CN115353505A - Synthesis method of (3, 3 '-bithiophene) -4,4' -dicarboxaldehyde - Google Patents
Synthesis method of (3, 3 '-bithiophene) -4,4' -dicarboxaldehyde Download PDFInfo
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- CN115353505A CN115353505A CN202211147772.9A CN202211147772A CN115353505A CN 115353505 A CN115353505 A CN 115353505A CN 202211147772 A CN202211147772 A CN 202211147772A CN 115353505 A CN115353505 A CN 115353505A
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- bromothiophene
- formaldehyde
- bithiophene
- carbaldehyde
- dioxaborolan
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- VDMDHVOUCVTPSR-UHFFFAOYSA-N 4-(4-formylthiophen-3-yl)thiophene-3-carbaldehyde Chemical compound O=CC1=CSC=C1C1=CSC=C1C=O VDMDHVOUCVTPSR-UHFFFAOYSA-N 0.000 title claims abstract description 30
- 238000001308 synthesis method Methods 0.000 title description 3
- ZDVHJQOCVBTMOF-UHFFFAOYSA-N 4-bromothiophene-3-carbaldehyde Chemical compound BrC1=CSC=C1C=O ZDVHJQOCVBTMOF-UHFFFAOYSA-N 0.000 claims abstract description 57
- RBIGKSZIQCTIJF-UHFFFAOYSA-N 3-formylthiophene Chemical compound O=CC=1C=CSC=1 RBIGKSZIQCTIJF-UHFFFAOYSA-N 0.000 claims abstract description 37
- 238000000034 method Methods 0.000 claims abstract description 28
- IPWKHHSGDUIRAH-UHFFFAOYSA-N bis(pinacolato)diboron Chemical compound O1C(C)(C)C(C)(C)OB1B1OC(C)(C)C(C)(C)O1 IPWKHHSGDUIRAH-UHFFFAOYSA-N 0.000 claims abstract description 24
- 239000003054 catalyst Substances 0.000 claims abstract description 18
- 238000006243 chemical reaction Methods 0.000 claims abstract description 16
- 230000002194 synthesizing effect Effects 0.000 claims abstract description 14
- 230000009471 action Effects 0.000 claims abstract description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 64
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 claims description 34
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 34
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 19
- 235000011056 potassium acetate Nutrition 0.000 claims description 17
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 17
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 claims description 16
- 239000002904 solvent Substances 0.000 claims description 15
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 14
- 239000002994 raw material Substances 0.000 claims description 14
- 238000010438 heat treatment Methods 0.000 claims description 11
- 239000003513 alkali Substances 0.000 claims description 10
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 6
- 239000002585 base Substances 0.000 claims description 6
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 6
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 6
- 238000001816 cooling Methods 0.000 claims description 6
- 230000008569 process Effects 0.000 claims description 6
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 claims description 5
- 239000000203 mixture Substances 0.000 claims description 4
- 230000001681 protective effect Effects 0.000 claims description 4
- 239000007787 solid Substances 0.000 claims description 4
- VGKLVWTVCUDISO-UHFFFAOYSA-N 3,4-dibromothiophene Chemical compound BrC1=CSC=C1Br VGKLVWTVCUDISO-UHFFFAOYSA-N 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- 238000003786 synthesis reaction Methods 0.000 claims description 3
- 230000015572 biosynthetic process Effects 0.000 claims description 2
- 230000008878 coupling Effects 0.000 claims description 2
- 238000010168 coupling process Methods 0.000 claims description 2
- 238000005859 coupling reaction Methods 0.000 claims description 2
- 238000000746 purification Methods 0.000 abstract description 3
- 238000000926 separation method Methods 0.000 abstract description 3
- 230000035484 reaction time Effects 0.000 description 12
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- 239000000243 solution Substances 0.000 description 5
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 239000006227 byproduct Substances 0.000 description 4
