CN109574967A - The method of aphthofurans derivative is synthesized using titanium tetrachloride as dehydrated reagent - Google Patents
The method of aphthofurans derivative is synthesized using titanium tetrachloride as dehydrated reagent Download PDFInfo
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- 238000000034 method Methods 0.000 title claims abstract description 22
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 title claims abstract description 15
- 239000003153 chemical reaction reagent Substances 0.000 title claims description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims abstract description 248
- 238000006243 chemical reaction Methods 0.000 claims abstract description 43
- ZQUZPFYNEARCQO-UHFFFAOYSA-N dinaphthalen-1-yl carbonate Chemical compound C1=CC=C2C(OC(OC=3C4=CC=CC=C4C=CC=3)=O)=CC=CC2=C1 ZQUZPFYNEARCQO-UHFFFAOYSA-N 0.000 claims abstract description 37
- 239000011259 mixed solution Substances 0.000 claims abstract description 21
- 239000011261 inert gas Substances 0.000 claims abstract description 5
- -1 alpha-naphthoxy Chemical group 0.000 claims abstract 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 claims description 40
- 230000015572 biosynthetic process Effects 0.000 claims description 32
- 238000003786 synthesis reaction Methods 0.000 claims description 32
- 235000019270 ammonium chloride Nutrition 0.000 claims description 20
- 238000000605 extraction Methods 0.000 claims description 20
- 238000010898 silica gel chromatography Methods 0.000 claims description 20
- 239000002904 solvent Substances 0.000 claims description 19
- 239000000243 solution Substances 0.000 claims description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 7
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- 238000006482 condensation reaction Methods 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 6
- 150000002367 halogens Chemical class 0.000 claims description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 230000002194 synthesizing effect Effects 0.000 claims description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 claims description 4
- 238000011017 operating method Methods 0.000 claims description 3
- 230000035484 reaction time Effects 0.000 claims description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 239000000460 chlorine Substances 0.000 claims description 2
- 239000012141 concentrate Substances 0.000 claims description 2
- 239000007789 gas Substances 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims description 2
- 150000001335 aliphatic alkanes Chemical class 0.000 claims 1
- 239000002994 raw material Substances 0.000 abstract description 8
- 238000006210 cyclodehydration reaction Methods 0.000 abstract description 5
- 238000004519 manufacturing process Methods 0.000 abstract description 5
- 230000008901 benefit Effects 0.000 abstract description 4
- 238000007086 side reaction Methods 0.000 abstract description 3
- 150000002576 ketones Chemical class 0.000 abstract description 2
- 238000010189 synthetic method Methods 0.000 abstract description 2
- 238000012805 post-processing Methods 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 66
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 36
- 229920006395 saturated elastomer Polymers 0.000 description 19
- 238000005160 1H NMR spectroscopy Methods 0.000 description 18
- 229910003074 TiCl4 Inorganic materials 0.000 description 18
- 125000003963 dichloro group Chemical group Cl* 0.000 description 18
- 229910052757 nitrogen Inorganic materials 0.000 description 18
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 15
- 239000003921 oil Substances 0.000 description 6
- 239000007788 liquid Substances 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000012230 colorless oil Substances 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 230000036632 reaction speed Effects 0.000 description 2
- 102000003839 Human Proteins Human genes 0.000 description 1
- 108090000144 Human Proteins Proteins 0.000 description 1
- CYTYCFOTNPOANT-UHFFFAOYSA-N Perchloroethylene Chemical compound ClC(Cl)=C(Cl)Cl CYTYCFOTNPOANT-UHFFFAOYSA-N 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 1
- CXACZHCEJHFNTG-UHFFFAOYSA-N [O].C1=CC=CC2=CC=CC=C12 Chemical compound [O].C1=CC=CC2=CC=CC=C12 CXACZHCEJHFNTG-UHFFFAOYSA-N 0.000 description 1
- 230000007131 anti Alzheimer effect Effects 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- MFMVRILBADIIJO-UHFFFAOYSA-N benzo[e][1]benzofuran Chemical class C1=CC=C2C(C=CO3)=C3C=CC2=C1 MFMVRILBADIIJO-UHFFFAOYSA-N 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 239000012024 dehydrating agents Substances 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000005265 energy consumption Methods 0.000 description 1
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 150000004780 naphthols Chemical class 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 229920000137 polyphosphoric acid Polymers 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 229910052719 titanium Inorganic materials 0.000 description 1
- 239000010936 titanium Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/92—Naphthofurans; Hydrogenated naphthofurans
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/93—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems condensed with a ring other than six-membered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J73/00—Steroids in which the cyclopenta[a]hydrophenanthrene skeleton has been modified by substitution of one or two carbon atoms by hetero atoms
- C07J73/001—Steroids in which the cyclopenta[a]hydrophenanthrene skeleton has been modified by substitution of one or two carbon atoms by hetero atoms by one hetero atom
- C07J73/003—Steroids in which the cyclopenta[a]hydrophenanthrene skeleton has been modified by substitution of one or two carbon atoms by hetero atoms by one hetero atom by oxygen as hetero atom
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The present invention discloses one kind using naphthoxy ketone as raw material, that is, under inert gas protection alpha-naphthoxy base ketone is dissolved in dry methylene chloride, TiCl is then slowly added dropwise by the method that cyclodehydration prepares aphthofurans derivative under the action of titanium tetrachloride4With the mixed solution of methylene chloride, isolated and purified to obtain the aphthofurans derivative after reaction.Synthetic method of the present invention, raw material are easy to get, low in cost, and reaction condition is mild, and easy to operate easily-controllable, side reaction is less, and post-processing is simple, and product yield is higher, and production cost is greatly saved, and have preferable economic benefit, are suitable for industrialized production.
