METHOD FOR SYNTHESIZING DIBENZOCYCLOHEPTANE DERIVATIVES BY SERIES CYCLIZATION OF FREE RADICALS UNDER ELECTROOXIDATION CONDITIONS

Abstract

Disclosed is a method for synthesizing dibenzcycloheptanone derivatives by series cyclization of free radicals under electrooxidation conditions, belonging to the technical field of organic synthesis. The disclosed method includes: taking o-propionyl biphenyl analogues and sodium benzenesulfinate analogues as raw materials, and electrifying and reacting the raw materials in an electrolytic cell to obtain dibenzocycloheptane derivatives. According to the application, benzenesulfinate anion is oxidized into benzenesulfonyl radical under the condition of constant current and electrolyte, then the radical attacks the α-position of alkynone reactant carbonyl to obtain an alkenyl radical, then the alkenyl radical is cyclized and added to another benzene ring by 7-endo-trig to realize the construction of seven-membered ring, and finally the dibenzocycloheptane analogue is obtained by deprotonation.

Claims

1. A method for synthesizing dibenzcycloheptanone derivatives by series cyclization of free radicals under electrooxidation conditions, comprising: using analogues as shown in a formula (I) and sodium benzenesulfinate analogues as raw materials, electrifying and reacting the raw materials in an electrolytic cell to obtain dibenzocycloheptane derivatives; wherein: ##STR00013## Ar is an alkyl or a halogen-substituted benzene ring; R.sup.1 is H, alkyl, halogen atom, ester, or alkoxy; and R.sup.2 is aryl in the formula (I); the sodium benzenesulfinate analogues have a structure as shown in a following formula (II): ##STR00014## as shown in the formula (II), R is H, alkyl, halogen atom, nitro, cyano or alkoxy; electrolyte solution in the electrolytic cell has a concentration of 0.1 mole per liter (mol/L); the electrolyte solution includes tetraethylammonium perchlorate as electrolyte, the electrolyte solution also includes a compound solvent of acetonitrile and water as solvents, and the acetonitrile is in a volume ratio of 3 : 1 to the water; and the electrolytic cell includes a carbon electrode graphite felt as an anode, and platinum or nickel as a cathode; and the electrifying and reacting is carried out under a reaction temperature of 50 degree Celsius (°C), a constant current of 4 milliampere (mA), and a reaction duration of 6 hours (h).

2. The method for synthesizing dibenzcycloheptanone derivatives by series cyclization of free radicals under electrooxidation conditions according to claim 1, wherein the Ar is an alkyl-substituted benzene ring.

3. The method for synthesizing dibenzcycloheptanone derivatives by series cyclization of free radicals under electrooxidation conditions according to claim 1, wherein the R.sup.1 is alkyl.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0032] FIG. 1 shows an .sup.1H NMR spectrum of a product prepared in Embodiment 1.

[0033] FIG. 2 shows a .sup.13C NMR spectrum of the product prepared in Embodiment 1.

[0034] FIG. 3 shows an .sup.1H NMR spectrum of a product prepared in Embodiment 2.

[0035] FIG. 4 shows a .sup.13C NMR spectrum of the product prepared in Embodiment 2.

[0036] FIG. 5 shows an .sup.1H NMR spectrum of a product prepared in Embodiment 3.

[0037] FIG. 6 shows a .sup.13C NMR spectrum of the product prepared in Embodiment 3.

[0038] FIG. 7 shows an .sup.1H NMR spectrum of a product prepared in Embodiment 4.

[0039] FIG. 8 shows a .sup.13C NMR spectrum of the product prepared in Embodiment 4.

[0040] FIG. 9 shows a .sup.1H NMR spectrum of a product prepared in Embodiment 5.

[0041] FIG. 10 shows a .sup.13C NMR spectrum of the product prepared in Embodiment 5.

