CN111454282A - Preparation of electron-deficient and electron-deficient conjugated extended isoindigo compounds - Google Patents
Preparation of electron-deficient and electron-deficient conjugated extended isoindigo compounds Download PDFInfo
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Abstract
On the basis of previous research of the applicant (see patent 201710238042.2, a thiazole isoindigo compound and a preparation method thereof, patent 201719999999.7, a thiazole isatin compound and a preparation method thereof for details), the invention introduces electron-deficient groups into a thiazole isoindigo structure or increases the number of fused rings of aromatic rings in isoindigo molecules, thereby beneficially exploring the synthesis of derivatives in isoindigo or thiazole isoindigo range and successfully preparing a series of electron-deficient and electron-deficient conjugated extended isoindigo compounds. The successful synthesis of the small molecular compound is beneficial to the construction of an n-type organic field effect transistor, and has important application prospect in the field of organic semiconductor materials.
Description
Technical Field
The invention relates to a preparation method of an electron-deficient and electron-deficient conjugated extended isoindigo compound, belonging to the field of heterocyclic compound synthesis and organic field effect transistor materials.
Background
Isoindigo, an isomer of the well-known pigment indigo, has received attention as an important building block in donor-acceptor (D-a) type conjugated polymers. At present, different structures of isoindigo are internationally transformed to respectively obtain thiophene isoindigo and pyridine isoindigo, in order to combine the advantages of the thiophene isoindigo and the pyridine isoindigo to obtain an electron-deficient quinoid structure, the difficult problem of synthesizing thiazole isoindigo is also overcome one by one. Up to now, reports about the application of thiazole isoindigo in organic photoelectric materials are limited to the preparation of thiazole isoindigo and trithiophenePolymer P (TzII-TTT) (T;)Chem. Eur. J.2018, 24, 9807-. However, the synthesis of receptor-receptor (a-a) type small molecules and polymers is still under search and development. The patent uses a technical route explored by scientific research teams led by professors of dawn waves to meaningfully explore the synthesis of an electron-deficient A-A molecular structure, and simultaneously, the method also tries to incorporate a benzene ring into the electron-deficient isoindigo structure to extend the conjugation range of the compound, finally synthesizes a series of electron-deficient and electron-deficient conjugated extended isoindigo derivatives with high yield, is beneficial to the batch production of thiazole isoindigo derivatives, is expected to obtain n-type field effect transistor materials, and has important application prospects in the field of organic semiconductor materials.
In conclusion, the research work on electron-deficient and electron-deficient conjugated extended isoindigo compounds is still a vacancy in the scientific research field, and therefore, the successful synthesis of the electron-deficient and electron-deficient conjugated extended isoindigo compounds has important research value and application prospect in the field of organic semiconductor materials.
Disclosure of Invention
The invention aims to apply the synthesis method of thiazole isoindigo in the patents 201710238042.2 and 201719999999.7 to the preparation of electron-deficient and electron-deficient conjugated extended isoindigo compounds.
Specifically, the structural general formula of the thiazole isoindigo compound is shown as (I):
wherein:
r is alkyl, benzyl, and other aromatic rings or aromatic heterocyclic rings which are connected with the modified N atom through methylene; x is selected from aromatic rings and aromatic heterocycles.
The invention proves the feasibility of applying nucleophilic reaction to synthesizing electron-deficient and electron-deficient conjugated extended isoindigo compounds, and supplements and perfects the synthesis method aiming at different situations. The chemical names of the compounds (I), (II) and (III) are (trans) [6, 6' -dipyrrolo [2,3-d ] respectively]Thiazoles]-5,5 'dione, (trans) -4, 4' -dichloro-5, 5 'dialkyl- [7, 7' -dithiazole [5,4-f]Indolyl radical]-6,6’(5H,5’H) -diketones and (trans) -5,5 '-dichloro- [8, 8' -dipyrrolo [2,3-g]Oxinoquinolinyl]-7,7’(6H,6’H) A diketone prepared by the process comprising 2-bromo-4-thiazoleamine salt, benzo [2 ]d]The target compounds shown in the structural general formulas (I), (II) and (III) are successfully obtained by using-thiazole-5-amine or oxine-6-amine as a raw material through a series of steps of acylation, coupling, reduction, oxamiding, hydrolysis, cyclization, polycondensation or acylation, alkylation, coupling, hydrolysis, cyclization, polycondensation and the like.
Detailed Description
The present invention is described in detail with reference to the following examples, but the following examples are only preferred embodiments of the present invention, and the scope of the present invention is not limited thereto, and any person skilled in the art can substitute or change the technical solution of the present invention and its inventive concept within the technical scope of the present invention.
