PDF

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CN104910105A
CN104910105A CN201510202778.5A CN201510202778A CN104910105A CN 104910105 A CN104910105 A CN 104910105A CN 201510202778 A CN201510202778 A CN 201510202778A CN 104910105 A CN104910105 A CN 104910105A
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straight
phenyl
heterocyclic radical
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CN104910105B (en
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曹松
张旭雪
代文朋
林赢银
吴伟
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East China University of Science and Technology
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    • 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
    • C07D307/38—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 substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D307/40—Radicals substituted by oxygen atoms
    • C07D307/46—Doubly bound oxygen atoms, or two oxygen atoms singly bound to the same carbon atom
    • 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
    • C07D307/64—Sulfur atoms
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
    • C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
    • C07D407/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Furan Compounds (AREA)

Abstract

The invention relates to a method for preparation of a polysubstituted furan derivative, the method comprises the following main steps: in the presence of a copper salt and an oxyacid salt of an IA element in the element periodic table, gem-difluoroolefin is reacted with an active methylene-containing compound in an aprotic organic solvent at 90-120 DEG C to obtain the target object (2,3,5-trisubstituted furan derivative). The method has the advantages of low cost, no use of a precious metal as a catalyst, an accessible and wide adaptable substrate, product diversity and the like.

Description

By the method preparing furane derivative derivative together with two fluoroolefin
Technical field
The present invention relates to a kind of method preparing furane derivative derivative, specifically, under relating to a kind of metal catalytic, react by together with two fluoroolefin and active methylene compound the method preparing furane derivative derivative.
Background technology
Furan nucleus, as the typical five yuan of oxygen heterocyclic ring of one, is present in multiple natural product widely.Polysubstituted furan compounds is not only the important intermediate of organic synthesis, all has a very wide range of applications in fields such as agricultural chemicals, medicine, spices, essence, dyestuffs.Below list and severally have bioactive substituted furan compound, wherein Ranitidine is as a kind of medicine for the treatment of stomach ulcer, is one of the most successful commercial medicine:
See document: (a) D.J.Gerhart, J.C.Coll, J.Chem.Ecol., 1993,19,2697; (b) A.F.Pozharskii, A.T.Soldatenkov, A.R.Katritzky, Heterocycles in Life and Society, Wiley, Chichester, 1997; (c) M.Elbandy, P.B.Shinde, H.T.Dang, J.Hong, K.S.Bae, J.H.Jung, J.Nat.Prod., 2008,71,869; (d) R.Jadulco, P.Proksch, V.Wray, B.A.Sudarsono, U. j.Nat.Prod., 2001,64,527; (e) joule J.A. (J.A.Joule), Mil Si K. (K.Mills) work. by industry really (C.Ye), tall and big refined (D.B.Gao) etc. translate.Heterocyclic chemistry (Heterocyclic Chemistry).Beijing: Science Press (Beijing:Science Press), 2004,335.
Up to now, the method of existing a large amount of combining polysubstituted furan derivative, except classical Pa Er Nore synthesis method (Paal – Knorr Synthesis) and the auspicious synthesis method of Fei Site – Binet (Feist – Benary Synthesis), by molecule or the method for intermolecular cycloaddition reaction combining polysubstituted furan have also been obtained the extensive concern of scientists.
The people such as Burger report under NaH existent condition, and 3,3-difluoro allyl ketone compounds is through the method (Monatshefte of Intramolecular cycloaddition combining polysubstituted furan derivative chemie, 2007,138,227).The people such as Ichikawa report the enols used method (Synlett, 200357) obtaining furan derivatives through internal nucleophilic substitution of 3,3-difluoro allyl ketones.
The deficiencies in the prior art are mainly manifested in: precious metal need be adopted as catalyzer, substrate is not easy to obtain and suitability is wideless, the substituted radical diversity of the furan derivatives of synthesis is limited.
Given this, this area is easy to get in the urgent need to a kind of low cost (avoid use precious metal be catalyzer), substrate and wide adaptability and product have the multifarious method being prepared furane derivative derivative by Fluorine containing olefine.This also becomes the technical issues that need to address of the present invention.
Summary of the invention
The present inventor is on the basis of prior art and scientific payoffs, through research deep further, find a kind ofly to adopt the metal of advantage of lower cost as catalyzer to prepare the method for furane derivative derivative, overcome the deficiencies in the prior art (if precious metal is catalyzer etc.).
The object of the invention is to, a kind of method by the standby furane derivative derivative (shown in formula I compound) of Fluorine containing olefine system (shown in formula II compound) is provided.
The key step of described method is: under oxysalt (alkali) existence condition having element in I A (race) in mantoquita (catalyzer) and the periodic table of elements, by compound shown in compound and formula III shown in formula II in aprotic organic solvent, be obtained by reacting target compound (shown in formula I compound) in 90C ~ 120C;
In formula, R 1for C 1~ C 4the alkyl of straight or branched, the C of halo 1~ C 4the alkyl of straight or branched, 5 ~ 6 yuan of aromatic ring yls or heterocyclic radical;
R 2for having the group (as cyano group, sulfonic group or substituted sulfonic acid base etc.) of sucting electronic effect, or (curve mark is the position of substitution, lower same);
A is C 4~ C 10aromatic ring yl or heterocyclic radical, or replace C 4~ C 10aromatic ring yl or heterocyclic radical;
Wherein, R 3for C 1~ C 4the alkyl of straight or branched, C 1~ C 4the alkoxyl group of straight or branched, phenyl, or r 4and R 5independently be selected from: hydrogen (H) or C 1~ C 3a kind of in the alkyl of straight or branched;
The heteroatoms of described heterocyclic radical be oxygen (O) or/and sulphur (S), heteroatoms number is 1 or 2;
The C of described replacement 4~ C 10aromatic ring yl or the substituting group of heterocyclic radical be selected from: in following groups one or two or more kinds (containing two kinds, lower with):
C 1~ C 4the alkyl of straight or branched, C 1~ C 4the alkoxyl group of straight or branched, halogen (F, Cl, Br are or/and I), phenyl, benzyloxy r 6s (R 6for C 1~ C 4the alkyl of straight or branched) or cyano group, substituting group number is the integer of 1 ~ 3.
The preparation of compound shown in formula II see document C.S.Thomoson, H.Martinez, W.R.Dolbier, Jr., J.Fluorine Chem.2013,150,53.
As shown from the above technical solution, the invention provides a kind of by together with two fluoroolefin and the method for reacting preparation 2,3,5-trisubstituted furans derivative containing active methylene compound.This method has low cost (avoid use precious metal be catalyzer), substrate is easy to get and wide adaptability and product have the advantages such as diversity.
Embodiment
In the present invention's preferred technical scheme:
Preferred catalyzer is cuprous (Cu +) salt, preferred catalyzer is cuprous halide (CuCl, CuBr or CuI etc.), and the catalyzer of recommendation is cuprous iodide (CuI).
In another preferred technical scheme of the present invention:
Preferred alkali is the carbonate (Na of element in I A (race) in the periodic table of elements 2cO 3, K 2cO 3or Cs 2cO 3deng), the alkali of recommendation is hydrochloric acid caesium (Cs 2cO 3).
In another preferred technical scheme of the present invention:
Preferred aprotic organic solvent is: DMF (DMF) or dimethyl sulfoxide (DMSO) (DMSO).