Description
Technical field
The present invention relates to the preparation methods of aphthofurans derivative, and in particular to using naphthoxy ketone as raw material, in four chlorinations
The method that cyclodehydration prepares aphthofurans derivative under the action of titanium.
Background technique
Aphthofurans is the core skeleton in many natural products and synthetic drug, the usual table of molecule with these skeletons
Reveal unique biological characteristics, such as with cytotoxicity, anti-oxidant and antifungal activity can be used as human protein kinase
Potential inhibitor, the double inhibitor of anti-Alzheimer disease.In addition aphthofurans derivative has very strong photochromism
Matter can occur quick and reversible color change when being irradiated with ultraviolet light or sunlight, put in the dark when being adsorbed in silica gel
Uncolored state (Dalton Transactions 2017,46 (28), 9076-9087.) can be restored to again after a few minutes.
Synthetic method about aphthofurans derivative is numerous, wherein using naphthoxy ketone as raw material dehydration Cyclization target
The method of product is simple and fast, and reaction raw materials naphthoxy ketone can be taken with naphthols with α-halogenatedketone under alkaline condition
Generation reaction is prepared.Someone reports very early for the research of this path synthesis aphthofurans derivative, but cyclodehydration reaction is logical
Often need the reaction condition of the harshness such as strong acid, high temperature or ultralow temperature.
For the naphthoxy ketone of open chain, most common condensation condition is exactly to make dehydrating agent with large excess of methane sulfonic acid,
One hour (J.Org.Chem.2000,65 (25), 8783-8785.) of reflux in methylene chloride.If made of phosphorus oxychloride
Dehydrated reagent is reacted using carbon dichloride as solvent, and 6 hours that need to flow back can just obtain aphthofurans derivative
(Indian Joumal of Chemistry, Section B 2015,54B (7), 940-943.).
For cricoid naphthoxy ketone, it is condensed relative difficulty point, needs more exacting terms.Such as with a large amount of poly
Phosphoric acid is used as solvent as dehydrated reagent again simultaneously, and 130 DEG C of stirrings, 3 hours aphthofurans Fourth Rings that can just obtain moderate yield are spread out
Biological (J.Heterocycl.Chem.2016,53 (3), 941-944.).
Existing aphthofurans derivative synthesizing process, cyclodehydration reaction usually require strong acid, high temperature or ultralow temperature
Deng harsh reaction condition, severe reaction conditions, energy consumption, and reaction yield is lower, it would be highly desirable to develop aphthofurans derivative
High-efficiency synthesis method.
Summary of the invention
The purpose of the present invention is to provide one kind using naphthoxy ketone as raw material, and knot is efficiently produced under the action of titanium tetrachloride
The single-minded aphthofurans derivative of structure.
To achieve the above object, technical solution provided by the invention is as follows: in the presence of titanium tetrachloride, lead to formula (I) or
Naphthoxy ketone shown in (I '), it is derivative to obtain aphthofurans shown in logical formula (II) or (II ') for generation condensation reaction in a solvent
Object, chemical equation are as follows:
Wherein, R1Selected from H, halogen；R2Selected from H, C1-C6Linear or branched alkyl group, R3Selected from phenyl, C1-C6Straight chain or branch
Alkyl group；Or R2And R3It is joined together to form-(CH2)n, n 3,4,5 or 6.Preferably, R1Selected from H, halogen, the halogen
For bromine or chlorine；R2Selected from H, C1-C4Straight chained alkyl, R3Selected from phenyl, C1-C4Straight chained alkyl；Or R2And R3Be joined together to form-
(CH2)n, n 3,4,5 or 6.
The method of above-mentioned synthesis aphthofurans derivative, the solvent be selected from methylene chloride, chloroform, carbon tetrachloride or
Toluene, it is preferable that the solvent is methylene chloride；The reaction carries out under inert gas protection.
The method of above-mentioned synthesis aphthofurans derivative, the reaction temperature are 0-120 DEG C, and the reaction time is that 0.1-6 is small
When, the molar ratio of the naphthoxy ketone and titanium tetrachloride is 1: (0.8-3).Preferably, the reaction temperature is room temperature, when reaction
Between be 0.1-2 hour, the molar ratio of the naphthoxy ketone and titanium tetrachloride is 1: (1-2).
The method of above-mentioned synthesis aphthofurans derivative, operating procedure are as follows: under inert gas protection, the naphthalene oxygen
In the presence of titanium tetrachloride and the solvent condensation reaction occurs for base ketone, after reaction through isolating and purifying to obtain the naphtho-
Furan derivatives.