- 238000004440 column chromatography Methods 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 238000001228 spectrum Methods 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- -1 (3, 3 '-bithiophene) -5,5' -dicarboxaldehyde Chemical compound 0.000 description 2
- UYWAPXIXMROYBD-UHFFFAOYSA-N 3-(2-formylthiophen-3-yl)thiophene-2-carbaldehyde Chemical compound S1C=CC(C2=C(SC=C2)C=O)=C1C=O UYWAPXIXMROYBD-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- IAAQEGBHNXAHBF-UHFFFAOYSA-N 3-thiophen-3-ylthiophene Chemical compound S1C=CC(C2=CSC=C2)=C1 IAAQEGBHNXAHBF-UHFFFAOYSA-N 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000002363 herbicidal effect Effects 0.000 description 1
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 238000007039 two-step reaction Methods 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/22—Radicals substituted by doubly bound hetero atoms, or by two hetero atoms other than halogen singly bound to the same carbon atom
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
The invention relates to a method for synthesizing (3, 3 '-bithiophene) -4,4' -dicarboxaldehyde, which comprises the following steps: reacting 4-bromothiophene-3-formaldehyde with bis (pinacolato) diboron under the action of a catalyst to obtain an intermediate 4- (4, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) thiophene-3-formaldehyde; under the action of a catalyst, 4- (4, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) thiophene-3-formaldehyde and 4-bromothiophene-3-formaldehyde are coupled to obtain (3, 3 '-bithiophene) -4,4' -dicarbaldehyde. The molar ratio of the 4-bromothiophene-3-formaldehyde to the bis (pinacolato) diboron is 1 (1.2-1.5). The molar ratio of the 4- (4, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) thiophene-3-formaldehyde to the 4-bromothiophene-3-formaldehyde is 1 (1.2-1.5). Compared with the prior art, the method has the advantages of mild reaction conditions, convenient operation, easy separation and purification and the like.
Description
Technical Field
The invention relates to the field of organic synthesis, in particular to a method for synthesizing (3, 3 '-bithiophene) -4,4' -dicarboxaldehyde.
Background
The (3, 3 '-bithiophene) -4,4' -diformaldehyde is an important intermediate and can be converted into the following organic small molecules with antifungal, anticancer, antibacterial, herbicidal or fluorescence emission properties, specifically as follows:
previously Mc Dowlel et al synthesized (3, 3 '-bithiophene) -4,4' -dicarbaldehyde by the following two-step reaction. However, the reaction is carried out at-78 ℃, all reaction reagents and equipment are required to be subjected to anhydrous treatment in advance, and the whole reaction process is protected by anhydrous water, so that the experimental operation is complicated, and the method specifically comprises the following steps:
disclosure of Invention
The present invention aims to overcome at least one of the above-mentioned drawbacks of the prior art by providing a method for synthesizing (3, 3 '-bithiophene) -4,4' -dicarbaldehyde.
The purpose of the invention can be realized by the following technical scheme:
the applicant tried a method for preparing (3, 3 '-bithiophene) -4,4' -dicarbaldehyde reported by Mc Dowell, but found that the second step of the above reaction process has a large amount of by-products and the polarity of the by-products and the target product are very close, and finally the purification methods such as column chromatography, recrystallization, etc. could not obtain pure (3, 3 '-bithiophene) -4,4' -dicarbaldehyde. The nuclear magnetic analysis of the reaction product revealed that the products of (3, 3 '-bithiophene) -4,4' -dicarboxaldehyde, (3, 3 '-bithiophene) -5,5' -dicarboxaldehyde, and (3, 3 '-bithiophene) -2,2' -dicarboxaldehyde 3 were simultaneously formed.
The nuclear magnetic spectrum of the mixture is shown in figure 3: A. the B and D signal peaks are (3, 3 '-bithiophene) -5,5' -dicarboxaldehyde, the I, E and G signal peaks are (3, 3 '-bithiophene) -2,2' -dicarboxaldehyde, the H, C and F signal peaks are the target product (3, 3 '-bithiophene) -4,4' -dicarboxaldehyde, in a ratio of about 3.