DETAILED DESCRIPTION OF THE EMBODIMENTS

[0042] Now various exemplary embodiments of the present application will be described in detail. This detailed description should not be taken as a limitation of the present application, but should be understood as a more detailed description of some aspects, characteristics and embodiments of the present application. It should be understood that the terms mentioned in the present application are only used to describe specific embodiments, and are not used to limit the present application.

[0043] In addition, for the numerical range in the present application, it should be understood that each intermediate value between the upper limit and the lower limit of the range is also specifically disclosed. Any stated value or intermediate value within the stated range, and any other stated value or intermediate value within the stated range are also included in the present application. The upper and lower limits of these smaller ranges can be independently included or excluded from the range.

[0044] Unless otherwise stated, all technical and scientific terms used herein have the same meanings commonly understood by those of ordinary skill in the field to which this application relates. Although the present application only describes preferred methods and materials, any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present application.

[0045] As used in this paper, the terms “comprising”, “including”, “having” and “containing” are all open terms, meaning including but not limited to.

Embodiment 1

[0046] O-propionyl biphenyl 1a (102.6 milligram (mg), 0.3 millimole (mmol), 1.0 equivalent (equiv.)), sodiump-toluenesulfonate 2a (106.8 mg, 0.6 mmol, 2.0 equiv.) and tetraethylammonium perchlorate (92 mg, 0.4 mmol, 0.1 mole per liter (M)) are accurately added into a reaction tube, and a mixed solvent Mecn/H.sub.2O (volume/volume, v/v, 3 : 1, 4 milliliters (mL)) is added into the tube at last, followed by reaction at 50 degree Celsius (°C) for 6 hours (h) under constant current; then all solvents are transferred to a round bottom flask, then the flask is added with silica and subjects to evaporation in vacuum; n-hexane/EtOAc (v/v, 3 : 1) is taken as eluent, then a corresponding product 3a is obtained by silica gel column chromatography with a yield of 75%, and the reaction is as follows:

##STR00007##

[0047] Nuclear magnetic resonance (NMR) data of the product: .sup.1H NMR (600 megahertz (MHz), CDCl3) δ7.87 (d, J = 7.9 Hz, 1H), 7.68 (td, J = 7.6, 1.6 Hz, 1H), 7.57-7.52 (m, 2H), 7.19 (t, J = 7.4 Hz, 2H), 7.09 (d, J = 8.3 Hz, 3H), 6.95 (d, J = 8.1 Hz, 2H), 6.71 (d, J = 2.4 Hz, 1H), 6.32 (d, J = 2.4 Hz, 1H), 3.85 (s, 3H), 3.20 (s, 3H), 2.30 (s, 3H). .sup.13C NMR (151 MHz, CDCl.sub.3) δ193.6, 161.3, 160.7, 146.9, 145.1, 143.5, 142.2, 140.3, 138.9, 138.3, 135.8, 131.2, 128.9, 128.8, 128.1, 128.0, 127.9, 126.8, 125.5, 118.3, 106.9, 99.6, 55.6, 55.6, 21.6. HR-MS(ESI)m/z calc. for C.sub.3OH.sub.25O.sub.5S[M+H].sup.+: 497.1417, found: 497.1398.

[0048] See FIG. 1 for the .sup.1H NMR spectrum of the product prepared in Embodiment 1, and FIG. 2 for the .sup.13C NMR spectrum of the product prepared in Embodiment 1.

