LU500625B1 - Synthetic Method of alpha, alpha, beta-tricarbonyl Sulfide Ylide Compound - Google Patents
Synthetic Method of alpha, alpha, beta-tricarbonyl Sulfide Ylide Compound Download PDFInfo
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- LU500625B1 LU500625B1 LU500625A LU500625A LU500625B1 LU 500625 B1 LU500625 B1 LU 500625B1 LU 500625 A LU500625 A LU 500625A LU 500625 A LU500625 A LU 500625A LU 500625 B1 LU500625 B1 LU 500625B1
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- B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
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- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
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Abstract
The present invention relates to a synthetic method of ?,?,?-tricarbonyl sulfide ylide compound. The sulfur oxide ylide shown in formula I: is used as a raw material, and the reaction is carried out under the action of a catalyst. In formula I, R is selected from substituted or unsubstituted alkyl, C6-10 aryl or C4-10 heterocycle, and the substituents include alkyl, alkoxy, cyano, nitro, halogen, the alkyl or alkoxy is substituted with 0, 1, or more halogen atoms.
Description
Synthetic Method of a,a,B-tricarbonyl Sulfide Ylide Compound LU500625 Technical Field The present invention belongs to the field of organic chemistry, and specifically relates to an a,a,f-tricarbonyl sulfide ylide compound and a synthesis method thereof. Background Technology As a kind of zwitterionic compound, sulfur ylide has a structure of adjacent carbanion stabilized by sulfide ions, it can be regarded as a nucleophile with a leaving group. Therefore, as a classic one-carbon synthon, Sulfur Ylide can be used to efficiently synthesize small ring compounds such as epoxy, aziridine, and cyclopropane by reacting with the electron-deficient TT System.
At present, for the synthesis of tetraketone compounds, toxic and harmful substances such as mercury and nitric acid are usually needed. Therefore, it is necessary to study a green and efficient method or reaction intermediate to solve such problems.
Summary of the Invention Based on the above problems, the present invention provides a method for synthesizing a,q,B-tricarbonylthio ylide compounds, which is characterized in that the synthesis method uses sulfur oxide ylides represented by formula | in an organic solvent as a raw material, the reaction is carried out under the action of a catalyst; among them, R in formula | is selected from substituted or unsubstituted alkyl, C6-10 aryl or C4-10 heterocyclic, and the substituents include alkyl, alkoxy, cyano, nitro, halogen, the alkyl group or alkoxy group is substituted with 0, 1 or more halogen atoms.
8e. pn Formula | In one embodiment, the R includes any of the following groups: x
CF OF OF OF CO A} A} A} A} A} F A} Cl A} 1
¢ Fetal © Ch, oy, AL US00625 Falu_ wm ge pas SS . Gary Le Ds . Fy ng GN Tog . So ORE LR ST ge TS STE In one embodiment, the catalyst includes: anhydrous copper acetate and/or silver trifluoroacetate; the organic solvent includes 1,4-dioxane.
In one embodiment, the reaction temperature is 70-110°C, the reaction time is 8-14 h, and the reaction atmosphere is oxygen; after the reaction, the product is purified by silica gel column chromatography.
The purification method is: after the reaction, it is added to column chromatography silica gel, the solvent is distilled off under reduced pressure, the product is spin-dried to the powdery silica gel adsorption product, and the sample is applied to the column and mixed with petroleum ether and ethyl acetate. The liquid is eluted and collected and concentrated under reduced pressure to obtain a,a,B-tricarbonylthio ylide compound.
In one embodiment, the ratio of the amount of sulfur oxide ylide to the substance of the catalyst is 1: (0.1-0.2); based on the amount of the sulfur oxide ylide shown in formula |, the addition amount of the organic solvent is 4-8 mL/mmol.
Another object of the present invention is to provide an a,a,f-tricarbonylthio ylide compound prepared according to the above-mentioned synthesis method, the a,a,f- tricarbonylthio ylide compound has the structure of formula II: pas SS y D. Formula I Among them, R in formula | is selected from substituted or unsubstituted alkyl, C6-10 aryl or C4-10 heterocyclic, and the substituents include alkyl, alkoxy, cyano, nitro, halogen, the alkyl group or alkoxy group is substituted with 0, 1 or more halogen atoms.
In one embodiment, the R includes the following groups: 2
| Sty LU500625 Ye N nn . ee . Ne N | . F . Lo € os .
Ë . td Gi, See wr WE | . a.
Fa He FOTN oF, Ne oN x + - N x x Spi x Aus + A N ge N N oF A NE Beneficial effects: The present invention discloses the synthetic method of a,a,p-tricarbonyl sulfide ylide compound. The raw materials of the invention are cheap and easy to synthesize, the catalyst is cheap and easy to obtain, the catalyst is highly efficient and green, and the substrate range is wide, and the electron withdrawing and electron donating groups are well tolerated. It also synthesizes sulfur ylides with heterocyclic substituents and alkane substituents. The highest rate can reach 82%, and the operation is simple.