Example 1
Preparation of 2- ((2-bromothiazol-4-yl) -amino) -2-oxo-acetic acid ethyl ester
Compound 1 (4.19 g, 30.7 mmol) was added to dichloromethane (53 m L) at 0 deg.C under argon, followed by the addition of triethylamine (12 m L) in turn, the reactant oxalylChloroethyl ester (6.6 g, 25.6 mmol), reaction for 30min with NH4Quenching reaction with Cl, adding saturated saline solution, and extracting with ethyl acetate for three times to obtain an oil phase; over anhydrous MgSO4g after drying, dichloromethane, triethylamine and ethyl acetate were distilled off under reduced pressure, the organic phase was concentrated and subjected to column chromatography (petroleum ether/ethyl acetate = 10: 1) to isolate compound 9 as a white solid 5.38 g with a yield of 75.2%.
1H NMR (600 MHz, CDCl3) 9.63, 9.58 (s, s, 1H), 7.72, 7.67 (s, s,1H), 4.43 (q,J= 7.2 Hz, 2H), 1.43 (t,J= 7.2 Hz, 3H);13C NMR (151
MHz, CDCl3) 159.6, 159.5, 153.6, 153.6, 151.2, 145.1, 143.7, 135.3,107.7, 105.7, 63.9, 14.0。
Preparation of ethyl 2- ((2-bromothiazol-4-yl) (4-decyltetradecane) amino) -2-oxoacetate
At room temperature, 11- (3-iodopropyl) heneicosane (2.98 g, 6.41 mmol), K2CO3(1.33 g, 9.62 mmol) are respectively added into the N, N-dimethylformamide (60 m L) solution of the compound 9, the reaction is carried out for 4-5 h under the temperature condition of 100 ℃, after the temperature is returned to room temperature, saturated NH is added4The reaction was quenched with Cl solution, the organic phase was extracted and washed with ethyl acetate and saturated brine, respectively, dried, and the organic solvent in the product system was removed by distillation under reduced pressure, and column chromatography (petroleum ether/ethyl acetate = 30: 1) gave 2.69 g of yellow oily liquid with a yield of 76.2%, in which,N-alkylated products andO-the ratio of alkylated products is 3: 1, it cannot be separated.
NOf the alkylation products1H NMR (600 MHz, CDCl3): 6.88 (d, J = 4.1 Hz, 1H),4.19 (q,J= 7.1 Hz, 2H), 3.83-3.75 (m, 2H), 1.40 (t,J= 7.1 Hz, 2H), 1.31-1.20 (m, 39H), 0.88 (t,J= 7.0 Hz, 9H);O-Of alkylated products1H NMR (600 MHz,CDCl3): 7.78 (s, 1H), 4.40 (q,J= 7.1 Hz, 2H), 3.90-3.83 (m, 2H), 1.64 (s,2H), 1.31-1.20 (m, 39H), 0.88 (t,J= 7.0 Hz, 9H);13C NMR (151 MHz, CDCl3):162.26, 162.07, 161.09, 161.00, 149.35, 146.93, 135.47, 126.00, 125.86,62.39, 62.09, 47.37, 33.48, 31.94, 30.45, 30.10, 29.72, 29.67, 26.63, 26.57,24.50, 22.70, 14.13, 13.90.
Preparation of ethyl 2- ([2, 2' -dithiazol ] -4-yl (4-decyltetradecane) amino) -2-oxo-acetate
To a 100m L stoppered tube at room temperature were added compounds 10a, 10b (2.69 g, 4.37 mmol), 2- (dibutyl (pentyl) stannyl) thiazole (2.45 g, 6.56 mmol), Pd (PPh) respectively3)4(0.51 g, 0.44 mmol), CuI (0.17 g, 0.88 mmol) and N, N-dimethylformamide (40 m L). before the reaction starts, argon is introduced for 20 min by means of an argon ball to remove air in a sealed tube, the reaction is carried out for 20-24 h at the temperature of 90 ℃, after the reaction is finished and the temperature is returned to the room temperature, saturated NH is added4Quenching the reaction with Cl solution, extracting the organic phase with ethyl acetate and washing the organic phase with saturated saline solution, drying, removing the organic solvent from the product system by distillation under reduced pressure, and performing column chromatography (petroleum ether/ethyl acetate = 30: 1) to obtain the final productN-Alkylated products andO1.80 g of a pale yellow oily liquid consisting of the alkylation product, in 66.4% yield.
NOf the alkylation products1H NMR (600 MHz, CDCl3): 7.90 (t,J= 3.2 Hz, 1H),7.48 (d,J= 2.2 Hz, 1H), 7.00 (s, 1H), 4.25-4.14 (m, 2H), 3.90-3.82 (m, 2H),1.42 (t,J= 6.1 Hz, 2H), 1.34-1.15 (m, 39H), 0.88 (t,J= 6.7 Hz, 9H).OOf the alkylation products1H NMR (600 MHz, CDCl3) : 7.98 (s, 1H), 7.43 (d,J= 2.4 Hz, 1H),7.03 (s, 1H), 4.42 (q,J= 7.0 Hz, 2H), 4.01-3.91 (s, 2H), 1.62 (s, 2H),1.34-1.15 (m, 39H), 0.88 (t,J= 6.7 Hz, 9H).13C NMR (151 MHz, CDCl3):162.48, 161.24, 160.48, 160.14, 144.15, 121.84, 121.03, 110.48, 62.07, 37.15,33.51, 31.94, 30.11, 29.72, 29.67, 29.38, 26.66, 24.57, 22.71, 14.14.