Embodiment 2

[0049] O-propionyl biphenyl 1b (115.8 mg, 0.3 mmol, 1.0 equiv.), sodium p-toluenesulfonate 2a (106.8 mg, 0.6 mmol, 2.0 equiv.), tetraethylammonium perchlorate (92 mg, 0.4 mmol, 0.1 M) are accurately added into a reaction tube, and a mixed solvent Mecn/H.sub.2O (v/v, 3:1, 4 mL) is added into the tube at last, followed by reaction at 50° C. for 6 h under constant current; then all the reagents are transferred to a round bottom flask, and the round bottom flask is added with silica and subjects to evaporation in vacuum; n-hexane/EtOAc (v/v, 3:1) is used as eluent, then a corresponding product 3b is obtained by silica gel column chromatography with a yield of 43.2%, where the reaction is as follows:

##STR00008##

[0050] NMR data of the product: .sup.1H NMR (600 MHz, CDCl.sub.3) δ7.84 (d, J = 7.9 Hz, 1H), 7.71-7.65 (td, J = 6.6, 2.4 Hz, 1H), 7.57-7.54 (m, 2H), 7.17 (d, J = 8.1 Hz, 2 H), 7.00 (d, J = 8.1 Hz, 2H), 6.71 (d, J = 2.4 Hz, 1H), 6.59 (d, J = 6.1 Hz, 2H), 6.35(d, J = 2.3 Hz, 2H), 5.90 (d, J = 29.2 Hz, 2H), 3.86 (s, 3H), 3.35 (s, 3H), 2.32 (s, 3H). .sup.13C NMR (101 MHz, CDCl.sub.3)δ193.6, 161.4, 160.9, 147.5, 146.5, 146.2, 145.2, 143.6, 142.2, 140.4, 139.1, 135.9, 132.2, 131.2, 128.9, 128.8, 128.1, 128.0, 125.7, 118.0, 107.1, 106.8, 101.1, 99.5, 55.8, 55.6, 21.6.HR-MS(ESI)m/z calc.for C.sub.30H.sub.25O.sub.5S[M+H].sup.+: 541.1316, found: 541.1293.

[0051] FIG. 3 shows the .sup.1H NMR spectrum of the product prepared in Embodiment 2, and FIG. 4 illustrates the .sup.13C NMR spectrum of the product prepared in Embodiment 2.

Embodiment 3

[0052] O-propionyl biphenyl 1c (106.8 mg, 0.3 mmol, 1.0 equiv.), sodium p-toluenesulfonate 2a (106.8 mg, 0.6 mmol, 2.0 equiv.) and tetraethylammonium perchlorate (92 mg, 0.4 mmol, 0.1 M) are accurately added into a reaction tube, then a mixed solvent Mecn/H.sub.2O ((v/v, 3:1, 4 mL) is added into the tube at last, followed by reaction at 50° C. for 6 h under constant current; then all solvents are transferred into a round bottom flask, and the flask is added with silica and then subjects to evaporation in vacuum; n-hexane/EtOAc (v/v, 3 : 1) is used as eluent, and a corresponding product 3c is obtained by silica gel column chromatography with a yield of 47.1%, where the reaction is as follows:

##STR00009##

[0053] NMR data of the product: .sup.1H NMR (600 MHz, CDCl.sub.3) δ7.88(d, J = 7.8 Hz, 1H),7.69(td, J= 7.2, 1.8 Hz, 1H), 7.61-7.56 (m, 2H), 7.11-7.05 (m, 3H), 7.00-6.96 (m, 3H), 6.72 (d, J = 2.4 Hz, 1H), 6.33 (d, J = 2.4 Hz, 1H), 3.85 (s, 3H), 3.21 (s, 3H), 2.31-2.14 (m, 6H). .sup.13C NMR (151 MHz, CDCl.sub.3) δ193.6, 161.3, 160.8, 147.1, 145.1, 143.3, 142.2, 140.3, 139.2, 138.1, 136.2, 135.8, 131.2, 128.9, 128.8, 128.7, 128.2, 127.8, 126.7, 125.5, 118.3, 106.9, 99.7, 55.7, 55.6, 21.5, 21.2. HR-MS(ESI) m/z calc.for C.sub.31H.sub.27O.sub.5S[M+H].sup.+: 511.1574, found: 511.1580.

[0054] See FIG. 5 for the .sup.1H NMR spectrum of the product prepared in Embodiment 3, and FIG. 6 for the .sup.13C NMR spectrum of the product prepared in Embodiment 3.