Based on the discovery, the invention provides a brand-new (3, 3 '-bithiophene) -4,4' -diformaldehyde synthesis method, which is used for solving the problems that the existing preparation process needs no water in the whole process, is complex to operate, cannot separate and purify products and the like, and comprises the following specific steps:
a method for synthesizing (3, 3 '-bithiophene) -4,4' -dicarboxaldehyde, which comprises the following steps:
reacting 4-bromothiophene-3-formaldehyde with bis (pinacolato) diboron under the action of a catalyst to obtain an intermediate 4- (4, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) thiophene-3-formaldehyde;
under the action of a catalyst, 4- (4, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) thiophene-3-formaldehyde and 4-bromothiophene-3-formaldehyde are coupled to obtain (3, 3 '-bithiophene) -4,4' -dicarboxaldehyde, and the reaction formula is shown as follows:
furthermore, the molar ratio of the 4-bromothiophene-3-formaldehyde to the bis (pinacolato) diboron is 1 (1.2-1.5).
Further, the molar ratio of the 4- (4, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) thiophene-3-formaldehyde to the 4-bromothiophene-3-formaldehyde is 1 (1.2-1.5).
Further, the specific synthesis process of 4- (4, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) thiophene-3-carbaldehyde is as follows:
under the protective atmosphere, sequentially adding 4-bromothiophene-3-formaldehyde, bis (pinacolato) diboron, a catalyst, alkali and a solvent;
then heating the reaction system until the 4-bromothiophene-3-formaldehyde is completely converted, stopping heating, and cooling to room temperature;
separating and purifying to obtain yellow solid 4- (4, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) thiophene-3-formaldehyde.
Further, the catalyst is Pd (dppf) Cl 2 The base comprises potassium carbonate, potassium acetate or cesium carbonate, preferably potassium acetate, and the solvent comprises tetrahydrofuran, toluene or 1,4 dioxane, preferably 1,4 dioxane.
Furthermore, the molar ratio of the 4-bromothiophene-3-formaldehyde, the bis (pinacolato) diboron, the catalyst and the alkali is 1 (1.2-1.5) to (0.05-0.1) to (1.5-3).
Further, the specific process for coupling 4- (4, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) thiophene-3-carbaldehyde with 4-bromothiophene-3-carbaldehyde is as follows:
under the protective atmosphere, sequentially adding 4- (4, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) thiophene-3-formaldehyde, 4-bromothiophene-3-formaldehyde, a solvent, a catalyst and alkali;
heating to complete conversion of 4- (4, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) thiophene-3-formaldehyde, stopping heating, and cooling to room temperature;
separating and purifying to obtain yellow solid (3, 3 '-bithiophene) -4,4' -dicarboxaldehyde.
Further, the catalyst is Pd (PPh) 3 ) 4 The alkali comprises potassium carbonate, potassium acetate or cesium carbonate, preferably potassium carbonate, the solvent is a mixture of tetrahydrofuran and water, and the volume ratio of the tetrahydrofuran to the water is (2-10) to 1, preferably 5.
Furthermore, the molar ratio of the 4- (4, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) thiophene-3-formaldehyde, the 4-bromothiophene-3-formaldehyde, the catalyst and the base is 1 (1.2-1.5) to (0.05-0.1) to (1.5-3).
Further, the preparation process of the 4-bromothiophene-3-formaldehyde intermediate comprises the following steps: 3, 4-dibromothiophene is used as a raw material to react with n-butyl lithium and DMF to obtain a 4-bromothiophene-3-formaldehyde intermediate.
