CN113735821A - Synthetic method of 3-substituted isothiocoumarin derivative - Google Patents

Synthetic method of 3-substituted isothiocoumarin derivative Download PDF

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CN113735821A
CN113735821A CN202110991266.7A CN202110991266A CN113735821A CN 113735821 A CN113735821 A CN 113735821A CN 202110991266 A CN202110991266 A CN 202110991266A CN 113735821 A CN113735821 A CN 113735821A
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CN113735821B (en
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张小红
张珠珠
张兴国
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Wenzhou University
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    • C07D335/00—Heterocyclic compounds containing six-membered rings having one sulfur atom as the only ring hetero atom
    • C07D335/04—Heterocyclic compounds containing six-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
    • C07D335/06—Benzothiopyrans; Hydrogenated benzothiopyrans
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    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D335/00—Heterocyclic compounds containing six-membered rings having one sulfur atom as the only ring hetero atom
    • C07D335/04—Heterocyclic compounds containing six-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
    • C07D335/08—Naphthothiopyrans; Hydrogenated naphthothiopyrans
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    • C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
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Abstract

The invention relates to a synthetic method of a 3-substituted isothiocoumarin derivative, which comprises the following steps: taking o-alkynyl oxime ether as a reaction substrate, sodium sulfide as a sulfur source, potassium carbonate as an alkali and N, N-dimethylformamide as a solvent, and reacting at 90 DEGoC stirred the reaction for 12-16 hours, after the reaction was complete, 1.2 mL of 1M HCl was added thereto and stirring was continued for 1 hour at room temperature. The method has the advantages of simple and easily obtained raw materials, relatively mild reaction conditions, wide substrate universality, novel preparation process, less pollution, low energy consumption and the like.

Description

Synthetic method of 3-substituted isothiocoumarin derivative
Technical Field
The invention relates to a preparation method of a 3-substituted isothiocoumarin derivative.
Background
The isothiocoumarin derivatives have a wide range of biological activities including anti-cancer, anti-trypanosomiasis (Eur. J. Med. Chem.2014, 7557-66), anti-inflammatory, anti-fertility, anti-allergic, insecticidal and photochemical activity. For example, isothiocoumarin-3-carboxylic acid and its sodium salt can inhibit the release of spasmodic agents and are useful in the treatment of asthma and allergic diseases (United State Patent number 3960892); in the evaluation of phytotoxic activity on exemplary arabidopsis seedling growth, isothiocoumarin derivatives were found to induce cell death in the root meristem and could be identified as potential herbicides: (ChemPlusChem. 2019, 84, 942-950). However, for the preparation of isothiocyanatesThe methods for daidzein-1-one are very limited and inadequate. With respect to the synthesis of isothiocoumarin, the isothiocoumarin skeleton has traditionally been constructed from highly volatile and malodorous carbon disulfide as a sulfur reagent(s) (ii)Yakugaku Zasshi. 1972, 92449 453) or by cyclization of o-toluamide with thiocarboxylate in the presence of a strong baseSynthesis, 1990, 12, 1133-1134). Alternatively, they are prepared by a multi-stage reaction starting from 2-arylethanol, homo-or phthalate esters using toluenethiol, potassium thiocyanate or rhodanine as sulfur reagent(s) ((Tetrahedron, 2000, 56, 6763–6767; Chem Heterocycl Comp. 2009, 45, 1276–1278; Heterocycl. Com.2010, 46, 140-145). Recently, the Gabrile group developed microwave-assisted dithio-cycloisomerization of 2-alkynylbenzoic acids using Lawson's reagent, of which 5-endo-digOr 6-endo-digCyclization is strongly dependent on the electronic nature of the alkyne, with poor regioselectivity.
The above method has the disadvantages of multi-step reaction, low economy, low yield, etc. Therefore, there is a great need to find general and simple methods to construct isothiocoumarin backbones with good regioselectivity and atom economy from readily available, tasteless and safe sulfur sources. Based on the reaction, the invention provides a novel method for synthesizing the isothiocoumarin derivative, which has the advantages of wide substrate application range, easily obtained raw materials, safety and no pollution.
Disclosure of Invention
Aiming at the defects existing in the prior stage, the invention provides a synthetic method of a 3-substituted isothiocoumarin derivative, which takes ortho-alkynyl oxime ether and sulfide as reaction raw materials, and has the advantages of simple technical process, high yield, less pollution, environmental protection and safety.
In order to achieve the purpose, the invention adopts the technical scheme that:
a synthetic method of a 3-substituted isothiocoumarin derivative comprises the following steps: taking o-alkynyl oxime ether as a reaction substrate, sodium sulfide as a sulfur source, potassium phosphate, cesium carbonate, potassium carbonate, 1, 8-diazabicycloundecen-7-ene or tetramethylethylenediamine as alkali, and N-methylpyrrolidone, N-dimethylacetamide, N-dimethylformamide or dimethylsulfoxide as a solvent in a solvent of 90-120oC, stirring and reacting for 12-16 hours, adding 1.2 mL of 1M HCl into the mixture after the reaction is finished, and continuously stirring the mixture at room temperature for 1 hour, wherein the chemical reaction formula is as follows:
Figure 71571DEST_PATH_IMAGE001
the-R is one of phenyl, 4-methylphenyl, 3-methylphenyl, 2-methylphenyl, 4-ethylphenyl, 4-tert-butylphenyl, 4-methoxyphenyl, 4-fluorophenyl, 4-chlorophenyl, 2-chlorophenyl, 4-bromophenyl, 4-trifluoromethylphenyl, n-butyl, cyclopropyl, 2-thienyl and 3-pyridyl;
the-R' is 4-methylphenyl, 5-methylphenyl, 4-methoxyphenyl, 5-methoxyphenyl, 4-fluorophenyl, 4-chlorophenyl, 5-trifluoromethylphenyl, benzo [ b ], [2 ]d][1,3]One of dioxolane, thiophene and 2-naphthyl; wherein the benzo [ b ], [d][1,3]The dioxolane has the formula:
Figure 936758DEST_PATH_IMAGE002
the expression of thiophene is:
Figure 544457DEST_PATH_IMAGE003
the expression of 2-naphthyl is:
Figure 127885DEST_PATH_IMAGE004
。
the preparation method adopted by the invention is that the isothiocoumarin derivative is synthesized by the reaction of the o-alkynyl oxime ether and the sodium sulfide under the promotion of alkali, the process is simple, no special instrument or mode is needed, the method is very suitable for the operation of people in the field, and the method has the advantages of simple operation, easy product obtaining and the like.
In a further embodiment of the present invention, the base is potassium carbonate.
In a further embodiment of the present invention, the solvent is N, N-dimethylformamide.
The method can directly synthesize the target product, does not need to separate intermediate products, can obtain the target product only by stirring and reacting under normal pressure, has the highest yield of 84 percent, greatly simplifies process engineering, reduces energy consumption and has excellent yield; in addition, the waste solution is less in the reaction process, and other polluted gases and liquid are not discharged, so that the method reduces the discharge of the waste solution, and has the advantages of protecting the environment and ensuring the health of operators; in addition, a series of isothiocoumarin derivatives can be prepared, and the method has good substrate universality. Therefore, the invention fills the blank of the method for preparing the isothiocoumarin derivative at the present stage, promotes the development of sulfur-containing heterocyclic organisms and provides a powerful guarantee for developing the medicine containing the isothiocoumarin derivative.
The mechanism of the invention is as follows: first, S2-Attack the carbon-carbon triple bond to obtain an anion A, and the anion A passes through the intramolecular6-endo-digCyclization produces the dianion B. The dianion B is selected from H2O abstracts hydrogen to obtain an intermediate C, which is then eliminated under alkaline conditions to obtain the key imine D with loss of CH3And (5) OH. Finally, imine D is hydrolyzed to provide isothiocoumarin derivatives. Possible reaction mechanisms the chemical reaction formula is as follows:
Figure 377601DEST_PATH_IMAGE005
Detailed Description
The invention discloses a synthesis method of a 3-substituted isothiocoumarin derivative, which comprises the steps of taking alkynyl oxime ether as a reaction substrate, taking sodium sulfide as a sulfur source, taking potassium phosphate, cesium carbonate, potassium carbonate, 1, 8-diazabicycloundecen-7-ene or tetramethylethylenediamine as an alkali, taking N-methylpyrrolidone, N-dimethylacetamide, N-dimethylformamide or dimethyl sulfoxide as a solvent, and dissolving the solvent in 90-120oC, stirring and reacting for 12-16 hours, adding 1.2 mL of 1M HCl into the mixture after the reaction is finished, and continuously stirring the mixture at room temperature for 1 hour, wherein the chemical reaction formula is as follows:
Figure 362875DEST_PATH_IMAGE001
the-R is one of phenyl, 4-methylphenyl, 3-methylphenyl, 2-methylphenyl, 4-ethylphenyl, 4-tert-butylphenyl, 4-methoxyphenyl, 4-fluorophenyl, 4-chlorophenyl, 2-chlorophenyl, 4-bromophenyl, 4-trifluoromethylphenyl, n-butyl, cyclopropyl, 2-thienyl and 3-pyridyl;
the-R' is 4-methylphenyl, 5-methylphenyl, 4-methoxyphenyl, 5-methoxyphenyl, 4-fluorophenyl, 4-chlorophenyl, 5-trifluoromethylphenyl, benzo [ b ], [2 ]d][1,3]Dioxolane (a)
Figure 266109DEST_PATH_IMAGE002
) Thiophene (a), (b), (c), (d) and a)
Figure 336833DEST_PATH_IMAGE003
) 2-naphthyl group(s) ((s))
Figure 390239DEST_PATH_IMAGE004
) One kind of (1).