Embodiment 4

[0055] O-propionyl biphenyl 1d (112.8 mg, 0.3 mmol, 1.0 equiv.), sodium p-toluenesulfonate 2a (106.8 mg, 0.6 mmol, 2.0 equiv.) and tetraethylammonium perchlorate (92 mg, 0.4 mmol, 0.1 M) are accurately added into a reaction tube, then a mixed solvent Mecn/H.sub.2O (v/v, 3 : 1, 4 mL) is added into the tube at last, followed by reaction at 50° C. for 6 h under constant current; then all solvents are transferred to a round bottom flask, and the flask is added with silica and subjects to evaporation in vacuum; n-hexane/EtOAc (v/v, 3 : 1) is used as eluent, and a corresponding product 3d is obtained by silica gel column chromatography with a yield of 50.3%, where the reaction is as follows:

##STR00010##

[0056] NMR data of the product: .sup.1H NMR (400 MHz, CDCl.sub.3) δ7.85 (d, J = 1.9 Hz, 1H), 7.54 (dd, J = 8.2, 1.9 Hz, 1H), 7.46 (d, J = 8.2 Hz, 1H), 7.28-7.12 (m, 5H), 7.01 (d, J = 8.1 Hz, 2H), 6.68 (d, J = 2.4 Hz, 1H), 6.34 (d, J = 2.4 Hz, 1H), 3.87 (s, 3H), 3.20 (s, 3H), 2.33 (s, 3H). .sup.13C NMR (101 MHz, CDCl.sub.3) δ192.6, 161.5, 160.8, 147.0, 143.8, 143.4, 142.3, 138.9, 138.9, 138.1, 137.5, 137.2, 129.1, 128.8, 128.2, 128.1, 128.0, 127.0, 126.8, 118.4, 106.8, 100.1, 55.7, 55.6, 21.6.HR-MS (ESI)m/z calc.for C.sub.30H.sub.24ClO.sub.5S[M+H].sup.+: 531.1028, found: 531.1008.

[0057] The .sup.1H NMR spectrum of the product prepared in Embodiment 4 is illustrated in FIG. 7, and the .sup.13C NMR spectrum of the product prepared in Embodiment 4 is shown in FIG. 8.

Embodiment 5

[0058] O-propionyl biphenyl 1e (104.4 mg, 0.3 mmol, 1.0 equiv.), sodium p-toluenesulfonate 2a (106.8 mg, 0.6 mmol, 2.0 equiv.), tetraethylammonium perchlorate (92 mg, 0.4 mmol, 0.1 M) are accurately added into a reaction tube, and a mixed solvent Mecn/H.sub.2O is added into the tube at last, followed by reaction at 50° C. for 6 h under constant current; then all solvents are transferred in to a round bottom flask, and the flask is added with silica and subjects to evaporation in vacuum; n-hexane/EtOAc(v/v, 3:1) is used as eluent, and a corresponding product 3e is obtained by silica gel column chromatography with a yield of 55.8%, where the reaction is as follows:

##STR00011##

[0059] NMR data of the product: .sup.1H NMR (600 MHz, CDCl.sub.3) δ7.64 (dd, J = 29.6, 5.1 Hz, 2H), 7.45 (d, J = 8.2 Hz, 2H), 7.28-7.24 (m, 2H), 7.11 (d, J = 8.3 Hz, 3H), 6.84 (d, J = 2.4 Hz, 1H), 6.32 (d, J = 2.3 Hz, 1H), 3.87 (s, 3H), 3.12 (s, 3H), 2.36 (s, 3H). .sup.13C NMR (151 MHz, CDCl.sub.3) δ184.1, 162.1, 161.9, 147.4, 143.9, 143.6, 140.9, 140.3, 139.8, 139.0, 135.7, 130.7, 129.1, 128.5, 128.1, 127.0, 119.0, 104.7, 99.7, 55.6, 55.5, 21.6. HR-MS (ESI) m/z calc. for C.sub.28H.sub.24ClO.sub.5S[M+H].sup.+: 503.0982, found: 503.0986.