Compared with the prior art, the method has the advantages of less by-products, easier separation and purification and the like because no by-products such as 3,3' -bithiophene with 5-position substitution or 2-position substitution are generated, and is an ideal method for preparing (3, 3' -bithiophene) -4,4' -dicarboxaldehyde.
Drawings
FIG. 1 is a nuclear magnetic spectrum of 4- (4, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) thiophene-3-carbaldehyde in each example;
FIG. 2 is a nuclear magnetic spectrum of (3, 3 '-bithiophene) -4,4' -dicarboxaldehyde in each example;
FIG. 3 is a nuclear magnetic spectrum of a prior art mixture.
Detailed Description
The invention is described in detail below with reference to the figures and specific embodiments. The present embodiment is implemented on the premise of the technical solution of the present invention, and a detailed implementation manner and a specific operation process are given, but the scope of the present invention is not limited to the following embodiments.
A method for synthesizing (3, 3 '-bithiophene) -4,4' -dicarboxaldehyde has the following reaction formula:
the method specifically comprises the following steps:
the first step of reaction: in a 500mL flask 3, 4-dibromothiophene (45.0218 g, 182.10 mmol) was dissolved in freshly prepared anhydrous ether (50 mL) under nitrogen, and n-BuLi (1.6M, 174.46mL) was added dropwise at-78 ℃. After stirring for 40 minutes, anhydrous oxygen-free N, N-dimethylformamide (20.4052 g, 279.14mmol) was added and stirring was continued for 2 hours to room temperature and then overnight. Adding saturated ammonium chloride solution to quench the reaction, extracting with diethyl ether, washing with saturated ammonium chloride solution, combining organic phases, and spin-drying the solvent to obtain an orange oily substance. Column chromatography separation (PE: EA =20: 1) gave 4-bromothiophene-3-carbaldehyde as a pale yellow oil (30.2197 g).
The second step of reaction: under the protection of nitrogen, 4-bromothiophene-3-formaldehyde, bis (pinacolato) diboron and Pd (dppf) Cl are sequentially added into a 250mL flask 2 Alkali, solvent [ 4-bromothiophene-3-formaldehyde, bis (pinacolato) diboron and Pd (dppf) Cl 2 And the molar ratio of the alkali to the solvent is 1: (1.2-1.5): (0.05-0.1): (1.5-3): 0.5-2L/mol]. Then the reaction system is heated to 4-bromothiophene-And (3) completely converting the 3-formaldehyde, stopping heating, cooling to room temperature, recovering the solvent, extracting with ethyl acetate, washing with a saturated ammonium chloride solution, combining organic phases, carrying out spin-drying to obtain a black oily substance, and separating by column chromatography (PE: EA = 2.
1 H NMR (500mhz, chloroform-d) δ 10.34 (s, 1H), 8.19 (d, J =3.0hz, 1h), 7.91 (d, J =3.1hz, 1h), 1.35 (s, 12H), as in fig. 1.
The third step of reaction: under the protection of nitrogen, 4- (4, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) thiophene-3-formaldehyde, 4-bromothiophene-3-formaldehyde, a mixed solution of tetrahydrofuran and water, and Pd (PPh) are sequentially added into a 250mL flask 3 ) 4 And a base. 4- (4, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) thiophene-3-carbaldehyde, 4-bromothiophene-3-carbaldehyde, pd (PPh) 3 ) 4 And the molar ratio of the alkali to the solvent is 1: (1.2-1.5): (0.05-0.1): (1.5-3): 0.5-2L/mol. Heating until 4- (4, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) thiophene-3-formaldehyde is completely converted, stopping heating, cooling to room temperature, then spin-drying the solvent, extracting with dichloromethane, washing with saturated ammonium chloride, combining organic phases, spin-drying the solvent to obtain brown oily matter, and performing column chromatography (PE: EA = 2.
1 H NMR (500mhz, chloroform-d) δ 10.34 (s, 1H), 8.19 (d, J =3.0hz, 1h), 7.91 (d, J =3.1hz, 1h), 1.35 (s, 12H), as in fig. 2.