After the reaction, filtration was performed, the filtrate was washed with a saturated sodium chloride solution, extracted with ethyl acetate and dried over anhydrous sodium sulfate, and the combined organic layers were subjected to rotary evaporation using a rotary evaporator to remove the solvent to obtain a residue. Eluting the residue with silica gel column with eluent prepared from ethyl acetate and petroleum ether at volume ratio (v: v), collecting eluate according to actual gradient, detecting by TLC, mixing eluates containing target product, removing solvent by rotary evaporator, and vacuum drying to obtain target product.
The first embodiment is as follows: 47.0 mg (0.2 mmol) of 2- (phenylethynyl) benzaldehyde o-methyloxime, 23.4 mg (0.3 mmol) of sodium sulfide and 55.2 mg (0.4 mmol) of potassium carbonate are added to 2 ml of solvent N, N-dimethylformamide. At 90oAfter stirring the reaction at C for 12 hours, 1.2 mL of 1M HCl was added thereto and stirring was continued at room temperature for 1 hour. After the reaction, the reaction solution was filtered to obtain a filtrate and washed with a saturated sodium chloride solution, extracted with ethyl acetate and dried over anhydrous sodium sulfate, and the filtrate was subjected to solvent removal with a rotary evaporator to obtain a residue, which remainedEluting the extract by a silica gel column with an eluent prepared from ethyl acetate and petroleum ether according to the volume ratio of 1:30, collecting the effluent according to the actual gradient, detecting by TLC, combining the effluent containing the target product, removing the solvent by rotating the combined effluent by a rotary evaporator, and drying in vacuum to obtain 40.1 mg of yellow solid 3-phenylisothiocoumarin with the yield of 84%.1H NMR (500 MHz, CDCl3) δ 8.31 (d, J = 8.0 Hz, 1H), 7.76 – 7.72 (m, 1H), 7.64 – 7.62 (m, 3H), 7.58 – 7.55 (m, 1H), 7.49 – 7.42 (m, 3H), 7.38 (s, 1H); 13C{1H} NMR (125 MHz, CDCl3) δ 187.3, 140.2, 138.5, 137.0, 134.0, 130.7, 129.5, 129.1, 128.7, 127.2, 126.7, 125.8, 119.2。
The second embodiment is as follows: 49.8 mg (0.2 mmol) of 2- (p-tolylethynyl) benzaldehyde o-methyloxime, 23.4 mg (0.3 mmol) of sodium sulfide and 55.2 mg (0.4 mmol) of potassium carbonate are added to 2 ml of solvent N, N-dimethylformamide. At 90oAfter stirring the reaction at C for 12 hours, 1.2 mL of 1M HCl was added thereto and stirring was continued at room temperature for 1 hour. After the reaction is finished, filtering the reaction liquid to obtain a filtrate, washing the filtrate with a saturated sodium chloride solution, extracting with ethyl acetate, drying with anhydrous sodium sulfate, removing the solvent from the filtrate with a rotary evaporator to obtain a residue, eluting the residue with an eluent prepared from ethyl acetate and petroleum ether according to the volume ratio of 1:30 through a silica gel column, collecting the effluent according to an actual gradient, detecting by TLC, combining the effluent containing the target product, removing the solvent from the combined effluent by rotating the rotary evaporator, and drying in vacuum to obtain 38.4 mg of yellow solid 3- (p-tolyl) isothiocoumarin with the yield of 76%.1H NMR (500 MHz, CDCl3) δ 8.21 (d, J = 8.0 Hz, 1H), 7.66 – 7.62 (m, 1H), 7.53 (d, J = 7.5 Hz, 1H), 7.47 – 7.43 (m, 3H), 7.27 (s, 1H), 7.19 (d, J = 7.5 Hz, 2H), 2.33 (s, 3H) ); 13C{1H} NMR (125 MHz, CDCl3) δ 187.6, 140.4, 139.9, 138.8, 134.3, 134.1, 130.7, 129.9, 128.6, 127.3, 126.7, 125.9, 118.6, 21.4。
The third concrete embodiment: 49.8 mg (0.2 mmol) of 2- (m-tolylethynyl) benzaldehyde o-methyloxime,23.4 mg (0.3 mmol) of sodium sulfide and 55.2 mg (0.4 mmol) of potassium carbonate are added to 2 ml of N, N-dimethylformamide as a solvent. At 90oAfter stirring the reaction at C for 12 hours, 1.2 mL of 1M HCl was added thereto and stirring was continued at room temperature for 1 hour. After the reaction is finished, filtering the reaction liquid to obtain a filtrate, washing the filtrate by using a saturated sodium chloride solution, extracting by using ethyl acetate, drying the filtrate by using anhydrous sodium sulfate, removing the solvent from the filtrate by using a rotary evaporator to obtain a residue, eluting the residue by using a silica gel column by using an eluent prepared from ethyl acetate and petroleum ether according to the volume ratio of 1:30, collecting the effluent according to an actual gradient, detecting by using TLC (thin layer chromatography), combining the effluent containing the target product, rotatably removing the solvent from the combined effluent by using the rotary evaporator, and drying in vacuum to obtain 33.8 mg of yellow solid 3- (m-tolyl) isothiocoumarin with the yield of 67%.1H NMR (400 MHz, CDCl3) δ 8.31 (d, J = 8.0 Hz, 1H), 7.76 – 7.71 (m, 1H), 7.63 (d, J = 8.0 Hz, 1H), 7.58 – 7.54 (m, 1H), 7.45 – 7.43 (m, 2H), 7.38 – 7.35 (m, 2H), 7.27 – 7.25 (m, 1H), 2.45 (s, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ 187.4, 140.4, 139.0, 138.6, 137.0, 134.0, 130.7, 130.4, 129.1, 128.6, 127.4, 127.2, 125.8, 123.9, 119.0, 21.5。
The fourth concrete embodiment: 49.8 mg (0.2 mmol) of 2- (o-tolylethynyl) benzaldehyde o-methyloxime, 23.4 mg (0.3 mmol) of sodium sulfide and 55.2 mg (0.4 mmol) of potassium carbonate are added to 2 ml of solvent N, N-dimethylformamide. At 90oAfter stirring the reaction at C for 12 hours, 1.2 mL of 1M HCl was added thereto and stirring was continued at room temperature for 1 hour. After the reaction is finished, filtering the reaction liquid to obtain a filtrate, washing the filtrate with a saturated sodium chloride solution, extracting with ethyl acetate, drying with anhydrous sodium sulfate, removing the solvent from the filtrate with a rotary evaporator to obtain a residue, eluting the residue with an eluent prepared from ethyl acetate and petroleum ether according to the volume ratio of 1:30 through a silica gel column, collecting the effluent according to an actual gradient, detecting by TLC, combining the effluent containing the target product, removing the solvent from the combined effluent by rotating the rotary evaporator, and drying in vacuum to obtain 28.2 mg of yellow solid 3- (o-tolyl) isothiocoumarin with the yield of 56%.1H NMR (400 MHz, CDCl3) δ 8.34 (d, J = 7.6 Hz, 1H), 7.74 – 7.72 (m, 1H), 7.59 – 7.57 (m, 2H), 7.34 – 7.26 (m, 4H), 7.06 (d, J = 2.8 Hz, 1H), 2.40 (s, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ 187.8, 140.6, 138.4, 136.9, 136.5, 134.0, 130.9, 130.5, 129.9, 129.4, 128.9, 127.3, 126.3, 125.9, 121.7, 20.2。
The fifth concrete embodiment: 52.6 mg (0.2 mmol) of 2- ((4-ethylphenyl) ethynyl) benzaldehyde o-methyloxime, 23.4 mg (0.3 mmol) of sodium sulfide and 55.2 mg (0.4 mmol) of potassium carbonate are added to 2 ml of solvent N, N-dimethylformamide. At 90oAfter stirring the reaction at C for 12 hours, 1.2 mL of 1M HCl was added thereto and stirring was continued at room temperature for 1 hour. After the reaction is finished, filtering the reaction liquid to obtain a filtrate, washing the filtrate with a saturated sodium chloride solution, extracting with ethyl acetate, drying with anhydrous sodium sulfate, removing the solvent from the filtrate with a rotary evaporator to obtain a residue, eluting the residue with an eluent prepared from ethyl acetate and petroleum ether according to the volume ratio of 1:30 through a silica gel column, collecting the effluent according to the actual gradient, detecting by TLC, combining the effluent containing the target product, removing the solvent from the combined effluent by rotating the rotary evaporator, and drying in vacuum to obtain 40.0 mg of yellow oil drop 3- (4-ethyl phenyl) isothiocoumarin with the yield of 75%.1H NMR (500 MHz, CDCl3) δ 8.29 (d, J= 8.0 Hz, 1H), 7.73 – 7.70 (m, 1H), 7.61 (d, J = 8.0 Hz, 1H), 7.55 – 7.51 (m, 3H), 7.35 (s, 1H), 7.29 (d, J = 8.0 Hz, 2H), 2.70 (q, J = 7.5 Hz, 2H), 1.28 (t, J = 7.5 Hz, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ 187.5, 146.1, 140.4, 138.7, 134.5, 134.0, 130.7, 128.7, 128.6, 127.3, 126.7, 125.8, 118.6, 28.7, 15.5。