[0060] FIG. 9 shows the .sup.1H NMR spectrum of the product prepared in Embodiment 5, and FIG. 10 shows the .sup.13C NMR spectrum of the product prepared in Embodiment 5.

Embodiment 6

[0061] The reaction of the present embodiment is optimized with conditions as follows:

[0062] O-propionyl biphenyl 1a (0.3 mmol, 1.0 equiv.), sodium p-toluenesulfonate 2a (0.9 mmol, 3.0 equiv.), electrolyte 0.1 M and solvent 4 mL are added into a reaction tube, followed by reaction for 6 h under constant current of 4 milliampere (mA) with graphite felt (GF) as anode and platinum (Pt) as cathode; then all solvents are transferred into a round bottom flask, then the flask is added with silica and subjects to evaporation in vacuum; n-hexane/EtOAc (v/v, 3 : 1) is used as eluent, then a product 3a is obtained by silica gel column chromatography, and the yield is calculated, where the reaction is as follows:

##STR00012##

[0063] See Table 1 for parameter optimization process and yield.

TABLE-US-00001 Solvent (v/v) Electrolyte Temperature (°C) Yield (%) 1 EtOH/H.sub.2O (3:1) Et.sub.4NClO.sub.4 50 0 2 DMF/H.sub.2O (3:1) Et.sub.4NClO.sub.4 50 0 3 1,4-Dioxane/H.sub.2O (3:1) Et.sub.4NClO.sub.4 50 39 4 DCE/MeCN/H.sub.2O (5:5:1) Et.sub.4NClO.sub.4 50 37 5 MeCN/H.sub.2O (3:1) Et.sub.4NClO.sub.4 50 73 6 MeCN/H.sub.2O (3:1) n-Bu.sub.4NI 50 32 7 MeCN/H.sub.2O (3:1) n-Bu.sub.4NPF.sub.6 50 56 8 MeCN/H.sub.2O (3:1) n-Bu.sub.4NBF.sub.4 50 64 9 MeCN/H.sub.2O (3:1) n-Bu.sub.4NClO.sub.4 50 43 10 MeCN/H.sub.2O (3:1) - 50 59 11.sup.[a] MeCN/H.sub.2O (3:1) Et.sub.4NClO.sub.4 50 68 12 MeCN/H.sub.2O (3:1) Et.sub.4NClO.sub.4 25 0 13 MeCN/H.sub.2O (3:1) Et.sub.4NClO.sub.4 60 50 14.sup.[b] MeCN/H.sub.2O (3:1) Et.sub.4NClO.sub.4 50 32 15.sup.[c] MeCN/H.sub.2O (3:1) Et.sub.4NClO.sub.4 50 60 16.sup.[d] MeCN/H.sub.2O (3:1) Et.sub.4NClO.sub.4 50 54 17.sup.[e] MeCN/H.sub.2O (3:1) Et.sub.4NClO.sub.4 50 0 18.sup.[f] MeCN/H.sub.2O (3:1) Et.sub.4NClO.sub.4 50 0

[0064] As can be seen from Table 1, [a] indicates that an addition amount of sodium p-toluenesulfonate 2a is 0.9 mmol, 3.0 equiv., [b] means a constant current of 3 mA, [c] indicates a constant current of 6 mA, [d] indicates GF as anode and nickel (Ni) as cathode, [e] represents Pt as anode and Pt as cathode, and [f] means no electricity.

[0065] The above-mentioned embodiments only describe the preferred mode of the application, but do not limit the scope of the application. On the premise of not departing from the design spirit of the application, all kinds of modifications and improvements made by ordinary technicians in the field to the technical scheme of the application shall fall within the scope of protection determined by the claims of the application.