Preparation of 4- (4-decyltetradecane) -2- (thiazol-2-yl) -4H-pyrrolo [2,3-d]Thiazole-5, 6-diones
At the temperature of 0 ℃, tetrahydrofuran (C)14 m L) and methanol (9.5 m L) into a 100m L round-bottom flask containing 11a and 11b (1.18 g,1.9 mmol) and dissolving them, dissolving L iOH solid (136.7 mg, 5.7 mmol) in water thoroughly and adding dropwise into the reaction flask, controlling the reaction time at 20-30min, allowing the product system to return to room temperature naturally after the reaction is finished, adjusting the pH of the reaction solution to 5-6 with hydrochloric acid solution, adding ethyl acetate and saturated brine to extract and wash the organic phase, anhydrous MgSO, respectively4Drying, filtering organic phase, removing organic solvent under reduced pressure distillation to obtain yellow hydrolysate, drying hydrolysate, dissolving in anhydrous tetrahydrofuran solvent (10m L), adding thionyl chloride reagent (1.1 m L, 16.4 mmol) dropwise into the reaction system at 0 deg.C under the protection of argon gas, reacting for a while, gradually darkening the reaction solution, and adding small amount of saturated NH4The reaction was quenched with Cl solution, extracted with dichloromethane, washed with saturated brine, dried over anhydrous MgSO4, concentrated, and isolated by flash column chromatography (petroleum ether/ethyl acetate = 10: 1) to give compound 27 (932.1 mg) as a red solid in 64.7% yield.
1H NMR (600 MHz, CDCl3): 8.04 (d,J= 2.8 Hz, 1H), 7.70 (d,J= 2.8Hz, 1H), 3.82 (t,J= 7.2 Hz, 2H), 1.79 (dd,J 1 = 14.5 Hz,J 2 = 7.1 Hz, 2H),1.44-1.06 (m, 39H), 0.88 (t,J= 7.0 Hz, 6H).13C NMR (151 MHz, CDCl3):176.16, 161.16, 159.37, 145.53, 143.93, 124.91, 120.98, 41.91, 36.94, 33.47,31.94, 30.46, 30.13, 29.73, 29.67, 29.37, 26.64, 25.20, 22.71, 14.14.
Preparation of (trans) -4,4 ' -bis (4-decyltetradecane) -2,2 ' -bis (thiazol-2-yl) - [6,6 ' -dipyrrolo [2,3-d]Thiazolyl idene group]-5,5’(4H,4’H) -diketones
Lawson's reagent (29.3 mg, 0.07 mmol) was added to a toluene solution (5.5 m L) of compound 27 (83.8 mg, 0.15 mmol) at room temperature under argon protection, the reaction was carried out at 60 ℃ for 3-4 h, after the reaction was completed, the product system was directly concentrated, the high boiling solvent toluene was removed, the sample was stirred, and blue solid compound 28 (73.0 mg) was isolated by column chromatography (petroleum ether/ethyl acetate = 20: 1) with 90% yield.
1H NMR (600 MHz, CDCl3): 7.94 (d,J= 3.1 Hz, 1H), 7.49 (d, 3.1 Hz,1H), 3.93 (t,J= 7.2 Hz, 2H), 1.92-1.75 (m, 2H), 1.36-1.44 (m, 39H), 0.87(t, J = 7.1 Hz, 6H).13C NMR (151 MHz, CDCl3): 169.86, 161.44, 144.80,129.36, 125.18, 121.77, 119.88, 110.78, 108.60, 46.11, 45.26, 41.83, 36.96,33.53, 31.93, 30.15, 29.74, 26.67, 25.31, 22.69, 19.55, 18.05, 17.45, 16.99,14.13.
Preparation of (trans) -2,2 ' -bis (5-bromothiazol-2-yl) -4,4 ' -bis (4-decyltetradecane) - [6,6 ' -dipyrrolo [2,3-d]Thiazolyl idene group]-5,5’(4H,4’H) -diketones
Compound 28 (0.29 g, 0.26 mmol) was sufficiently dissolved in chloroform (25 m L) solvent under ice-bath conditions at 0 ℃, N-bromosuccinimide (0.13 g, 0.71 mmol) was added in portions to the starting material solution, the reaction was carried out for approximately two to three days, and after the reaction was completed, the product system was concentrated, stirred with silica gel, and separated by column chromatography (petroleum ether/ethyl acetate = 100: 1) to obtain compound 29 (0.23 g) as a blue solid in a yield of 68.5%.