The method of above-mentioned synthesis aphthofurans derivative, operating procedure are as follows: it is specific steps are as follows: in inertia
Under gas shield, naphthoxy ketone is dissolved in the solvent, TiCl is then slowly added dropwise4It is carried out with the mixed solution of the solvent
Condensation reaction is isolated and purified to obtain the aphthofurans derivative after reaction, wherein the solvent is anhydrous solvent.
Wherein, described the step of isolating and purifying are as follows: saturated aqueous ammonium chloride is added and is quenched, then is extracted with dichloromethane,
Dichloromethane solution obtained by hybrid extraction is concentrated under reduced pressure, and concentrate carries out the isolated aphthofurans of silica gel column chromatography again
Derivative.
Compared with existing aphthofurans derivative synthesizing process, the present invention is had the advantage that
(1) aphthofurans derivative is prepared using technical solution of the present invention, wide application range of substrates is cyclic annular and chain
The condensation reaction preparation aphthofurans derivative can smoothly occur for naphthoxy ketone, have practical application value.
(2) a series of aphthofurans derivatives can be efficiently prepared using technical solution of the present invention, it is only necessary to make
With laboratory common solvent, single step reaction, easy to operate, reaction condition is mild (room temperature reaction), and reaction speed is fast, and (0.1-2 is small
When, the interior energy fully reacting of usual half an hour), it is energy-saving, production cost is reduced, industrialized production is conducive to.
(3) technical solution of the present invention is closed as cyclodehydration reagent, naphthoxy ketone as one step of raw material using titanium tetrachloride
At product of the present invention, regioselectivity is good, and side reaction is few, and principal product only has aphthofurans derivative, the easily separated purification of product, after
Processing is simple, and achieves preferable yield (80% or so).
To sum up, technical solution of the present invention uses titanium tetrachloride as catalyst, naphthoxy ketone as raw material one-step synthesis sheet
Invention product, reaction system is simple, and reaction condition is mild (normal-temperature reaction), and reaction speed is fast, energy-saving；Regioselectivity
Good, side reaction is few, and subsequent product convenient separation has significant economic benefit and social benefit, it can be achieved that industrialized production.
Specific embodiment
It is illustrated in detail by way of the following examples the present invention, but the present invention is not only limitted in embodiment.
Embodiment 1: the synthesis of aphthofurans derivative I I a
In 25mL two mouth flask under nitrogen protection, naphthoxy ketone I a (1mmol) and dry methylene chloride is added
(5mL), is then slowly added dropwise TiCl4The mixed solution of (1mmol) and methylene chloride (5mL).It (is supervised after the reaction was completed by TLC
Survey), saturated aqueous ammonium chloride (10mL) is added and is quenched, then (3 × 10mL) is extracted with dichloromethane.Dichloro obtained by hybrid extraction
Dichloromethane is concentrated under reduced pressure, then carrying out the isolated target product II a of silica gel column chromatography is colourless liquid, yield 82%.
1H NMR (600MHz, CDCl3) δ 8.39 (d, J=8.3Hz, 1H), 7.97 (d, J=8.1Hz, 1H), 7.72 (d, J
=8.9Hz, 1H), 7.64 (d, J=8.9Hz, 1H), 7.59 (t, J=7.6Hz, 1H), 7.55 (s, 1H), 7.49 (t, J=
7.5Hz, 1H), 2.64 (s, 3H)；13C NMR (150MHz, CDCl3) δ 153.34,141.16,130.61,129.09,128.95,
126.17,125.29,124.08,123.12,122.04,117.58,112.70.11.37.
Embodiment 2: the synthesis of aphthofurans derivative I I ' a
In 25mL two mouth flask under nitrogen protection, naphthoxy ketone I ' a (1mmol) and dry methylene chloride is added
(5mL), is then slowly added dropwise TiCl4The mixed solution of (2mmol) and methylene chloride (5mL).It (is supervised after the reaction was completed by TLC
Survey), saturated aqueous ammonium chloride (10mL) is added and is quenched, then (3 × 10mL) is extracted with dichloromethane.Dichloro obtained by hybrid extraction
Dichloromethane is concentrated under reduced pressure, then carrying out the isolated target product II ' a of silica gel column chromatography is colourless liquid, yield 70%.
1H NMR (600MHz, CDCl3) δ 8.29 (d, J=8.2Hz, 1H), 7.94 (d, J=8.2Hz, 1H), 7.67 (d, J
=8.5Hz, 1H), 7.61 (d, J=8.5Hz, 1H), 7.60-7.55 (m, 2H), 7.48 (t, J=7.5Hz, 1H), 2.34 (s,
3H)；GC-MS (m/z): 182.1 [M]+.