Example 1
In this example, the raw materials were used in the following amounts: 4-bromothiophene-3-carbaldehyde (2.0125g, 10.53mmol), bis (pinacolato) diboron (3.7625g, 15.80mmol) and Pd (dppf) Cl 2 (0.7683g, 1.05mmol), potassium acetate (3.0482g, 31.60mmol), 1, 4-dioxane (21.1 ml), 4- (4, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) thiophene-3-carbaldehyde (2.1312g, 8.95mmol), 4-bromothiophene-3-carbaldehyde (2.0525g, 12.64mmol), pd (PPh) 3 ) 4 (1.0314g, 0.89mmol), potassium carbonate (3.6485 g,26.40 mmol), tetrahydrofuran and water (THF: 14.9ml, H) 2 O:3.0 ml), reaction time 35h. Yield: 68 percent.
Example 2
In this example, the raw materials were used in the following amounts: 4-bromothiophene-3-carbaldehyde (2.0238g, 10.59mmol), bis (pinacolato) diboron (4.0351g, 15.89mmol), pd (dppf) Cl 2 (0.7756 g, 1.06mmol), potassium acetate (3.1189g, 31.78mmol), toluene (21.2 ml), 4- (4, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) thiophene-3-carbaldehyde (2.0168g, 8.47mmol), 4-bromothiophene-3-carbaldehyde (1.9410 g, 10.16 mmol), pd (PPh) 3 ) 4 (0.9788g, 0.85mmol), potassium carbonate (3.5117g, 25.41mmol), tetrahydrofuran and water (THF: 11.3ml, H) 2 O:5.6 ml), reaction time: 38h. Yield: 62 percent.
Example 3
In this example, the raw materials were used in the following amounts: 4-bromothiophene-3-carbaldehyde (2.0388g, 10.67mmol), bis (pinacolato) diboron (4.0656g, 16.01mmol), pd (dppf) Cl 2 (0.7829g, 1.07mmol), potassium acetate (3.1424g, 32.02mmol), tetrahydrofuran (21.3 ml), 4- (4, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) thiophene-3-carbaldehyde (2.1097g, 8.86mmol), 4-bromothiophene-3-carbaldehyde (2.0308 g, 10.63mmol), pd (PPh) 3 ) 4 (1.0285g, 0.89mmol), potassium carbonate (3.6734g, 26.58mmol), tetrahydrofuran and water (THF: 16.1ml, H) 2 O:1.6 ml), reaction time: 37h. Yield: and 64 percent.
Example 4
In this example, the raw materials were used in the following amounts: 4-bromothiophene-3-carbaldehyde (2.1136g, 11.06mmol), bis (pinacolato) diboron (4.2154g, 16.60mmol), pd (dppf) Cl 2 (0.8122g, 1.11mmol), potassium carbonate (4.5869g, 33.19mmol), 1, 4-dioxane (22.1 ml), 4- (4, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) thiophene-3-carbaldehyde (2.0549g, 8.63mmol), 4-bromothiophene-3-carbaldehyde (1.9792g, 10.36mmol), pd (PPh) 3 ) 4 (1.0054g, 0.87mmol), potassium acetate (2.5408 g, 25.89 mmol), tetrahydrofuran and water (THF: 14.4ml, H) 2 O:2.9 ml), reaction time: 40h. Yield: 60 percent.
Example 5
In this example, the raw materials were used in the following amounts: 4-bromothiophene-3-Formaldehyde (2.0516g, 10.74mmol), bis (pinacolato) diboron (4.0910g, 16.11mmol), pd (dppf) Cl 2 (0.7829g, 1.07mmol), cesium carbonate (10.4979g, 32.22mmol), 1,4 dioxane (21.5 ml), 4- (4, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) thiophene-3-carbaldehyde (1.9168g, 8.05mmol), 4-bromothiophene-3-carbaldehyde (1.8474g, 9.67mmol), pd (PPh) 3 ) 4 (0.9360g, 0.81mmol), cesium carbonate (7.8751g, 24.17 mmol), tetrahydrofuran and water (THF: 13.4ml, H) 2 O:2.7 ml), reaction time: 44h. Yield: 53 percent.