1H NMR (600 MHz, CDCl3): 7.79 (s, 1H), 3.90 (t,J= 7.2 Hz, 2H),1.90-1.71 (m, 2H), 1.37-1.10 (m, 39H), 0.87 (q,J= 6.9 Hz, 6H).13C NMR (151MHz, CDCl3): 169.54, 164.60, 162.34, 145.90, 119.56, 112.39, 108.82, 41.65,36.99, 33.53, 31.95, 30.57, 30.20, 29.79, 29.39, 29.33, 26.70, 25.27, 14.14.
Preparation of (trans) -2,2 '- (4, 4' -bis (4-decyltetradecane) -5,5 '-dioxo-4, 4', 5,5 '-tetrahydro- [6, 6' -pyrrolo [2,3-d]Thiazolyl idene group]-2, 2' -ylidene) bis (thiazole-5-cyano)
Compound 15 (94.2 mg, 7.4 × 10)-2mmol), cyano reagent K4[Fe(CN)6]（18.6 mg, 4.4×10-2mmol), palladium catalyst Pd (OAc)2(3.3 mg, 0.15 mmol), ligand dppf (8.2 mg, 0.15 mmol), Na2CO3（7.8 mg, 7.4×10-2mmol) was added to a 10m L sealed tube, and N, N-dimethylformamide (2 m L) was added to dissolve, the reaction was carried out at 140 ℃ for 2-3 h, after completion of the reaction, the product system was stirred with silica gel to room temperature, and separation was carried out by column chromatography (petroleum ether/ethyl acetate/chloroform = 300: 8: 8) to obtain compound 30 (38.8 mg) as a green solid with a yield of 45%.
Example 2
Preparation of ethyl 2- ([2, 5' -dithiazol ] -4-yl (2-octyldodecane) amino) -2-oxoacetate
Compounds 17a and 17b (0.47 g, 0.84 mmol) were dissolved in N, N-dimethylformamide (4 m L) in a 15 m L stoppered tube, and 5- (trimethyltin) thiazole (0.32 g, 1.29 mmol), Pd (PPh) as a palladium catalyst, and added3)4(0.10 g, 0.09 mmol) and CuI (0.03 g, 0.17 mmol), reacting at 90 deg.C for 20-24 h, and adding saturated NH when the temperature is returned to room temperature4The reaction was quenched with Cl solution, the organic phase was extracted with ethyl acetate, washed with saturated brine, anhydrous MgSO4Drying, filtering, concentrating, and separating by column chromatography (petroleum ether/ethyl acetate = 30: 1) to obtain light yellowN-Alkylated isomers andO-the alkylated isomer compounds 31a and 31b (0.25 g) were obtained in 54% yield.
Preparation of 4- (2-octyldodecane) -2- (thiazol-5-yl) -4H-pyrrolo [2,3-d]Thiazole-5, 6-diones
Adding isomer 31a and 31b compounds (94.5 mg, 0.17 mmol), binary solvent methanol (1 m L) and tetrahydrofuran (3 m L) into a 100m L reaction flask, dissolving L iOH (12 mg, 0.50 mmol) in 1.2 m L water, dropwise adding L iOH aqueous solution into the reaction flask, reacting at 0 deg.C in ice bath for 20-30min, adding hydrochloric acid solution into the reaction solution until the raw materials are completely consumed, adjusting pH to 5-6, extracting the organic phase with dichloromethaneWashing the organic phase with saturated brine, anhydrous MgSO4Drying and concentration gave compound 32 as a yellow solid.
Under the protection of argon, compound 32 (57.4 mg, 0.10 mmol) was dissolved in dry tetrahydrofuran (4 m L) in a 100m L flask, cooled in an ice bath, and then SOCl was added dropwise2(0.1 m L, 1.4 mmol), the ice bath was removed, the temperature was increased overnight, saturated NH was added4The reaction was quenched with Cl solution. Extracting with ethyl acetate, washing with water, washing with saturated saline solution, and anhydrous MgSO4And (5) drying. The organic phase was concentrated and isolated by flash column chromatography (petroleum ether/ethyl acetate = 10: 1) to give compound 33 (46.2 mg) in 85.4% yield.
Preparation of (trans) -4,4 ' -bis (2-octyldodecane) -2,2 ' -bis (thiazol-5-yl) - [6,6 ' -dipyrrolo [2,3-d]Thiazolyl idene group]-5,5’[4H,4’H]-diketones
Lawson's reagent (0.18 g, 0.44 mmol) was added to a toluene solution (10m L) of compound 33 (0.46 mg, 0.89 mmol) under argon atmosphere, the reaction was carried out at 60 ℃ for 3-4 h, after the reaction was completed, the product system was directly concentrated, the high boiling point solvent toluene was removed, the sample was stirred, and compound 34 (0.38 g) was isolated as a blue solid by column chromatography (petroleum ether/ethyl acetate = 20: 1) with 85% yield.