Brief Description of Drawings Figure 1 is a single crystal structure diagram of the a,q,B-tricarbonylthio ylide compound prepared in Embodiment 1.
Detailed Description of the Presently Preferred Embodiments The technical solution of the present invention will be further described in detail below in conjunction with specific embodiments.
The raw material sulfur oxide ylide used in the present invention can be prepared by itself according to the existing literature, for example, the literature Y. Yuan, X.-F. Wu, Org. Lett. 2019, 21,5310. The present invention provides the following synthesis method: Under argon conditions, at room temperature, trimethylsulfoxide iodide (5.0 g, 20.6 mmol) is added to THF (30 mL) dissolved in potassium tert-butoxide (3.0 g, 27.2 mmol), after being sufficiently stirred to dissolve, the resulting mixture is refluxed for 2 hours. Then, the reaction mixture is cooled to O °C, and then acid chloride (7.0 mmol) is added, it is warmed to room temperature and stirred overnight. After the reaction, the solvent is distilled off under reduced 3 pressure, and 15 ml of water is added and extracted with ethyl acetate (3x50 ml). The organic LU500625 solution is dried over anhydrous Na2S04, added to 100-200 mesh column chromatography silica gel, and distilled under reduced pressure to remove the solvent. The crude product is separated by silica gel column chromatography and eluted with ethyl acetate. With the help of TLC elution tracking detection, the eluate containing the target product is collected, and the target product eluate is combined and concentrated under reduced pressure to obtain the sulfur oxide ylide compound represented by formula I.
The synthetic route is: O 0 i potassium tert-butoxide O lo ak N —3 THF ASS | In some embodiments of the present invention: ©, jo) In Embodiment 1, R is ‚in Embodiment 2, R is , In Embodiment 3, R co GC or is F , in Embodiment 4, R isBr , in Embodiment 5, R is © , in F f x Cc" y Embodiment 6, R is , In Embodiment 7, R is F , in Embodiment 8, R is oF oF or MeO , in Embodiment 9, R is NC , in Embodiment 10, R is O2N OC" oy in Embodiment 11, R is , in Embodiment 12, R is \ O | in Embodiment 13, R J" is .
The raw material used in the present invention with substituents of acid chlorides can be purchased commercially. Embodiment 1 The structural formula of the a,a,ß-tricarbonylthio ylide compound prepared in this embodiment is as follows: 4
C LU500625 0 O / X Ys II-1 The preparation method is as follows: sulfur oxide ylide (0.4 mmol, 78.4 mg), Cu(OAC)a (0.04 mmol, 7.2 mg), CF,COOAg(0.04 mmol, 8.8 mg) is added to a 25 ml schlenk tube equipped with a magnetic stirrer. Under reduced pressure, the reaction tube is replaced with oxygen three times. After 2 ml of anhydrous 1,4-dioxane is added, the reaction is stirred at 90°C for 12 hours. After the reaction, 200 mesh column chromatography silica gel is added, and the solvent is distilled off under reduced pressure. The crude product is separated by silica gel column chromatography and used as a mixture of petroleum ether and ethyl acetate (petroleum ether: ethyl acetate=1:2) Elution, with the help of TLC elution tracking detection, the eluate containing the target product is collected, the target product eluate is combined, concentrated under reduced pressure, the a,a,B-tricarbonylthio ylide compound represented by formula Ill-3 is obtained with a yield of 81%. The substance is a white solid with a melting point of 234.6-235.8 °C. An X-ray diffraction tester is used to test the single crystal structure of the a,a,B-tricarbonylthio ylide compound to obtain a structural analysis diagram as shown in Figure 1.
Characterization data: "H NMR (400 MHz, CDCIs) 6 7.80-7.73 (m, 2H), 7.55-7.47 (m, 3H),
7.38 (t, J= 7.7 Hz, 2H), 7.35-7.29 (m, 1H), 7.18 (t, J = 7.7 Hz, 2H), 3.78 (s, 6H). °C NMR (101 MHz, DMSO-d6) à 191.9, 189.2, 186.3, 140.9, 134.0, 133.9, 131.8, 129.5, 129.1, 128.9, 128.2,
102.3, 42.0. HRMS m/z (ESI) calcd for C1gH1s04S (M+H)+ 329.0842, found 329.0843. Embodiment 2 The structural formula of the a,a,f-tricarbonylthio ylide compound prepared in this embodiment is as follows:
O 0 x II-2 The preparation method is as follows: 4-methylphenyl sulfur oxide ylide (0.4 mmol, 84 mg), Cu(OAc)» (0.04 mmol, 7.2 mg), CF,COOAg (0.04 mmol, 8.8 mg) is added to a 25 ml schlenk tube equipped with a magnetic stirrer. Under reduced pressure, the reaction tube is replaced with oxygen three times. After 2 ml of anhydrous 1,4-dioxane is added, the reaction is stirred at 90°C for 12 hours. After the reaction, 200 mesh column chromatography silica gel is added, and the solvent is distilled off under reduced pressure. The crude product is separated by silica gel column chromatography and used as a mixture of petroleum ether and ethyl acetate (petroleum ether: ethyl acetate=1:1) Elution, with the help of TLC elution tracking detection, the eluate containing the target product is collected, the target product eluate is combined, concentrated under reduced pressure, the a,a,B-tricarbonylthio ylide compound represented by formula Ill-2 is obtained with a yield of 81%. The substance is a white solid with a melting point of 203.0-204.2 °C.