Example 6
In this example, the raw materials were used in the following amounts: 4-bromothiophene-3-carbaldehyde (2.0228g, 10.59mmol), bis (pinacolato) diboron (4.0326g, 15.88mmol), pd (dppf) Cl 2 (0.7756g, 1.06mmol), potassium acetate (3.1169g, 31.76mmol), 1, 4-dioxane (5.3 ml), 4- (4, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) thiophene-3-carbaldehyde (1.7644g, 7.41mmol), 4-bromothiophene-3-carbaldehyde (1.7003g, 8.90mmol), pd (PPh) 3 ) 4 (0.8551g, 0.74mmol), potassium carbonate (3.0722g, 26.40 mmol), tetrahydrofuran and water (THF: 3.1ml, H) 2 0.6ml of O) and the reaction time is 52h. Yield: 49 percent.
Example 7
In this example, the raw materials were used in the following amounts: 4-bromothiophene-3-carbaldehyde (2.0357g, 10.66mmol), bis (pinacolato) diboron (4.0580g, 15.98mmol), pd (dppf) Cl 2 (0.7829g, 1.07mmol), potassium acetate (3.1375g, 31.97mmol), 1, 4-dioxane (10.7 ml), 4- (4, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) thiophene-3-carbaldehyde (2.9g, 8.42mmol), 4-bromothiophene-3-carbaldehyde (1.9295g, 10.10mmol), pd (PPh) 3 ) 4 (0.9707g, 0.84mmol), potassium carbonate (3.4909 g, 25.26 mmol), tetrahydrofuran and water (THF: 7.0ml, H) 2 O:1.4 ml), reaction time: 40h. Yield: and 63 percent.
Example 8
In this example, the raw materials were used in the following amounts: 4-bromothiophene-3-carbaldehyde (2.3511g, 12.31mmol), bis (pinacolato) diboron (4.6877g, 18.46mmol), pd (dppf) Cl 2 (0.4537g, 0.62mmol), potassium acetate (3.6233 g)36.92 mmol), 1,4 dioxane (24.6 ml), 4- (4, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) thiophene-3-carbaldehyde (2.3740g, 9.97mmol), 4-bromothiophene-3-carbaldehyde (2.2848g, 11.96mmol), pd (PPh) 3 ) 4 (0.5778g, 0.50mmol), potassium carbonate (4.1336 g, 29.91 mmol), tetrahydrofuran and water (THF: 16.6ml, H) 2 O:3.3 ml), reaction time 62h. Yield: 65 percent.
Example 9
In this example, the raw materials were used in the following amounts: 4-bromothiophene-3-carbaldehyde (2.4125g, 12.63mmol), bis (pinacolato) diboron (3.8472g, 15.15mmol), pd (dppf) Cl 2 (0.9219g, 1.26mmol), potassium acetate (1.8588g, 18.94mmol), 1,4 dioxane (25.3 ml), 4- (4, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) thiophene-3-carbaldehyde (2.0739g, 8.71mmol), 4-bromothiophene-3-carbaldehyde (1.9964g, 10.45mmol), pd (PPh) 3 ) 4 (1.0054g, 0.87mmol), potassium carbonate (1.8063 g, 13.07 mmol), tetrahydrofuran and water (THF: 14.5ml, H) 2 O:2.9 ml), and the reaction time is 39h. Yield: 51 percent.