The sixth specific embodiment: 58.2 mg (0.2 mmol) of 2- ((4- (tert-butyl) phenyl) ethynyl) benzaldehyde o-methyloxime, 23.4 mg (0.3 mmol) of sodium sulfide and 55.2 mg (0.4 mmol) of potassium carbonate are added to 2 ml of solvent N, N-dimethylformamide. At 90oAfter stirring the reaction at C for 12 hours, 1.2 mL of 1M HCl was added thereto and stirring was continued at room temperature for 1 hour. After the reaction is finished, the reaction solution is filteredFiltering to obtain filtrate, washing with saturated sodium chloride solution, extracting with ethyl acetate, drying with anhydrous sodium sulfate, removing solvent from the filtrate with a rotary evaporator to obtain residue, eluting the residue with silica gel column with eluent prepared from ethyl acetate and petroleum ether according to the volume ratio of 1:30, collecting effluent according to actual gradient, detecting by TLC, combining the effluent containing the target product, removing solvent from the combined effluent by rotating with the rotary evaporator, and drying under vacuum to obtain 48.6 mg of yellow oil drop 3- (4- (tert-butyl) phenyl) isothiocoumarin with the yield of 83%.1H NMR (500 MHz, CDCl3) δ 8.30 (d, J = 8.0 Hz, 1H), 7.72 (t, J = 7.0 Hz, 1H), 7.63 (d, J = 8.0 Hz, 1H), 7.58 – 7.53 (m, 3H), 7.49 (d, J = 8.5 Hz, 2H), 7.37 (s, 1H), 1.36 (s, 9H); 13C{1H} NMR (125 MHz, CDCl3) δ 187.4, 152.9, 140.2, 138.6, 134.2, 133.9, 130.6, 128.5, 127.2, 126.4, 126.1, 125.8, 118.5, 34.8, 31.2。
The seventh specific embodiment: 53.0 mg (0.2 mmol) of 2- ((4-methoxyphenyl) ethynyl) benzaldehyde o-methyloxime, 23.4 mg (0.3 mmol) of sodium sulfide and 55.2 mg (0.4 mmol) of potassium carbonate are added to 2 ml of the solvent N, N-dimethylformamide. At 90oAfter stirring the reaction at C for 12 hours, 1.2 mL of 1M HCl was added thereto and stirring was continued at room temperature for 1 hour. After the reaction is finished, filtering the reaction liquid to obtain filtrate, washing the filtrate by using saturated sodium chloride solution, extracting by using ethyl acetate, drying the filtrate by using anhydrous sodium sulfate, removing the solvent from the filtrate by using a rotary evaporator to obtain a residue, eluting the residue by using silica gel column by using eluent prepared by using ethyl acetate and petroleum ether according to the volume ratio of 1:30, collecting effluent according to actual gradient, detecting by TLC (thin layer chromatography), combining the effluent containing a target product, removing the solvent from the combined effluent by using the rotary evaporator in a rotating way, and drying in vacuum to obtain 31.1 mg of yellow solid 3- (4-methoxyphenyl) isothiocoumarin with the yield of 58%.1H NMR (400 MHz, CDCl3) δ 8.28 (d, J = 7.6 Hz, 1H), 7.71 (s, 1H), 7.61 – 7.52 (m, 4H), 7.29 (s, 1H), 6.98 (d, J = 7.6 Hz, 2H), 3.86 (s, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ 187.5, 160.9, 140.2, 138.9, 134.1, 130.6, 129.7, 128.4, 128.1, 127.2, 125.9, 118.0, 114.7, 55.6。
The eighth embodiment: 50.6 mg (0.2 mmol) of 2- ((4-fluorophenyl) ethynyl) benzaldehyde o-methyloxime, 23.4 mg (0.3 mmol) of sodium sulfide and 55.2 mg (0.4 mmol) of potassium carbonate are added to 2 ml of the solvent N, N-dimethylformamide. At 90oAfter stirring the reaction at C for 12 hours, 1.2 mL of 1M HCl was added thereto and stirring was continued at room temperature for 1 hour. After the reaction is finished, filtering the reaction liquid to obtain a filtrate, washing the filtrate with a saturated sodium chloride solution, extracting with ethyl acetate, drying with anhydrous sodium sulfate, removing the solvent from the filtrate with a rotary evaporator to obtain a residue, eluting the residue with an eluent prepared from ethyl acetate and petroleum ether according to the volume ratio of 1:30 through a silica gel column, collecting the effluent according to the actual gradient, detecting by TLC, combining the effluent containing the target product, removing the solvent from the combined effluent by rotating the rotary evaporator, and drying in vacuum to obtain 33.3 mg of yellow solid 3- (4-fluorophenyl) isothiocoumarin with the yield of 65%.1H NMR (400 MHz, CDCl3) δ 8.29 (d, J = 8.0 Hz, 1H), 7.73 (t, J = 8.0 Hz, 1H), 7.62 – 7.53 (m, 4H), 7.31 (s, 1H), 7.15 (t, J = 8.8 Hz, 2H); 13C{1H} NMR (125 MHz, CDCl3) δ 187.0, 163.6 (d, J C-F = 248.8 Hz), 139.2, 138.5, 134.2, 133.4, 130.8, 128.9, 128.7, 127.3, 126.0, 119.3, 116.3 (d, J C-F = 22.5 Hz); 19F NMR (470 MHz, CDCl3) δ -111.28 (s, 1F)。
The specific embodiment is nine: 53.8 mg (0.2 mmol) of 2- ((4-chlorophenyl) ethynyl) benzaldehyde o-methyloxime, 23.4 mg (0.3 mmol) of sodium sulfide and 55.2 mg (0.4 mmol) of potassium carbonate are added to 2 ml of solvent N, N-dimethylformamide. At 90oAfter stirring the reaction at C for 12 hours, 1.2 mL of 1M HCl was added thereto and stirring was continued at room temperature for 1 hour. After the reaction is finished, filtering the reaction solution to obtain filtrate, washing the filtrate by using saturated sodium chloride solution, extracting by using ethyl acetate, drying the ethyl acetate by using anhydrous sodium sulfate, removing the solvent from the filtrate by using a rotary evaporator to obtain residue, and enabling the residue to pass through a silica gel column, and washing the residue by using ethyl acetate and petroleum ether according to the volume ratio of 1:30Eluting the solution, collecting the effluent according to the actual gradient, detecting by TLC, combining the effluent containing the target product, removing the solvent by rotating the combined effluent by a rotary evaporator, and drying in vacuum to obtain 37.6 mg of yellow solid 3- (4-chlorophenyl) isothiocoumarin with the yield of 69 percent.1H NMR (400 MHz, CDCl3) δ 8.30 (d, J = 8.0 Hz, 1H), 7.76 – 7.72 (m, 1H), 7.63 (d, J = 8.0 Hz, 1H), 7.59 – 7.55 (m, 3H), 7.44 (d, J = 8.4 Hz, 2H), 7.35 (s, 1H); 13C{1H} NMR (125 MHz, CDCl3) δ 186.9, 139.0, 138.4, 135.8, 135.6, 134.2, 130.8, 129.5, 129.1, 128.1, 127.3, 126.0, 119.5。
The specific embodiment ten: 53.8 mg (0.2 mmol) of 2- ((2-chlorophenyl) ethynyl) benzaldehyde o-methyloxime, 23.4 mg (0.3 mmol) of sodium sulfide and 55.2 mg (0.4 mmol) of potassium carbonate are added to 2 ml of solvent N, N-dimethylformamide. At 90oAfter stirring the reaction at C for 12 hours, 1.2 mL of 1M HCl was added thereto and stirring was continued at room temperature for 1 hour. After the reaction is finished, filtering the reaction liquid to obtain filtrate, washing the filtrate by using saturated sodium chloride solution, extracting by using ethyl acetate, drying the filtrate by using anhydrous sodium sulfate, removing the solvent from the filtrate by using a rotary evaporator to obtain a residue, eluting the residue by using silica gel column by using eluent prepared by using ethyl acetate and petroleum ether according to the volume ratio of 1:30, collecting effluent according to actual gradient, detecting by TLC (thin layer chromatography), combining the effluent containing a target product, removing the solvent from the combined effluent by using the rotary evaporator in a rotating way, and drying in vacuum to obtain 29.9 mg of yellow solid 3- (2-chlorophenyl) isothiocoumarin with the yield of 55%.1H NMR (500 MHz, CDCl3) δ 8.33 (d, J = 8.0 Hz, 1H), 7.76 – 7.73 (m, 1H), 7.61 – 7.58 (m, 2H), 7.49 (d, J = 7.5 Hz, 1H), 7.44 – 7.43 (m, 1H), 7.38 – 7.32 (m, 2H), 7.19 (s, 1H); 13C{1H} NMR (125 MHz, CDCl3) δ 187.3, 138.0, 137.6, 135.9, 134.1, 133.2, 131.5, 130.8, 130.6, 130.5, 129.2, 127.4, 127.2, 125.9, 123.0。