Preparation of (trans) -2,2 ' -bis (2-bromothiazol-5-yl) -4,4 ' -bis (2-octyldodecane) - [6,6 ' -dipyrrolo [2,3-d]Thiazolyl idene group]-5,5’(4H,4’H) -diketones
Compound 34 (0.27 g, 0.27 mmol) was sufficiently dissolved in chloroform (10m L) solvent at room temperature, cooled in an ice bath, N-bromosuccinimide (0.12 g, 0.67 mmol) was added in portions to the raw material solution, and the reaction was carried out for approximately two to three days, after the end of the reaction, the product system was concentrated, stirred with silica gel, and separated by column chromatography (petroleum ether/ethyl acetate = 50: 1) to obtain compound 35 (0.25 g) as a blue solid in 79% yield.
Example 3
Preparation ofN- (2-bromothiazol-4-yl) -2-octyldodecanamide
Adding triethylamine (5.4 m L, 38.7 mmol) into a DCM (30 m L) solution of 2-bromo-4-thiazoleamine hydrochloride (9.23 g, 35.5 mmol) at room temperature, cooling the reaction solution to 0 ℃, dropwise adding 2-octyl dodecane acyl chloride (4.7 g, 14.2 mmol), reacting for 20 min, evaporating DCM and triethylamine under reduced pressure, and adding saturated NH after the reaction is finished4Quenching with Cl, extracting the organic phase with ethyl acetate, washing the organic phase with saturated brine, anhydrous MgSO4Drying, concentration and isolation by column chromatography (petroleum ether/ethyl acetate = 30: 1) gave 9.7 g of the compound as a yellow liquid with a yield of 73.4%.
Preparation of 2-octyl-N- (2- (4- (trifluoromethyl) phenyl) thiazol-4-yl) dodecanamide
Using N, N-dimethylformamide (10m L)N- (2-Bromothiazol-4-yl) -2-octyldodecanoamide (0.91 g,1.93 mmol) was dissolved in a 100m L sealed tube, and 4,4,5, 5-tetramethyl-2- (4- (trifluoromethyl) phenyl) -1,3, 2-dioxaborolan (1.05 g, 3.86 mmol), palladium catalyst Pd were added2(dba)3(36.0 mg, 0.04 mmol), ligand triphenylphosphine (56.3 mg, 0.21 mmol), K2CO3(1.15 g, 8.21 mmol) and two drops of trioctylmethylammonium chloride, the reaction was carried out at 90 ℃ for one to two days, and after the reaction was complete, saturated NH was used to bring the temperature back to room temperature4The reaction was quenched with Cl, the organic phase was extracted with ethyl acetate, washed with saturated brine, and anhydrous MgSO4Drying, concentration and isolation by column chromatography (petroleum ether/ethyl acetate = 50: 1) gave compound 36 (0.61 g) as a yellow liquid in 58.8% yield.
Preparation ofN- (2-octyldodecane) -2- (4- (trifluoromethyl) phenyl) thiazole-4-amide
To a 10m L closed tube, compound 36 (0.86 g, 1.59 mmol) was added and then dissolved with 1, 4-dioxane (4 m L). the reaction was cooled to 0 ℃ and under argon, L iAlH was added in portions4(0.45 g, 11.9 mmol), heated to 70 ℃ for 2 h. After the reaction is finished, cooling the reaction liquid to 0 ℃, and dropwise adding a small amount of H2The reaction was quenched with O, then extracted with DCM and the residue filtered off. MgSO (MgSO)4The organic phase was dried and concentrated and the product obtained was directly taken to the next reaction.
Preparation of ethyl 2- ((2-octyldodecane) (2- (4- (trifluoromethyl) phenyl) thiazol-4-yl) amino-2-oxoacetate
Compound 37, 10m L dried tetrahydrofuran was added to a 100ml reaction flask, cooled in an ice bath and then DIPEA (0.30 g, 2.3 mmol), oxalyl chloride monoethyl ester (0.34 g, 2.5 mmol) were added dropwise, respectively, reacted overnight, saturated NH was added4The reaction was quenched with Cl solution. Extracting with ethyl acetate, washing with water, washing with saturated saline solution, and anhydrous MgSO4Drying, concentration and flash column chromatography (petroleum ether/ethyl acetate = 20: 1) gave compound 38 (0.66 g) as a yellow liquid in 70% yield.
Preparation of ethyl 2- ((2-octyldodecane) (2- (4- (trifluoromethyl) phenyl) thiazol-4-yl) amino-2-oxoacetate
To a 100ml reaction flask was added compound 26 (0.1 g, 0.16 mmol), MeOH (2M L) and THF (10M L), cooled in an ice bath and 1M L iOH (11.6 mg, 0.5 mmol) was added dropwise, the reaction was allowed to proceed for 20-30min, and after completion of the reaction, saturated NH was added4The reaction was quenched with Cl solution. Extracting with ethyl acetate, washing with water, washing with saturated saline solution, and anhydrous MgSO4And (5) drying. The organic phase is concentrated to obtain the crude compound 39 which is directly used for the next reaction without purification.