Characterization data: "H NMR (400 MHz, CDCIs) à 7.65 (d, J= 8.1 Hz, 2H), 7.41 (d, J =
8.0 Hz, 2H), 7.18 (d, J= 7.9 Hz, 2H), 6.98 (d, J= 7.8 Hz, 2H), 3.74 (s, 6H), 2.39 (s, 3H), 2.27 (s, 3H). °C NMR (101 MHz, CDCls) 6 191.9, 189.9, 186.2, 144.6, 142.3, 137.2, 131.0, 129.5,
129.1, 129.0, 128.5, 99.5, 43.5, 21.8, 21.5. HRMS m/z (ESI) calcd for CzoH2004S (M+H)*
357.1155, found 357.1154. Embodiment 3 The structural formula of the a,a,f-tricarbonylthio ylide compound prepared in this embodiment is as follows: 6
F LU500625 0 0 / X Zo
F II-3 The preparation method is as follows: 4-fluorophenyl sulfur oxide ylide (0.4 mmol, 85.6 mg), Cu(OAc)» (0.04 mmol, 7.2 mg), CF,COOAg (0.04 mmol, 8.8 mg) is added to a 25 ml schlenk tube equipped with a magnetic stirrer. Under reduced pressure, the reaction tube is replaced with oxygen three times. After 2 ml of anhydrous 1,4-dioxane is added, the reaction is stirred at 90°C for 12 hours. After the reaction, 200 mesh column chromatography silica gel is added, and the solvent is distilled off under reduced pressure. The crude product is separated by silica gel column chromatography and used as a mixture of petroleum ether and ethyl acetate (petroleum ether: ethyl acetate=1:2) Elution, with the help of TLC elution tracking detection, the eluate containing the target product is collected, the target product eluate is combined, concentrated under reduced pressure, the a,a,B-tricarbonylthio ylide compound represented by formula Ill-3 is obtained with a yield of 73%. The substance is a white solid with a melting point of 213.7-214.3 °C. Characterization data: '"H NMR (400 MHz, DMSO-de) 6 7.81-7.73 (m, 2H), 7.53 (dd, J =
8.5, 5.7 Hz, 2H), 7.32 (t, J = 8.8 Hz, 2H), 6.98 (t, J = 8.8 Hz, 2H), 3.90 (s, 6H). "°C NMR (101 MHz, DMSO-de) à 190.6, 188.0, 185.8, 165.7 (d, J= 253.0 Hz), 164.3 (d, J= 249.2 Hz), 137.5 (d, J= 2.9 Hz), 132.4 (d, J= 9.6 Hz), 131.8 (d, J= 9.1 Hz), 130.5 (d, J= 2.7 Hz), 116.2 (d, J =
22.2 Hz), 115.1 (d, J = 21.9 Hz), 102.1, 41.9. °F NMR (376 MHz, DMSO-de) & -104.51, -
108.62. HRMS m/z (ESI) calcd for C1sH14F204S (M+Na)* 387.0473, found 387.0473. Embodiment 4 The structural formula of the a,a,f-tricarbonylthio ylide compound prepared in this embodiment is as follows: 7
Br LU500625 0 0 /
SS Br II-4 The preparation method is as follows: 4-bromophenyl sulfur oxide ylide (0.4 mmol, 109.6 mg), Cu(OAc)» (0.04 mmol, 7.2 mg), CF,COOAg (0.04 mmol, 8.8 mg) is added to a 25 ml schlenk tube equipped with a magnetic stirrer. Under reduced pressure, the reaction tube is replaced with oxygen three times. After 2 ml of anhydrous 1,4-dioxane is added, the reaction is stirred at 90°C for 12 hours. After the reaction, 200 mesh column chromatography silica gel is added, and the solvent is distilled off under reduced pressure. The crude product is separated by silica gel column chromatography and used as a mixture of petroleum ether and ethyl acetate (petroleum ether: ethyl acetate=1:1) Elution, with the help of TLC elution tracking detection, the eluate containing the target product is collected, the target product eluate is combined, concentrated under reduced pressure, the a,a,B-tricarbonylthio ylide compound represented by formula Ill-4 is obtained with a yield of 71%. The substance is a white solid with a melting point of 215.8-217.4 °C. Characterization data: '"H NMR (400 MHz, DMSO-de) 6 7.73-7.69 (m, 2H), 7.62 (d, J =
8.5 Hz, 2H), 7.42-7.35 (m, 4H), 3.89 (s, 6H). °C NMR (101 MHz, DMSO-ds) à 191.0, 188.2,
185.8, 140.0, 132.8, 132.2, 131.3, 131.2, 131.0, 128.3, 125.4, 101.6, 42.0. HRMS m/z (ESI) calcd for C1gH14Br204S (M+Na)* 506.8872, found 506.8871. Embodiment 5 The structural formula of the a,a,f-tricarbonylthio ylide compound prepared in this embodiment is as follows: 8
C F LU500625 0 O / O Yo
SN Im-5 The preparation method is as follows: 3-fluorophenyl sulfur oxide ylide (0.4 mmol, 85.6 mg), Cu(OAc)» (0.04 mmol, 7.2 mg), CF,COOAg (0.04 mmol, 8.8 mg) is added to a 25 ml schlenk tube equipped with a magnetic stirrer. Under reduced pressure, the reaction tube is replaced with oxygen three times. After 2 ml of anhydrous 1,4-dioxane is added, the reaction is stirred at 90°C for 12 hours. After the reaction, 200 mesh column chromatography silica gel is added, and the solvent is distilled off under reduced pressure. The crude product is separated by silica gel column chromatography and used as a mixture of petroleum ether and ethyl acetate (petroleum ether: ethyl acetate=1:1) Elution, with the help of TLC elution tracking detection, the eluate containing the target product is collected, the target product eluate is combined, concentrated under reduced pressure, the a,a,B-tricarbonylthio ylide compound represented by formula Ill-5 is obtained with a yield of 65%. The substance is a white solid with a melting point of 214.7-216.5 °C.