The first specific embodiment: 62.6 mg (0.2 mmol) of 2- ((4-bromophenyl) ethynyl) benzaldehyde o-methyloxime, 23.4 mg (0.3 mmol) of sodium sulfideAnd 55.2 mg (0.4 mmol) of potassium carbonate were added to 2 ml of N, N-dimethylformamide as a solvent. At 90oAfter stirring the reaction at C for 12 hours, 1.2 mL of 1M HCl was added thereto and stirring was continued at room temperature for 1 hour. After the reaction is finished, filtering the reaction liquid to obtain a filtrate, washing the filtrate with a saturated sodium chloride solution, extracting with ethyl acetate, drying with anhydrous sodium sulfate, removing the solvent from the filtrate with a rotary evaporator to obtain a residue, eluting the residue with an eluent prepared from ethyl acetate and petroleum ether according to the volume ratio of 1:30 through a silica gel column, collecting the effluent according to the actual gradient, detecting by TLC, combining the effluent containing the target product, removing the solvent from the combined effluent by rotating the rotary evaporator, and drying in vacuum to obtain 47.8 mg of yellow solid 3- (4-bromophenyl) isothiocoumarin with the yield of 76%.1H NMR (500 MHz, CDCl3) δ 8.30 (d, J = 8.0 Hz, 1H), 7.74 (t, J = 7.5 Hz, 1H), 7.64 – 7.56 (m, 4H), 7.50 – 7.48 (m, 2H), 7.36 (s, 1H); 13C{1H} NMR (125 MHz, CDCl3) δ 186.9, 139.1, 138.4, 136.1, 134.2, 132.5, 130.9, 129.1, 128.3, 127.4, 126.0, 124.0, 119.5。
The specific example twelve: 60.6 mg (0.2 mmol) of 2- ((4- (trifluoromethyl) phenyl) ethynyl) benzaldehyde o-methyloxime, 23.4 mg (0.3 mmol) of sodium sulfide and 55.2 mg (0.4 mmol) of potassium carbonate are added to 2 ml of solvent N, N-dimethylformamide. At 90oAfter stirring the reaction at C for 12 hours, 1.2 mL of 1M HCl was added thereto and stirring was continued at room temperature for 1 hour. After the reaction is finished, filtering the reaction liquid to obtain filtrate, washing the filtrate with saturated sodium chloride solution, extracting with ethyl acetate, drying with anhydrous sodium sulfate, removing the solvent from the filtrate with a rotary evaporator to obtain a residue, eluting the residue with an eluent prepared from ethyl acetate and petroleum ether according to the volume ratio of 1:30 through a silica gel column, collecting the effluent according to the actual gradient, detecting by TLC, combining the effluent containing the target product, removing the solvent from the combined effluent by rotating the rotary evaporator, and drying in vacuum to obtain 39.4 mg of yellow solid 3- (4-trifluoromethylphenyl) isothiocoumarin with the yield of 64%.1H NMR (500 MHz, CDCl3) δ 8.29 (d, J = 8.0 Hz, 1H), 7.77 – 7.70 (m, 5H), 7.64 (d, J = 8.0 Hz, 1H), 7.60 – 7.56 (m, 1H), 7.41 (s, 1H); 13C{1H} NMR (125 MHz, CDCl3) δ 186.5, 140.5, 138.5, 138.1, 134.3, 131.5 (q, J C-F = 32.5 Hz), 131.0, 129.4, 127.5, 127.2, 126.2, 126.0, 124.0 (q, J C-F = 270.0 Hz), 120.5; 19F NMR (470 MHz, CDCl3) δ -62.75 (s, 3F)。
The specific example thirteen: 43.6 mg (0.2 mmol) of 2- (hex-1-yn-1-yl) benzaldehyde o-methyloxime, 23.4 mg (0.3 mmol) of sodium sulfide and 55.2 mg (0.4 mmol) of potassium carbonate are added to 2 ml of solvent N, N-dimethylformamide. At 90oAfter stirring the reaction at C for 12 hours, 1.2 mL of 1M HCl was added thereto and stirring was continued at room temperature for 1 hour. After the reaction is finished, filtering the reaction solution to obtain a filtrate, washing the filtrate with a saturated sodium chloride solution, extracting with ethyl acetate, drying with anhydrous sodium sulfate, removing the solvent from the filtrate with a rotary evaporator to obtain a residue, eluting the residue with an eluent prepared from ethyl acetate and petroleum ether according to the volume ratio of 1:30 through a silica gel column, collecting the effluent according to the actual gradient, detecting by TLC, combining the effluent containing the target product, removing the solvent from the combined effluent by rotating the rotary evaporator, and drying in vacuum to obtain 32.9 mg of yellow oil drop 3-butyl isothiocoumarin with the yield of 75%.1H NMR (500 MHz, CDCl3) δ 8.23 (d, J = 8.5 Hz, 1H), 7.67 – 7.64 (m, 1H), 7.48 – 7.46 (m, 2H), 6.92 (s, 1H), 2.61 (t, J = 7.5 Hz, 2H), 1.69 – 1.63 (m, 2H), 1.43 – 1.36 (m, 2H), 0.94 (t, J = 7.5 Hz, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ 187.7, 142.7, 138.6, 133.8, 129.8, 128.0, 127.2, 125.7, 118.8, 36.8, 31.7, 22.1, 13.8。
The specific embodiment fourteen: 40.4 mg (0.2 mmol) of 2- (cyclopropylethynyl) benzaldehyde o-methyloxime, 23.4 mg (0.3 mmol) of sodium sulfide and 55.2 mg (0.4 mmol) of potassium carbonate are added to 2 ml of solvent N, N-dimethylformamide. At 90oAfter stirring the reaction at C for 12 hours, 1.2 mL of 1M HCl was added thereto and stirring was continued at room temperature for 1 hour. After the reaction, the reaction solution was filtered to obtain a filtrate, which was then washed with a saturated sodium chloride solutionExtracting with ethyl acetate, drying with anhydrous sodium sulfate, removing the solvent from the filtrate with a rotary evaporator to obtain a residue, eluting the residue with an eluent prepared from ethyl acetate and petroleum ether according to a volume ratio of 1:30 through a silica gel column, collecting the effluent according to an actual gradient, detecting by TLC, combining the effluent containing a target product, removing the solvent from the combined effluent by rotating the rotary evaporator, and drying in vacuum to obtain 24.6 mg of yellow oil drop 3-cyclopropyl isothiocoumarin with a yield of 61%.1H NMR (500 MHz, CDCl3) δ 8.22 (d, J = 8.0 Hz, 1H), 7.65 (t, J = 7.5 Hz, 1H), 7.48 – 7.46 (m, 2H), 6.92 (s, 1H), 1.94 (t, J= 7.5 Hz, 1H), 1.02 – 0.98 (m, 2H), 0.91 – 0.88 (m, 2H); 13C{1H} NMR (125 MHz, CDCl3) δ 187.5, 144.3, 138.7, 133.9, 129.8, 128.0, 127.5, 125.8, 117.4, 17.2, 8.1。
The specific embodiment fifteen: 48.2 mg (0.2 mmol) of 2- (thien-2-ylethynyl) benzaldehyde o-methyloxime, 23.4 mg (0.3 mmol) of sodium sulfide and 55.2 mg (0.4 mmol) of potassium carbonate are added to 2 ml of the solvent N, N-dimethylformamide. At 90oAfter stirring the reaction at C for 12 hours, 1.2 mL of 1M HCl was added thereto and stirring was continued at room temperature for 1 hour. After the reaction is finished, filtering the reaction liquid to obtain filtrate, washing the filtrate by using saturated sodium chloride solution, extracting by using ethyl acetate, drying the filtrate by using anhydrous sodium sulfate, removing the solvent from the filtrate by using a rotary evaporator to obtain a residue, eluting the residue by using silica gel column by using eluent prepared by using ethyl acetate and petroleum ether according to the volume ratio of 1:20, collecting effluent according to actual gradient, detecting by TLC (thin layer chromatography), combining the effluent containing a target product, removing the solvent from the combined effluent by using the rotary evaporator in a rotating way, and drying in vacuum to obtain 36.3 mg of yellow solid 3- (thiophene-2-yl) isothiocoumarin with the yield of 74%.1H NMR (500 MHz, CDCl3) δ 8.26 (d, J= 7.5 Hz, 1H), 7.72 – 7.69 (m, 1H), 7.58 (d, J = 8.0 Hz, 1H), 7.54 – 7.51 (m, 1H), 7.38 (d, J = 5.0 Hz, 1H), 7.35 (s, 1H), 7.33 (d, J = 4.0 Hz, 1H), 7.10 – 7.08 (m, 1H); 13C{1H} NMR (125 MHz, CDCl3) δ 186.4, 140.0, 138.5, 134.2, 133.5, 130.6, 128.7, 128.3, 127.5, 126.9, 126.1, 125.9, 117.9。