Preparation of 4- (2-octyldodecane) -2- (4- (trifluoromethyl) phenyl) -4H-pyrrolo [2,3-d]Thiazole-5, 6-diones
To a 100m L flask under argon atmosphere, the above compound 39 was added, dissolved in dry tetrahydrofuran (10m L), cooled in an ice bath, and then added dropwise SOCl2(0.1 m L, 1.4 mmol), the ice bath was removed, the temperature was increased overnight, saturated NH was added4The reaction was quenched with Cl solution. Extracting with ethyl acetate, washing with water, washing with saturated saline solution, and anhydrous MgSO4And (5) drying. The organic phase was concentrated and isolated by flash column chromatography (petroleum ether/ethyl acetate = 10: 1) to give compound 40 as a red-brown solid 74.3 mg, yield 79.5%.
Preparation of (trans) -4, 4-Bis (2-octyldodecane) -2,2 '-bis- (4-trifluoromethyl) phenyl) - [6, 6' -dipyrrolo [2,3-d]Thiazolyl idene group]5,5’(4H,4H’) -diketones
Under argon atmosphere Lawson's reagent (38.8 mg, 9.7 × 10)-2mmol) was added to a toluene solution (5 m L) of compound 40 (0.1 g, 0.19 mmol) and the reaction was carried out at 60 ℃ for 3-4 h, after completion of the reaction, the product system was directly concentrated to remove the high boiling solvent toluene, and the sample was stirred and separated by column chromatography (petroleum ether/ethyl acetate = 20: 1) to give compound 41 (80.3 g) as a blue solid in 83.4% yield.
Example 4
Preparation of ethyl 2- ((2-octyldodecane) (2- (pentafluoro-benzene) thiazol-4-yl) amino) -2-oxoacetate
To a 100m L stoppered tube was added compounds 17a, 17b (2.50 g, 4.47 mmol), trimethyl (pentafluorobenzene) stannane (2.2 g, 6.70 mmol), Pd (PPh) at room temperature3)4(0.52 g, 0.45 mmol), CuI (0.17 g, 0.89 mmol) and N, N-dimethylformamide (10m L). before the reaction starts, argon is introduced for 20 min by means of an argon ball to remove air in a sealed tube, the reaction is carried out for 20-24 h at the temperature of 90 ℃, after the reaction is finished and the temperature is returned to the room temperature, saturated NH is added4Quenching the reaction with Cl solution, extracting the organic phase with ethyl acetate and washing the organic phase with saturated saline solution, drying, removing the organic solvent from the product system by distillation under reduced pressure, and performing column chromatography (petroleum ether/ethyl acetate = 30: 1) to obtain the final productN-Alkylated products andO1.63 g of a pale yellow oily liquid constituted by the alkylation product, with a yield of 56.5%.
Preparation of 4- (2-octyldodecane) -2- (pentafluorobenzene) -4H-pyrrolo [2,3-d]Thiazole-5, 6-diones
Adding a binary solvent consisting of tetrahydrofuran (13 m L) and methanol (8.5 m L) to the mixture of compounds 42a and 42b (0 deg.C)1.63 g, 2.52 mmol) of 100m L round-bottomed flask and dissolving, dissolving L iOH solid (0.18 g, 7.56 mmol) in water sufficiently and adding dropwise into the reaction flask, controlling the reaction time to be 20-30min, after the reaction is finished, naturally returning the product system to room temperature, adjusting the pH of the reaction solution to 5-6 by hydrochloric acid solution, then adding ethyl acetate and saturated saline water to extract and wash the organic phase respectively, and anhydrous MgSO4Drying, filtering organic phase, removing organic solvent under reduced pressure distillation to obtain yellow hydrolysate, drying hydrolysate, dissolving in anhydrous tetrahydrofuran solvent (10m L), adding thionyl chloride reagent (1.4 m L, 20.2 mmol) dropwise into the reaction system at 0 deg.C under the protection of argon gas, gradually darkening the reaction solution with the reaction time, standing overnight, and adding small amount of saturated NH4The reaction was quenched with Cl solution, extracted with dichloromethane, washed with saturated brine, dried over anhydrous MgSO4, concentrated, and isolated by flash column chromatography (petroleum ether/ethyl acetate = 10: 1) to give compound 44 (0.92 g) as a red solid in 60.6% yield.
Preparation of (trans) -4,4 ' -bis (2-octyldodecane) -2,2 ' -bis (pentafluorobenzene) - [6,6 ' -dipyrrolo [2,3-d]Thiazolyl idene group]-5,5’(4H,4’H) -diketones
Lawson's reagent (0.31 g, 0.77 mmol) is added to a toluene solution (15 m L) of compound 44 (0.92 g, 1.53 mmol) at room temperature under argon protection, the reaction is carried out at 60 ℃ for 3-4 h, after the reaction is finished, the product system is directly concentrated, the high boiling point solvent toluene is removed, the sample is stirred, and blue solid compound 45 (0.73 g) is separated by column chromatography (petroleum ether/ethyl acetate = 20: 1) with the yield of 80.8%.