In a further preferred technical solution of the present invention:
R 1for C 1~ C 3the alkyl of straight or branched; R 2for cyano group or Phenylsulfonic acid base
A is C 6~ C 10aromatic ring yl or heterocyclic radical, or replace C 6~ C 10aromatic ring yl or heterocyclic radical;
Wherein, the heteroatoms of described heterocyclic radical is O or S, and heteroatoms number is 1 or 2;
The C of described replacement 6~ C 10aromatic ring yl or the substituting group of heterocyclic radical be selected from one or two or more kinds in following groups (containing two kinds):
C 1~ C 3the alkoxyl group of straight or branched, R 6s-, halogen (F, Cl, Br are or/and I) or phenyl, R 6for C 1~ C 3the alkyl of straight or branched, substituting group number is the integer of 1 ~ 3.
Preferred R further 1for methyl or ethyl.
Preferred A is further naphthyl or substituted-phenyl;
The substituting group of described substituted-phenyl is selected from: halogen (F, Cl, Br are or/and I), in phenyl or methoxyl group one or two or more kinds;
Preferred A is a kind of in following groups:
In a further preferred technical solution of the present invention:
R 1for C 1~ C 3the alkyl of straight or branched, the C of halo 1~ C 3the alkyl of straight or branched, phenyl or quinary heterocyclic radical, the heteroatoms of described quinary heterocyclic radical is O or S;
R 2for r 3for C 1~ C 3the alkyl of straight or branched, C 1~ C 3the alkoxyl group of straight or branched, phenyl or r 4and R 5independently be selected from: H or C 1~ C 3a kind of in the alkyl of straight or branched;
A is C 4~ C 10aromatic ring yl or heterocyclic radical, or replace C 4~ C 10aromatic ring yl or heterocyclic radical;
Wherein, the heteroatoms of described heterocyclic radical is O or S, and heteroatoms number is 1 or 2; The C of described replacement 4~ C 10aromatic ring yl or the substituting group of heterocyclic radical be selected from one or two or more kinds in following groups (containing two kinds):
C 1~ C 4the alkyl of straight or branched, C 1~ C 3the alkoxyl group of straight or branched, halogen (F, Cl, Br are or/and I), phenyl, benzyloxy r 6s (R 6for C 1~ C 3the alkyl of straight or branched) or cyano group, substituting group number is the integer of 1 ~ 3.
Preferred R further 1for methyl, ethyl, n-propyl, sec.-propyl, phenyl, furyl, halo (F, Cl, Br are or/and I) methyl;
Further preferred R 1for: methyl, ethyl, sec.-propyl, phenyl, 2-furyl or difluoromethyl (CF 2h).
Preferred R further 2for r 3for methyl, ethyl, sec.-propyl, phenyl, methoxyl group, oxyethyl group or r 4and R 5independently be selected from: a kind of in methyl, ethyl or propyl group.
Preferred A is C further 4or C 7heterocyclic radical, C 10aromatic ring yl, or replace hexa-atomic aromatic ring yl;
Wherein, the heteroatoms of described heterocyclic radical is O or S, and heteroatoms number is 1 or 2; The substituting group of the hexa-atomic aromatic ring yl of described replacement is selected from one or two or more kinds in following groups:
C 1~ C 4the alkyl of straight or branched, C 1~ C 3the alkoxyl group of straight or branched, halogen (F, Cl, Br are or/and I), phenyl, benzyloxy r 6s-(R 6for C 1~ C 3the alkyl of straight or branched) or cyano group, substituting group number is the integer of 1 ~ 3;
Further preferred A is thienyl, naphthyl or substituted-phenyl;
Wherein, the substituting group of described substituted-phenyl is selected from one or two or more kinds in following groups:
Methyl, the tertiary butyl, methoxyl group, phenyl, halogen (F, Cl, Br or I), benzyloxy or cyano group, substituting group number is 1 or 2.
Preferred A is a kind of in following groups further again:
Below by embodiment, the invention will be further described, and its object is only better to understand content of the present invention.Therefore, protection scope of the present invention is not limited by the cases cited.
Embodiment 1
The synthesis of 2-methyl-3-ethanoyl-5-(4-p-methoxy-phenyl) furans (chemical compounds I-1):
Under argon shield condition, by the CuI (9.55mg, 0.05mmol) that takes and Cs 2cO 3(652mg, 2.0mmol) be placed in dry 25mL two mouthfuls of flasks, add the DMSO of 5mL drying, add compound ii-1 (170mg successively, 1.0mmol) with compound III-1 (200mg, 2.0mmol), open and stir, about 12h (determining the time of stopped reaction with TLC) is reacted under 90 DEG C of conditions, be cooled to room temperature, with saturated aqueous common salt and extraction into ethyl acetate three times, merge organic phase, underpressure distillation removing ethyl acetate, residue by silicagel column column chromatography for separation (normal hexane: ethyl acetate=25:1 (V/V)), obtain white solid (chemical compounds I-1), fusing point 94.6-95.3 DEG C, yield 88%.
1H NMR(400MHz,CDCl 3):δ7.56(d,J＝8.8Hz,2H),6.91(d,J＝8.8Hz,2H),6.69(s,1H),3.82(s,3H),2.63(s,3H),2.43(s,3H)； 13C NMR(100MHz,CDCl 3):δ194.2,159.4,157.2,151.7,125.2,123.2,122.9,114.2,103.4,55.3,29.1,14.5；HRMS(EI):calcd for C 14H 14O 3[M] +:230.0943,found:230.0942。
Embodiment 2
The synthesis of 2-methyl-3-ethanoyl-5-(4-benzyloxy-phenyl) furans (chemical compounds I-2):
Except with except the compound ii-1 in compound ii-2 alternate embodiment 1, all the other steps are identical with embodiment 1, obtain white solid (chemical compounds I-2), fusing point 119.9-120.5 DEG C, yield 90%.
1H NMR(400MHz,CDCl 3):δ7.56(d,J＝8.8Hz,2H),7.43–7.36(m,5H),6.99(d,J＝8.8Hz,2H),6.70(s,1H),5.08(s,2H),2.64(s,3H),2.42(s,3H)； 13C NMR(100MHz,CDCl 3):δ194.2,158.6,157.3,151.7,136.8,128.6,128.1,127.5,125.2,123.3,123.2,115.2,103.6,70.1,29.2,14.5；HRMS(EI):calcd for C 20H 18O 3[M] +:306.1256,found:306.1255。
Embodiment 3
The synthesis of 2-methyl-3-ethanoyl-5-(methylenedioxyphenyl) furans (chemical compounds I-3):
Except with except the compound ii-1 in compound ii-3 alternate embodiment 1, all the other steps are identical with embodiment 1, obtain white solid (chemical compounds I-3), fusing point 101.9-102.8 DEG C, yield 91%.
1H NMR(400MHz,CDCl 3):δ7.15(dd,J＝8.8,1.6Hz,1H),7.10(d,J＝1.6Hz,1H),6.82(d,J＝8.0Hz,1H),6.69(s,1H),5.98(s,2H),2.64(s,3H),2.44(s,3H)； 13C NMR(100MHz,CDCl 3):δ194.1,157.4,151.5,148.1,147.4,124.3,123.2,117.7,108.7,104.5,103.9,101.3,29.1,14.5；HRMS(EI):calcd for C 14H 12O 4[M] +:244.0736,found:244.0735。
Embodiment 4
The synthesis of 2-methyl-3-ethanoyl-5-(3,4-Dimethoxyphenyl) furans (chemical compounds I-4):
Except with except the compound ii-1 in compound ii-4 alternate embodiment 1, all the other steps are identical with embodiment 1, obtain white solid (chemical compounds I-4), fusing point 93.2-94.2 DEG C, yield 80%.