The specific embodiment is sixteen: 47.2 mg (0.2 mmol) of 2- (pyridin-3-ylethynyl) benzaldehyde o-methyloxime, 23.4 mg (0.3 mmol) of sodium sulfide and 55.2 mg (0.4 mmol) of potassium carbonate were added to 2 ml of a solvent, N-dimethylformamide. At 90oAfter stirring the reaction at C for 12 hours, 1.2 mL of 1M HCl was added thereto and stirring was continued at room temperature for 1 hour. After the reaction is finished, filtering the reaction liquid to obtain filtrate, washing the filtrate by using saturated sodium chloride solution, extracting by using ethyl acetate, drying the filtrate by using anhydrous sodium sulfate, removing the solvent from the filtrate by using a rotary evaporator to obtain a residue, eluting the residue by using silica gel column by using eluent prepared by using ethyl acetate and petroleum ether according to the volume ratio of 1:10, collecting effluent according to actual gradient, detecting by TLC (thin layer chromatography), combining the effluent containing a target product, removing the solvent from the combined effluent by using the rotary evaporator in a rotating way, and drying in vacuum to obtain 37.5 mg of yellow solid 3- (pyridine-3-yl) isothiocoumarin with the yield of 78%.1H NMR (500 MHz, CDCl3) δ 8.88 (d, J = 2.0 Hz, 1H), 8.66 – 8.65 (m, 1H), 8.29 (d, J = 8.0 Hz, 1H), 7.90 – 7.87 (m, 1H), 7.77 – 7.74 (m, 1H), 7.64 (d, J = 8.0 Hz, 1H), 7.60 – 7.56 (m, 1H), 7.41 – 7.38 (m, 2H); 13C{1H} NMR (125 MHz, CDCl3) δ 186.5, 150.5, 147.7, 138.1, 136.8, 134.3, 134.2, 133.1, 131.0, 129.4, 127.4, 126.0, 123.8, 120.4。
Specific example seventeen: 49.8 mg (0.2 mmol) of 4-methyl-2- (phenylethynyl) benzaldehyde o-methyloxime, 23.4 mg (0.3 mmol) of sodium sulfide and 55.2 mg (0.4 mmol) of potassium carbonate are added to 2 ml of solvent N, N-dimethylformamide. At 90oAfter stirring the reaction at C for 12 hours, 1.2 mL of 1M HCl was added thereto and stirring was continued at room temperature for 1 hour. After the reaction is finished, filtering the reaction solution to obtain filtrate, washing the filtrate with saturated sodium chloride solution, extracting with ethyl acetate, drying with anhydrous sodium sulfate, removing the solvent from the filtrate with a rotary evaporator to obtain residue, eluting the residue with an eluent prepared from ethyl acetate and petroleum ether according to the volume ratio of 1:30 through a silica gel column, collecting the effluent according to actual gradient, detecting by TLC, combining the effluent containing the ethyl acetate and the petroleum etherAnd (3) the effluent containing the target product, the combined effluent is rotated by a rotary evaporator to remove the solvent, and the solvent is dried in vacuum to obtain 36.3 mg of yellow solid 6-methyl-3-phenylisothiocoumarin with the yield of 72%.1H NMR (500 MHz, CDCl3) δ 8.19 (d, J = 8.0 Hz, 1H), 7.62 – 7.61 (m, 2H), 7.48 – 7.41 (m, 4H), 7.36 (d, J = 8.0 Hz, 1H), 7.31 (s, 1H), 2.50 (s, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ 187.1, 145.1, 140.4, 138.8, 137.3, 130.7, 130.2, 129.5, 129.2, 126.8, 126.0, 125.4, 119.3, 21.9。
The specific embodiment eighteen: 49.8 mg (0.2 mmol) of 5-methyl-2- (phenylethynyl) benzaldehyde o-methyloxime, 23.4 mg (0.3 mmol) of sodium sulfide and 55.2 mg (0.4 mmol) of potassium carbonate are added to 2 ml of solvent N, N-dimethylformamide. At 90oAfter stirring the reaction at C for 12 hours, 1.2 mL of 1M HCl was added thereto and stirring was continued at room temperature for 1 hour. After the reaction is finished, filtering the reaction liquid to obtain filtrate, washing the filtrate by using saturated sodium chloride solution, extracting by using ethyl acetate, drying the filtrate by using anhydrous sodium sulfate, removing the solvent from the filtrate by using a rotary evaporator to obtain a residue, eluting the residue by using silica gel column by using eluent prepared by using ethyl acetate and petroleum ether according to the volume ratio of 1:30, collecting effluent according to actual gradient, detecting by TLC (thin layer chromatography), combining the effluent containing a target product, removing the solvent from the combined effluent by using the rotary evaporator in a rotating way, and drying in vacuum to obtain 37.3 mg of yellow solid 7-methyl-3-phenylisothiocoumarin with the yield of 74%.1H NMR (500 MHz, CDCl3) δ 8.11 (s, 1H), 7.62 (d, J = 7.0 Hz, 2H), 7.56 – 7.52 (m, 2H), 7.47 – 7.42 (m, 3H), 7.35 (s, 1H), 2.50 (s, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ 187.6, 139.3, 139.0, 137.3, 136.3, 135.4, 130.8, 129.4, 129.2, 127.3, 126.8, 125.6, 119.2, 21.6。
The specific examples are nineteen: 53.0 mg (0.2 mmol) of 4-methoxy-2- (phenylethynyl) benzaldehyde o-methyloxime, 23.4 mg (0.3 mmol) of sodium sulfide and 55.2 mg (0.4 mmol) of potassium carbonate are added to 2 ml of the solvent N, N-dimethylformamide. At 90oAfter stirring the reaction at C for 12 hours, 1.2 mL of 1M was addedHCl was stirred at room temperature for 1 h. After the reaction is finished, filtering the reaction liquid to obtain filtrate, washing the filtrate with saturated sodium chloride solution, extracting with ethyl acetate, drying with anhydrous sodium sulfate, removing the solvent from the filtrate with a rotary evaporator to obtain a residue, eluting the residue with an eluent prepared from ethyl acetate and petroleum ether according to the volume ratio of 1:30 through a silica gel column, collecting the effluent according to the actual gradient, detecting by TLC, combining the effluent containing the target product, removing the solvent from the combined effluent by rotating the rotary evaporator, and drying in vacuum to obtain 33.2 mg of yellow solid 6-methoxy-3-phenylisothiocoumarin with the yield of 62%.1H NMR (500 MHz, CDCl3) δ 8.25 (d, J = 9.0 Hz, 1H), 7.62 (d, J = 7.0 Hz, 2H), 7.48 – 7.43 (m, 3H), 7.30 (s, 1H), 7.10 (d, J = 9.0 Hz, 1H), 7.00 (s, 1H), 3.94 (s, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ 186.1, 164.2, 141.5, 141.0, 137.3, 129.6, 129.2, 128.4, 126.9, 121.7, 119.3, 117.0, 112.6, 55.8。
The specific embodiment twenty: 53.0 mg (0.2 mmol) of 5-methoxy-2- (phenylethynyl) benzaldehyde o-methyloxime, 23.4 mg (0.3 mmol) of sodium sulfide and 55.2 mg (0.4 mmol) of potassium carbonate are added to 2 ml of the solvent N, N-dimethylformamide. At 90oAfter stirring the reaction at C for 12 hours, 1.2 mL of 1M HCl was added thereto and stirring was continued at room temperature for 1 hour. After the reaction is finished, filtering the reaction liquid to obtain filtrate, washing the filtrate with saturated sodium chloride solution, extracting with ethyl acetate, drying with anhydrous sodium sulfate, removing the solvent from the filtrate with a rotary evaporator to obtain a residue, eluting the residue with an eluent prepared from ethyl acetate and petroleum ether according to the volume ratio of 1:30 through a silica gel column, collecting the effluent according to the actual gradient, detecting by TLC, combining the effluent containing the target product, removing the solvent from the combined effluent by rotating the rotary evaporator, and drying in vacuum to obtain 30.6 mg of yellow solid 7-methoxy-3-phenylisothiocoumarin with the yield of 57%.1H NMR (500 MHz, CDCl3) δ 7.72 (s, 1H), 7.61 (d, J = 7.0 Hz, 2H), 7.56 (d, J = 8.5 Hz, 1H), 7.47 – 7.40 (m, 3H), 7.35 – 7.31 (m, 2H), 3.93 (s, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ 187.3, 160.1, 137.2, 132.6, 132.3, 129.3, 129.2, 128.7, 126.7, 123.8, 118.9, 106.4, 55.9。
The specific embodiment twenty one: 50.6 mg (0.2 mmol) of 4-fluoro-2- (phenylethynyl) benzaldehyde o-methyloxime, 23.4 mg (0.3 mmol) of sodium sulfide and 55.2 mg (0.4 mmol) of potassium carbonate are added to 2 ml of solvent N, N-dimethylformamide. At 90oAfter stirring the reaction at C for 12 hours, 1.2 mL of 1M HCl was added thereto and stirring was continued at room temperature for 1 hour. After the reaction is finished, filtering the reaction liquid to obtain filtrate, washing the filtrate by using saturated sodium chloride solution, extracting by using ethyl acetate, drying the filtrate by using anhydrous sodium sulfate, removing the solvent from the filtrate by using a rotary evaporator to obtain a residue, eluting the residue by using silica gel column by using eluent prepared by using ethyl acetate and petroleum ether according to the volume ratio of 1:30, collecting effluent according to actual gradient, detecting by TLC (thin layer chromatography), combining the effluent containing a target product, removing the solvent from the combined effluent by using the rotary evaporator in a rotating way, and drying in vacuum to obtain 28.7 mg of yellow solid 6-fluoro-3-phenylisothiocoumarin with the yield of 56%.1H NMR (500 MHz, CDCl3) δ 8.33 – 8.30 (m, 1H), 7.61 – 7.59 (m, 2H), 7.46 – 7.45 (m, 3H), 7.28 – 7.21 (m, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ 185.9, 166.1 (d, J C-F = 255.0 Hz), 142.6, 141.2 (d, J C-F = 10.0 Hz), 136.8, 129.9, 129.4, 129.3, 126.8, 124.1, 118.4, 117.0 (d, J C-F = 22.5 Hz), 115.7 (d, J C-F = 21.3 Hz); 19F NMR (470 MHz, CDCl3) δ -103.71 (s, 1F)。