Characterization data: "H NMR (400 MHz, DMSO-de) à 7.56 (t, J = 5.2 Hz, 2H), 7.50 (m, 1H), 7.44 (d, J= 9.4 Hz, 1H), 7.31 (s, 1H), 7.29 (s, 1H), 7.24 (q, J= 7.7 Hz, 1H), 7.15 (t, J =
8.0 Hz, 1H), 3.92 (s, 6H). "°C NMR (101 MHz, DMSO-de) à 190.3 (d, J= 2.2 Hz), 187.8, 185.4,
162.4 (d, J = 245.6 Hz), 161.8 (d, J = 245.5 Hz), 143.1 (d, J= 6.6 Hz), 135.9 (d, J = 6.3 Hz),
131.4 (d, J= 7.9 Hz), 130.6 (d, J = 7.9 Hz), 125.8 (d, J= 2.9 Hz), 125.0 (d, J= 3.0 Hz), 121.2 (d, J = 21.6 Hz), 118.4 (d, J = 21.0 Hz), 116.0 (d, J = 22.5 Hz), 115.4, 102.4, 41.9. °F NMR (376 MHz, DMSO-de) à -112.14, -113.34. HRMS m/z (ESI) calcd for C1sH14F204S (M+Na)*
387.0473, found 387.0472.
Embodiment 6 The structural formula of the a,a,f-tricarbonylthio ylide compound prepared in this embodiment is as follows: 9
L Oo O
O J F OY / 9 II-6 The preparation method is as follows: 2-fluorophenyl sulfur oxide ylide (0.4 mmol, 85.6 mg), Cu(OAc)» (0.04 mmol, 7.2 mg), CF,COOAg(0.04 mmol, 8.8 mg) is added to a 25 ml schlenk tube equipped with a magnetic stirrer. Under reduced pressure, the reaction tube is replaced with oxygen three times. After 2 ml of anhydrous 1,4-dioxane is added, the reaction is stirred at 90°C for 12 hours. After the reaction, 200 mesh column chromatography silica gel is added, and the solvent is distilled off under reduced pressure. The crude product is separated by silica gel column chromatography and used as a mixture of petroleum ether and ethyl acetate (petroleum ether: ethyl acetate=1:2) Elution, with the help of TLC elution tracking detection, the eluate containing the target product is collected, the target product eluate is combined, concentrated under reduced pressure, the a,a,B-tricarbonylthio ylide compound represented by formula IIl-6 is obtained with a yield of 60%. The substance is a yellow solid with a melting point of 164.6-166.8 °C.
Characterization data: "H NMR (400 MHz, DMSO-d) 6 7.81 (m, 1H), 7.74-7.67 (m, 1H),
7.42-7.28 (m, 4H), 7.16-7.09 (m, 1H), 7.06 (t, J = 7.4 Hz, 1H), 3.81 (s, 6H). "°C NMR (101 MHz, DMSO-ds) 6 187.8, 183.4, 162.1 (d, J = 256.2 Hz), 159.3 (d, J = 247.4 Hz), 136.6 (d, J = 9.2 Hz), 132.5 (d, J= 8.5 Hz), 130.8 (d, J= 1.8 Hz), 129.9 (d, J= 3.3 Hz), 129.5 (d, J= 15.8 Hz), 125.3 (d, J = 3.3 Hz), 124.3 (d, J= 3.4 Hz), 122.1 (d, J = 10.6 Hz), 117.1, 116.9, 115.8,
115.6, 41.8. "°F NMR (376 MHz, DMSO-ds) & -109.58, -115.44. HRMS m/z (ESI) calcd for C1gH14F204S (M+Na)* 387.0471, found 387.0472.