Example 10
In this example, the raw materials were used in the following amounts: 4-bromothiophene-3-carbaldehyde (2.0755g, 10.86mmol), bis (pinacolato) diboron (3.5856g, 14.12mmol), pd (dppf) Cl 2 (0.7976g, 1.09mmol), potassium acetate (2.1326g, 21.73mmol), 1,4 dioxane (21.7 ml), 4- (4, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) thiophene-3-carbaldehyde (1.9144g, 8.04mmol), 4-bromothiophene-3-carbaldehyde (1.9964g, 10.45mmol), pd (PPh) 3 ) 4 (0.9245g, 0.80mmol), potassium carbonate (2.2223 g, 16.08 mmol), tetrahydrofuran and water (THF: 13.4ml, H) 2 O:2.7 ml), reaction time 43h. Yield: 59 percent.
Example 11
In this example, the raw materials were used in the following amounts: 4-bromothiophene-3-carbaldehyde (2.0621g, 10.79mmol), bis (pinacolato) diboron (3.8370g, 15.11mmol), pd (dppf) Cl 2 (0.7902g, 1.08mmol), potassium acetate (2.6478g, 26.98mmol), 1, 4-dioxane (21.6 ml), 4- (4, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) thiophene-3-carbaldehyde (2.0049g, 8.42mmol), 4-bromoThiophene-3-carbaldehyde (2.2524g, 11.79mmol), pd (PPh) 3 ) 4 (0.9707g, 0.84mmol), potassium carbonate (2.9077 g, 21.04 mmol), tetrahydrofuran and water (THF: 14.0ml, H) 2 O:2.8 ml), and the reaction time is 39h. Yield: and 63 percent.
Example 12
In this example, the raw materials were used in the following amounts: 4-bromothiophene-3-carbaldehyde (0.1055g, 0.55mmol), bis (pinacolato) diboron (0.2104g, 0.83mmol) and Pd (dppf) Cl 2 (0.0439g, 0.06mmol), potassium acetate (0.1629g, 1.66mmol), 1, 4-dioxane (1.1 ml), 4- (4, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) thiophene-3-carbaldehyde (0.1131g, 0.47mmol), 4-bromothiophene-3-carbaldehyde (0.1089g, 0.56mmol), pd (PPh) 3 ) 4 (0.0578g, 0.05mmol), potassium carbonate (0.1976g, 1.43 mmol), tetrahydrofuran and water (THF: 0.8ml, H) 2 0.2ml of O) and 38 hours of reaction time. Yield: and 69 percent.
While the invention has been described with reference to a preferred embodiment, it will be understood by those skilled in the art that various changes may be made and equivalents may be substituted for elements thereof without departing from the scope of the invention. However, any simple modification, equivalent change and modification of the above embodiments according to the technical essence of the present invention are within the protection scope of the technical solution of the present invention.
Claims (10)
1. A method for synthesizing (3, 3 '-bithiophene) -4,4' -dicarboxaldehyde is characterized by comprising the following steps:
reacting 4-bromothiophene-3-formaldehyde with bis (pinacolato) diboron under the action of a catalyst to obtain an intermediate 4- (4, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) thiophene-3-formaldehyde;
under the action of a catalyst, 4- (4, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) thiophene-3-formaldehyde and 4-bromothiophene-3-formaldehyde are coupled to obtain (3, 3 '-bithiophene) -4,4' -dicarboxaldehyde.
2. The method for synthesizing (3, 3 '-bithiophene) -4,4' -dicarbaldehyde according to claim 1, wherein the molar ratio of 4-bromothiophene-3-carbaldehyde to bis (pinacolato) diboron is 1 (1.2-1.5).
3. The method for synthesizing (3, 3 '-bithiophene) -4,4' -dicarboxaldehyde according to claim 1, wherein the molar ratio of 4- (4, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) thiophene-3-carbaldehyde to 4-bromothiophene-3-carbaldehyde is 1 (1.2-1.5).