The specific embodiment twenty two: 53.8 mg (0.2 mmol) of 4-chloro-2- (phenylethynyl) benzaldehyde o-methyloxime, 23.4 mg (0.3 mmol) of sodium sulfide and 55.2 mg (0.4 mmol) of potassium carbonate are added to 2 ml of the solvent N, N-dimethylformamide. At 90oAfter stirring the reaction at C for 12 hours, 1.2 mL of 1M HCl was added thereto and stirring was continued at room temperature for 1 hour. After the reaction, the reaction solution was filtered to obtain a filtrate and washed with a saturated sodium chloride solution, extracted with ethyl acetate and dried over anhydrous sodium sulfate, and the filtrate was subjected to solvent removal with a rotary evaporator to obtain a residue, which was passed through a silica gel column and used in the next stepEluting ethyl acetate and petroleum ether by using eluent prepared according to the volume ratio of 1:30, collecting effluent according to actual gradient, detecting by TLC, combining the effluent containing a target product, removing the solvent by rotating the combined effluent by using a rotary evaporator, and drying in vacuum to obtain 38.6 mg of yellow solid 6-chloro-3-phenylisothiocoumarin with the yield of 71%.1H NMR (400 MHz, CDCl3) δ 8.23 (d, J = 8.8 Hz, 1H), 7.62 – 7.60 (m, 3H), 7.51 – 7.46 (m, 4H), 7.28 (s, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 186.4, 142.5, 140.7, 139.9, 136.8, 130.0, 129.9, 129.4, 129.2, 127.7, 126.9, 125.6, 118.1。
The specific embodiment twenty three: 53.8 mg (0.2 mmol) of 5-chloro-2- (phenylethynyl) benzaldehyde o-methyloxime, 23.4 mg (0.3 mmol) of sodium sulfide and 55.2 mg (0.4 mmol) of potassium carbonate are added to 2 ml of the solvent N, N-dimethylformamide. At 90oAfter stirring the reaction at C for 12 hours, 1.2 mL of 1M HCl was added thereto and stirring was continued at room temperature for 1 hour. After the reaction is finished, filtering the reaction liquid to obtain filtrate, washing the filtrate with saturated sodium chloride solution, extracting with ethyl acetate, drying with anhydrous sodium sulfate, removing the solvent from the filtrate with a rotary evaporator to obtain a residue, eluting the residue with an eluent prepared from ethyl acetate and petroleum ether according to the volume ratio of 1:30 through a silica gel column, collecting the effluent according to the actual gradient, detecting by TLC, combining the effluent containing the target product, removing the solvent from the combined effluent by rotating the rotary evaporator, and drying in vacuum to obtain the yellow solid 7-chloro-3-phenylisothiocoumarin 41.3 mg with the yield of 76%.1H NMR (500 MHz, CDCl3) δ 8.27 (d, J = 1.5 Hz, 1H), 7.67 (dd, J = 8.5, 2.0 Hz, 1H), 7.62 – 7.57 (m, 3H), 7.49 – 7.45 (m, 3H), 7.34 (s, 1H); 13C{1H} NMR (125 MHz, CDCl3) δ 186.2, 141.0, 136.93, 136.89, 134.9, 134.3, 132.1, 129.9, 129.3, 128.2, 126.9, 125.6, 118.3。
The specific embodiment twenty four: 60.6 mg (0.2 mmol) of 2- (phenylethynyl) -5- (trifluoromethyl) benzaldehyde o-methyloxime, 23.4 mg (0.3 mmol) of sodium sulfide and 55.2 mg (0.4 mmol) of potassium carbonate are added to 2 ml of the solvent N, N-dimethylIn formamide. At 90oAfter stirring the reaction at C for 12 hours, 1.2 mL of 1M HCl was added thereto and stirring was continued at room temperature for 1 hour. After the reaction is finished, filtering the reaction liquid to obtain filtrate, washing the filtrate with saturated sodium chloride solution, extracting with ethyl acetate, drying with anhydrous sodium sulfate, removing the solvent from the filtrate with a rotary evaporator to obtain a residue, eluting the residue with an eluent prepared from ethyl acetate and petroleum ether according to the volume ratio of 1:30 through a silica gel column, collecting the effluent according to the actual gradient, detecting by TLC, combining the effluent containing the target product, removing the solvent from the combined effluent by rotating the rotary evaporator, and drying in vacuum to obtain yellow solid 3-phenyl-7- (trifluoromethyl) isothiocoumarin 43.1 mg with the yield of 70%.1H NMR (400 MHz, CDCl3) δ 8.57 (s, 1H), 7.92 (d, J = 8.4 Hz, 1H), 7.74 (d, J = 8.0 Hz, 1H), 7.64 – 7.62 (m, 2H), 7.50 – 7.47 (m, 3H), 7.40 (s, 1H); 13C{1H} NMR (125 MHz, CDCl3) δ 186.2, 143.7, 141.0, 136.6, 131.5, 130.6 (q, J C-F = 33.8 Hz), 130.2, 130.0, 129.4, 127.0, 126.9, 123.7 (q, J C-F = 271.3 Hz), 123.64, 118.2; 19F NMR (470 MHz, CDCl3) δ -62.70 (s, 3F)。
The specific embodiment is twenty five: 57.0 mg (0.2 mmol) of 1- (phenylethynyl) -2-naphthaldehyde o-methyloxime, 23.4 mg (0.3 mmol) of sodium sulfide and 55.2 mg (0.4 mmol) of potassium carbonate are added to 2 ml of solvent N, N-dimethylformamide. At 90oAfter stirring the reaction at C for 12 hours, 1.2 mL of 1M HCl was added thereto and stirring was continued at room temperature for 1 hour. After the reaction is finished, filtering reaction liquid to obtain filtrate, washing the filtrate by saturated sodium chloride solution, extracting by ethyl acetate, drying by anhydrous sodium sulfate, removing the solvent from the filtrate by a rotary evaporator to obtain residues, leaching the residues by a silica gel column by eluent prepared by ethyl acetate and petroleum ether according to the volume ratio of 1:30, collecting the effluent according to the actual gradient, detecting by TLC, combining the effluent containing the target product, removing the solvent from the combined effluent by the rotary evaporator in a rotating way, and drying in vacuum to obtain yellow solid 2-phenylbenzo [ alpha ], [ beta ] -phenyl-benzenef]Isothiocoumarin 31.1 mg, 54% yield.1H NMR (500 MHz, CDCl3) δ 8.59 (s, 1H), 8.33 – 8.30 (m, 2H), 7.93 – 7.92 (m, 2H), 7.71 (s, 4H), 7.52 – 7.51 (m, 2H); 13C{1H} NMR (125 MHz, CDCl3) δ 186.9, 142.9, 138.0, 136.7, 136.1, 130.6, 129.8, 129.4, 129.3, 129.1, 127.5, 127.2, 125.3, 124.4, 121.8, 114.2。
Specific example twenty-six: 48.2 mg (0.2 mmol) of 3- (phenylethynyl) thiophene-2-carbaldehyde o-methyloxime, 23.4 mg (0.3 mmol) of sodium sulfide and 55.2 mg (0.4 mmol) of potassium carbonate are added to 2 ml of solvent N, N-dimethylformamide. At 120oAfter stirring the reaction at C for 12 hours, 1.2 mL of 1M HCl was added thereto and stirring was continued at room temperature for 1 hour. After the reaction is finished, filtering the reaction solution to obtain filtrate, washing the filtrate with saturated sodium chloride solution, extracting with ethyl acetate, drying the filtrate with anhydrous sodium sulfate, removing the solvent from the filtrate with a rotary evaporator to obtain a residue, eluting the residue with an eluent prepared from ethyl acetate and petroleum ether according to the volume ratio of 1:20 through a silica gel column, collecting the effluent according to the actual gradient, detecting by TLC, combining the effluent containing the target product, removing the solvent from the combined effluent by rotating the rotary evaporator, and drying in vacuum to obtain a yellow solid 5-phenylthieno [2,3-c]Isothiocoumarin 34.2 mg, 70% yield.1H NMR (400 MHz, CDCl3) δ 7.85 (d, J = 5.2 Hz, 1H), 7.62 – 7.60 (m, 2H), 7.54 (s, 1H), 7.47 – 7.44 (m, 3H), 7.36 (d, J = 5.2 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 179.7, 147.7, 145.6, 136.8, 134.7, 132.2, 129.8, 129.3, 128.3, 127.2, 115.6.