Embodiment 7 The structural formula of the a,a,f-tricarbonylthio ylide compound prepared in this embodiment is as follows:
F C F LU500625
F J F m-7 The preparation method is as follows: 3,5-difluorophenyl sulfur oxide ylide (0.4 mmol,
92.8 mg), Cu(OAc)2 (0.04 mmol, 7.2 mg), CF,COOAg (0.04 mmol, 8.8 mg) is added to a 25 ml schlenk tube equipped with a magnetic stirrer. Under reduced pressure, the reaction tube is replaced with oxygen three times. After 2 ml of anhydrous 1,4-dioxane is added, the reaction is stirred at 90°C for 12 hours. After the reaction, 200 mesh column chromatography silica gel is added, and the solvent is distilled off under reduced pressure. The crude product is separated by silica gel column chromatography and used as a mixture of petroleum ether and ethyl acetate (petroleum ether: ethyl acetate=1:1) Elution, with the help of TLC elution tracking detection, the eluate containing the target product is collected, the target product eluate is combined, concentrated under reduced pressure, the a,a,B-tricarbonylthio ylide compound represented by formula Ill-7 is obtained with a yield of 58%. The substance is a white solid with a melting point of 236.5-237.6 °C.
Characterization data: "H NMR (400 MHz, DMSO-ds) à 7.63 (s, 1H), 7.43 (s, 2H), 7.25 (s, 3H), 3.94 (s, 6H). ‘°C NMR (101 MHz, DMSO-de) à 188.6, 186.4, 184.6, 163.8 (dd, J = 54.1,
12.3 Hz), 161.3 (dd, J= 53.3, 12.3 Hz), 144.2 (t, J= 8.3 Hz), 136.7 (t, J= 8.1 Hz), 112.7-112.1 (m, 2C), 109.8 (t, J = 26.2 Hz), 106.7 (t, J = 25.9 Hz), 102.3, 41.9. °F NMR (376 MHz, DMSO- de) à -107.96, -109.28. HRMS m/z (ESI) calcd for C1sH12F404S (M+Na)* 324.0284, found
324.0284.
Embodiment 8 The structural formula of the a,a,f-tricarbonylthio ylide compound prepared in this embodiment is as follows: 11
OMe LU500625 O 0 A 0 OMe II-8 The preparation method is as follows: 4-methoxyphenyl sulfur oxide ylide (0.4 mmol,
90.4 mg), Cu(OAC)- (0.04 mmol, 7.2 mg), CF,COOAg (0.04 mmol, 8.8 mg) is added to a 25 ml schlenk tube equipped with a magnetic stirrer. Under reduced pressure, the reaction tube is replaced with oxygen three times. After 2 ml of anhydrous 1,4-dioxane is added, the reaction is stirred at 90°C for 12 hours. After the reaction, 200 mesh column chromatography silica gel is added, and the solvent is distilled off under reduced pressure. The crude product is separated by silica gel column chromatography and used as a mixture of petroleum ether and ethyl acetate (petroleum ether: ethyl acetate=1:2) Elution, with the help of TLC elution tracking detection, the eluate containing the target product is collected, the target product eluate is combined, concentrated under reduced pressure, the a,a,B-tricarbonylthio ylide compound represented by formula Ill-8 is obtained with a yield of 72%. The substance is a white solid with a melting point of 191.6-192.7 °C. Characterization data: "H NMR (400 MHz, DMSO-ds) à 7.61 (d, J = 8.5 Hz, 2H), 7.40 (d, J = 8.4 Hz, 2H), 6.97 (d, J = 8.5 Hz, 2H), 6.64 (d, J = 8.4 Hz, 2H), 3.86 (s, 6H), 3.84 (s, 3H),
3.66 (s, 3H). ‘°C NMR (101 MHz, DMSO-d) à 191.0, 188.3, 186.2, 163.8, 162.3, 133.5, 131.8,
131.5, 127.0, 114.2, 113.3, 102.2, 56.1, 55.7, 41.9. HRMS m/z (ESI) calcd for CzoHz006S (M+H)* 389.1053, found 389.1060. Embodiment 9 The structural formula of the a,a,f-tricarbonylthio ylide compound prepared in this embodiment is as follows: 12
CN LU500625 O 0 A 0
CN II-9 The preparation method is as follows: 4-cyanophenyl sulfur oxide ylide (0.4 mmol, 88.4 mg), Cu(OAc)» (0.04 mmol, 7.2 mg), CF,COOAg (0.04 mmol, 8.8 mg) is added to a 25 ml schlenk tube equipped with a magnetic stirrer. Under reduced pressure, the reaction tube is replaced with oxygen three times. After 2 ml of anhydrous 1,4-dioxane is added, the reaction is stirred at 90°C for 12 hours. After the reaction, 200 mesh column chromatography silica gel is added, and the solvent is distilled off under reduced pressure. The crude product is separated by silica gel column chromatography and used as a mixture of petroleum ether and ethyl acetate (petroleum ether: ethyl acetate=1:2) Elution, with the help of TLC elution tracking detection, the eluate containing the target product is collected, the target product eluate is combined, concentrated under reduced pressure, the a,a,B-tricarbonylthio ylide compound represented by formula Ill-9 is obtained with a yield of 56%. The substance is a white solid with a melting point of 232.2-233.9 °C.