Embodiment 3: the synthesis of aphthofurans derivative I I b
In 25mL two mouth flask under nitrogen protection, naphthoxy ketone I b (1mmol) and dry methylene chloride is added
(5mL), is then slowly added dropwise TiCl4The mixed solution of (1mmol) and methylene chloride (5mL).It (is supervised after the reaction was completed by TLC
Survey), saturated aqueous ammonium chloride (10mL) is added and is quenched, then (3 × 10mL) is extracted with dichloromethane.Dichloro obtained by hybrid extraction
Dichloromethane is concentrated under reduced pressure, then carrying out the isolated target product II b of silica gel column chromatography is weak yellow liquid, yield 92%.
1H NMR (600MHz, CDCl3) δ 8.40 (d, J=8.3Hz, 1H), 7.96 (d, J=8.1Hz, 1H), 7.65 (d, J
=8.8Hz, 1H), 7.63-7.53 (m, 2H), 7.53-7.38 (m, 1H), 2.57 (s, 3H), 2.49 (s, 3H)；13C NMR
(150MHz, CDCl3) δ 151.26,149.92,130.66,128.94,128.73,125.79,123.97,123.76,
123.24,123.04,112.11,111.74,11.77,11.41.
Embodiment 4: the synthesis of aphthofurans derivative I I ' b
In 25mL two mouth flask under nitrogen protection, naphthoxy ketone I ' b (1mmol) and dry methylene chloride is added
(5mL), is then slowly added dropwise TiCl4The mixed solution of (1mmol) and methylene chloride (5mL).It (is supervised after the reaction was completed by TLC
Survey), saturated aqueous ammonium chloride (10mL) is added and is quenched, then (3 × 10mL) is extracted with dichloromethane.Dichloro obtained by hybrid extraction
Dichloromethane is concentrated under reduced pressure, then carrying out the isolated target product II ' b of silica gel column chromatography is yellow liquid, yield 80%.
1H NMR (400MHz, CDCl3) δ 8.26 (d, J=8.3Hz, 1H), 7.92 (d, J=8.2Hz, 1H), 7.64 (d, J
=8.5Hz, 1H), 7.61-7.51 (m, 2H), 7.51-7.36 (m, 1H), 2.50 (s, 3H), 2.24 (s, 3H)；13C NMR
(101MHz, CDCl3) δ 149.84,148.88,130.88,128.34,126.00,125.65,124.30,122.50,
121.08,119.74,117.88,110.86,12.00,8.14.
Embodiment 5: the synthesis of aphthofurans derivative I I ' c
In 25mL two mouth flask under nitrogen protection, naphthoxy ketone I ' c (1mmol) and dry methylene chloride is added
(5mL), is then slowly added dropwise TiCl4The mixed solution of (1mmol) and methylene chloride (5mL).It (is supervised after the reaction was completed by TLC
Survey), saturated aqueous ammonium chloride (10mL) is added and is quenched, then (3 × 10mL) is extracted with dichloromethane.Dichloro obtained by hybrid extraction
Dichloromethane is concentrated under reduced pressure, then carrying out the isolated target product II ' c of silica gel column chromatography is colourless liquid, yield 79%.
1H NMR (600MHz, CDCl3) δ 8.27 (d, J=8.2Hz, 1H), 7.92 (d, J=8.2Hz, 1H), 7.64 (d, J
=8.5Hz, 1H), 7.61-7.58 (m, 1H), 7.56 (t, J=7.6Hz, 1H), 7.44 (t, J=7.5Hz, 1H), 2.72 (q, J
=7.6Hz, 2H), 2.51 (s, 3H), 1.30 (t, J=7.6Hz, 3H)；13C NMR (150MHz, CDCl3) δ 149.36,
149.04,130.82,128.32,126.00,124.83,124.33,122.46,121.22,119.74,118.07,117.30,
17.08,14.82,12.02；HRMS(ESI)calcd for C15H15O(M+H)+: 211.1117, Found:211.1113.
Embodiment 6: the synthesis of aphthofurans derivative I I d
In 25mL two mouth flask under nitrogen protection, naphthoxy ketone I d (1mmol) and dry methylene chloride is added
(5mL), is then slowly added dropwise TiCl4The mixed solution of (1mmol) and methylene chloride (5mL).It (is supervised after the reaction was completed by TLC
Survey), saturated aqueous ammonium chloride (10mL) is added and is quenched, then (3 × 10mL) is extracted with dichloromethane.Dichloro obtained by hybrid extraction
Dichloromethane is concentrated under reduced pressure, then carrying out the isolated target product II d of silica gel column chromatography is yellow oil, yield 70%.
1H NMR (600MHz, CDCl3) δ 8.20 (s, 1H), 7.84 (s, 1H), 7.59 (s, 1H), 7.55-7.44 (m, 2H),
7.39 (d, J=22.5Hz, 2H), 2.92 (s, 2H), 1.70 (s, 2H), 1.42 (s, 2H), 0.91 (d, J=2.1Hz, 3H)；13C
NMR (150MHz, CDCl3) δ 153.47,140.69,130.72,129.07,128.92,126.22,125.36,124.02,
123.40,122.83,121.50,112.79,31.14,25.78,22.73,14.03.