The specific embodiment is twenty-seven: 55.8 mg (0.2 mmol) of 6- (phenylethynyl) benzo [2 ]d] [1,3]Dioxol-5-carboxaldehyde o-methyloxime, 23.4 mg (0.3 mmol) of sodium sulfide and 55.2 mg (0.4 mmol) of potassium carbonate were added to 2 ml of N, N-dimethylformamide as a solvent. At 100oAfter stirring the reaction at C for 16 h, 1.2 mL of 1M HCl was added thereto and stirring was continued at room temperature for 1 h. After the reaction, the reaction solution was filtered to obtain a filtrate, which was washed with a saturated sodium chloride solution, extracted with ethyl acetate, dried over anhydrous sodium sulfate, and the filtrate was removed from the solution by a rotary evaporatorObtaining residues, leaching the residues with a silica gel column by using an eluent prepared from ethyl acetate and petroleum ether according to the volume ratio of 1:30, collecting the effluent according to actual gradient, detecting by TLC, combining the effluent containing the target product, removing the solvent by rotating the combined effluent by using a rotary evaporator, and drying in vacuum to obtain the yellow solid 7-phenylisothiocoumarin [6,7-d][1,3]Dioxine 38.5 mg, yield 68%.1H NMR (500 MHz, CDCl3) δ 7.68 (s, 1H), 7.59 (d, J = 7.0 Hz, 2H), 7.45 – 7.41 (m, 3H), 7.25 (s, 1H), 6.98 (s, 1H), 6.12 (s, 2H); 13C{1H} NMR (125 MHz, CDCl3) δ 185.5, 153.1, 149.1, 139.4, 137.1, 136.4, 129.5, 129.2, 126.8, 123.6, 119.1, 108.4, 104.3, 102.5。
The specific embodiment twenty eight: 47.0 mg (0.2 mmol) of 2- (phenylethynyl) benzaldehydeOMethyl oxime, 23.4 mg (0.3 mmol) of sodium sulfide and 84.8 mg (0.4 mmol) of potassium phosphate are added to 2 ml of N, N-dimethylformamide as solvent. At 90oAfter stirring the reaction at C for 12 hours, 1.2 mL of 1M HCl was added thereto and stirring was continued at room temperature for 1 hour. After the reaction is finished, filtering the reaction liquid to obtain filtrate, washing the filtrate by using saturated sodium chloride solution, extracting by using ethyl acetate, drying the filtrate by using anhydrous sodium sulfate, removing the solvent from the filtrate by using a rotary evaporator to obtain a residue, eluting the residue by using silica gel column by using eluent prepared by using ethyl acetate and petroleum ether according to the volume ratio of 1:30, collecting effluent according to actual gradient, detecting by TLC (thin layer chromatography), combining the effluent containing a target product, removing the solvent from the combined effluent by using the rotary evaporator in a rotating way, and drying in vacuum to obtain 29.5 mg of yellow solid 3-phenylisothiocoumarin with the yield of 62%.
Specific example twenty-nine: 47.0 mg (0.2 mmol) of 2- (phenylethynyl) benzaldehydeOMethyl oxime, 23.4 mg (0.3 mmol) of sodium sulfide and 130.4 mg (0.4 mmol) of cesium carbonate were added to 2 ml of solvent N, N-dimethylformamide. At 90oAfter stirring the reaction at C for 12 hours, 1.2 mL of 1M HCl was added thereto and stirring was continued at room temperature for 1 hour. After the reaction, the reaction solution was filtered to obtain a filtrate, which was washed with a saturated sodium chloride solution, extracted with ethyl acetate and dried over anhydrous sodium sulfate, and the filtrate was filteredRemoving the solvent by using a rotary evaporator to obtain a residue, eluting the residue by using a silica gel column by using an eluent prepared from ethyl acetate and petroleum ether according to the volume ratio of 1:30, collecting the effluent according to the actual gradient, detecting by using TLC (thin layer chromatography), combining the effluent containing the target product, removing the solvent by using the rotary evaporator for the combined effluent in a rotating way, and drying in vacuum to obtain 36.2 mg of yellow solid 3-phenylisothiocoumarin with the yield of 76%.
Thirty of the specific embodiments: 47.0 mg (0.2 mmol) of 2- (phenylethynyl) benzaldehydeOMethyl oxime, 23.4 mg (0.3 mmol) of sodium sulfide and 60.8 mg (0.4 mmol) of 1, 8-diazabicycloundec-7-ene were added to 2 ml of solvent N, N-dimethylformamide. At 90oAfter stirring the reaction at C for 12 hours, 1.2 mL of 1M HCl was added thereto and stirring was continued at room temperature for 1 hour. After the reaction is finished, filtering the reaction liquid to obtain filtrate, washing the filtrate with saturated sodium chloride solution, extracting with ethyl acetate, drying with anhydrous sodium sulfate, removing the solvent from the filtrate with a rotary evaporator to obtain a residue, eluting the residue with an eluent prepared from ethyl acetate and petroleum ether according to the volume ratio of 1:30 through a silica gel column, collecting the effluent according to the actual gradient, detecting by TLC, combining the effluent containing the target product, removing the solvent from the combined effluent by rotating the rotary evaporator, and drying in vacuum to obtain 30.5 mg of yellow solid 3-phenylisothiocoumarin with the yield of 64%.
The specific embodiment is thirty-one: 47.0 mg (0.2 mmol) of 2- (phenylethynyl) benzaldehydeOMethyl oxime, 23.4 mg (0.3 mmol) of sodium sulfide and 46.4 mg (0.4 mmol) of tetramethylethylenediamine were added to 2 ml of N, N-dimethylformamide as a solvent. At 90oAfter stirring the reaction at C for 12 hours, 1.2 mL of 1M HCl was added thereto and stirring was continued at room temperature for 1 hour. After the reaction is finished, filtering the reaction solution to obtain filtrate, washing the filtrate with saturated sodium chloride solution, extracting with ethyl acetate, drying with anhydrous sodium sulfate, removing the solvent from the filtrate with a rotary evaporator to obtain residue, eluting the residue with an eluent prepared from ethyl acetate and petroleum ether according to the volume ratio of 1:30 through a silica gel column, collecting the effluent according to the actual gradient, detecting by TLC, combining the effluent containing the target product, removing the solvent from the combined effluent by rotating the rotary evaporator, and really removing the solvent from the combined effluentAir-dried to give 31.9 mg of 3-phenylisothiocoumarin as a yellow solid in 67% yield.