Characterization data: "H NMR (400 MHz, DMSO-ds) à 7.99 (d, J = 8.3 Hz, 2H), 7.90 (d, J=8.1Hz 2H), 7.72 (d, J = 7.9 Hz, 2H), 7.63 (d, J = 8.0 Hz, 2H), 3.90 (s, 6H). ‘°C NMR (101 MHz, DMSO-ds) à 190.5, 187.7, 183.2, 144.9, 136.9, 133.2, 132.3, 129.9, 129.3, 118.7, 118.6,
116.1, 113.5, 102.7, 42.0. HRMS m/z (ESI) calcd for C2oH144N204S (M+H)* 379.0747, found
379.0745.
Embodiment 10 The structural formula of the a,a,f-tricarbonylthio ylide compound prepared in this embodiment is as follows: 13
NO, LU500625 0 y pe Yo NO, II-10 The preparation method is as follows: 4-nitrophenyl sulfur oxide ylide (0.4 mmol, 96.4 mg), Cu(OAc)» (0.04 mmol, 7.2 mg), CF,COOAg (0.04 mmol, 8.8 mg) is added to a 25 ml schlenk tube equipped with a magnetic stirrer. Under reduced pressure, the reaction tube is replaced with oxygen three times. After 2 ml of anhydrous 1,4-dioxane is added, the reaction is stirred at 90°C for 12 hours. After the reaction, 200 mesh column chromatography silica gel is added, and the solvent is distilled off under reduced pressure. The crude product is separated by silica gel column chromatography and used as a mixture of petroleum ether and ethyl acetate (petroleum ether: ethyl acetate=1:1) Elution, with the help of TLC elution tracking detection, the eluate containing the target product is collected, the target product eluate is combined, concentrated under reduced pressure, the a,a,B-tricarbonylthio ylide compound represented by formula 111-10 is obtained with a yield of 61%. The substance is a white solid with a melting point of 197.1-198.7 °C. Characterization data: "H NMR (400 MHz, DMSO-ds) 6 8.31 (d, J = 8.4 Hz, 2H), 8.10 (d, J= 8.3 Hz, 2H), 8.02 (d, J = 8.3 Hz, 2H), 7.72 (d, J = 8.3 Hz, 2H), 3.91 (s, 6H). ‘°C NMR (101 MHz, DMSO-ds) à 190.3, 187.3, 183.6, 150.6, 148.9, 146.6, 138.4, 130.7, 129.7, 124.4, 123.5,
102.0, 42.1. HRMS m/z (ESI) calcd for C1sH14N20sS (M+H)* 419.0544, found 419.0545. Embodiment 11 The structural formula of the a,a,f-tricarbonylthio ylide compound prepared in this embodiment is as follows: 14
GC LU500625 o O / = So I-11 The preparation method is as follows: 2-naphthyl sulfur oxide ylide (0.4 mmol, 98.4 mg), Cu(OAC)2(0.04 mmol, 7.2 mg), CF,COOAg (0.04 mmol, 8.8 mg) is added to a 25 ml schlenk tube equipped with a magnetic stirrer. Under reduced pressure, the reaction tube is replaced with oxygen three times. After 2 ml of anhydrous 1,4-dioxane is added, the reaction is stirred at 90°C for 12 hours. After the reaction, 200 mesh column chromatography silica gel is added, and the solvent is distilled off under reduced pressure. The crude product is separated by silica gel column chromatography and used as a mixture of petroleum ether and ethyl acetate (petroleum ether: ethyl acetate=1:2) Elution, with the help of TLC elution tracking detection, the eluate containing the target product is collected, the target product eluate is combined, concentrated under reduced pressure, the a,a,B-tricarbonylthio ylide compound represented by formula Ill-11 is obtained with a yield of 42%. The substance is a white solid with a melting point of 239.8-241.2 °C.