1H NMR(400MHz,CDCl 3):δ7.21(d,J＝8.4Hz,1H),7.15(s,1H),6.89(d,J＝8.4Hz,1H),6.72(s,1H),3.95(s,3H),3.91(s,3H),2.66(s,3H),2.45(s,3H)； 13C NMR(100MHz,CDCl 3):δ194.1,157.3,151.7,149.3,149.0,123.3,123.2,116.6,111.5,107.2,103.8,56.0,29.2,14.5；HRMS(EI):calcd for C 15H 16O 4[M] +:260.1049,found:260.1050。
Embodiment 5
The synthesis of 2-methyl-3-ethanoyl-5-(4-methylthio group phenyl) furans (chemical compounds I-5):
Except with except the compound ii-1 in compound ii-5 alternate embodiment 1, all the other steps are identical with embodiment 1, obtain white solid (chemical compounds I-5), fusing point 88.6-89.2 DEG C, yield 89%.
1H NMR(400MHz,CDCl 3):δ7.55(d,J＝8.4Hz,2H),7.26(d,J＝8.4Hz,2H),6.79(s,1H),2.65(s,3H),2.50(s,3H),2.44(s,3H)； 13C NMR(100MHz,CDCl 3):δ194.0,157.7,151.4,138.3,126.8,126.7,124.1,123.3,104.7,29.1,15.7,14.5；HRMS(EI):calcd for C 14H 14O 2S[M] +:246.0715,found:246.0716。
Embodiment 6
The synthesis of 2-methyl-3-ethanoyl-5-(3,4-3,5-dimethylphenyl) furans (chemical compounds I-6):
Except with except the compound ii-1 in compound ii-6 alternate embodiment 1, all the other steps are identical with embodiment 1, obtain white solid (chemical compounds I-6), fusing point 133.6-134.5 DEG C, yield 80%.
1H NMR(400MHz,CDCl 3):δ7.42(s,1H,),7.37(d,J＝8.0Hz,1H),7.14(d,J＝8.0Hz,1H),6.77(s,1H),2.65(s,3H),2.43(s,3H),2.29(s,3H),2.27(s,3H)； 13C NMR(100MHz,CDCl 3):δ194.2,157.5,152.0,137.0,136.4,130.0,127.6,124.9,123.2,121.2,104.2,29.2,19.8,19.6,14.5；HRMS(EI):calcd for C 15H 16O 2[M] +:228.1150,found:228.1151。
Embodiment 7
The synthesis of 2-methyl-3-ethanoyl-5-(2,3-3,5-dimethylphenyl) furans (chemical compounds I-7):
Except with except the compound ii-1 in compound ii-7 alternate embodiment 1, all the other steps are identical with embodiment 1, obtain white solid (chemical compounds I-7), fusing point 64.5-65.2 DEG C, yield 81%.
1H NMR(400MHz,CDCl 3):δ7.44–7.40(m,1H),7.17–7.13(m,2H),6.67(s,1H),2.67(s,3H),2.46(s,3H),2.37(s,3H),2.35(s,3H)； 13C NMR(100MHz,CDCl 3):δ194.2,157.5,151.9,137.5,134.0,130.0,129.9,126.1,125.6,123.0,108.9,29.2,20.8,17.1,14.5。
Embodiment 8
The synthesis of 2-methyl-3-ethanoyl-5-(4-tert-butyl-phenyl) furans (chemical compounds I-8):
Except with except the compound ii-1 in compound ii-8 alternate embodiment 1, all the other steps are identical with embodiment 1, obtain white solid (chemical compounds I-8), fusing point 81.9-82.9 DEG C, yield 87%.
1H NMR(400MHz,CDCl 3):δ7.56(d,J＝8.4Hz,2H),7.40(d,J＝8.4Hz,2H),6.78(s,1H),2.64(s,3H),2.43(s,3H),1.33(s,9H)； 13C NMR(100MHz,CDCl 3):δ194.1,157.6,151.9,151.0,127.2,125.7,123.5,123.2,104.4,34.7,31.3,29.1,14.5；HRMS(EI):calcd for C 17H 20O 2[M] +:256.1463,found:256.1465。
Embodiment 9
The synthesis of 2-methyl-3-ethanoyl-5-(4-phenyl) furans (chemical compounds I-9):
Except with except the compound ii-1 in compound ii-9 alternate embodiment 1, all the other steps are identical with embodiment 1, obtain white solid (chemical compounds I-9), fusing point 109.9-110.9 DEG C, yield 81%.
1H NMR(400MHz,CDCl 3):δ7.72–7.70(m,2H),7.63–7.60(m,4H),7.46–7.43(m,2H),7.37–7.33(m,1H),6.87(s,1H),2.67(s,3H),2.46(s,3H)； 13C NMR(100MHz,CDCl 3):δ194.1,158.1,151.5,140.5,140.4,128.9,127.5,127.4,126.9,124.1,123.4,105.2,29.2,14.6；HRMS(EI):calcd for C 19H 16O 2[M] +:276.1150,found:276.1151。
Embodiment 10
The synthesis of 2-methyl-3-ethanoyl-5-(1-naphthalene) furans (chemical compounds I-10):
Except with except the compound ii-1 in compound ii-10 alternate embodiment 1, all the other steps are identical with embodiment 1, obtain yellow oil (chemical compounds I-10), yield 85%.
1H NMR(400MHz,CDCl 3):δ8.33(d,J＝8.4Hz,1H),7.88–7.82(m,2H),7.70(d,J＝7.2Hz,1H),7.56–7.47(m,3H),6.91(s,1H),2.71(s,3H),2.48(s,3H)； 13C NMR(100MHz,CDCl 3):δ194.1,158.2,151.1,134.0,130.3,129.0,128.7,127.6,126.8,126.3,126.1,125.3,125.2,123.2,109.5,29.2,14.6；HRMS(EI):calcd for C 17H 14O 2[M] +:250.0994,found:250.0995。
Embodiment 11
The synthesis of 2-methyl-3-ethanoyl-5-(4-chloro-phenyl-) furans (chemical compounds I-11):
Except with except the compound ii-1 in compound ii-11 alternate embodiment 1, all the other steps are identical with embodiment 1, obtain white solid (chemical compounds I-11), fusing point 114.1-114.7 DEG C, yield 72%.
1H NMR(400MHz,CDCl 3):δ7.56(d,J＝8.4Hz,2H),7.35(d,J＝8.4Hz,2H),6.83(s,1H),2.65(s,3H),2.44(s,3H)； 13C NMR(100MHz,CDCl 3):δ193.8,158.1,150.6,133.5,129.0,128.4,124.9,123.4,105.5,29.1,14.5；HRMS(EI):calcd for C 13H 11ClO 2[M] +:234.0448,found:234.0449。
Embodiment 12
The synthesis of 2-methyl-3-ethanoyl-5-(3-bromophenyl) furans (chemical compounds I-12):
Except with except the compound ii-1 in compound ii-12 alternate embodiment 1, all the other steps are identical with embodiment 1, obtain white solid (chemical compounds I-12), fusing point 98.0-98.6 DEG C, yield 75%.