Example 5
Preparation of 4-chlorobenzo [2 ]d]Thiazole-5-amides
Compound 13 (0.15 g,1 mmol) was dissolved in dry tetrahydrofuran in a 100m L flaskPlacing a condensing reflux device above the reaction bottle, adding N-chlorosuccinimide (0.13 g, 0.1 mmol) in batches under argon atmosphere, reacting at 70 deg.C for about 1 h, and after the reaction is finished and the temperature is returned to room temperature, adding saturated NH4The reaction was quenched with Cl solution, the organic phase was extracted with dichloromethane, washed with saturated brine, anhydrous MgSO4Drying, concentration and column chromatography (petroleum ether/ethyl acetate = 3: 1) gave compound 46 (0.15 g) as a yellow oil in 83% yield.
2- ((4-chlorobenzo 2 [ ]d]Thiazol-5-yl) amino) -2-oxoacetic acid ethyl ester
Compound 46 (0.15 g), 15 m L dry tetrahydrofuran were added to a 100ml reaction flask, cooled in an ice bath and then DIPEA (0.16 g, 1.2 mmol), oxalyl chloride monoethyl ester (0.17 g, 1.2 mmol) and reacted for 10-20 min, saturated NH was added4The reaction was quenched with Cl solution. Extracting with ethyl acetate, washing with water, washing with saturated saline solution, and anhydrous MgSO4Drying, concentration and flash column chromatography (petroleum ether/ethyl acetate = 3: 1) gave 47 (0.18 g) as a pale yellow oil in 77% yield.
Preparation of 2- ((4-chlorobenzo 2 [ ]d]-Thiazol-5-yl) (2-octyldodecane) amino) -2-oxoacetic acid ethyl ester
9- (bromomethyl) nonadecane (0.40 g, 1.1 mmol), K, was added at room temperature2CO3(0.15 g, 1.1 mmol) were added to a solution of Compound 47 (0.21 g, 0.74 mmol) in N, N-dimethylformamide (10m L), the reaction was carried out at 100 ℃ for 4-5 h, the temperature was returned to room temperature, and saturated NH was added4The reaction was quenched with Cl solution, and the organic phase was extracted and washed with ethyl acetate and saturated brine, respectively, dried, and the organic solvent in the product system was removed by distillation under reduced pressure, and column chromatography (petroleum ether/ethyl acetate = 10: 1) gave compound 48 (0.28 g) as a yellow oily liquid in a yield of 68%.
Preparation of 4-chloro-5- (2-octyldodecane) -5H-a thiazole [5,4,f]-indole-6, 7-diones
To a 100m L flask, under argon atmosphere, was added the above compound 48 (0.28 g, 0.50 mmol) dried tetrakisTetrahydrofuran (10m L) was dissolved, cooled in an ice bath, and then SOCl was added dropwise2(0.1 m L, 1.4 mmol), the ice bath was removed, the temperature was increased overnight, saturated NH was added4The reaction was quenched with Cl solution. Extracting with ethyl acetate, washing with water, washing with saturated saline solution, and anhydrous MgSO4And (5) drying. The organic phase was concentrated and isolated by flash column chromatography (petroleum ether/ethyl acetate = 10: 1) to give 50 as a reddish brown solid, 0.16 g, 62% yield.
Preparation of (trans) -4,4 ' -dichloro-5, 5 ' -bis (2-octyldodecane) - [6,6 ' -dithiazole [5,4-f]Indolyl radical]-7,7 '(5H, 5' H) -dione
Lawson's reagent (61.9 mg, 0.15 mmol) was added to a toluene solution (10m L) of compound 49 (0.16 g, 0.31 mmol) under argon atmosphere, the reaction was carried out at 60 ℃ for 3-4 h, after the reaction was completed, the product system was directly concentrated, the high boiling point solvent toluene was removed, the sample was stirred, and separated by column chromatography (petroleum ether/ethyl acetate = 20: 1) to obtain compound 51 (0.14 g) as a blue solid with a yield of 91%.
Example 6
Preparation of 5-chloroquinolin-6-amine
Dissolving compound 20 (1.00 g, 6.89 mmol) in dry tetrahydrofuran in a reaction bottle of 100m L, placing a condensing reflux device above the reaction bottle, adding N-chlorosuccinimide (0.92 g, 6.89 mmol) in batches under argon atmosphere, reacting at 70 deg.C for about 1 h, and after the reaction is finished and the temperature is returned to room temperature, using saturated NH4The reaction was quenched with Cl solution, the organic phase was extracted with dichloromethane, washed with saturated brine, anhydrous MgSO4Drying, concentration and column chromatography (petroleum ether/ethyl acetate = 3: 1) gave compound 21 (0.98 g) as a yellow oil in 79.5% yield.