Embodiment 7: the synthesis of aphthofurans derivative I I ' e
In 25mL two mouth flask under nitrogen protection, naphthoxy ketone I ' e (1mmol) and dry methylene chloride is added
(5mL), is then slowly added dropwise TiCl4The mixed solution of (1mmol) and methylene chloride (5mL).It (is supervised after the reaction was completed by TLC
Survey), saturated aqueous ammonium chloride (10mL) is added and is quenched, then (3 × 10mL) is extracted with dichloromethane.Dichloro obtained by hybrid extraction
Dichloromethane is concentrated under reduced pressure, then carrying out the isolated target product II ' e of silica gel column chromatography is brown oil, yield 71%.
1H NMR (600MHz, CDCl3) δ 8.36 (d, J=8.2Hz, 1H), 7.97 (d, J=8.2Hz, 1H), 7.94 (s,
1H), 7.90 (d, J=8.6Hz, 1H), 7.76-7.69 (m, 3H), 7.62 (t, J=7.6Hz, 1H), 7.52 (dt, J=15.6,
4.4Hz, 3H), 7.40 (t, J=7.4Hz, 1H)；LC-MS(ESI)calcd for C18H13O(M+H)+: 245.1, Found:
245.0.
Embodiment 8: the synthesis of aphthofurans derivative I I f
In 25mL two mouth flask under nitrogen protection, naphthoxy ketone I f (1mmol) and dry methylene chloride is added
(5mL), is then slowly added dropwise TiCl4The mixed solution of (1mmol) and methylene chloride (5mL).It (is supervised after the reaction was completed by TLC
Survey), saturated aqueous ammonium chloride (10mL) is added and is quenched, then (3 × 10mL) is extracted with dichloromethane.Dichloro obtained by hybrid extraction
Dichloromethane is concentrated under reduced pressure, then carrying out the isolated target product II f of silica gel column chromatography is yellow oil, yield 78%.
1H NMR (400MHz, CDCl3) δ 8.25 (d, J=8.2Hz, 1H), 7.94 (d, J=8.1Hz, 1H), 7.75-7.60
(m, 2H), 7.60-7.50 (m, 1H), 7.50-7.37 (m, 1H), 3.21-3.03 (m, 2H), 2.85 (t, J=4.8Hz, 2H),
2.14-1.86 (m, 4H)；13C NMR (150MHz, CDCl3) δ 153.30,151.48,130.55,129.48,128.73,
125.68,123.82,123.65,123.52,122.51,114.34,112.29,23.75,23.16,23.12,22.62.
Embodiment 9: the synthesis of aphthofurans derivative I I ' f
In 25mL two mouth flask under nitrogen protection, naphthoxy ketone I ' f (1mmol) and dry methylene chloride is added
(5mL), is then slowly added dropwise TiCl4The mixed solution of (1mmol) and methylene chloride (5mL).It (is supervised after the reaction was completed by TLC
Survey), saturated aqueous ammonium chloride (10mL) is added and is quenched, then (3 × 10mL) is extracted with dichloromethane.Dichloro obtained by hybrid extraction
Dichloromethane is concentrated under reduced pressure, then carrying out the isolated target product II ' f of silica gel column chromatography is yellow oil, yield 86%.
1H NMR (400MHz, CDCl3) δ 8.29 (d, J=8.3Hz, 1H), 7.93 (d, J=8.2Hz, 1H), 7.65 (d, J
=8.4Hz, 1H), 7.61-7.50 (m, 2H), 7.51-7.37 (m, 1H), 2.99-2.81 (m, 2H), 2.81-2.61 (m, 2H),
2.14-1.96 (m, 2H), 1.96-1.80 (m, 2H)；LCMS(ESI)calcd for C16H15O(M+H)+: 223.1, Found:
223.3.
Embodiment 10: the synthesis of aphthofurans derivative I I g
In 25mL two mouth flask under nitrogen protection, naphthoxy ketone I g (1mmol) and dry methylene chloride is added
(5mL), is then slowly added dropwise TiCl4The mixed solution of (1mmol) and methylene chloride (5mL).It (is supervised after the reaction was completed by TLC
Survey), saturated aqueous ammonium chloride (10mL) is added and is quenched, then (3 × 10mL) is extracted with dichloromethane.Dichloro obtained by hybrid extraction
Dichloromethane is concentrated under reduced pressure, then carrying out the isolated target product II g of silica gel column chromatography is white solid, yield 77%.
1H NMR (400MHz, CDCl3) δ 8.04 (dd, J=9.2,5.4Hz, 2H), 7.68-7.53 (m, 2H), 7.49 (d, J
=8.9Hz, 1H), 3.00 (t, J=4.8Hz, 2H), 2.83 (t, J=5.0Hz, 2H), 2.04-1.84 (m, 4H)；13C NMR
(101MHz, CDCl3) δ 153.90,151.49,131.77,130.66,128.77,126.83,125.16,122.65,
122.60,117.46,114.14,113.28,23.72,23.02,23.01,22.54；HRMS(ESI)calcd for
C16H14BrO(M+H)+: 301.0223, Found:301.0220.