1H NMR(400MHz,CDCl 3):δ7.65(s,1H),7.42(d,J＝7.6Hz,1H),7.27(d,J＝8.0Hz,1H,),7.14–7.10(m,1H),6.74(s,1H),2.54(s,3H),2.33(s,3H)； 13C NMR(100MHz,CDCl 3):δ193.9,158.5,150.0,131.8,130.6,130.3,126.6,123.3,123.0,122.1,106.2,29.2,14.5；HRMS(EI):calcd for C 13H 11BrO 2[M] +:277.9942,found:277.9943。
Embodiment 13
The synthesis of 2-methyl-3-ethanoyl-5-(3-iodophenyl) furans (chemical compounds I-13):
Except with except the compound ii-1 in compound ii-13 alternate embodiment 1, all the other steps are identical with embodiment 1, obtain white solid (chemical compounds I-13), fusing point 74.5-75.2 DEG C, yield 61%.
1H NMR(400MHz,CDCl 3):δ7.99–7.98(m,1H),7.60–7.57(m,2H),7.13–7.09(m,1H),6.85(s,1H),2.65(s,3H),2.44(s,3H)； 13C NMR(100MHz,CDCl 3):194.0,158.5,149.8,136.5,132.4,131.8,130.4,123.3,122.7,106.2,94.6,29.2,14.6；HRMS(EI):calcd for C 13H 11IO 2[M] +:325.9804,found:325.9805。
Embodiment 14
The synthesis of 2-methyl-3-ethanoyl-5-(4-cyano-phenyl) furans (chemical compounds I-14):
Except with except the compound ii-1 in compound ii-14 alternate embodiment 1, all the other steps are identical with embodiment 1, obtain white solid (chemical compounds I-14), fusing point 182.3-183.1 DEG C, yield 53%.
1H NMR(400MHz,CDCl 3):δ7.73(d,J＝8.4Hz,2H),7.67(d,J＝8.4Hz,2H),7.03(s,1H),2.69(s,3H),2.47(s,3H)； 13C NMR(100MHz,CDCl 3):δ193.6,159.4,149.6,133.8,132.7,123.9,123.6,118.7,110.8,108.3,29.2,14.6；HRMS(EI):calcd for C 14H 11NO 2[M] +:225.0790,found:225.0793。
Embodiment 15
The synthesis of 2-methyl-3-ethanoyl-5-(2-thiophene) furans (chemical compounds I-15):
Except with except the compound ii-1 in compound ii-15 alternate embodiment 1, all the other steps are identical with embodiment 1, obtain white solid (chemical compounds I-15), fusing point 61.2-62.1 DEG C, yield 84%.
1H NMR(400MHz,CDCl 3):δ7.24–7.22(m,2H),7.03(dd,J＝5.2,3.6Hz,1H),6.67(s,1H),2.62(s,3H),2.41(s,3H)； 13C NMR(100MHz,CDCl 3):δ193.9,157.5,147.2,132.6,127.7,124.6,123.1,105.0,29.1,14.4；HRMS(EI):calcd for C 14H 11NO 2[M] +:206.0402,found:206.0403。
Embodiment 16
The synthesis of 2-ethyl-3-propionyl-5-(4-p-methoxy-phenyl) furans (chemical compounds I-16):
Except with except the compound III-1 in compound III-2 alternate embodiment 1, all the other steps are identical with embodiment 1, obtain white solid (chemical compounds I-16), fusing point 74.5-75.2 DEG C, yield 85%.
1H NMR(400MHz,CDCl 3):δ7.57(d,J＝8.8Hz,2H),6.92(d,J＝8.8Hz,2H),6.69(s,1H),3.82(s,3H),3.07(q,J＝7.6Hz,2H),2.77(q,J＝7.2Hz,2H),1.30(t,J＝7.6Hz,3H),1.18(t,J＝7.2Hz,3H)； 13C NMR(100MHz,CDCl 3):δ197.1,162.1,159.3,151.6,125.2,123.1,121.6,114.2,103.1,55.3,34.4,21.8,12.1,7.9；HRMS(EI):calcd for C 13H 11IO 2[M] +:258.1256,found:258.1255。
Embodiment 17
The synthesis of 2-sec.-propyl-3-(2-methylpropionyl)-5-(4-p-methoxy-phenyl) furans (chemical compounds I-17):
Except being set to except 120 DEG C by the compound III-1 in compound III-3 alternate embodiment 1 and temperature of reaction, all the other steps are identical with embodiment 1, obtain white solid (chemical compounds I-17), fusing point 71.2-72.0 DEG C, yield 88%.
1H NMR(400MHz,CDCl 3):δ7.58(d,J＝8.8Hz,2H),6.92(d,J＝8.8Hz,2H),6.70(s,1H),3.88–3.81(m,1H),3.79(s,3H),3.19–3.09(m,1H),1.33(d,J＝6.8Hz,6H),1.19(d,J＝6.8Hz,6H)； 13C NMR(100MHz,CDCl 3):δ200.8,166.0,159.3,151.4,125.1,123.2,119.9,114.2,103.1,55.2,38.4,27.7,20.7,18.7；HRMS(EI):calcd for C 13H 11IO 2[M] +:286.1569,found:286.1570。
Embodiment 18
The synthesis of 3-(2-methyl-5-(4-p-methoxy-phenyl)) furyl ethyl formate (chemical compounds I-18):
Except with except the compound III-1 in compound III-4 alternate embodiment 1, all the other steps are identical with embodiment 1, obtain white solid (chemical compounds I-18), fusing point 62.1-62.9 DEG C, yield 82%.
1H NMR(400MHz,CDCl 3):δ7.51(d,J＝8.8Hz,2H),6.86(d,J＝8.8Hz,2H),6.71(s,1H),4.28(q,J＝7.2Hz,2H),3.75(s,3H),2.59(s,3H),1.34(t,J＝7.2Hz,3H)ppm； 13C NMR(100MHz,CDCl 3):δ164.0,159.2,157.8,151.8,125.0,123.1,115.3,114.1,103.8,60.1,55.1,14.3,13.7。
Embodiment 19
The synthesis of 3-(2-methyl-5-(4-p-methoxy-phenyl)) methyl furoate (chemical compounds I-19):
Except with except the compound III-1 in compound III-5 alternate embodiment 1, all the other steps are identical with embodiment 1, obtain white solid (chemical compounds I-19), fusing point 79.4-81.2 DEG C, yield 80%.
1H NMR(400MHz,CDCl 3):δ7.54(d,J＝8.8Hz,2H),6.90(d,J＝8.8Hz,2H),6.72(s,1H),3.83(s,3H),3.80(s,3H),2.62(s,3H)； 13C NMR(100MHz,CDCl 3):δ164.5,159.3,158.1,151.9,125.1,123.1,115.0,114.2,103.7,55.2,51.3,13.8。
Embodiment 20
The synthesis of 3-(2-ethyl-5-(4-p-methoxy-phenyl)) furyl ethyl formate (chemical compounds I-20):
Except with except the compound III-1 in compound III-6 alternate embodiment 1, all the other steps are identical with embodiment 1, obtain white solid (chemical compounds I-20), fusing point 45.7-46.2 DEG C, yield 86%.