The specific embodiment is thirty-two: 47.0 mg (0.2 mmol) of 2- (phenylethynyl) benzaldehydeOMethyl oxime, 23.4 mg (0.3 mmol) of sodium sulfide and 84.8 mg (0.4 mmol) of potassium phosphate are added to 2 ml of N-methylpyrrolidone as solvent. At 90oAfter stirring the reaction at C for 12 hours, 1.2 mL of 1M HCl was added thereto and stirring was continued at room temperature for 1 hour. After the reaction is finished, filtering the reaction liquid to obtain filtrate, washing the filtrate by using saturated sodium chloride solution, extracting by using ethyl acetate, drying the filtrate by using anhydrous sodium sulfate, removing the solvent from the filtrate by using a rotary evaporator to obtain a residue, eluting the residue by using silica gel column by using eluent prepared by using ethyl acetate and petroleum ether according to the volume ratio of 1:30, collecting effluent according to actual gradient, detecting by TLC (thin layer chromatography), combining the effluent containing a target product, removing the solvent from the combined effluent by using the rotary evaporator in a rotating way, and drying in vacuum to obtain 13.8 mg of yellow solid 3-phenylisothiocoumarin with the yield of 29%.
The specific embodiment is thirty-three: 47.0 mg (0.2 mmol) of 2- (phenylethynyl) benzaldehydeOMethyl oxime, 23.4 mg (0.3 mmol) of sodium sulfide and 84.8 mg (0.4 mmol) of potassium phosphate are added to 2 ml of solvent N, N-dimethylacetamide. At 90oAfter stirring the reaction at C for 12 hours, 1.2 mL of 1M HCl was added thereto and stirring was continued at room temperature for 1 hour. After the reaction is finished, filtering the reaction liquid to obtain filtrate, washing the filtrate by using saturated sodium chloride solution, extracting by using ethyl acetate, drying the filtrate by using anhydrous sodium sulfate, removing the solvent from the filtrate by using a rotary evaporator to obtain a residue, eluting the residue by using silica gel column by using eluent prepared by using ethyl acetate and petroleum ether according to the volume ratio of 1:30, collecting effluent according to actual gradient, detecting by TLC (thin layer chromatography), combining the effluent containing a target product, removing the solvent from the combined effluent by using the rotary evaporator in a rotating way, and drying in vacuum to obtain 24.8 mg of yellow solid 3-phenylisothiocoumarin with the yield of 52%.
The specific embodiment is thirty-four: 47.0 mg (0.2 mmol) of 2- (phenylethynyl) benzaldehydeOMethyl oxime, 23.4 mg (0.3 mmol) of sodium sulfide and 84.8 mg (0.4 mmol) of potassium phosphate are added to 2 ml of dimethyl sulfoxide solvent. At 90oC lower stirringAfter stirring for 12 hours, 1.2 mL of 1M HCl was added thereto and stirring was continued at room temperature for 1 hour. After the reaction is finished, filtering the reaction liquid to obtain filtrate, washing the filtrate with saturated sodium chloride solution, extracting with ethyl acetate, drying with anhydrous sodium sulfate, removing the solvent from the filtrate with a rotary evaporator to obtain a residue, eluting the residue with an eluent prepared from ethyl acetate and petroleum ether according to the volume ratio of 1:30 through a silica gel column, collecting the effluent according to the actual gradient, detecting by TLC, combining the effluent containing the target product, removing the solvent from the combined effluent by rotating the rotary evaporator, and drying in vacuum to obtain 10.5 mg of yellow solid 3-phenylisothiocoumarin with the yield of 22%.
In the embodiment of the invention, o-alkynyl oxime ether is used as a reaction substrate, sodium sulfide is used as a sulfur source, potassium carbonate is used as alkali, N, N-dimethylformamide is used as a solvent, and the reaction is carried out in the presence of 90-120 parts ofoC, stirring and reacting for 12-16 hours. In the first to sixteenth embodiments, R in the o-alkynyl oxime ether is substituted by different substituents as variables, and in the seventeenth to twenty seventh embodiments, R' in the o-alkynyl oxime ether is substituted by different substituents as variables, and it is noted that the substituent with strong electron-withdrawing property on the phenyl group and the alkyl group can also be well used by the method of the present invention; examples twenty-eight to thirty-one are base variants and examples thirty-two to thirty-four are solvent variants.
According to the invention, the intermediate product does not need to be separated, the target product can be directly synthesized by simple raw materials, the process is simplified, the energy consumption is low, the waste solution discharge is reduced, the environmental pollution is reduced, and the yield reaches 84% at most; in the above embodiment, a series of 3-substituted isothiocoumarin derivatives can be prepared by reacting o-alkynyl oxime ethers containing different substituents with sodium sulfide, and the method has certain substrate universality and operation simplicity. The present invention is not limited to the above embodiments, and those skilled in the art can implement the present invention in other embodiments according to the disclosure of the present invention, or make simple changes or modifications on the design structure and idea of the present invention, and fall into the protection scope of the present invention.

Claims (4)

1. 3-substituted isothio incenseThe synthesis method of the coumarin derivative comprises the following steps: taking o-alkynyl oxime ether as a reaction substrate, sodium sulfide as a sulfur source, potassium phosphate, cesium carbonate, potassium carbonate, 1, 8-diazabicycloundecen-7-ene or tetramethylethylenediamine as an alkali, N-methylpyrrolidone, N-dimethylacetamide, N-dimethylformamide or dimethyl sulfoxide as a solvent, and dissolving the mixture in 90-120 parts of a solventoC, stirring and reacting for 12-16 hours, adding 1.2 mL of 1M HCl into the mixture after the reaction is finished, and continuously stirring the mixture at room temperature for 1 hour, wherein the chemical reaction formula is as follows:
Figure 244731DEST_PATH_IMAGE001
the-R is one of phenyl, 4-methylphenyl, 3-methylphenyl, 2-methylphenyl, 4-ethylphenyl, 4-tert-butylphenyl, 4-methoxyphenyl, 4-fluorophenyl, 4-chlorophenyl, 2-chlorophenyl, 4-bromophenyl, 4-trifluoromethylphenyl, n-butyl, cyclopropyl, 2-thienyl and 3-pyridyl;
the-R' is 4-methylphenyl, 5-methylphenyl, 4-methoxyphenyl, 5-methoxyphenyl, 4-fluorophenyl, 4-chlorophenyl, 5-trifluoromethylphenyl, benzo [ b ], [2 ]d][1,3]One of dioxolane, thiophene and 2-naphthyl; wherein the benzo [ b ], [d][1,3]The dioxolane has the formula:
Figure 724254DEST_PATH_IMAGE002
the expression of thiophene is:
Figure 692210DEST_PATH_IMAGE003
the expression of 2-naphthyl is:
Figure 788342DEST_PATH_IMAGE004
。
2. the method for synthesizing a 3-substituted isothiocoumarin derivative according to claim 1, wherein: the base is potassium carbonate.
3. The method for synthesizing a 3-substituted isothiocoumarin derivative according to claim 1, wherein: the solvent is N, N-dimethylformamide.
4. The method for synthesizing a 3-substituted isothiocoumarin derivative according to claim 1, wherein: and filtering after the reaction is finished, washing the filtrate by using a saturated sodium chloride solution, extracting by using ethyl acetate, drying by using anhydrous sodium sulfate, carrying out rotary evaporation on the combined organic layers by using a rotary evaporator to remove the solvent to obtain a residue, carrying out column layer separation on the residue through a silica gel column, carrying out elution by using an eluent, collecting an effluent containing the target product, combining the effluent, and removing the solvent by vacuum concentration to obtain the target product.
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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105949161A (en) * 2016-06-28 2016-09-21 温州大学 Preparation method of 3-arylmercapto flavonoid compound
CN110372660A (en) * 2019-06-28 2019-10-25 天津大学 The synthetic method of isocoumarin analog derivative
CN111303114A (en) * 2020-03-13 2020-06-19 郑州大学 Synthesis method for synthesizing 3-sulfonylation sulfo-flavonoid compound

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105949161A (en) * 2016-06-28 2016-09-21 温州大学 Preparation method of 3-arylmercapto flavonoid compound
CN110372660A (en) * 2019-06-28 2019-10-25 天津大学 The synthetic method of isocoumarin analog derivative
CN111303114A (en) * 2020-03-13 2020-06-19 郑州大学 Synthesis method for synthesizing 3-sulfonylation sulfo-flavonoid compound

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
BENJAMIN WILLY等: "Microwave-assisted three-component coupling-addition-SNAr (CASNAR) sequences to annelated 4H-thiopyran-4-ones", 《ORG. BIOMOL. CHEM.》, 23 October 2009 (2009-10-23), pages 90 - 95 *
GUANYINSHENG QIU等: "Multicatalytic One-Pot Reaction of 1-(2-Alkynylphenyl)ketoximes for Generation of Indole Derivatives", 《ORG. LETT.》, 20 August 2010 (2010-08-20), pages 3975 - 3977 *
XIAOBO YANG等: "Domino reactions of 1-(2-alkoxyaryl)-3-akylprop-2-yn-1-ones with sodium sulfide leading to thiochromen-4-one derivatives", 《RSC ADV.》, 11 May 2012 (2012-05-11), pages 6549 - 6554 *

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