Embodiment 11: the synthesis of aphthofurans derivative I I h
In 25mL two mouth flask under nitrogen protection, naphthoxy ketone I h (1mmol) and dry methylene chloride is added
(5mL), is then slowly added dropwise TiCl4The mixed solution of (1mmol) and methylene chloride (5mL).It (is supervised after the reaction was completed by TLC
Survey), saturated aqueous ammonium chloride (10mL) is added and is quenched, then (3 × 10mL) is extracted with dichloromethane.Dichloro obtained by hybrid extraction
Dichloromethane is concentrated under reduced pressure, then carrying out the isolated target product II h of silica gel column chromatography is white solid, yield 73%.
1H NMR (600MHz, CDCl3) δ 8.06 (s, 1H), 7.93 (d, J=8.7Hz, 1H), 7.60 (dd, J=18.5,
8.8Hz, 2H), 7.51 (d, J=8.9Hz, 1H), 3.06 (t, J=6.8Hz, 2H), 3.00-2.89 (m, 2H), 2.77-2.56
(m, 2H)；13C NMR (150MHz, CDCl3) δ 162.72,157.31,131.53,130.44,128.92,125.91,125.81,
122.09,122.02,121.83,117.87,114.03,27.87,25.00,23.82；HRMS(ESI)calcd for
C15H12BrO(M+H)+: 287.0066, Found:287.0068.
Embodiment 12: the synthesis of aphthofurans derivative I I i
In 25mL two mouth flask under nitrogen protection, naphthoxy ketone I i (1mmol) and dry methylene chloride is added
(5mL), is then slowly added dropwise TiCl4The mixed solution of (1mmol) and methylene chloride (5mL).It (is supervised after the reaction was completed by TLC
Survey), saturated aqueous ammonium chloride (10mL) is added and is quenched, then (3 × 10mL) is extracted with dichloromethane.Dichloro obtained by hybrid extraction
Dichloromethane is concentrated under reduced pressure, then carrying out the isolated target product II i of silica gel column chromatography is yellow solid, yield 70%.
1H NMR (400MHz, CDCl3) δ 8.05 (d, J=8.1Hz, 1H), 7.90 (d, J=8.1Hz, 1H), 7.59 (s,
2H), 7.51 (t, J=7.4Hz, 1H), 7.43 (t, J=7.5Hz, 1H), 3.16-2.99 (m, 2H), 2.91 (t, J=7.2Hz,
2H), 2.73-2.52 (m, 2H)；13C NMR (101MHz, CDCl3) δ 162.04,157.29,130.35,128.45,127.54,
125.76,124.23,124.11,123.11,122.21,121.74,113.02,27.91,25.00,23.94；HRMS(ESI)
calcd for C15H13O(M+H)+: 209.0961, Found:209.0960.
Embodiment 13: the synthesis of aphthofurans derivative I I j
In 25mL two mouth flask under nitrogen protection, naphthoxy ketone I j (1mmol) and dry methylene chloride is added
(5mL), is then slowly added dropwise TiCl4The mixed solution of (1mmol) and methylene chloride (5mL).It (is supervised after the reaction was completed by TLC
Survey), saturated aqueous ammonium chloride (10mL) is added and is quenched, then (3 × 10mL) is extracted with dichloromethane.Dichloro obtained by hybrid extraction
Dichloromethane is concentrated under reduced pressure, then carrying out the isolated target product II j of silica gel column chromatography is white solid, yield 72%.
1H NMR (400MHz, CDCl3) δ 8.46 (d, J=8.4Hz, 1H), 7.94 (d, J=8.1Hz, 1H), 7.63 (d, J
=8.8Hz, 1H), 7.61-7.52 (m, 2H), 7.45 (t, J=7.5Hz, 1H), 3.37-3.17 (m, 2H), 3.03 (d, J=
5.9Hz, 2H), 2.13-1.77 (m, 6H)；13C NMR (101MHz, CDCl3) δ 155.81,150.72,130.82,129.10,
128.81,125.64,124.05,123.65,123.12,123.04,118.30,112.18,29.63,28.51,27.97,
26.06 25.75；HRMS(ESI)calcd for C17H17O(M+H)+: 237.1274, Found:237.1276.
Embodiment 14: the synthesis of aphthofurans derivative I I ' g
In 25mL two mouth flask under nitrogen protection, naphthoxy ketone I ' g (1mmol) and dry methylene chloride is added
(5mL), is then slowly added dropwise TiCl4The mixed solution of (1mmol) and methylene chloride (5mL).It (is supervised after the reaction was completed by TLC
Survey), saturated aqueous ammonium chloride (10mL) is added and is quenched, then (3 × 10mL) is extracted with dichloromethane.Dichloro obtained by hybrid extraction
Dichloromethane is concentrated under reduced pressure, then carrying out the isolated target product II ' g of silica gel column chromatography is white solid, yield 77%.