1H NMR(400MHz,CDCl 3):δ7.58(d,J＝8.8Hz,2H),6.92(d,J＝9.2Hz,2H),6.75(s,1H),4.31(q,J＝7.2Hz,2H),3.83(s,3H),3.07(q,J＝7.6Hz,2H),1.37(t,J＝7.2Hz,3H),1.32(t,J＝7.6Hz,3H)； 13C NMR(100MHz,CDCl 3):δ164.1,162.9,159.2,151.7,125.1,123.2,114.4,114.2,103.9,60.1,55.3,21.3,14.4,12.4。
Embodiment 21
The synthesis of 3-(2-phenyl-5-(4-p-methoxy-phenyl)) furyl ethyl formate (chemical compounds I-21):
Except with except the compound III-1 in compound III-7 alternate embodiment 1, all the other steps are identical with embodiment 1, obtain white solid (chemical compounds I-21), fusing point 63.2-64.0 DEG C, yield 85%.
1H NMR(400MHz,CDCl 3):δ8.12(d,J＝7.6Hz,2H),7.67(d,J＝8.8Hz,2H),7.51–7.42(m,3H),6.97(s,1H),6.95(d,J＝8.8Hz,2H),4.36(q,J＝7.2Hz,2H),3.81(s,3H),1.39(t,J＝7.0Hz,3H)； 13C NMR(100MHz,CDCl 3):δ163.7,159.6,155.8,152.5,129.9,129.2,128.3,128.2,125.5,122.7,115.8,114.3,106.4,60.6,55.3,14.3。
Embodiment 22
The synthesis of 2-phenyl-3-ethanoyl-5-(4-p-methoxy-phenyl) furans (chemical compounds I-22):
Except being set to except 120 DEG C by the compound III-1 in compound III-8 alternate embodiment 1 and temperature of reaction, all the other steps are identical with embodiment 1, obtain yellow oil (chemical compounds I-22), yield 38%.
1H NMR(400MHz,CDCl 3):δ7.98–7.95(m,2H),7.67(d,J＝8.4Hz,2H),7.49–7.43(m,3H),6.95(d,J＝9.2Hz,2H),6.89(s,1H),3.84(s,3H),2.46(s,3H)； 13C NMR(100MHz,CDCl 3):δ194.2,159.7,155.1,152.7,130.1,129.6,128.5,128.3,125.6,124.2,122.6,114.3,105.6,55.4,29.9；HRMS(EI):calcd for C 19H 16O 3[M] +:292.1099,found:292.1104。
Embodiment 23
The synthesis of 2-methyl-3-benzoyl-5-(4-p-methoxy-phenyl) furans (chemical compounds I-23):
Except being set to except 120 DEG C by the compound III-1 in compound III-8 alternate embodiment 1 and temperature of reaction, all the other steps are identical with embodiment 1, obtain yellow oil (chemical compounds I-23), yield 42%.
1H NMR(400MHz,CDCl 3):δ7.83(d,J＝7.6Hz,2H),7.57–7.52(m,3H),7.48–7.44(m,2H),6.89(d,J＝8.8Hz,2H),6.66(s,1H),3.78(s,3H),2.57(s,3H)； 13C NMR(100MHz,CDCl 3):δ191.4,159.4,158.4,151.7,139.2,132.2,129.0,128.4,125.2,123.0,122.3,114.2,104.9,55.3,14.4；HRMS(EI):calcd for C 19H 16O 3[M] +:292.1099,found:292.1103。
Embodiment 24
The synthesis of 2-phenyl-3-benzoyl-5-(4-p-methoxy-phenyl) furans (chemical compounds I-24):
Except being set to except 120 DEG C by the compound III-1 in compound III-9 alternate embodiment 1 and temperature of reaction, all the other steps are identical with embodiment 1, obtain yellow oil (chemical compounds I-24), yield 50%.
1H NMR(400MHz,CDCl 3):δ7.92–7.90(m,2H),7.80–7.78(m,2H),7.71(d,J＝8.8Hz,2H),7.56–7.52(m,1H),7.44–7.40(m,2H),7.36–7.31(m,3H),6.98(d,J＝8.8Hz,2H),6.82(s,1H),3.86(s,3H)； 13C NMR(100MHz,CDCl 3):δ192.0,159.7,154.4,152.6,138.1,132.9,129.9,129.8,128.9,128.4,128.3,127.4,125.6,122.9,122.7,114.3,107.2,55.4；HRMS(EI):calcd for C 18H 16O 4S[M] +:354.1256,found:354.1255。
Embodiment 25
The synthesis of 3-(2-(2-furyl)-5-(4-p-methoxy-phenyl)) furyl ethyl formate (chemical compounds I-25):
Except being set to except 120 DEG C by the compound III-1 in compound III-10 alternate embodiment 1 and temperature of reaction, all the other steps are identical with embodiment 1, obtain white solid (chemical compounds I-25), fusing point 110.9-111.8 DEG C, yield 84%.
1H NMR(400MHz,CDCl 3):δ7.65(d,J＝8.8Hz,2H),7.57–7.56(m,1H),7.55(dd,J＝3.6,0.6Hz,1H),6.92(d,J＝8.8Hz,2H),6.87(s,1H),6.56(dd,J＝3.6,1.6Hz,1H),3.88(s,3H),3.81(s,3H)ppm； 13C NMR(100MHz,CDCl 3):δ163.3,159.6,152.4,147.5,144.7,143.3,125.5,122.4,114.2,114.0,113.1,112.0,105.4,55.2,51.6。
Embodiment 26
The synthesis of 3-(2-methyl-5-(4-p-methoxy-phenyl)) furoyl dimethylamine (chemical compounds I-26):
Except being set to except 120 DEG C by the compound III-1 in compound III-11 alternate embodiment 1 and temperature of reaction, all the other steps are identical with embodiment 1, obtain white solid (chemical compounds I-26), fusing point 114.5-115.5 DEG C, yield 84%.
1H NMR(400MHz,CDCl 3):δ7.55(d,J＝8.8Hz,2H),6.91(d,J＝8.8Hz,2H),6.49(s,1H),3.83(s,3H),3.09(s,6H),2.44(s,3H)； 13C NMR(100MHz,CDCl 3):δ166.5,159.1,152.1,151.6,125.1,123.4,117.8,114.2,103.7,55.3,29.7,13.2；HRMS(EI):calcd for C 15H 17NO 3[M] +:259.1208,found:259.1207。
Embodiment 27
The synthesis of 3-(2-difluoromethyl-5-(4-p-methoxy-phenyl)) furyl ethyl formate (chemical compounds I-27):
Except being set to except 120 DEG C by the compound III-1 in compound III-11 alternate embodiment 1 and temperature of reaction, all the other steps are identical with embodiment 1, obtain white solid (chemical compounds I-27), fusing point 87.3-88.2 DEG C, yield 16%.
1H NMR(400MHz,CDCl 3):δ7.66(d,J＝8.8Hz,2H),7.23(t,J＝52.6Hz,1H),6.94(d,J＝8.4Hz,2H),6.83(s,1H),4.36(q,J＝7.2Hz,2H),3.84(s,3H),1.39(t,J＝7.2Hz,3H)； 13C NMR(100MHz,CDCl 3):δ162.1,160.3,155.5,147.3(t, 2J CF＝23.1Hz),126.1,121.7,121.1(t, 3J CF＝5.9Hz),114.3,106.8(t, 1J CF＝233.7Hz),103.8,61.3,55.4,14.2； 19F NMR(376MHz,CDCl 3):δ–116.6(d,J＝52.6Hz,2F)；HRMS(EI):calcd for C 15H 14F 2O 4[M] +:296.0860,found:296.0863。
Embodiment 28
The synthesis of 2-sec.-propyl-3-(2-methylpropionyl)-5-(3,4-3,5-dimethylphenyl) furans (chemical compounds I-28):
Replace compound ii-1 except with compound ii-6, compound III-3 replaces compound III-1 and temperature of reaction is set to outside 120 DEG C, and all the other steps are identical with embodiment 1, obtain yellow oil (chemical compounds I-28), yield 90%.