Characterization data: "H NMR (400 MHz, DMSO-de) à 8.25 (s, 1H), 8.09 (s, 1H), 8.01 (d, J= 8.1 Hz, 1H), 7.86 (d, J= 8.1 Hz, 1H), 7.73 (t, J= 7.3 Hz, 3H), 7.64 (t, J= 7.0 Hz, 1H), 7.58 (t, J= 7.1 Hz, 1H), 7.53-7.44 (m, 2H), 7.38-7.26 (m, 2H), 7.04 (t, J= 6.9 Hz, 1H), 4.01 (s, 6H). BC NMR (101 MHz, DMSO-de) à 191.8, 189.4, 186.2, 138.3, 135.5, 134.3, 132.2, 131.5(2C),
131.1, 130.4, 130.0, 129.2, 128.5, 128.4, 128.0, 127.9, 127.7, 127.3, 126.4, 125.2, 124.1,
102.9, 42.0. HRMS m/z (ESI) calcd for C2sH2004S (M+H)* 429.1155, found 429.1161. Embodiment 12 The structural formula of the a,a,f-tricarbonylthio ylide compound prepared in this embodiment is as follows:
— LU500625 a UO 0 O / O Yo 70 II-12 The preparation method is as follows: 2-furan sulfur oxide ylide (0.4 mmol, 74.4 mg), Cu(OAC)2(0.04 mmol, 7.2 mg), CF,COOAg (0.04 mmol, 8.8 mg) is added to a 25 ml schlenk tube equipped with a magnetic stirrer. Under reduced pressure, the reaction tube is replaced with oxygen three times. After 2 ml of anhydrous 1,4-dioxane is added, the reaction is stirred at 90°C for 12 hours. After the reaction, 200 mesh column chromatography silica gel is added, and the solvent is distilled off under reduced pressure. The crude product is separated by silica gel column chromatography and used as a mixture of petroleum ether and ethyl acetate (petroleum ether: ethyl acetate=1:4) Elution, with the help of TLC elution tracking detection, the eluate containing the target product is collected, the target product eluate is combined, concentrated under reduced pressure, the a,a,B-tricarbonylthio ylide compound represented by formula 111-12 is obtained with a yield of 55%. The substance is a white solid with a melting point of 184.9-187.2 °C. Characterization data: '"H NMR (400 MHz, DMSQ-ds) 68.02 (d, J = 1.7 Hz, 1H), 7.58 (dd, J= 1.7, 0.8 Hz, 1H), 7.41-7.24 (m, 1H), 6.96 (dd, J = 3.6, 0.8 Hz, 1H), 6.73 (dd, J= 3.6, 1.7 Hz, 1H), 6.46 (dd, J = 3.5, 1.7 Hz, 1H), 3.86 (s, 6H). "°C NMR (101 MHz, DMSO-de) à 183.6,
180.0, 175.2, 152.9, 150.2, 149.0, 146.5, 121.3, 117.5, 113.1, 112.5, 100.0, 41.9. HRMS m/z (ESI) calcd for C14H1206S (M+H)* 309.0427, found 309.0432. Embodiment 13 The structural formula of the a,a,f-tricarbonylthio ylide compound prepared in this embodiment is as follows: 0 O / O se II-13 16
The preparation method is as follows: cyclohexyl sulfur oxide ylide (0.4 mmol, 80.8 mg), LU500625 Cu(OAC)2(0.04 mmol, 7.2 mg), CF,COOAg (0.04 mmol, 8.8 mg) is added to a 25 ml schlenk tube equipped with a magnetic stirrer. Under reduced pressure, the reaction tube is replaced with oxygen three times. After 2 ml of anhydrous 1,4-dioxane is added, the reaction is stirred at 90°C for 12 hours. After the reaction, 200 mesh column chromatography silica gel is added, and the solvent is distilled off under reduced pressure. The crude product is separated by silica gel column chromatography and used as a mixture of petroleum ether and ethyl acetate (petroleum ether: ethyl acetate=2:1) Elution, with the help of TLC elution tracking detection, the eluate containing the target product is collected, the target product eluate is combined, concentrated under reduced pressure, the a,a,B-tricarbonylthio ylide compound represented by formula 111-13 is obtained with a yield of 51%. The substance is a white solid with a melting point of 129.8-133.4 °C.
Characterization data: '"H NMR (400 MHz, DMSO-ds) à 3.63 (s, 6H), 3.11 (s, 1H), 1.91 (d, J = 9.2 Hz, 2H), 1.74-1.67 (m, 6H), 1.62 (d, J = 11.7 Hz, 2H), 1.31-1.10 (m, 11H). "°C NMR (101 MHz, DMSO-de) à 205.1, 197.0, 187.4, 96.3, 46.9, 46.2, 42.7, 29.2, 28.4, 26.2, 26.1, 26.0,
25.8. HRMS m/z (ESI) calcd for C1sH1804S (M+H)* 341.1781, found 341.1784.
The preparation method of compound A: in a 50 mL three-necked flask, the a,a,B- tricarbonylthio ylide (0.15 mmol, 49.2 mg) shown in IIl-1 is dissolved in 5 mL of hot methanol. Under stirring, 5 mL of 25% methylamine aqueous solution is added. After stirring for 1 minute, sodium borohydride (0.4 mmol, 18.9 mg) is added. After being cooled, a yellow solid is separated and recrystallized from methanol to obtain product A (21.6 mg, 44% yield).
Characterization data of compound A: yellow solid (21.6 mg, 44%), m.p. 122.4-124.8 °C; "H NMR (400 MHz, DMSO-de) à 7.60-7.55 (m, 2H), 7.44-7.38 (m, 4H), 7.34 (t, J= 7.5 Hz, 3H),
7.26 (t, J=7.2 Hz, 1H), 4.47 (d, J= 1.9 Hz, 1H), 3.87 (d, J = 1.7 Hz, 1H), 3.40 (s, 3H), 3.08 (s, 3H), 2.09 (s, 3H). *C NMR (101 MHz, DMSO-de) 6 183.6, 143.8, 140.8, 129.5, 128.7, 128.7,
128.5, 128.3, 127.4, 78.7, 77.1, 70.0, 41.3, 38.2. HRMS m/z (ESI) calcd for C19H21NO2S (M+H)* 328.1366, found 328.1368.