4. The method for synthesizing (3, 3 '-bithiophene) -4,4' -dicarboxaldehyde according to claim 1, wherein the specific synthesis process of 4- (4, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) thiophene-3-carboxaldehyde is as follows:
under the protective atmosphere, sequentially adding 4-bromothiophene-3-formaldehyde, bis (pinacolato) diboron, a catalyst, alkali and a solvent;
then heating the reaction system until the 4-bromothiophene-3-formaldehyde is completely converted, stopping heating, and cooling to room temperature;
separating and purifying to obtain yellow solid 4- (4, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) thiophene-3-formaldehyde.
5. The method for synthesizing (3, 3 '-bithiophene) -4,4' -dicarboxaldehyde according to claim 4, wherein the catalyst is Pd (dppf) Cl 2 The base comprises potassium carbonate, potassium acetate or cesium carbonate, preferably potassium acetate, and the solvent comprises tetrahydrofuran, toluene or 1,4 dioxane, preferably 1,4 dioxane.
6. The method for synthesizing (3, 3 '-bithiophene) -4,4' -dicarboxaldehyde according to claim 4, wherein the molar ratio of the 4-bromothiophene-3-carbaldehyde to the bis (pinacolato) diboron to the catalyst to the base is 1 (1.2-1.5) to (0.05-0.1) to (1.5-3).
7. The method for synthesizing (3, 3 '-bithiophene) -4,4' -dicarboxaldehyde according to claim 1, wherein the specific process for coupling 4- (4, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) thiophene-3-carbaldehyde and 4-bromothiophene-3-carbaldehyde is as follows:
under the protective atmosphere, sequentially adding 4- (4, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) thiophene-3-formaldehyde, 4-bromothiophene-3-formaldehyde, a solvent, a catalyst and alkali;
heating to complete conversion of 4- (4, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) thiophene-3-formaldehyde, stopping heating, and cooling to room temperature;
separating and purifying to obtain yellow solid (3, 3 '-bithiophene) -4,4' -dicarboxaldehyde.
8. The method for synthesizing (3, 3 '-bithiophene) -4,4' -dicarboxaldehyde according to claim 7, wherein the catalyst is Pd (PPh) 3 ) 4 The alkali comprises potassium carbonate, potassium acetate or cesium carbonate, preferably potassium carbonate, and the solvent is a mixture of tetrahydrofuran and water, wherein the volume ratio of the tetrahydrofuran to the water is (2-10) to 1, preferably 5.
9. The method of claim 7, wherein the molar ratio of 4- (4, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl) thiophene-3-carbaldehyde to 4-bromothiophene-3-carbaldehyde to the catalyst to the base is 1 (1.2-1.5): 0.05-0.1): 1.5-3.
10. The method for synthesizing (3, 3 '-bithiophene) -4,4' -dicarboxaldehyde according to claim 1, wherein the preparation process of the 4-bromothiophene-3-carboxaldehyde intermediate comprises the following steps: 3, 4-dibromothiophene is used as a raw material to react with n-butyl lithium and DMF to obtain a 4-bromothiophene-3-formaldehyde intermediate.
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| CN102558139A (en) * | 2011-12-30 | 2012-07-11 | 南京工业大学 | Method for synthesizing 3, 4-thiophenedicarboxaldehyde |
| US20180362493A1 (en) * | 2017-06-20 | 2018-12-20 | Saint Louis University | Dinaphthothiophene compounds |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102558139A (en) * | 2011-12-30 | 2012-07-11 | 南京工业大学 | Method for synthesizing 3, 4-thiophenedicarboxaldehyde |
| US20180362493A1 (en) * | 2017-06-20 | 2018-12-20 | Saint Louis University | Dinaphthothiophene compounds |
Non-Patent Citations (1)
| Title |
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| KEKE PEIA ET AL: "Highly fluorescence emissive 5, 50-distyryl-3, 30-bithiophenes: Synthesis, crystal structure, optoelectronic and thermal properties" * |
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