1H NMR (400MHz, CDCl3) δ 8.25 (d, J=8.3Hz, 1H), 7.91 (d, J=8.2Hz, 1H), 7.63 (d, J
=8.5Hz, 1H), 7.54 (ddd, J=8.5,5.5,2.0Hz, 2H), 7.43 (ddd, J=8.1,6.9,1.2Hz, 1H), 3.14-
2.97 (m, 2H), 2.89-2.71 (m, 2H), 2.00-1.75 (m, 6H)；13C NMR (101MHz, CDCl3) δ 155.84,
148.15,130.78,128.34,125.99,125.66,124.24,122.47,121.22,119.76,117.70,117.15,
30.77,29.35,28.42,26.54,23.47.
Embodiment 15: the synthesis of aphthofurans derivative I I k
In 25mL two mouth flask under nitrogen protection, naphthoxy ketone Ik (1mmol) and dry methylene chloride is added
(5mL), is then slowly added dropwise TiCl4The mixed solution of (1mmol) and methylene chloride (5mL).It (is supervised after the reaction was completed by TLC
Survey), saturated aqueous ammonium chloride (10mL) is added and is quenched, then (3 × 10mL) is extracted with dichloromethane.Dichloro obtained by hybrid extraction
Dichloromethane is concentrated under reduced pressure, then carrying out the isolated target product IIk of silica gel column chromatography is yellow oil, yield 65%.
1H NMR (400MHz, CDCl3) δ 8.29 (d, J=9.0Hz, 1H), 8.06 (d, J=2.0Hz, 1H), 7.56 (ddd,
J=25.1,13.7,5.5Hz, 3H), 3.34-3.09 (m, 2H), 3.01 (d, J=6.1Hz, 2H), 2.06-1.76 (m, 6H)；13C
NMR (101MHz, CDCl3) δ 156.41,150.74,132.13,130.98,128.68,127.17,124.81,123.20,
123.00,118.09,117.23,113.21,29.51,28.46,27.87,25.97,25.70；HRMS(ESI)calcd for
C17H16BrO(M+H)+: 315.0379, Found:315.0381.
Embodiment 16: the synthesis of aphthofurans derivative I Il
In 25mL two mouth flask under nitrogen protection, naphthoxy ketone Il (1mmol) and dry methylene chloride is added
(5mL), is then slowly added dropwise TiCl4The mixed solution of (1mmol) and methylene chloride (5mL).It (is supervised after the reaction was completed by TLC
Survey), saturated aqueous ammonium chloride (10mL) is added and is quenched, then (3 × 10mL) is extracted with dichloromethane.Dichloro obtained by hybrid extraction
Dichloromethane is concentrated under reduced pressure, then carrying out the isolated target product IIl of silica gel column chromatography is yellow oil, yield 66%.
1H NMR (400MHz, CDCl3) δ 8.37 (d, J=8.3Hz, 1H), 7.95 (d, J=8.1Hz, 1H), 7.62 (q, J
=8.8Hz, 2H), 7.58-7.52 (m, 1H), 7.50-7.42 (m, 1H), 3.30-3.12 (m, 2H), 3.12-2.88 (m, 2H),
1.96 (dt, J=12.6,6.3Hz, 2H), 1.89-1.73 (m, 2H), 1.68-1.53 (m, 2H), 1.46 (dd, J=11.2,
5.5Hz, 2H)；13C NMR (101MHz, CDCl3) δ 154.96,151.33,130.64,128.98,128.58,125.83,
123.80,123.76,123.04,122.55,115.64,112.39,29.58,28.14,26.67,25.96,25.75,
23.25；HRMS(ESI)calcd for C18H19O(M+H)+: 251.1430, Found:251.1435.
Embodiment 17: the synthesis of aphthofurans derivative I I ' i
In 25mL two mouth flask under nitrogen protection, naphthoxy ketone I ' i (1mmol) and dry methylene chloride is added
(5mL), is then slowly added dropwise TiCl4The mixed solution of (2mmol) and methylene chloride (5mL).It (is supervised after the reaction was completed by TLC
Survey), saturated aqueous ammonium chloride (10mL) is added and is quenched, then (3 × 10mL) is extracted with dichloromethane.Dichloro obtained by hybrid extraction
Dichloromethane is concentrated under reduced pressure, then carrying out the isolated target product II ' i of silica gel column chromatography is colorless oil, yield 70%.
1H NMR (400MHz, CDCl3) δ 8.29 (d, J=8.3Hz, 1H), 7.93 (d, J=8.2Hz, 1H), 7.65 (d, J
=8.5Hz, 1H), 7.57 (t, J=8.1Hz, 2H), 7.45 (t, J=7.4Hz, 1H), 3.18-2.99 (m, 2H), 2.99-2.82
(m, 2H), 2.03-1.72 (m, 4H), 1.68-1.44 (m, 4H)；13C NMR (101MHz, CDCl3) δ 154.31,148.79,
130.84,128.38,126.01,125.18,124.26,122.48,121.30,119.80,117.69,114.96,28.34,
27.60,26.46,26.10,25.58,21.61.