Preparation method of compound B: in a 50 mL three-necked flask, the a,a,B-tricarbonyl sulfide ylide (0.3 mmol, 98.4 mg) shown in Ill-1 is dissolved in 10 mL of hot methanol, and then 3 mL of 80% hydrazine hydrate is added, after three minutes, the product is precipitated, and it is recrystallized with methanol to obtain a pure product (21.6 mg, 44% yield).
Characterization data of compound B: yellow solid (28.2 mg, 29%), m.p. 181.8-183.7 °C; "TH NMR (400 MHz, DMSO-d) 6 8.16 (d, J= 7.3 Hz, 2H), 7.54 (d, J= 6.0 Hz, 2H), 7.42 (t, J =
8.3 Hz, 6H), 3.99 (s, 6H). °C NMR (101 MHz, DMSO-de) à 164.5, 157.4, 156.6, 137.1, 135.8,
129.9, 129.2, 129.1, 129.0, 128.1, 127.7, 110.1, 40.8. HRMS m/z (ESI) calcd for C1sH1sN20>S (M+H)* 325.1005, found 325.1007.
17
Finally, it should be noted that the above embodiments are only used to illustrate the LU500625 technical solutions of the present invention and not to limit them.
Although the present invention has been described in detail with reference to the preferred embodiments, those of ordinary skill in the art should understand that the technical solutions of the present invention can be carried out.
Modifications or equivalent replacements without departing from the purpose and scope of the technical solution of the present invention should be covered by the scope of the claims of the present invention. 18
Claims (7)
1. Synthetic method of a,a,B-tricarbonyl sulfide ylide compound, characterized in that the synthesis method is carried out in an organic solvent with sulfur oxide ylide represented by formula | as a raw material, and carried out under the action of a catalyst reaction; G0 IN Se a SE Formula | The a, a, B-tricarbonylthio ylide compound has the structure of formula Il:
R 2 x x Formula ll Among them, R in formula | is selected from substituted or unsubstituted alkyl, C6-10 aryl or C4-10 heterocyclic, and the substituents include alkyl, alkoxy, cyano, nitro, halogen, and the alkyl group or alkoxy group is substituted with 0, 1 or more halogen atoms; The catalyst includes: anhydrous copper acetate and/or silver trifluoroacetate; the reaction atmosphere is oxygen.
2. The synthetic method of a,a,B-tricarbonyl sulfide ylide compound according to claim 1, characterized in that the R includes any of the following groups: i Ne AS © esp NY ep Sy Sy € 1 x D [SES Sag LS NE x N , LE Lu VF . E ho EE a” Des ~ J > As x S > Le. x “es ~ Gi ~ | Fal oe D NX DD i et Se - YF x RE À 2 pape Su” 1 À x SN = FE CMa” SP FLY . GF 1 NOT 1 SNS . Ty Pet Aa CO Se N u . Ve î “et . Sn, Re gp ar A NTN ;
3. The synthetic method of a,a,B-tricarbonyl sulfide ylide compound according to claim 1, characterized in that the organic solvent comprises 1,4-dioxane. 19
4. The synthetic method of a,a,B-tricarbonyl sulfide ylide compound according to claim 1, LU500625 characterized in that the reaction temperature is 70-110°C, and the reaction time is 8-14 h; after the reaction, the product is purified by silica gel column chromatography.
5. The synthetic method of a,a,B-tricarbonyl sulfide ylide compound according to claim 1, characterized in that the ratio of the amount of sulfur oxide ylide and the substance of the catalyst is 1: (0.1-0.2); the amount of the sulfur oxide ylide shown in Formula | is that the addition amount of the organic solvent is 4-8 mL/mmol.
6. The synthetic method of a,a,B-tricarbonyl sulfide ylide compound according to claims 1 to 5, characterized in that the a, a, B-tricarbonylthio ylide compound has the structure of formula II: Gap”
A SOR Formula I Among them, R in formula | is selected from substituted or unsubstituted alkyl, C6-10 aryl or C4-10 heterocyclic, and the substituents include alkyl, alkoxy, cyano, nitro, halogen, the alkyl group or alkoxy group is substituted with 0, 1 or more halogen atoms.
7. The synthetic method of a,a,B-tricarbonyl sulfide ylide compound according to claim 6, characterized in that the R includes the following groups: i . | . . a) i we > jr. rt x SN A AN Me ge” i od a Toy 45 or at NTN Sa , SNE . LET LT x £ Fup ey © Che YT Sr NT . Lo . » x . i x ter x k x Fale SE D. fi Port (y SE (y (y FCT ean Ana SE ey | we on | EE Ry ES ; x ory ei pu 4 L A N % X % { | J TN PS Heo SN OT a ye Rp A ES . Na {3 N Se 10° roc” net ar rs ce va Te Neely .
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