1H NMR(400MHz,CDCl 3):δ7.45(s,1H),7.41(d,J＝7.6Hz,1H),7.15(d,J＝7.6Hz,1H),6.79(s,1H),3.91–3.81(m,1H),3.23–3.12(m,1H),2.32(s,3H),2.28(s,3H),1.37(d,J＝7.2Hz,6H),1.22(d,J＝6.8Hz,6H)； 13C NMR(100MHz,CDCl 3):δ200.9,166.3,151.7,136.9,136.3,130.0,127.9,124.9,121.3,119.9,103.9,38.4,27.8,20.7,19.8,19.6,18.8；HRMS(EI):calcd for C 19H 24O 2[M] +:284.1776,found:284.1777。
Embodiment 29
The synthesis of 2-ethyl-3-propionyl-5-(4-tert-butyl-phenyl) furans (chemical compounds I-29):
Replace compound ii-1 except with compound ii-8, compound III-2 is replaced outside compound III-1, and all the other steps are identical with embodiment 1, obtain white solid (chemical compounds I-29), fusing point 66.2-67.0 DEG C, yield 70%.
1H NMR(400MHz,CDCl 3):δ7.59(d,J＝8.4Hz,2H),7.42(d,J＝8.4Hz,2H),6.80(s,1H),3.10(q,J＝7.6Hz,2H),2.80(q,J＝7.2Hz,2H),1.34(s,9H),1.32(t,J＝7.6Hz,3H),1.19(t,J＝7.2Hz,3H)； 13C NMR(100MHz,CDCl 3):δ197.1,162.5,151.8,150.9,127.4,125.7,123.5,121.7,104.1,34.7,34.4,31.3,21.8,12.1,7.9；HRMS(EI):calcd for C 19H 24O 2[M] +:284.1776,found:284.1777。
Embodiment 30
The synthesis of 3-(2-methyl-5-(4-phenyl)) furyl ethyl formate (chemical compounds I-30):
Replace compound ii-1 except with compound ii-9, compound III-4 is replaced outside compound III-1, and all the other steps are identical with embodiment 1, obtain white solid (chemical compounds I-30), fusing point 93.4-94.2 DEG C, yield 92%.
1H NMR(400MHz,CDCl 3):δ7.72(d,J＝8.4Hz,2H),7.63(d,J＝8.4Hz,4H),7.48–7.44(m,2H),7.39–7.35(m,1H),6.95(s,1H),4.34(q,J＝7.6Hz,2H),2.68(s,3H),1.40(t,J＝7.0Hz,3H)； 13C NMR(100MHz,CDCl 3):δ164.1,158.8,151.5,140.5,140.3,129.0,128.9,127.5,127.4,126.9,124.1,115.5,105.7,60.3,14.4,14.0。
Embodiment 31
The synthesis of 2-ethyl-3-propionyl-5-(1-naphthyl) furans (chemical compounds I-31):
Replace compound ii-1 except with compound ii-10, compound III-2 is replaced outside compound III-1, and all the other steps are identical with embodiment 1, obtain yellow oil (chemical compounds I-31), yield 68%.
1H NMR(400MHz,CDCl 3):δ8.36(d,J＝8.0Hz,1H),7.92–7.85(m,2H),7.73(d,J＝7.2Hz,1H),7.59–7.50(m,3H),6.94(s,1H),3.18(q,J＝7.6Hz,2H),2.86(q,J＝7.2Hz,2H),1.38(t,J＝7.4Hz,3H),1.23(t,J＝7.4Hz,3H)； 13C NMR(100MHz,CDCl 3):δ197.2,163.1,151.0,134.0,130.3,129.0,128.7,127.7,126.8,126.2,126.1,125.3,125.2,121.6,109.1,34.6,21.9,12.2,8.0；HRMS(EI):calcd for C 19H 18O 2[M] +:278.1307,found:278.1309。
Embodiment 32
The synthesis of 3-(2-methyl-5-(4-chloro-phenyl-)) methyl furoate (chemical compounds I-32):
Replace compound ii-1 except with compound ii-11, compound III-5 is replaced outside compound III-1, and all the other steps are identical with embodiment 1, obtain white solid (chemical compounds I-32), fusing point: 102.8-103.8 DEG C, yield 91%.
1H NMR(400MHz,CDCl 3):δ7.42(d,J＝8.4Hz,2H),7.22(d,J＝8.4Hz,2H),6.74(s,1H),3.74(s,3H),2.53(s,3H)； 13C NMR(100MHz,CDCl 3):δ163.2,157.9,149.6,132.2,127.9,127.4,123.7,114.2,104.8,50.4,12.8。
Embodiment 33
The synthesis of 2-sec.-propyl-3-(2-methylpropionyl)-5-(3-bromophenyl) furans (chemical compounds I-33):
Replace compound ii-1 except with compound ii-12, compound III-3 is replaced outside compound III-1, and all the other steps are identical with embodiment 1, obtain yellow oil (chemical compounds I-33), yield 71%.
1H NMR(400MHz,CDCl 3):δ7.78(t,J＝2.0Hz,1H),7.57(dt,J＝8.0,1.2Hz,1H),7.40(dq,J＝8.0,1.2Hz,1H),7.26(t,J＝8.0Hz,1H),6.87(s,1H),3.87–3.77(m,1H),3.20–3.09(m,1H),1.33(d,J＝6.8Hz,6H),1.20(d,J＝6.8Hz,6H)； 13C NMR(100MHz,CDCl 3):δ200.6,167.3,149.7,132.1,130.5,130.3,126.5,122.9,122.2,120.0,105.9,38.5,27.8,20.7,18.7；HRMS(EI):calcd for C 17H 19BrO 2[M] +:334.0568,found:334.0566。
Embodiment 34
The synthesis of 2-sec.-propyl-3-(2-methylpropionyl)-5-(2-thiophene) furans (chemical compounds I-34):
Replace compound ii-1 except with compound ii-15, compound III-3 replaces compound III-1 and temperature of reaction is outside 120 DEG C, and all the other steps are identical with embodiment 1, obtain yellow oil (chemical compounds I-34), yield 82%.
1H NMR(400MHz,CDCl 3):δ7.26(dd,J＝3.6,1.2Hz,1H),7.22(dd,J＝5.2,1.2Hz,1H),7.03(dd,J＝4.8,3.6Hz,1H),6.67(s,1H),3.86–3.76(m,1H),3.16–3.06(m,1H),1.31(d,J＝6.8Hz,6H),1.19(d,J＝6.8Hz,6H)； 13C NMR(100MHz,CDCl 3):δ200.6,166.4,146.9,132.9,127.7,124.4,123.0,119.8,104.7,38.4,27.7,20.6,18.7；HRMS(EI):calcd for C 15H 18O 2S[M] +:262.1028,found:262.1029。
Embodiment 35
The synthesis of 3-(2-phenyl-5-(2-thiophene)) furyl ethyl formate (chemical compounds I-35):
Replace compound ii-1 except with compound ii-15, compound III-7 replaces compound III-1 and temperature of reaction is outside 120 DEG C, and all the other steps are identical with embodiment 1, obtain white solid (chemical compounds I-35), fusing point 59.2-60.2 DEG C, yield 80%.