Embodiment 18: the synthesis of aphthofurans derivative I Im
In 25mL two mouth flask under nitrogen protection, naphthoxy ketone Im (1mmol) and dry methylene chloride is added
(5mL), is then slowly added dropwise TiCl4The mixed solution of (1mmol) and methylene chloride (5mL).It (is supervised after the reaction was completed by TLC
Survey), saturated aqueous ammonium chloride (10mL) is added and is quenched, then (3 × 10mL) is extracted with dichloromethane.Dichloro obtained by hybrid extraction
Dichloromethane is concentrated under reduced pressure, then carrying out the isolated target product IIm of silica gel column chromatography is colorless oil, yield 62%.
1H NMR (600MHz, CDCl3) δ 8.20 (s, 1H), 8.07 (s, 1H), 7.60 (s, 2H), 7.52 (s, 1H), 3.13
(s, 2H), 2.98 (s, 2H), 1.93 (s, 2H), 1.78 (s, 2H), 1.58 (s, 2H), 1.45 (s, 2H)；13C NMR (150MHz,
CDCl3) δ 155.53,151.36,131.97,130.89,128.89,126.97,124.71,122.76,122.71,117.36,
115.51,113.39,29.46,27.98,26.64,25.96,25.66,23.25；HRMS(ESI)calcd for C18H18BrO
(M+H)+: 329.0536, Found:329.0534.
Claims (10)
1. synthesizing the method for aphthofurans derivative using titanium tetrachloride as dehydrated reagent, it is characterised in that: deposited in titanium tetrachloride
Under, lead to naphthoxy ketone shown in formula (I) or (I '), condensation reaction occurs in a solvent and obtains shown in logical formula (II) or (II ')
Aphthofurans derivative, chemical equation is as follows:
Wherein, R1Selected from H, halogen；R2Selected from H, C1-C6Linear or branched alkyl group, R3Selected from phenyl, C1-C6Linear chain or branched chain alkane
Base；Or R2And R3It is joined together to form-(CH2)n, n 3,4,5 or 6.
2. the method for synthesis aphthofurans derivative as described in claim 1, which is characterized in that the solvent is selected from dichloromethane
Alkane, chloroform, carbon tetrachloride or toluene.
3. the method for synthesis aphthofurans derivative as claimed in claim 2, which is characterized in that the solvent is methylene chloride.
4. the method for synthesis aphthofurans derivative as described in claim 1, which is characterized in that wherein, R1Selected from H, halogen, institute
Stating halogen is bromine or chlorine；R2Selected from H, C1-C4Straight chained alkyl, R3Selected from phenyl, C1-C4Straight chained alkyl；Or R2And R3It links together
Formation-(CH2)n, n 3,4,5 or 6.
5. the method for synthesis aphthofurans derivative as described in claim 1, which is characterized in that the reaction is in inert gas
The lower progress of protection.
6. the method for synthesis aphthofurans derivative as described in claim 1, which is characterized in that the reaction temperature is 0-120
DEG C, the reaction time is 0.1-6 hours, and the molar ratio of the naphthoxy ketone and titanium tetrachloride is 1: (0.8-3).
7. the method for synthesis aphthofurans derivative as claimed in claim 6, which is characterized in that the reaction temperature is room temperature,
Reaction time is 0.1-2 hours, and the molar ratio of the naphthoxy ketone and titanium tetrachloride is 1: (1-2).
8. the method for synthesizing aphthofurans derivative as described in any one of claim 1-7, operating procedure are as follows: lazy
Under property gas shield, condensation reaction occurs in the presence of titanium tetrachloride and the solvent for the naphthoxy ketone, passes through after reaction
It isolates and purifies to obtain the aphthofurans derivative.
9. the method for synthesis aphthofurans derivative as claimed in claim 8, specific steps are as follows: being protected in inert gas
Under shield, naphthoxy ketone is dissolved in the solvent, TiCl is then slowly added dropwise4Be condensed with the mixed solution of the solvent anti-
It answers, is isolated and purified to obtain the aphthofurans derivative after reaction, wherein the solvent is anhydrous solvent.
10. the method for synthesis aphthofurans derivative as claimed in claim 9, described the step of isolating and purifying are as follows: saturation is added
Aqueous ammonium chloride solution is quenched, then is extracted with dichloromethane, and dichloromethane solution obtained by hybrid extraction is concentrated under reduced pressure, concentrate again into
The isolated aphthofurans derivative of row silica gel column chromatography.
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| CN112939903A (en) * | 2021-03-08 | 2021-06-11 | 重庆医科大学 | Method for preparing furan compound from aryl ketone bromide |
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| Title |
|---|
| 张秋: "四氯化钛作用下α-芳氧基酮的脱水反应：区域选择性合成苯并呋喃和萘并呋喃类化合物", 《中国优秀硕士学位论文全文数据库 (工程科技Ⅰ辑)》 * |
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| CN112661627A (en) * | 2020-12-31 | 2021-04-16 | 南京理工大学 | Method for synthesizing 1-naphthoic acid from naphthalene and carbon dioxide |
| CN112939903A (en) * | 2021-03-08 | 2021-06-11 | 重庆医科大学 | Method for preparing furan compound from aryl ketone bromide |
| CN112939903B (en) * | 2021-03-08 | 2023-05-26 | 重庆医科大学 | Method for preparing furan compounds from bromoaryl ketone |
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