Preparation of ethyl 2- ((5-chloroquinolin-6-yl) amino) -2-oxoacetate
To a 100ml reaction flask was added compound 21 (0.98 g, 5.46 mmol), 15 m L dry tetrakisAfter cooling with an ice bath, DIPEA (1.06 g, 8.18 mmol) and oxalyl chloride monoethyl ester (1.12 g, 8.18 mmol) were added dropwise, and the reaction was carried out for 10-20 min. Adding saturated NH4The reaction was quenched with Cl solution. Extracting with ethyl acetate, washing with water, washing with saturated saline solution, and anhydrous MgSO4Drying, concentration and flash column chromatography (petroleum ether/ethyl acetate = 3: 1) gave compound 22 (1.11 g) as a pale yellow oil in 72.6% yield.
Preparation of ethyl 2- ((5-chloroquinolin-6-yl) (2-octyldodecane) amino) -2-oxoacetate
9- (bromomethyl) nonadecane (2.87 g, 7.94 mmol), K, was added at room temperature2CO3(1.10 g, 7.94 mmol) were added to a solution of Compound 22 (1.11 g, 3.97 mmol) in N, N-dimethylformamide (10m L), the reaction was carried out at 100 ℃ for 4-5 h, the temperature was returned to room temperature, and saturated NH was added4The reaction was quenched with Cl solution, and the organic phase was extracted and washed with ethyl acetate and saturated brine, respectively, dried, and the organic solvent in the product system was removed by distillation under reduced pressure, and column chromatography (petroleum ether/ethyl acetate = 10: 1) gave compound 23a (1.39 g) as a yellow oily liquid with a yield of 62.4%.
Preparation of 5-chloro-6- (2-octyldodecane) -6H-pyrrolo [2,3-g]Quinoline-7, 8-diones
Adding binary solvent composed of tetrahydrofuran (10m L) and methanol (7 m L) into 100m L round-bottom flask containing compound 23a (1.39 g, 2.48 mmol) at 0 deg.C, dissolving L iOH solid (0.18 g,7.44 mmol) in water, adding dropwise into the reaction flask, controlling reaction time at 20-30min, allowing the product system to naturally rise to room temperature, adjusting pH of the reaction solution to 5-6 with hydrochloric acid solution, adding ethyl acetate and saturated saline, extracting and washing organic phase, anhydrous MgSO, respectively4Drying, filtering the organic phase, removing the organic solvent under reduced pressure to obtain yellow hydrolyzate, drying the hydrolyzate thoroughly, adding anhydrous tetrahydrofuran solvent (10m L), dissolving, and adding thionyl chloride reagent (1.4 m L, 20.00) at 0 deg.C under protection of argonmmol) is added into the reaction system drop by drop, the color of the reaction solution gradually deepens along with the prolonging of the reaction time, and a small amount of saturated NH is added overnight4The reaction was quenched with Cl solution, extracted with dichloromethane, washed with saturated brine, anhydrous MgSO4Drying, concentration and flash column chromatography (petroleum ether/ethyl acetate = 10: 1) gave compound 25a (0.74 g) as a red solid in 58.3% yield.
Preparation of (trans) -5,5 ' -dichloro-6, 6 ' -bis (2-octyldodecane) - [8,8 ' -dipyrrolo [2,3-g]Quinolylidene radicals]-7,7’[6H,6’H]-diketones
Adding Lawson reagent (0.29 g, 0.72 mmol) into toluene solution (10m L) of compound 25a (0.74 g, 1.45 mmol) under argon atmosphere, reacting at 60 deg.C for 3-4 h, directly concentrating the product system after reaction, removing high boiling point solvent toluene, stirring, and separating by column chromatography (petroleum ether/ethyl acetate = 30: 1) to obtain blue solid compound 26a (0.62 g), yield 86.7%.
Claims (3)
1. The electron-deficient conjugated extended indigo compound and the preparation method thereof, the structural general formula of the isoindigo compound is shown as (I), (II) and (III):
wherein R is alkyl, benzyl, or other aromatic ring or aromatic heterocycle connected with the modified N atom through methylene; x can be an electron-deficient aromatic ring or an aromatic heterocycle such as thiazole, trifluorotoluene, pentafluorobenzene, 5-cyanothiazole and the like.
2. The electron-deficient and electron-deficient conjugated extended isoindigo compound and the synthesis method thereof are characterized in that any compound with the structural general formula can be synthesized according to acylation, coupling, reduction, oxamiding, hydrolysis, cyclization and polycondensation or the sequence of oxamiding, alkylation, coupling, hydrolysis, cyclization and polycondensation, only the reaction substrates are different, the specific synthesis method is shown as the routes (IV), (V), (VI) and (VII), the routes adopt the conventional organic synthesis reaction,
3. the compounds 8, 19, 26 according to claims 2-3 have the general structural formulae (I-1), (II-1) and (III-1):
it is characterized in that R is alkyl, modified or unmodified benzyl, and other aromatic rings or aromatic heterocycles which are connected with the modified N atom through methylene; x is selected from aromatic rings and aromatic heterocycles.
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