1H NMR(400MHz,CDCl 3):δ8.06–8.03(m,2H),7.45–7.36(m,3H),7.31(dd,J＝3.6,0.8Hz,1H),7.23(dd,J＝5.2,1.2Hz,1H),7.02(dd,J＝4.8,3.6Hz,1H),6.91(s,1H),4.30(q,J＝7.2Hz,2H),1.33(t,J＝7.2Hz,3H)； 13C NMR(100MHz,CDCl 3):δ163.4,156.1,148.1,132.5,129.5,129.4,128.4,128.2,127.9,125.1,123.6,115.7,107.8,60.7,14.3；HRMS(EI):calcd for C 17H 14O 3S[M] +:298.0664,found:298.0665。
Embodiment 36
The synthesis of 3-(2-(2-furans)-5-(2-thiophene)) methyl furoate (chemical compounds I-36):
Replace compound ii-1 except with compound ii-15, compound III-10 replaces compound III-1 and temperature of reaction is outside 120 DEG C, and all the other steps are identical with embodiment 1, obtain white solid (chemical compounds I-36), fusing point 72.5-73.3 DEG C, yield 82%.
1H NMR(400MHz,CDCl 3):δ7.45–7.44(m,2H),7.24(dd,J＝3.6,0.8Hz,1H),7.15(dd,J＝5.0,1.0Hz,1H),6.92(dd,J＝4.8,3.6Hz,1H),6.74(s,1H),6.44–6.43(m,1H),3.75(s,3H)； 13CNMR(100MHz,CDCl 3):δ161.9,146.8,146.6,143.2,142.5,131.0,126.7,124.1,122.8,112.8,112.5,111.0,105.8,50.6；HRMS(EI):calcd for C 14H 10O 4S[M] +:274.0300,found:274.0302。
Embodiment 37
The synthesis of 2-methyl-3-cyano group-5-(4-p-methoxy-phenyl) furans (chemical compounds I-37):
Except being except 120 DEG C by compound III-10 replacement compound III-1 and temperature of reaction, all the other steps are identical with embodiment 1, obtain white solid (chemical compounds I-37), fusing point 90.4-91.2 DEG C, yield 80%.
1H NMR(400MHz,CDCl 3):δ7.53(d,J＝9.2Hz,2H),6.92(d,J＝9.2Hz,2H),6.50(s,1H),3.83(s,3H),2.52(s,3H)； 13C NMR(100MHz,CDCl 3):δ160.2,159.8,153.6,125.4,121.9,114.3,103.6,95.6,55.4,13.3。
Embodiment 38
The synthesis of 2-methyl-3-cyano group-5-(methylenedioxyphenyl) furans (chemical compounds I-38):
Replace compound ii-1 except with compound ii-3, compound III-13 replaces compound III-1 and temperature of reaction is outside 120 DEG C, and all the other steps are identical with embodiment 1, obtain white solid (chemical compounds I-38), fusing point 150.8-151.7 DEG C, yield 76%.
1H NMR(400MHz,CDCl 3):δ7.12(dd,J＝8.0,1.6Hz,1H),7.05(d,J＝1.6Hz,1H),6.83(d,J＝8.4Hz,1H),6.50(s,1H),6.00(s,2H),2.52(s,3H)； 13C NMR(100MHz,CDCl 3):δ160.4,153.3,148.2,147.9,123.3,118.1,114.2,108.7,104.6,104.2,101.4,95.7,13.3。
Embodiment 39
The synthesis of 2-methyl-3-cyano group-5-(4-phenyl) furans (chemical compounds I-39):
Replace compound ii-1 except with compound ii-9, compound III-13 replaces compound III-1 and temperature of reaction is outside 120 DEG C, and all the other steps are identical with embodiment 1, obtain white solid (chemical compounds I-39), fusing point 177.6-178.3 DEG C, yield 90%.
1H NMR(400MHz,CDCl 3):δ7.70–7.62(m,6H),7.50–7.46(m,2H),7.41–7.37(m,1H),6.70(s,1H),2.58(s,3H)； 13C NMR(100MHz,CDCl 3):δ161.0,153.3,141.2,140.2,128.9,127.9,127.7,127.5,127.0,124.4,114.2,105.5,96.0,13.4；HRMS(EI):calcd for C 18H 13NO[M] +:259.0997,found:259.0999。
Embodiment 40
The synthesis of 2-methyl-3-cyano group-5-(-naphthyl) furans (chemical compounds I-40):
Replace compound ii-1 except with compound ii-10, compound III-13 replaces compound III-1 and temperature of reaction is outside 120 DEG C, and all the other steps are identical with embodiment 1, obtain white solid (chemical compounds I-40), fusing point 57.5-58.1 DEG C, yield 76%.
1H NMR(400MHz,CDCl 3):δ8.25–8.23(m,1H),7.92–7.88(m,2H),7.68–7.66(m,1H),7.60–7.49(m,3H),6.72(s,1H),2.59(s,3H)； 13C NMR(100MHz,CDCl 3):δ161.3,152.9,133.9,130.1,129.7,128.8,127.2,126.7,126.5,126.3,125.3,124.8,114.2,109.7,95.7,13.4；HRMS(EI):calcd for C 16H 11NO[M] +:233.0841,found:233.0840。
Embodiment 41
The synthesis of 2-methyl-3-cyano group-5-(4-chloro-phenyl-) furans (chemical compounds I-41):
Replace compound ii-1 except with compound ii-11, compound III-13 replaces compound III-1 and temperature of reaction is outside 120 DEG C, and all the other steps are identical with embodiment 1, obtain white solid (chemical compounds I-41), fusing point 70.5-71.2 DEG C, yield 81%.
1H NMR(400MHz,CDCl 3):δ7.53(d,J＝8.4Hz,2H),7.37(d,J＝8.8Hz,2H),6.66(s,1H),2.55(s,3H)； 13C NMR(100MHz,CDCl 3):δ161.2,152.5,134.3,129.2,127.5,125.2,113.9,105.8,96.0,13.4；HRMS(EI):calcd for C 16H 11NO[M] +:217.0294,found:217.0295。
Embodiment 42
The synthesis of 2-methyl-3-benzenesulfonyl-5-(4-p-methoxy-phenyl) furans (chemical compounds I-42):
Except being except 120 DEG C by compound III-14 replacement compound III-1 and temperature of reaction, all the other steps are identical with embodiment 1, obtain white solid (chemical compounds I-42), fusing point 104.4-105.4 DEG C, yield 80%.
1H NMR(400MHz,CDCl 3):δ7.98–7.96(m,2H),7.60–7.51(m,5H),6.92–6.89(m,2H),6.66(s,1H),3.82(s,3H),2.65(s,3H)； 13C NMR(100MHz,CDCl 3):δ158.7,154.1,151.9,141.5,132.1,128.2,125.8,124.3,123.3,121.0,113.2,101.6,54.3,12.0；HRMS(EI):calcd for C 18H 16O 4S[M] +:328.0769,found:328.0770。
Embodiment 43
The synthesis of 2-methyl-3-benzenesulfonyl-5-(4-methylthio group phenyl) furans (chemical compounds I-43):
Replace compound ii-1 except with compound ii-5, compound III-14 replaces compound III-1 and temperature of reaction is outside 120 DEG C, and all the other steps are identical with embodiment 1, obtain white solid (chemical compounds I-43), fusing point 87.5-88.4 DEG C, yield 76%.
1H NMR(400MHz,CDCl 3):δ7.97–7.95(m,2H),7.59–7.47(m,5H),7.22(d,J＝8.4Hz,2H),6.74(s,1H),2.65(s,3H),2.48(s,3H)； 13C NMR(100MHz,CDCl 3):δ155.6,152.5,142.4,139.2,133.2,129.3,126.9,126.4,125.8,124.5,124.2,103.8,15.5,13.1；HRMS(EI):calcd for C 19H 24O 2[M] +:344.0541,found:344.0542。
Embodiment 44
The synthesis of 2-methyl-3-benzenesulfonyl-5-(4-phenyl) furans (chemical compounds I-44):
Replace compound ii-1 except with compound ii-9, compound III-14 replaces compound III-1 and temperature of reaction is outside 120 DEG C, and all the other steps are identical with embodiment 1, obtain white solid (chemical compounds I-44), fusing point 169.3-170.3 DEG C, yield 80%.
1H NMR(400MHz,CDCl 3):δ8.01–7.99(m,2H),7.67–7.60(m,7H),7.57–7.54(m,2H),7.48–7.44(m,2H),7.39–7.35(m,1H),6.84(s,1H),2.69(s,3H)； 13C NMR(100MHz,CDCl 3):δ155.9,152.6,142.4,141.1,140.2,133.3,129.4,128.9,128.0,127.7,127.5,126.9,124.6,124.3,104.4,13.2；HRMS(EI):calcd for C 19H 24O 2[M] +:374.0977,found:374.0978。

Claims (15)

1. the method for compound shown in a preparation formula I, it is characterized in that, the key step of described method is: under the oxysalt existence condition having element in I A in mantoquita and the periodic table of elements, by compound shown in compound and formula III shown in formula II in aprotic organic solvent, in 90C ~ 120C reaction, obtain target compound;
In formula, R 1for C 1~ C 4the alkyl of straight or branched, the C of halo 1~ C 4the alkyl of straight or branched, 5 ~ 6 yuan of aromatic ring yls or heterocyclic radical;
R 2for having the group of sucting electronic effect, or
A is C 4~ C 10aromatic ring yl or heterocyclic radical, or replace C 4~ C 10aromatic ring yl or heterocyclic radical;
Wherein, R 3for C 1~ C 4the alkyl of straight or branched, C 1~ C 4the alkoxyl group of straight or branched, phenyl, or r 4and R 5independently be selected from: hydrogen or C 1~ C 3a kind of in the alkyl of straight or branched;
The heteroatoms of described heterocyclic radical be O or/and S, heteroatoms number is 1 or 2;
The C of described replacement 4~ C 10aromatic ring yl or the substituting group of heterocyclic radical be selected from: in following groups one or two or more kinds:
C 1~ C 4the alkyl of straight or branched, C 1~ C 4the alkoxyl group of straight or branched, halogen, phenyl, benzyloxy, R 6s or cyano group, R 6for C 1~ C 4the alkyl of straight or branched, substituting group number is the integer of 1 ~ 3.
2. the method for claim 1, is characterized in that, wherein, and R 1for C 1~ C 3the alkyl of straight or branched; R 2for cyano group or Phenylsulfonic acid base; A is C 6~ C 10aromatic ring yl or heterocyclic radical, or replace C 6~ C 10aromatic ring yl or heterocyclic radical;
Wherein, the heteroatoms of described heterocyclic radical is O or S, and heteroatoms number is 1 or 2;
The C of described replacement 6~ C 10aromatic ring yl or the substituting group of heterocyclic radical be selected from one or two or more kinds in following groups:
C 1~ C 3the alkoxyl group of straight or branched, R 6s-, halogen or phenyl, R 6for C 1~ C 3the alkyl of straight or branched, substituting group number is the integer of 1 ~ 3.
3. method as claimed in claim 2, is characterized in that, wherein, and R 1for methyl or ethyl.
4. method as claimed in claim 2, it is characterized in that, wherein, A is naphthyl or substituted-phenyl;
The substituting group of described substituted-phenyl is selected from: halogen, in phenyl or methoxyl group one or two or more kinds.
5. method as claimed in claim 4, is characterized in that, wherein, A is a kind of in following groups:
6. the method for claim 1, is characterized in that, wherein, and R 1for C 1~ C 3the alkyl of straight or branched, the C of halo 1~ C 3the alkyl of straight or branched, phenyl or quinary heterocyclic radical, the heteroatoms of described quinary heterocyclic radical is O or S;
R 2for r 3for C 1~ C 3the alkyl of straight or branched, C 1~ C 3the alkoxyl group of straight or branched, phenyl or r 4and R 5independently be selected from: H or C 1~ C 3a kind of in the alkyl of straight or branched;
A is C 4~ C 10aromatic ring yl or heterocyclic radical, or replace C 4~ C 10aromatic ring yl or heterocyclic radical;
Wherein, the heteroatoms of described heterocyclic radical is O or S, and heteroatoms number is 1 or 2; The C of described replacement 4~ C 10aromatic ring yl or the substituting group of heterocyclic radical be selected from one or two or more kinds in following groups:
C 1~ C 4the alkyl of straight or branched, C 1~ C 3the alkoxyl group of straight or branched, halogen, phenyl, benzyloxy, R 6s or cyano group, R 6for C 1~ C 3the alkyl of straight or branched.Substituting group number is the integer of 1 ~ 3.
7. method as claimed in claim 6, is characterized in that, wherein, and R 1for methyl, ethyl, n-propyl, sec.-propyl, phenyl, furyl, halogenated methyl.
8. method as claimed in claim 7, is characterized in that, wherein, and R 1for: methyl, ethyl, sec.-propyl, phenyl, 2-furyl or difluoromethyl.
9. method as claimed in claim 6, is characterized in that, wherein, and R 2for r 3for methyl, ethyl, sec.-propyl, phenyl, methoxyl group, oxyethyl group or r 4and R 5independently be selected from: a kind of in methyl, ethyl or propyl group.
10. method as claimed in claim 6, it is characterized in that, wherein, A is C 4or C 7heterocyclic radical, C 10aromatic ring yl, or replace hexa-atomic aromatic ring yl;
Wherein, the heteroatoms of described heterocyclic radical is O or S, and heteroatoms number is 1 or 2; The substituting group of the hexa-atomic aromatic ring yl of described replacement is selected from one or two or more kinds in following groups:
C 1~ C 4the alkyl of straight or branched, C 1~ C 3the alkoxyl group of straight or branched, halogen, phenyl, benzyloxy, R 6s-or cyano group, R 6for C 1~ C 3the alkyl of straight or branched, substituting group number is the integer of 1 ~ 3.
11. methods as claimed in claim 10, is characterized in that, wherein, A is thienyl, naphthyl or substituted-phenyl;
Wherein, the substituting group of described substituted-phenyl is selected from one or two or more kinds in following groups:
Methyl, the tertiary butyl, methoxyl group, phenyl, F, Cl, Br, I, benzyloxy, or cyano group, substituting group number is 1 or 2.
12. methods as claimed in claim 11, is characterized in that, wherein, A is a kind of in following groups:
13., as the method in claim 1 ~ 12 as described in any one, is characterized in that, wherein used catalyst is cuprous salt.
14. methods as claimed in claim 13, is characterized in that, wherein said catalyzer cuprous halide.
15., as the method in claim 1 ~ 12 as described in any one, is characterized in that, wherein alkali used is the carbonate of element in I A in the periodic table of elements.
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CN112341409B (en) * 2019-08-07 2022-05-24 江西师范大学 Preparation method of polysubstituted furan compound

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